Daily Archives: February 17, 2022

Kootenay Gambling Support is bringing awareness to a rise in online gambling Rossland News – Rossland News

Posted: February 17, 2022 at 8:34 am

Kootenay Gambling Support is trying to bring more awareness to the fact that online gambling has significantly increased since the pandemic began. To that end, they are hosting a Gambling Awareness campaign in March 2022.

The Online Prevalence Gambling Study 2020 found that first-time online gamblers found that the convenience, 24/7 availability and comfort of playing from home were factors in them continuing to gamble.

Kootenay Gambling Support wants to bring awareness to gambling and the services and information available. Supports are also free and open for loved ones affected by someones gambling behaviours.They educate people who choose to gamble to make responsible choices to keep their habits healthy.

Kootenay Gambling Support will host a series of small events that they will post to their website and Facebook page [Kootenay Gambling Support]. They are launching a regional online contest titled Finding your Balance. People from the Kootenays can share their photos and stories about how they achieve balance during the pandemic. Share a high-resolution picture (300 pixels/inch) accompanied by a story, poem, haiku, or any appropriate description with a maximum of 50 words on the Facebook page with #GAM2022 or through email wkprevention@gmail.com.

Entries are eligible for a draw of three gift certificate prizes for your favourite local business. The value of the prizes will range from 1st prize $500, second prize $300 and third prize $150. Winners will be announced during the second week of April.

Kootenay Gambling Support continues to monitor the COVID-19 situation closely. They continue to offer responsible and problem gambling awareness and education services, early-intervention support, Indigenous services, and problem gambling counselling, free of charge, to citizens of British Columbia. In-person and virtual service options are available (telephone and videoconferencing), including counselling and outreach support.

For more information on any of these services, contact the Gambling Support Line at 1-888-795-6111, check our website at Kootenay Gambling Support or send us an email at michelle.prevention.education@gmail.com to connect with a local provider.

READ: Bet on it: a lot of money is going to change hands Super Bowl weekend

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Kootenay Gambling Support is bringing awareness to a rise in online gambling Rossland News - Rossland News

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What Are The Most Legit Online Casinos In The UK? – Salon Priv Magazine

Posted: at 8:34 am

When it comes to security, you cant be too careful and online gamblers are well aware of this reality. Assuming you are a UK gaming enthusiast, planning to enjoy the finest games at online casinos, your mission is simplified. Thats because the United Kingdom Gambling Commission regulates casinos that cater to local players.

Their license is widely regarded as the most reliable in the world and it holds gambling operators to the highest security standards. Once you narrow down the search to UK GC licensed casinos, you should also consider these factors when joining any of these operators.

Prospective players appreciate online casinos that offer generous bonuses to newcomers and existing members. These financial incentives are essential for boosting bankrolls, but also to offset the proverbial house edge. If you play at the most legit mobile casinos like fruityking.co.uk in the UK, you are certain to enjoy the bonus and the resulting winnings.

The only condition is to play by the rules and meet the wagering requirements before cashing out. Legitimate casinos will make these terms and conditions crystal-clear, so players will know precisely what to expect. The last thing you need to worry about is the bonus fine print.

When you find a reliable online casino in the UK, you are tempted to stick to it for many years to come. Thats why it is so important to find gambling operators capable of rewarding you in the long run. Ongoing and recurrent promotions are fine, but you should also aim for casinos that have a fully-fledged loyalty program.

These usually culminate with players attaining VIP status, which in turn, makes them eligible for special benefits. If you can trust the casino to provide you with these well-deserved rewards, your long-term experience will be greatly enhanced.

Online casinos allow players to try the games for free indefinitely using the play money they provide. However, since online gambling is so much fun when winning real money, players will eventually want to make a deposit. A wide selection of payment methods is a good sign, especially when they include only respectable banking options.

A trustworthy casino will encrypt the information shared by players, which includes both private data and financial transactions details. All these layers of security shouldnt come at the price of speed and both deposits and withdrawals should be processed quickly.

Even the most complex and amazing casinos should be easy to navigate. The security protocols used by the gambling operators to protect players dont have to be visible. What is important for players seeking the most legit online casinos in the UK is to browse an intuitive website.

An easy sign-up process, a site optimized for mobile devices, and professional customer support are all to be expected. Players who need assistance should have several channels of communication at their disposal to get help promptly.

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What Are The Most Legit Online Casinos In The UK? - Salon Priv Magazine

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Follicular Lymphoma: a Focus on Current and Emerging Therapies – Cancer Network

Posted: at 8:33 am

Abstract

Follicular lymphoma (FL) is the most common indolent lymphoma and is characterized by a relapsing and remitting course. In addition to significant biologic heterogeneity, the clinical trajectory for patients is variable, with some being observed for many years, and others having aggressive disease requiring multiple treatment courses. Unfortunately, FL remains incurable, and continues to cause early mortality. Improved understanding of the genetic and immune biology of FL has led to several FDA-approved therapies in the relapsed and refractory setting, including PI3K inhibitors; immunomodulatory agents; the EZH2 inhibitor, tazemetostat; and anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, axicabtagene ciloleucel. This review outlines the current approach to the diagnosis and treatment of FL with a focus on emerging investigational therapies, including targeted protein inhibitors, antibody-drug conjugates, monoclonal antibodies, bispecific antibodies, and novel combination strategies.

Key Words: follicular lymphoma; treatment; novel therapies

Follicular lymphoma (FL) is an incurable B-cell lymphoid neoplasm with significant biological and clinical heterogeneity. As the most common indolent lymphoma and second most common non-Hodgkin lymphoma (NHL), it has a relapsing and remitting course with risk of transformation to aggressive disease.1,2 Most patients present with advanced disease and will eventuallyrequire treatment for symptomatic disease. Given the range of clinical behaviors, the decision of when to treat is equally important as how to treat, noting that therapeutic goals include meaningful remission, symptom palliation, and prolongation of life.

While the majority of patients have survival approximating 2 decades, a subset of patients have aggressive disease with poor outcomes.3 Unfortunately, baseline identification of these patients remains challenging. Approximately 20% of patients with FL have progressive disease within 2 years of initial chemoimmunotherapy and a 5-year overall survival (OS) of 50%.4 Cumulative toxicity from repeated exposure to palliative cytotoxic chemotherapy also contributes to morbidity and mortality. While antiCD20-based chemoimmunotherapy remains an important standard of care, more rational and biologically driven agents are either approved or in development. In this review, we examine the current approach to the diagnosis and treatment of FL with a focus on targeted therapy and other novel agents.

A diagnosis of FL requires histologic examination of a lymph node biopsy for assessment of nodal architecture and grading.5 FL is characterized by neoplastic germinal center B-cells growing in densely packed follicles with distortion of the normal nodal architecture. Grading depends on the number of centroblasts/high-power field. Grade 1-3a are considered indolent, whereas 3b is more aggressive and clinically approached as diffuse large B-cell lymphoma (DLBCL).6 The classic immunophenotype includes the B-cell antigens CD19, CD20, and CD79a; lymphoid progenitor marker, CD10; and nuclear proteins, BCL-2 and BCL-6. Unlike mantle cell lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma, it is negative for CD5.

Cytogenetically, FL is characterized by the translocation t(14;18), which occurs in up to 90% of cases, as a result of aberrant V(D)J recombination. This results in BCL-2 protein overexpression and increased cell survival (Figure 1).7 As a hallmark of FL, it is necessary, but alone insufficient, for lymphomagenesis.8-10 An important recent finding is early mutations in genes coding for chromatin modifying proteins.11-13 These epimutations are a second hallmark of FL and include: KMT2D (~70-80%), CREBBP (~65-70%), EZH2 (~25%), and EP300 (~14%).12,14 These transcriptionally repressive mutations result in increased germinal center proliferation, differentiation block, and immune evasion.15-17 Along with the BCL2 translocation, these mutations are early events occurring in a common progenitor cell.

Through divergent clonal evolution, other mutations are subsequently acquired including mutations in genes involved in immune modulation (TNFRSF14); JAK-STAT signaling (STAT6, SOCS1); and B-cell receptorNF-kB signaling (CARD11, TNFAIP3, MYD88).12 While conventional karyotyping and fluorescent in situ hybridization (FISH) for t(14;18) are part of the standard evaluation for FL, genomic sequencing is limited to testing for the EZH2 mutation when tazemetostat is being considered.18 Nonetheless, next-generation sequencing has revealed the diverse mutational landscape of FL and provides insight into disease pathogenesis, as well as opportunities for more precise therapeutic strategies.

The treatment of FL must consider individual parameters and balance the risk of cumulative toxicity versus remission and palliation of symptoms. The conventional approach to FL is clinical observation until there is an indication to treat, typically based on criteria of the Groupe dEtude des Lymphomes Folliculaires (GELF) or National Comprehensive Cancer Network (NCCN).19,20 There are several prognostic indices in FL including the Follicular Lymphoma International Prognostic Index (FLIPI), FLIPI-2, and m7-FLIPI, but none dictate the timing or type of treatment at an individual patient level.14,21,22

The m7-FLIPI and gene expression profiling panels include genomic features, but have varied performance and are not validated for clinical practice.23 Staging with positron emission tomography (PET) imaging helps to identify the extent of disease and preferred sites for biopsy when histologic transformation to DLBCL is suspected, as this occurs in up to 15% of patients.3 The assumption here is that higher uptake values correspond with more rapid cell turnover and aggressive histology. This is somewhat controversial, and PET alone does not appear to predict histologic transformation.24 Nonetheless, PET imaging does result in disease upstaging in approximately 10% to 60% of cases, which often has treatment implications.25,26

For patients with stage I-II disease, there are several options including observation, rituximab (Rituxan), chemoimmunotherapy, or radiation, with the majority of patients having similar excellent long-term survival regardless of initial approach.27 Approximately 70% of patients have advanced disease (stage III or IV) at diagnosis.3,28 Asymptomatic patients with low disease burden may be actively monitored. When treatment is indicated for patients with low tumor-burden advanced disease, rituximab monotherapy is often used, given the high overall response rate (ORR; complete remission [CR] plus partial remission [PR]) of 71%, low toxicity, and long median time to treatment failure of approximately 4 years, which delays the need for cytotoxic therapy.29

When selecting initial treatment for patients with high tumor burden and symptomatic advanced FL, there are several considerations regarding the chemotherapy backbone, the anti-CD20 antibody, the use of maintenance strategies, and whether to opt for a nonchemotherapy regimen (Figure 2). Based on the StiL (NCT00991211) and BRIGHT (NCT00877006) trials, bendamustine and rituximab (BR) or rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), are both options with ORR >90%.30,31

BR has become a preferred option based on superior progression-free survival (PFS) over R-CHOP (70 vs 31 months, respectively) and it is also not associated with alopecia, anthracycline-associated cardiotoxicity, vinca alkaloid-associated neuropathy, or steroid-associated risks. R-CHOP may be preferred in cases where occult transformation is suspected, or immune suppression associated with bendamustine is to be avoided. In patients treated with R-CHOP or rituximab with cyclophosphamide, vincristine, and prednisone (R-CVP), maintenance therapy with rituximab every8 weeks for 2 years compared with placebo improves PFS, but not OS, based on the PRIMA study (NCT00140582).32

It is unclear whether this extends to patients treated with BR. In the GALLIUM study (NCT01332968), chemoimmunotherapy with obinutuzumab (Gazyva) versus rituximab improved PFS, with no difference in OS, but did result in high grade 3-5 adverse events, including infusion-related events and infections.33,34 The use of maintenance therapy is controversial, and even more so during the COVID-19 pandemic. Among surveyed physicians who treat indolent lymphomas with a maintenance therapy strategy, 53% hold rituximab maintenance to allow for vaccination.35 Lenalidomide (Revlimid)with rituximab is an alternative to chemoimmunotherapy with similar response rates, PFS, and OS to chemoimmunotherapy (R-CHOP, BR, or R-CVP).36 Similar to chemoimmunotherapy, it is a fixed-duration treatment, but with a much longer time frame at 18 months. It remains an option for patients wishing to avoid cytotoxic chemotherapy.

