Category Archives: Gene Medicine

PUBLIC RELEASE DATE:

3-Sep-2014

Contact: Kathryn Ryan kryan@liebertpub.com 914-740-2100 Mary Ann Liebert, Inc./Genetic Engineering News

New Rochelle, NY, September 3, 2014Robin Ali, PhD, University College London, Jean Bennett, MD, PhD, Perelman School of Medicine, University of Pennsylvania, and William Hauswirth, PhD, University of Florida College of Medicine, are co-recipients of the Pioneer Award, recognized for their leadership and contributions to the field of gene therapy to treat retinal degeneration leading to blindness. Human Gene Therapy, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers, is commemorating its 25th anniversary by bestowing this honor on the leading Pioneers in the field of cell and gene therapy selected by a blue ribbon panel* and publishing a Pioneer Perspective by the award recipients.

Dr. Ali, Professor of Human Molecular Genetics, led proof-of-concept studies demonstrating the feasibility of using gene therapy to repair photoreceptor defects in the eye and of using cell transplantation for retinal repair. He also had a pioneering role in the first clinical trial for inherited retinal degeneration.

Dr. Bennett, Professor of Ophthalmology, Cell and Developmental Biology, recalls her first experiences with molecular biology and gene transfer technology, acquired in the lab of Dr. W. French Anderson, known as "the father of gene therapy." She describes her developing career, including the decision to go to medical school and to focus her research on developing adeno-associated virus (AAV) gene therapy techniques for restoring vision to patients affected by retinal degeneration in her Pioneer Perspective article entitled "My Career Path for Developing Gene Therapy for Blinding Diseases: The Importance of Mentors, Collaborators, and Opportunities," available on the Human Gene Therapy website.

Dr. Hauswirth, Rybaczki-Bullard Professor of Ophthalmology, traces his involvement in the field of retinal gene therapy to his early interest in studying the interaction between light and biological molecules. He provides a historical perspective on the discovery of the gene mutations responsible for several of the most common inherited eye diseases and the advances in AAV gene therapy technology being developed and applied to deliver replacement genes. His Pioneer Perspective, entitled "Retinal Gene Therapy Using Adeno-Associated Viral Vectors: Multiple Applications for a Small Virus," is available on the Human Gene Therapy website.

"These groups brought forward the first convincing clinical results of in vivo gene therapy, which paved the way for the current renaissance we are seeing in the field," says James M. Wilson, MD, PhD, Editor-in-Chief of Human Gene Therapy, and Director of the Gene Therapy Program, Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia.

###

*The blue ribbon panel of leaders in cell and gene therapy, led by Chair Mary Collins, PhD, MRC Centre for Medical Molecular Virology, University College London selected the Pioneer Award recipients. The Award Selection Committee selected scientists that had devoted much of their careers to cell and gene therapy research and had made a seminal contribution to the field--defined as a basic science or clinical advance that greatly influenced progress in translational research.

Follow this link:
Pioneer Award recipients Robin Ali, Ph.D., Jean Bennett, M.D., Ph.D., and William Hauswirth, Ph.D.

PUBLIC RELEASE DATE:

29-Aug-2014

Contact: Rushmie A Nofsinger rushmie.nofsinger@tufts.edu 508-839-7910 Tufts University, Health Sciences Campus

NORTH GRAFTON, Mass. (August 29, 2014, 2 PM US Eastern Time)The current method to treat acute toxin poisoning is to inject antibodies, commonly produced in animals, to neutralize the toxin. But this method has challenges ranging from safety to difficulties in developing, producing and maintaining the anti-serums in large quantities.

New research led by Charles Shoemaker, Ph.D., professor in the Department of Infectious Disease and Global Health at the Cummings School of Veterinary Medicine at Tufts University, shows that gene therapy may offer significant advantages in prevention and treatment of botulism exposure over current methods. The findings of the National Institutes of Health funded study appear in the August 29 issue of PLOS ONE.

Shoemaker has been studying gene therapy as a novel way to treat diseases such as botulism, a rare but serious paralytic illness caused by a nerve toxin that is produced by the bacterium Clostridium botulinum. Despite the relatively small number of botulism poisoning cases nationally, there are global concerns that the toxin can be produced easily and inexpensively for bioterrorism use. Botulism, like E. coli food poisoning and C. difficile infection, is a toxin-mediated disease, meaning it occurs from a toxin that is produced by a microbial infection.

