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Aims/hypothesis We previously reported that obese individuals with the metabolic syndrome (at risk), compared with obese individuals without the metabolic syndrome (healthy obese), have elevated serum AGEs that strongly correlate with insulin resistance, oxidative stress and inflammation. We hypothesised that a diet low in AGEs (L-AGE) would improve components of the metabolic syndrome in obese individuals, confirming high AGEs as a new risk factor for the metabolic syndrome. Methods A randomised 1 year trial was conducted in obese individuals with the metabolic syndrome in two parallel groups: L-AGE diet vs a regular diet, habitually high in AGEs (Reg-AGE). Participants were allocated to each group by randomisation using random permuted blocks. At baseline and at the end of the trial, we obtained anthropometric variables, blood and urine samples, and performed OGTTs and MRI measurements of visceral and subcutaneous abdominal tissue and carotid artery. Only investigators involved in laboratory determinations were blinded to dietary assignment. Effects on insulin resistance (HOMA-IR) were the primary outcome. Results Sixty-one individuals were randomised to a Reg-AGE diet and 77 to an L-AGE diet; the data of 49 and 51, respectively, were analysed at the study end in 2014. The L-AGE diet markedly improved insulin resistance; modestly decreased body weight; lowered AGEs, oxidative stress and inflammation; and enhanced the protective factors sirtuin 1, AGE receptor 1 and glyoxalase I. The Reg-AGE diet raised AGEs and markers of insulin resistance, oxidative stress and inflammation. There were no effects on MRI-assessed measurements. No side effects from the intervention were identified. HOMA-IR came down from 3.1 ± 1.8 to 1.9 ± 1.3 ( p  < 0.001) in the L-AGE group, while it increased from 2.9 ± 1.2 to 3.6 ± 1.7 ( p  < 0.002) in the Reg-AGE group. Conclusions / interpretation L-AGE ameliorates insulin resistance in obese people with the metabolic syndrome, and may reduce the risk of type 2 diabetes, without necessitating a major reduction in adiposity. Elevated serum AGEs may be used to diagnose and treat ‘at-risk’ obesity. Trial registration ClinicalTrials.gov NCT01363141 Funding The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases (DK091231)

Understanding the synchronization of systems of coupled oscillators has a rich history in the study of dynamical systems and applications in numerous fields, where decades of work have demonstrated the complex interplay between the properties of these systems and the oscillators' ability to synchronize. We bring the tools of evolutionary game theory (EGT) to the study of coupled oscillatory systems, with the neurons of the suprachiasmatic nucleus as a motivating example. We cast the oscillatory system as a collection of agents, one for each oscillator, that play a game with one another where the payoffs are based on their phases. We find that even one of the simplest models of these systems yields a rich diversity of outcomes linked to classical games - the prisoner's dilemma, the snowdrift game, etc. - based on the relative costs and benefits of synchronization in the organism. Within this complexity lies a simplicity as well, as we consistently find a simple condition, under various assumptions, between the cost and benefit parameters which leads to the overall synchronization within the population of agents. This simple framework opens the door to a plethora of mathematical and biological questions for future study.

BACKGROUND: Research biopsies (RBs) are essential to understanding tumor biology and mechanisms of resistance and to advancing precision medicine. However, RBs have associated risks and may not benefit the patient. OBJECTIVES: The purpose of this integrative review is to summarize and synthesize the current literature on the experience, attitudes, and understandingof patients with cancer related to RBs. METHODS: Articles from January 2010 to February 2017 were retrieved via a search of MEDLINE®. Articles included reported on the willingness, perceptions, understanding, attitudes, and/or experience of patients with cancer related to RBs. FINDINGS: Nine of 216 identified studies were selected. Studies exploring patient willingness toundergo RBs (n = 6) identified RBs as a potential barrier to clinical trial participation. Studies exploring patient understanding and informed consent (n = 3) revealed variable patient knowledge of the risks and benefits of RBs.

