Prenatal factors contribute to the emergence of kwoshiorkor or marasmus in severe undernutrition: evidence for the predictive adaptation model

Severe acute malnutrition in childhood manifests as oedematous (kwashiorkor, marasmic kwashiorkor) and non-oedematous (marasmus) syndromes with very different prognoses. Kwashiorkor differs from marasmus in the patterns of protein, amino acid and lipid metabolism when patients are acutely ill as well as after rehabilitation to ideal weight for height. Metabolic patterns among marasmic patients define them as metabolically thrifty, while kwashiorkor patients function as metabolically profligate. Such differences might underlie syndromic presentation and prognosis. However, no fundamental explanation exists for these differences in metabolism, nor clinical pictures, given similar exposures to undernutrition. We hypothesized that different developmental trajectories underlie these clinical-metabolic phenotypes: if so this would be strong evidence in support of predictive adaptation model of developmental plasticity

Elective affinities of the Protestant ethic : Weber and the chemistry of capitalism

Peer reviewedPostprin

Ultra-fine dark matter structure in the Solar neighbourhood

The direct detection of dark matter on Earth depends crucially on its density and its velocity distribution on a milliparsec scale. Conventional N-body simulations are unable to access this scale, making the development of other approaches necessary. In this paper, we apply the method developed in Fantin et al. 2008 to a cosmologically-based merger tree, transforming it into a useful instrument to reproduce and analyse the merger history of a Milky Way-like system. The aim of the model is to investigate the implications of any ultra-fine structure for the current and next generation of directional dark matter detectors. We find that the velocity distribution of a Milky Way-like Galaxy is almost smooth, due to the overlap of many streams of particles generated by multiple mergers. Only the merger of a 10^10 Msun analyse can generate significant features in the ultra-local velocity distribution, detectable at the resolution attainable by current experiments.Comment: 9 pages, 6 figures, accepted for publication in MNRA

The U.S. training institute for dissemination and implementation research in health

Abstract Background The science of dissemination and implementation (D&I) is advancing the knowledge base for how best to integrate evidence-based interventions within clinical and community settings and how to recast the nature or conduct of the research itself to make it more relevant and actionable in those settings. While the field is growing, there are only a few training programs for D&I research; this is an important avenue to help build the field’s capacity. To improve the United States’ capacity for D&I research, the National Institutes of Health and Veterans Health Administration collaborated to develop a five-day training institute for postdoctoral level applicants aspiring to advance this science. Methods We describe the background, goals, structure, curriculum, application process, trainee evaluation, and future plans for the Training in Dissemination and Implementation Research in Health (TIDIRH). Results The TIDIRH used a five-day residential immersion to maximize opportunities for trainees and faculty to interact. The train-the-trainer-like approach was intended to equip participants with materials that they could readily take back to their home institutions to increase interest and further investment in D&I. The TIDIRH curriculum included a balance of structured large group discussions and interactive small group sessions. Thirty-five of 266 applicants for the first annual training institute were accepted from a variety of disciplines, including psychology (12 trainees); medicine (6 trainees); epidemiology (5 trainees); health behavior/health education (4 trainees); and 1 trainee each from education & human development, health policy and management, health services research, public health studies, public policy and social work, with a maximum of two individuals from any one institution. The institute was rated as very helpful by attendees, and by six months after the institute, a follow-up survey (97% return rate) revealed that 72% had initiated a new grant proposal in D&I research; 28% had received funding, and 77% had used skills from TIDIRH to influence their peers from different disciplines about D&I research through building local research networks, organizing formal presentations and symposia, teaching and by leading interdisciplinary teams to conduct D&I research. Conclusions The initial TIDIRH training was judged successful by trainee evaluation at the conclusion of the week’s training and six-month follow-up, and plans are to continue and possibly expand the TIDIRH in coming years. Strengths are seen as the residential format, quality of the faculty and their flexibility in adjusting content to meet trainee needs, and the highlighting of concrete D&I examples by the local host institution, which rotates annually. Lessons learned and plans for future TIDIRH trainings are summarized

Effect of halo modelling on WIMP exclusion limits

WIMP direct detection experiments are just reaching the sensitivity required to detect galactic dark matter in the form of neutralinos. Data from these experiments are usually analysed under the simplifying assumption that the Milky Way halo is an isothermal sphere with maxwellian velocity distribution. Observations and numerical simulations indicate that galaxy halos are in fact triaxial and anisotropic. Furthermore, in the cold dark matter paradigm galactic halos form via the merger of smaller subhalos, and at least some residual substructure survives. We examine the effect of halo modelling on WIMP exclusion limits, taking into account the detector response. Triaxial and anisotropic halo models, with parameters motivated by observations and numerical simulations, lead to significant changes which are different for different experiments, while if the local WIMP distribution is dominated by small scale clumps then the exclusion limits are changed dramatically.Comment: 9 pages, 9 figures, version to appear in Phys. Rev. D, minor change

