Advantages of Percent Weight Loss as a Method of Reporting Weight Loss after Roux-en-Y Gastric Bypass

Objective: Although Roux-en-Y gastric bypass (RYGB) is a generally effective treatment for severe obesity, weight loss (WL) after this operation is highly variable. Accurate predictors of outcome would thus be useful in identifying those patients who would most benefit from this invasive therapy. WL has been characterized using several different metrics, including the number of BMI units lost (ΔBMI), percent baseline WL (%WL), and percent excess body WL (%EBWL). To identify clinically relevant predictors most sensitively it is necessary to avoid confounding by other factors, including preoperative BMI (pBMI), the strongest known predictor of RYGB-induced WL. Design and Methods To determine the WL measure least associated with pBMI, we analyzed outcomes of 846 patients undergoing RYGB. Results: Patients in this cohort had an average pBMI of 50.0 kg/m2. At weight nadir, they lost an average 19.4 kg/m2, 38.7% WL, and 81.2% EBWL. pBMI was strongly and positively associated with ΔBMI at both one year (r=0.56, p=4.7×10−51) and nadir (r=0.58, p=2.8×10−77) and strongly but negatively associated with %EBWL at one year (r=−0.52, p=3.8×10−44) and nadir (r=−0.45, p=7.2×10−43). In contrast, pBMI was not significantly associated with %WL at one year (r=0.04, p=0.33), and only weakly associated at nadir (r=0.13, p=0.0002). Conclusions: Of the metrics examined, %WL is the parameter describing WL after RYGB least influenced by pBMI. It thus improves comparison of WL outcomes across studies of patients undergoing surgery and facilitates the most sensitive identification of novel predictors of surgery-induced WL. We therefore recommend that %WL be adopted more broadly in reporting weight loss after RYGB

Natural braneworld inflation and baryogenesis

In natural inflation models, the inflaton is a pseudo Nambu-Goldstone boson and the flatness of the potential is protected by shift symmetries. In this framework, a successful inflation requires the global symmetry to be spontaneously broken at a scale close to the Planck mass. Such a high value of the spontaneous breaking scale may not be legitimate in an effective field theory. On the other hand, if natural inflation occurs during the nonconventional high-energy era in braneworld cosmology, the conditions for the inflaton slow rolling can be eased and the spontaneous breaking scale can be lowered to values below the Planck scale. We examine the observational constraints on this scenario and study the possibility that the baryon asymmetry of the universe is generated by the decay of the pseudo Nambu-Goldstone boson during the reheating era.Comment: 12 pages, 2 figures; comments added, references updated. Final version to appear in Phys. Lett.

Improving access to and engagement with mental health services among young people from refugee backgrounds: service user and provider perspectives

Limited research has been conducted worldwide on the experiences that children and young people from refugee backgrounds have with mental health services, despite evidence that they have significant vulnerability to the development of mental health problems and to suicidal behaviour and that those with mental ill-health typically underutilise services. The authors were particularly interested in barriers and facilitators to service access and engagement, and conducted two qualitative research projects to improve understanding of the issues – the first with service providers experienced in the refugee area and the second with young refugee service users. The aim of this project was to compare the perspectives of professionals and service users and to identify similarities and differences. The perspectives of the service users and providers were strikingly similar. The analysis identified 21 implications for policy makers, agencies and practitioners, which ranged from issues concerning cultural sensitivity, background matching and mental health literacy to accessibility, setting boundaries and expectations and implementing a holistic and outreach approach. There is a range of specific, practical measures that policy makers and service providers can introduce to enhance access to and engagement with mental health services for young people from refugee backgrounds

Healthcare providers' perception of the referral system in maternal care facilities in Aceh, Indonesia: A cross-sectional study

