Search

In this paper, I reviewed the emerging field of endoscopic surgery and present data supporting the contention that endoscopy can now be used to treat many foregut diseases that have been traditionally treated surgically. Within each topic, the content will progress as follows: "lessons learned", "technical considerations" and "future opportunities". Lessons learned will provide a brief background and update on the most current literature. Technical considerations will include my personal experience, including tips and tricks that I have learned over the years. Finally, future opportunities will address current unmet needs and potential new areas of development. The foregut is defined as "the upper part of the embryonic alimentary canal from which the pharynx, esophagus, lung, stomach, liver, pancreas, and part of the duodenum develop". Foregut surgery is well established in treating conditions such as gastroesophageal reflux disease (GERD), achalasia, esophageal diverticula, Barrett's esophagus (BE) and esophageal cancer, stomach cancer, gastric-outlet obstruction, and obesity. Over the past decade, remarkable progress in interventional endoscopy has culminated in the conceptualization and practice of endoscopic foregut surgery for various clinical conditions summarized in this paper. Regarding GERD, there are now several technologies available to effectively treat it and potentially eliminate symptoms, and the need for long-term treatment with proton pump inhibitors. For the first time, fundoplication can be performed without the need for open or laparoscopic surgery. Long-term data going out 5-10 years are now emerging showing extended durability. In respect to achalasia, per-oral endoscopic myotomy (POEM) which was developed in Japan, has become an alternative to the traditional Heller's myotomy. Recent meta-analysis show that POEM may have better results than Heller, but the issue of post-POEM GERD still needs to be addressed. There is now a resurgence of endoscopic treatment of Zenker's diverticula with improved technique (Z-POEM) and equipment; thus, patients are choosing flexible endoscopic treatment as opposed to open or rigid endoscopy options. In regard to BE, endoscopic submucosal dissection (ESD) which is well established in Asia, is now becoming more mainstream in the West for the treatment of BE with high grade dysplasia, as well as early esophageal cancer. In combination with all the ablation technologies (radiofrequency ablation, cryotherapy, hybrid argon plasma coagulation), the entire spectrum of Barrett's and related dysplasia and early cancer can be managed predominantly by endoscopy. Importantly, in regard to early gastric cancer and submucosal tumors (SMTs) of the stomach, ESD and full thickness resection (FTR) can excise these lesions en-bloc and endoscopic suturing is now used to close large defects and perforations. For treatment of patients with malignant gastric outlet obstruction (GOO), endoscopic gastro-jejunostomy is now showing better results than enteral stenting. G-POEM is also emerging as a treatment option for patients with gastroparesis. Obesity has become an epidemic in many western countries and is becoming also prevalent in Asia. Endoscopic sleeve gastroplasty (ESG) is now becoming an established treatment option, especially for obese patients with body mass index between 30 and 35. Data show an average weight loss of 16 kg after ESG with long-term data confirming sustainability. Finally, in respect to endo-hepatology, there are many new endoscopic interventions that have been developed for patients with liver disease. Endoscopic ultrasound (EUS)-guided liver biopsy and EUS-guided portal pressure measurement are exciting new frontiers for the endo-hepatologists.

Throughout history, researchers who examine the structure and function of the brain debate one another about how cortical areas are defined, as well as how these areas should be named. Different pieces of empirical evidence are used to define brain areas and it is important to preserve the accurate history of this evidence and the timeline of studies that lead to areal definitions that are either still used today or have been modified. As such, this paper traces the early history of a brain area located at the junction between the occipital and temporal lobes of the macaque known as TEO. This historical analysis leads to four main findings. First, even though Bonin and Bailey are credited with the definition of area TEO in 1947, they did not have the cytoarchitectonic evidence to support the distinction of TEO from adjacent areas. Second, the first evidence definitively separating area TEO from TE was actually based on connectivity as identified with strychnine neuronography by Petr et al. in 1949. Third, causal evidence from ablation studies conducted by Iwai and Mishkin (Experimental Neurology 25(4):585-594, 1969) supported this distinction by showing that TEO and TE were functionally distinct from one another. Fourth, researchers in the 1970s began referring to TEO as posterior inferotemporal (PIT) and TE as anterior inferotemporal (AIT), which is an important historical clarification as the PIT/AIT nomenclature is presently attributed to studies conducted more than a decade later. Altogether, this paper aims to preserve the historical origin of area TEO, as well as the empirical evidence that was used to originally differentiate this cortical expanse from surrounding areas.

