On defining the Hamiltonian beyond quantum theory

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

An adeno-associated viral vector transduces the rat hypothalamus and amygdala more efficient than a lentiviral vector

<p>Abstract</p> <p>Background</p> <p>This study compared the transduction efficiencies of an adeno-associated viral (AAV) vector, which was pseudotyped with an AAV1 capsid and encoded the green fluorescent protein (GFP), with a lentiviral (LV) vector, which was pseudotyped with a VSV-G envelop and encoded the discosoma red fluorescent protein (dsRed), to investigate which viral vector transduced the lateral hypothalamus or the amygdala more efficiently. The LV-dsRed and AAV1-GFP vector were mixed and injected into the lateral hypothalamus or into the amygdala of adult rats. The titers that were injected were 1 × 10⁸or 1 × 10⁹genomic copies of AAV1-GFP and 1 × 10⁵transducing units of LV-dsRed.</p> <p>Results</p> <p>Immunostaining for GFP and dsRed showed that AAV1-GFP transduced significantly more cells than LV-dsRed in both the lateral hypothalamus and the amygdala. In addition, the number of LV particles that were injected can not easily be increased, while the number of AAV1 particles can be increased easily with a factor 100 to 1000. Both viral vectors appear to predominantly transduce neurons.</p> <p>Conclusions</p> <p>This study showed that AAV1 vectors are better tools to overexpress or knockdown genes in the lateral hypothalamus and amygdala of adult rats, since more cells can be transduced with AAV1 than with LV vectors and the titer of AAV1 vectors can easily be increased to transduce the area of interest.</p

Neuropeptide delivery to the brain: a von Willebrand factor signal peptide to direct neuropeptide secretion

<p>Abstract</p> <p>Background</p> <p>Multiple neuropeptides, sometimes with opposing functions, can be produced from one precursor gene. To study the roles of the different neuropeptides encoded by one large precursor we developed a method to overexpress minigenes and establish local secretion.</p> <p>Results</p> <p>We fused the signal peptide from the Von Willebrand Factor (VWF) to a furin site followed by a processed form of the Agouti related protein (AgRP), AgRP_83-132or α-melanocyte stimulating hormone. <it>In vitro</it>, these minigenes were secreted and biologically active. Additionally, the proteins of the minigenes were not transported into projections of primary neurons, thereby ensuring local release. <it>In vivo </it>administration of VWF-AgRP_83-132, using an adeno-associated viral vector as a delivery vehicle, into the paraventricular hypothalamus increased body weight and food intake of these rats compared to rats which received a control vector.</p> <p>Conclusions</p> <p>This study demonstrated that removal of the N-terminal part of full length AgRP and addition of a VWF signal peptide is a successful strategy to deliver neuropeptide minigenes to the brain and establish local neuropeptide secretion.</p

A Best Evidence Medical Education (BEME) systematic review of: What works best for health professions students using mobile (hand-held) devices for educational support on clinical placements? BEME Guide No. 52

Background: Ingrained assumptions about clinical placements (clerkships) for health professions students pursuing primary basic qualifications might undermine best educational use of mobile devices. Question: What works best for health professions students using mobile (hand-held) devices for educational support on clinical placements? Methods: A Best Evidence Medical Education (BEME) effectiveness-review of ‘justification’ complemented by ‘clarification’ and ‘description’ research searched: MEDLINE, ERIC (Educational Resource Information Center), Web of Science, CINAHL (Cumulative Index to Nursing and Allied Health Literature), PsycInfo, Cochrane Central, Scopus (1988-2016). Reviewer-pairs screened titles/abstracts. One pair coded, extracted, and synthesized evidence, working within the pragmatism paradigm. Summary of results: From screening 2,279 abstracts, 49 articles met inclusion-criteria, counting four systematic reviews for context. The 45 articles of at least Kirkpatrick K2 primary research mostly contributed K3 (39/45, 86.7%), mixed methods (21/45, 46.7%), and S4-strength (about one-half) evidence. Mobile devices particularly supported student: assessment; communication; clinical decision-making; logbook/notetaking; and accessing information (in about two-thirds). Informal and hidden curricula included: ---concerns about: disapproval; confidentiality and privacy; security ---distraction by social connectivity and busy clinical settings; ---mixed messages about policy. Discussion & Conclusion: This idiosyncratic evidence-base of modest robustness suggested that mobile devices provide potentially powerful educational support on clinical placement, particularly with student transitions, metalearning, and care contribution. Explicit policy must tackle informal and hidden curricula though, addressing concerns about transgressions