There is no standard treatment or sequence of treatments for relapsed/refractory FL (RR-FL), but the number of options is increasing. Approximately 20% of patients have early relapse and progression of disease within 24 months (POD24), and these patients have poor outcomes.4 Unfortunately, upfront identification of these patients is not possible, and more effective treatments for these patients are needed. For all patients with RR-FL, a chemoimmunotherapy regimen (BR, R-CHOP, or R-CVP) different from the first-line therapy is an option.

There is limited data on R-CHOP after BR, but second-line BR in patients with indolent NHL with previous rituximab (39%) or CHOP (54%) had an ORR of 82% and PFS of 34 months.37 Rituximab monotherapy is also effective for some patients with low tumor burden and previous rituximab-based regimens with an ORR 55% to 64% and PFS of 14 months.38,39 Obinutuzumab with either bendamustine or CHOP may improve outcomes by overcoming rituximab refractoriness, especially for relapses within 6 to 12 months.40,41 In transplant-eligible patients with chemosensitive disease to first salvage, consolidative autologous stem cell transplantation (auto-SCT) appears to improve long-term survival based on several retrospective analyses.

Among patients with POD24, auto-SCT has an improved 5-year OS of approximately 77% vs 59% among those without auto-SCT.42 Similar results were observed for patients undergoing auto-SCT within 1 year of treatment failure, with a 5-year OS of 73% compared with 60% without auto-SCT.43 It should be noted, however, that the benefit of auto-SCT may simply be due to a favorable response to second-line therapy and randomized studies are needed.

In the era of increased alternative treatments, the use of auto-SCT has been substantially reduced. The use of allogeneic-SCT, a historical option with curative potential in FL, has also declined. While the preferred therapy for high-risk patients with early relapse has yet to be defined, targeted therapy beyond anti-CD20 monoclonal antibodies has been reshaping the treatment landscape of FL since 2014 (Table 1), with several new trials focusing on this population, including a US Intergroup Study S1608 (NCT03269669).

Lenalidomide is an immunomodulatory drug with direct cytotoxicity to lymphoma cells via inhibition of the E3 ubiquitin ligase, cereblon, as well as indirect antitumor effects mediated through changes in the tumor microenvironment.44 Lenalidomide with rituximab is an active regimen in rituximab-sensitive relapsed FL, as demonstrated in the AUGMENT trial (NCT01938001) with an ORR of 80% (CR 35%) compared with an ORR of 55% (CR 20%) for rituximab alone.39 The combination had a 2-year OS and median PFS of 95% and 39.4 months compared with 86% and 13.9 months, respectively, for rituximab alone. The combination had a higher incidence of all grades of infections (63% vs 49%, respectively), neutropenia (58% vs 23%), and cutaneous reactions (32% vs 12%). Of the grade 3 or 4 adverse events, a higher incidence of neutropenia (50% vs 13%) was also observed with the combination. This study led to the regulatory approval of lenalidomide with rituximab in patients with RR-FL.

Inhibition of PI3K signaling has been a largely successful approach, with 4 FDA-approved agents in RR-FL.45 PI3K mediates proximal intracellular B-cell receptor signaling, as well as cell survival signals received from the tumor microenvironment. Idelalisib ( isoform inhibitor; Zydelig) was the first of these agents to be approved and a major breakthrough in the RR-FL space. The ORR was 57% (CR 6%) with a median duration of response (DOR) of 12.5 months and median PFS of 11 months in very heavily pretreated patients.46 Unfortunately, significant toxicities, including neutropenia, diarrhea, transaminitis, and pneumonia, limited its development. Copanlisib (pan-isoform inhibitor; Aliqopa); duvelisib ( and isoform inhibitor; Copiktra); and umbralisib ( isoform and CK1 inhibitor; Ukoniq) are also approved for RR-FL with comparable efficacy and improved toxicity profiles.47-49 They all have an ORR ranging from 42% to 59%, median DOR of 10 to 12 months, and median PFS of 9.5 to 11 months. They have regulatory approval for patients with multiply relapsed FL, based on activity in the heavily pretreated setting.

Approximately 25% of patients with FL have a gain of function mutation in the histone methyltransferase protein, EZH2, with consequent increased expression of genes involved in cell proliferation.12,14,50 Although it contributes to lymphomagenesis, EZH2 gene mutations are associated with improved PFS.50 Tazemetostat (Tazverik) is an EZH2 inhibitor that targets this epimutation. It is the first biomarker-directed therapy in FL and has been approved as a third-line option in RR-FL, with an ORR of 69% and CR rate of 13%.51 With a median follow-up of 22 months, the median PFS was 13.8 months, and median OS was not reached. It also appears to have activity in patients without an EZH2 gene mutation, with ORR of 35% and similar median PFS and OS. There were few significant treatment-related adverse events, with 3% of patients having grade 3 or 4 myelosuppression and a low discontinuation rate of 8%. Its favorable toxicity profile makes it an attractive oral option.

While targeted agents have clinical activity in RR-FL, long-term remission is still lacking and most require prolonged treatment courses. CAR T-cell therapy has revolutionized the treatment of aggressive lymphomas like DLBCL, and is also now an option for RR-FL, although follow-up remains short. Axicabtagene ciloleucel (axi-cel; Yescarta) is an anti-CD19 CAR T-celltherapy that received accelerated approval in March 2021 for adult patients with RR-FL ( 2 lines of prior therapy) based on the results of the phase 2 study ZUMA-5.52 In a preliminary report of updated results (median follow-up of 31 months), 86 patients with RR-FL had an ORR of 94% (CR 79%), median DOR and PFS of 38.6 months and 39.6 months, respectively, while OS was not reached.53 The incidence of cytokine release syndrome (CRS) and neurotoxicity grade 3 were 6% and 15%, respectively.

The phase 2 ELARA trial (NCT03568461) evaluating tisagenlecleucel (tisa-cel) in patients with RR-FL ( 2 lines of prior therapy) had an ORR 86% (CR 69%) without any grade 3 CRS, and only 3% with grade 3 neurotoxicity.54 At a median follow-up of 16.9 months, the median DOR, PFS, and OS were not reached, but 1-year PFS was 67%. The phase 2 TRANSCEND FL trial (NCT04245839) using lisocabtagene maraleucel is ongoing. One of the most crucial challenges is patient selection for CAR T, which remains a costly andaggressive approach. Long-term follow-up and real-world data for CAR T-cell therapy from the commercial setting will be important guides influencing patient selection.

Beyond the commercially approved targeted therapies in FL, there are multiple emerging agents that target the biology of FL (Figure 3). These are reviewed briefly in the following section, which also highlights novel investigational use of these treatments in FL (Table 2).

Antibody-drug conjugates (ADCs) offer an appealing means of antigen-based drug delivery, with several in development. In a phase 2 study in patients with RR-FL, the anti-CD79b ADC, polatuzumab vedotin, (pola; Polivy) was combined with rituximab and resulted in an ORR of 70% (CR 45%) with a 9.4-month DOR.55 The PFS was 15.3 months with a 2-year OS of 88%. The most common grade 3-4 adverse events were neutropenia (15%) and diarrhea (10%); however, although no grade 3-4 neuropathy was observed, 40% had grade 1-2 neuropathy.

In preliminary reports of early-phase studies evaluating pola combinations in RR-FL, pola with BR did not improve treatment response.56 Pola with obinutuzumab/lenalidomide had an ORR of 76% (CR of 65%), while pola with obinutuzumab/venetoclax had an ORR of 71% (CR of 57%), and long-term results with updated survival are anticipated.57,58 In a phase 1 study including 14 patients with RR-FL, the anti-CD19 ADC, loncastuximab tesirine (Zynlonta), had an ORR of 79% (CR of 65%), and cytopenias were the most common adverse effect.59

Although checkpoint blockade monotherapy has low response rates in RR-FL, combinations may be more active. A phase 1/2 trial (NCT02631577) using obinutuzumab, atezolizumab (Tecentriq), and lenalidomide (G-atezo-len) in patients with RR-FL reported an ORR of 78% (CR of 72%), median DOR of 38 months, and 2-year PFS of 65%.60 Cytopenias were the most common grade 3 adverse event and occurred in 71% of patients. While the majority of toxicities were manageable, the discontinuation rate of any study drug was 29%.

In a preliminary report of pembrolizumab with rituximab in patients with RR-FL (NCT02446457), the ORR was 80% (CR of 60%), and although safe, the benefit of pembrolizumab (Keytruda) over rituximab monotherapy was unclear, as this trial included patients with rituximab-sensitive disease.61 In the frontline phase 2 trial (1st FLOR study; NCT03245021), immune priming with nivolumab (Opdivo), followed by rituximab and nivolumab had an ORR of 92% (CR of 54%), with a favorable toxicity profile.62 Larger studies and a longer follow-up are needed to clarify the role of checkpoint inhibitors as first-line nonchemotherapy options.

Antibodies with novel targets are also under investigation in FL. The anti-CD47 antibody, magrolimab (Hu5F9-G4), blocks CD47 on lymphoma cells to enhance macrophage-mediated phagocytosis. In a phase 1 study of patients with RR-NHL, which included 7 patients with RR-FL, magrolimab with rituximab resulted in an ORR of 71% (5/7) and CR rate of 43% (3/7).63 Although small, these numbers are encouraging, with many patients having rituximab-refractory disease. The phase 2 portion of this study (NCT02953509) is currently recruiting.

Another trial investigating venetoclax (Venclexta) with obinutuzumab and magrolimab (VENOM) in relapsed/refractory indolent lymphomas is recruiting, and the results are eagerly anticipated (NCT04599634). Tafasitamab (Monjuvi) is an anti-CD19 antibody approved in combination with lenalidomide for relapsed/refractory DLBCL, but has low activity as a monotherapy in FL.64 A phase 3 trial (InMIND) of tafasitamab plus lenalidomide/rituximab versus lenalidomide/rituximab alone in patients with RR-FL or marginal zone lymphoma will determine whether there is a role for tafasitamab in RR-FL (NCT04680052).

Bispecific antibodies or bispecific T-cell engagers (BiTes) are novel protein constructs with separate B-cell (CD20) and T-cell targeting (CD3) domains. Mosunetuzumab, glofitamab, odronextamab, and epcoritamab are bispecific antibodies being investigated in early-phase RR-FL trials (Table 3), which have shown promising results with ORR ranging from 80% to 100% (CR from 50% to 75%) in heavily pretreated patients.65-69 Bispecific antibodies provide an off-the-shelf form of T-cell mediated therapy, with the goal of achieving the durable remissions seen with CAR T-cell therapy. Unlike CAR T-cell therapy, they appear to have a lower risk of CRS and neurotoxicity, and favorable responses in patients relapsing after CAR T-cell therapy. The optimal clinical use of bispecific antibodies remains unknown, and trials including novel combinations in FL are ongoing: mosunetuzumab and lenalidomide (NCT04246086); and epcoritamab with lenalidomide/rituximab or BR (NCT04663347).

