Small-scale intraspecific life history variation in herbivorous spider mites (Tetranychus pacificus) is associated with host plant cultivar.

Life history variation is a general feature of arthropod systems, but is rarely included in models of field or laboratory data. Most studies assume that local processes occur identically across individuals, ignoring any genetic or phenotypic variation in life history traits. In this study, we tested whether field populations of Pacific spider mites (Tetranychus pacificus) on grapevines (Vitis vinifera) display significant intraspecific life history variation associated with host plant cultivar. To address this question we collected individuals from sympatric vineyard populations where either Zinfandel or Chardonnay were grown. We then conducted a "common garden experiment" of mites on bean plants (Phaseolus lunatus) in the laboratory. Assay populations were sampled non-destructively with digital photography to quantify development times, survival, and reproductive rates. Two classes of models were fit to the data: standard generalized linear mixed models and a time-to-event model, common in survival analysis, that allowed for interval-censored data and hierarchical random effects. We found a significant effect of cultivar on development time in both GLMM and time-to-event analyses, a slight cultivar effect on juvenile survival, and no effect on reproductive rate. There were shorter development times and a trend towards higher juvenile survival in populations from Zinfandel vineyards compared to those from Chardonnay vineyards. Lines of the same species, originating from field populations on different host plant cultivars, expressed different development times and slightly different survival rates when reared on a common host plant in a common environment

Sequential Monte Carlo Methods in the nimble and nimbleSMC R Packages

nimble is an R package for constructing algorithms and conducting inference on hierarchical models. The nimble package provides a unique combination of flexible model specification and the ability to program model-generic algorithms. Specifically, the package allows users to code models in the BUGS language, and it allows users to write algorithms that can be applied to any appropriate model. In this paper, we introduce the nimbleSMC R package. nimbleSMC contains algorithms for state-space model analysis using sequential Monte Carlo (SMC) techniques that are built using nimble. We first provide an overview of state-space models and commonly-used SMC algorithms. We then describe how to build a state-space model in nimble and conduct inference using existing SMC algorithms within nimbleSMC. SMC algorithms within nimbleSMC currently include the bootstrap filter, auxiliary particle filter, ensemble Kalman filter, IF2 method of iterated filtering, and a particle Markov chain Monte Carlo (MCMC) sampler. These algorithms can be run in R or compiled into C++ for more efficient execution. Examples of applying SMC algorithms to linear autoregressive models and a stochastic volatility model are provided. Finally, we give an overview of how model-generic algorithms are coded within nimble by providing code for a simple SMC algorithm. This illustrates how users can easily extend nimble's SMC methods in high-level code

Adipocyte JAK2 Regulates Hepatic Insulin Sensitivity Independently of Body Composition, Liver Lipid Content, and Hepatic Insulin Signaling.

Disruption of hepatocyte growth hormone (GH) signaling through disruption of Jak2 (JAK2L) leads to fatty liver. Previously, we demonstrated that development of fatty liver depends on adipocyte GH signaling. We sought to determine the individual roles of hepatocyte and adipocyte Jak2 on whole-body and tissue insulin sensitivity and liver metabolism. On chow, JAK2L mice had hepatic steatosis and severe whole-body and hepatic insulin resistance. However, concomitant deletion of Jak2 in hepatocytes and adipocytes (JAK2LA) completely normalized insulin sensitivity while reducing liver lipid content. On high-fat diet, JAK2L mice had hepatic steatosis and insulin resistance despite protection from diet-induced obesity. JAK2LA mice had higher liver lipid content and no protection from obesity but retained exquisite hepatic insulin sensitivity. AKT activity was selectively attenuated in JAK2L adipose tissue, whereas hepatic insulin signaling remained intact despite profound hepatic insulin resistance. Therefore, JAK2 in adipose tissue is epistatic to liver with regard to insulin sensitivity and responsiveness, despite fatty liver and obesity. However, hepatocyte autonomous JAK2 signaling regulates liver lipid deposition under conditions of excess dietary fat. This work demonstrates how various tissues integrate JAK2 signals to regulate insulin/glucose and lipid metabolism

Evidence for Shared Genetic Aetiology Between Schizophrenia, Cardiometabolic, and Inflammation-Related Traits: Genetic Correlation and Colocalization Analyses.

