From Flips to Clicks: The Evolution of Conducting Research Through Books vs. The Internet – Egyptian Streets

From Flips to Clicks: The Evolution of Conducting Research Through Books vs. The Internet

Once upon a time, the internet had yet to exist and when one needed to conduct research of any sort, they had to solely rely on books heaps and piles of books.

Imagine being at school or university these days, being given an assignment that requires a lot of research in a certain subject or topic and having to rely solely on using the library and no, not the computers at the library, but the actual books at the library.

For most students these days, or more specifically those who fall under the demographic of millennials and Generation Z, having to conduct research solely through books might actually be unimaginable. Why go through the physical and time consuming process of skimming through piles of books, when the answers one could be looking for could literally be found just a click away?

That being said, however, there are undoubtedly pros and cons to each method of research. While searching for answers through the internet could be a lot faster and efficient, a lot of the time one will not be able to really go in depth on a certain subject or topic by solely relying on internet searches.

Researching Through the Internet

Google, its almost everyones go-to source for any sort of information one might be seeking. From specific questions on topics such as philosophy to those of a more minute scale such as asking about how to boil an egg Google always has the answer, or at least an answer that will stand out amongst a sea of many.

The internet truly is a marvel, and when thinking about the fact that one can access countless sources of information through the click or a button, it definitely puts things into perspective in terms of how far technology has advanced.

However as with most technological advances, as well as generally most things in life, nothing comes without downfalls of some sort.

As previously mentioned, although searching for something through the internet is faster and more efficient, it is not as reliable as trying to search for something through specific books, for example.

The internet is so vast and wide, that people will find themselves bombarded with such a wide variety of information, most of which may not be backed up by a sufficient amount of research, nor reliable sources.

Indeed, the internet can provide a lot in a short amount of time, but because of its wide reach and accessibility, this very fact also makes it its downfall; anyone these days can publish anything on the internet it doesnt make it accurate or reliable.

Researching Through Books

In todays fast-paced world, barely anyone has the patience or time to read, let alone skim, through books these days.

In addition to this, when it comes to conducting research through books, one must first also search for the most appropriate books that would best fit their subject or topic.

While this method may not seem time efficient these days, it may actually provide a lot more sufficient and reliable information for the topic of which one could be conducting research for.

The beauty of books that discuss certain topics, is that more often that not the person or author who wrote and published the book is a professional or academic with years of experience on the matter.

As such, the information gathered and placed into the book is a lot more reliable than a random internet search, because it consists of years of effort and studies all ultimately placed together in this one place.

However, it is worth keeping in mind that there are also many books published by people who lack credentials; it just may be slightly easier to point those out in book form than sources found online.

Also, more often than not, sources found on the internet may cite or suggest certain books for further reading and delving into the topic more deeply.

For this reason, and in order to truly provide fact-based research which is both reliable and unique, conducting research by skimming through certain books can make all the difference.

The Ultimate Prognosis

Perhaps the best thing to do when conducting any sort of research these days, would be to try to balance between searching for information through the internet as well as skimming through books.

The internet could be a great resource for simple background information; the sort of information one would include in a study or assignment that just slightly begins to touch the surface of a certain topic.

In order to delve deeper into a topic or subject however, to truly enrich the research one is conducting, academic or professional support through books that specifically tackle the topic at hand can tie everything together perfectly.

That being said, the next time one goes about conducting research of any sort, perhaps re-visiting physical books is worth a try.

A particularly great, and little known, resource that one can use in Egypt is the Egyptian Knowledge Bank. The Egyptian Knowledge Bank acts as a digital library, thriving with numerous diverse resources, exclusively for Egyptian citizens.

According to their official website, The Egyptian Knowledge Bank grants all Egyptians from all ages access to the largest amount of knowledge, cultural and scientific content whether they be basic, applied, technology, human or management sciences. Even public cultural books, including books targeting children, to be used through all computers, as well as smart phones and tablets around the country. One can access this resource by using their national ID number.

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From Flips to Clicks: The Evolution of Conducting Research Through Books vs. The Internet - Egyptian Streets

AR Wallace Is Evolution’s Last Man Standing – Discovery Institute

Image: Alfred Russel Wallace, via Wikimedia Commons.

American zoologist T. D. A. Cockerell, writing for The Dialon April 16, 1911, reviewed Alfred Russel Wallaces then-recently releasedThe World of Life. He wrotecautiously but approvingly.

Being thus a work of philosophy as well as science, it necessarily covers much debatable ground. Those of us who are not prepared to follow Dr. Wallace in all the intricacies of his personal faith, may nevertheless feel very strongly that he has done well in bringing forward his solution of the riddle of the ages, the result of more than fifty years of thought.

Indeed Cockerells confidence is confirmed today more than ever. A new edition of Wallace book, Intelligent Evolution: How WallacesWorld of LifeChallenged Darwinism, is out now, edited by science historian Michael Flannery. In his Foreword to the new book, William A. Dembski notes how current scholarship is demolishing the neo-Darwinian paradigm and confirming Wallace at almost every turn. Dembski says that staunch Darwinian defender [Jerry]Coynes one going theory may be steadilygoing away.

When we look at that first generation of modern evolutionists, from Charles Darwin and Thomas Henry Huxley to John Tyndall and Herbert Spencer, only Wallaces postulation of an Overruling Intelligence to explain the complexities of humanity and nature has stood the test of time. To understand his enduring presence in biology as well as natural theology,The World of Lifeis indispensable. Once his thought is placed in context and illuminated by the latest research and historiography, as it is inIntelligent Evolution, youll understand why Wallace remains evolutions last man standing. Order yourcopytoday.

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AR Wallace Is Evolution's Last Man Standing - Discovery Institute

‘Homegrown’: An Insight Into the Evolution of Music – berkeleyhighjacket.com

One of the best rock albums released recently is 46 years old. Though Neil Youngs latest album, Homegrown, came out in June of 2020, it was actually recorded in the early 1970s. Young wrote the album after his breakup with actress Carrie Snodgress and held off on releasing it for close to a half a century to spare himself the pain. That same emotional struggle is apparent in the album and makes an intense emotional listen.

Beyond being a fantastic record, Homegrown is a time capsule from a different musical era. In late August of 1973, around the time the album was created, the number one song on the Cash Box Top 100 was Live and Let Die by Paul McCartney and Wings. The number one song on the BillBoard Top 100 today is WAP by Cardi B and Megan Thee Stallion. Essentially nothing on the current charts is anything that would be considered rock music. Instead, the songs in todays top charts are from the R&B, hip hop, rap, and/or pop genres. Seeing the stylistic differences between past and present music, it can seem that there is a large musical gap between then and now. Nonetheless, saying rock music is dead would be false. Rock shares a very similar history and ancestry to rap, hip hop, and R&B. Rather than die out, the rock & roll of the past has evolved into the pop, hip hop, and R&B of today.

Rock, as a genre, has never meant just one thing and has never been easy to define; perhaps it is indefinable. However, all rock shares a derivation from African American jazz, rhythm, blues, and country music from the 1950s. It usually involves the use of drums, one or more guitars (often electric), a bass, a keyboard or piano, and some sort of vocals. Though it is typically played in a 4/4 time signature, there are forms of blues rock in 12/8. It also shares a similar verse/chorus structure to its sister genre, pop music. These vague guidelines with innumerable twists and variations are what defines rock music, a style which dominated popular music from sometime in the 60s through the 80s and into the 90s, when rap and hip hop took over by storm.

Hip hop and rock have more musical similarities than it may seem at first. They are both typically built on backbeats in 4/4 and are largely centered around the human voice. Both can be traced back to the rhythm and blues and are both, in a sense, subgenres of this style. The two styles are sometimes bridged with artists like the Beastie Boys, Run-D.M.C, and Rage Against the Machine, who walk the line between rock and hip hop. Artists like them show how closely connected hip hop and rock are. Today, bands like Death Grips continue to exist somewhere between the worlds of rock and hip hop, demonstrating that these genres are intertwined by nature.

Seeing as these two major genres in addition to funk, soul, and R&B all have their roots in the same place, it can be inferred that rock did not start falling out of the Top 100 charts because its popularity was diminishing, rather, the genre shifted and changed into something new, as music has always done.

Though the success of Homegrown may seem like it came out of left field, it actually serves as an indicator to how related the music of today really is to that of the past. Hearing this album shouldnt be a sad reminder of something dead and gone, rather an insight into the constantly changing and evolving multi-laned world of music. In essence, Youngs album from 1970 is a wonderful reminder of musical traditions.

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'Homegrown': An Insight Into the Evolution of Music - berkeleyhighjacket.com

New York Islanders: The Evolution of Matt Martin – Empire Sports Media

The New York Islanders drafted Matt Martin in the 5th round of the 2008 NHL Entry Draft. Since then, Matt Martin has been the staple/identity of Islanders hockey. Hard-hitting, physical forechecking, and a lot of chirping. Martin has grown as a player since being drafted. He went from a head-hunting enforcer to a get in front of the net grinder. Not only has this change impacted the Islanders positively, but also added years to his career.

Young Matt Martin played a lot like Ross Johnston does. Both of them are big bodies who stuck up for their best players. For Martin, it was John Tavares, for Johnston, it is Mat Barzal. Dont get me wrong, Martin is still an enforcer, but hes an offensive enforcer.

Barry Trotz has made Martin an offensive threat for the first time in his whole career. Matt Martin currently has four playoff goals, and all of them were clutch goals. Having a 4th liner who can score along with creating opportunities through the forecheck is huge. He can still deliver the big hits too, but not as frequent. My only criticism is that he takes bad penalties at bad times. Too many stick infractions in the closing minutes of the third. Other than that, Martin is a great player.

Sadly, Matt Martins contract is over with the Islanders after the season ends. Since the Islanders have to sign Mat Barzal, Devon Toews, and Ryan Pulock, the chance that Martin gets resigned is very slim. I would keep Martin over Johnston, though.

Theres no reason to break up that 4th line chemistry just because theres a younger version of young Matt Martin. Martin should command $2-$2.5 million in free agency, close to Johnstons contract. Im not saying get rid of Johnston for Martin, but if thats how it has to happen, thats how it must happen. The 4th line is crucial to the Islanders success, its the entire identity of who the Islanders are. The Islanders must keep Martin somehow.

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New York Islanders: The Evolution of Matt Martin - Empire Sports Media

Darwin’s apostles and evolutionary science: fighting fake news – Albany Times Union

Dr. Abby Hafer has her doctorate in zoology from Oxford University and currently teaches at Curry College. She has authored the book Unintelligent Design, among others, and claims to be famous for testicles. (Not her own; see below.) I heard her recent talk about what todays fighters against fake news can learn from Darwins apostles.

She started by suggesting that pre-Trump we could not have imagined an American president establishing a bizarre, counter-factual, evidence-free narrative, yet succeeding in gulling much of the population. But Welcome to my world, Hafer said every evolutionary biologist has always had to deal with such an environment of factual denialism. Objective reality exists! she insisted, steadfastly disregarding all the evidence to the contrary.

The Darwin apostles Hafer discussed were scientists who fought, against powerful entrenched interests, to gain acceptance for the concept of evolution by natural selection. After a long hard campaign they succeeded to a great degree (despite pockets of resistance, notably including a high proportion of Americans). Hafer cited publication, in 1889, of a book, Lux Mundi, in which notables in the Church of England discussed reconciling their faith with evolution which they already assumed was true.

John William Draper was a scientist who authored History of the Conflict Between Religion and Science in 1874. The lesson Hafer took from his efforts: dont quail from battling fundamentalist religion, but work with religious people wherever its possible.

Alfred Russel Wallace was of course the guy who figured out evolution at about the same time as Darwin. Darwin had long feared publishing would cause a big backlash. But Wallace, Hafer said, struck a different kind of terror into Darwin: not getting credit. So he finally finished up the book hed been working on for two decades. (He and Wallace actually reached an agreement about public presentation of the theory. In this negotiation Darwin had much back-up from colleagues. I recall one writer saying they took Wallace to the cleaners.)

Joseph Hooker was one scientist who had long actually fought against the idea of biological evolution. But ultimately, he said, the conviction was forced upon an unwilling convert. He couldnt fight the facts. That was intellectual integrity.

Darwins greatest proponent was Thomas Henry Huxley. Hafer discussed his lengthy battle with Richard Owen, who maintained that brain differences ruled out any close connection between humans and apes. Huxley showed Owen was just wrong on the anatomical facts: Before I have done with that mendacious humbug I will nail him out like a kite to a barn door, an example to all evil doers.

Huxley was indefatigable, working the social media of his day newspapers. Letters to the editor, and replies, were a very big thing.

One audience member remarked that many people who most need to hear such messages refuse to listen. Hafer acknowledged this, and how a lot of these issues have become politicized. But she held that persistent efforts to debate such issues, vigorously battling error, in the public square, can have an effect. And Americans are actually leaving evangelical Christianity in droves, indeed angry because they feel theyve been lied to.

A point she emphasized was that to overcome biases you have to tailor the message to engage people. Mention was made of Galileos experiments with the motions of balls, illustrating his ideas in a visually unarguable way. Hafer also pointed to her own work on how the human body actually shows un-intelligent design.* A prime example is testicles, hanging vulnerably outside the body cavity, whereas many other animals have them safely inside. Its because human testicles have to be kept cooler. (I asked whether there was any connection between testicles and Galileos balls and she gave a straight-faced answer.) Anyhow, the point was that when you start talking about testicles, people sit up and listen.

She also said the current pandemic is a golden opportunity to make people grasp the importance of being serious toward science. And the virus, of course, evolved.If it werent for evolution, thered never be any new diseases.

Hafer avowed that we are struggling today not only for the soul of this nation but for its brain.Its integrity. Scientists are on the front lines of this battle.

She channeled Martin Niemoller: First they came for the evolutionary biologists . . . .

* Heres my earlier discussion of that: https://rationaloptimist.wordpress.com/2011/04/11/unintelligent-design--why-evolution-explains-the-human-body-and-intelligent-design-does-not/

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Darwin's apostles and evolutionary science: fighting fake news - Albany Times Union

The Evolution of Wesley Crusher – Star Trek

One of my favorite characters on The Next Generation is Wesley Crusher. Ive always been a fan of the underdog, and Wesley fits that bill perfectly, a prodigy on board a ship of Starfleets best and brightest. Hes more than just a wonder kid I found him to be one of the most complex and well-developed characters on the series, with his arc being one of the more fascinating journeys on a series which has several great ones. The series presents Wesley as someone who represents the best ideals of a Starfleet officer candidate, a keen study with a passionate interest in science. However, he could sometimes struggle under pressure of high expectations placed upon him from an early age. It was only towards the end of the series when we finally see that Wesley feels content in leaving Starfleet to realize his goals.

Evolution does a good job at establishing that Wesley isnt a perfect person, and has plenty of learning to do on his path that would see him join The Traveler in Journeys End. He doesnt always get everything right and whats more, time after time throughout the series hes constantly placed in environments where adults are too busy for him, constantly overlook his skills, or are too overbearing.