While BCL2 translocation and epigenetic dysregulation are both frequent features in FL, the efficacy of existing agents has been modest. The BCL2 inhibitor, venetoclax, had low monotherapy activity in FL with an ORR of 38% (CR of 14%),70 but combination strategies are in development. A preliminary report of the first trial to combine a Bruton tyrosine kinase (BTK) inhibitor, ibrutinib (Imbruvica), with venetoclax in RR-FL showed an ORR of 83% (CR of 33%) with manageable toxicity (NCT02956382).71 Several frontline trials using venetoclax-based combinations include the following: venetoclax, oral azacitidine (CC-486), and obinutuzumab (NCT04722601); venetoclax, lenalidomide, and obinutuzumab (NCT03980171); and venetoclax, ibrutinib, and obinutuzumab (NCT04450173).

The phase 2 PrECOG 0403 trial with frontline venetoclax, bendamustine, and obinutuzumab (NCT03113422) for patients with high tumor-burden FL (n = 56) showed an ORR of 93% (CR of 73%), 2-year estimated PFS of 86%, and 2-year estimated OS of 94% at a median follow-up of 21 months.72 Despite the efficacy, the rate of grade 3 adverse events was high, at 84%, most notably due to tumor lysis, cytopenias, and infections. Unfortunately, this toxicity will preclude its use, but alternative dosing strategies to mitigate adverse effects are being explored. Tazemetostat is also being evaluated in combination with rituximab (NCT04762160), and in combination with lenalidomide and rituximab (NCT04224493).

While chemoimmunotherapy, lenalidomide with rituximab, or rituximab alone are standard first or subsequent line options for advanced FL, the treatment choices for RR-FL have evolved over the last several years. Additional agents for multiply relapsed patients include PI3K inhibitors, tazemetostat, and CAR T-cell therapy. Patient selection for CAR T-cell therapy is evolving, and the optimal sequencing with other therapies remains unknown. There are many emerging investigational products, including ADCs, anti-CD47 monoclonal antibodies, bispecific antibodies, checkpoint-based therapy, and novel combination strategies that are being evaluated. Individualized approaches, trial end points with quality-of-life measures, and information to guide sequencing of available regimens and agents are all desperately needed. These efforts, coupled with ongoing discovery in the biology of FL, are imperative to improving outcomes for patients with FL.

AUTHOR AFFILIATIONS:

Kirk E. Cahill, MD1; and Sonali M. Smith, MD1

1Department of Medicine, Section of Hematology/Oncology, University of Chicago Medicine Comprehensive Cancer Center, Chicago, IL.

Funding: None

Corresponding author

Sonali M. Smith, MD; Elwood V. Jensen Professor in Medicine; Chief, Section of Hematology/Oncology; Department of Medicine; The University of Chicago Medicine; 5841 S. Maryland Ave., MC 2115; Chicago, IL 60637; Email: smsmith@medicine.bsd.uchicago.edu

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Follicular Lymphoma: a Focus on Current and Emerging Therapies - Cancer Network

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Synthego Raises $200 Million to Accelerate the Field of CRISPR-Based Medicines from Early-phase Research to the Clinic – Yahoo Finance

Posted: at 8:32 am

- Company Appoints Avi Raval as Chief Financial Officer -

REDWOOD CITY, Calif., Feb. 17, 2022 /PRNewswire/ -- Synthego, the genome engineering company, today announced it has raised $200 million of growth capital, including a Series E financing led by Perceptive Advisors. Also participating in the round were new investors SoftBank Vision Fund 2, Declaration Partners, Laurion Capital Management, Logos Capital, GigaFund and Chimera Abu Dhabi and existing investors Wellington Management, RA Capital Management and Moore Strategic Ventures. The company also recently appointed Avi Raval as chief financial officer.

(PRNewsfoto/Synthego)

"CRISPR has become a powerful discovery tool, and the field is now at an inflection point. The promise of translating insights into clinical applications to treat a myriad of serious diseases, including cancer and genetic disorders, is within reach. With Synthego's full stack of proprietary platforms, clinical-grade manufacturing capabilities, and strong relationships in industry, academia and the investor community, we are well positioned to help our customers usher in this new era of genetic and cellular medicines, ultimately ensuring these therapies are accessible to all patients," said Paul Dabrowski, co-founder and CEO of Synthego.

Synthego will use the proceeds from the Series E financing to accelerate the creation of a cell and gene therapy discovery and development ecosystem to help researchers scale and simplify the translation of new discoveries into novel therapeutics for serious diseases. Specifically, Synthego plans to expand both the capacity and capabilities of its Halo and Eclipse Platforms for research and discovery applications, continuing to drive broad accessibility of genome engineering tools and genome engineered cells. Synthego will also invest in next-generation technologies such as CRISPROff, a light-based system for specific and precise CRISPR editing, and increase its Good Manufacturing Practice (GMP) manufacturing capabilities to support its customers' clinical and therapeutic programs.

Story continues

The development of next-generation CRISPR-based cellular and genetic medicines requires the ability to rapidly discover new biology, deploy advanced bioinformatics, optimize and perform precision genome editing, and seamlessly translate from research into clinical settings. Synthego's vertically integrated approach, with continued investments in extensive genome engineering capacity, machine learning-based optimizations, proprietary high throughput manufacturing hardware and software, and an expanding precision genome editing tool kit, is providing customers and partners with an increasingly comprehensive path to discovering, developing, optimizing and manufacturing novel CRISPR-based cell and gene therapies.

"Synthego is uniquely positioned at the intersection of engineering and discovery science," said Sam Chawla, portfolio manager of Perceptive Advisors. "We could not be more excited to be partnering with the company at this important inflection point in its evolution."

"CRISPR-based genome engineering is rapidly transforming the landscape of discovery biology and ushering in a new era of cellular and genetic medicines that have enormous potential," said Mike Altman, managing director of Perceptive Advisors. "Given Synthego's success in scaling and optimizing genome engineering technologies, and standardizing quality and efficacy for both discovery and clinical applications, it is a key player in this remarkable field, and we are excited to support the team."

The importance and potential of accelerating scientific discovery and development through new technologies has been demonstrated during the past year. Synthego brought together more than 12,000 CRISPR researchers at the largest annual global CRISPR conference, leveraged its Eclipse Platform to rapidly accelerate critical programs in COVID-19 research and neurodegenerative diseases, and is enabling the rapid translation of CRISPR-based cell and gene therapies into the clinic through the ISO 9001 certification of its GMP manufacturing capabilities.

Appointment of Avi Raval as Chief Financial Officer

Mr. Raval has more than 20 years of financial and strategic experience. Prior to joining Synthego, he was a managing director and founding member of the health care group at Perella Weinberg Partners. During his tenure, he advised health care companies on a wide variety of public and private financings, strategic matters and mergers and acquisitions, and served as chief operating officer for the firm's advisory business. Mr. Raval spent the first seven years of his investment banking career at J.P. Morgan. He holds a B.A. from the University of Pennsylvania and an MBA from the Wharton School of Business.

"I am honored and excited to join the Synthego team," said Mr. Raval. "In my many years of experience, I've seen few companies with Synthego's potential to transform the way new medicines are discovered and delivered. I look forward to contributing to our team's strategic and financing initiatives to accelerate the development and commercialization of products that enable genome engineering at an unprecedented scale and speed."

Cowen served as sole placement agent to Synthego for the private placement.

About Synthego

Synthego was founded to revolutionize genome engineering technology, helping translate genomics into the clinic and ultimately making engineered biological therapies accessible to all patients. The company leverages machine learning, automation and gene editing to build platforms for science at scale. With its foundations in engineering disciplines, the company's platforms vertically integrate proprietary hardware, software, bioinformatics, chemistries and molecular biology to advance both basic research and therapeutic development programs. With its technologies cited in hundreds of peer-reviewed publications and utilized by thousands of commercial and academic researchers and therapeutic drug developers, Synthego is at the forefront of innovation, enabling the next generation of medicines by delivering genome editing at an unprecedented scale. For more information on Synthego, please visit the company's website at http://www.Synthego.com.

Cision

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WEF Global Risks Report 2022 Imagines … – technocracy.news

Posted: at 8:31 am

Hiding behind the respectability of scholarship, wealth and position, the WEF offers a smorgasbord of propaganda and fear-producing possibilities: Vaccine inequality, social fractures. geopolitical tensions, environmental collapse, global warming disaster, cybersecurity failure, migration disorder, war in space.

All of this is to prepare the world for the necessity of a Great Reset, aka Technocracy, that will facilitate the greatest transfer of wealth in world history, leading to Klaus Schwabs smiling prediction, You will own nothing and be happy. Like driving zoo animals with an electric cattle prod, fear is the primary tool to scare people into predictable submission and compliance. TN Editor

As 2022 begins, COVID-19 and its economic and societal consequences continue to pose a critical threat to the world. Vaccine inequality and a resultant uneven economic recovery risk compounding social fractures and geopolitical tensions. In the poorest 52 countrieshome to 20% of the worlds peopleonly 6% of the population had been vaccinated at the time of writing. By 2024, developing economies (excluding China) will have fallen 5.5% below their pre-pandemic expected GDP growth, while advanced economies will have surpassed it by 0.9%widening the global income gap.

The resulting global divergence will create tensionswithin and across bordersthat risk worsening the pandemics cascading impacts and complicating the coordination needed to tackle common challenges including strengthening climate action, enhancing digital safety, restoring livelihoods and societal cohesion and managing competition in space.

TheGlobal Risks Report2022 presents the results of the latest Global Risks Perception Survey (GRPS), followed by an analysis of key risks emanating from current economic, societal, environmental and technological tensions. The report concludes with reflections on enhancing resilience, drawing from the lessons of the last two years of the COVID-19 pandemic. The key findings of the survey and the analysis are summarized below.

Asked to take a view of the past two years, respondents to the GRPS perceive societal risksin the form of social cohesion erosion, livelihood crises and mental health deteriorationas those that have worsened the most since the pandemic began. Only 16% of respondents feel positive and optimistic about the outlook for the world, and just 11% believe the global recovery will accelerate. Most respondents instead expect the next three years to be characterized by either consistent volatility and multiple surprises or fractured trajectories that will separate relative winners and losers.

For the next five years, respondents again signal societal and environmental risks as the most concerning. However, over a 10-year horizon, the health of the planet dominates concerns: environmental risks are perceived to be the five most critical long-term threats to the world as well as the most potentially damaging to people and planet, with climate action failure, extreme weather and biodiversity loss ranking as the top three most severe risks. Respondents also signaled debt crises and geoeconomic confrontations as among the most severe risks over the next 10 years.

Technological riskssuch as digital inequality and cybersecurity failureare other critical short-and medium-term threats to the world according to GRPS respondents, but these fall back in the rankings towards the long term and none appear among the most potentially severe, signaling a possible blind spot in risk perceptions.