Research biopsies (RBs) are essential to understanding tumor biology and mechanisms of resistance and to advancing precision medicine. However, RBs have associated risks and may not benefit the patient. The purpose of this integrative review is to summarize and synthesize the current literature on the experience, attitudes, and understanding of patients with cancer related to RBs. Articles from January 2010 to February 2017 were retrieved via a search of MEDLINE®. Articles included reported on the willingness, perceptions, understanding, attitudes, and/or experience of patients with cancer related to RBs. Nine of 216 identified studies were selected. Studies exploring patient willingness to undergo RBs (n = 6) identified RBs as a potential barrier to clinical trial participation. Studies exploring patient understanding and informed consent (n = 3) revealed variable patient knowledge of the risks and benefits of RBs.

Spatial heterogeneity is an inherent part of landscapes and often has important consequences for the movements, distribution, or persistence of many wildlife species. Quantifying the composition, configuration, and connectivity of suitable habitat and its consequences for populations can provide valuable information about both the ecology and management of many species. This type of information may be particularly useful for informing the conservation and management of threatened or endangered species. The gopher tortoise (Gopherus polyphemus) is a species of high conservation concern due to the decline of populations across its range and its role in the ecosystem. To help inform conservation of this species, I assessed connectivity of suitable habitat across a broad portion of the gopher tortoise's range, quantified habitat connectivity under various management alternatives at selected sites in Alabama, and developed a spatially explicit population projection model to predict the future population consequences of various management strategies. This research provides evidence for a broad-scale pattern of changing habitat connectivity across a large portion of the gopher tortoise's range and highlights the importance of considering management effects on connectivity at finer scales. Results from the population projection demonstrate the importance of considering a spatial component when projecting population size into the future and indicate a need for further research on gopher tortoise survival rates. The models developed in this research demonstrate the utility of these types of spatial analyses for informing conservation and management, and could be adapted to other species of conservation concern.

Common models of synchronizable oscillatory systems consist of a collection of coupled oscillators governed by a collection of differential equations. The ubiquitous Kuramoto models rely on an {\\em a priori} fixed connectivity pattern facilitates mutual communication and influence between oscillators. In biological synchronizable systems, like the mammalian suprachaismatic nucleus, enabling communication comes at a cost -- the organism expends energy creating and maintaining the system -- linking their development to evolutionary selection. Here, we introduce and analyze a new evolutionary game theoretic framework modeling the behavior and evolution of systems of coupled oscillators. Each oscillator in our model is characterized by a pair of dynamic behavioral traits: an oscillatory phase and whether they connect and communicate to other oscillators or not. Evolution of the system occurs along these dimensions, allowing oscillators to change their phases and/or their communication strategies. We measure success of mutations by comparing the benefit of phase synchronization to the organism balanced against the cost of creating and maintaining connections between the oscillators. Despite such a simple setup, this system exhibits a wealth of nontrivial behaviors, mimicking different classical games -- the Prisoner's Dilemma, the snowdrift game, and coordination games -- as the landscape of the oscillators changes over time. Despite such complexity, we find a surprisingly simple characterization of synchronization through connectivity and communication: if the benefit of synchronization \\(B(0)\\) is greater than twice the cost \\(c\\), \\(B(0) > 2c\\), the organism will evolve towards complete communication and phase synchronization. Taken together, our model demonstrates possible evolutionary constraints on both the existence of a synchronized oscillatory system and its overall connectivity.