Funder: MQ: Transforming Mental Health; Grant(s): MQDS17/40BACKGROUND: Schizophrenia commonly co-occurs with cardiometabolic and inflammation-related traits. It is unclear to what extent the comorbidity could be explained by shared genetic aetiology. METHODS: We used GWAS data to estimate shared genetic aetiology between schizophrenia, cardiometabolic, and inflammation-related traits: fasting insulin (FI), fasting glucose, glycated haemoglobin, glucose tolerance, type 2 diabetes (T2D), lipids, body mass index (BMI), coronary artery disease (CAD), and C-reactive protein (CRP). We examined genome-wide correlation using linkage disequilibrium score regression (LDSC); stratified by minor-allele frequency using genetic covariance analyzer (GNOVA); then refined to locus-level using heritability estimation from summary statistics (ρ-HESS). Regions with local correlation were used in hypothesis prioritization multi-trait colocalization to examine for colocalisation, implying common genetic aetiology. RESULTS: We found evidence for weak genome-wide negative correlation of schizophrenia with T2D (rg = -0.07; 95% C.I., -0.03,0.12; P = .002) and BMI (rg = -0.09; 95% C.I., -0.06, -0.12; P = 1.83 × 10-5). We found a trend of evidence for positive genetic correlation between schizophrenia and cardiometabolic traits confined to lower-frequency variants. This was underpinned by 85 regions of locus-level correlation with evidence of opposing mechanisms. Ten loci showed strong evidence of colocalization. Four of those (rs6265 (BDNF); rs8192675 (SLC2A2); rs3800229 (FOXO3); rs17514846 (FURIN)) are implicated in brain-derived neurotrophic factor (BDNF)-related pathways. CONCLUSIONS: LDSC may lead to downwardly-biased genetic correlation estimates between schizophrenia, cardiometabolic, and inflammation-related traits. Common genetic aetiology for these traits could be confined to lower-frequency common variants and involve opposing mechanisms. Genes related to BDNF and glucose transport amongst others may partly explain the comorbidity between schizophrenia and cardiometabolic disorders

Relationships Effecting College Students’ Perception of Family Influence Impacting their Health and Lifestyle

The purpose of this cross-sectional, nonexperimental descriptive design study was to determine college students’ perception of family influence impacting their health and lifestyle. The sample included 120 college students in a faithbased institution and each student completed a Likert-type survey (4-point agreement scale) that investigated their perception of health, and the degree of influence peers and family had on their health. This second data analysis reports correlations between variables and group differences related to health perceptions and behaviours. The strongest correlation is between ‘family demonstration of positive health habits’ and ‘personal health practices being like my families’ (r = 0.671, p \u3c 0.01), a moderate relationship supported by other weaker positive correlations to specific health outcomes. Negative correlations between ‘my friends display more positive health habits than family’ and both ‘family has influenced my idea of health’ and ‘my health practices are similar to my family’ indicate the potential for other contextual factors to effect family impact. While differences relating to health influence and outcomes between groups formed by age, gender, ethnicity, family structure and religion were found, the variable related to most healthy lifestyle transmission elements was ‘My family demonstrates positive health habits’. Recommendations supporting improved societal health are offered, together with suggestions for further research. Group classifications that are fixed but might inform interactions with elements of cohorts are identified, together with group memberships which might be changed to enhance health options. Caution in the generalisation of these findings is advised due to the explained limitations of this study

OP21 Positivity thresholds of total infliximab and adalimumab anti-drug antibody assay: The prevalence of clearing and transient anti-drug antibodies in a national therapeutic drug monitoring service

Background Anti-drug antibodies can affect biopharmaceutical pharmacokinetics by increasing or decreasing drug clearance. Drug-tolerant (total), unlike drug-sensitive (free), antibody assays permit antibodies to be measured in the presence of a drug. We sought to confirm the positivity threshold of our total anti-tumour necrosis factor (TNF) antibody ELISA assays in a sample of healthy volunteers and to use this threshold to report the prevalence of clearing and transient antibodies in patients treated with infliximab and adalimumab. Methods Serum was obtained from a random sample of 498 anti-TNF-naïve healthy adults recruited to the Exeter Ten Thousand study and tested for total anti-drug antibodies to infliximab and adalimumab. Using recommendations for confirmatory anti-drug antibody validation, we used bootstrapping to calculate the 80% one-sided lower confidence interval [CI] of the 99th centile to define assay thresholds. We used paired drug and anti-drug antibody levels derived from our national therapeutic drug monitoring service to report the distribution of clearing (antibody positive, drug negative) vs. non-clearing (antibody positive, drug positive) antibodies. In patients with at least two test results, antibodies were classified as transient (single positive test with subsequent negative test) or persistent (at least two positive tests). Results The 80% one-sided lower CI of the 99th centile titre for total anti-drug antibody to infliximab and adalimumab were 8.7 AU/ml and 5.9 AU/ml, respectively. Using the manufacturer’s recommended threshold of 10 AU/ml for both total anti-TNF antibody assays, in healthy individuals, the prevalence of positive antibodies to infliximab and adalimumab was 1% (5/498) and 0.2% (1/498), respectively. Using the manufacturer’s threshold, at the time of last testing, of 7447 and 4054 patients treated with infliximab and adalimumab; 20.9% (n = 1,554) and 8.0% (n = 326) had clearing antibodies and 26.5% (n = 1973) and 12.1% (n = 490) had non-clearing antibodies, respectively (Figure 1). Using our newly defined threshold in the same cohorts; 21.1% (n = 1573) and 8.4% (n = 339) had clearing antibodies and 28.0% (n = 2083) and 20.0% (n = 812) had non-clearing antibodies, to infliximab and adalimumab, respectively. Amongst patients with at least two tests, most developed persistent antibodies (Figure 2). Irrespective of anti-TNF drug, or threshold used, less than 10% patients developed transient antibodies. graphic graphic Conclusion We report lower positivity thresholds for the IDKmonitor® total anti-TNF antibody ELISA assays than the manufacturer, in particular, for adalimumab. Transient antibody formation is uncommon: most patients develop persistent anti-drug antibodies that lead to drug clearance.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.published version, accepted version (12 month embargo), submitted versio