In Journeys End Wesleys mother, Dr. Beverly Crusher, returns to the ship and finds it hard to reconnect with him, leading the young man to seek solace elsewhere in Dr. Stubbs. The subtle teleplay from Michael Piller presents Dr. Stubbs and Wesleys other role model figure, Captain Picard, as alternatives to one another, looking at the impact both would have as surrogate fathers for a teenager without one. Whilst the dedicated scientist is clearly imperfect and flawed, hes the same sort of person that Wesley could end up as in the years to come if he doesnt keep his humanity in check. Its easy to see why Dr. Stubbs is initially appealing, as he comes across initially as an alternative to Picard, their characters share a mutual hunger for science and the unknown whilst their passion for baseball is incredibly heartfelt.

However, Dr. Stubbs lets his ego consume him to the point where it puts lives on the Enterprise in danger, placing Wesley in a situation where he must realize that his own mistakes may make him responsible. The fact that he might be struggling is hard for him to admit, and his scenes with his mother and Guinan keep him grounded and steer him back towards the right track.. Its these moments that separate him from Dr. Stubbs, keeping his influence restricted to a cautionary tale and humanizing Wesley without losing his appeal as a character.

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His struggles and hard work pay off consistently over the series, but not without great cost as we see him pursue his Starfleet Academy dreams. Coming of Age and Mnage Troi arent afraid to show Wesley failing, showing he has no easy route towards his ambition. Coming of Age sees his first attempt at passing the Starfleet entrance exams fail; but ultimately he sacrifices those dreams in Mnage Troi where he comes into his own and saves key crewmembers of the Enterprise instead of taking part in the entrance examination. He loses the opportunity to enter the Academy, but is in turn promoted to the rank of a full Ensign. Given his achievements so far in the series, it feels completely earned.

In Final Mission Wesley finally joins Starfleet Academy, but only after more hard work. After being stranded on a desert planet as a direct result of a mining shuttle accident, Wesley is forced into a situation where he has to work to save Picards life after the death of Captain Dirgo. Its an episode that goes from strength to strength, highlighting how much the friendship between Wesley and Picard has evolved from their early days of animosity, with their farewell being one of the more tender and emotionally charged moments of the series. Their bond is heavy and sincere, working as much as a stepping stone for Picards development as it does for Wesley, with Picard reminded of his own youth and mortality as he spends most of the episode completely reliant on Wesleys help. Its a touching moment when Picard admits that he doesnt see Wesley as just a child anymore, but as someone who he envies, being just at the beginning of the adventure.

StarTrek.com

The scenes between Picard and Wesley in Final Mission act as a driving force for the younger man in the rest of the series. The Game sees Wesley in his element again, saving the ship from an addictive game consuming every member of the crew with the aid of Ensign Robin Lefler. Its a classic hangout episode of the series thats just so much fun to watch, and revels in once again placing Wesley directly in his element, while The First Duty takes him out of his comfort zone again almost immediately and puts him in one of the most difficult positions that any crew member has had to be in. In The First Duty, Wesley he faces consequences for his actions that stay with him until the end of his time on the series.

The first duty of every Starfleet officer is to the truth, is a good mantra to have, one of the best but it can be challenging in practice. The audience has become so used to situations where Wesley ends up saving the day to the point where he thinks hes almost invincible himself, which is a trait shared with the rest of Nova Squadron who believe they can do nothing wrong. But the tragedy is that they are falible. They lack the experience of actual officers and, more importantly, they lack the knowledge about when not to act. This leads to heartbreaking consequences and the death of a squadron member in an easily-preventable training accident as their world comes crashing down around them. Forced into a position where his training group are covering up their roles in the death of a crewmember, Wesley is faced with an uncomfortable choice: does he take the hard, but honorable route in betraying his friends and jeopardizing not just his future but theirs? Or does he lie, and take the easy way out?

If Final Mission was about reinforcing the relationship between Picard and Wesley, The First Duty is the episode that almost tore it apart. Wesleys relationship with both Beverly and Picard is placed completely under the spotlight when they learn the truth. Ill never not find it devastating when his mother realizes that Wesley might actually be lying about his involvement in the incident. Coupled with Picards speech that eventually sees him make a good, but tough call in admitting what really happened in the training exercise, The First Duty demonstrates its capability to deliver truly poignant moments that prove to be character-defining, leaving Wesley to cope with consequences that affect his entire career.

StarTrek.com

Wesley is still living with the fallout on his mind in his last appearance in Journeys End, where its clear from the moment that he returns to the Enterprise that he is unsettled with his role in Starfleet Academy and wants a new challenge. His potential remains unfulfilled, until he joins up with The Traveler, who wishes to mentor him and provide the answers that he needs to decide his future. For too long he has been following in his fathers shoes instead of taking his own path in life, and The Traveler gives him the chance to do just that with an entire universe to explore. In the case of Journeys End, the title feels like a misnomer. Instead of an ending, for Wesley Crusher, its the start of something new.

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Milo (he/him) is a critic from the UK who regularly reviews TV, movies and comics. You can find him on twitter at @Milo_AFC.

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The Evolution of Wesley Crusher - Star Trek

Dr. Pennell on the Evolution of Targeting HER2 in Lung Cancer – OncLive

Nathan A. Pennell, MD, PhD, discusses the evolution of targeting HER2 in lung cancer.

Nathan A. Pennell, MD, PhD,an associate professor in theDepartment of Medicine and director of the Lung Cancer Medical Oncology Program at theTaussig Cancer Institute of Cleveland Clinic,discusses the evolution of targeting HER2 in lung cancer.

HER2 is a target that has been around for a long time because it is used routinely in the treatment of patients with breast cancer, says Pennell. In lung cancer, it has beenrecognizedthatHER2mutations in the HER2 tyrosine kinase domain have been present in the disease for a long time; roughly2% of lung adenocarcinomas haveHER2mutations, adds Pennell.

Unfortunately, thecurrent data on targeting HER2 haveproven to bedisappointing, according to Pennell. TKIs that target EGFR and HER2, such as afatinib (Gilotrif), have had trials,but have demonstrated relatively marginal efficacy and an effect that is short lived. However, that seems to have changed recently with the emergence of the antibody-drug conjugates (ADCs).

ADCs have shown demonstrated promising efficacy in phase 2 trials withHER2-mutant lung cancer. Over the past few years,sometrials examining these agents in lung cancer have been presented at medical meetings.For example, findings froma phase 2 trialwithado-trastuzumab emtansine (Kadcyla; T-DM1) were reported,and this agent is already available for useinHER2-positive breast cancer.The agentwas examinedina cohort of patients withHER2-mutant lung cancerandwas found to elicit an impressive overall response rate of44%with a promising duration of control, says Pennell. This agent was probably used off label for HER2-positive lung cancer after these data were presented, Pennell adds.

Then, an oral presentation was delivered during the2020 ASCO Virtual Scientific Meetingon the phase 2 DESTINY-Lung01trial, which evaluated the ADC fam-trastuzumab deruxtecan-nxki (Enhertu) inHER2-mutated lung cancer. The agent showed an impressive response rate of 61.9%, which is comparable with what is expectedwith otherEGFR inhibitors inEGFR-mutant lung cancer.Trastuzumab deruxtecan also hadan estimated progression-free survival of 14 months. For the first time,the field is starting to see targeted drugs for this patient population that mirror targeted drugs that have been developed for other molecular alterations in lung cancer, concludes Pennell.

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Dr. Pennell on the Evolution of Targeting HER2 in Lung Cancer - OncLive

‘A villain of the times’: The evolution of Zozobra – KOAT New Mexico

Old Man Gloom is 96 years old and he still looks great. But he never looks the same. Each year he grows taller, wears new clothes or has a different hair style. The evolution of Old Man Gloom is ever changing.Hes one of the most notorious characters in New Mexico. You can call him a chameleon of the times. I feel in love with the guy. I would say he was my first boyfriend, said Zozobra Deputy Event Chair Judith Moir.Black and white photos show Zozobra in the early years and key points in our history. As the years go on, Old Man Gloom becomes the monsters we need him to be. He becomes the villain of America. All the planning and design for Zozobra is done around the decade of his history, said Moir.In 1982, the marionette has buttons along his top and a black belt. Then two years later, in 1984, he ditched some of his buttons for a bow tie, which would become his iconic look in the years to come. Then in 1985 and 1986, Old Man Gloom had orange hair.Then the '90s Zozobra rocked yellow locks along with his bow tie. Fast forward to the early 2000s. Old Man Zoom donned several looks. The easiest change to see was his hair, from white to purple to orange. Other than the fact that has gotten bigger, I think the biggest change that we have done was in 2014, we added the decades project, said Moir.The decades project starts with the 1920s and is a way to highlight each decade as we get closer to Old Man Glooms 100th birthday. He was a snidely whiplash guy with a big mustache. Then we moved on to the '30s. He was old, bald and fat because that was the depression era. Zozobra had a little white hair left on this head and one button on his top.Then came 2016. The '40s we have the WWII era. That was a really big deal for us. That was really important because we were able to mark the 75th anniversary of the holocaust, said Moir. The marionette was dressed for the occasion with his double-breasted top, a fedora and a black tie.Part of the decades project is to teach kids about their past, not just Zozobra's past but what happened in New Mexico, what happened in the world, said Moir. That same year, the night before the event, a candlelight vigil was held to pay tribute to the victims and survivors of the Holocaust. Then in 2017, it was all about honoring the '50s. He was wearing a cardigan sweater and I would like to say he was father knows worst, instead of father knows best, said Moir. Zozobra had red hair to match his red nails.Then came the '60s. We really rolled out the entire hippie era 3:42 he tried to give the peace sign, but because he is Zozobra he really couldn't do that, said Moir.2018 was all groovy baby, with staff dressed in tie-dye as Old Man Gloom wore a bolo tie and had silver hair.Then last year, in 2019, disco was out to play. Coming in at 50 feet, 6 inches tall, it was all about the John Travolta look. Zozobra wore a white suit, gold medallion and blonde hair. His eyes were the memorable avocado green color and his lips were burnt orange. That was the first time his lips have changed color.2020 2 was slated to take us back to the '80s, but that is on hold until next year. Event organizers want this years focus to be the coronavirus. Zozobra will not wear a mask. Instead this show will honor first responders like our health care workers. The big question is, what will them marionette look like? His gray hair will take on the look of the virus itself, with orange pingpong balls and red hair scrunchies. His cuff-links will resemble murder hornets and they will be dipped in gold to bring out his formal attire. Last but not least, the buttons on his jacket will be stamped with the year 2020.

Old Man Gloom is 96 years old and he still looks great. But he never looks the same. Each year he grows taller, wears new clothes or has a different hair style. The evolution of Old Man Gloom is ever changing.

Hes one of the most notorious characters in New Mexico. You can call him a chameleon of the times. I feel in love with the guy. I would say he was my first boyfriend, said Zozobra Deputy Event Chair Judith Moir.

Black and white photos show Zozobra in the early years and key points in our history. As the years go on, Old Man Gloom becomes the monsters we need him to be. He becomes the villain of America. All the planning and design for Zozobra is done around the decade of his history, said Moir.

In 1982, the marionette has buttons along his top and a black belt. Then two years later, in 1984, he ditched some of his buttons for a bow tie, which would become his iconic look in the years to come. Then in 1985 and 1986, Old Man Gloom had orange hair.

Then the '90s Zozobra rocked yellow locks along with his bow tie. Fast forward to the early 2000s. Old Man Zoom donned several looks. The easiest change to see was his hair, from white to purple to orange. Other than the fact that has gotten bigger, I think the biggest change that we have done was in 2014, we added the decades project, said Moir.

The decades project starts with the 1920s and is a way to highlight each decade as we get closer to Old Man Glooms 100th birthday. He was a snidely whiplash guy with a big mustache. Then we moved on to the '30s. He was old, bald and fat because that was the depression era. Zozobra had a little white hair left on this head and one button on his top.

Then came 2016. The '40s we have the WWII era. That was a really big deal for us. That was really important because we were able to mark the 75th anniversary of the holocaust, said Moir. The marionette was dressed for the occasion with his double-breasted top, a fedora and a black tie.

Part of the decades project is to teach kids about their past, not just Zozobra's past but what happened in New Mexico, what happened in the world, said Moir. That same year, the night before the event, a candlelight vigil was held to pay tribute to the victims and survivors of the Holocaust.

Then in 2017, it was all about honoring the '50s. He was wearing a cardigan sweater and I would like to say he was father knows worst, instead of father knows best, said Moir. Zozobra had red hair to match his red nails.

Then came the '60s. We really rolled out the entire hippie era 3:42 he tried to give the peace sign, but because he is Zozobra he really couldn't do that, said Moir.

2018 was all groovy baby, with staff dressed in tie-dye as Old Man Gloom wore a bolo tie and had silver hair.

Then last year, in 2019, disco was out to play. Coming in at 50 feet, 6 inches tall, it was all about the John Travolta look. Zozobra wore a white suit, gold medallion and blonde hair. His eyes were the memorable avocado green color and his lips were burnt orange. That was the first time his lips have changed color.

2020 2 was slated to take us back to the '80s, but that is on hold until next year. Event organizers want this years focus to be the coronavirus. Zozobra will not wear a mask. Instead this show will honor first responders like our health care workers.

The big question is, what will them marionette look like? His gray hair will take on the look of the virus itself, with orange pingpong balls and red hair scrunchies. His cuff-links will resemble murder hornets and they will be dipped in gold to bring out his formal attire. Last but not least, the buttons on his jacket will be stamped with the year 2020.

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'A villain of the times': The evolution of Zozobra - KOAT New Mexico

Teachers Day 2020: An Evolution in the teaching techniques and opportunity for the personal growth of the teachers – The Financial Express

By Rajeev Tiwari and Anurag Gupta

COVID19 has unexpectedly led to a tough time for People, Companies, Businesses across the globe. But it is just another test of the strong resoluteness and unwavering attitude of human beings of not losing the hope even in the most adverse times, and a testimonial to the firm desire in our quest to find a tangible working solution in the most adverse conditions. If simply put, it is an eye opener for the world to see how mankind can stay strong even during the worst of times and walk towards the path of light when all they can find is darkness.

COVID19 has proven once again that the Teacher Community can fight all odds so as to deliver the best in class teaching methodology to their beloved students. They are willing to walk that extra mile to ensure that their students dont suffer a loss even during a situation which has led half the world into trauma. So first of all, a Grand Salute to every Teacher in the World.

In India, around March-April 2020 every student, parents were worried that how the education of the students will proceed in these tough times, but the Teaching community was very quick to adopt a blend of Digital Technologies and give it a personalized touch so as to deliver the best in class education to the students. They made sure they adapted all the necessary strategies and techniques which would not only be helpful for the students but also be a method that can be followed even when things turn normal. Teaching online is one of the techniques, that not every teacher was accustomed with, but learned during the pandemic only to provide the best of education to their students.

In these tough times, Digital Technologies that have proved very useful-

1. Conducting Online Classes via Zoom, MS Team, Google Meet

2. Online Virtual Class environment Lot of companies in EdTech space like Google Class, ClomoLMS, etc have come with Integrated Solution to offer End to Solution Covering Attendance Tracking, Lessons, Assignment, Quizzes, Gradebook and offering End to Online Class Delivery along with tracking students progress like in a normal offline mode.

3. Conducting Webinar and Tech Capsules Online to students, teachers so as to give an exposure to new trends to the stakeholders via an Interactive Webinar and Panel Discussions.

