Reynolds stress correction by machine learning methods with physical constraints

For the past three decade, Reynolds Average Navier-Stokes models have been widely used in the industry to simulate complex flows. However, these models suffer from limitations. Indeed there are still large discrepancies in the Reynolds stresses between the RANS model and high-fidelity data provided by DNS or experiments. This paper presents a strategy to correct the Menter SST model using an explicit algebraic model and two different neural networks: an multilayer perceptron (MLP) and a generative adversarial network (GAN). Moreover, in order to preserve the physical properties of the Reynolds stress tensor, we introduce a penalisation term in the loss of the GAN

Are Residents' Extended Shifts Associated With Adverse Events?

Szklo-Coxe discusses a new prospective study in PLoS Medicine that examined the relationship between residents' work patterns and adverse clinical events

Knowledge and utilization of prevention of mother-to-child transmission of HIV services among pregnant women in Tanzania

Background: Human Immunodeficiency Virus (HIV) infection among children is mainly vectored through mother-to-child transmission. Prevention of mother-to-child-transmission strategy is highly effective; however, its accessibility and utilization is affected by the lack of knowledge among other factors. Methods: A cross-sectional study was conducted among antenatal care attendees in two districts in Tanzania to determine their knowledge and utilization of the prevention of MTCT services. Results:  We interviewed 160 antenatal care attendees aged 18-45 years with a mean (SD) age of 30.4 (6.3) years; 74 (46.2 %) were HIV-infected. HIV-infected women demonstrated significantly correct knowledge of HIV (p=0.001) and AIDS (p=0.014) than uninfected individuals. HIV-infected women also significantly demonstrated correct knowledge of mother-to-child transmission during pregnancy than HIV-uninfected women (p=0.016) and during delivery (p=0.005). A significant proportion of HIV-positive women compared to HIV-negative women were aware that correct use of antiretroviral during pregnancy can reduce the risk of mother-to-child-transmission of HIV (p<0.039), but only 6 (3.75%) of all women were aware that correct use of antiretroviral during delivery can significantly reduce the risk of mother-to-child-transmission. HIV-infected women had significant comprehensive knowledge of HIV/AIDS (p=0.001) and prevention of mother-to-child transmission of HIV (p=0.006) than HIV-negative women. Comprehensive knowledge prevention of mother-to-child transmission of HIV was low among the study participants. Male partners’ involvement in maternal antenatal care was significantly higher among HIV-infected women than males from the HIV-infected women group (p<0.006). Conclusion: The study demonstrated inadequate knowledge of PMTCT among women who made ANC visits. HIV uninfected women had poorer knowledge compared to the HIV-infected ones. Routine HIV counseling and testing services were highly accepted among these women

Your evidence or mine? : Systematic evaluation of reviews of marine protected area effectiveness

Marine protected areas (MPAs) are a key strategy for mitigating the impacts of fisheries, but their designation can be controversial, and there is uncertainty surrounding when and where MPAs are most effective. Evidence synthesis that collates primary research on MPA effectiveness can provide a crucial bridge between research, policy and practice. However, reviews vary in scope and rigour, meaning decision-makers face the challenge of identifying appropriate reviews. Documenting differences amongst reviews can therefore support nonspecialists in locating the most relevant and rigorous reviews and can also assist researchers in targeting evidence gaps. We addressed these priorities by systematically searching for reviews examining effectiveness of MPAs for biodiversity, critically appraising methods used and categorizing review scope. The 27 reviews assessed overlapped in scope (suggesting some redundancy) and differed substantially in reliability. Key strengths related to the effects of MPAs on fish abundance and the influence of MPA size and age on effectiveness. However, several gaps were noted, with some questions not addressed and others lacking highly reliable syntheses – importantly, the latter may create the perception that particular questions have been adequately addressed, potentially deterring new syntheses. Our findings indicate key aspects of review conduct that could be improved (e.g. documenting critical appraisal of primary research, evaluating potential publication bias) and can facilitate evidence-based policy by guiding nonspecialists to the most reliable and relevant reviews. Lastly, we suggest that future reviews with broader taxonomic coverage and considering the influence of a wider range of MPA characteristics on effectiveness would be beneficial

Screening of MAMLD1 Mutations in 70 Children with 46,XY DSD: Identification and Functional Analysis of Two New Mutations

More than 50% of children with severe 46,XY disorders of sex development (DSD) do not have a definitive etiological diagnosis. Besides gonadal dysgenesis, defects in androgen biosynthesis, and abnormalities in androgen sensitivity, the Mastermind-like domain containing 1 (MAMLD1) gene, which was identified as critical for the development of male genitalia, may be implicated. The present study investigated whether MAMLD1 is implicated in cases of severe 46,XY DSD and whether routine sequencing of MAMLD1 should be performed in these patients