The 2021-2022 GRPS included a question on international risk mitigation efforts. Artificial intelligence, space exploitation, cross-border cyberattacks and misinformation and migration and refugees are the areas where most respondents believe the current state of risk mitigation efforts fall short of the challengethat is, efforts are not started or in early development. Meanwhile, for trade facilitation, international crime and weapons of mass destruction, large majorities perceived risk mitigation efforts to be established or effective.

Economic challenges flowing from the pandemic persist. The outlook remains weak: at the time of writing, the global economy was expected to be 2.3% smaller by 2024 than it would have been without the pandemic. Rising commodity prices, inflation and debt are emerging risks. Moreover, with another spike in COVID-19 cases towards the end of 2021, the pandemic continues to stifle countries ability to facilitate a sustained recovery.

The economic fallout from the pandemic is compounding with labour market imbalances, protectionism, and widening digital, education and skills gaps that risk splitting the world into divergent trajectories. In some countries, rapid vaccine rollout, successful digital transformations and new growth opportunities could mean a return to pre-pandemic trends in the short term and the possibility of a more resilient outlook over a longer horizon. Yet many other countries will be held back by low rates of vaccination, continued acute stress on health systems, digital divides and stagnant job markets. These divergences will complicate the international collaboration needed to address the worsening impacts of climate change, manage migration flows and combat dangerous cyber-risks.

Short-term domestic pressures will make it harder for governments to focus on long-term priorities and will limit the political capital allocated to global concerns. Social cohesion erosion is a top short-term threat in 31 countriesincluding Argentina, France, Germany, Mexico and South Africa from the G20. Disparities that were already challenging societies are now expected to widen51 million more people are projected to live in extreme poverty compared to the pre-pandemic trendat the risk of increasing polarization and resentment within societies. At the same time, domestic pressures risk stronger national interest postures and worsening fractures in the global economy that will come at the expense of foreign aid and cooperation.

Respondents to the GRPS rank climate action failure as the number one long-term threat to the world and the risk with potentially the most severe impacts over the next decade. Climate change is already manifesting rapidly in the form of droughts, fires, floods, resource scarcity and species loss, among other impacts. In 2020, multiple cities around the world experienced extreme temperatures not seen for yearssuch as a record high of 42.7C in Madrid and a 72-year low of 19C in Dallas, and regions like the Arctic Circle have averaged summer temperatures 10C higher than in prior years. Governments, businesses and societies are facing increasing pressure to thwart the worst consequences. Yet a disorderly climate transition characterized by divergent trajectories worldwide and across sectors will further drive apart countries and bifurcate societies, creating barriers to cooperation.

Given the complexities of technological, economic and societal change at this scale, and the insufficient nature of current commitments, it is likely that any transition that achieves the net-zero goal by 2050 will be disorderly. While COVID-19 lockdowns saw a global dip in greenhouse gas (GHG) emissions, upward trajectories soon resumed: the GHG emission rate rose faster in 2020 than the average over the last decade. Countries continuing down the path of reliance on carbon-intensive sectors risk losing competitive advantage through a higher cost of carbon, reduced resilience, failure to keep up with technological innovation and limited leverage in trade agreements. Yet shifting away from carbon-intense industries, which currently employ millions of workers, will trigger economic volatility, deepen unemployment and increase societal and geopolitical tensions. Adopting hasty environmental policies could also have unintended consequences for naturethere are still many unknown risks from deploying untested biotechnical and geoengineering technologies. And poorly regulated green markets could create monopolies, while lack of public support for land use transitions or new pricing schemes could create political complications that further slow action. A transition that fails to account for societal implications will exacerbate inequalities within and between countries, heightening geopolitical frictions.

Growing dependency on digital systemsintensified by COVID-19has altered societies. Over the last 18 months, industries have undergone rapid digitalization, workers have shifted to remote working where possible, and platforms and devices facilitating this change have proliferated. At the same time, cybersecurity threats are growingin 2020, malware and ransomware attacks increased by 358% and 435% respectivelyand are outpacing societies ability to effectively prevent or respond to them. Lower barriers to entry for cyberthreat actors, more aggressive attack methods, a dearth of cybersecurity professionals, and patchwork governance mechanisms are all aggravating the risk.

Attacks on large and strategic systems will carry cascading physical consequences across societies, while prevention will inevitably entail higher costs. Intangible riskssuch as disinformation, fraud, and lack of digital safetywill also impact public trust in digital systems. Greater cyber threats also risk driving states apart if governments continue to follow unilateral paths to control risks. As attacks become more severe and broadly impactful, already-sharp tensions between governments impacted by cybercrime and governments complicit in their commission will rise as cybersecurity becomes another wedge for divergencerather than cooperationamong nation-states.

Growing insecurity resulting from economic hardship, intensifying impacts of climate change and political instability are already forcing millions to leave their homes in search of a better future abroad. Involuntary migration is a top long-term concern for GRPS respondents, while 60% of them see migration and refugees as an area where international mitigation efforts have not started or are in early development. In 2020, there were over 34 million people displaced abroad globally from conflict alonea historical high. However, in many countries, the lingering effects of the pandemic, increased economic protectionism, and new labour market dynamics are resulting in higher barriers to entry for migrants who might seek opportunity or refuge.

These higher barriers to migration, and their spill-over effect on remittancesa critical lifeline for some developing countriesrisk precluding a potential pathway to restoring livelihoods, maintaining political stability and closing income and labour gaps. At the time of writing, the United States faced over 11 million unfilled jobs in general and the European Union had a deficit of 400,000 drivers just in the trucking industry. In the most extreme cases, humanitarian crises will worsen since vulnerable groups have no choice but to embark on more dangerous journeys. In 2021, 4,800 migrants, including families and children, perished or went missing during the journey. Migration pressures will also exacerbate international tensions as it is increasingly used as a geopolitical instrument. Destination-country governments will have to manage diplomatic relationships and immigrant skepticism among their populations.

While humans have been exploring space for decades, recent years have witnessed increased activity, not only creating new opportunities but also signaling an emerging realm of risk, particularly with growing militarization and weaponization in the arena. New commercial satellite market entrants are disrupting incumbents traditional influence over the global space commons in delivering satellite services, notably internet-related communications. A greater number and range of actors operating in space could generate frictions if space exploration and exploitation are not responsibly managed. With limited and outdated global governance in place to regulate space alongside diverging national-level policies, risks are intensifying.

One consequence of accelerated space activity is a higher risk of collisions, which could lead to a proliferation of space debris and impact the orbits that host infrastructure for key systems on Earth, damage valuable space equipment, or spark international tensions. Limited governance tools increase the likelihood of space activity escalating geopolitical tensions, and recent weapons tests in space underscore such risks. Increased space activity could also lead to unknown environmental impacts or raise costs for public goods such as weather monitoring or climate change surveillance.

In 2021, countries deployed new mechanisms to respond to a public health crisis with shifting characteristics, leading to both successes and failures. Two interlinked factors were critical for effective management of the pandemic: first, the readiness of governments to adjust and modify response strategies according to changing circumstances; and second, their ability to maintain societal trust through principled decisions and effective communication.

Reflecting on the distinct resilience goals of governments, businesses and communities will help ensure that agendas are aligned in achieving a whole-of-society approach to tackling critical risks of any nature. For governments, balancing costs, regulating for resilience, and adjusting data-sharing arrangements to ensure sharper crisis management are key to galvanizing stronger interaction between public and private sectors. Businessesrecognizing that better national-level preparedness is critical for planning, investing, and executing their strategiescan leverage opportunities in areas such as supply chains, codes of conduct within their industry, and inclusion of a resilience dimension into workforce benefit offerings.

Communities can help local governments to join up with national efforts, improve communication and support grassroots resilience efforts. At an organizational level, strategies such as grounding resilience analyses in key delivery outcomes, appreciating systemic vulnerabilities and embracing a diversity of approaches can help leaders build better resilience as well.

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Major LGBTQ+ organisations spark international review of the EHRC – Stonewall

Posted: at 8:31 am

All of us need our human rights protected and upheld. This is a fundamental value that rises above the politics of the day.

That is why the United Nations has robust mechanisms in place internationally to ensure that National Human Rights Institutions (NRHIs) can operate independently of the changing priorities of any government.

These are known as the Paris Principles the minimum standards required for NHRIs to meet to be considered effective and credible. For an NRHI to achieve an A status, which allows them to participate at the UN Human Rights Council, they must be fully compliant with these principles.

We believe that recent statements made by the Equalityand Human Rights Commission (EHRC), Great Britains NHRI, indicate that they can no longer be considered compliant with the Paris Principles, and are no longer fit for purpose as a National Human Rights Institution.

This week, a coalition ofLGBTQ+ and trans focusedcharitiesand human rights bodies, led by Stonewall and supported by the Good Law Project, wroteto the United Nations and the Global Alliance of National Human Rights Institutions (GANRHI) to formallysubmit evidence to support calls fora Special Review of theAstatus ofEHRC asGreat Britains National Human Rights Institution.

The submission is prompted by the EHRCs recent, and significant, change in stance on theissue of trans rights. Their recent statements on GRA reform in Scotland, and the conversion therapy ban in England and Wales, not only reverse their long-held positions, but are in stark contrast to international human rights standards. The EHRCs stance seeks to strip trans people of legal protections, and pose a grave threat to the abilityoftrans people to participate in daily life with dignity and respect.

The 19-page submission outlines substantial evidence that reveals the numerous ways the EHRC now finds itself falling short of international standards.

The 19-page submission outlines substantial evidence that reveals the numerous ways the EHRC now finds itself falling short of international standards. It outlines a complete absence of financial autonomy from the UK Government, and cites excessive governmental interference including politically motivated appointments to the Chair and Board, many of whom have repeatedly and publicly demonstrated their opposition to the expansion of human rights, and whose appointments have drawn widespread criticism from NGOs.

The signatories of this exercise accept that UK Government policy changes based on their democratic mandate.

However, the important point of NHRIs is that they should operate according to the principle of acting independently, free from political inference, and focus on upholding international human rights standards regardless of the politics of the day.

The politicisation of GB'shuman rights body to take a determinedly anti-trans stance has placedtrans peoplein the firing line.

The politicisation of the GBs human rights body to take a determinedly anti-trans stance has placedtrans peoplein the firing line.

But the EHRCsattempt to create ahierarchyofhuman rights in Great Britain is a very real threat to everyone, particularly those of us protected by the Equality Act. That is why we have taken swift action to call for an international review, and domestically, we are calling for the Women & Equalities Select Committee to hold a review into the matter.

It is difficult to see how the EHRC can continue to hold itscurrent status, given how compromised it appears to be, and how farfrom Paris Principles compliance it has drifted. We call on the UK Government to show leadership byensuring we have a revived and truly independent EHRC that is fit for purpose.

