Gross Domestic Product (GDP) and productivity of schizophrenia trials: an ecological study

The 5000 randomised controlled trials (RCTs) in the Cochrane Schizophrenia Group's database affords an opportunity to research for variables related to the differences between nations of their output of schizophrenia trials. Ecological study – investigating the relationship between four economic/demographic variables and number of schizophrenia RCTs per country. The variable with closest correlation was used to predict the expected number of studies. GDP closely correlated with schizophrenia trial output, with 76% of the total variation about the Y explained by the regression line (r = 0.87, 95% CI 0.79 to 0.92, r2 = 0.76). Many countries have a strong tradition of schizophrenia trials, exceeding their predicted output. All nations with no identified trial output had GDPs that predicted zero trial activity. Several nations with relatively small GDPs are, nevertheless, highly productive of trials. Some wealthy countries seem either not to have produced the expected number of randomised trials or not to have disseminated them to the English-speaking world. This hypothesis-generating study could not investigate causal relationships, but suggests, that for those seeking all relevant studies, expending effort searching the scientific literature of Germany, Italy, France, Brazil and Japan may be a good investment

On the nonlinear dynamics of the traveling-wave solutions of the Serre system

We numerically study nonlinear phenomena related to the dynamics of traveling wave solutions of the Serre equations including the stability, the persistence, the interactions and the breaking of solitary waves. The numerical method utilizes a high-order finite-element method with smooth, periodic splines in space and explicit Runge-Kutta methods in time. Other forms of solutions such as cnoidal waves and dispersive shock waves are also considered. The differences between solutions of the Serre equations and the Euler equations are also studied.Comment: 28 pages, 20 figures, 3 tables, 33 references. Other author's papers can be downloaded at http://www.denys-dutykh.com

The current status of the case report: Terminal or viable?

The case report, which has a long history in medicine, has seen its fortune wax and wane with time. We discuss the challenges facing the continued survival of the case report, including the inability of journals to cope with the increased load and increased cost of publication, ethical issues, the impact factor and the rise of evidence-based medicine. We highlight the important role that the case report will continue to play in medical research and education, as a means of sharing information and detecting novelty through observations. Most importantly, the case report serves as a stepping stone for young physicians and practitioners into the world of medical writing

Translational outcomes in a full gene deletion of ubiquitin protein ligase E3A rat model of Angelman syndrome.

Angelman syndrome (AS) is a rare neurodevelopmental disorder characterized by developmental delay, impaired communication, motor deficits and ataxia, intellectual disabilities, microcephaly, and seizures. The genetic cause of AS is the loss of expression of UBE3A (ubiquitin protein ligase E6-AP) in the brain, typically due to a deletion of the maternal 15q11-q13 region. Previous studies have been performed using a mouse model with a deletion of a single exon of Ube3a. Since three splice variants of Ube3a exist, this has led to a lack of consistent reports and the theory that perhaps not all mouse studies were assessing the effects of an absence of all functional UBE3A. Herein, we report the generation and functional characterization of a novel model of Angelman syndrome by deleting the entire Ube3a gene in the rat. We validated that this resulted in the first comprehensive gene deletion rodent model. Ultrasonic vocalizations from newborn Ube3am-/p+ were reduced in the maternal inherited deletion group with no observable change in the Ube3am+/p- paternal transmission cohort. We also discovered Ube3am-/p+ exhibited delayed reflex development, motor deficits in rearing and fine motor skills, aberrant social communication, and impaired touchscreen learning and memory in young adults. These behavioral deficits were large in effect size and easily apparent in the larger rodent species. Low social communication was detected using a playback task that is unique to rats. Structural imaging illustrated decreased brain volume in Ube3am-/p+ and a variety of intriguing neuroanatomical phenotypes while Ube3am+/p- did not exhibit altered neuroanatomy. Our report identifies, for the first time, unique AS relevant functional phenotypes and anatomical markers as preclinical outcomes to test various strategies for gene and molecular therapies in AS

Model refactoring using examples: a search‐based approach

One of the important challenges in model‐driven engineering is how to improve the quality of the models' design in order to help designers understand them. Refactoring represents an efficient technique to improve the quality of a design while preserving its behavior. Most of existing work on model refactoring relies on declarative rules to detect refactoring opportunities and to apply the appropriate refactorings. However, a complete specification of refactoring opportunities requires a huge number of rules. In this paper, we consider the refactoring mechanism as a combinatorial optimization problem where the goal is to find good refactoring suggestions starting from a small set of refactoring examples applied to similar contexts. Our approach, named model refactoring by example, takes as input an initial model to refactor, a set of structural metrics calculated on both initial model and models in the base of examples, and a base of refactoring examples extracted from different software systems and generates as output a sequence of refactorings. A solution is defined as a combination of refactoring operations that should maximize as much as possible the structural similarity based on metrics between the initial model and the models in the base of examples. A heuristic method is used to explore the space of possible refactoring solutions. To this end, we used and adapted a genetic algorithm as a global heuristic search. The validation results on different systems of real‐world models taken from open‐source projects confirm the effectiveness of our approach. Copyright © 2014 John Wiley & Sons, Ltd.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108085/1/smr1644.pd

Diversification and reproductive isolation: cryptic species in the only New World high-duty cycle bat, Pteronotus parnellii