Shoemaker's previously reported antitoxin treatments use proteins produced from the genetic material extracted from alpacas that were immunized against a toxin. Alpacas, which are members of the camelid family, produce an unusual type of antibody that is particularly useful in developing effective, inexpensive antitoxin agents. A small piece of the camelid antibody called a VHH can bind to and neutralize the botulism toxin. The research team has found that linking two or more different toxin-neutralizing VHHs results in VHH-based neutralizing agents (VNAs) that have extraordinary antitoxin potency and can be produced as a single molecule in bacteria at low cost. Additionally, VNAs have a longer shelf life than traditional antibodies so they can be better stored until needed.

The newly published PLOS ONE study assessed the long-term efficacy of the therapy and demonstrated that a single gene therapy treatment led to prolonged production of VNA in blood and protected the mice from subsequent exposures to C. botulinum toxin for up to several months. Virtually all mice pretreated with VNA gene therapy survived when exposed to a normally lethal dose of botulinum toxin administered up to nine weeks later. Approximately 40 percent survived when exposed to this toxin as late as 13 or 17 weeks post-treatment. With gene therapy the VNA genetic material is delivered to animals by a vector that induces the animals to produce their own antitoxin VNA proteins over a prolonged period of time, thus preventing illness from toxin exposures.

The second part of the study showed that mice were rapidly protected from C. botulinum toxin exposure by the same VNA gene therapy, surviving even when treated 90 minutes after the toxin exposure.

"We envision this treatment approach having a broad range of applications such as protecting military personnel from biothreat agents or protecting the public from other toxin-mediated diseases such as C. difficile and Shiga toxin-producing E. coli infections," said Shoemaker, the paper's senior author. "More research is being conducted with VNA gene therapy and it's hard to deny the potential of this rapid-acting and long-lasting therapy in treating these and several other important illnesses."

See more here:
Mice study shows efficacy of new gene therapy approach for toxin exposures

The current method to treat acute toxin poisoning is to inject antibodies, commonly produced in animals, to neutralize the toxin. But this method has challenges ranging from safety to difficulties in developing, producing and maintaining the anti-serums in large quantities.

New research led by Charles Shoemaker, Ph.D., professor in the Department of Infectious Disease and Global Health at the Cummings School of Veterinary Medicine at Tufts University, shows that gene therapy may offer significant advantages in prevention and treatment of botulism exposure over current methods. The findings of the National Institutes of Health funded study appear in the August 29 issue of PLOS ONE.

Shoemaker has been studying gene therapy as a novel way to treat diseases such as botulism, a rare but serious paralytic illness caused by a nerve toxin that is produced by the bacterium Clostridium botulinum. Despite the relatively small number of botulism poisoning cases nationally, there are global concerns that the toxin can be produced easily and inexpensively for bioterrorism use. Botulism, like E. coli food poisoning and C. difficile infection, is a toxin-mediated disease, meaning it occurs from a toxin that is produced by a microbial infection.

Shoemaker's previously reported antitoxin treatments use proteins produced from the genetic material extracted from alpacas that were immunized against a toxin. Alpacas, which are members of the camelid family, produce an unusual type of antibody that is particularly useful in developing effective, inexpensive antitoxin agents. A small piece of the camelid antibody -- called a VHH -- can bind to and neutralize the botulism toxin. The research team has found that linking two or more different toxin-neutralizing VHHs results in VHH-based neutralizing agents (VNAs) that have extraordinary antitoxin potency and can be produced as a single molecule in bacteria at low cost. Additionally, VNAs have a longer shelf life than traditional antibodies so they can be better stored until needed.

The newly published PLOS ONE study assessed the long-term efficacy of the therapy and demonstrated that a single gene therapy treatment led to prolonged production of VNA in blood and protected the mice from subsequent exposures to C. botulinum toxin for up to several months. Virtually all mice pretreated with VNA gene therapy survived when exposed to a normally lethal dose of botulinum toxin administered up to nine weeks later. Approximately 40 percent survived when exposed to this toxin as late as 13 or 17 weeks post-treatment. With gene therapy the VNA genetic material is delivered to animals by a vector that induces the animals to produce their own antitoxin VNA proteins over a prolonged period of time, thus preventing illness from toxin exposures.