Signatories

Good Law Project

Liberty

Feminist Gender Equality Network

Allsorts

Tonic Housing

Global Butterflies

Quotes from signatories

The EHRC is walking away from its duties to uphold basic human rights for trans and non-binary people. It no longer commands our confidence, and we fear what it now intends. It will take some strong and swift actions to convince us that it is on our side, actions we no longer think it is capable of. -TransActual

As the UKs leading charity supporting trans people, we join Stonewall in calling on the UN to review the A status of the Equality and Human Rights Commission. The EHRCs biased approach to trans rights raises big questions around its integrity and so-called independence. The EHRC uses its A status as evidence of its credibility on its website a credibility that creates an authority which is currently contributing to the roll-back of trans rights in the UK. We ask for a thorough examination of the EHRC through the lens of the UN, because the public deserve an impartial watchdog, not one that drives government agendas. -Mermaids

"As independent human rights organisations we must uphold human rights equally, regardless of political whim or public opinion. The EHRCs recent announcements however, run contrary to this basic principle. Far from pushing UK governments to go further and strengthen equality and rights protections for LGBT people it is calling for UK governments to pause their plans. It has also made suggestions about conversion therapy which actively undermine the health and well-being of trans people in the UK right now. The departure from its purpose is as staggering as it is unacceptable. The EHRCs role as a National Human Rights Institution must be reviewed. -Martha Spurrier, Director of Liberty.

"The past years have seen LGBT and other human rights organisations lose faith in the EHRC to serve as an independent body, or one that works for the protection of our rights. It has shown again and again it will take dangerous, swingeing moves against marginalised people if it deems it politically expedient to do so. This is doubly true, as the last few weeks have shown, for the trans and non-binary people whose rights it should be standing up for, not seeking to undermine." - Gendered Intelligence

At GIRES, our aim is to ensure that national and international legislation and practice meet the needs of trans and gender diverse people. We call on EHRC and our Government to work with trans communities now, to call out prejudice and discrimination, improve our existing equality legislation, strengthen our fight for trans human rights, in the UK and elsewhere. - Cat Burton, GIRES Chair and Shaan Knan, GIRES Vice Chair

"The EHRC is subject to a level of oversight and micro-management from the Department which is just not consistent with being a UN Human Rights Institution. They are supposed to be independent from Government but the EHRC looks much more like a tool of Government." - Jolyon Maugham, Director of the Good Law Project

As a national LGBT+ specialist infrastructureand membership organisation, Consortium share the serious concerns raised by member organisations and allies about the direction of the EHRC. We are deeply troubled by the threat that the EHRCs actions pose to the human rights of trans people. We stand with all trans and non-binary people in defending their human rights, dignity and safety In the UK and globally. - LGBT Consortium

A review of the EHRC is urgently needed. As a UN-accredited National Human Rights Institution, it should operate according to the Paris Principles, which include the commitment to promote and protect all human rights and to contribute to a world where everyone, everywhere fully enjoys their rights. We believe the EHRC fail in this. Defending trans and non-binary peoples rights, dignity and safety is critical. - Rob Cookson, Deputy Chief Executive, LGBT Foundation

This submission clearly sets out our concerns about undue UK Government influence on the EHRC. The EHRC also seems to be riding roughshod over the arrangements that are in place to ensure proper consultation in Scotland on devolved matters including gender recognition reform. - Tim Hopkins, director of the Equality Network

"We are supporting this submission, because as a feminist organisation with members worldwide and one committed to equality for everyone including trans people, we are concerned and disgusted by the activities of the EHRC and its failure to support the human rights of trans people in the UK. We believe the UN and the international community as a whole needs to take action against the EHRC's threat to human rights of many groups of people in the UK." - Feminist Gender Equality Network

The way the EHRC is constituted makes it institutionally unfit for purpose. It is subject to unacceptable levels of political and financial control and thus cannot meaningfully be regarded as an independent reviewer of human rights within the UK. This follows serious shortcomings called out previously in the Women and Equality Select Committee report as well. EHRC has now advocated multiple policies which pose a serious threat to the human rights of trans individuals. We demand a complete overhaul. - Trans Safety Network

Galop has significant concerns about the EHRC's views on trans rights. As the largest organisation in the UK working directly with LGBT+ victims of abuse, we believe its current position will have serious negative impacts on those we support, and on our community as a whole. - Galop

Under the direction of Baroness Falkner, the Equality and Human Rights Commission has proved time and again that it is no longer fit for purpose, or global recognition as an independent human rights body. We stand with Stonewall and other LGBTQIA+ charities and human rights organisations in condemning the EHRCs failure in its mission to encourage equality and diversity, eliminate unlawful discrimination, and protect and promote the human rights of everyone in Britain. - Sparkle The National Transgender Charity

Our concerns about EHRCs change in approach in Scotland, resulting in the potential adverse impact on the human rights of young LGBTI people, are included within this submission. They are echoed in an open letter to Scottish Government by our Trans Rights Youth Commission who recently highlighted that EHRC are meant to be defenders of our human rights while clearly expressing their hurt and anger to this change in stance. We welcome this request to GANHRI and add our voice calling for a Special Review -Dr Mhairi Crawford, Chief Executive of LGBT Youth Scotland

"With EHRC's complete reversal on their own positions they have shown that current leadership is actively hostile to trans people in the UK and cannot be considered fit for purpose as a human rights organisation." - Gemma Dellbridge, Operations Director, Be Trans Support and Community

Government interference with the EHRC has led to it being unfit for purpose which we believe is strategic in the UK's escalating hostile environment towards marginalised communities. A special review by the UN will give hope to many that although this small island may appear adrift, we are seen and heard by much greater countries internationally. - Carla Ecola, Co-founder, The LGBTQI+ Outside Project

Spectra welcomes this rigorous and detailed initiative from Stonewall calling for a special review of the EHRC. Concerns with organisational independence from government together with the failure of the EHRC to attend to issues of trans equality have eroded the EHRC's reputation, underscoring the necessity of action. -Spectra

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Government to set up Military Base in the Afram Plains – GhanaWeb

Posted: at 8:31 am

Seth Acheampong, Eastern Regional Minister has visited the site fir the new military base

The Government will set up a military base in Akyemfuor near Maame Krobo in the Afram Plains South District to tackle growing insecurity associated with conflicts between cattle herdsmem and local farmers.

Akyemfuor Asiedu Agyemang, the Chief of Abetifi and also Adontenhene of Kwahu Traditional Area, allotted the 50-acre land to the state for the construction of the camp dubbed, Forward Operation Base.

Provision of the land has been hailed as a good intervention that would assist the Government to help tame recurring conflicts between local farmers and Fulani cattle herdsmen, and further improve general security in the Afram Plains.

Mr Seth Acheampong, Eastern Regional Minister and Chairman of the Regional Security Committee, visited the site on Wednesday in the company of top military officers, including Brigadier-General Michael Amoah-Ayisi, General Officer Commanding Southern Sector and Brigadier-General Gyane Adoh Richard, Director for Planning and Research Development.

The team inspected the land and was also shown temporary structures at Kwanin that have been provided by the chiefs to accommodate personnel as efforts were being made to construct the permanent camp.

Mr Acheampong told the Ghana News Agency in an interview that the establishment of the Special Forces base had become imperative because several efforts to get the security issues in the Afram Plains addressed had proved ineffective.

The objective of the establishment of the military base is to ensure that there is peace in the community. Crop farming is an economic activity and similarly, cattle farming is truly an economic event and we should not despise what they(Fulani Herds men) do, he said.

All that the government require is for these farmers to live interdependently and grow the community progressively, he added. This is the reason of engaging and setting up the camp so that whenever conflicts arise, they can step in to restore peace.

He stressed that the setting up of the Forward Operation Base would certainly happen at Akyemfuor with the inspection of the parcel of land, We are commencing it.

He added, A journey of a thousand miles always begins with a start so coming here today is building up the foundation that will help us to achieve the overall objective of permanent stay of the military men here in Afram Plains South District.

Also speaking with the GNA, Mr Evans Kyei Ntiri, District Chief Executive of Afram Plains South District, explained that the issues with crop farmers and Fulani cattle herdsmen had been occurring seasonally, and that, he believed with the presence of a military base it would be curbed.

Afram Plains has one of the biggest markets in the Eastern Region, generating substantial revenue, but people who trade in and out of the geographical enclave do not get a safe passage due to rampant robbery attacks and theft, which local farmers blame on the trans-human cattle herdsmen.

This has often erupted into conflicts between the farmers and the herdsmen, escalating insecurity in the predominantly farming area.

But Mr Ntiri assured residents and traders of a lasting solution and urged them to calm down tempers because those security issues were going to be things of the past following the establishment of the military base.

He expressed the hope that within one month, the military personnel would arrive as it had been said.

He praised the Chiefs and people of the area, especially Akyemfuor Asiedu Agyemang for giving out the land, as well as Daasebre Akuamoah Agyapong, Paramount Chief of Kwahu Traditional Area, for his continuous support to finding a lasting solution to the menace.

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Alt-Right Armory Podcaster Faces Charges of Possessing Machine Guns – The New York Times

Posted: at 8:30 am

In arguing that the younger Mr. Berger, who does not have a criminal history, was a threat and should be detained until trial, prosecutors cited the anti-government and anti-law enforcement views espoused on his podcast.

In one episode, Mr. Berger said a white man with a rifle can be very dangerous to the system indeed if he has the right motivation and also praised the values of Eric Frein, who was convicted and sentenced to death in the 2014 ambush killing of a Pennsylvania state trooper, prosecutors said in court documents.

Mr. Berger and an unidentified co-host also discuss targeting the police, along with legislators, lobbyists and left-wing billionaires, for assassination, prosecutors said.

They halfheartedly claim that the discussion is a prank and a playful thought, and they are not advocating for violence, but it is clear that the discussions are serious, prosecutors wrote.

A magistrate judge granted the prosecutors motion to keep the younger Mr. Berger detained. The judge released the elder Mr. Berger on $25,000 bail. He could not be reached at his home on Saturday night. If convicted, they face up to 30 years in prison, prosecutors said.

In the pilot episode of his podcast on Jan. 14, 2019, the younger Mr. Berger explained the origin of his love of guns.

It started when he was 5 years old, shooting milk cartons with an air pistol in the Poconos in Northeastern Pennsylvania. But it wasnt until after he went to a shooting range for his birthday, when he was 9 or 10, shortly after watching Dirty Harry, the 1971 movie starring Clint Eastwood in the role of a homicide division inspector who uses brutal tactics against criminals, that Mr. Berger became hooked on guns, he said.

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Selling the Metaverse – The American Conservative

Posted: at 8:29 am

Marc Andreessen on a panel at the Fortune Global Forum at the Fairmont Hotel on November 3, 2015 in San Francisco, California. (Photo by Kimberly White/Getty Images for Fortune)

Last Christmas Eve, I was driving with my 17-year-old nephew through an industrial part of northeast Portland, Oregon, when he pointed out some new graffiti on a wall near his house. How Does The Metaverse, someone had written, in quite beautiful blue script, Help Poor People?

This struck me as a very poignant thing to spraypaint on a wall in a run-down section of a midsize American city, not far from a huge and heart-rendingly grim homeless encampment on Columbia Avenue. Whoever wrote it must have had a sense that a massive change in how humans live and interact was looming before us all. We can be sure that they didnt know what this Metaverse would look like, since no one knows exactly. But they knew enough to be alarmed by it, and they must have had a sense that ordinary people wouldnt have much say in how it shaped up and impacted their lives. They knew that there was no point in writing their congressman or the local newspaper to discuss whether or not Americans really want to live out their lives in a digital simulacrum of reality, or to question whether it makes sense for us to deploy massive portions of our nations capital and brainpower toward building this simulacrum. Those sorts of questions get answered by investors and tech executives, and almost no one in power in this country thinks they ought to fall under the purview of our democracy or public debate. So they were left to scrawl a plaintive little protest, on a wall between a weed dispensary and a Vietnamese grocery.