What can one say on convergence to stationarity of a finite state Markov chain that behaves \"locally\" like a nearest neighbor random walk on \\({\\mathbb Z}\\) ? The model we consider is a version of nearest neighbor lazy random walk on the state space \\( \\{0,\\dots,N\\}\\): the probability for staying put at each site is \\(\\frac 12\\), the transition to the nearest neighbors, one on the right and one on the left, occurs with probability \\(\\frac14\\) each, where we identify two sites, \\(J_0\\) and \\(J_N\\) as, respectively, the neighbor of \\(0\\) from the left and the neighbor of \\(N\\) from the right (but \\(0\\) is not a neighbor of \\(J_0\\) and \\(N\\) is not neighbor of \\(J_N\\)). This model is a discrete version of diffusion with redistribution on an interval studied by several authors in recent past, and for which the the exponential rates of convergence to stationarity were computed analytically, but had no intuitive or probabilistic interpretation, except for the case where the jumps from the endpoints are identical (or more generally have the same distribution). We study convergence to stationarity probabilistically, by finding an efficient coupling. The coupling identifies the \"bottlenecks\" responsible for the rates of convergence and also gives tight computable bounds on the total variation norm of the process between two starting points. The adaptation to the diffusion case is straightforward.

Raising awareness of human indifference and cruelty toward animals, The Global Guide to Animal Protection includes more than 180 introductory articles that survey the extent of worldwide human exploitation of animals from a variety of perspectives. In addition to entries on often disturbing examples of human cruelty toward animals, the book provides inspiring accounts of attempts by courageous individuals--including Jane Goodall, Shirley McGreal, Birute Mary Galdikas, Richard D. Ryder, and Roger Fouts--to challenge and change exploitative practices. As concern for animals and their welfare grows, this volume will be an indispensable aid to general readers, activists, scholars, and students interested in developing a keener awareness of cruelty to animals and considering avenues for reform. Also included is a special foreword by Archbishop Desmond Tutu, urging readers to seek justice and protection for all creatures, humans and animals alike.

This study focuses on the lives and work of black women journalists before the advent of the Civil War. Before 1900, in both slave and free families, the women were the natural leaders who served as role models and teachers for their own families, as well as for their neighbors and brethren. Black women journalists were the most visible and significant teachers, lecturers, and writers of the period--making their presence known in the classroom, in the public auditoriums, and in the newsroom. In this dissertation, special attention is devoted to the types of issues addressed by these women in relation to the concerns of the black population during this period. Other topics examined include the interrelationships between these women and the black community (political activism, religious involvement, etc.), the socialization process of the women journalists (i.e.--professional acceptance, community acceptance, societal restraints), and their personal philosophies on key concerns of the period and the societal influences that helped to shape these beliefs. The study is not only an attempt to understand the reasoning behind the women's philosophies and their choice of topics, but also an effort to determine how societal and personal necessity shaped these concerns. Of particular interest is the women's motivation to speak out when American society publicly and privately condemned such actions and to address topics only men had endeavored to broach in the past--actions that were destined to draw opposition and criticism from whites, as well as blacks. This study emphasizes the writings of Maria W. Stewart, Sarah Mapps Douglass, Susan Paul, Mary Miles Bibb, Mary Ann Shadd Cary, Harriet Myers, and Amelia Shadd. Both Bibb and Myers were married to newspapermen, Henry Bibb of the Voice of the Fugitive in Canada and Stephen Myers of the Northern Star and Freeman's Advocate in Albany, N.Y., respectively. Cary published her own newspaper, The Provincial Freeman, in Canada, with the assistance of her sister Amelia Shadd. Stewart, Douglass, and Paul were primarily correspondents. All the women wrote for newspapers between 1830 and 1860, with some contributing articles to newspapers and journals after the war.

Tom Glavine: Responses to \"Goodbye, Glavine,\" Sports, Dec. 6 A joke that Jerry Seinfeld made several years ago is now truer than ever in pro sports. Seinfeld said that we really don't root for the players, we root for the uniforms the players are in. It has become a necessity that you not get too emotionally involved with individual players, as they will leave your favorite team at some point, usually for more money. I hope those players filling out the Mets uniforms will once again finish behind those guys wearing the Braves uniforms. Good riddance to Tom Glavine. There is nothing any pro athlete has ever done --- or will do --- that's worth $35 million. Glavine is the poster child for the travesty of professional sports run amok.