The second part of the study showed that mice were rapidly protected from C. botulinum toxin exposure by the same VNA gene therapy, surviving even when treated 90 minutes after the toxin exposure.

"We envision this treatment approach having a broad range of applications such as protecting military personnel from biothreat agents or protecting the public from other toxin-mediated diseases such as C. difficile and Shiga toxin-producing E. coli infections," said Shoemaker, the paper's senior author. "More research is being conducted with VNA gene therapy and it's hard to deny the potential of this rapid-acting and long-lasting therapy in treating these and several other important illnesses."

Story Source:

The above story is based on materials provided by Tufts University. Note: Materials may be edited for content and length.

Read more from the original source:
Efficacy of new gene therapy approach for toxin exposures shown in mouse study

Gene therapy is an experimental technique that uses genes to treat or prevent disease. In the future, this technique may allow doctors to treat a disorder by inserting a gene into a patients cells instead of using drugs or surgery. Researchers are testing several approaches to gene therapy, including:

Replacing a mutated gene that causes disease with a healthy copy of the gene.

Inactivating, or knocking out, a mutated gene that is functioning improperly.

Introducing a new gene into the body to help fight a disease.

Although gene therapy is a promising treatment option for a number of diseases (including inherited disorders, some types of cancer, and certain viral infections), the technique remains risky and is still under study to make sure that it will be safe and effective. Gene therapy is currently only being tested for the treatment of diseases that have no other cures.

MedlinePlus from the National Library of Medicine offers a list of links to information about genes and gene therapy.

Educational resources related to gene therapy are available from GeneEd.

The Genetic Science Learning Center at the University of Utah provides an interactive introduction to gene therapy and a discussion of several diseases for which gene therapy has been successful.

The Centre for Genetics Education provides an introduction to gene therapy, including a discussion of ethical and safety considerations.

KidsHealth from Nemours offers a fact sheet called Gene Therapy and Children.

Original post:
What is gene therapy? - Genetics Home Reference

PUBLIC RELEASE DATE:

25-May-2014

Contact: Scott LaFee slafee@ucsd.edu 619-543-6163 University of California - San Diego

Researchers at the University of California, San Diego School of Medicine have identified a mutated gene common to adenosquamous carcinoma (ASC) tumors the first known unique molecular signature for this rare, but particularly virulent, form of pancreatic cancer.

The findings are published in the May 25 advance online issue of Nature Medicine.

Pancreatic cancer is the fourth leading cause of cancer-related death in the United States, with roughly 45,220 new cases diagnosed and more than 38,400 deaths annually. Both numbers are rising. ASC cases are infrequent, but typically have a worse prognosis than more common types of pancreatic cancer.

"There has been little progress in understanding pancreatic ASC since these aggressive tumors were first described more than a century ago," said co-senior author Miles F. Wilkinson, PhD, professor in the Department of Reproductive Medicine and a member of the UC San Diego Institute for Genomic Medicine. "One problem has been identifying mutations unique to this class of tumors."

In their paper, Wilkinson, co-senior author Yanjun Lu, PhD, of Tongji University in China, and colleagues report that ASC pancreatic tumors have somatic or non-heritable mutations in the UPF1 gene, which is involved in a highly conserved RNA degradation pathway called nonsense-mediated RNA decay or NMD. It is the first known example of genetic alterations in an NMD gene in human tumors.

NMD has two major roles. First, it is a quality control mechanism used by cells to eliminate faulty messenger RNA (mRNA) molecules that help transcribe genetic information into the construction of proteins essential to life. Second, it degrades a specific group of normal mRNAs, including those encoding proteins promoting cell growth, cell migration and cell survival. Loss of NMD in these tumors may "release the brakes on these molecules, and thereby driving tumor growth and spread," said Wilkinson.

###

Continue reading here:
Gene mutation found for aggressive form of pancreatic cancer

May 23, 2014

Image Caption: Microscopic image of human cells (stained purple), showing the primary cilium (green). A new study shows how FTO, a gene commonly associated with obesity, contributes to weight gain. Changes in this gene indirectly affect the function of the cilium -- a hair-like appendage found on brain and other cells. Irregularities in the cilium, in turn, can affect receptors for leptin, which suppresses appetite. Credit: Lab of Rudolph L. Leibel, M.D.