John Avise's career has coincided with, and to a considerable degree, guided the rise and expansion of molecular ecology and molecular evolution. Indeed, he has been a preeminent leader in both fields. John's first scientific paper on the evolutionary genetics of cave fishes, published in 1972 as an outcome of his Master's thesis, quickly became a Citation Classic. This early application of protein electrophoresis to natural populations was conducted in Robert K. Selander's laboratory at the University of Texas. It was probably the first multi‐locus allozyme survey of any fish species. It was an auspicious beginning for a highly productive and highly successful scientific career. John has published nearly 300 scientific articles, plus nine books — and still counting. He enjoys the rare distinction of being a ‘Highly Cited Author’ on the ISI Web of Knowledge list.Listing the scientific milestones in John's career would take much space. A sample should suffice. In the late 1970s at the University of Georgia, he introduced, with Bob Lansman, mitochondrial (mt) DNA methods to population biology. Wes Brown, working independently of Avise and Lansman during this same time period, was the other pioneer who recognized and documented the distinctive molecular and transmission properties of mtDNA that make it such a powerful tool for research in population genetics. mtDNA remains one of the most popular and successful molecular systems for a great variety of studies in molecular ecology and evolution.John Avise is the acknowledged father of the field of phylogeography. He coined the term, defined the discipline's major principles, wrote the leading textbook (Phylogeography), and provided many of the field's earliest and still most fascinating empirical results. He was among the early leaders who came to appreciate the multi‐dimensional genetic perspectives in conservation biology, as witnessed in Conservation Genetics, an early compendium that he co‐edited with Jim Hamrick. John has been a tireless advocate for nature and for natural history studies. He has led the successful melding of molecular genetics with traditional biological and field observations. His seminal and widely used textbook, Molecular Markers, Natural History, and Evolution (now in its second edition), remains the basic reference and touchstone for these studies.John has investigated a great variety of genetic processes in nature, often in collaboration with others, notably his 24 graduate students, of which many have become prominent scientists. Influential and oft‐classic papers that emerged from Avise's lab have encompassed, among other topics: histocompatibility polymorphisms and clonal diversity in coral reef invertebrates; phylogeographic analyses of individual species and regional biotas, such as the terrestrial, maritime, and freshwater faunas of the southeastern United States; genetic analysis of hybridization and introgression phenomena in vertebrate and invertebrate taxa, which include the introduction and application of cytonuclear disequilibrium statistics; population genetics and evolution of endangered species of marine turtles; population genetics of clonal vertebrates, including gynogenetic and hybridogenetic fishes and polyembryonic mammals; speciation patterns and processes in birds, fishes, and other animal groups; genetic analyses of mating systems and reproductive behaviors in many invertebrates, reptiles, amphibians, and fishes; and much, much more.John Avise's many achievements have been recognized with numerous awards and honors. Among them: Sloan Fellowship in Molecular Evolution, Pew Fellowship in Marine Conservation, Caesar Kleberg Foundation Medal for Wildlife Conservation, Brewster Memorial Award from the American Ornithologists’ Union, and Wilhelmine Key Award from the American Genetics Association. He is a fellow of the American Association for the Advancement of Science, and has been elected to the American Academy of Arts and Sciences and the National Academy of Sciences. John has served as President of the Society for the Study of Evolution, the American Genetics Association, and the Society for Molecular Biology and Evolution. He has served on the editorial boards of 15 journals in molecular biology, ecology, evolution, and conservation.John was born in Grand Rapids, Michigan in 1948 and attended the University of Michigan, receiving a B.S. degree in Natural Resources. His Master's degree in Zoology at the University of Texas preceded a two‐year stint as a lab technician for Michael H. Smith at the Savannah River Ecology Laboratory in Aiken, South Carolina. He then joined Francisco Ayala's research group at the University of California, Davis, where he received his Ph.D. in Genetics. In 1975, he joined the faculty at the University of Georgia (UGA) and worked his way up the ranks from Assistant Professor to Distinguished Professor of Genetics. He retired from UGA in 2005 to assume his current position of Distinguished Professor of Ecology and Evolutionary Biology at the University of California, Irvine. His research and writing continue unabated and he is co‐organizing with Ayala a colloquium series sponsored by the National Academy of Sciences, under the umbrella title In the Light of Evolution, with each colloquium devoted to a different biological topic that is important to society as well as scientifically interesting. The first colloquium, entitled Adaptation and Complex Design, was held at the Beckman Center of the National Academy of Sciences in Irvine, December 1–2, 2006. The second colloquium, on Biodiversity and Extinction, will be held December 7–8, 2007, also at the Academy's Beckman Center in Irvine.John has written ‘trade’ books for audiences beyond the scientific community. They include Captivating Life, an autobiography as well as a historical record of the birth and development of molecular ecology; The Genetic Gods, an essay on evolution and religion; The Hope, Hype, and Reality of Genetic Engineering, on genetically modified organisms; Genetics in the Wild, a compilation of nature's most intriguing genetic phenomena; and, most recently, Evolutionary Pathways in Nature, a thoughtful and broadly‐encompassing examination of the power and utility of phylogenetic perspectives in biology.John thinks of himself as a natural historian at heart, a geneticist in mindset, and a concerned environmentalist in his gut. I am pleased to convey his deep appreciation for this year's Molecular Ecology Prize, which he graciously accepts on behalf of his students and postdocs, who are listed below.