All these offer a great opportunity to teachers for their own personal growth and a new learning path that extends a possibility of adopting the best of Digital Technologies for Education Delivery, Using AI and Analytics to track down the growth of the students and offer a data based Career Progression Path and at the same time integrating it with apersonal touch, ethos, compassion, wisdom and ethics of a great Teacher.

(The authors are Founder at STEMROBO and Tinker Coders, Views expressed are their own.)

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Teachers Day 2020: An Evolution in the teaching techniques and opportunity for the personal growth of the teachers - The Financial Express

World Ultrasound Market Analysis and Forecasts 2020-2025 with Company Evolution Matrix and Company Profiles – Yahoo Finance

DUBLIN, Sept. 4, 2020 /PRNewswire/ -- The "Ultrasound Market by Technology (Diagnostic (2D, 3D, Doppler), Therapeutic (HIFU, ESWL)), Display (Color, B&W), Portability (Trolley, Compact, POC), Applications (Gynecology, Urology, Cardiology, Orthopedic), End user (Hospitals) - Global Forecasts to 2025" report has been added to ResearchAndMarkets.com's offering.

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The ultrasound market is projected to reach USD 8.2 billion by 2025 from USD 6.1 billion in 2020, at a CAGR of 6.1% during the forecast period. Growth of the market is mainly attributed to the technological advancements; increasing incidences of target diseases; rising patient preference for minimally invasive procedures; and growing public and private investments, funding, and grants are driving the growth of the global ultrasound market. However, stringent government regulations may restrict the growth of this market to a certain extent in the coming years.

Therapeutic ultrasound technology segment to register significant growth, during the forecast period.

On the basis of technology, the ultrasound market is segmented into diagnostic ultrasound and therapeutic ultrasound devices. The therapeutic ultrasound segment is expected to grow at a significant rate over the forecast period. Therapeutic ultrasound technologies include focused ultrasound and shockwave lithotripsy. The growth of this market is driven mainly by ongoing technological innovations in the field of focused ultrasound as well as the expansion of its application horizons.

The color ultrasound devices segment is expected to witness the highest growth in the ultrasound market, by device display, during the forecast period.

On the basis of the device display, the ultrasound market is segmented into black & white ultrasound and color ultrasound devices. The color ultrasound devices segment is expected to grow at the highest CAGR during the forecast period owing to the benefits offered by these devices, such as better image quality and higher image resolution. Also, the growing availability of advanced color ultrasound devices, coupled with the continuous decline in product cost across major countries and expanding distribution networks of major manufacturers across emerging countries, are expected to support the growth of this market segment during the forecast period.

The trolley/cart-based ultrasound systems segment is expected to account for the largest share of the ultrasound market, by system portability.

Based on system portability, the ultrasound market is segmented into trolley/cart-based ultrasound systems, compact/handheld ultrasound systems, and point-of-care (PoC) ultrasound systems. In 2019, the trolley/cart-based ultrasound systems segment is expected to account for the largest market share due to the growing adoption of these systems across major markets (as a result of their increasing use in emergency care and acute care settings in hospitals and healthcare institutions).

Asia Pacific market is expected to grow at the highest CAGR during the forecast period.

The Asia Pacific market is estimated to grow at the highest CAGR during the forecast period majorly due to the increasing healthcare expenditure across the region's major countries (especially India and China), growing public awareness about the therapeutic potential of ultrasound technologies, a continuous decrease in device costs (due to growing localized manufacturing and the presence of global market players), rising prevalence of target diseases, and the ongoing trend of device miniaturization.

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Key Topics Covered:

1 Introduction

2 Research Methodology

3 Executive Summary

4 Premium Insights

5 Market Overview

6 Ultrasound Market, by Technology

7 Ultrasound Market, by Device Display

8 Ultrasound Market, by System Portability

9 Ultrasound Market, by Application

10 Ultrasound Market, by End User

11 Ultrasound Market, by Region

12 Competitive Landscape

13 Company Evolution Matrix and Company Profiles

For more information about this report visit https://www.researchandmarkets.com/r/25w2b4

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World Ultrasound Market Analysis and Forecasts 2020-2025 with Company Evolution Matrix and Company Profiles - Yahoo Finance

Entertainment Evolution: What’s Happening to Content Due to COVID-19 (Part 1) – Disruptive Competition Project

Much of the content, industries, and people we enjoy watching has been upended by the COVID-19 pandemic. Live entertainment such as sporting events, concerts, and festivals has been particularly impacted. Among many negative impacts to the music industry, the most noticeable has been the cancellation of concerts and festivals worldwide. And sports, an industry that goes hand-in-hand with live entertainment, are struggling to maintain their 2020 seasons under the weight of the pandemic. This post is the first in a two-part series covering the shifts in entertainment due to COVID-19.

The music industry is experiencing massive upheaval due to COVID-19; everything from cancelled live concerts and festivals to delayed album releases, instrument and equipment sales, and the volume of music released has been affected. However, as most music festivals have been cancelled, many artists are pursuing live music through streaming events. Many creators are utilizing popular digital services as a means of holding virtual concerts. Artists, small and large alike, are performing live through services such as Instagram, YouTube, and Twitch. BTS, a K-pop group popular throughout the world, hosted Bang Bang Con: The Live in June, a live hour and a half online concert which received over 750,000 viewers across 107 countries and territories. And Fortnite partnered with Travis Scott this past April to hold Astronomical, a series of live in-game events centered around Travis Scotts music with multiple tour dates for players around the world to participate. Epic Games (the creator of Fortnite) reported that 27 million unique players participated in the Travis Scott event live 45 million times. More recently, a webcast series called Verzuz which pits artists against each other live on Instagram and allows the audience to vote on the winner, has garnered attention.

While the first major income stream for the music industry is live music, the second is recorded music, which includes streaming, digital downloads, licensing of music for movies, games, TV and advertising, and more. Many of these revenue streams have not been as negatively affected. In fact, streaming music now makes up nearly half of global recorded music revenue. However, the Coronavirus has altered how people are listening to music and as festivals and concerts are only just returning (some as an experiment in determining how the virus spreads), on-demand consumption of music is on the rise. Spotify recently reported that the daily habits of its consumers have shifted. Many bands and individual creators are utilizing popular digital services as a means of releasing their new music. Famously, Lil Nas X first uploaded the tune to Old Town Road on TikTok. Individuals are making more music than ever before and many services are playing host to these new creations. Further emphasizing the streaming and on-demand opportunities in the music industry, Amazon just expanded its music service by integrating Twitch live streams, which has seen rapid growth from musicians moving to the platform. Spotify appears to be following suit and developing a virtual events section as well.

Live professional sports have also experienced setbacks due to the Coronavirus, many of which paused or cancelled their seasons earlier this year. However, some sports at the collegiate and professional levels are attempting to make a comeback. While the Big Ten and PAC-12 have both decided to postpone their competitions through the end of this calendar year, the AAC, SEC, and Big 12 have yet to alter their plans. The NHL petitioned Canada to host their teams and hold their post season tournament up north. The MLB is also reportedly considering a playoff bubble similar to the NHL. While the MLS resumed play in a bubble with the MLS is Back Tournament, its actually set to become the first major North American sports league to try to hold games with fans in the stands. The MLS recently announced the continuation of the season, allowing teams to play back in their home markets with limited capacity for fans in the stadium. The NCAA had to cancel March Madness this year; however, the NBA has had success with their bubble and resumed their season July 30. The U.S. Open was live-streamed in August without fans. Additionally, the 2020 INDY 500 was watchable and streamable live and had no fans in the stands. While increased vigilance and heightened safety guidelines will likely continue for some time, sports as live entertainment are returning.

Live streaming video game services are also seeing growth due to the upward trend of the industry as a whole. And some sports are even turning to e-sports as a way to give consumers the sporting entertainment they want in one form or another. NASCAR recently embraced e-sports and in March Fox Sports said it would stream the full season of NASCARs virtual race series. Further, while the pandemic has forced the cancellation or postponement of certain e-sport events, e-sports as a whole is actually gaining notoriety as a result of this pandemic. Global e-sports revenue is expected to grow just beyond $1 billion by 2020 and live streaming is key to that growth.

After experiencing the disruption to their previous standards of business that COVID-19 has brought about, many individuals, businesses, and organizations have been forced to alter their practices to continue to operate through the changes wrought by the pandemic. However, even throughout the Coronavirus, one thing remains clear: live entertainment has gone digital and its still highly attractive. The next post in this series will discuss movies, television, and video games.

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Entertainment Evolution: What's Happening to Content Due to COVID-19 (Part 1) - Disruptive Competition Project

Ball Hill: The evolution of Coventry’s busiest shopping street – Coventry Live

Walsgrave Road, known locally as Ball Hill, was at one point a bustling centre for shopping, serving the residents of Stoke and Wyken for years.

Ask any local taxi driver to take you to Ball Hill and they'll know where to go.

Many Coventrians will have memories of picking up a bargain in Stardust or getting a slap up breakfast at the Rosebud cafe, or even queuing up outside Britton's sport shop for the latest CCFC strip.

Many of those shops are still there and Ball Hill remains a busy stretch, serving as one of the city's major bus routes.

But as Covid-19 put a stop to much of the footfall that once inhabited our region's high streets, how has Ball Hill fared? Have there been any shop closures and what do locals think?

Here's what happened when we paid a visit.

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We visited Ball Hill on a busy Thursday lunchtime, just as the sun arrived. A feeling of familiarity crept in as we queued up to the main junction to access the shopping area, most commuters into Coventry will have sat in a traffic jam on this stretch.

As we parked the car and wandered up to the top of the hill, families and couples milled about doing their shopping, and a huge queue snaked up to the high street from the bank.

We start at the top of the hill and head into Ade's plaza salon, a hair and beauty supplier who has had to diversify so she can keep her shop open.

Owner Ade Osunwe said: "Everyone is afraid. It is not easy, we are just trying to cope, it was busier before lockdown."

Her shop has been open since 2015, but it was only post-lockdown that she had to widen her offering from hair and beauty to general goods so that she could attract a bigger customer base.

The shelves groan as containers of peanuts and milk powder sit next to wigs and curl cream. Ms Osunwe said: "The rent on this high street is expensive. Everyone is shopping online now - the Government need to think of us.

"I have four children and we are not on benefits - how will we survive?"

We head across the road to the key and shoe repair shop, which current owner Dave Oates informed us has operated in this capacity for more than 80 years.

Mr Oates, who has owned the shop for five years, said: "The last three weeks have been really good, with students coming back landlords often come to me to get their keys cut."

And how has the shop recovered as shoppers have returned? "We do have regular customers and walk-ins, when we started [the shop] there were key cutters and shoe repairs everywhere, but slowly it's become a dying trade" he said.

Mr Oates said that trade just hasn't been the same since Covid-19, and despite the last few weeks "going back to normal", they were twice as busy last September.

As we continue down the hill, some of the businesses have their shutters rolled down and some have permanently closed like the Age UK charity shop.

A sign in the window read: "As this shop has permanently closed, please do not leave any donations outside this shop, thank you."

The was an incredibly popular spot for avid bargain hunters, at one point selling clothes for 99p, but it did not make it out of the Covid-19 lockdown.

A few doors down there is an empty unit where the once popular Boss Shoes stood. The family-ran shoe shop, which had been in the city for 32 years and had a warehouse in Tile Hill, closed at the start of the year.

A couple of hundred yards further down, we pop into the indoor arcade which houses a barber shop, butcher's shop, sweet shop and key cutters among others.

At the centre of Ball Hill is Coventry's Music Museum - a treasure trove of music history and with its very own 2-Tone village, it was voted one of the best museums in the Midlands on TripAdvisor a few years ago.

We finish off at Fiveways Fish Bar, on the corner of the busy Brays Lane and Clay Lane junction. The popular chippy has been in the area for 25 years and was closed for six weeks at the height of the Covid-19 pandemic.

Owner Mr Singh, who owns another chip shop locally, said that things have not returned to normal in the area. "It is definitely quieter, before the street was very busy. We are still busy at lunchtime, everywhere is the same," he said.

The area sits across the Upper Stoke ward and Lower Stoke ward. Public Health England 2017 data shows this part of the city to have just over 17,682 residents. The age group with the most people in is 25-64 and the smallest age group is the those aged over 85.

We asked local residents what they thought of the area and if they had any memories.

Martin Winstanley said: "1980. 269, Walsgrave Road. Bargain Bathrooms in between Stardust and The Rosebud Cafe. They did the best Polish sausage mash and cabbage! I worked selling bathrooms as a Saturday job. Great memories!"

Another resident added: "We live just by where youre standing - on Marlborough Road - it was fantastic to be able to shop during the Covid-19 lockdown, many of the independents really were a lifeline!"

Look: memories of Ball Hill over the years

Despite some of the local favourites closing down over this past year, Ball Hill remains a bit of an anomaly, with many of the independent businesses still standing, managing to trade over generations.

It is perhaps the only road in Coventry where you can get a fry up, order new blinds and do your weekly shop as you wait for your tyres to be fitted.

Things may have changed over the years, but one thing that is certain is that Ball Hill will never be quiet.

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Ball Hill: The evolution of Coventry's busiest shopping street - Coventry Live

Evolutionary theory of economic decisions | Stanford News – Stanford University News

Making decisions in the face of uncertainty has never been easy. But the global pandemic has raised the stakes for many previously mundane choices: how to travel, where to get food, when to send kids back to school.

A decision to keep a mixed herd of highly productive goats and drought tolerant camels may help a household survive rare but severe water shortages, even if it doesnt maximize long-term accumulation of wealth. (Image credit: iStock)

Understanding how humans have made high-stakes decisions over evolutionary time may help to explain our choices in the present day including our tendency to veer from the preferences predicted by economic models, according to a new study from scholars at Stanford University and the Santa Fe Institute.

Rather than starting with utility the happiness or value I get out of making my decision now lets think about how the brain was constructed over evolutionary history, said study co-author James Holland Jones, a biological anthropologist at Stanfords School of Earth, Energy & Environmental Sciences (Stanford Earth). The research was published in the journal Evolutionary Human Sciences.

The pairs proposal adds a new perspective to long-running scholarly debates over why practices designed to improve the standard of living among subsistence populations dont take hold, such as the seemingly slow adoption of new farming technologies among poor, small-scale farmers, and more recently, the unwillingness of the poorest poor to adopt microfinance and other development schemes.

There is an inclination to think of the poorest people as being natural entrepreneurs because they have nothing to lose economically, Jones explained. However, the evolutionary logic we employ suggests that the poorest poor have everything to lose and are, in fact, closer to losing it than better-off people. Our model predicts that very poor people would be especially risk-averse.

It also points to the weakness of lean systems in the face of uncommon but severe threats, such as the coronavirus. One of the things were seeing right now is a world that has been optimized for efficiency and is extremely vulnerable to risk, he said. If you scale back organizations to keep them running at a mean level thats high, and you dont have a lot of slack, when a crisis hits youre in trouble.

According to the theory of expected utility, a staple of modern economics, people should always carefully weigh the likelihood of an event along with the prizes or consequences that would accrue from our decision and then choose the option with the highest average payoff. Of course, we rarely calculate these averages in practice, as behavioral economists have long recognized. Yet an assumption that our brains will behave as if we made decisions this way maximizing personal gain at every turn is still baked into many public and economic policies.