Columbia University Medical Center

Researchers have discovered how a gene commonly linked to obesityFTOcontributes to weight gain. The study shows that variations in FTO indirectly affect the function of the primary cilium, a little-understood hair-like appendage on brain and other cells. Specific abnormalities of cilium molecules, in turn, increase body weight, in some instances, by affecting the function of receptors for leptin, a hormone that suppresses appetite. The findings, made in mice, suggest that it might be possible to modify obesity through interventions that alter the function of the cilium, according to scientists at Columbia University Medical Center (CUMC).

If our findings are confirmed, they could explain how common genetic variants in the gene FTO affect human body weight and lead to obesity, said study leader Rudolph L. Leibel, MD, the Christopher J. Murphy Memorial Professor of Diabetes Research, professor of pediatrics and medicine, and co-director of the Naomi Berrie Diabetes Center at CUMC. The better we can understand the molecular machinery of obesity, the better we will be able to manipulate these mechanisms and help people lose weight.

The study was published on May 6 in the online edition of Cell Metabolism.

Since 2007, researchers have known that common variants in the fat mass and obesity-associated protein gene, also known as FTO, are strongly associated with increased body weight in adults. But it was not understood how alterations in FTO might contribute to obesity. Studies have shown that knocking out FTO in mice doesnt necessarily lead to obesity, and not all humans with FTO variants are obese, said Dr. Leibel. Something else is going on at this location that we were missing.

In experiments with mice, the CUMC team observed that as FTO expression increased or decreased, so did the expression of a nearby gene, RPGRIP1L. RPGRIP1L is known to play a role in regulating the primary cilium. Aberrations in the cilium have been implicated in rare forms of obesity, said Dr. Leibel. But it wasnt clear how this structure might be involved in garden-variety obesity.

Dr. Leibel and his colleague, George Stratigopoulos, PhD, associate research scientist, hypothesized that common FTO variations in noncoding regions of the gene do not change its primary function, which is to produce an enzyme that modifies DNA and RNA. Instead, they suspected that FTO variations indirectly affect the expression of RPGRIP1L. When Dr. Stratigopoulos analyzed the sequence of FTOs intronits noncoding, or nonprotein-producing, portionwe found that it serves as a binding site for a protein called CUX1, said Dr. Leibel. CUX1 is a transcription factor that modifies the expression of RPGRIP1L.

Next, Dr. Stratigopoulos set out to determine whether RPGRIP1L plays a role in obesity. He created mice lacking one of their two RPGRIP1L genes, in effect, reducing but not eliminating the genes function. (Mice that lack both copies of the gene have several serious defects that would obscure the effects on food intake.) Mice with one copy of RPGRIP1L had a higher food intake, gained significantly more weight, and had a higher percentage of body fat than controls.

Read more:
How Does Common Obesity Gene Contribute To Weight Gain?

PUBLIC RELEASE DATE:

22-May-2014

Contact: Karin Eskenazi ket2116@cumc.columbia.edu 212-342-0508 Columbia University Medical Center

NEW YORK, NY (May 22, 2014) Researchers have discovered how a gene commonly linked to obesityFTOcontributes to weight gain. The study shows that variations in FTO indirectly affect the function of the primary cilium, a little-understood hair-like appendage on brain and other cells. Specific abnormalities of cilium molecules, in turn, increase body weight, in some instances, by affecting the function of receptors for leptin, a hormone that suppresses appetite. The findings, made in mice, suggest that it might be possible to modify obesity through interventions that alter the function of the cilium, according to scientists at Columbia University Medical Center (CUMC).

"If our findings are confirmed, they could explain how common genetic variants in the gene FTO affect human body weight and lead to obesity," said study leader Rudolph L. Leibel, MD, the Christopher J. Murphy Memorial Professor of Diabetes Research, professor of pediatrics and medicine, and co-director of the Naomi Berrie Diabetes Center at CUMC. "The better we can understand the molecular machinery of obesity, the better we will be able to manipulate these mechanisms and help people lose weight."

The study was published on May 6 in the online edition of Cell Metabolism.