Implementation strategies for knowledge products in primary healthcare: A systematic review of systematic reviews

BACKGROUND: The underuse or overuse of knowledge products leads to waste in healthcare, and primary care is no exception. OBJECTIVE: We aimed to characterize which knowledge products are frequently implemented, the implementation strategies used in primary care, and the implementation outcomes that are measured. METHODS: We performed a systematic review of systematic reviews (SR) using the Cochrane systematic approach to include eligible SR. The inclusion criteria were: any primary care contexts; healthcare professionals and patients; any EPOC implementation strategies of specified knowledge products; any comparator; and any implementation outcomes based on the Proctor framework. We searched the Medline, EMBASE, CINAHL, Ovid PsycINFO, Web of Science, and Cochrane Library databases from their inception to October 2019, without any restriction. We searched the references of the included SR. Pairs of reviewers independently performed selection, data extraction and methodological quality assessment with AMSTAR 2. Data extraction was informed by EPOC taxonomy for implementation strategies and the Proctor framework for implementation outcomes. We performed a descriptive analysis and summarized the results using a narrative synthesis. RESULTS: Of the 11,101 records identified, 81 SR were included. Forty-seven SR involved healthcare professionals alone. Fifteen SR were of high or moderate methodological quality. Most of them addressed one type of knowledge product (56/81), common clinical practice guidelines (26/56) or management, and behavioural or pharmacological health interventions (24/56). Mixed strategies were used for implementation (67/81), predominantly educational-based (meetings in 60/81, materials distribution in 59/81, and academic detailing in 45/81), reminder (53/81) and audit and feedback (40/81) strategies. Education meetings (P=.13) and academic detailing (P=.11) seem to be more used when the population is composed of Healthcare professionals alone. The improvement of the adoption of knowledge products was the most commonly measured outcome (72/81). The evidence level was reported in 10/81 SR on 62 outcomes (including 48 improvement of adoption), of which 16 outcomes were of moderate or high level. CONCLUSIONS: Clinical practice guidelines and management, behavioural or pharmacological health interventions are the most commonly implemented knowledge products through the mixed use of educational, reminders and audit and feedback strategies. There is need for a strong methodology for the SR of RCTs to explore their effectiveness and the whole cascade of implementation outcomes. CLINICALTRIAL: Not applicable

Rituximab or Cyclosporine in the Treatment of Membranous Nephropathy

Background: B-cell anomalies play a role in the pathogenesis of membranous nephropathy. B-cell depletion with rituximab may therefore be noninferior to treatment with cyclosporine for inducing and maintaining a complete or partial remission of proteinuria in patients with this condition. Methods: We randomly assigned patients who had membranous nephropathy, proteinuria of at least 5 g per 24 hours, and a quantified creatinine clearance of at least 40 ml per minute per 1.73 m(2) of body-surface area and had been receiving angiotensin-system blockade for at least 3 months to receive intravenous rituximab (two infusions, 1000 mg each, administered 14 days apart; repeated at 6 months in case of partial response) or oral cyclosporine (starting at a dose of 3.5 mg per kilogram of body weight per day for 12 months). Patients were followed for 24 months. The primary outcome was a composite of complete or partial remission of proteinuria at 24 months. Laboratory variables and safety were also assessed. Results: A total of 130 patients underwent randomization. At 12 months, 39 of 65 patients (60%) in the rituximab group and 34 of 65 (52%) in the cyclosporine group had a complete or partial remission (risk difference, 8 percentage points; 95% confidence interval [CI], -9 to 25; P=0.004 for noninferiority). At 24 months, 39 patients (60%) in the rituximab group and 13 (20%) in the cyclosporine group had a complete or partial remission (risk difference, 40 percentage points; 95% CI, 25 to 55; P<0.001 for both noninferiority and superiority). Among patients in remission who tested positive for anti-phospholipase A(2) receptor (PLA2R) antibodies, the decline in autoantibodies to anti-PLA2R was faster and of greater magnitude and duration in the rituximab group than in the cyclosporine group. Serious adverse events occurred in 11 patients (17%) in the rituximab group and in 20 (31%) in the cyclosporine group (P=0.06). Conclusions: Rituximab was noninferior to cyclosporine in inducing complete or partial remission of proteinuria at 12 months and was superior in maintaining proteinuria remission up to 24 months. (Funded by Genentech and the Fulk Family Foundation; MENTOR ClinicalTrials.gov number, .) In a randomized, controlled trial involving patients with membranous nephropathy, rituximab was noninferior to cyclosporine in inducing complete or partial remission of proteinuria at 12 months and was superior in maintaining proteinuria remission for up to 24 months.Genentech; Fulk Family Foundation6 month embargo; published July 4, 2019This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