We might expect evolutionary systems to mirror markets, with organisms that act rationally out-competing those not behaving rationally, said Jones, an associate professor of Earth system science at Stanford Earth and a senior fellow at the Stanford Woods Institute for the Environment. The catch is that you cant outcompete something if youre extinct.

In addition to influencing policy, business and financial markets, theories of how we make decisions have filtered into popular culture through books like Nudge and Thinking Fast and Slow. However, they tend to deal poorly with choices that humans have faced for the vast majority of their history on Earth namely, those shaped not by market forces, but by environmental variables like temperature or rainfall. In this context, boom times cant compensate for a single lethal bust. Just one bad heat wave, drought, cold snap or flood can leave a household hungry or worse. Variance is what drives you to extinction, Jones said.

As a result, when it comes to preferences that evolve by natural selection, he said, we should expect to see people undervalue long shots that could be profitable, play it safe when things look risky and generally overestimate the likelihood of rare bad outcomes.

On the timescale of evolution, the salient outcome of a decision is how it contributes to fitness, meaning the proportion of the population through time that carries your DNA. Unlike utility, fitness is a measure that multiplies over time. If any generation in your lineage has zero offspring in it, its game over, Jones said. It is a general aversion to zeros that leads to pessimism.

At the same time, fitness plays out over such long timescales that it cant directly influence our behavior. The things that do shape our choices day to day are more like utility in that they can rise and fall without bringing catastrophe. Psychological mechanisms, like satiety or sexual gratification, or something like love of your children, can motivate you in the immediate. They promote fitness in the long run, but they are not the thing actually being maximized over time, he said.

Maximizing fitness leads us to be more pessimistic in our economic decisions than utility models predict. The optimal level of pessimism to promote survival depends on the exact universe the organism occupies, the authors write. For example, hunters targeting rare, big game may stand to bring home more calories if they succeed, but their household could go hungry if they fail. Herders have to weigh not only the productivity of their animals, but also their susceptibility to drought and disease.

Any time where you have to avoid zero, pessimism will pay off, because youd rather leave money on the table than run the risk of going extinct, Jones said.

When social distancing restrictions loosen enough to conduct group experiments, Jones and co-author Michael Price, PhD 15, who studies complex systems as a fellow at the Santa Fe Institute, plan to test their theory with games challenging participants to maximize payoffs that multiply over time or that are hidden but associated with some tangible proxy. By formalizing and eventually testing the theory, the researchers write, they hope to stimulate more work on the possible evolutionary foundations of key results from behavioral economics.

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Evolutionary theory of economic decisions | Stanford News - Stanford University News

US Teachers Evolving on Science of Evolution – T.H.E. Journal

Science Education

Asurvey done in 2007 found that only a third of public high schoolbiology teachers were able to present the subject of evolution in away that satisfied national science experts. And 13 percent ofteachers offered creationism as a "valid scientific alternative"to evolution.

Twelveyears later, teaching practices related to evolution are much better,according to arecently published report.The researchers found "substantial reductions" increationist instruction and a "substantial increase" in thetime that high school teachers devote to human evolution and theevolutionary process in general. The findings were published in thejournal Evolution:Education and Outreach.The researchers came from PennState Universityand the NationalCenter for Science Education.

Whythe uptake in more scientifically astute instruction? The researcherspointed to three changes:

Broad adoption of the Next Generation Science Standards or state standards that borrow heavily from NGSS;

Improvements in pre-service teacher education; and

Changing practices of in-service teachers through improved professional development.

Theproject analyzed data from the "Survey of American ScienceTeachers" which was done between February and May 2019. Whilethe survey included both high school and middle school samples, thisreport relied on high school responses, in particular.

Inboth surveys more than 95 percent of high school biology teachersreported covering evolution to some degree. But there was a 60percent increase in the average number of class hours devoted tohuman evolution in the 2019 survey, an increase from 4.1 hours to 7.7hours.

Also,there was "considerable movement" in how teachers respondedto a question asking them whether they "emphasize the broadconsensus that evolution is a fact, even as scientists disagree aboutthe specific mechanisms through which evolution occurred." Theshare of teachers who disagreed with that statement declined from 22percent to 13 percent, and the percentage who agreed grew from 74percent to 79 percent. Those who "strongly agreed" rosefrom 30 percent to 47 percent.

Theproportion of teachers who reported discussing creationism andintelligent design in classes dropped from 23 percent to 14 percent.And where it was discussed, the researchers pointed out, "someteachers may raise the topic of creationism in the context ofexplaining why it is not scientific." To understand responsesbetter, the survey included two additional questions:

"I emphasize that intelligent design is a valid, scientific alternative to Darwinian explanations for the origin of species"; and

"I emphasize that many reputable scientists view creationism or intelligent design as valid alternatives to Darwinian theory."

Thenumber of teachers disagreeing with the first statement rose from 32percent to 58 percent, a change "largely driven by a sharp dropin the number of teachers who declined to answer this question,"from 53 percent to 29 percent. And there was a big increase "inthe percentage of teachers strongly disagreeing with each statement."The researchers interpreted that to mean that "more teachers areconfident in their acceptance of evolution and rejection ofcreationism."

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US Teachers Evolving on Science of Evolution - T.H.E. Journal

Minnesota Football: The evolution of the slot cornerback – The Daily Gopher

What is a slot cornerback?

First of all, it is important to establish that under defensive coordinator Joe Rossi the Gopher defense has operated out of a base 4-2-5 formation. That means four defensive linemen, two linebackers, and five defensive backs. Here is a typical look:

Fresno State is in a four wide receiver set, so the Gophers have Coney Durr and Terell Smith as their outside corners, with Chris Williamson in at slot corner on the wide side of the field and safety Jordan Howden providing help over the top. Antoine Winfield Jr. is playing center field as the free safety. Thomas Barber and Kamal Martin are your linebackers, with the more athletic Martin split out to cover the inside receiver on the short side of the hash. The four defensive linemen are Winston DeLattiboudere, Micah Dew-Treadway, Sam Renner, and Carter Coughlin.

Why the 4-2-5? The formation, which is also referred to as the nickel defense, was championed in the 21st century as the answer to the spread offense. TCU head coach Gary Patterson is perhaps the schemes most renowned innovator, having originally utilized it to counter power running teams before evolving it to defend the prolific up-tempo offenses of the Big 12.

I wont get too much into the weeds on the nuances of the 4-2-5 Google Gary Patterson, 4-2-5 for ample supplemental reading but the foundational tenet of the scheme is to flood the field with speed. Athleticism is emphasized over size, even at defensive end, where fleet-footed outside linebackers have been converted into undersized rush ends who can cause problems for slower offensive tackles. Its an aggressive style of defense, one in which the goal is to use mismatches up front to generate pressure, attack gaps, and spill the ball to the perimeter.

The proliferation of the 4-2-5 has seen the role of the nickelback evolve from backup third cornerback to one of the most versatile defenders in modern football. Today, slot corners need be able to blitz the quarterback as pass rushers, step up in the run game as linebackers, and hold their own in coverage as defensive backs. Thats a lot to ask of one player.

Chris Williamson, a transfer from Florida, made the slot corner position his home in his two seasons at Minnesota. He became such a critical part of the Gophers defense that I am more concerned about how Joe Rossi will replace his production than I am about filling the shoes of All-American safety Antoine Winfield Jr.

Seriously.

One of the challenges of playing slot corner is that the slot receiver position is no longer relegated to lesser pass catchers. Teams top targets in the passing game are lining up inside more than ever before. That puts a lot of pressure on slot corners, who are already in a precarious position due to their alignment. They dont have the benefit of using the sideline as leverage or squeezing receivers into the boundary. Slot corners have to play both an inside and outside release. With more area to cover, one false step could spell doom.

Which brings me to a fourth down play against Penn State. On 4th and Goal at the 5, the Nittany Lions lined up in trips formation with three wide receivers on the wide side of the field, and KJ Hamler was in the slot with tight end Pat Freiermuth. Freiermuth ran a slant to try and disrupt the defenders in coverage as Hamler ran a fade to the corner of the end zone. But Williamson reads the route, breaks on Hamlers hip, turns his head, and bats the ball out of bounds.

But as I mentioned previously, pass coverage is only one part of the position.

The slot cornerback also needs to be able to play close to the line of scrimmage, almost functioning as a third linebacker at times. Not every nickel corner who can hold their own in pass coverage is also a reliable tackler. You have to be physical and able to make tackles in space.

Williamson and Justus Harris were relied upon heavily against Georgia Southern last season, both operating out of the slot corner position but playing near the line of scrimmage to help stifle the Eagles option offense in run support. The pair helped limit Georgia Southern to 123 rushing yards (well below their season average of 253.2 yards per game).

Here, Williamson comes in from across the formation to drop the ball carrier for a minimal gain on third down after Thomas Barber whiffs on the tackle.

Last but not least, rushing the passer. On this second down play against Fresno State, Joe Rossi gets creative. DeLattiboudere takes the right tackle upfield and Thomas Barber blitzes, occupying both the right guard and the running back in pass protection. Williamson, sprinting in from his slot corner position, runs through an opening so big that he never even breaks stride en route to the sack. Coughlin is following close behind, ready to take a crack at the quarterback if Williamson cant finish the play, but he requires no such assistance.

Senior Justus Harris is the most experienced slot corner on the roster, but his game action has been limited mostly to special teams. Redshirt freshman Solomon Brown and incoming freshman Jalen Glaze are both expected to compete with Harris at slot corner, but the lack of a clear successor to Williamson is a concern. Williamson was an unsung hero of the defense last season, and replacing his production will be no small task.

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Minnesota Football: The evolution of the slot cornerback - The Daily Gopher

Rapid and robust evolution of collateral sensitivity in Pseudomonas aeruginosa antibiotic-resistant mutants – Science Advances

INTRODUCTION

Antibiotic effectiveness, currently compromised by the spread of antibiotic resistance (AR), requires not only innovation but also conservation, which may allow for improved use of current antibiotics (1). For this conservation, understanding of the trade-offs associated with AR acquisitionsuch as increased susceptibility to a second drug after use of the first, a phenomenon first described in the 1950s as collateral sensitivity (2)might be particularly relevant. Various studies have been undertaken trying to exploit the evolutionary constraint imposed by collateral sensitivity patterns (3, 4), such as combinatory therapy (5, 6) or alternating collaterally susceptible drug pairs (79).

Despite progress in study of the collateral sensitivity phenomenon, some questions remain to be answered. In particular, there is still only limited information on the evolutionary conservation of collateral sensitivity patterns, not only between different species (10, 11) but also within different members from the same species (1215). In the case of Pseudomonas aeruginosa, some studies have revealed that isolates of this pathogen obtained from patients with chronic infections and treated with distinct antibiotic classes present convergence in their collateral sensitivity phenotypes (9), while others have described major differences in the collateral sensitivity patterns associated with the acquisition of resistance to one antibiotic between replicates of the same strain of P. aeruginosa evolving in parallel (13). These discrepancies may lie in the degree of reproducibility of the evolutionary pathways leading to AR. In this respect, it is known that the type of resistance mutations present in a given genetic background may be restricted because of epistatic interactions (10, 1621) and that the cumulative acquisition of AR mutations in different loci reduces the variety of pathways, leading to AR (22, 23). Since contingency may be relevant not only for AR evolution but also for the acquired collateral sensitivity phenotype (24), knowing the degree of conservation of collateral sensitivity patterns associated with the use of a specific drug in different genetic backgrounds, particularly in the case of mutants already presenting a phenotype of AR, is of special interest.

In a previous study, we observed that P. aeruginosa PA14 populations experimentally evolved in the presence of ceftazidime displayed a robust collateral sensitivity to amikacin (25), as a consequence of selection of large chromosomal deletions upon 1 day of adaptive laboratory evolution (ALE) (25). The chromosomal deletions included hmgA, which encodes an enzyme whose lack of activity leads to the hyperproduction of the brown pigment pyomelanin (26); galU, whose inactivation reduces ceftazidime susceptibility (27); and mexXY, which encodes a multidrug resistance (MDR) efflux pump that contributes to P. aeruginosa intrinsic aminoglycosides resistance (28). Up to 13% of patients with cystic fibrosis (CF) are infected by P. aeruginosa pyomelanin-producing mutants (29) that, in agreement with the phenotype of the mutants selected after ALEs, are also hypersusceptible to aminoglycosides (30). Although the fact that pyomelanin increases resistance to oxidative stress and favors bacterial persistence in chronic lung infections (26) has been considered the most likely explanation for in vivo selection of those mutants, this genetic event has also been reported in different strains of P. aeruginosa subjected to ALE in the presence of other -lactams (3134). Therefore, it remains to be established whether these deletions are selected by the antibiotic treatment or merely represent an adaptation to the lung environment of patients with CF (35), as was previously proposed (34, 35). Even further, it remains to be answered whether these deletions are selected upon ceftazidime treatment in different genetic backgrounds of P. aeruginosa, in particular, in mutants resistant to other antibiotics; or on the contrary, whether the evolutionary robustness of this genetic event, and of its phenotypic effects, is limited. In this study, by constructing a set of resistant mutants previously identified in different ALE experiments of P. aeruginosa PA14 (16, 36) in the presence of antibiotics, and by submitting them, as well as the wild-type PA14 strain, to ALE in the presence of ceftazidime, we have determined the robustness of an early event of ceftazidime resistance evolution that is associated with collateral sensitivity to tobramycin. Further, by the recreation of heterogeneous pyomelanogenic populations belonging to each genetic background and the alternation of tobramycin with ceftazidime, we found that driving evolution toward hypersusceptibility to the first drug is generally feasible, at least in the genetic backgrounds analyzed. This finding supports the possibility of rationally designing treatments based on collateral sensitivity convergence in P. aeruginosa.

As mentioned above, the conservation of collateral sensitivity to a given drug within different genetic backgrounds of a species may be contingent on the degree of conservation of the evolutionary routes toward resistance to the first drug used for selection. We and others have reported the early selection of large chromosomal deletions that contain genes encoding the intrinsic aminoglycosides resistance efflux pump MexXY (28), when ALE experiments in the presence of different -lactams, including ceftazidime (31), piperacillin (32), or meropenem (33, 34), were performed. These data suggest that this genetic event could be one of the first evolutionary steps in the evolution of P. aeruginosa toward -lactam resistance. However, since these studies were limited to a single wild-type genetic background, it remained to be analyzed whether a similar evolutionary pattern could be followed by P. aeruginosa PA14 strains presenting different genetic backgrounds, in particular, different antibiotic-resistant mutants. That being so, collateral sensitivity to aminoglycosides, such as tobramycin, a drug that forms part of usual therapy regimens against P. aeruginosa (37), would also be conserved.

Our first objective was to analyze the evolutionary conservation of ceftazidime resistance evolution in different genetic backgrounds, consisting of mutants derived from different P. aeruginosa PA14 ALEs in the presence of antibiotics (see table S1). It has been recently suggested that AR mutations may associate with either robust or variable collateral sensitivity patterns in different genetic backgrounds, depending on whether they lead to target or regulatory alterations, respectively (10). Taking this hypothesis into account and resorting to previous different in-house ALE experiments (16, 36), we constructed a broad spectrum of strains containing single mutations that affect regulatory proteins (NfxB, ParR, or MexZ), nonregulatory proteins (NuoD or OrfN), or simultaneously containing both types of mutations. The mutant containing mutations in nfxB, phoQ, frr, and pmrB was dubbed MDR6, and the mutant containing mutations in fusA, orfN, pmrB, mexZ, gabP, ptsP, and nuoD was dubbed MDR12 (see table S1 for detailed information). The susceptibility of each mutant to different antibiotics, including those of interest in this studytobramycin and ceftazidimeis shown in Table 1.

