A realist synthesis of educational interventions to improve nutrition care competencies and delivery by doctors and other healthcare professionals

Objective: To determine what, how, for whom, why, and in what circumstances educational interventions improve the delivery of nutrition care by doctors and other healthcare professionals work. Design: Realist synthesis following a published protocol and reported following Realist and Meta-narrative Evidence Synthesis: Evolving Standards (RAMESES) guidelines. A multidisciplinary team searched MEDLINE, CINAHL, ERIC, EMBASE, PsyINFO, Sociological Abstracts, Web of Science, Google Scholar and Science Direct for published and unpublished (grey) literature. The team identified studies with varied designs; appraised their ability to answer the review question; identified relationships between contexts, mechanisms and outcomes (CMOs); and entered them into a spreadsheet configured for the purpose. The final synthesis identified commonalities across CMO configurations. Results: Over half of the 46 studies from which we extracted data originated from the USA. Interventions that improved the delivery of nutrition care improved skills and attitudes rather than just knowledge; provided opportunities for superiors to model nutrition care; removed barriers to nutrition care in health systems; provided participants with local, practically relevant tools and messages; and incorporated non-traditional, innovative teaching strategies. Operating in contexts where student and qualified healthcare professionals provided nutrition care in developed and developing countries, these interventions yielded health outcomes by triggering a range of mechanisms, which included feeling competent, feeling confident and comfortable, having greater self-efficacy, being less inhibited by barriers in healthcare systems and feeling that nutrition care was accepted and recognised. Conclusions: These findings show how important it is to move education for nutrition care beyond the simple acquisition of knowledge. They show how educational interventions embedded within systems of healthcare can improve patients’ health by helping health students and professionals to appreciate the importance of delivering nutrition care and feel competent to deliver it

Chromatin environment and cellular context specify compensatory activity of paralogous MEF2 transcription factors

Compensation among paralogous transcription factors (TFs) confers genetic robustness of cellular processes, but how TFs dynamically respond to paralog depletion on a genome-wide scale in vivo remains incompletely understood. Using single and double conditional knockout of myocyte enhancer factor 2 (MEF2) family TFs in granule neurons of the mouse cerebellum, we find that MEF2A and MEF2D play functionally redundant roles in cerebellar-dependent motor learning. Although both TFs are highly expressed in granule neurons, transcriptomic analyses show MEF2D is the predominant genomic regulator of gene expression in vivo. Strikingly, genome-wide occupancy analyses reveal upon depletion of MEF2D, MEF2A occupancy robustly increases at a subset of sites normally bound to MEF2D. Importantly, sites experiencing compensatory MEF2A occupancy are concentrated within open chromatin and undergo functional compensation for genomic activation and gene expression. Finally, motor activity induces a switch from non-compensatory to compensatory MEF2-dependent gene regulation. These studies uncover genome-wide functional interdependency between paralogous TFs in the brain

Factors affecting outcomes of open surgical repair of pararenal aortic aneurysms: A 10-year experience

PurposeFew large series document surgical outcomes for patients with pararenal abdominal aortic aneurysms (PAAAs), defined as aneurysms including the juxtarenal aorta or renal artery origins that require suprarenal aortic clamping. No standard endovascular alternatives presently exist; however, future endovascular branch graft repairs ultimately must be compared with the gold standard of open repair. To this end, we present a 10-year experience.MethodsBetween 1993 and 2003, 3058 AAAs were repaired. Perioperative variables, morbidity, and mortality were retrospectively assessed. Renal insufficiency was defined as a rise in the concentration of serum creatinine by ≥0.5 mg/dL. Factors predicting complications were identified by multivariate analyses. Morbidity and 30-day mortality were evaluated with multiple logistic regression analysis.ResultsOf a total of 3058 AAA repairs performed, 247 were PAAAs (8%). Mean renal ischemia time was 23 minutes (range, 5 to 60 minutes). Cardiac complications occurred in 32 patients (13%), pulmonary complications in 38 (16%), and renal insufficiency in 54 (22%). Multivariate analysis associated myocardial infarction with advanced age (P = .01) and abnormal preoperative serum creatinine (>1.5 mg/dL) (P = .08). Pulmonary complications were associated with advanced age (P = .03), renal artery bypass (P = .02), increased mesenteric ischemic time (P = .01), suprarenal aneurysm repair (P < .0008), and left renal vein division (P = .01). Renal insufficiency was associated with increased mesenteric ischemic time (P = .001), supravisceral clamping (P = .04), left renal vein division (P = .04), and renal artery bypass (P = .0002), but not renal artery reimplantation or endarterectomy. New dialysis was required in 3.7% (9/242). Abnormal preoperative serum creatinine (>1.5 mg/dL) was predictive of the need for postoperative dialysis (10% vs 2%; P = .04). Patients with normal preoperative renal function had improved recovery (93% vs 36%; P = .0002). The 30-day surgical mortality was 2.5% (6/247) but was not predicted by any factors, and in-hospital mortality was 2.8% (7/247). Median intensive care and hospital stays were 3 and 9 days, respectively, and longer stays were associated with age at surgery (P = .007 and P = .0002, respectively) and any postoperative complication.ConclusionsPAAA repair can be performed with low mortality. Renal insufficiency is the most frequent complication, but avoiding renal artery bypass, prolonged mesenteric ischemia time, or left renal vein transection may improve results