BackgroundNepal was a monarchy, then a dictatorship, then a democracy. This paper reviews how tobacco control progressed in Nepal in the context of these changes in government from 1950 through 2006.MethodsWe triangulated tobacco industry documents, newspaper articles and key informant interviews.ResultsUntil 1983, the tobacco industry was mostly state owned. Transnational tobacco companies entered the Nepalese market through ventures with Surya Tobacco Company Private Limited (with Imperial Tobacco Company and British American Tobacco) in 1983 and Seti Cigarette Factory Limited (with Philip Morris International [PMI]) in 1985. Seminars and conferences on tobacco, celebrations of World No Tobacco Day (WNTD) and efforts by WHO helped promote tobacco control in Nepal beginning in the 1970s. Tobacco advocates in Nepal pushed the government to issue executive orders banning smoking in public places in 1992 and tobacco advertising in electronic media in 1998, and to introduce a tobacco health tax in 1993. The tobacco industry lobbied against these measures and succeeded in keeping the tobacco tax low by challenging it in court. Tobacco advocates sued the government in 2003 and 2005, resulting in a June 2006 Supreme Court decision upholding the smoking and advertising bans and requiring the government to enact a comprehensive tobacco control law.ConclusionsPolitical instability, conflict, weak governance and the dictatorship significantly affect tobacco control activities in low-income and middle-income countries. Nepal shows that tobacco control advocates can take advantage of global events, such as WNTD, and use domestic litigation to maintain support from civil societies and to advocate for stronger tobacco control policies.

This paper is part of the celebration of the 50th anniversary of founding of the journal Hormones and Behavior, the official journal of the Society for Behavioral Neuroendocrinology. All sex differences in phenotypic development stem from the sexual imbalance in X and Y chromosomes, which are the only known differences in XX and XY zygotes. The sex chromosome genes act within cells to cause differences in phenotypes of XX and XY cells throughout the body. In the gonad, they determine the type of gonad, leading to differences in secretion of testicular vs. ovarian hormones, which cause further sex differences in tissue function. These current ideas of sexual differentiation are briefly contrasted with a hormones-only view of sexual differentiation of the last century. The multiple, independent action of diverse sex-biasing agents means that sex-biased factors can be synergistic, increasing sex differences, or compensatory, making the two sexes more equal. Several animal models have been fruitful in demonstrating sex chromosome effects, and interactions with gonadal hormones. MRI studies of human brains demonstrate variation in brain structure associated with both differences in gonadal hormones, and in the number of X and Y chromosomes. Five unanswered questions are posed as a challenge to future investigators to improve understanding of sexual differentiation throughout the body.

BACKGROUND:The electronic cigarette (e-cigarette) industry has grown in size and organizational complexity in recent years, most notably with the entry of major tobacco companies in 2012 and the proliferation of vape shops. Many brands maintain retail websites that present e-cigarette marketing claims and sell directly to consumers. Understanding of the evolving composition of different types of e-cigarette brand websites is currently underdeveloped. OBJECTIVE:This paper presents how e-cigarette brand websites surveyed in 2013-2014 evolved by 2016-2017, and how the websites run by different types of e-cigarette producers currently differ. METHODS:In 2016-2017, we revisited 466 e-cigarette brand websites surveyed in 2013-2014, 288 of which were extant, and identified 145 new English-language websites. We compared product designs, marketing claims, and age-based warnings presented by types of e-cigarette producers: major tobacco companies, independent vape shops, and independent internet-only companies. RESULTS:Among the 433 websites examined in 2016-2017, 12 were owned by major tobacco companies, 162 operated a physical vape shop, and 259 were internet-only operations. Closed-system product designs were sold by 83% (10/12) of tobacco-owned brands. In comparison, 29.0% (47/162, P

Rituximab is a human/murine, chimeric anti-CD20 monoclonal antibody with established efficacy, and a favorable and well-defined safety profile in patients with various CD20-expressing lymphoid malignancies, including indolent and aggressive forms of B-cell non-Hodgkin lymphoma. Since its first approval 20 years ago, intravenously administered rituximab has revolutionized the treatment of B-cell malignancies and has become a standard component of care for follicular lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, and mantle cell lymphoma. For all of these diseases, clinical trials have demonstrated that rituximab not only prolongs the time to disease progression but also extends overall survival. Efficacy benefits have also been shown in patients with marginal zone lymphoma and in more aggressive diseases such as Burkitt lymphoma. Although the proven clinical efficacy and success of rituximab has led to the development of other anti-CD20 monoclonal antibodies in recent years (e.g., obinutuzumab, ofatumumab, veltuzumab, and ocrelizumab), rituximab is likely to maintain a position within the therapeutic armamentarium because it is well established with a long history of successful clinical use. Furthermore, a subcutaneous formulation of the drug has been approved both in the EU and in the USA for the treatment of B-cell malignancies. Using the wealth of data published on rituximab during the last two decades, we review the preclinical development of rituximab and the clinical experience gained in the treatment of hematologic B-cell malignancies, with a focus on the well-established intravenous route of administration. This article is a companion paper to A. Davies, et al., which is also published in this issue.FundingF. Hoffmann-La Roche Ltd., Basel, Switzerland.