MICs 2-fold of the MICs for the wild-type PA14 strain are highlighted in bold. TOB, tobramycin; TGC, tigecycline; CAZ, ceftazidime; CIP, ciprofloxacin; IPM, imipenem.

To determine whether chromosomal deletions containing mexXY would be early selected during P. aeruginosa evolution in presence of ceftazidime in the set of mutants mentioned above, as it was the case in the wild-type strain PA14 (25), four biological replicates of each single (nfxB177, parR87, mexZ43, orfN50, and nuoD184) and multiple mutants (MDR6 and MDR12), and the wild-type PA14 strain, were subjected to ALE in presence or absence of ceftazidime (a total of 64 populations) for 3 days. Upon 1 day of experimental evolution, almost every P. aeruginosa population challenged with antibiotic hyperproduced pyomelanin (27 of 32 populations; Fig. 1A). This result is consistent with the presence of deletions that include hmgA, as those described in our previous study, because pyomelanin accumulation is due to the lack of homogentisate 1,2-dioxygenase activity provided by HmgA (26). Since we had previously determined a cause-effect relationship between the presence of chromosomal deletions containing hmgA and mexXY and the hyperproduction of pyomelanin and hypersusceptibility to aminoglycosides, respectively (25), the susceptibility of each final population to tobramycin was analyzed. All the pyomelanogenic populations obtained after the short-term evolution in presence of ceftazidime were resistant to ceftazidime and hypersusceptible to tobramycin, when compared to the parental strain from which they evolved (Fig. 1B and table S2), even when the mutants were originally less susceptible to tobramycin than the wild-type P. aeruginosa PA14 strain. In particular, tobramycin minimal inhibitory concentration (MIC) was reduced by up to 4-fold in PA14, 2.6-fold in nfxB177, 3-fold in parR87, 7.9-fold in orfN50, 6-fold in mexZ43, 5.3-fold in MDR6, and 10.7-fold in MDR12. Consistent with the linkage between pyomelanin production and deletion of a chromosomal region containing mexXY, nonpyomelanogenic populations (parR87, replicate 1; and nuoD184, all replicates) were not tobramycin hypersusceptible (Fig. 1B and table S2). Further analysis of the results from the experimental evolution study has revealed that six of eight genetic backgrounds presented a significantly (P < 0.01 in all cases) reduced MIC to tobramycin, compared to their parental strains, after the ceftazidime short-term evolution. To further analyze whether chromosomal deletions containing mexXY could be associated with the phenotype of hypersusceptibility, every evolved population, as well as their original parental strain, was genotyped (fig. S1A). A 163-bp polymerase chain reaction (PCR) fragment corresponding to mexXY was detected in every parental strain, as well as in nonpyomelanogenic populations (parR87, replicate 1; and nuoD184, all replicates) and in a pyomelanogenic mixed population (PA14, replicate 2). Consistent with the observed increase in tobramycin susceptibility of most evolved populations (table S2), every pyomelanogenic tobramycin-hypersusceptible population lacked mexXY (fig. S1A). Overall, these results suggest that chromosomal deletions containing mexXY are consistently selected at first steps of ceftazidime resistance evolution in P. aeruginosa, at least in the genetic backgrounds analyzed. To further test whether this observation could be conditioned by the number of replicates used during the assay for each genetic background, 32 replicates of one of the mutants (mexZ43) were subjected to evolution under the same conditions used before, in presence or absence of ceftazidime. We observed that upon 1 day of experimental evolution, a high number of mexZ43 populations challenged with antibiotic hyperproduced pyomelanin (28 of 32 populations; Fig. 1D), just 4 of 32 populations did not become pyomelanogenic (Fig. 1D). Although we are aware that there is a space for unpredictability of ceftazidime resistance evolution in the mutants analyzed, the results here described suggest that alternative genetic evolutionary trajectories in ceftazidime resistance evolution may be limited, and that phenotypic convergence toward collateral sensitivity to tobramycin is robust in P. aeruginosa, even in the case of antibiotic-resistant mutants, as those here analyzed (table S1), after ceftazidime treatment (table S2). However, we are fully aware that all mutants described here derive from P. aeruginosa PA14, and the generalization of our results to other strains will require the analysis of the effect of short-term ceftazidime evolution on a broad and diverse set of clinical strains of P. aeruginosa.

(A) Scheme of the resultant phenotype after the evolution of PA14, single (nfxB177, parR87, mexZ43, orfN50, and nuoD184) and multiple (MDR6 and MDR12) mutants, in the presence of CAZ [left part of (A)] or in the absence of antibiotic [LB; right part of (A)] for 3 days (see Materials and Methods). Pyomelanin hyperproduction was observed in 27 of 32 populations evolved in the presence of CAZ (red-colored cells). (B) Diagram showing convergence toward hypersusceptibility to TOB in the different genetic backgrounds and replicates, analyzed after short-term evolution on CAZ. In all cases, acquisition of a pyomelanogenic phenotype is associated with collateral sensitivity to TOB, irrespective of the genetic background of the evolving strain. MIC values of TOB and CAZ are included in table S2. (C) Isolation of pyomelanogenic clones from each 27 pyomelanogenic population [left part of (A); red-colored cells] obtained in the presence of CAZ. As shown in the figure, the early steps of evolution in presence of CAZ of P. aeruginosa, which lead to collateral sensitivity to TOB and pyomelanin production, are conserved among the different antibiotic-resistant mutants analyzed. (D) Pyomelanogenic phenotype of mexZ43 mutant after 1-day evolution in the presence of CAZ or in the absence of antibiotic (LB). Pyomelanin hyperproduction was observed in 28 of 32 populations evolved on CAZ. Photo credits for (C) and (D): Ins Poveda, Centro Nacional de Biotecnologa. Permission for using these images is not required.

We have shown that ceftazidime selects, in the short term, pyomelanogenic mutants presenting collateral sensitivity to tobramycin in P. aeruginosa, at least in the set of resistant mutants analyzed here (table S1). Nevertheless, there is an extensive heterogeneity within populations of P. aeruginosa in the CF lungs (38), frequently including mutants already presenting a pyomelanogenic phenotype (29, 30), which is usually associated with a reduced susceptibility to ceftazidime. Since this heterogeneity might impair the chances of exploiting the observed tobramycin collateral sensitivity associated with the use of ceftazidime in these heterogeneous populations, we tested the possibility of alternating the antibiotics, first, by using tobramycin and then second, ceftazidime, for reducing the chances of pyomelanogenic heterogeneous populations to escape from the antibiotic challenge.

The strategy would consist of three stages: A first step on tobramycin may force extinction of the ceftazidime-resistant (tobramycin-hypersusceptible) part of the populations, a second step on ceftazidime may drive evolution toward tobramycin hypersusceptibility, and then the extinction of the tobramycin-hypersusceptible cells after switching back to tobramycin (Fig. 2) would be expected. Although this strategy would be also potentially applicable to populations not resistant to ceftazidime, being reduced to a first step on ceftazidime followed by a second one on tobramycin, we decided to analyze its effectiveness in a more complex situation of clinical relevance, as it is the case of heterogeneous pyomelanogenic populations. In particular, diverse populations derived from the set of mutants were analyzed in this work (see table S1). To that end, we isolated a pyomelanogenic clone from each of the 27 pyomelanogenic populations obtained after ceftazidime short-term evolution (Fig. 1A). To note here that although the original clones from which these populations were derived belonged to a diverse set of genetic backgrounds, consisting of antibiotic-resistant mutants that contain mutations in regulatory, nonregulatory, or both types of proteins (Table 1 and table S1), all the isolated clones that hyperproduced pyomelanin (Fig. 1C) were significantly (P < 0.001 in all cases) more susceptible to tobramycin than their respective parental strain (table S3), and lacked mexXY (fig. S1B). Then, we recreated a total of 27 heterogeneous pyomelanogenic populations by mixing each of the 27 pyomelanogenic clones with its respective parental strain in a 1:1 ratio. The heterogeneous populations were dubbed PA14 +1 to +4, nfxB177 +1 to +4, parR87 +2 to +4, mexZ43 +1 to +4, orfN50 +1 to +4, MDR6 +1 to +4, and MDR12 +1 to +4. These populations were first subjected to tobramycin short-term evolution for 3 days (see Materials and Methods), and the capacity of these populations to either evolve toward tobramycin resistance or to go extinct was analyzed (Fig. 3). Since pyomelanogenic clones are less susceptible to ceftazidime (i.e., >256 g/ml in all the parR87 clones; see b data in table S4) than the parental strain from which they evolved (1 g/ml in parR87; see a data in table S4), ceftazidime MIC values were used to verify the extinction of the pyomelanogenic part of each population. After 3 days of evolution in the presence of tobramycin, the ceftazidime MICs for every population (i.e., 1 g/ml in parR87 heterogeneous populations; see the First step (TOB) data in table S4) were close to the ceftazidime MIC for the parental strain [compare First Step (TOB) to the a and b MIC data in table S4]. These data support that the pyomelanogenic part of every population is extinct after the first step of sequential evolution. To further confirm the extinction of the pyomelanogenic clones, the phenotype (green/yellow versus brown color) of 20 clones from each of the 27 populations, a total of 540 clones, were isolated and grown in liquid medium (brown color is poorly appreciated in colonies) to detect any escape of ceftazidime-resistant cells from tobramycin treatment. As shown in Fig. 3B, none of the clones produced pyomelanin, confirming the extinction of the pyomelanogenic part of every population, a fact that was previously hinted by the ceftazidime MIC values of the resultant populations (see table S4). Besides that, each resultant population presented an increased tobramycin MIC, up to 48-fold, depending on the genetic background and replicate (table S4).

Evolution of a heterogeneous population containing a pyomelanogenic (CAZ resistant) subpopulation starts when TOB is added at time zero (t0). In the presence of TOB, there is an extinction of TOB-hypersusceptible pyomelanogenic mutants (red-colored cells) and TOB becomes ineffective (t1). Then, treatment is switched to CAZ, and TOB-resistant cells (contoured gray-colored cells) become TOB-hypersusceptible (t2). Treatment would be switched back to TOB, resulting in the elimination of TOB-hypersusceptible cells (t3). This strategy would also be potentially applicable to initial populations not resistant to CAZ (t1), being reduced to a first step on CAZ (leading to t2), followed by a second step on TOB (resulting in t3).

(A) Diagram showing the evolution of heterogeneous populations (dubbed +1, +2, +3, and +4) containing each parental strain: PA14, nfxB177, parR87, mexZ43, orfN50, MDR6, or MDR12 and four individual pyomelanogenic clones belonging to the same genetic background, during first step of sequential evolution in the presence of TOB (left) and second step in the presence of CAZ (right), for 6 days (see Materials and Methods). In the case of parR87, only three pyomelanogenic clones from independent CAZ-evolved populations (see Fig. 1, A and C) could be isolated. Hypersusceptibility to TOB (contoured and noncontoured red-colored cells) is observed in 23 of 27 populations (see table S4), and pyomelanin production (noncontoured red-colored cells) is observed in 17 of 27 populations. (B) Analysis of extinction of the pyomelanogenic part of the heterogeneous pyomelanogenic populations after a first step of sequential evolution in the presence of TOB [(A) section, left]. The phenotype (color) of 20 clones isolated from each heterogeneous population, after 3 days of TOB evolution, was observed in liquid medium and compared with the color (brown) of each pyomelanogenic parental strain (upper left corner of each plate). In agreement with data shown in table S4, which points to the extinction of pyomelanogenic populations by comparison of CAZ MIC value of each heterogeneous population with the ones of their parental strains and pyomelanogenic clones, the color of the 540 clones analyzed indicated that pyomelanogenic clones were extinct after first step of sequential evolution on TOB. Photo credits for (B): Fernando Sanz-Garca, Centro Nacional de Biotecnologa.

At this point, we specifically focused on the switch from tobramycin to ceftazidime, the second step of the sequential evolution (Fig. 2). Although we had observed conservation of tobramycin collateral sensitivity after evolution in presence of ceftazidime within the analyzed set of mutants of P. aeruginosa (Fig. 1 and table S2), a critical point would be to determine whether this genetic event would also be selected by ceftazidime in the tobramycin-resistant mutants obtained after the first step of evolution of the populations in the presence of tobramycin. Hence, we switched the selective pressure from tobramycin to ceftazidime (see Materials and Methods). As shown in Fig. 3, 17 of 27 populations hyperproduced pyomelanin. A second critical point emerged here: The degree of sensitization to tobramycin of highly resistant mutants to the said antibiotic was uncertain. To determine whether these populations presented an increased susceptibility to tobramycin, as it was observed in the wild-type PA14 background and in most of mutants analyzed in this work (Fig. 1 and table S2), the tobramycin MIC was determined in all the evolved populations. Twenty-three of 27 populations presented an important increase in their sensitivity to tobramycin after switching the selective pressure from tobramycin to ceftazidime, reducing the MIC by up to 128-fold in PA14, 48-fold in nfxB177, 21-fold in parR87, 96-fold in orfN50, 43-fold in mexZ43, 4-fold in MDR6, and 11-fold in MDR12 (Fig. 4 and table S4). This analysis revealed that five of seven heterogeneous pyomelanogenic populations presented a substantially reduced MIC to tobramycin after the second step of sequential evolution on ceftazidime (table S4). These results suggest that it could be possible to exploit the tobramycin collateral sensitivity associated with the use of ceftazidime by switching back selective pressure to tobramycin, although there may be some limitations depending on the genetic background. This was the case of the multiple resistant mutants MDR6 and MDR12, which did not present a relevant reduction in tobramycin MIC after the switch to ceftazidime.

Evolution of TOB MICs (g/ml) of heterogeneous pyomelanogenic populations after sequential evolution on TOB/CAZ (see Fig. 3). Each plot shows the TOB MIC values for a parental strain (PA14, parR87, orfN50, nfxB177, mexZ43, MDR6, or MDR12), indicated as t0 in the x axis, and for four heterogeneous pyomelanogenic populations (represented as black circles) after first evolution on TOB (indicated as TOB in the x axis), followed by second evolution on CAZ (indicated as CAZ in the x axis). Only three heterogeneous pyomelanogenic populations of parR87 were analyzed. TOB MICs decreased after switching from TOB to CAZ by up to 128-fold in PA14, 48-fold in nfxB177, 21-fold in parR87, 96-fold in orfN50, 43-fold in mexZ43, 4-fold in MDR6, and 11-fold in MDR12. MIC values are shown in table S4.

The fact that some populations were hypersusceptible to tobramycin, even without having suffered chromosomal deletions containing mexXY (6 of 27 populations; Fig. 3 and fig. S1C) or being mixed populations (4 of 27 populations; Fig. 3 and fig. S1C), indicates that reciprocal collateral sensitivity between ceftazidime and tobramycin may occur even in the absence of these deletions, a feature that remains to be explored in detail. Overall, our results indicate that this strategy could potentially be applicable from complex situations similar to the ones explored in the current work (heterogeneous pyomelanogenic ceftazidime-resistant populations) to other ones (populations not resistant to ceftazidime).