Since 2007, researchers have known that common variants in the fat mass and obesity-associated protein gene, also known as FTO, are strongly associated with increased body weight in adults. But it was not understood how alterations in FTO might contribute to obesity. "Studies have shown that knocking out FTO in mice doesn't necessarily lead to obesity, and not all humans with FTO variants are obese," said Dr. Leibel. "Something else is going on at this location that we were missing."

In experiments with mice, the CUMC team observed that as FTO expression increased or decreased, so did the expression of a nearby gene, RPGRIP1L. RPGRIP1L is known to play a role in regulating the primary cilium. "Aberrations in the cilium have been implicated in rare forms of obesity," said Dr. Leibel. "But it wasn't clear how this structure might be involved in garden-variety obesity."

Dr. Leibel and his colleague, George Stratigopoulos, PhD, associate research scientist, hypothesized that common FTO variations in noncoding regions of the gene do not change its primary function, which is to produce an enzyme that modifies DNA and RNA. Instead, they suspected that FTO variations indirectly affect the expression of RPGRIP1L. "When Dr. Stratigopoulos analyzed the sequence of FTO's intronits noncoding, or nonprotein-producing, portionwe found that it serves as a binding site for a protein called CUX1," said Dr. Leibel. "CUX1 is a transcription factor that modifies the expression of RPGRIP1L."

Next, Dr. Stratigopoulos set out to determine whether RPGRIP1L plays a role in obesity. He created mice lacking one of their two RPGRIP1L genes, in effect, reducing but not eliminating the gene's function. (Mice that lack both copies of the gene have several serious defects that would obscure the effects on food intake.) Mice with one copy of RPGRIP1L had a higher food intake, gained significantly more weight, and had a higher percentage of body fat than controls.

Originally posted here:
Study shows how common obesity gene contributes to weight gain

Contact Information

Available for logged-in reporters only

Newswise BALTIMORE May 21, 2014. Researchers at the University of Maryland School of Medicine have identified a mutation in a fat-storage gene that appears to increase the risk for type 2 diabetes and other metabolic disorders, according to a study published online today in the New England Journal of Medicine.

The researchers discovered the mutation in the hormone-sensitive lipase (HSL) gene by studying the DNA of more than 2,700 people in the Old Order Amish community in Lancaster County, Pa. HSL is a key enzyme involved in breaking down stored fat (triglycerides) into fatty acids, thereby releasing energy for use by other cells.

We found that Amish people with this mutation have defects in fat storage, increased fat in the liver, high triglycerides, low "good" (HDL) cholesterol, insulin resistance and increased risk of developing type 2 diabetes, says the studys senior author, Coleen M. Damcott, Ph.D., an assistant professor of medicine in the Division of Endocrinology, Diabetes and Nutrition and member of the Program for Personalized and Genomic Medicine at the University of Maryland School of Medicine.

In this study, 5.1 percent of the Old Order Amish study participants had at least one copy of the mutation. Four people had two copies of the mutation and consequently produced no HSL enzyme, Dr. Damcott says. The mutation is less common in non-Amish Caucasians of European descent (0.2%), thus the higher prevalence of the mutation in the Amish makes it possible to characterize its full range of effects.

Future studies of this gene will allow us to look more closely at the effects of its deficiency on human metabolism to better understand the function of the HSL protein and its impact on fat and glucose metabolism, Dr. Damcott says. These studies will also examine the potential of using HSL as a drug target for treating type 2 diabetes and related complications.

She notes that type 2 diabetes is a complex disease whose susceptibility is often determined by interactions between genetics and lifestyle factors, such as overeating and physical inactivity. Susceptibility genes for diabetes may be involved in several different metabolic pathways in the body, including storage and release of fat for energy.

Discovery of this mutation adds to the growing list of insights gained from genomic studies that can be used to develop new treatments and customize existing treatments for type 2 diabetes and related metabolic disorders, Dr. Damcott says.

E. Albert Reece, M.D., Ph.D., M.B.A., vice president for medical affairs at the University of Maryland and the John Z. and Akiko K. Bowers Distinguished Professor and dean of the University of Maryland School of Medicine, says, This discovery offers intriguing new evidence of how genetics may play a role in how people develop type 2 diabetes and provides a possible target for medical intervention. Through our Program for Personalized and Genomic Medicine, we are always striving to devise effective therapies to fit an individuals genetic make-up.