On the formation of string cavitation inside fuel injectors

The formation of vortex or ‘string’ cavitation has been visualised in the flow upstream of the injection hole inlet of an automotive-sized optical diesel fuel injector nozzle operating at pressures up to 2,000 bar. Three different nozzle geometries and three-dimensional flow simulations have been employed to describe how, for two adjacent nozzle holes, their relative positions influenced the formation and hole-to-hole interaction of the observed string cavitation vortices. Each hole was shown to contain two counter-rotating vortices: the first extending upstream on axis with the nozzle hole into the nozzle sac volume and the second forming a single ‘bridging’ string linked to the adjacent hole. Steady-state and transient fuel injection conditions were shown to produce significantly different nozzle-flow characteristics with regard to the formation and interaction of these vortices in the geometries tested, with good agreement between the experimental and simulation results being achieved. The study further confirms that the visualised vortices do not cavitate themselves but act as carriers of gas-phase components within the injector flow

Deciphering interplay between Salmonella invasion effectors

Bacterial pathogens have evolved a specialized type III secretion system (T3SS) to translocate virulence effector proteins directly into eukaryotic target cells. Salmonellae deploy effectors that trigger localized actin reorganization to force their own entry into non-phagocytic host cells. Six effectors (SipC, SipA, SopE/2, SopB, SptP) can individually manipulate actin dynamics at the plasma membrane, which acts as a ‘signaling hub’ during Salmonella invasion. The extent of crosstalk between these spatially coincident effectors remains unknown. Here we describe trans and cis binary entry effector interplay (BENEFIT) screens that systematically examine functional associations between effectors following their delivery into the host cell. The results reveal extensive ordered synergistic and antagonistic relationships and their relative potency, and illuminate an unexpectedly sophisticated signaling network evolved through longstanding pathogen–host interaction

Gender, school and academic year differences among Spanish university students at high-risk for developing an eating disorder: An epidemiologic study

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to assess the magnitude of the university population at high-risk of developing an eating disorder and the prevalence of unhealthy eating attitudes and behaviours amongst groups at risk; gender, school or academic year differences were also explored.</p> <p>Methods</p> <p>A cross-sectional study based on self-report was used to screen university students at high-risk for an eating disorder. The sample size was of 2551 university students enrolled in 13 schools between the ages of 18 and 26 years. The instruments included: a social-demographic questionnaire, the Eating Disorders Inventory (EDI), the Body Shape Questionnaire (BSQ), the Symptom Check List 90-R (SCL-90-R), and the Self-Esteem Scale (RSE). The sample design is a non-proportional stratified sample by academic year and school. The prevalence rate was estimated controlling academic year and school. Logistic regression analysis was used to investigate adjusted associations between gender, school and academic year.</p> <p>Results</p> <p>Female students presented unhealthy weight-control behaviours as dieting, laxatives use or self-induced vomiting to lose weight than males. A total of 6% of the females had a BMI of 17.5 or less or 2.5% had amenorrhea for 3 or more months. In contrast, a higher proportion of males (11.6%) reported binge eating behaviour. The prevalence rate of students at high-risk for an eating disorder was 14.9% (11.6–18) for males and 20.8% (18.7–22.8) for females, according to an overall cut-off point on the EDI questionnaire. Prevalence rates presented statistically significant differences by gender (p < 0.001) but not by school or academic year.</p> <p>Conclusion</p> <p>The prevalence of eating disorder risk in university students is high and is associated with unhealthy weight-control practices, similar results have been found in previous studies using cut-off points in questionnaires. These results may be taken into account to encourage early detection and a greater awareness for seeking treatment in order to improve the diagnosis, among students on university campuses.</p

Molecular Dynamics Analysis of Apolipoprotein-D - Lipid Hydroperoxide Interactions: Mechanism for Selective Oxidation of Met-93