Objectives Our study investigates the barriers perceived by staff in the referral systems in maternal healthcare facilities across Aceh province in Indonesia. Design With a cross-sectional approach, two sets of surveys were administered during September to October 2016 in 32 sampling units of our study. We also collected referral data in the form of the frequency of ingoing and outgoing referral cases per facility. Setting In three districts, Aceh Besar, Banda Aceh and Bireuen, a total of 32 facilities including hospitals, community health centres, and private midwife clinics that met the criteria of providing at least basic emergency obstetric and neonatal care (BEonC) were covered. Participants Across the 32 healthcare centres, 149 members of staff (mainly midwives) agreed to participate in our surveys. Primary and secondary outcome measures The first survey consisted of 65 items focusing on organisational measures as well as case numbers for example, patient counts, mortality rate and complications. The second survey with 68 items asked healthcare providers about a range of factors including attitudes towards the referral process in their facility and potential barriers to a well-functioning system in their district. Results Overall, mothers'/families' consent as well as the complex administration process were found to be the main barriers (36% and 12%, respectively). Healthcare providers noted that information about other facilities has the biggest room for improvement (37%) rather than transport, timely referral of mothers and babies, or the availability of referral facilities. Conclusions The largest barrier perceived by healthcare providers in our study was noted to be family consent and administrative burden. Moreover, lack of information about the referral system itself and other facilities seemed to be affecting healthcare providers and mothers/families alike and improvements perhaps through a shared information system is needed

Associations Between \u3cem\u3eSLC16A11\u3c/em\u3e Variants and Diabetes in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

Five sequence variants in SLC16A11 (rs117767867, rs13342692, rs13342232, rs75418188, and rs75493593), which occur in two non-reference haplotypes, were recently shown to be associated with diabetes in Mexicans from the SIGMA consortium. We aimed to determine whether these previous findings would replicate in the HCHS/SOL Mexican origin group and whether genotypic effects were similar in other HCHS/SOL groups. We analyzed these five variants in 2492 diabetes cases and 5236 controls from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), which includes U.S. participants from six diverse background groups (Mainland groups: Mexican, Central American, and South American; and Caribbean groups: Puerto Rican, Cuban, and Dominican). We estimated the SNP-diabetes association in the six groups and in the combined sample. We found that the risk alleles occur in two non-reference haplotypes in HCHS/SOL, as in the SIGMA Mexicans. The haplotype frequencies were very similar between SIGMA Mexicans and the HCHS/SOL Mainland groups, but different in the Caribbean groups. The SLC16A11 sequence variants were significantly associated with risk for diabetes in the Mexican origin group (P = 0.025), replicating the SIGMA findings. However, these variants were not significantly associated with diabetes in a combined analysis of all groups, although the power to detect such effects was 85% (assuming homogeneity of effects among the groups). Additional analyses performed separately in each of the five non-Mexican origin groups were not significant. We also analyzed (1) exclusion of young controls and, (2) SNP by BMI interactions, but neither was significant in the HCHS/SOL data. The previously reported effects of SLC16A11 variants on diabetes in Mexican samples was replicated in a large Mexican-American sample, but these effects were not significant in five non-Mexican Hispanic/Latino groups sampled from U.S. populations. Lack of replication in the HCHS/SOL non-Mexicans, and in the entire HCHS/SOL sample combined may represent underlying genetic heterogeneity. These results indicate a need for future genetic research to consider heterogeneity of the Hispanic/Latino population in the assessment of disease risk, but add to the evidence suggesting SLC16A11 as a potential therapeutic target for type 2 diabetes

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

Feasibility of Early Infant Diagnosis of HIV in Resource-Limited Settings: The ANRS 12140-PEDIACAM Study in Cameroon