There are hardly any better ways in American life to express political objections to the tech- and capital-driven changes that have so reshaped our lives in the past decadesfrom the industrialization of American agriculture to mass adoption of the media technologies that have done so much to destroy our brains and public debate. One of our last vestiges of mainstream consensus is that we talk about these shifts as irresistible, not subject to serious objection. But something strange is happening with the idea of the Metaverse, a basket of consumer technologies that might someday add up to an immersive and interconnected virtual world where many very powerful people hope we may soon be socializing, looking at art, buying property, and generally conducting our individual human lives through the prism of a mass-produced consumer headset. The systems that work to convince us that consumer technologies are inevitably a step forward in the march of human progress are fraying. No one was going around spraypainting anti-iPhone slogans on buildings back in 2009. The Metaverse is being planned, but it is going to take some effort to sell it.

Last spring, the early web pioneer, billionaire investor, and Facebook board member Marc Andreessen did an interview that got a lot of attention in the small world of people who theorize about tech, and almost none outside of it. It was with a pseudonymous figure who writes under the name Niccolo Soldo, who alternates between obviously satirical forays and genuinely weighty questions about how tech has reshaped human life in the past few years. About halfway through, Soldo asked Andreessen a question about whether our world of constant screen-based communication was hurting our collective mental health.

Your question is a great example of what I call Reality Privilege, Andreessen answered, before going into a world-historical vision of what the Metaverse would offer to humanity. Reality Privilege was an idea hed borrowed from the virtual reality developer Beau Cronin, who wrote way back in 2015 that physical reality, such as we experience as we go through the world in our human bodies, was a painful and unpleasant experience for manymaybe even mostof us. So it was a mark of privilege, comfort and luck, to think of non-digital reality as being truer or more worthwhile than one experienced through a screen. If its hard to imagine much about your life that could be improved by porting to a new platform, Cronin wrote about virtual-reality worlds, then maybe youre not the target user here. Consider the possibility that a visceral defense of the physical, and an accompanying dismissal of the virtual as inferior or escapist, is a result of superuser privileges. You are one of the Verified Users of the real. Congratulations for now, but beware the platform shift ahead.

At the time, Cronin was struggling with addiction and mental health issues, which may have had something to do with the fact that he cited traveling for in-person meetings as one aspect of reality he personally found to be onerous. He offered a prediction that, at least with regard to those meetings, has already largely come true: In ten years time, he wrote, well find absurd many of the activities we waste our physical presence on today.

But even Cronin seemed taken aback by Andreesens later elaboration of the Reality Privilege concept, and the intense discussion it produced in the tiny world of people who follow this sort of thing. A small percent of people live in a real-world environment that is rich, even overflowing, with glorious substance, Andreessen told Soldo. Beautiful settings, plentiful stimulation, and many fascinating people to talk to, and to work with, and to date. But these are just the lucky among us. Everyone else, he said, the vast majority of humanity, lacks Reality Privilegetheir online world is, or will be, immeasurably richer and more fulfilling than most of the physical and social environment around them in the quote-unquote real world.

It turned out that Andreessen had a very direct answer to the question of how the Metaverse would help poor people. The Reality Privileged, he said, call this conclusion dystopian, and demand that we prioritize improvements in reality over improvements in virtuality. To which I say: reality has had 5,000 years to get good, and is clearly still woefully lacking for most people; I dont think we should wait another 5,000 years to see if it eventually closes the gap. We should buildand we are buildingonline worlds that make life and work and love wonderful for everyone, no matter what level of reality deprivation they find themselves in.

So heres an immensely influential billionaire, with a huge personal stake in the development of the Metaverse, leveraging the language of privilege to suggest that the opinions of people who protest that were being lead towards dystopia are definitionally invalid. And Im going to offer a prediction: you will hear more arguments like this in the near future. But this is less of a new line of thinking than it may appear at first. Andreessen is just stating things more clearly than anyone had to back before we knew how ruinous the consumer technologies sold to us as social progress would be to our lives and society. Because if we can see how this Metaverse is being sold, maybe we might not end up buying it.

* * *

This interview took place several months before Facebook announced, in late October 2021, that it was changing its name to Meta and reorienting the company around building this new Metaverse. I mention this because the timeline is important. It seems safe to assume that many people reading this had never even heard of the Metaverse before Facebooks name-change produced a burst of coverage about the idea, almost all of it taking it as a given that this Metaverse would soon be a reality. They were right, in a way, to take it for granted. We are building this new world, Andreessen had said, and he meant it.

That morning in October, a host for NPRs Morning Edition brought on a tech reporter for the Verge to talk about what the Metaverse would look like. The ground for this interview had obviously been laid far in advance, with select tech reporters briefed by Facebook with embargoed talking points so theyd be ready to spread the news once Meta was ready for its big unveiling. But the NPR host asked a question that the Verge reporter was quite obviously unprepared for. So who wants this Metaverse? he asked. I mean, is this filling a demand? The reporter stammered audibly. The unspoken rule that we are supposed to uncritically embrace tech offerings like this had been violated. Uh, he said, well, its not built yet. He changed the subject.

But this was only partly true. Within days of the announcement, Nike filed a trademark application for digital sneakers. There was already a burgeoning market for virtual real estate in virtual worlds with names like The Sandbox and Decentraland. A subsidiary of Pricewaterhouse Coopers disclosed in December that it had been buying land in The Sandbox, a project of a Hong Kongbased company that has made prominent partnerships with Snoop Dogg and announced plans to build a virtual-reality concert venue in partnership with Warner Music. Its like buying land in Manhattan 250 years ago, one investor told the Wall Street Journal. Facebook-now-Meta invested $10 billion last year in developing its own large corner of the Metaverse, with the idea that soon Metaverse worlds created by Apple and Google and various gaming companies could be integrated into a more or less seamless virtual reality experience. There was already an infrastructure in place to sell the world on a product most people didnt yet even know existed.

But this world must exist, if youre thinking about the needs of corporate America. Because almost all our major innovations in the past 50 years have been in the form communications technologies and financial tinkering. The Metaverse offers a vital new avenue for profits and growth, in an economy increasingly decoupled, as gentle phrasing has it, from material reality. People may spend their time hanging out on Twitter and Facebook, as the tech writer and Twitter gadfly Noah Smith wrote recently, but with a few exceptions, they still produce and sell stuff in the real world. The more complex and flexible of a virtual reality the Metaverse creates, the more humans will actually be able to innovate new goods and services within that reality.

This gives you a more realistic picture of this Metaverse than what you usually get from slavish media reports about a beautiful, seamless new world. Its a jumble of half-developed products and speculative corporate forays, more notable at this point for the strange and inventive ways that companies have planned to monetize every aspect of virtual-world life than for any immersive VR experiences. The closest thing we have to the Metaverse as planned by Andreessen are video games, and the most radical innovations in these game-worlds are decentralized currencies and the ability (limited as yet, but growing) for inhabitants to invest in things like land and houses that they would have no hope of affording in the physical reality as we know it. But with investors already moving into the market, it may soon be as difficult for a young person to imagine buying a house in Decentraland as in the real world.

This is where the selling comes in. The Metaverse on offer in the next few years is going to be like the internet we already have, only more so: more ways to consume time and attention, more ways to get you to spend money, more ways for corporations and brands to get involved in areas of life we once knew as profound and on some level private, like intimate communication or our experience of art. This internet we have today is a disaster. Everyone knows this, even the people responsible for creating it. Many of those very people now feel very defensive and concerned that our collective enchantment with their offerings may be wearing off.

I talked recently with Nir Eyal, who has made a career and personal brand for himself by founding a company selling ads for Facebook and then consulting for tech giants on how to harness compulsive behaviors for profit. We were talking about whether its actually possible for people to choose whether or not to adopt consumer technologies that are designed and sold on a mass scale. He laughed off our developing societal anxiety about the power of Facebook-now-Meta in shaping our world. Look, how many more stories about how Facebook is hijacking our brain do we need? he asked me. My narrative is about personal empowerment, not of victimization.

He meant that we all have a choice, as individual consumers, how much we engage with the products that these companies build, so it would be misplaced to question their right to build them or to blame them for the impact theyve had on our own real world. Weve moved from skepticism to now cynicism, he complained. Now theres nothing that tech can do right. Its all about this cynical power struggle. The viewpoint is now that because these companies have power, they will abuse power.

Every new technology we kind of freak out, he said later about the Metaverse. So, on one hand, Im not surprised that theres a moral panic around the new technology revolution. But on the other hand, I am kind of surprised that we dont learn the lessonthat how we get through this stuff is we adapt our behaviors, and by adopting new technologies to help us get through the last generation of technologies.

This was an unintentionally revealing way of describing how consumer technology works today. It seems strange to think that we have to get used to new modes of livingwe must get through them, as Eyal saysin order to accommodate our lives to a new technology that does not actually fill any pre-existing human need. Most people dont adopt these technologies because they consciously decide that theyre a valuable addition to their personal lives. We accept them in response to a complex of social and economic pressures that arise when a technology achieves mass adoption. Only a lucky few people in our society today have enough privilege to decide whether or not to use a smartphone. The same thing will have to come true for the Metaverse, if its going to work as planned.

* * *

Shortly after the interview where Andreessen outlined the idea of Reality Privilege, the tech writer Nicholas Carr, a Pulitzer finalist for his book The Shallows, described Andreessen as the Metaverses Statue of Liberty.

He stands just outside the virtual worlds golden door, Carr put it, illuminating the surrounding darkness with a holographic torch, welcoming the downtrodden to a new and better life. It was a winkingly funny image for anyone who knows much about Andreessen, a stout figure with a famously large and eggish bald head.

But Carr understood the subtle ways that conversations among powerful people in tech can shape the way that the media talks about this sort of thing. Thats how the selling of something like the Metaverse really gets done.

He mentioned that Andreessen has been called the Obi-Wan to Mark Zuckerbergs Luke Skywalker. Its tempting to dismiss all this as just more bad craziness from Big Techs fiercely adolescent mind, he said. But that would be a mistake. Andreessen had been thinking about the concept of Reality Privilege since at least 2017, when he brought it up in a conversation with the tech journalist Kara Swisher at a Code conference forum. Andreessen is revealing his worldview and his ultimate goals, Carr said. He has the influence and the resources to, if not create the future, at least push the future in the direction he prefers.

You can already see this power at work. Virtual worlds, immersive online experiences, digital economiesthese concepts are new and different and often uncomfortable, the investor and tech blogger Rex Woodbury wrote soon after Andreessens interview came out. Even I occasionally find it all a little dystopian. But the concept of Reality Privilege resonates. Not everyone has the chance to live in Manhattan. Who was he, with all his privilege, to argue against a chance for the reality-impoverished to live there virtually?

But he doesnt have much of a choice either way. This sexy VR future grows nearer with every advance in computer power, an op-ed in the Los Angeles Times by Rob Brooks, an Australian biologist, stated recently. With faster processors, better haptics, and teledildonic (look it up yourself!) sex toys that can be controlled remotely, two or more people will have the chance to participate in the same VR-enhanced, physically satisfying sex scene, while each remains in the comfort and safety of their own home.

