Maternal periconceptional and first trimester protein restriction in beef heifers: effects on maternal performance and early fetal growth

This study evaluated the effect of protein restriction during the periconception (PERI) and first trimester (POST) periods on maternal performance, physiology and early fetal growth. Yearling nulliparous heifers (n = 360) were individually fed a diet high or low in protein (HPeri and LPeri respectively) beginning 60 days before conception. From 24 to 98 days post-conception (dpc), half of each treatment group changed to the alternative post-conception high- or low-protein diet (HPost and LPost respectively), yielding four groups in a 2 × 2 factorial design with a common diet until parturition. Protein restriction was associated with lower bodyweight subsequent to reduced (but positive) average daily weight gain (ADG) during the PERI and POST periods. During the POST period, ADG was greater in LPeri than HPeri heifers and tended to be greater in LPost than HPost heifers during the second and third trimester. Bodyweight was similar at term. The pregnancy rate did not differ, but embryo loss between 23 and 36 dpc tended to be greater in LPeri than HPeri heifers. Overall, a greater proportion of male fetuses was detected (at 60 dpc 63.3% male vs 36.7% female). Protein restriction altered maternal plasma urea, non-esterified fatty acids, progesterone, leptin and insulin-like growth factor 1 at critical stages of fetal development. However, profiles varied depending on the sex of the conceptus.Katrina J. Copping, Andrew Hoare, I. Caroline McMillen, Raymond J. Rodgers, Charles R. Wallace and Viv E.A. Perr

TrustedPals: Secure Multiparty Computation Implemented with Smart Cards

We study the problem of Secure Multi-party Computation (SMC) in a model where individual processes contain a tamper-proof security module, and introduce the TrustedPals framework, an efficient smart card based implementation of SMC for any number of participating entities in such a model. Security modules can be trusted by other processes and can establish secure channels between each other. However, their availability is restricted by their host, that is, a corrupted party can stop the computation of its own security module as well as drop any message sent by or to its security module. We show that in this model SMC can be implemented by reducing it to a fault-tolerance problem at the level of security modules. Since the critical part of the computation can be executed locally on the smart card, we can compute any function securely with a protocol complexity which is polynomial only in the number of processes (that is, the complexity does not depend on the function which is computed), in contrast to previous approaches

Effectiveness of a web-based intervention to prevent anxiety in the children of parents with anxiety:Protocol for a Randomized Controlled Trial

BACKGROUND: Anxiety is the most common childhood mental health condition and is associated with impaired child outcomes, including increased risk of mental health difficulties in adulthood. Anxiety runs in families: when a parent has anxiety, their child has a 50% higher chance of developing it themselves. Environmental factors are predominant in the intergenerational transmission of anxiety and, of these, parenting processes play a major role. Interventions that target parents to support them to limit the impact of any anxiogenic parenting behaviors are associated with reduced anxiety in their children. A brief UK-based group intervention delivered to parents within the UK National Health Service led to a 16% reduction in children meeting the criteria for an anxiety disorder. However, this intervention is not widely accessible. To widen access, a 9-module web-based version of this intervention has been developed. This course comprises psychoeducation and home practice delivered through text, video, animations, and practice tasks. OBJECTIVE: This study seeks to evaluate the feasibility of delivering this web-based intervention and assess its effectiveness in reducing child anxiety symptoms. METHODS:  This is the protocol for a randomized controlled trial (RCT) of a community sample of 1754 parents with self-identified high levels of anxiety with a child aged 2-11 years. Parents in the intervention arm will receive access to the web-based course, which they undertake at a self-determined rate. The control arm receives no intervention. Follow-up data collection is at months 6 and months 9-21. Intention-to-treat analysis will be conducted on outcomes including child anxiety, child mental health symptoms, and well-being; parental anxiety and well-being; and parenting behaviors. RESULTS: Funding was received in April 2020, and recruitment started in February 2021 and is projected to end in October 2022. A total of 1350 participants have been recruited as of May 2022. CONCLUSIONS: The results of this RCT will provide evidence on the utility of a web-based course in preventing intergenerational transmission of anxiety and increase the understanding of familial anxiety. TRIAL REGISTRATION: ClinicalTrials.gov NCT04755933; https://clinicaltrials.gov/ct2/show/NCT04755933 INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/4070

Periconception and first trimester diet modifies appetite, hypothalamic gene expression, and carcass traits in bulls

Nulliparous yearling beef heifers (n=360) were used to evaluate the effects of maternal dietary protein during the periconception and first trimester periods of gestation on postnatal growth, feedlot performance, carcass characteristics, and the expression of genes associated with appetite in the arcuate nucleus of their male progeny. Heifers were individually fed a diet of 1.18g crude protein (CP)/day High protein (HPeri) or 0.62g CP/day Low protein (LPeri) beginning 60days before conception. From 24 to 98days post-conception (dpc), half of each treatment group changed to the alternative post-conception diet and were fed 1.49g CP/day (HPost) or 0.88g CP/day (LPost) yielding four treatment groups in a 2×2 factorial design. From day 98 of gestation, heifers received a common diet until parturition. Calves were weaned at 183days and developed on pasture before feedlot entry. Bulls underwent a 70-day Residual Feed Intake (RFI) feedlot test commencing at 528days of age. Feedlot entry and final body weight (BW), feedlot average daily gain (ADG) and RFI were not different (p>0.05). Progeny of dams that had a change in diet (LPeri/HPost and HPeri/LPost) had 9% higher daily dry matter intake (DMI) during the RFI test (p<0.05) than progeny of dams that received low diet throughout both the peri-conception period and first trimester (LPeri/LPost). Further, mRNA expression of the appetite-stimulating agouti-related protein (AGRP) was increased in the arcuate nucleus of High Peri/LPost bulls (p<0.05). Longissimus dorsi muscle cross sectional area, carcass dressing percentage, and estimated retail beef yield (RBY) were all higher (p<0.05), and rump (P8) fat tended to be lower (p=0.07), for bulls from HPost dams despite no difference in carcass weight (p<0.05). This study is of commercial importance to the livestock industry as specific periods of maternal dietary supplementation may increase feed intake, enhance progeny muscling, and alter fat deposition leading to improvement in efficiency of meat production in beef cattle.Katrina J. Copping, Matthew J. Callaghan, Geert H. Geesink, Jessica R. Gugusheff, I. Caroline McMillen, Raymond J. Rodgers, Beverly S. Muhlhausler, Mini A. Vithayathil and Viv E. A. Perr

