Fixation artefact in an intra-operative frozen section: a potential cause of misinterpretation

The intra-operative histological assessment of fresh tissue can provide valuable diagnostic information and guide surgical management, however, even a limited exposure to standard fixation agents can potentially compromise analysis. Defined handling strategies should exist to facilitate the receipt of all specimens, in their optimal state, by the laboratory

The return trip effect: Why the return trip often seems to take less time

Three studies confirm the existence of the return trip effect: The return trip often seems shorter than the initial trip, even though the distance traveled and the actual time spent traveling are identical. A pretest shows that people indeed experience a return trip effect regularly, and the effect was found on a bus trip (Study 1), a bicycle trip (Study 2), and when participants watched a video of someone else traveling (Study 3). The return trip effect also existed when another, equidistant route was taken on the return trip, showing that it is not familiarity with the route that causes this effect. Rather, it seems that a violation of expectations causes this effect

A comparative evaluation of PDQ-Evidence

BACKGROUND: A strategy for minimising the time and obstacles to accessing systematic reviews of health system evidence is to collect them in a freely available database and make them easy to find through a simple ‘Google-style’ search interface. PDQ-Evidence was developed in this way. The objective of this study was to compare PDQ-Evidence to six other databases, namely Cochrane Library, EVIPNet VHL, Google Scholar, Health Systems Evidence, PubMed and Trip. METHODS: We recruited healthcare policy-makers, managers and health researchers in low-, middle- and highincome countries. Participants selected one of six pre-determined questions. They searched for a systematic review that addressed the chosen question and one question of their own in PDQ-Evidence and in two of the other six databases which they would normally have searched. We randomly allocated participants to search PDQ-Evidence first or to search the two other databases first. The primary outcomes were whether a systematic review was found and the time taken to find it. Secondary outcomes were perceived ease of use and perceived time spent searching. We asked open-ended questions about PDQ-Evidence, including likes, dislikes, challenges and suggestions for improvements. RESULTS: A total of 89 people from 21 countries completed the study; 83 were included in the primary analyses and 6 were excluded because of data errors that could not be corrected. Most participants chose PubMed and Cochrane Library as the other two databases. Participants were more likely to find a systematic review using PDQ-Evidence than using Cochrane Library or PubMed for the pre-defined questions. For their own questions, this difference was not found. Overall, it took slightly less time to find a systematic review using PDQ-Evidence. Participants perceived that it took less time, and most participants perceived PDQ-Evidence to be slightly easier to use than the two other databases. However, there were conflicting views about the design of PDQ-Evidence. CONCLUSIONS: PDQ-Evidence is at least as efficient as other databases for finding health system evidence. However, using PDQ-Evidence is not intuitive for some people

I Lie? We Lie! Why? Experimental Evidence on a Dishonesty Shift in Groups

Unethical behavior such as dishonesty, cheating and corruption occurs fre-quently in organizations or groups. Recent experimental evidence suggests that there isa stronger inclination to behave immorally in groups than individually. We ask if this isthe case, and if so, why. Using a parsimonious laboratory setup, we study how individualbehavior changes when deciding as a group member. We observe a strong dishonestyshift. This shift is mainly driven by communication within groups and turns out to be inde-pendent of whether group members face payoff commonality or not (i.e., whether othergroup members benefit from one’s lie). Group members come up with and exchange morearguments for being dishonest than for complying with the norm of honesty. Thereby,group membership shifts the perception of the validity of the honesty norm and of itsdistribution in the population

Cardiopulmonary exercise performance and factors associated with aerobic capacity in neuromuscular diseases

Introduction/Aims: Aerobic deconditioning, due to lower levels of physical activity, could impact independence for people with neuromuscular conditions. We report the maximal cardiopulmonary response in a cohort of people with Charcot Marie Tooth disease type 1A (CMT 1A) and inclusion body myositis (IBM). We also explored potential predictors of aerobic capacity with measures of physical impairment and functional performance. Methods: Participants underwent maximal cardiopulmonary exercise testing (CPET) using a semi-recumbent cycle ergometer. Data were analyzed to determine the peak O2 consumption (VO2 peak), anaerobic threshold (AT), maximum heart rate (MHR), ventilatory equivalent for CO2 slope (VE/VCO2), and respiratory exchange ratio (RER). Impairment, functional and patient reported measures were also recorded. Predicted CPET variables were calculated based on published normative data for age, gender, and weight. Results: Twenty-two people with CMT and 17 people with IBM were recruited. Both groups showed significantly lower VO2 peak, MHR, AT, and VE/VCO2. The CMT group overall performed better than the IBM group, with significantly higher VO2 peak, MHR, and AT, but lower VE/VCO2. Linear regression analysis demonstrated that VO2 peak was related to body fat percentage and 6-min walk distance for both groups, and steps per day for the IBM group. Discussion: Lower than predicted CPET variables were observed that were not explained by cardiopulmonary limitations or reduced effort, implicating peripheral factors in limiting the cycling task. Regression analysis implied prediction of VO2 peak by body fat percentage and 6-min walk distance. Six-minute walk distance could be a potential proxy measure of cardiopulmonary fitness

Mapping gene associations in human mitochondria using clinical disease phenotypes