Discovery of X-ray Pulsations from the Compact Central Source in the Supernova Remnant 3C 58

We report on high time resolution observations of the SNR 3C 58 using the High Resolution Camera on the Chandra X-ray Observatory. These data show a point-like central source, from which we detect 65.68 ms pulsations at 6.7 sigma significance. We interpret these pulsations as corresponding to a young rotation-powered pulsar (PSR J-205+6449) which is associated with, and powers, 3C 58. Analysis of archival RXTE data from three years earlier confirms these pulsations, and allows us to determine a spin-down rate of P-dot=1.93x10^-13 s/s. Assuming a magnetic dipole model for PSR J0205+6449, we infer a surface magnetic field of 3.6x10^12 G. The characteristic age for this pulsar is 5400 yr, indicating either that 3C 58 was not the supernova of 1181 CE, or that the pulsar's initial spin period was ~60 ms.Comment: 11 pages, 4 figures, 1 tabl

Increasing condom use in heterosexual men: development of a theory-based interactive digital intervention

Increasing condom use to prevent sexually transmitted infections is a key public health goal. Interventions are more likely to be effective if they are theory- and evidence-based. The Behaviour Change Wheel (BCW) provides a framework for intervention development. To provide an example of how the BCW was used to develop an intervention to increase condom use in heterosexual men (the MenSS website), the steps of the BCW intervention development process were followed, incorporating evidence from the research literature and views of experts and the target population. Capability (e.g. knowledge) and motivation (e.g. beliefs about pleasure) were identified as important targets of the intervention. We devised ways to address each intervention target, including selecting interactive features and behaviour change techniques. The BCW provides a useful framework for integrating sources of evidence to inform intervention content and deciding which influences on behaviour to target

The detection of sub-solar mass dark matter halos

Dark matter halos of sub-solar mass are the first bound objects to form in cold dark matter theories. In this article, I discuss the present understanding of "microhalos'', their role in structure formation, and the implications of their potential presence, in the interpretation of dark matter experiments.Comment: 18 pages, 7 figures. Invited contribution to NJP Focus Issue on "Dark Matter and Particle Physics

Metformin Improves Peripheral Insulin Sensitivity in Youth With Type 1 Diabetes

Context: Type 1 diabetes in adolescence is characterized by insulin deficiency and insulin resistance (IR), both thought to increase cardiovascular disease risk. We previously demonstrated that adolescents with type 1 diabetes have adipose, hepatic, and muscle IR, and that metformin lowers daily insulin dose, suggesting improved IR. However, whether metformin improves IR in muscle, hepatic, or adipose tissues in type 1 diabetes was unknown. Objective: Measure peripheral, hepatic, and adipose insulin sensitivity before and after metformin or placebo therapy in youth with obesity with type 1 diabetes. Design: Double-blind, placebo-controlled clinical trial. Setting: Multi-center at eight sites of the T1D Exchange Clinic Network. Participants: A subset of 12- to 19-year-olds with type 1 diabetes (inclusion criteria: body mass index ≥85th percentile, HbA1c 7.5% to 9.9%, insulin dosing ≥0.8 U/kg/d) from a larger trial (NCT02045290) were enrolled. Intervention: Participants were randomized to 3 months of metformin (N = 19) or placebo (N = 18) and underwent a three-phase hyperinsulinemic euglycemic clamp with glucose and glycerol isotope tracers to assess tissue-specific IR before and after treatment. Main outcome measures: Peripheral insulin sensitivity, endogenous glucose release, rate of lipolysis. Results: Between-group differences in change in insulin sensitivity favored metformin regarding whole-body IR [change in glucose infusion rate 1.3 (0.1, 2.4) mg/kg/min, P = 0.03] and peripheral IR [change in metabolic clearance rate 0.923 (-0.002, 1.867) dL/kg/min, P = 0.05]. Metformin did not impact insulin suppression of endogenous glucose release (P = 0.12). Adipose IR was not assessable with traditional methods in this highly IR population. Conclusions: Metformin appears to improve whole-body and peripheral IR in youth who are overweight/obese with type 1 diabetes

Multiplex PCR and Next Generation Sequencing for the Non-Invasive Detection of Bladder Cancer

Highly sensitive and specific urine-based tests to detect either primary or recurrent bladder cancer have proved elusive to date. Our ever increasing knowledge of the genomic aberrations in bladder cancer should enable the development of such tests based on urinary DNA