A Molecular Signature of Proteinuria in Glomerulonephritis

Proteinuria is the most important predictor of outcome in glomerulonephritis and experimental data suggest that the tubular cell response to proteinuria is an important determinant of progressive fibrosis in the kidney. However, it is unclear whether proteinuria is a marker of disease severity or has a direct effect on tubular cells in the kidneys of patients with glomerulonephritis. Accordingly we studied an in vitro model of proteinuria, and identified 231 “albumin-regulated genes” differentially expressed by primary human kidney tubular epithelial cells exposed to albumin. We translated these findings to human disease by studying mRNA levels of these genes in the tubulo-interstitial compartment of kidney biopsies from patients with IgA nephropathy using microarrays. Biopsies from patients with IgAN (n = 25) could be distinguished from those of control subjects (n = 6) based solely upon the expression of these 231 “albumin-regulated genes.” The expression of an 11-transcript subset related to the degree of proteinuria, and this 11-mRNA subset was also sufficient to distinguish biopsies of subjects with IgAN from control biopsies. We tested if these findings could be extrapolated to other proteinuric diseases beyond IgAN and found that all forms of primary glomerulonephritis (n = 33) can be distinguished from controls (n = 21) based solely on the expression levels of these 11 genes derived from our in vitro proteinuria model. Pathway analysis suggests common regulatory elements shared by these 11 transcripts. In conclusion, we have identified an albumin-regulated 11-gene signature shared between all forms of primary glomerulonephritis. Our findings support the hypothesis that albuminuria may directly promote injury in the tubulo-interstitial compartment of the kidney in patients with glomerulonephritis

Technology Transfers and the Clean Development Mechanism in a North-South General Equilibrium Model

This paper analyzes the potential welfare gains of introducing a technology transfer from Annex I to non-Annex I in order to mitigate greenhouse gas emissions. Our analysis is based on a numerical general equilibrium model for a world economy comprising two regions, North (Annex I) and South (non-Annex I). As our model allows for labor mobility between the formal and informal sectors in the South, we are also able to capture additional aspects of how the transfer influences the Southern economy. In a cooperative equilibrium, a technology transfer from the North to the South is clearly desirable from the perspective of a global social planner, since the welfare gain for the South outweighs the welfare loss for the North. However, if the regions do not cooperate, then the incentives to introduce the technology transfer appear to be relatively weak from the perspective of the North; at least if we allow for Southern abatement in the pre-transfer Nash equilibrium. Finally, by adding the emission reductions associated with the Kyoto agreement to an otherwise uncontrolled market economy, the technology transfer leads to higher welfare in both regions

Guidelines for Family-Centered Care in the Neonatal, Pediatric, and Adult ICU.

OBJECTIVE: To provide clinicians with evidence-based strategies to optimize the support of the family of critically ill patients in the ICU. METHODS: We used the Council of Medical Specialty Societies principles for the development of clinical guidelines as the framework for guideline development. We assembled an international multidisciplinary team of 29 members with expertise in guideline development, evidence analysis, and family-centered care to revise the 2007 Clinical Practice Guidelines for support of the family in the patient-centered ICU. We conducted a scoping review of qualitative research that explored family-centered care in the ICU. Thematic analyses were conducted to support Population, Intervention, Comparison, Outcome question development. Patients and families validated the importance of interventions and outcomes. We then conducted a systematic review using the Grading of Recommendations, Assessment, Development and Evaluations methodology to make recommendations for practice. Recommendations were subjected to electronic voting with pre-established voting thresholds. No industry funding was associated with the guideline development. RESULTS: The scoping review yielded 683 qualitative studies; 228 were used for thematic analysis and Population, Intervention, Comparison, Outcome question development. The systematic review search yielded 4,158 reports after deduplication and 76 additional studies were added from alerts and hand searches; 238 studies met inclusion criteria. We made 23 recommendations from moderate, low, and very low level of evidence on the topics of: communication with family members, family presence, family support, consultations and ICU team members, and operational and environmental issues. We provide recommendations for future research and work-tools to support translation of the recommendations into practice. CONCLUSIONS: These guidelines identify the evidence base for best practices for family-centered care in the ICU. All recommendations were weak, highlighting the relative nascency of this field of research and the importance of future research to identify the most effective interventions to improve this important aspect of ICU care