We have recently described that P. aeruginosa replicate populations subjected to ribosome-targeting antibiotics may present common changes in the susceptibility to other antibiotics, besides those used along selection (16, 36). However, important differences have been described in the collateral sensitivity phenotype among replicate populations of the same P. aeruginosa strain adapted to one antibiotic (13). We have recently reported that a loss-of-function mutant of P. aeruginosa PA14, differing from its parental strain in the activity of just one regulator, not directly linked to AR, presents different patterns of collateral sensitivity and cross-resistance phenotype when it acquires resistance to ribosome-targeting antibiotics (16). Since historical contingency may restrict the evolution of collateral sensitivity and cross-resistance phenotypic outcomes, we wondered whether the populations obtained after tobramycin and ceftazidime sequential evolution, besides presenting a convergent hypersusceptibility to tobramycin, may converge toward the phenotypes of cross-resistance or collateral sensitivity to antibiotics found in other structural families. To address this question, the MICs of a set of antibiotics were determined for the 27 populations. A general pattern of cross-resistance to aztreonam, imipenem, and chloramphenicol, as well as significant collateral sensitivity to fosfomycin, tobramycin, and tetracycline, was observed (P < 0.0001 in all cases) (Fig. 5 and table S5). Since the combination fosfomycin-tobramycin has been found to be synergistic against biofilms of CF P. aeruginosa strains (39) and against P. aeruginosa PAO1 in anaerobic environments (40), we propose that the switch back to tobramycin (Fig. 2) could also be replaced, if necessary, by the combination fosfomycin-tobramycin. To analyze the relative efficacy of the two possible options, we subjected the resultant populations obtained after tobramycin/ceftazidime sequential evolution to ALE in either tobramycin or the combination fosfomycin-tobramycin, applying twice the MIC of each parental strain. We observed that 8 of 27 populations were able to escape from the switch back to tobramycin (orfN50 +3, mexZ43 +2 and +3, MDR6 +1 and +3, and MDR12 +2 to +4). This result agrees with the fact that although most of the populations (23 of 27) presented an important reduction in the tobramycin MIC after sequential evolution on tobramycin and ceftazidime, by up to 128-fold in PA14, 48-fold in nfxB177, 21-fold in parR87, 96-fold in orfN50, 43-fold in mexZ43, 4-fold in MDR6, and 11-fold in MDR12 (Fig. 4), tobramycin MIC values were close to those of parental strains. None of the populations survived the combination fosfomycin-tobramycin, possibly due to the synergistic effect of these antibiotics (39). We therefore propose that use of the fosfomycin-tobramycin combination is more effective than switching back to tobramycin after that treatment.

Collateral sensitivity and cross-resistance to antibiotics from different structural families were analyzed in the 27 populations obtained after sequential evolution. A population is classified as susceptible or resistant when there was an MIC change with respect to the parental strain value. Triangles indicate antibiotics where a predominant change toward resistance (red) or susceptibility (green) with respect to the parental strain was observed. Thickness of the triangle depends on the percentage of conservation of said phenotype. MIC values (g/ml) are included in table S5. AMK, amikacin; ATM, aztreonam; FOF, fosfomycin; ERY, erythromycin; CHL, chloramphenicol; LEV, levofloxacin; TET, tetracycline.

Bacterial evolution is known to be one of the main causes of the current AR problem; but in-depth analysis of this evolution could also help to tackle this issue through the exploitation of the evolutionary trade-offs (as collateral sensitivity) associated with AR acquisition (2, 4). However, the feasibility of this approach requires the collateral sensitivity phenotypes of different resistant mutants to be robust and reproducible (41). In this study, we describe the robustness of collateral sensitivity to tobramycin associated with the short-term use of ceftazidime in an array of P. aeruginosa antibiotic-resistant mutants, chosen on the basis of their differences both in resistance phenotype and in the functions affected by the mutations that they harbor. We propose that the observed evolutionary trade-offs could be exploited for treating both clonal and heterogeneous pyomelanogenic infections. Patients with CF are usually infected by heterogeneous P. aeruginosa populations (38) that include pyomelanogenic mutants (29, 30), which frequently present resistance to -lactams, a feature that could compromise the use of ceftazidime. However, we have found that it is possible to drive the extinction of the pyomelanogenic mutants, first, by using tobramycin and then second, by driving the evolution of the remaining population toward tobramycin hypersusceptibility, using ceftazidime. A bottleneck for the application of this strategy would be the durability over time of tobramycin hypersusceptibility. However, it is important to highlight that the populations obtained after tobramycin/ceftazidime alternation present also collateral sensitivity to fosfomycin. We observed that it is possible to replace the switch back to tobramycin by a fosfomycin-tobramycin combination, which results in higher efficacy. These results point to the possibility of exploiting specific evolutionary trade-offs for tackling the problem of AR. However, we are aware that a detailed analysis determining the degree of conservation of the short-term ceftazidime resistance evolution in a broad and diverse set of clinical strains of P. aeruginosa would be required. Overall, our results and those of others, previously described (41) suggest that the analysis of phenotypic convergence and, in particular, the aspects that deal with the collateral sensitivity of P. aeruginosa AR mutants, is an important step forward in the rational design of therapeutic approaches capable of reducing the AR burden.

Bacteria were grown in LB at 37C, with shaking at 250 rpm in glass tubes. MICs of ceftazidime, aztreonam, imipenem, tobramycin, amikacin, tigecycline, tetracycline, ciprofloxacin, levofloxacin, chloramphenicol, fosfomycin, and erythromycin were determined at 37C in Mueller-Hinton (MH) agar, using E-test strips (MIC Test Strip, Liofilchem).

Four single mutants of P. aeruginosa (nfxB177, parR87, mexZ43, and nuoD184) were constructed by inserting each mutant allele (table S1) by homologous recombination into the wild-type PA14, while the orfN50 single mutant was previously obtained (16). Mutant alleles were obtained by PCR from previous in-house evolved populations (16, 36), leaving approximately 500 bp upstream and downstream the corresponding single-nucleotide polymorphism, using the oligonucleotides described in table S6. PCR products containing Hind III restriction sites were cloned into the Hind IIIdigested and dephosphorylated pEX18Ap vector (42) and then introduced by transformation into the conjugative Escherichia coli S17-1 strain. Subsequently, conjugation and mutant selection were performed, as described elsewhere (42), using carbenicillin (350 g/ml) and 10% sucrose. In all cases, the presence of the mutations was confirmed by Sanger sequencing. To obtain mutants containing multiple mutations, 10 independent resistant clones from end point evolved populations (16) on tobramycin or tigecycline were selected and mutations confirmed by Sanger sequencing. From them, two multiple mutants (table S1), tobramycin or tigecycline resistant, respectively, were chosen. The mutant allele of lasR was replaced by homologous recombination with that of the wild type in the two selected clones, using the above-described strategy and oligonucleotides encompassed in table S6.

Five single mutants, two multiple mutants, and PA14, four replicates of each, were subjected to short-term ALE in presence or absence of ceftazidime, resulting in a total of 64 independent bacterial populations (32 populations grown in presence of ceftazidime and 32 control populations grown without antibiotic). Cultures were grown at 37C and 250 rpm for 3 days. Every day, the cultures were diluted (1/125), adding 8 l of bacteria in 1 ml of fresh LB, either containing or lacking ceftazidime at the concentration that hinders the growth of each P. aeruginosa genetic background under these culture conditions (4 g/ml for PA14, mexZ43, and MDR12; 5 g/ml for nfxB177, orfN50, and MDR6; 3 g/ml for parR87; and 2 g/ml for nuoD184). During the 3 days, the concentration of ceftazidime was maintained. Every replicate population was preserved at 80C at the end of the experimental evolution. In addition, the MIC of the antibiotic used for selection in populations (ceftazidime) and of the one to which ceftazidime evolution gives rise to collateral sensitivity (tobramycin), was determined at 37C in MH agar using E-test strips.

Pyomelanogenic clones were isolated from every individual pyomelanogenic replicate population of each genetic background previously submitted to short-term evolution in the presence of ceftazidime, resulting in a total of 27 pyomelanogenic clones (see above). Overnight bacterial cultures from each pyomelanogenic clone and its parental strain were normalized to an optical density at 600 nm of 4.0 and then mixed in a 1:1 (pyomelanogenic clone:parental strain) ratio, obtaining 27 heterogeneous populations. Cultures were grown at 37C and 250 rpm for 6 days. Every day, during the first 3 days, the cultures were diluted (1/125) in fresh LB containing the tobramycin concentration that hinders the growth of each P. aeruginosa genetic background under these culture conditions (1 g/ml for PA14; 1.5 g/ml for nfxB177, parR87, mexZ43, and MDR6; 4 g/ml for orfN50; and 12 g/ml for MDR12). During the 3 days, the concentration of tobramycin was maintained. At the end of the first step of sequential experimental evolution, every replicate population was preserved at 80C, and the MIC of ceftazidime and tobramycin was determined at 37C in MH agar using E-test strips. The 27 populations were grown, from glycerol stocks, and every day, during the last 3 days, the cultures were diluted (1/125) in fresh LB containing ceftazidime, as described in the above-mentioned section of Material and Methods (see the Short-term ALE in presence of ceftazidime section). Every final population was preserved at 80C at the end of the second step of sequential experimental evolution, and the MIC of tobramycin was determined at 37C in MH agar using E-test strips.

The presence of chromosomal deletions including mexXY in the different genetic backgrounds and their respective evolved populations was analyzed by determining the absence of a 163-bp PCR fragment belonging to mexXY in 2% agarose gel. Primers used for mexXY genotyping are included in table S6.

Data were subjected to pre hoc and post hoc analyses to identify relevant differences, using either analysis of variance (ANOVA), Friedmans, or 2 tests and Dunnetts or Fishers exact test with Hochberg correction, as implemented in R.

Acknowledgments: We thank J. Ramn Valverde, from the Servicio de Computacin Cientfica del CNB, for the helpful discussion and the assistance with the manuscript, and I. Poveda, from the Servicio de Fotografa del CNB, for the photograph support. Funding: This work was supported by the Instituto de Salud Carlos III (grant number RD16/0016/0011), cofinanced by the European Development Regional Fund A Way to Achieve Europe, by grant S2017/BMD-3691 InGEMICS-CM, funded by Comunidad de Madrid (Spain) and European Structural and Investment Funds and by the Spanish Ministry of Economy and Competitivity (BIO2017-83128-R). F.S.-G. is the recipient of a FPU fellowship from MINECO. Author contributions: S.H.-A. participated in the design of the study and performed experimental work, and F.S.-G. performed experimental work. J.L.M. participated in the design of the study. All authors participated in writing the manuscript and approved the submitted version. Competing interests: All authors declare that they have no competing interests. Data and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Additional data related to this paper may be requested from the authors.

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Rapid and robust evolution of collateral sensitivity in Pseudomonas aeruginosa antibiotic-resistant mutants - Science Advances

The evolution of Extinction Rebellion | Environment – The Guardian

In November 2017, Roger Hallam looked up from his cup of tea in a central London cafe and made a bold prediction. He had been walking me through the principles behind a new air pollution campaign he was organising, which involved small groups of activists blocking some of Londons busiest junctions, when he paused, mid-sentence. Of course, this is just small-scale stuff compared to what is coming, Hallam said. The scale of the ecological crisis is a different thing. It is going to change everything.

The air pollution campaign, Stop Killing Londoners, had yet to gain traction with politicians or the media, but Hallam didnt seem too concerned. He explained that it was partly being used to road-test civil disobedience tactics. Within a year or so we will have thousands of people on the streets, blocking large parts of central London for days on end, he said. Hundreds will be arrested and the government will be forced to sit down and tell the truth about the climate emergency.

It seemed fanciful at the time. Hallam, a charismatic, committed and sometimes divisive figure, was splitting his time between his organic farm in Wales and Kings College London, where he was researching a PhD about political activism. Earlier that year, he had staged a hunger strike, which led Kings College to divest from fossil fuels. Despite this recent victory, and an air of certainty that would become familiar to those who dealt with him in the months to come, there was still little to suggest Hallams predictions would come to pass almost word for word within 18 months. Nothing he had been involved in before had achieved the kind of impact that he was now prophesying. The movement that would carry out these protests, Extinction Rebellion (XR), didnt yet exist.

Extinction Rebellion, which would be founded a few months later, was the brainchild of a small group of activists, academics and friends, including Hallam, and Gail Bradbrook, a similarly unorthodox environmentalist. The daughter of a coal miner from South Elmsall in Yorkshire, Bradbrook studied for a PhD in molecular biophysics before working on various social justice campaigns, such as tax justice and the Occupy movement. But by 2016, disillusioned by how little political progress these groups had made, Bradbrook came to the conclusion that she was missing vital information about how to bring about meaningful change. There was something else that nagged at her, too an awareness of something deeper inside her that needed addressing. (In conversation, Bradbrook moves easily between detailed analysis of the latest climate science and organisational theory to discussions of spirituality. She often holds prayer sessions before meetings.)

In March 2016, Bradbrook travelled to Costa Rica in search of enlightenment. There, in a story that has become part of XR lore, she took a series of powerful psychedelic drugs. The most fucking terrifying thing I have done in my entire life, she told me later. But I was willing to do it because I needed help. Before the hallucinogenic trip began, she offered up a prayer to be shown the codes for social change. Those words would have a key role to play in the emergence of XR.

A few months after she returned to the UK, Bradbrook met Hallam for the first time. Their initial conversation lasted four hours Hallam complained that he had a headache by the end as they discussed the unfolding environmental crisis, the inability of the current system to even recognise the oncoming chaos, and theories about how to transform politics. As Hallam stood up and prepared to leave, he half-jokingly told Bradbrook that the ideas he had laid out about how to transform society were the codes she needed. The hairs on the back of my neck stood up, Bradbrook said later. It was exactly the phrase I had used during my prayer in Costa Rica.

Over the coming months, Bradbrook and Hallam continued their conversations, along with a loose grouping of like-minded people, who eventually formed Rising Up, a network of activists committed to peaceful civil disobedience. It wasnt until April 2018 that, in Bradbrooks home on a hillside overlooking the Cotswold town of Stroud, the idea of Extinction Rebellion was born. At the Stroud meeting, as it has become known, a core group of about 15 long-time campaigners, activists and academics decided that after years of small-scale political campaigns, about everything from fracking to migrant rights, they were, in Bradbrooks words, ready to go for the big one. As another of those present, Simon Bramwell, who was Bradbrooks partner at the time, recalled later: It was [then] that we decided to go for broke. We decided to throw all of our energy and intelligence at something that could change the planet.

But before such grand aims could be achieved, there were more mundane tasks. Agreeing on a name for the new group turned into a 25-step process that went on for weeks. It was an absolute mission, said Clare Farrell, another XR co-founder, who has a background in sustainable fashion and design. When Extinction Rebellion was first suggested, Farrell recalled that there was quite a bit of disquiet, because some people thought it was too harsh. But eventually it won.