BACKGROUND: Early infant diagnosis (EID) of HIV is a key-point for the implementation of early HAART, associated with lower mortality in HIV-infected infants. We evaluated the EID process of HIV according to national recommendations, in urban areas of Cameroon. METHODS/FINDINGS: The ANRS12140-PEDIACAM study is a multisite cohort in which infants born to HIV-infected mothers were included before the 8(th) day of life and followed. Collection of samples for HIV DNA/RNA-PCR was planned at 6 weeks together with routine vaccination. The HIV test result was expected to be available at 10 weeks. A positive or indeterminate test result was confirmed by a second test on a different sample. Systematic HAART was offered to HIV-infected infants identified. The EID process was considered complete if infants were tested and HIV results provided to mothers/family before 7 months of age. During 2007-2009, 1587 mother-infant pairs were included in three referral hospitals; most infants (n = 1423, 89.7%) were tested for HIV, at a median age of 1.5 months (IQR, 1.4-1.6). Among them, 51 (3.6%) were HIV-infected. Overall, 1331 (83.9%) completed the process by returning for the result before 7 months (median age: 2.5 months (IQR, 2.4-3.0)). Incomplete process, that is test not performed, or result of test not provided or provided late to the family, was independently associated with late HIV diagnosis during pregnancy (adjusted odds ratio (aOR) = 1.8, 95%CI: 1.1 to 2.9, p = 0.01), absence of PMTCT prophylaxis (aOR = 2.4, 95%CI: 1.4 to 4.3, p = 0.002), and emergency caesarean section (aOR = 2.5, 95%CI: 1.5 to 4.3, p = 0.001). CONCLUSIONS: In urban areas of Cameroon, HIV-infected women diagnosed sufficiently early during pregnancy opt to benefit from EID whatever their socio-economic, marital or disclosure status. Reduction of non optimal diagnosis process should focus on women with late HIV diagnosis during pregnancy especially if they did not receive any PMTCT, or if complications occurred at delivery

Modified Gravity and Cosmology

In this review we present a thoroughly comprehensive survey of recent work on modified theories of gravity and their cosmological consequences. Amongst other things, we cover General Relativity, Scalar-Tensor, Einstein-Aether, and Bimetric theories, as well as TeVeS, f(R), general higher-order theories, Horava-Lifschitz gravity, Galileons, Ghost Condensates, and models of extra dimensions including Kaluza-Klein, Randall-Sundrum, DGP, and higher co-dimension braneworlds. We also review attempts to construct a Parameterised Post-Friedmannian formalism, that can be used to constrain deviations from General Relativity in cosmology, and that is suitable for comparison with data on the largest scales. These subjects have been intensively studied over the past decade, largely motivated by rapid progress in the field of observational cosmology that now allows, for the first time, precision tests of fundamental physics on the scale of the observable Universe. The purpose of this review is to provide a reference tool for researchers and students in cosmology and gravitational physics, as well as a self-contained, comprehensive and up-to-date introduction to the subject as a whole.Comment: 312 pages, 15 figure

Enzyme replacement therapy for mucopolysaccharidosis VI: evaluation of long-term pulmonary function in patients treated with recombinant human N-acetylgalactosamine 4-sulfatase

Pulmonary function is impaired in untreated mucopolysaccharidosis type VI (MPS VI). Pulmonary function was studied in patients during long-term enzyme replacement therapy (ERT) with recombinant human arylsulfatase B (rhASB; rhN-acetylgalactosamine 4-sulfatase). Pulmonary function tests prior to and for up to 240 weeks of weekly infusions of rhASB at 1 mg/kg were completed in 56 patients during Phase 1/2, Phase 2, Phase 3 and Phase 3 Extension trials of rhASB and the Survey Study. Forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and, in a subset of patients, maximum voluntary ventilation (MVV), were analyzed as absolute volume in liters. FEV1 and FVC showed little change from baseline during the first 24 weeks of ERT, but after 96 weeks, these parameters increased over baseline by 11% and 17%, respectively. This positive trend compared with baseline continued beyond 96 weeks of treatment. Improvements from baseline in pulmonary function occurred along with gains in height in the younger group (5.5% change) and in the older patient group (2.4% change) at 96 weeks. Changes in MVV occurred earlier within 24 weeks of treatment to approximately 15% over baseline. Model results based on data from all trials showed significant improvements in the rate of change in pulmonary function during 96 weeks on ERT, whereas little or no improvement was observed for the same time period prior to ERT. Thus, analysis of mean percent change data and longitudinal modeling both indicate that long-term ERT resulted in improvement in pulmonary function in MPS VI patients