Asimadoline and its potential for the treatment of diarrhea-predominant irritable bowel syndrome: a review

Irritable bowel syndrome (IBS) is a multifactorial condition with principal symptoms of pain and altered bowel function. The kappa-opioid agonist asimadoline is being evaluated in Phase III as a potential treatment for IBS. Asimadoline, to date, has shown a good safety profile and the target Phase III population – diarrhea-predominant IBS patients with at least moderate pain – was iteratively determined in a prospective manner from a Phase II dose-ranging study. The clinical data in support of this population are reviewed in this article. Furthermore, the scientific rationale for the use of asimadoline in the treatment of IBS is reviewed. Considering the high patient and societal burdens of IBS, new treatments for IBS represent therapeutic advances

Food security and marine capture fisheries: characteristics, trends, drivers and future perspectives

World population is expected to grow from the present 6.8 billion people to about 9 billion by 2050. The growing need for nutritious and healthy food will increase the demand for fisheries products from marine sources, whose productivity is already highly stressed by excessive fishing pressure, growing organic pollution, toxic contamination, coastal degradation and climate change. Looking towards 2050, the question is how fisheries governance, and the national and international policy and legal frameworks within which it is nested, will ensure a sustainable harvest, maintain biodiversity and ecosystem functions, and adapt to climate change. This paper looks at global fisheries production, the state of resources, contribution to food security and governance. It describes the main changes affecting the sector, including geographical expansion, fishing capacity-building, natural variability, environmental degradation and climate change. It identifies drivers and future challenges, while suggesting how new science, policies and interventions could best address those challenges

The Escape Problem for Irreversible Systems

The problem of noise-induced escape from a metastable state arises in physics, chemistry, biology, systems engineering, and other areas. The problem is well understood when the underlying dynamics of the system obey detailed balance. When this assumption fails many of the results of classical transition-rate theory no longer apply, and no general method exists for computing the weak-noise asymptotics of fundamental quantities such as the mean escape time. In this paper we present a general technique for analysing the weak-noise limit of a wide range of stochastically perturbed continuous-time nonlinear dynamical systems. We simplify the original problem, which involves solving a partial differential equation, into one in which only ordinary differential equations need be solved. This allows us to resolve some old issues for the case when detailed balance holds. When it does not hold, we show how the formula for the mean escape time asymptotics depends on the dynamics of the system along the most probable escape path. We also present new results on short-time behavior and discuss the possibility of focusing along the escape path.Comment: 24 pages, APS revtex macros (version 2.1) now available from PBB via `get oldrevtex.sty

Towards Machine Wald

The past century has seen a steady increase in the need of estimating and predicting complex systems and making (possibly critical) decisions with limited information. Although computers have made possible the numerical evaluation of sophisticated statistical models, these models are still designed \emph{by humans} because there is currently no known recipe or algorithm for dividing the design of a statistical model into a sequence of arithmetic operations. Indeed enabling computers to \emph{think} as \emph{humans} have the ability to do when faced with uncertainty is challenging in several major ways: (1) Finding optimal statistical models remains to be formulated as a well posed problem when information on the system of interest is incomplete and comes in the form of a complex combination of sample data, partial knowledge of constitutive relations and a limited description of the distribution of input random variables. (2) The space of admissible scenarios along with the space of relevant information, assumptions, and/or beliefs, tend to be infinite dimensional, whereas calculus on a computer is necessarily discrete and finite. With this purpose, this paper explores the foundations of a rigorous framework for the scientific computation of optimal statistical estimators/models and reviews their connections with Decision Theory, Machine Learning, Bayesian Inference, Stochastic Optimization, Robust Optimization, Optimal Uncertainty Quantification and Information Based Complexity.Comment: 37 page

Eye Absence Does Not Regulate Planarian Stem Cells during Eye Regeneration

Dividing cells called neoblasts contain pluripotent stem cells and drive planarian flatworm regeneration from diverse injuries. A long-standing question is whether neoblasts directly sense and respond to the identity of missing tissues during regeneration. We used the eye to investigate this question. Surprisingly, eye removal was neither sufficient nor necessary for neoblasts to increase eye progenitor production. Neoblasts normally increase eye progenitor production following decapitation, facilitating regeneration. Eye removal alone, however, did not induce this response. Eye regeneration following eye-specific resection resulted from homeostatic rates of eye progenitor production and less cell death in the regenerating eye. Conversely, large head injuries that left eyes intact increased eye progenitor production. Large injuries also non-specifically increased progenitor production for multiple uninjured tissues. We propose a model for eye regeneration in which eye tissue production by planarian stem cells is not directly regulated by the absence of the eye itself. Keywords: planarian; regeneration; stem cell; eye; tissue turnover; target blind; progenitor; neoblastNational Institutes of Health (U.S.) (Grant R01GM080639