Nuclear genes encode most mitochondrial proteins, and their mutations cause diverse and debilitating clinical disorders. To date, 1,200 of these mitochondrial genes have been recorded, while no standardized catalog exists of the associated clinical phenotypes. Such a catalog would be useful to develop methods to analyze human phenotypic data, to determine genotype-phenotype relations among many genes and diseases, and to support the clinical diagnosis of mitochondrial disorders. Here we establish a clinical phenotype catalog of 174 mitochondrial disease genes and study associations of diseases and genes. Phenotypic features such as clinical signs and symptoms were manually annotated from full-text medical articles and classified based on the hierarchical MeSH ontology. This classification of phenotypic features of each gene allowed for the comparison of diseases between different genes. In turn, we were then able to measure the phenotypic associations of disease genes for which we calculated a quantitative value that is based on their shared phenotypic features. The results showed that genes sharing more similar phenotypes have a stronger tendency for functional interactions, proving the usefulness of phenotype similarity values in disease gene network analysis. We then constructed a functional network of mitochondrial genes and discovered a higher connectivity for non-disease than for disease genes, and a tendency of disease genes to interact with each other. Utilizing these differences, we propose 168 candidate genes that resemble the characteristic interaction patterns of mitochondrial disease genes. Through their network associations, the candidates are further prioritized for the study of specific disorders such as optic neuropathies and Parkinson disease. Most mitochondrial disease phenotypes involve several clinical categories including neurologic, metabolic, and gastrointestinal disorders, which might indicate the effects of gene defects within the mitochondrial system. The accompanying knowledgebase (http://www.mitophenome.org/) supports the study of clinical diseases and associated genes

The deuteron: structure and form factors

A brief review of the history of the discovery of the deuteron in provided. The current status of both experiment and theory for the elastic electron scattering is then presented.Comment: 80 pages, 33 figures, submited to Advances in Nuclear Physic

Autoimmune and autoinflammatory mechanisms in uveitis

The eye, as currently viewed, is neither immunologically ignorant nor sequestered from the systemic environment. The eye utilises distinct immunoregulatory mechanisms to preserve tissue and cellular function in the face of immune-mediated insult; clinically, inflammation following such an insult is termed uveitis. The intra-ocular inflammation in uveitis may be clinically obvious as a result of infection (e.g. toxoplasma, herpes), but in the main infection, if any, remains covert. We now recognise that healthy tissues including the retina have regulatory mechanisms imparted by control of myeloid cells through receptors (e.g. CD200R) and soluble inhibitory factors (e.g. alpha-MSH), regulation of the blood retinal barrier, and active immune surveillance. Once homoeostasis has been disrupted and inflammation ensues, the mechanisms to regulate inflammation, including T cell apoptosis, generation of Treg cells, and myeloid cell suppression in situ, are less successful. Why inflammation becomes persistent remains unknown, but extrapolating from animal models, possibilities include differential trafficking of T cells from the retina, residency of CD8(+) T cells, and alterations of myeloid cell phenotype and function. Translating lessons learned from animal models to humans has been helped by system biology approaches and informatics, which suggest that diseased animals and people share similar changes in T cell phenotypes and monocyte function to date. Together the data infer a possible cryptic infectious drive in uveitis that unlocks and drives persistent autoimmune responses, or promotes further innate immune responses. Thus there may be many mechanisms in common with those observed in autoinflammatory disorders

The search for transient astrophysical neutrino emission with IceCube-DeepCore

We present the results of a search for astrophysical sources of brief transient neutrino emission using IceCube and DeepCore data acquired between 2012 May 15 and 2013 April 30. While the search methods employed in this analysis are similar to those used in previous IceCube point source searches, the data set being examined consists of a sample of predominantly sub-TeV muon-neutrinos from the Northern Sky (-5 degrees < delta < 90 degrees) obtained through a novel event selection method. This search represents a first attempt by IceCube to identify astrophysical neutrino sources in this relatively unexplored energy range. The reconstructed direction and time of arrival of neutrino events are used to search for any significant self-correlation in the data set. The data revealed no significant source of transient neutrino emission. This result has been used to construct limits at timescales ranging from roughly 1 s to 10 days for generic soft-spectra transients. We also present limits on a specific model of neutrino emission from soft jets in core-collapse supernovae

Identification of errors introduced during high throughput sequencing of the T cell receptor repertoire

<p>Abstract</p> <p>Background</p> <p>Recent advances in massively parallel sequencing have increased the depth at which T cell receptor (TCR) repertoires can be probed by >3log10, allowing for saturation sequencing of immune repertoires. The resolution of this sequencing is dependent on its accuracy, and direct assessments of the errors formed during high throughput repertoire analyses are limited.</p> <p>Results</p> <p>We analyzed 3 monoclonal TCR from TCR transgenic, Rag^-/-mice using Illumina^®sequencing. A total of 27 sequencing reactions were performed for each TCR using a trifurcating design in which samples were divided into 3 at significant processing junctures. More than 20 million complementarity determining region (CDR) 3 sequences were analyzed. Filtering for lower quality sequences diminished but did not eliminate sequence errors, which occurred within 1-6% of sequences. Erroneous sequences were pre-dominantly of correct length and contained single nucleotide substitutions. Rates of specific substitutions varied dramatically in a position-dependent manner. Four substitutions, all purine-pyrimidine transversions, predominated. Solid phase amplification and sequencing rather than liquid sample amplification and preparation appeared to be the primary sources of error. Analysis of polyclonal repertoires demonstrated the impact of error accumulation on data parameters.</p> <p>Conclusions</p> <p>Caution is needed in interpreting repertoire data due to potential contamination with mis-sequence reads. However, a high association of errors with phred score, high relatedness of erroneous sequences with the parental sequence, dominance of specific nt substitutions, and skewed ratio of forward to reverse reads among erroneous sequences indicate approaches to filter erroneous sequences from repertoire data sets.</p