Mapping the cis-regulatory architecture of the human retina reveals noncoding genetic variation in disease

The interplay of transcription factors and cis-regulatory elements (CREs) orchestrates the dynamic and diverse genetic programs that assemble the human central nervous system (CNS) during development and maintain its function throughout life. Genetic variation within CREs plays a central role in phenotypic variation in complex traits including the risk of developing disease. We took advantage of the retina, a well-characterized region of the CNS known to be affected by pathogenic variants in CREs, to establish a roadmap for characterizing regulatory variation in the human CNS. This comprehensive analysis of tissue-specific regulatory elements, transcription factor binding, and gene expression programs in three regions of the human visual system (retina, macula, and retinal pigment epithelium/choroid) reveals features of regulatory element evolution that shape tissue-specific gene expression programs and defines regulatory elements with the potential to contribute to Mendelian and complex disorders of human vision

Multi-Messenger Gravitational Wave Searches with Pulsar Timing Arrays: Application to 3C66B Using the NANOGrav 11-year Data Set

When galaxies merge, the supermassive black holes in their centers may form binaries and, during the process of merger, emit low-frequency gravitational radiation in the process. In this paper we consider the galaxy 3C66B, which was used as the target of the first multi-messenger search for gravitational waves. Due to the observed periodicities present in the photometric and astrometric data of the source of the source, it has been theorized to contain a supermassive black hole binary. Its apparent 1.05-year orbital period would place the gravitational wave emission directly in the pulsar timing band. Since the first pulsar timing array study of 3C66B, revised models of the source have been published, and timing array sensitivities and techniques have improved dramatically. With these advances, we further constrain the chirp mass of the potential supermassive black hole binary in 3C66B to less than $(1.65\pm0.02) \times 10^9~{M_\odot}$ using data from the NANOGrav 11-year data set. This upper limit provides a factor of 1.6 improvement over previous limits, and a factor of 4.3 over the first search done. Nevertheless, the most recent orbital model for the source is still consistent with our limit from pulsar timing array data. In addition, we are able to quantify the improvement made by the inclusion of source properties gleaned from electromagnetic data to `blind' pulsar timing array searches. With these methods, it is apparent that it is not necessary to obtain exact a priori knowledge of the period of a binary to gain meaningful astrophysical inferences.Comment: 14 pages, 6 figures. Accepted by Ap

Ecosystem Interactions Underlie the Spread of Avian Influenza A Viruses with Pandemic Potential

Despite evidence for avian influenza A virus (AIV) transmission between wild and domestic ecosystems, the roles of bird migration and poultry trade in the spread of viruses remain enigmatic. In this study, we integrate ecosystem interactions into a phylogeographic model to assess the contribution of wild and domestic hosts to AIV distribution and persistence. Analysis of globally sampled AIV datasets shows frequent two-way transmission between wild and domestic ecosystems. In general, viral flow from domestic to wild bird populations was restricted to within a geographic region. In contrast, spillover from wild to domestic populations occurred both within and between regions. Wild birds mediated long-distance dispersal at intercontinental scales whereas viral spread among poultry populations was a major driver of regional spread. Viral spread between poultry flocks frequently originated from persistent lineages circulating in regions of intensive poultry production. Our analysis of long-term surveillance data demonstrates that meaningful insights can be inferred from integrating ecosystem into phylogeographic reconstructions that may be consequential for pandemic preparedness and livestock protection.National Institutes of Health (U.S.) (NIH Centers for Excellence in Influenza Research and Surveillance (CEIRS, contract # HHSN266200700010C))National Institutes of Health (U.S.) (NIH Centers for Excellence in Influenza Research and Surveillance (CEIRS, contract # HHSN272201400008C))National Institutes of Health (U.S.) (NIH Centers for Excellence in Influenza Research and Surveillance (CEIRS, contract # HHSN272201400006C)

Improving the diagnosis and treatment of urinary tract infection in young children in primary care:results from the ‘DUTY’ prospective diagnostic cohort study