According to Bradbrook, the group quickly realised it needed to appeal beyond what she called the leftist echo chamber. The campaign would aim not only to tap into progressive concerns about social justice and equality, but also traditionally conservative themes such as national security and protecting family. XRs goals were boiled down to three demands of the government: to tell the truth about the climate and ecological emergency; to halt biodiversity loss and commit to net zero emissions by 2025; and to follow the lead of a citizens assembly. A presentation titled Heading for Extinction and What to Do About It was developed, and quickly became known as the talk. It starkly outlined the scale of the crisis and the dire consequences of inaction, as well as XRs belief that if enough ordinary people took to the streets for peaceful civil disobedience, then radical change was possible.

Then came the hard work of building a movement from scratch in just a few months. Farrell remembers that those early meetings had a different atmosphere to other campaigns she had been involved in: It felt to me straight away like a group of people who were serious, who were very interested in how the system works and how to change it. She recalled the excitement of working with experts in so many different fields, from design to science, philosophy and politics. It was the breadth of the collaboration that was really fundamental.

Hallam told me at the time that they did not want it to simply be an online phenomenon, which he feared could flare up and then disappear again just as quickly. Instead, XR needed people to go out into their own communities, explain, recruit and then rebel. From the summer of 2018 onwards, volunteers began touring the country, giving the talk to people gathered in libraries and meeting halls, cafes and universities, pubs and churches. These meetings were sometimes tense affairs, as the scale of the climate crisis was laid out. But there was also a sense of relief among many of those present that their fears about the crisis were being acknowledged, and that they were being told there was something they could do.

On 31 October 2018, XR formally launched its campaign with a Declaration of Rebellion outside the Houses of Parliament. It had been billed as a small, symbolic act that would probably attract a couple of hundred people. In a taste of what was to come, more than 1,000 turned up and took a spontaneous decision to occupy the road outside parliament. The groups first big test came the following month, when it held a day-long demonstration aiming to block five bridges across the Thames in central London. On a beautiful winters day, thousands turned out, blocking the bridges and bringing chaos to central London in the biggest act of peaceful civil disobedience seen in London for decades.

Five months later, in April 2019, came the protest that the group had been working towards since its foundation. Thousands of people occupied key sites across London for almost two weeks. More than 1,000 were arrested for what were peaceful, respectful, sometimes joyful, protests. The arrests were a key part of XRs strategy, which drew particular inspiration from the civil rights movements in the US and Gandhis independence struggle in India. By encouraging as many protesters as possible to get themselves arrested, XRs plan devised chiefly by Hallam was to overwhelm the court system, with the aim of winning support and forcing change.

The protests turned XR into a movement of global significance, with scores of XR groups springing up in cities around the world, as well as in towns and cities across the UK. By the end, XRs representatives were sitting down for talks with senior politicians and ministers in the UK. Supporters and funders many of whom had been sceptical before April showered praise and money on the new movement, and in the weeks that followed, the UK parliament and scores of councils around the country declared a climate emergency. XR had changed the conversation around the crisis. Now it had a big question to answer: what next?

Within XR there was elation about the success of Aprils rebellion, as well as exhaustion and uncertainty about the future. A lot of these people had been involved in lots of would-be uprisings that they had hoped would take off but hadnt, so they were wary of pinning too much hope on this, said Daze Aghaji, a 20-year-old student and an early member of XR Youth, the influential youth wing of the movement. And then, when it did all come together, it was a bit like: Oh, OK what do we do now?

Hundreds of new people had come forward to join the movement in the weeks after the April protests, many of them giving up their jobs to dedicate themselves to XR full-time. This influx boosted XRs organisational capacity, but also brought new ideas about what the group should be, and competing theories about how to achieve the change needed to tackle the climate crisis.

Among the key figures to emerge during the April rebellion was Farhana Yamin. Her experience as a former UN lawyer who had helped draft the Paris agreement and worked on many of the key climate treaties of the past three decades enhanced XRs credibility, and she became one of the groups most convincing public advocates. Over lunch at a north London cafe a few months later, she told me she had joined XR after becoming disillusioned with her world of diplomacy, thinktanks and policymakers. I had been working with people who were not telling the truth about where we are, and are in a state of euphoric, egocentric denial, she told me. When she was asked to join XR, she agreed immediately. I saw [coverage of] the October rebellion, when people laid down and got arrested and Greta was there, and I thought: yes, that is what we need, that is what I want to do. It looked beautiful.

Amid all the praise for XRs achievements up to that point, there had also been some significant criticism. From the left, some argued that XRs beyond politics framing fatally overlooked the role that neoliberal capitalism, driven by the right, played in the ecological crisis exploiting people and natural resources, particularly in the global south, for the benefit of a wealthy minority. There was also growing criticism from black and ethnic minority groups, who said XRs tactic of encouraging mass arrests ignored the reality of police racism, and effectively made the protests the preserve of privileged white people.

Meanwhile, from the right, critics branded those involved in Extinction Rebellion variously as middle-class layabouts or drug-addled hippies, dangerous killjoys or extremist anarchists. During the April 2019 protests, Daily Mail headlines described the group as a radical far-Left eco-rabble and detailed how the Extinction Rebellion eco-mob plotted chaos in London from vegetarian caf in leafy market town. (XRs critics have left no cliche unmolested, wrote James Butler in the London Review of Books.)

After April, new recruits also had to be fitted into XRs decentralised structure, which includes an organising hub of circles, each with around a dozen or more individuals who focus on particular themes, from actions to finance, legal support to regenerative culture. On top of this, there are around 485 XR groups spread across more than 70 countries, with about 130 in the UK. There are also scores of affiliated groups based around shared identities, such as XR doctors, XR farmers or XR Muslims. People do not formally join XR, and there is no central membership list. Local groups can plan and carry out their own actions as long as they follow XRs 10 core principles and values, including a commitment to non-violence and focusing on systemic problems rather than blaming and shaming individuals.

Although XRs structure aims, as its website says, to build a participatory, decentralised and inclusive movement, some complain that it allows those with the loudest voices often white, middle-class men to dominate. Others complain of endless meetings, labyrinthine decision-making processes, and the sprawling network of WhatsApp groups the organisation has spawned.

According to Ronan McNern, a veteran of the Occupy movement and a key figure in XRs communications operations, the months after the April rebellion were dominated by internal wrangling. On one side were Hallam and his backers, who were pushing for an escalation in provocative direct action to keep the momentum going. They believed that a relatively small group of people, prepared to keep escalating their disruptive, peaceful, direct action could bring about systemic change quickly especially if the elite in the country are in terminal decline, as Hallam regularly insisted. On the other side were people who argued the good will and moral high ground achieved in April should be used to build a broader movement, within the UK and internationally.

An increasingly important voice in those discussions was XR Youth, a semi-autonomous group that had been created at the start of 2019. I felt pretty early on that as a young person I didnt really fit into main XR, said Aghaji. There was so much love of young people, but not in the right way. I would go to some things and everyone would be like, Do social media! Kids love social media! I was like, this is so sweet, but it is not where we need to be. Another founding member of XR Youth, Nils Agger, 26, who was also one of XRs original co-founders, agreed. I had been feeling for a while that there was something missing, there were just not that many people my own age.

From the start, XR Youth wanted to approach the climate crisis from a more international perspective, to highlight the role of activists in the global south, and to change the perception that this was a struggle for the future, rather than for the present. The message, said Aghaji, was save ourselves rather than save our grandchildren.

As the summer went on and internal disputes about XRs future grew more intense, the conflict came to a head over a proposed action to shut down Heathrow airport. Those in favour, including Hallam, wanted to fly drones within the Heathrow exclusion zone in order to bring the airport to a standstill for days. For others in XR, this represented a counterproductive step-change in the level of civil disobedience. They warned that there could be serious safety concerns, and a real risk that the public goodwill built up in April would be lost.

Towards the end of July, after a series of gruelling discussions, events took an unexpected turn. During a key strategy meeting in Stroud attended by Hallam, Bradbrook and other leading figures, there was a sudden commotion at the door. Aghaji, Agger and half a dozen members of XR youth had turned up, unannounced. Bearing cinnamon rolls with We Love You written in icing on top, they occupied the meeting and read out their three demands, one of which was that the Heathrow plans should not go ahead.

At first they were like: What are you doing coming in here demanding things? recalled Aghaji. But we were like: This is literally what you have taught us to do. Agger said it was a strange feeling, as one of XRs founders, to be occupying an XR meeting: It was us trying to make some kind of intervention in the way XR was working. Heathrow was just the tip of the iceberg. Another member of XR Youth made an emotional speech outlining their concerns. It was very emotionally charged, and very teary, Aghaji said. But, she added, it was a turning point.

A few days later, XR abandoned plans for the Heathrow protest and Bradbrook released a statement on behalf of XR, apologising for failing to address adult privilege within the group, and promising to heal the division and hurts between us. In early September, Hallam and a few others went on to attempt to close down Heathrow anyway, under the banner of a new organisation, Heathrow Pause. The protest, which had already drained so much of XRs energy, fell flat. No planes were stopped or delayed. Several participants were arrested, including Hallam who, after breaching bail conditions by returning to the airport after his initial detention, was subsequently remanded in custody.

In the weeks following the Heathrow protests, hundreds of people who had been arrested during the April rebellion began to appear before the courts. Zo Blackler, a journalist turned activist who oversaw the courts process for XR, said it was a reminder of what the movement was really about: We were presented in the media throughout April as being a young persons movement, or a crusties movement, or a white middle-class movement, or whatever it was that that particular newspaper hated about us. But to her, the hearings showed what those attacks had failed to acknowledge. It was an extraordinary experience to be there having that many people come together and read out their statements about why they had done what they had done. It was very moving. People were crying, and it felt very much as if the judges were listening and responding to what they were hearing. (Earlier this year, one judge said: This is going to be my last Extinction Rebellion trial for a little while. I think they only allow us to do so many of these before our sympathies start to overwhelm us.)

As XR headed towards its October Rebellion labelled internally as the difficult second album the euphoria of April had dissipated, but despite the splits and disputes, the movement had continued to grow, boasting hundreds of groups around the world. Less than 12 months after XRs launch, many were confident that the October rebellion would repeat, or even outdo, its previous success.

One crucial reason XR had risen so far so fast was timing. In the decade before it was founded, the climate movement in the UK had been relatively quiet. Before 2008, a vibrant activist network from Climate Camp, which saw protesters come together to carry out civil disobedience against major carbon emitters, to campaigns against the third runway at Heathrow and Kingsnorth power station had forced the climate crisis up the agenda. And these social movements were at least partially responsible for progress at a political level. In 2008, the Labour government brought in the Climate Change Act, the worlds first long-term, legally binding framework for radically reducing emissions, which committed the UK to an 80% emission reduction by 2050. Among many activists, there was at least some hope that the political class was beginning to grasp the enormity of the challenge ahead.

But when the financial crisis hit in 2008, the focus of politics, and protest, changed, as opposition to austerity became the most urgent concern for campaigning groups from Occupy to UK Uncut, the 2011 student protests to the Peoples Assembly. Paolo Gerbaudo, an academic at Kings College London who studies social movements and had been involved in environmental protests at the Copenhagen climate summit in 2009, said that before the financial crash, the climate emergency felt like the challenge of our time, but afterwards, it had largely slipped off the social and political agenda.

The unfolding ecological crisis, however, had not been put on hold. During the 2010s, evidence of climate breakdown rising temperatures, melting ice, failing harvests continued to mount. As the scientific warnings grew ever more dire, there was a deepening feeling among those who were paying attention that traditional environmental campaigning was failing, and that politicians were not delivering with potentially catastrophic consequences. It was into this context that XR emerged.

In the Autumn of 2018, just as XR launched, UN scientists at the Intergovernmental Panel on Climate Change published an unusually stark report, which warned world leaders that we had only 12 years to make radical changes and avoid the most devastating effects of the climate crisis. According to Blackler, the new movement managed to tap into this feeling of frustration and fear by acknowledging the scale of the crisis, and persuading people that collectively they had the power to change things. We gave people something they could come along to and plug into really easily, she said. XRs message was simple: civil disobedience could actually get results. People suddenly understood that although a few million on a march would achieve nothing, if you could get a comparatively small number to do civil disobedience, you can effect change much, much faster.

As XRs October 2019 rebellion approached, the scientific warnings were becoming, if anything, more dire. The school strike movement, led by Greta Thunberg, had mobilised hundreds of thousands of young people around the world, and public figures such as David Attenborough and Pope Francis were lining up to sound the alarm on the climate and ecological emergency. Everything seemed primed for a repeat of Aprils success.

In reality, it proved impossible to recreate the surprise and novelty that defined the earlier protests. Although XR held more sites in October and said it had more people arrested 1,837, compared with 1,138 in April the protests failed to catch the publics imagination in the same way. Actions that would have been headline news just six months earlier such as hundreds of breastfeeding mothers closing down Google HQ were now seen as par for the course by the media. Other factors also counted against XR. The weather was colder, and the days shorter. Police tactics were harsher and the UK was in the midst of Brexit convulsions.

XR was also criticised for tactical missteps. Early in the morning of 17 October, a number of protesters climbed on top of a tube train at Canning Town station in order to disrupt rush-hour services. Commuters reacted with anger, and scuffles broke out, with one protester being dragged from the roof of the train. The incident only lasted a few minutes, but the footage, which was widely shared, was damaging for XR, and highlighted some of the challenges facing the movement. How do you control what actions go ahead in a decentralised structure? Did the decision to carry out the protest highlight the lack of class and racial diversity within XR? Those who had decided to go ahead with the action did not seem to realise that by targeting the tube at that time of day, the people affected would not be bankers or financiers, but working-class Londoners, many on zero-hours contracts. Many observers also expressed bewilderment at the fact that climate protesters had chosen to target public transport at all.

The UK general election, which took place a couple of months later, was another flashpoint within XR. The Labour party offered a raft of policies to rapidly decarbonise the economy and invest in sustainable, well-paid, unionised jobs: its so-called green industrial revolution. For many people concerned about the climate crisis, this was a cause worth rallying behind. But during the election campaign, XR to the dismay of both Labour party activists and some inside the movement did not mobilise behind Labours climate offer, preferring instead to target all three main parties with hunger strikes and people dressed in bee costumes under the slogan Bee-yond politics. One irate XR figure called me to express her dismay at the group targeting Labour in the run-up to the election. There are some of us who have been in meetings all day really trying to stop this, she said. It is crazy, depressing, but we lost. It is going ahead.

The clash came down to two competing ideas about XRs ultimate purpose. For some, it was a vehicle to transform the political landscape, making it possible for existing institutions to put forward radical environmental policies. For others, the existing structures were incapable of overseeing the transition needed, and had to be overhauled and replaced. Reflecting on these tensions earlier in the year, one insider told me that XR had reached a point where the founders needed to take a step back: It is the classic startup or founder syndrome, where an organisation reaches a point where the founders need to let go and let something else emerge.

At the start of 2020, following Labours general election defeat and the relative letdown of its most recent rebellion, XR found itself at a crossroads. There was concern about the direction of travel, about how well we have managed to decentralise, Bradbrook told me. People [were] getting cross with each other and finger-pointing.

In February, XR released a new strategy document that appeared to move away from occupying and holding sites for days on end, instead emphasising targeted civil disobedience in cities around the country. Plans were announced for a rolling rebellion that would take place in London in May, targeting the underlying causes of the climate and ecological emergency government, media and finance.