The Origin of Behavior

We propose a single evolutionary explanation for the origin of several behaviors that have been observed in organisms ranging from ants to human subjects, including risk-sensitive foraging, risk aversion, loss aversion, probability matching, randomization, and diversification. Given an initial population of individuals, each assigned a purely arbitrary behavior with respect to a binary choice problem, and assuming that offspring behave identically to their parents, only those behaviors linked to reproductive success will survive, and less reproductively successful behaviors will disappear at exponential rates. When the uncertainty in reproductive success is systematic, natural selection yields behaviors that may be individually sub-optimal but are optimal from the population perspective; when reproductive uncertainty is idiosyncratic, the individual and population perspectives coincide. This framework generates a surprisingly rich set of behaviors, and the simplicity and generality of our model suggest that these derived behaviors are primitive and nearly universal within and across species

Bycatch of franciscana dolphins Pontoporia blainvillei and the dynamic of artisanal fisheries in the species' southernmost area of distribution

Na Argentina, a toninha é um dos cetáceos mais vulneráveis devido às capturas por rede de pesca artesanal. O presente estudo teve como objetivo estimar as capturas acidentais no sul da província de Buenos Aires, através de entrevistas aos capitães de barcos de pesca artesanal, entre os anos 2006-2009. As capturas foram reportadas para redes de emalhe e de camarão; com as mais altas frequências entre outubro e fevereiro, a 5 km da costa e 10-20 m de profundidade. A mortalidade acidental média anual estimada foi de 107 golfinhos (IC 95% = 87-129), 92 em redes de emalhe (IC 95% = 73-112) e 15 em redes de camarão (IC 95% = 8-25), com uma captura de 0,029 golfinhos/km de rede de emalhe (IC 95% = 0,023-0,036) e 0,024/rede de camarão (IC 95% = 0,012-0,035). As flutuações anuais responderam principalmente às diferenças nos dias de pesca. Considerando o último levantamento estimativo feito para o norte costeiro da província, estima-se uma mortalidade entre 360-539 golfinhos/ano em toda a província de Buenos Aires. Esses valores correspondem de 2,5-3,7% da abundância populacional da Argentina; o que traria como consequência um declínio populacional da espécie, tornando-se fundamental encontrar alternativas de pesca para a área.In Argentina, the franciscana dolphin is one of the most vulnerable cetaceans regularly entangled in coastal artisanal fishery nets. The aim of this paper is to estimate the species' incidental mortality on the Southern coast of Buenos Aires province through interviews with the captains of artisanal fishing vessels, in the period 2006-2009. Franciscana bycatch was reported for gillnets and shrimper gear all year round but it occurred more frequently between October and February, at 5 km offshore and 10-20 m depth. The estimated mean annual incidental mortality was 107 dolphins (CI 95% = 87-129), 92 caught in gillnets (CI 95% = 73-112) and 15 in shrimpers' gear (CI 95% = 8-25) with a capture per unit effort of 0.029 dolphins per km of gillnet (CI 95% = 0.023-0.036) and 0.022 per shrimpe r's net (CI 95% = 0.012-0.035). Annual fluctuations were due to differences in the number of gillnetting fishing days. If mortality estimates for the Northern coast are also taken into account, values attain a maximum of 360-539 dolphins bycaught in the entire Buenos Aires province, representing 2.5-3.7% of the species' abundance in Argentina. This will inevitably lead to the decline of franciscana dolphin populations in the near future unless alternative fishing grounds are identified and alternative gearadopted

Are we working towards global research priorities for management and conservation of sea turtles?

In 2010, an international group of 35 sea turtle researchers refined an initial list of more than 200 research questions into 20 metaquestions that were considered key for management and conservation of sea turtles. These were classified under 5 categories: reproductive biology, biogeography, population ecology, threats and conservation strategies. To obtain a picture of how research is being focused towards these key questions, we undertook a systematic review of the peer-reviewed literature (2014 and 2015) attributing papers to the original 20 questions. In total, we reviewed 605 articles in full and from these 355 (59%) were judged to substantively address the 20 key questions, with others focusing on basic science and monitoring. Progress to answering the 20 questions was not uniform, and there were biases regarding focal turtle species, geographic scope and publication outlet. Whilst it offers some meaningful indications as to effort, quantifying peer-reviewed literature output is ob viously not the only, and possibly not the best, metric for understanding progress towards informing key conservation and management goals. Along with the literature review, an international group based on the original project consortium was assigned to critically summarise recent progress towards answering each of the 20 questions. We found that significant research is being expended towards global priorities for management and conservation of sea turtles. Although highly variable, there has been significant progress in all the key questions identified in 2010. Undertaking this critical review has highlighted that it may be timely to undertake one or more new prioritizing exercises. For this to have maximal benefit we make a range of recommendations for its execution. These include a far greater engagement with social sciences, widening the pool of contributors and focussing the questions, perhaps disaggregating ecology and conservatio