See original here:
University of Maryland Researchers Identify Mutation in Fat-Storage Gene That Appears to Increase Type 2 Diabetes Risk

Researchers at Karolinska Institutet in Sweden have for the first time identified a gene driving the development of pernicious adipose tissue in humans. The findings imply, which are published in the scientific journal Cell Metabolism, that the gene may constitute a risk factor promoting the development of insulin resistance and type 2 diabetes.

Adipose tissue can expand in two ways: by increasing the size and/or the number of the fat cells. It is well established that subjects with few but large fat cells, so-called hypertrophy, display an increased risk of developing type 2-diabetes. In the current study, researchers identified a gene, EBF1, which according to these new findings drive the development of the unhealthy adipose tissue. This gene encodes a protein that controls a set of other genes, a so-called transcription factor, and regulates the formation of new fat cells as well as their metabolic function.

The investigators compared adipose tissue from subjects with small or large fat cells and found that EBF1 was closely linked to hypertrophy. Individuals with large fat cells had markedly lower EBF1 expression in their adipose tissue, displayed altered lipid mobilisation and were insulin resistant. Insulin resistance -- a condition characterised by reduced cellular response to the hormone insulin that is released when the blood glucose levels rise after a meal -- is an important causal factor underlying the increased risk of diabetes in individuals with hypertrophic adipose tissue. Insulin resistance leads to increased circulating levels of glucose and lipids in the blood.

In collaboration with Professor Mark C. Horowitz at Yale School of Medicine, U.S. the researchers also investigated genetically modified mice expressing lower levels of the murine variant of the human EBF1-gene. It turned out that these mice developed adipose hypertrophy and displayed increased lipid mobilisation from fat cells. When the mice were put on high-fat diet they became insulin resistant.

"Our findings represent an important step forward in the understanding of how adipose tissue links to the development of metabolic disease," comments Professor Peter Arner, one of the principal investigators at Karolinska Institutet along with Hui Gao, Niklas Mejhert and Mikael Rydn. "This is the first time someone has identified a gene which may cause malfunctioning adipose tissue in (hu)man. In the future, it might be possible to develop drugs that improve EBF1 function in adipose tissue, which could be used to treat type 2-diabetes."

Story Source:

The above story is based on materials provided by Karolinska Institutet. Note: Materials may be edited for content and length.

See the rest here:
Gene behind unhealthy adipose tissue identified

Albany, New York (PRWEB) May 22, 2014

Gene therapy involves use of DNA as a pharmaceutical agent to treat diseases. It is one of the most important developments in the field of medicine that has potential to treat various lethal diseases such as HIV, cancer and cystic fibrosis. In the long run, biotechnology and clinical trial industries will benefit from developments in gene therapy and provide potential treatment solutions for various incurable diseases.

Browse the full report - http://www.transparencymarketresearch.com/gene-therapy-market.html.

In the present scenario, various pharmaceutical companies are using clinical data to validate the concept of gene therapy. Moreover, many venture capital investors are also showing their interest in gene therapy, and are investing heavily in its development. However, gene therapy is highly dependent on the regulatory approvals and most of the products are currently in clinical trial phase. Most of these gene therapy products are for cancer and cardiovascular diseases, and are in Phase III/ Phase II of clinical trials.

In addition, growing popularity of DNA vaccines boost advances in gene therapy and is likely to be practiced in clinics in the near future, with a number of therapy programs now in phase II/III trials, showing promising results.

Get report sample - http://www.transparencymarketresearch.com/sample/sample.php?flag=B&rep_id=1838.

Some of the major players operating in the market are AnGes MG, BioSante Pharmaceuticals, GenVec, Genzyme Corporation, Oxford BioMedica, Transgene, Urigen Pharmaceuticals and Vical.

This research report analyzes this market depending on its market segments, major geographies, and current market trends. Geographies analyzed under this research report include:

This report provides comprehensive analysis of:

This report is a complete study of current trends in the market, industry growth drivers, and restraints. It provides market projections for the coming years. It includes analysis of recent developments in technology, Porters five force model analysis and detailed profiles of top industry players. The report also includes a review of micro and macro factors essential for the existing market players and new entrants along with detailed value chain analysis.

Follow this link:
Global Gene Therapy Market: Analysis, Size, Share, Growth, Trends and Forecast 2013 - 2019