791 research outputs found

    On defining the Hamiltonian beyond quantum theory

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    Energy is a crucial concept within classical and quantum physics. An essential tool to quantify energy is the Hamiltonian. Here, we consider how to define a Hamiltonian in general probabilistic theories, a framework in which quantum theory is a special case. We list desiderata which the definition should meet. For 3-dimensional systems, we provide a fully-defined recipe which satisfies these desiderata. We discuss the higher dimensional case where some freedom of choice is left remaining. We apply the definition to example toy theories, and discuss how the quantum notion of time evolution as a phase between energy eigenstates generalises to other theories.Comment: Authors' accepted manuscript for inclusion in the Foundations of Physics topical collection on Foundational Aspects of Quantum Informatio

    Evidence for directional selection at a novel major histocompatibility class I marker in wild common frogs (Rana temporaria) exposed to a viral pathogen (Ranavirus).

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    (c) 2009 Teacher et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Whilst the Major Histocompatibility Complex (MHC) is well characterized in the anuran Xenopus, this region has not previously been studied in another popular model species, the common frog (Rana temporaria). Nor, to date, have there been any studies of MHC in wild amphibian host-pathogen systems. We characterise an MHC class I locus in the common frog, and present primers to amplify both the whole region, and specifically the antigen binding region. As no more than two expressed haplotypes were found in over 400 clones from 66 individuals, it is likely that there is a single class I locus in this species. This finding is consistent with the single class I locus in Xenopus, but contrasts with the multiple loci identified in axolotls, providing evidence that the diversification of MHC class I into multiple loci likely occurred after the Caudata/Anura divergence (approximately 350 million years ago) but before the Ranidae/Pipidae divergence (approximately 230 mya). We use this locus to compare wild populations of common frogs that have been infected with a viral pathogen (Ranavirus) with those that have no history of infection. We demonstrate that certain MHC supertypes are associated with infection status (even after accounting for shared ancestry), and that the diseased populations have more similar supertype frequencies (lower F(ST)) than the uninfected. These patterns were not seen in a suite of putatively neutral microsatellite loci. We interpret this pattern at the MHC locus to indicate that the disease has imposed selection for particular haplotypes, and hence that common frogs may be adapting to the presence of Ranavirus, which currently kills tens of thousands of amphibians in the UK each year

    Lesson learned from early and long-term results of 327 cases of coexisting surgical abdominal diseases and aortic aneurysms treated in open and endovascular surgery

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    Patients with abdominal aortic aneurysm (AAA) frequently have other abdominal pathologies of surgical interest (other diseases, OD). Out of 1,375 elective open aortic replacements for AAA, 315 cases with OD were subdivided in Group 1 (82 patients with “clean wound” OD) and Group 2 (233 patients with “clean-contaminated wound” OD). The results of the sub-groups in which OD was treated at the same time as AAA were analysed (1a, 66 cases and 2a, 86 cases) and compared with OD not treated at the same time as AAA (1b, 16 cases and 2b, 147 cases). EVAR was done in 12 patients with a infrarenal AAA and concomitant abdominal disease. In this group post-operative complications occured in two patients (endoleaks) and no sign of endograft infection was developed. Mean follow-up was 36 months. Mortality was 0% in Group 1a, 1b, 2b and 5.8% in Group 2a. In Group 1a there were one haemoperitoneum, one ischaemic colitis and one graft infection. In Group 1b there were 4 nefrectomies for renal carcinoma and three emergency hernia repairs within 18 months from AAA operation. In Group 2a the follow-up was uneventful. In Group 2b there was no acute complication of OD and 57.2% of patients were subsequently operated for OD. In the EVAR group the 30-day and late mortality rates were 0 and 25%, respectively and all deaths were cancer-related. Contemporary correction of OD in open surgery for AAA should be performed in clean wound cases, while clean-contaminated operations can be done only in selected cases. EVAR is a valid alternative technique to open vascular surgery for the concomitant treatment of aortic aneurysms and abdominal pathologies

    Application of multiple statistical tests to enhance mass spectrometry-based biomarker discovery