You may not have realized how highly planned the future of sex in the Metaverse already is. Be careful about objecting to it, or you may be accused of prudishness. I side with the machines and against the puritans, Brooks wrote. I think artificial intimacy could deliver a more relaxed, inclusive, and humane sexuality, but only if societies have enough maturity to give it a chance.

All of this is being designed, planned, and promulgated to the public as fait accompli, despite the fact that a vote on whether or not to move society into the Metaverse would fail badly. Analysts at Morgan Stanley said the metaverse could represent an $8 trillion opportunity, Business Insider wrote recently in a piece outlining the large-scale plans and investments for the Metaverse of 14 major corporations. But it would be a challenge to get people interested in using it. A recent poll found that only 33 percent of Americans were interested in spending money on digital items in the Metaverse. Generation Z, Insider fretted, needs more convincing that the Metaverse is the shape of things to come.

Its too late to stop them from building them. But somehow I still think it may be possible to build a politics that resists the forces leading us into dystopia and continues the 5,000-year project of improving the reality we already have. Even tech executives are starting to sound worried about where this is all heading. This metaverse is going to be far more pervasive and powerful than anything else, Tim Sweeney, the founder of Epic Games, said recently. If one central company gains control of this, they will become more powerful than any government and be god on Earth.

Thats not quite true. They wont be god on Earth. Theyll be god in the Metaverse. Our only option now is to build an Earth thats preferable to it.

James Pogue is the author of Chosen Country: A Rebellion in the West.

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Selling the Metaverse - The American Conservative

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ESL and EPB: through the lens of Self Efficacy Theory | PRBM – Dove Medical Press

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Introduction

Greening the Management philosophy has become increasingly popular on academic and business fronts.1 In pursuit of greening the management plan, it is realized that organizations having environmentally conscientious employees would reap strategic advantages.2 The vitality of employees in sustaining organizations green initiatives has resulted in an increasing scholarly interest in identifying the predictors and the mediating mechanisms that facilitate employees pro-environmental behavior (EPB).36 According to Graves, Sarkis,6 employees pro-environmental behavior is

a broad set of environmentally-responsible activities such as learning more about the environment, developing and applying ideas for reducing the companys environmental impact, developing green processes and products, recycling and reusing, and questioning practices that hurt the environment.

Such behavior by the employees is essential for realizing organizations green initiatives.7,8

Leaders role is critical in shaping and nurturing employees desired behavior.911 A growing scholarship has explored the influence of different leadership styles in shaping EPB.1214 However, only a few studies are there for environmentally specific servant leadership (ESL).7 Servant leadership is built on the premise of others oriented leadership approach that establishes a one-to-one relationship with followers by prioritizing their needs and interests.15 Under this leadership philosophy, the leader alters employees perspectives from self-centered to pro social to go beyond the call for duty.16 To align with green leadership literature, the authors grounded ESL in the Liden, Wayne10 servant leadership model, which emphasized the leadership role in

emotional healing, green value creation, conceptual skills, green empowerment, helping subordinates to realize environmental goals, putting the environment first, and behaving ethically towards the environment.

In response to the calls for research and to better understand the underlying mechanisms of ESL,1517 we identified green self-efficacy as a mediating channel that explains the relationship between ESL and EPB.

Though servant leaders treat all employees equally, employees individual differences may lead them to respond differently.18 Thus, exploring the underlying mechanisms of the relationship between ESL and EPB is highly meaningful. Efficacy theory19 accentuates that individuals self-efficacious belief is strongly linked with their resulting performance.20 It is emphasized that to act pro-environmentally, employees need to care about the community at large. It is advanced that ESL can catalyze this state of caring by nurturing employees self-efficacy needs. Self-efficacy at the workplace refers to an employees realization of his/her potential to accomplish the assigned task.19 Instead of general self-efficacy, we employ green self-efficacy, being more effective in predicting employees environment-related behaviors.21 We argue that ESL supplements the four essentials of employees green self-efficacy, ie, mastery experience, vicarious experience, verbal persuasion, and psychological feedback, which in turn foster EPB. Theoretical underpinnings of servant leadership and self-efficacy theory support the postulation that employees green self-efficacy is vital to realize EPB.

The authors claim three distinctive value-additions of this research to the knowledge of employee pro-environmental behavior and environmentally specific leadership. First, advancing self-efficacy theory, this research explores green self-efficacy as the mediating channel through which ESL predicts EPB. Secondly, it supplements the limited empirical investigations by responding to multiple calls for research to examine servant leaderships role in shaping EPB.13,22 Third, concerning EPB, the energy sector is a comparatively new context despite being highly relevant due to its share in adversely impacting the environment.13

During the last decade, a shift in the focus of leadership studies has been started towards environmental issues,2325 and environmentally specific constructs of various leadership styles have emerged.2629 To date, environmentally specific or green transformational leadership attracted a significant share of studies predicting its influence on employees environment-related behaviors. However, only recently, Tuan (2018) conceptualized environmentally specific servant leadership that has started attracting researchers in this area.13 Building on Liden, Wayne10 model of servant leadership, our conceptualization of environmentally specific servant leadership emphasizes the leadership role in

emotional healing, green value creation, conceptual skills, green empowerment, helping subordinates to realize environmental goals, putting the environment first, and behaving ethically towards the environment.13

Theoretically, ESL is perhaps the most suitable amongst the positive leadership styles in influencing EPB.7 However, very few studies examined ESL in relation to employees behaviors towards protecting the environment. This study intends to advance the ESL literature by exploring its influence on EPB.

EPB is defined as

a broad set of environmentally-responsible activities such as learning more about the environment, developing and applying ideas for reducing the companys environmental impact, developing green processes and products, recycling and reusing, and questioning practices that hurt the environment.6

It is usually difficult for organizations to explicitly specify all of such behaviors in the formal job descriptions. Thus, the performance of EPB demands an extra call for duty from the employees and is critical for achieving the corporate greening objectives,7 improving organizations financial performance,30 and also in protecting the eco-system.9 EPB represents their ethical conviction towards preserving the environment and is consistent with the philosophy of servant leadership, where transforming followers as environmental servants is a top priority.

Servant leaders considered it their primary responsibility to serve others, including employees, customers, and the community.31,32 Serving a wider spectrum, including protecting the environment, would activate EPB.13 Environmentally specific servant leaders do not consider economic gains when it comes to protecting the environment and encouraging followers to value it.33 Instead, they offer their subordinates the required training and knowledge and sensitize them to participate in pro-environmental initiatives.7 Such leaders believe in followers green empowerment and act as role models by behaving ethically towards the environment.26 They build close relationships with the employees and enhance their conceptual skills while helping them to realize environmental goals.

In addition to the arguments above, empirical evidence also supports the postulation that ESL is positively linked with employees environment-related outcomes.3335 Therefore, the following is hypothesized:

H1: Environmentally specific servant leadership positively influences EPB.

Bandura36 defined self-efficacy as a belief in ones capabilities to organize and execute the courses of action required to produce given attainments. Choi37 contended that field-specific self-efficacy has an enhanced capability to predict the behavior in that field. In this study, the authors operationalized green self-efficacy as employees belief about their competencies to engage and accomplish environment-related tasks.13 It refers to employees evaluation of their capabilities to accomplish pro-environmental targets.38 There exists a positive association between green self-efficacy and EPB.13,39 Extant research has examined the intervening role of general self-efficacy between servant leadership and employees outcomes, eg, creativity,20 citizenship behavior,40 and proactivity.41 However, research has not unraveled the mediating role of green self-efficacy in explaining the relationship between ESL and EPB. This study is an attempt to bridge this knowledge gap.

Bandura36 maintained that individuals belief in their efficacy depends on four foundations: mastery experience, vicarious experience, verbal persuasion, and psychological feedback. We advance that ESL would enhance employees green self-efficacy through these four self-efficacy sources. According to Bandura,36 mastership experience, when one has perceived expertise about a task, is the vital ingredient of self-efficacy. Environmentally specific servant leaders, through empowerment, encouraging aptitude, and facilitation of subordinates to find and resolve green issues on their jobs would help them accomplish green tasks. Because of such leaders close one-to-one relationship with followers, they assign each follower an activity that best fits his/her potential. Such leaders would also offer their subordinates opportunities to develop green skills to advance their careers in green jobs. Moreover, an environmentally specific servant leader coaches and develops followers, which increases their skills level related to the environmental tasks. Consequently, subordinates receive positive feedback about their accomplishments, which uplifts their mastery experience.

Secondly, the vicarious experiences of employees also shape their self-efficacy belief. Vicarious experience occurs when one witnesses others completing a task successfully.42 Environmentally specific servant leaders possess advanced conceptual skills and the green knowledge of tasks being carried out in the organization. Thus, they are well equipped to assist and support the subordinates. Through their approach of leading by example, such leaders prove their authority as a role model worth imitating.13 The course of role modeling augments employees belief that if their leaders can complete a task successfully, they can succeed in such activities.19

Bandura36 enlisted social persuasion as the third way to develop self-efficacy. Employees could be convinced to believe that they have the expertise and skills to succeed. The verbal appreciation and encouragement from the environmentally specific servant leaders help employees overcome their self-doubts. Such leaders encourage followers and display trust in employees abilities (Joseph & Winston, 2005), thus extracting the best from employees efforts.

Lastly, environmentally specific servant leaders make genuine efforts to understand and support employees by emphasizing building long-term relationships. Furthermore, such leaders regulate the emotions of their subordinates in a positive way, which reduces stress and creates such an environment in which employees feel psychologically safe, which ultimately enhances their self-efficacious belief.42 From this discussion, it is argued that ESL improves employees green self-efficacy, which aids employees to demonstrate pro-environmental behavior on the jobs actively. Therefore, the following is postulated:

H2: The positive influence of ESL on EPB is mediated through employees green self-efficacy.

The theoretical model is presented in Figure 1.

Figure 1 Theoretical Model.

This studys population comprised employees and their respective supervisors from Pakistans energy sector. Selecting the respondents from this sector is profoundly meaningful because of its significant share of greenhouse gas emissions in the country, nearly fifty percent.7 Besides, due to the $33 billion foreign investment, this sector is undergoing rapid expansion and entrusted to enhance the share of renewable energy from two percent to thirty percent by 2030 in the countrys energy mix.43 Then, this is one of the few comprehensive sectors in Pakistan comprising generation, dispatch, and distribution of energy. Further, it must adhere to the sustainability parameters for seeking loans and aids from international donor agencies.

The study fulfills requirements laid down in the declaration of Helsinki. Researchers explained the purpose and aims of the study in the questionnaire. A statement clearly indicated that the participation was purely voluntary and the participants could exit at any stage. The study was not invasive in any respect and did not pose any harm, whether mental, physical or in terms of their professional reputation/interactions. They were assured of anonymity and confidentiality and that the data shall be used in aggregate without identifying any individual. The information collected from all participants in this research project was kept securely by the authors on a dedicated computer and was not shared or transmitted to anyone else. This study was carried out after the approval by the University Research Supervisor and the Research Ethics Committee of Tianjin University of Finance and Economics. As per legal requirements in Pakistan, no further ethical approvals were required from any authority because the study did not involve any manipulation and was not invasive.