Global geologic map of asteroid (101955) Bennu indicates heterogeneous resurfacing in the past 500,000 years

Global geologic maps are useful tools for efficient interpretation of a planetary body, and they provide global context for the diversity and evolution of the surface. We used data acquired by the OSIRIS-REx spacecraft to create the first global geologic map of the near-Earth asteroid (101955) Bennu. As this is the first geologic map of a small, non-spherical, rubble-pile asteroid, we discuss the distinctive mapping challenges and best practices that may be useful for future exploration of similar asteroids, such as those to be visited with the Hera and Janus missions. By mapping on two centimeter-scale global image mosaics (2D projected space) and a centimeter-scale global shape model (3D space), we generated three input maps respectively describing Bennu's shape features, geologic features, and surface texture. Based on these input maps, we defined two geologic units: the Smooth Unit and the Rugged Unit. The units are differentiated primarily on the basis of surface texture, concentrations of boulders, and the distributions of lineaments, mass movement features, and craters. They are bounded by several scarps. The Rugged Unit contains abundant boulders and signs of recent mass movement. It also has fewer small (<20 m), putatively fresh craters than the Smooth Unit, suggesting that such craters have been erased in the former. Based on these geologic indicators, we infer that the Rugged Unit has the younger surface of the two. Differential crater size-frequency distributions and the distribution of the freshest craters suggest that both unit surfaces formed ~10–65 million years ago, when Bennu was located in the Main Asteroid Belt, and the Smooth Unit has not been significantly resurfaced in the past 2 million years. Meanwhile, the Rugged Unit has experienced resurfacing within the past ~500,000 years during Bennu's lifetime as a near-Earth asteroid. The geologic units are consistent with global diversity in slope, surface roughness, normal albedo, and thermal emission spectral characteristics. The site on Bennu where the OSIRIS-REx mission collected a regolith sample is located in the Smooth Unit, in a small crater nested within a larger one. So although the Smooth Unit is an older surface than the Rugged Unit, the impact-crater setting indicates that the material sampled was recently exposed. Several similarities are apparent between Bennu and asteroid (162173) Ryugu from a global geologic perspective, including two geologic units distinguishable by variations in the number density of boulders, as well as in other datasets such as brightness

Genome-wide association study identifies 30 Loci Associated with Bipolar Disorder

This paper is dedicated to the memory of Psychiatric Genomics Consortium (PGC) founding member and Bipolar disorder working group co-chair Pamela Sklar. We thank the participants who donated their time, experiences and DNA to this research, and to the clinical and scientific teams that worked with them. We are deeply indebted to the investigators who comprise the PGC. The views expressed are those of the authors and not necessarily those of any funding or regulatory body. Analyses were carried out on the NL Genetic Cluster Computer (http://www.geneticcluster.org ) hosted by SURFsara, and the Mount Sinai high performance computing cluster (http://hpc.mssm.edu).Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P<1x10-4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (GWS, p < 5x10-8) in the discovery GWAS were not GWS in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis 30 loci were GWS including 20 novel loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene-sets including regulation of insulin secretion and endocannabinoid signaling. BDI is strongly genetically correlated with schizophrenia, driven by psychosis, whereas BDII is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential new biological mechanisms for BD.This work was funded in part by the Brain and Behavior Research Foundation, Stanley Medical Research Institute, University of Michigan, Pritzker Neuropsychiatric Disorders Research Fund L.L.C., Marriot Foundation and the Mayo Clinic Center for Individualized Medicine, the NIMH Intramural Research Program; Canadian Institutes of Health Research; the UK Maudsley NHS Foundation Trust, NIHR, NRS, MRC, Wellcome Trust; European Research Council; German Ministry for Education and Research, German Research Foundation IZKF of Münster, Deutsche Forschungsgemeinschaft, ImmunoSensation, the Dr. Lisa-Oehler Foundation, University of Bonn; the Swiss National Science Foundation; French Foundation FondaMental and ANR; Spanish Ministerio de Economía, CIBERSAM, Industria y Competitividad, European Regional Development Fund (ERDF), Generalitat de Catalunya, EU Horizon 2020 Research and Innovation Programme; BBMRI-NL; South-East Norway Regional Health Authority and Mrs. Throne-Holst; Swedish Research Council, Stockholm County Council, Söderström Foundation; Lundbeck Foundation, Aarhus University; Australia NHMRC, NSW Ministry of Health, Janette M O'Neil and Betty C Lynch

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: A systematic analysis for the Global Burden of Disease Study 2015

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods: We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings: Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation: Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding: Bill & Melinda Gates Foundation