Just a few weeks later, as the coronavirus pandemic began sweeping across the UK, the prospect of mass demonstrations receded and XRs plans had to be put on hold. The groups finances had been in a parlous state since October, and they had been hoping for an influx of donations during the May demonstrations. When they were cancelled, XR was forced to scale back its headquarters in London and stop all living allowance payments that had previously supported volunteers in need.

The crisis also had a profound impact on the movement in other ways, according to Blackler. There was a certain point when I remember thinking, Everyone in the country is thinking about their own mortality all the time, and it was such a strange moment, she said. But that is what we need people to be doing to be thinking about these big, existential issues and the mortality of our world.

For many environmentalists, the political response to the devastating pandemic had redrawn the boundaries of the possible. Things that they had repeatedly been told were naive or impossible such as shutting down swathes of the global economy overnight, and trillion-dollar investment packages were suddenly happening. Last year, when XR unveiled its demand for zero carbon by 2025, it was widely criticised as unrealistic. Now, such demands seemed less outlandish. The Overton window has been smashed wide open, Bradbrook told me.

Over the summer, this sense of political possibility grew, as Black Lives Matter protests exploded around the world and millions of people took to the streets to demand fundamental changes to policing and the end of structural racism. According to Blackler, the crises of 2020 have underscored the fact that climate change, structural inequality and racism all have the same root, and that is our global financial system. The protests also refocused attention on the existing criticism of XR from black and ethnic minority groups. On 1 July, XR put out a statement apologising for its previous mistakes: We recognise now that our tactic of arrest has made it easier for people of privilege to participate and that our behaviours and attitudes fed into the system of white supremacy. Were sorry this recognition comes so late.

The BLM protests had created space for XR to have really hard but crucial conversations, said Aghaji. It is a time of maturing. XR fucks up so often because we became way too big too quickly, and none of us foresaw that happening. Now, especially with Covid-19, we have had time to look at ourselves.

In July, XR announced plans for its next rebellion, which will begin on 1 September, when activists plan to peacefully disrupt parliament until the government agrees to debate the groups three demands. In its statement, XR identified an intersection of global crises including climate breakdown, Covid-19, racial injustice and economic inequality as symptoms of a toxic economic system propped up by corrupt politicians that is driving us to extinction. Aghaji saw the statement as further proof that XR was learning to play team sports. She said there were ongoing conversations between XR and multiple movements, and was optimistic about what those new relationships would create during Septembers rebellion.

A few weeks later, in a sign that perhaps a more consensual approach was gaining the upper hand in XR, the group announced that Hallam whom Bradbrook had previously described as XRs biggest asset and worst liability no longer had a formal role with the group. In a statement posted to Facebook on 28 July, Hallam stated that he would be devoting himself to a new direct action organisation/anti-political party, Beyond Politics. I believe immediate high level direct action is a right and duty of all citizens to bring down this genocidal government and those liberal institutions which passively stand by as the greatest crime in human history is taking place, he wrote. Earlier that month, Beyond Politics had targeted the headquarters of several NGOs including Greenpeace and Amnesty, pouring paint over walls and floors and handing over letters demanding they write to their members, urging them to rise up against the government. Meanwhile, XR groups have continued to stage smaller protests, including opposition to HS2 and a demonstration at the British Grand Prix on 2 August during which four protesters were arrested.

Speaking at the beginning of the year, back at her home in Stroud where XR was launched, Bradbrook was reluctant to speculate about the future. There is just arrogance in even having an opinion, she said. But after a pause, she began to imagine a couple of scenarios: one dystopian, one utopian. In the first, humanity destroys itself, and perhaps the universe learns something from that. In the second, a truly global citizens assembly is established, humanity reunites, and we use the sort of energy that has previously been used in a war to go into a rapid healing situation. It is all possible.

She paused again, before adding: I cant think of anything else I would rather do with my life. It is such an honour to try. What else can we all do?

Follow the Long Read on Twitter at @gdnlongread, and sign up to the long read weekly email here

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The evolution of Extinction Rebellion | Environment - The Guardian

The Evolution Of Shea Theodore Is Complete – SinBin.vegas

Alex Ovechkins office is in the circle on the power play. Patrice Bergerons is at the faceoff dot. Tom Wilsons is in the penalty box. Now Shea Theodore officially staked claim to his new office after an incredible display of passing during the round-robin.

In the 3rd period of last nights round-robin game against the Avalanche, Theodore found himself in a familiar place with the puck. He surveyed the ice, picked out Marchessault, and fired a 100+ foot pass, tape-to-tape to #81 which set up the go-ahead penalty shot.

It was kind of a broken play because Nate was coming out of the box. He was in the zone and he decided to change. Shea had perfect position and it was an unreal pass. -Jonathan Marchessault

Youll have to use your imagination to fill in just how incredible this pass is, but here it is.

That was just one of Theodores many brilliant passes from that very spot. Here are two more from the same game. (There are a few others from the rest of the round-robin, but three gifs in the same article is already a little overwhelming.)

At this point, thats pretty much what we expect from Shea. -Marchessault

But Theodores brilliance throughout the entire round-robin goes well beyond just stretch passes from his newly minted office. Posting four points on two goals and two assists plus an assist on the penalty shot goal, he was Vegas most dangerous offensive weapon behind the $9.5 million man, Mark Stone. Shea averaged 24 minutes a game playing against three of the best lines in the league, he recorded 11 shots on goal during the three-game stretch and was on the ice for seven Vegas goals, tied with William Karlsson for the most of any Golden Knight.

He has the ability to raise his level depending on the moment and how important the game is and I thought you saw that tonight. -Pete DeBoer

Theodores growth as a player with the Golden Knights has been tremendous since he was first acquired at the Expansion Draft. After coming from Anaheim where he competed in 20 playoff games as a rookie, Theodore didnt even make the Golden Knights roster out of the initial training camp. (Theres a strong argument to be made that this was expansion team roster management, but it happened nonetheless.)

He put up 29 points in his first season in Vegas while playing just over 20 minutes a night in a slightly sheltered role. In the playoffs, he was able to tally 10 points in 20 games but had a tough series against Washington which left a sour taste heading into year two. Prior to that season, he held out of camp looking for a long-term deal, which he eventually got, but is starting to look like an incredible bargain for the Golden Knights.

The evolution of his game continued earning a bit more ice time and mustering up 37 points in 79 games in 2018-19. Then in the playoff series against the Sharks, he posted seven assists and eight points and laid the groundwork for what weve seen this year. 46 points total, 18 in 22 games under DeBoer, and an increased defensive role has seen Theodore unseat Nate Schmidt as the Golden Knights clear #1 defenseman.

Tonight, he was elite. I think this guy is going to be in the Norris conversation for years to come here. -DeBoer

Shea was good the first year with us but his game where its at right now, when you talk about top 10 defensemen in the league he has to be up there. Hes improved so much since the beginning of the Golden Knights and his game this year was unbelievable. Hes definitely a big part of our offense. -Marchessault

Theodore has become a household name to any and all Golden Knights fans, but the hockey world as a whole still hasnt quite caught on.

Thats about to change though as the Golden Knights prepare for what they hope to be a deep playoff run. If they go as far as everyone in Vegas hopes, not only is he probably going to become a star in the eyes of the many more hockey fans, but hes got a real shot finding his name inscribed on the Conn Smythe trophy along the way.

Excerpt from:

The Evolution Of Shea Theodore Is Complete - SinBin.vegas

Pizza ovens, inflatable tents and USB charging: the evolution of camping – The Guardian

It used to be considered a low-tech holiday, but while campers who want to get off-grid can still find quiet spots to pitch up and spark up the Trangia, others are unfolding their portable pizza ovens and plugging in their projectors.

Advances in technology, and the rise of glamping and festivals, mean that some holidaymakers are packing a whole range of home comforts alongside their traditional camping gear.

People are making things a bit more bespoke, said Mike Attwooll, product buyer at the camp shop Attwoolls. You go out for the day and back to your base at night and its like home.

Ten years ago electrical hook-ups were unusual, but now they are the norm, he said, as campers look to plug in phones and run equipment they would previously have left behind. He had recently seen photos of someone holding a film night in their tent using a mini-projector, he said.

James Warner Smith of the website Cool Camping said technology had brought modern campers a whole range of choices. Some guys have developed a folding pizza oven that you can take with you. It does rotisserie chicken too, he said. Theres a no-electricity coffee maker, and there are quite few stoves that have USB ports in them so you can charge your phone while you are cooking. One of these, the 149.99 Tegology Tegstove, won investment on Dragons Den.

Attwooll said he had recently been looking at a brochure from the 1960s and many products were the same, but that recent innovations meant better versions were available.

The most important things are what youre sleeping under and what youre sleeping on, he said. Eighty-five per cent of family tents are now inflatable, and campers pump up sturdy beams instead of metal poles.

Iain Geddes, senior technical adviser the Camping and Caravanning Club, said affordable inflatable tents were one of the few big sudden changes in the market. Suddenly I was getting calls from people, like one from a single mum saying can I put one of these up on my own, he said. The fact that the answer was yes has made camping accessible for some who would struggle with traditional tents.

Deflating airbeds have ruined many camping trips, and are now being replaced with a new generation of self-inflating mats which offer comfort and reliability. And there have been changes in sleeping bag technology, which mean those who want a bit more comfort under canvas can get it. Attwooll cites a bag aimed at women which has thicker material at the bottom, and another launched this year by Vango - which comes with a thermal heatpad that can be plugged into a power pack.

Visit any campsite though and you will probably still see at least one bell tent. These have enjoyed a renaissance in recent years, which Warner Smith puts down, in part, to social media. In the Instagram age people have an idea of what things should look like, so they will pitch their bell tent and put up some bunting.

He said changes were being inspired by trips to festivals, and by glamping sites that offer fixed tents, pods and shepherds huts beautifully decorated and kitted out with comfortable beds.

You have a lot of sites where this is a mixture of fixed tents and traditional pitches, and people are seeing the glamping and bringing some of it to their own experience, he said. At the same time there has been the growth of music festivals. Campsite owners have seen the food trucks and some sites will now have them at the weekend.

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Pizza ovens, inflatable tents and USB charging: the evolution of camping - The Guardian

Paper Mario: The Evolution of the RPG Series | CBR – CBR – Comic Book Resources

Paper Mario is drastically different from the RPG it used to be. Here's how it got from The Thousand-Year Door to The Origami King.

ThePaper Marioseries has come a long way in its 20-year journey and managed to keep fans interested while welcoming new players into the fold. Its latest installment is worlds away from the original game, but Nintendo has managed to transition the series from a beloved RPG into an adventure game, with very few blips along the way.

Here's how Paper Mario became what it is today.

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Paper Mario was meant to be a sequel toSuper Mario RPG, but things changed when developerSquare Soft left Nintendo for Sony over the lack of storage space on the N64's cartridges. Square maintained certain rights to Super Mario RPG, which forced Nintendo to start over.

Intelligent Systems became the developer and at first,it wasn't sure how to tackle the project.Then Junior Designer Naohiko Aoyama came up with a rough design of 2D characters in a 3D world and submitted it to the team. This led to Paper Mario's ultimate design and name.

Paper Mario, or Paper Mario 64, was designed to be a RPG for kids. The writing was easy to understand and the style was cute, colorful and unique. Combat was turn-based, like many RPGs at the time, but it was simplified. Rather than managing several party members, it focused on Mario to fight, use equipment and level. Partner characters were easy to use and equipment was basic, with progression-based upgrades. It was an all-ages RPG, but it also had secrets, optional bosses and extra systems that made gameplay rewarding even for veteran gamers.

Paper Mario: The Thousand-Year Doorintroduced new gameplay in the form of Mario's paper abilities. He could turn into a paper airplane, roll up or turn sideways to become paper thin. There were new partners and abilities for puzzles. Combat remained the same, but took place on a stage with an audience to help or hinder Mario. The stage visually represented leveling progress, as it got bigger and better at certain levels. This game is frequently named the best in the series.

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Intelligent Systems wanted the next game to have completely different gameplay. The idea to makeSuper Paper Marioa platformer with the ability to rotate the world came from Ryota Kawade, Paper Mario's Chief Director at the time. This was the first and only time the series completely left the RPG genre.

Thegame took place in the sewers of theMushroom Kingdom as an homage to Warp Pipes. Action-platforming replaced turn-based combat and the game introduced new villains. Like Super Mario Bros. 2, players could choose different characters from the series as they progressed. Partners had abilities, but these were focused more on finding secrets and progressing through worlds.

AlthoughSuper Paper Mario received praise, many fans were disappointed. It was a huge departure from the previous games and there was concern the series wouldn't be a RPG anymore. They were partially correct.

Paper Mario:Sticker Star was originally designed like the RPG games but was scrapped when Miyamoto said it felt too much like TTYD. He told Intelligent Systems that story wasnt important and to not focus on it. This advice was based on a Super Paper Mario survey from Club Nintendo, a discontinued service, where only 1 percent of players said story mattered -- which makes sense, because Super Paper Mariowas a platformer, not a RPG. Because of Miyamoto's advice, Sticker Star was hollow. It remains the least-liked game in the series.

Meanwhile, Nintendo instructed Intelligent Systems to stick with basic Mario characters and avoid unique versions like Koops or the Gourmet Shy-Guy, unless entirely new characters were being created. This is why, in newer Paper Mario games, there are only villains like King Ollie or standard Toads and Koopas, rather than someone like Goombaria.

When Paper Mario: Color Splash was revealed, fans were skeptical because it looked like Sticker Star. However,the world was more engaging with a good story and added comedy. Puzzles were fewer, but better and the Paint Hammer presented a fun progression and challenge for completionists. Unfortunately, Color Splash retained the terrible, irrelevant combat of Sticker Star.Paper Mario was slowly finding its new footing as an adventure game.

RELATED: Nintendo Bans 'Modifying' Mario Villains - Each Game Must Create Its Own

The Origami Kingmanaged to find a good balance for Paper Mario'snew adventure style. Intelligent Systems created new uses for existing characters and crafted a new villain and companion. It also fixed combat by tying it into puzzle-solving and made it relevant to the world. For example, an enemy may be blocking a hidden Toad or access to a puzzle, giving players a reason to battle again.

The Origami King alsotranslated Color Splash's Hammer into confetti to fit the story and built on the completion aspect by adding hidden Toads, blocks and even collectibles. Most importantly, rich storytelling returned.

Paper Mario started out as an RPG because it was an upcoming genre and Nintendo wanted to make a title that anyone could pick up and play. As gaming evolved, adventure games became the simpler genre, so Intelligent Systems reinvented the series. It changed everything about Paper Mario and while its unlikelythere will be a return to the RPG format,Paper Mario is finding its new footing.

KEEP READING: Paper Mario: Tips, Tricks & Strategies for New Origami King Players

Dungeons & Dragons 5e: How to Run a Dark Souls-Themed Campaign

An avid gamer with a poochy sidekick living just outside of Ottawa, Ontario. When not gaming she dons capes for writing, creating digital art, and sometimes game development. Games she's worked on can even be found on the app stores. Also loves metal music, horror movies, and a good book.

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Paper Mario: The Evolution of the RPG Series | CBR - CBR - Comic Book Resources