Background: Recent studies suggest reduction of radical-propagating fatty acid hydroperoxides to inert hydroxides by interaction with apolipoprotein-D (apoD) Met93 may represent an antioxidant function for apoD. The nature and structural consequences of this selective interaction are unknown. Methodology/Principal Findings: Herein we used molecular dynamics (MD) analysis to address these issues. Longtimescale simulations of apoD suggest lipid molecules are bound flexibly, with the molecules free to explore multiple conformations in a binding site at the entrance to the classical lipocalin ligand-binding pocket. Models of 5s- 12s- and 15s hydroperoxyeicosatetraenoic acids were created and the lipids found to wrap around Met93 thus providing a plausible mechanism by which eicosatetraenoic acids bearing hydroperoxides on different carbon atoms can interact with Met93 to yield Met93 sulfoxide (Met93SO). Simulations of glycosylated apoD indicated that a second solvent exposed Met at position 49 was shielded by a triantennerary N-glycan attached to Asn45 thereby precluding lipid interactions. MD simulations of apoD showed B-factors of the loop containing Met93SO were higher in the oxidized protein, indicating increased flexibility that is predicted to destabilize the protein and promote self-association. Conclusions/Significance: These studies provide novel insights into the mechanisms that may contribute to the antioxidant function of apoD and the structural consequences that result if Met93SO is not redox-cycled back to its native state

The Cochrane Skin Group: a vanguard for developing and promoting evidence-based dermatology

Aim The Cochrane Skin Group (CSG) is part of the international Cochrane Collaboration (http://www.cochrane.org/). The CSG prepares, maintains and disseminates high quality evidence-based summaries on the prevention, diagnosis and treatment of skin diseases. We present a synopsis of the history, scope and priorities of the CSG. In addition, we report outcomes of CSG reviews and critically assess clinical value. Methods Descriptive analysis of systematic reviews published by the CSG since its inception including output, impact factor, associated methodological studies, and influence in clinical guidelines, promoting patient and public engagement and in triggering new primary research. Results The CSG started in 1997, and has published 61 reviews, 34 protocols and 31 registered titles by August 2013. The CSG scope includes 1000 skin diseases; 80% of reviews cover the top ten diagnoses and 40% of reviews provide clear guidance for clinical practice. CSG reviews had an impact factor of 6.1 in 2011 which places it alongside top dermatology journals. CSG reviews are typically broad in focus and have been shown to be of better quality than non-Cochrane reviews. They are highly cited in clinical guidelines. Several reviews have identified evidence gaps that have led to better primary research. Conclusions The CSG has emerged as a vanguard of evidence-based dermatology by growing a community interested in applying best external evidence to the care of skin patients and by identifying topics for research. CSG reviews are high impact, clinically relevant and have tangibly influenced international dermatology clinical practice guidelines and new research

Testing the cognitive-behavioural maintenance models across DSM-5 bulimic-type eating disorder diagnostic groups: A multi-centre study

The original cognitive-behavioural (CB) model of bulimia nervosa, which provided the basis for the widely used CB therapy, proposed that specific dysfunctional cognitions and behaviours maintain the disorder. However, amongst treatment completers, only 40–50 % have a full and lasting response. The enhanced CB model (CB-E), upon which the enhanced version of the CB treatment was based, extended the original approach by including four additional maintenance factors. This study evaluated and compared both CB models in a large clinical treatment seeking sample (N = 679), applying both DSM-IV and DSM-5 criteria for bulimic-type eating disorders. Application of the DSM-5 criteria reduced the number of cases of DSM-IV bulimic-type eating disorders not otherwise specified to 29.6 %. Structural equation modelling analysis indicated that (a) although both models provided a good fit to the data, the CB-E model accounted for a greater proportion of variance in eating-disordered behaviours than the original one, (b) interpersonal problems, clinical perfectionism and low self-esteem were indirectly associated with dietary restraint through over-evaluation of shape and weight, (c) interpersonal problems and mood intolerance were directly linked to binge eating, whereas restraint only indirectly affected binge eating through mood intolerance, suggesting that factors other than restraint may play a more critical role in the maintenance of binge eating. In terms of strength of the associations, differences across DSM-5 bulimic-type eating disorder diagnostic groups were not observed. The results are discussed with reference to theory and research, including neurobiological findings and recent hypotheses