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    <p>Abstract</p> <p>Background</p> <p>Mass spectrometry-based biomarker discovery has long been hampered by the difficulty in reconciling lists of discriminatory peaks identified by different laboratories for the same diseases studied. We describe a multi-statistical analysis procedure that combines several independent computational methods. This approach capitalizes on the strengths of each to analyze the same high-resolution mass spectral data set to discover consensus differential mass peaks that should be robust biomarkers for distinguishing between disease states.</p> <p>Results</p> <p>The proposed methodology was applied to a pilot narcolepsy study using logistic regression, hierarchical clustering, t-test, and CART. Consensus, differential mass peaks with high predictive power were identified across three of the four statistical platforms. Based on the diagnostic accuracy measures investigated, the performance of the consensus-peak model was a compromise between logistic regression and CART, which produced better models than hierarchical clustering and t-test. However, consensus peaks confer a higher level of confidence in their ability to distinguish between disease states since they do not represent peaks that are a result of biases to a particular statistical algorithm. Instead, they were selected as differential across differing data distribution assumptions, demonstrating their true discriminatory potential.</p> <p>Conclusion</p> <p>The methodology described here is applicable to any high-resolution MALDI mass spectrometry-derived data set with minimal mass drift which is essential for peak-to-peak comparison studies. Four statistical approaches with differing data distribution assumptions were applied to the same raw data set to obtain consensus peaks that were found to be statistically differential between the two groups compared. These consensus peaks demonstrated high diagnostic accuracy when used to form a predictive model as evaluated by receiver operating characteristics curve analysis. They should demonstrate a higher discriminatory ability as they are not biased to a particular algorithm. Thus, they are prime candidates for downstream identification and validation efforts.</p

    Motor Adaptation Scaled by the Difficulty of a Secondary Cognitive Task

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    Background: Motor learning requires evaluating performance in previous movements and modifying future movements. The executive system, generally involved in planning and decision-making, could monitor and modify behavior in response to changes in task difficulty or performance. Here we aim to identify the quantitative cognitive contribution to responsive and adaptive control to identify possible overlap between cognitive and motor processes. Methodology/Principal Findings: We developed a dual-task experiment that varied the trial-by-trial difficulty of a secondary cognitive task while participants performed a motor adaptation task. Subjects performed a difficulty-graded semantic categorization task while making reaching movements that were occasionally subjected to force perturbations. We find that motor adaptation was specifically impaired on the most difficult to categorize trials. Conclusions/Significance: We suggest that the degree of decision-level difficulty of a particular categorization differentially burdens the executive system and subsequently results in a proportional degradation of adaptation. Our results suggest

    Evaluation of the efficacy and safety of olanzapine as an adjunctive treatment for anorexia nervosa in adolescent females: a randomized, double-blind, placebo-controlled trial

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    <p>Abstract</p> <p>Background</p> <p>Anorexia Nervosa (AN) is a serious, debilitating condition that causes significant physical, emotional, and functional impairment. The condition is characterized by destructive weight loss behaviours and a refusal to maintain body weight at or above a minimally normal weight for age and height. AN often develops in adolescence and is a predominantly female disorder. Treatment for AN typically involves medical, nutritional and psychological interventions. Pharmacotherapy is also often used; however, the literature on the effectiveness of these drugs in a pediatric population is very limited. Olanzapine, which is an 'atypical' antipsychotic, is becoming more widespread in the treatment of AN. Olanzapine is hypothesized to facilitate weight gain, while decreasing levels of agitation and decreasing resistance to treatment in young women with AN. This randomized, double-blind placebo-controlled trial seeks to examine the effectiveness and safety of olanzapine in female youth with AN.</p> <p>Methods/Design</p> <p>Adolescent females between the ages of 12 and 17 diagnosed with AN (either restricting or binge/purge type) or Eating Disorder Not Otherwise Specified with a Body Mass Index of less than or equal to 17.5, will be offered inclusion in the study. Patients will be randomly assigned to receive either olanzapine or placebo. Patients assigned to receive olanzapine will start at a low dose of 1.25 mg/day for three days, followed by 2.5 mg/day for four days, 5 mg/day for one week, then 7.5 mg/day (the target dose chosen) for 10 weeks. After 10 weeks at 7.5 mg the medication will be tapered and discontinued over a period of two weeks. The effectiveness of olanzapine versus placebo will be determined by investigating the change from baseline on measures of eating attitudes and behaviors, depression and anxiety, and change in Body Mass Index at week 12, and after a follow-up period at week 40. It is anticipated that 67 participants will be recruited over two years to complete enrollment.</p> <p>Discussion</p> <p>Randomized controlled trials designed to measure the safety and effectiveness of olanzapine in comparison to placebo are desperately needed, particularly in the adolescent population.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN23032339</p

    Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

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    Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

    Differential Scanning Fluorimetry provides high throughput data on silk protein transitions

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    Here we present a set of measurements using Differential Scanning Fluorimetry (DSF) as an inexpensive, high throughput screening method to investigate the folding of silk protein molecules as they abandon their first native melt conformation, dehydrate and denature into their final solid filament conformation. Our first data and analyses comparing silks from spiders, mulberry and wild silkworms as well as reconstituted ‘silk’ fibroin show that DSF can provide valuable insights into details of silk denaturation processes that might be active during spinning. We conclude that this technique and technology offers a powerful and novel tool to analyse silk protein transitions in detail by allowing many changes to the silk solutions to be tested rapidly with microliter scale sample sizes. Such transition mechanisms will lead to important generic insights into the folding patterns not only of silks but also of other fibrous protein (bio)polymers
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