Professor Steven L. Wechsler, a world-renowned eye researcher and virologist, passed away unexpectedly on June 12, 2016 at the age of 68. Many scientists came to know Professor Wechsler as a gifted researcher in the field of ocular Herpes Simplex Virus (HSV-1) latency, reactivation, and pathogenesis. Professor Wechsler published over 150 peer-reviewed scientific papers during his career, pushing forward the frontiers of his field eye research. His colleagues would say, 'Steve literally wrote the book on herpes latency and reactivation.' He was the first to show that the HSV-1 latency-associated transcript (LAT) is essential for the HSV-1 high spontaneous reactivation phenotype and that LAT has anti-apoptosis activity. This discovery of LAT's anti-apoptosis activity, which is a key factor in how the LAT gene enhances reactivation, was published in Science in 2000 and created a new paradigm that greatly increased understanding of HSV-1 latency and reactivation. In collaboration with Professor Lbachir BenMohamed, an immunologist, they later demonstrated that LAT also acts as an immune evasion gene. He was a caring scientist who truly enjoyed working and sharing his experience and expertise with young researchers. He will be remembered as a significant pillar within scientific and ocular herpes research communities worldwide. Professor Wechsler's dedication to science, his compassionate character, and wonderful sense of humor were exemplary. We, who were his friends and colleagues, will mourn his passing deeply.

This paper presents the results of a consensus-driven process identifying 50 priority research questions for historical ecology obtained through crowdsourcing, literature reviews, and in-person workshopping. A deliberative approach was designed to maximize discussion and debate with defined outcomes. Two in-person workshops (in Sweden and Canada) over the course of two years and online discussions were peer facilitated to define specific key questions for historical ecology from anthropological and archaeological perspectives. The aim of this research is to showcase the variety of questions that reflect the broad scope for historical-ecological research trajectories across scientific disciplines. Historical ecology encompasses research concerned with decadal, centennial, and millennial human-environmental interactions, and the consequences that those relationships have in the formation of contemporary landscapes. Six interrelated themes arose from our consensus-building workshop model: (1) climate and environmental change and variability; (2) multi-scalar, multi-disciplinary; (3) biodiversity and community ecology; (4) resource and environmental management and governance; (5) methods and applications; and (6) communication and policy. The 50 questions represented by these themes highlight meaningful trends in historical ecology that distill the field down to three explicit findings. First, historical ecology is fundamentally an applied research program. Second, this program seeks to understand long-term human-environment interactions with a focus on avoiding, mitigating, and reversing adverse ecological effects. Third, historical ecology is part of convergent trends toward transdisciplinary research science, which erodes scientific boundaries between the cultural and natural.

The goal of this paper is to analyze storage projects constructed and planned in California since 1980, in contrast with storage constructed before that date. As a result of California’s highly variable climate, storage is an essential tool for agricultural and urban water users. Today, the state regulates approximately 1,250 reservoirs, with a combined storage of 42 million acre-feet. Federal agencies regulate approximately 200 additional reservoirs. The vast majority of this surface storage was constructed before 1978, when New Melones Dam, the last large on-stream water supply reservoir in California, was completed. The role of storage in meeting future needs remains a high-profile issue in the California water debate. For example, funding for new storage was the largest item in Proposition 1, the most recent water bond voters approved. This analysis included a review of existing literature, such as the California Department of Water Resources Division of Dam Safety database, California Water Commission documents about new storage proposals, water agency documents, and interviews with water agency staff and others. Water managers face dramatically different conditions today, in comparison to conditions before 1980. These conditions have led to new approaches to water storage that represent a dramatic departure from past storage projects. During the past 37 years, a wide range of new water storage strategies have been planned and implemented. These facilities have created a combined new storage capacity greater than that of Lake Shasta, California’s largest reservoir. These new storage strategies suggest the need to revisit the fundamental definition of water storage. With limited potential for new storage drawing from the state’s rivers, California must choose storage projects wisely. By learning from successful strategies in recent decades, decision-makers can make better storage investment decisions to help reverse declines in ecosystem health and improve water supply reliability.