PURPOSE Up to 50% of urinary tract infections (UTIs) in young children are missed in primary care. Urine culture is essential for diagnosis, but urine collection is often difficult. Our aim was to derive and internally validate a 2-step clinical rule using (1) symptoms and signs to select children for urine collection; and (2) symptoms, signs, and dipstick testing to guide antibiotic treatment. METHODS We recruited acutely unwell children aged under 5 years from 233 primary care sites across England and Wales. Index tests were parent-reported symptoms, clinician-reported signs, urine dipstick results, and clinician opinion of UTI likelihood (clinical diagnosis before dipstick and culture). The reference standard was microbiologically confirmed UTI cultured from a clean-catch urine sample. We calculated sensitivity, specificity, and area under the receiver operator characteristic (AUROC) curve of coefficient-based (graded severity) and points-based (dichotomized) symptom/sign logistic regression models, and we then internally validated the AUROC using bootstrapping. RESULTS Three thousand thirty-six children provided urine samples, and culture results were available for 2,740 (90%). Of these results, 60 (2.2%) were positive: the clinical diagnosis was 46.6% sensitive, with an AUROC of 0.77. Previous UTI, increasing pain/crying on passing urine, increasingly smelly urine, absence of severe cough, increasing clinician impression of severe illness, abdominal tenderness on examination, and normal findings on ear examination were associated with UTI. The validated coefficient- and points-based model AUROCs were 0.87 and 0.86, respectively, increasing to 0.90 and 0.90, respectively, by adding dipstick nitrites, leukocytes, and blood. CONCLUSIONS A clinical rule based on symptoms and signs is superior to clinician diagnosis and performs well for identifying young children for noninvasive urine sampling. Dipstick results add further diagnostic value for empiric antibiotic treatment

The NANOGrav 11-Year Data Set: Arecibo Observatory Polarimetry And Pulse Microcomponents

We present the polarization pulse profiles for 28 pulsars observed with the Arecibo Observatory by the North American Nanohertz Observatory for Gravitational Waves (NANOGrav) timing project at 2.1 GHz, 1.4 GHz, and 430 MHz. These profiles represent some of the most sensitive polarimetric millisecond pulsar profiles to date, revealing the existence of microcomponents (that is, pulse components with peak intensities much lower than the total pulse peak intensity). Although microcomponents have been detected in some pulsars previously, we present microcomponents for PSRs B1937+21, J1713+0747, and J2234+0944 for the first time. These microcomponents can have an impact on pulsar timing, geometry, and flux density determination. We present rotation measures for all 28 pulsars, determined independently at different observation frequencies and epochs, and find the Galactic magnetic fields derived from these rotation measures to be consistent with current models. These polarization profiles were made using measurement equation template matching, which allows us to generate the polarimetric response of the Arecibo Observatory on an epoch-by-epoch basis. We use this method to describe its time variability, and find that the polarimetric responses of the Arecibo Observatory's 1.4 and 2.1 GHz receivers vary significantly with time.Comment: 41 pages, 20 figure

The NANOGrav 12.5-Year Data Set: Dispersion Measure Mis-Estimation with Varying Bandwidths

Noise characterization for pulsar-timing applications accounts for interstellar dispersion by assuming a known frequency-dependence of the delay it introduces in the times of arrival (TOAs). However, calculations of this delay suffer from mis-estimations due to other chromatic effects in the observations. The precision in modeling dispersion is dependent on the observed bandwidth. In this work, we calculate the offsets in infinite-frequency TOAs due to mis-estimations in the modeling of dispersion when using varying bandwidths at the Green Bank Telescope. We use a set of broadband observations of PSR J1643-1224, a pulsar with an excess of chromatic noise in its timing residuals. We artificially restricted these observations to a narrowband frequency range, then used both data sets to calculate residuals with a timing model that does not include short-scale dispersion variations. By fitting the resulting residuals to a dispersion model, and comparing the ensuing fitted parameters, we quantify the dispersion mis-estimations. Moreover, by calculating the autocovariance function of the parameters we obtained a characteristic timescale over which the dispersion mis-estimations are correlated. For PSR J1643-1224, which has one of the highest dispersion measures (DM) in the NANOGrav pulsar timing array, we find that the infinite-frequency TOAs suffer from a systematic offset of ~22 microseconds due to DM mis-estimations, with correlations over ~1 month. For lower-DM pulsars, the offset is ~7 microseconds. This error quantification can be used to provide more robust noise modeling in NANOGrav's data, thereby increasing sensitivity and improving parameter estimation in gravitational wave searches.Comment: 15 pages, 7 figure

Versatility in phospho-dependent molecular recognition of the XRCC1 and XRCC4 DNA-damage scaffolds by aprataxin-family FHA domains

Aprataxin, aprataxin and PNKP-like factor (APLF) and polynucleotide kinase phosphatase (PNKP) are key DNA-repair proteins with diverse functions but which all contain a homologous forkhead-associated (FHA) domain. Their primary binding targets are casein kinase 2-phosphorylated forms of the XRCC1 and XRCC4 scaffold molecules which respectively coordinate single-stranded and double-stranded DNA break repair pathways. Here, we present the high-resolution X-ray structure of a complex of phosphorylated XRCC4 with APLF, the most divergent of the three FHA domain family members. This, combined with NMR and biochemical analysis of aprataxin and APLF binding to singly and multiply-phosphorylated forms of XRCC1 and XRCC4, and comparison with PNKP reveals a pattern of distinct but overlapping binding specificities that are differentially modulated by multi-site phosphorylation. Together, our data illuminate important differences between activities of the three phospho-binding domains, in spite of a close evolutionary relationship between them