<p>Abstract</p> <p>Background</p> <p>Molecular techniques are increasingly employed to recognize the presence of cryptic species, even among commonly observed taxa. Previous studies have demonstrated that bats using high-duty cycle echolocation may be more likely to speciate quickly. <it>Pteronotus parnellii</it> is a widespread Neotropical bat and the only New World species to use high-duty cycle echolocation, a trait otherwise restricted to Old World taxa. Here we analyze morphological and acoustic variation and genetic divergence at the mitochondrial COI gene, the 7^th intron region of the y-linked <it>Dby</it> gene and the nuclear recombination-activating gene 2, and provide extensive evidence that <it>P. parnellii</it> is actually a cryptic species complex.</p> <p>Results</p> <p>Central American populations form a single species while three additional species exist in northern South America: one in Venezuela, Trinidad and western Guyana and two occupying sympatric ranges in Guyana and Suriname. Reproductive isolation appears nearly complete (only one potential hybrid individual found). The complex likely arose within the last ~6 million years with all taxa diverging quickly within the last ~1-2 million years, following a pattern consistent with the geological history of Central and northern South America. Significant variation in cranial measures and forearm length exists between three of the four groups, although no individual morphological character can discriminate these in the field. Acoustic analysis reveals small differences (5–10 kHz) in echolocation calls between allopatric cryptic taxa that are unlikely to provide access to different prey resources but are consistent with divergence by drift in allopatric species or through selection for social recognition.</p> <p>Conclusions</p> <p>This unique approach, considering morphological, acoustic and multi-locus genetic information inherited maternally, paternally and bi-parentally, provides strong support to conclusions about the cessation of gene flow and degree of reproductive isolation of these cryptic species.</p

Evidence of Oxidative Stress and Secondary Mitochondrial Dysfunction in Metabolic and Non-Metabolic Disorders

Abstract: Mitochondrial dysfunction and oxidative stress have been implicated in the pathogenesis of a number of diseases and conditions. Oxidative stress occurs once the antioxidant defenses of the body become overwhelmed and are no longer able to detoxify reactive oxygen species (ROS). The ROS can then go unchallenged and are able to cause oxidative damage to cellular lipids, DNA and proteins, which will eventually result in cellular and organ dysfunction. Although not always the primary cause of disease, mitochondrial dysfunction as a secondary consequence disease of pathophysiology can result in increased ROS generation together with an impairment in cellular energy status. Mitochondrial dysfunction may result from either free radical-induced oxidative damage or direct impairment by the toxic metabolites which accumulate in certain metabolic diseases. In view of the importance of cellular antioxidant status, a number of therapeutic strategies have been employed in disorders associated with oxidative stress with a view to neutralising the ROS and reactive nitrogen species implicated in disease pathophysiology. Although successful in some cases, these adjunct therapies have yet to be incorporated into the clinical management of patients. The purpose of this review is to highlight the emerging evidence of oxidative stress, secondary mitochondrial dysfunction and antioxidant treatment efficacy in metabolic and non-metabolic diseases in which there is a current interest in these parameters

Current-induced transition from particle-by-particle to concurrent intercalation in phase-separating battery electrodes

Many battery electrodes contain ensembles of nanoparticles that phase-separate on (de)intercalation. In such electrodes, the fraction of actively intercalating particles directly impacts cycle life: a vanishing population concentrates the current in a small number of particles, leading to current hotspots. Reports of the active particle population in the phase-separating electrode ​lithium iron phosphate (​LiFePO4; ​LFP) vary widely, ranging from near 0% (particle-by-particle) to 100% (concurrent intercalation). Using synchrotron-based X-ray microscopy, we probed the individual state-of-charge for over 3,000 ​LFP particles. We observed that the active population depends strongly on the cycling current, exhibiting particle-by-particle-like behaviour at low rates and increasingly concurrent behaviour at high rates, consistent with our phase-field porous electrode simulations. Contrary to intuition, the current density, or current per active internal surface area, is nearly invariant with the global electrode cycling rate. Rather, the electrode accommodates higher current by increasing the active particle population. This behaviour results from thermodynamic transformation barriers in ​LFP, and such a phenomenon probably extends to other phase-separating battery materials. We propose that modifying the transformation barrier and exchange current density can increase the active population and thus the current homogeneity. This could introduce new paradigms to enhance the cycle life of phase-separating battery electrodes

Approaches to integrating genetic data into ecological networks

As molecular tools for assessing trophic interactions become common, research is increasingly focused on the construction of interaction networks. Here, we demonstrate three key methods for incorporating DNA data into network ecology and discuss analytical considerations using a model consisting of plants, insects, bats and their parasites from the Costa Rica dry forest. The simplest method involves the use of Sanger sequencing to acquire long sequences to validate or refine field identifications, for example of bats and their parasites, where one specimen yields one sequence and one identification. This method can be fully quantified and resolved and these data resemble traditional ecological networks. For more complex taxonomic identifications, we target multiple DNA loci, for example from a seed or fruit pulp sample in faeces. These networks are also well resolved but gene targets vary in resolution and quantification is difficult. Finally, for mixed templates such as faecal contents of insectivorous bats, we use DNA metabarcoding targeting two sequence lengths (157 and 407 bp) of one gene region and a MOTU, BLAST and BIN association approach to resolve nodes. This network type is complex to generate and analyse, and we discuss the implications of this type of resolution on network analysis. Using these data, we construct the first molecular-based network of networks containing 3,304 interactions between 762 nodes of eight trophic functions and involving parasitic, mutualistic and predatory interactions. We provide a comparison of the relative strengths and weaknesses of these data types in network ecology