Researchers contacted Pakistans Ministry of Energy (Power Division), explained the objective of this research, ensuring the participants privacy, and requested permission for data collection. Employees working at entry-level managerial positions with at least 1 year of experience and their respective supervisors were the studys potential participants. The Ministrys representative shared a list containing names, designations, and email addresses of 2453 employees and their respective 887 supervisors. The systematic random sampling where every 4th employee and the particular supervisor selected as potential participants. Two questionnaires for employees and their immediate supervisors, prepared with Google Docs (see Supplementary Material), were performed online during JuneJuly 2021 with a three-week time-gap to lessen common method bias.44 Online data collection strategy was adopted because the data were collected during COVID-19 and it was convenient to approach the potential participants online rather physically. Although such a research design reduces the final response rate, this study has gathered a reasonable response from the participants. Potential participants were voluntarily requested to fill out the survey. The first wave survey was performed on 613 employees. In that wave, the questionnaire contained questions about employees demographics, green self-efficacy, environmentally specific servant leadership, and the immediate supervisors name to match responses at a later stage. At the end of the first wave, 406 usable responses with a response rate of 66.23% were received. Three weeks after the first wave, the second-wave survey began to collect responses on EPB from the immediate supervisors of already participating subordinates. For the final analysis, 381 matched dyads (employee-supervisor) were gathered. The authors also employed the commonly used method for testing the common method bias, ie Harmans single-factor test.44 In the present research, without factor rotation, the characteristic root of the common factor with the greatest explanatory power is 10.52 that explains 35.62% of the total variance. No single factor explains most covariance of independent variables and dependent variables, confirming that common method bias is not an issue in this research. The sample profile of the participants is presented in Table 1.

Table 1 Sample Profile of Participants

The authors used established measures for tapping all the constructs in this study. Responses were solicited through a 7-point Likert scale, one representing strongly disagree and seven as strongly agree. Employees rated their supervisors as environmentally specific servant leadership through a 12-item scale adapted by Tuan.26 Employees response regarding their green self-efficacy was measured with a 6-item instrument developed by Chen and Chang.38 Finally, each employees immediate supervisor was asked to evaluate EPB on a 10-item measure introduced by Robertson and Barling.45 All the items of the constructs are enlisted in Appendix-A.

The analysis of this research is carried out through the partial least squares structural equation modeling (PLS-SEM) method by using Smart-PLS 3.3.3 software (Boenningstedt, Germany). The PLS-SEM technique is preferred for various reasons. First, PLS-SEM has established its dominance over other statistical techniques for meditation analysis.46 Second, the study at hand is prediction-oriented, where PLS-SEM best suits.46,47 Third, it is comprised of the modern statistical tools of analysis48 and offers improved statistical power.49 Using the PLS-SEM technique, the analysis was performed in the following two stages:

Confirmatory composite analysis (CCA) has recently been advocated by scholars as a systematic methodological process for examining the measurement model in PLS-SEM.50 In CCA, the nature of the constructs, reflective or formative, is specified at the beginning. The study at hand contained all the constructs as reflective lower-order. The CCA was performed in the following steps:

Items loadings evaluation is the first step of CCA in the evaluation of the measurement model. An item loading above 0.708 and the t-statistic above 1.96 under two-tailed is considered significant.50 Items loadings along with t-statistics are enlisted in Table 2.

Table 2 Confirmatory Composite Analysis

The second step in CCA evaluates construct-level reliability. Cronbachs alpha () and composite reliability (C.R) are widely used statistics for the evaluation of construct-level reliability. The threshold values for and C.R are from 0.70 to 0.95.49 The values for and C.R are presented in Table 2 and are within the threshold range for all constructs.

The convergent validity of all the constructs is assessed in the third step of CCA. The average variance extracted (AVE) is the most commonly used statistic for establishing convergent validity of constructs.49 The threshold value of AVE is above 0.50. AVE values for all the constructs are shown in Table 2.

Lastly, CCA is performed to establish the uniqueness of the constructs. The heterotrait-monotrait (HTMT) ratio of correlations46 is the recommended metric, and its values should be below 0.90.49 HTMP values presented in Table 3 settle the distinctness of the constructs.

Table 3 Discriminant Validity

Assessment of the structural model (SM) was carried out by performing the following steps:

Ensuring that multi collinearity is not a potential problem is the first step in the assessment of SM. The variance inflation factor (VIF) is a widely used metric in this regard. The VIF value below three is the threshold in the latest instructions.50 VIF values are well within the limit and are presented in Table 2.

Evaluation of directed and mediation hypotheses is the second step in SM assessment. The bootstrapping approach of the PLS algorithm is employed to obtain the path coefficient () values for all the hypothesized paths. The latest guidelines have recommended reporting percentile bootstrap confidence intervals where for the statistical significance of a structural path, its confidence intervals should not have a zero value.49,51 To understand the nature of mediation, ie partial or full after assessment of the indirect effect, it is essential to look at the strength of the direct effect. If, after introducing the mediating variable(s), the direct effect is still significant, the mediation would be partial, and if that direct effect becomes non-significant, then the mediation would be full.51 To substantiate the mediation results, value for Variance Accounted For (VAF) was calculated which decides about the nature of mediation. As a rule of thumb, the VAF value <0.2, 0.2 but 0.8, and >0.8 means No mediation, Partial mediation, and Full mediation, respectively.52 Results for the assessment of SM are presented in Table 4.

Table 4 Assessment of the Structural Model

Lastly, the structural models quality indicators, including coefficient of determination (R2) and predictive relevance (Q2), are also needed to be presented in the assessment of the structural model. The coefficient of determination highlights the variance explained by independent variables(s) in the dependent variable(s). The R2 threshold values 0.19, 0.33, and 0.67 are considered as small, moderate, and substantial, respectively (Chin, 1998). Similarly, the predictive relevance (Q2) describes the predictive accuracy of a structural model. For the purpose of generating Q2 values, the PLS-SEM blindfolding procedure was employed. Table 4 enlists R2 and Q2 values of the SM. Results of the SM are also presented in Figure 2.

Figure 2 Structural Model Results.

This study aimed to explore environmentally specific servant leaderships mechanisms in predicting EPB through mediating role of employees green self-efficacy.

Our results accentuate the direct effect of ESL on EPB, which is in line with the findings of the past studies.12,26,33 Servant leadership characterized by environmental focus aims at investing in green training and development of employee behaviors while offering constructive feedback in a timely manner and backing up your employees in their green initiatives. Environmentally specific-servant leaders offer employees autonomy and encouragement, which increases their involvement in taking part in green tasks. This finding echoes with past research wherein ESL was shown to influence the employees green or environment-related behaviors.1,7,13 The servant leaders caring attitude towards community and green values helps establish such credibility that he/she is seen as an exemplary figure among followers who copy his/her behavior. Servant leaders under green philosophy equip employees with the necessary environmental knowledge and sharpen their skills and abilities, which in turn help them to engage in EPB.13

Then, the finding establishes that employees green self-efficacy mediates the relationship of ESL with EPB. Environmentally specific servant leaders not just behave and pose responsibly, they also make every effort to provide support and direction, establish autonomy among employees, allocate resources, and extend green training to employees with the aim of growing them as an environmental servant-leader for the future.10,12 The repeated action and learning mechanism from feedback establishes a sense of self-efficacy among employees that they are capable of achieving such positive environmental tasks once they commit. Hence, our results conclude that green self-efficacy acts as a channel through which ESL influences EPB. Environmentally specific servant leaders ensure the basic essentials of self-efficacy through empowerment, extending a chance to participate in pro-environmental tasks freely and displaying a genuine concern towards the initiatives that are important initiatives for employees professional growth. In return, employees engaged in pro-environmental behavior. The results reveal that the nature of mediation in this study is partial mediation which means that other intervening variables also in addition to employees green self-efficacy that may explain the relationship between ESL and EPB.

This paper makes a contribution to the green and pro-environmental literature from multiple management perspectives. First, this study responds to multiple calls for the paper to investigate the relationship between environmentally-specific servant leadership and EPB.7,13 Secondly, this study furthers the scope of self-efficacy theory by incorporating green and pro-environmental behaviors into the existing body of knowledge on green management practices. This is done by studying the mediation effects of green self-efficacy between ESL and EPB. Third, it responds to calls for research on examining the possible mediating effect of employees green self-efficacy from the perspective of servant leadership and EPB.53

The results also indicate managerial implications for green practices in Pakistans energy sector. The need for environmentally specific servant leaders echoes with the growing attention of organizations on establishing green human resource practices as part of their corporate social responsibility initiatives. Leadership roles are often considered informal mechanisms, supplementing formal HRM policies written in company rule books. Organizational policies must incorporate green self-efficacy into the work climate through positive reinforcement. Results reiterate that ESL is a key driver of employees pro-environmental behaviors, indicating that policymakers should engrain their human resource practices to prioritize green behaviors in the hiring and selection process to hire servant leaders who are inclined towards green behaviors. Whereas for the existing workforce and the managerial staff, green training programs should be devised and developed. This helps inculcate pro-environmental attitudes and enhances ESL behavior. The focus needs to be laid on grooming employees to build servant leadership practices that they identify with due to inspiration. These practices help organizations develop future environmentally specific servant leaders (Liden et al, 2008; Luu, 2018).

Despite offering valuable insights into the relationship between ESL and EPB, this research has its limitations. The cross-sectional design of this study does not establish causality between independent and dependent variables. We suggest aspiring researchers design longitudinal investigations based on this model. Second, it may not be possible to assess whether individual differences (eg, personality traits, values, and interest in the subject of the study) potentially could have skewed the data, this must be noted as a limitation of this study because authors did not gather data on these variables and could not assess this aspect. Third, we gathered data from employee-supervisor dyads from the energy sector of Pakistan; a better level of generalizability can be achieved by future researchers by conducting replication studies in another sector or industry. Fourth, this study included individual-level mediators and green self-efficacy in the relationship between ESL and EPB. It is suggested that team-level or group-based self-efficacy may be observed to examine its effect on EPB. Lastly, future studies may further explore mediating or moderating roles of other job-related factors, such as employee-supervisor value congruence, leader-identification, employees green job crafting, and green locus of control. In the rapidly growing knowledge stream of employees pro-environmental behavior, this study intended to explore employees green self-efficacy as the underlying mechanism of environmentally specific servant leadership (ESL) in influencing employees pro-environmental behavior (EPB). The perspective of self-efficacy theory was employed to understand the influence of ESL in predicting EPB. Our findings highlighted that environmentally specific servant leadership has a significant direct impact on employees pro-environmental behavior and employees green self-efficacy partially mediates the positive influence of ESL on EPB.

This study was carried out after the approval by the University Research Supervisor and the Research Ethics Committee of Tianjin University of Finance and Economics. No additional ethical approvals were required since the study was not invasive and did not involve manipulation of any kind. Participants were informed that participation was voluntary, and that they could exit at any stage. The study did not pose any harm mentally, physically or to professional relationships/reputation of participants. The study was designed in such a way as not to obtain any personal information of the respondents. They were assured of anonymity and that their personal identification information (eg name and email id) will not be shared with anyone and will be kept strictly confidential. The information collected from all participants in this research project was kept securely by the authors on a dedicated computer and was not shared or transmitted to anyone else.

The authors declare no competing interests in this work.

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ESL and EPB: through the lens of Self Efficacy Theory | PRBM - Dove Medical Press

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