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Supplementary Figure 3- Translation of the TGFB1 mRNA is maintained in A549 205 cells. Polysomal and non-polysomal mRNAs were harvested from A549 and MCF-10A cells harboring a non15 silencing control shRNA (scr) or the eIF3e shRNA (205). Each gradient fraction was collected and subsequently used as a template for qRT-PCR analysis of the TGFB1 mRNA. The abundance of mRNA in each fraction is plotted as a percentage of total mRNA. Graphs are representative of at least three independent experiments.

Supplementary Figure 4 - A549 cells harboring an eIF3e targeting shRNA (205) were treated with the TGF-β signaling inhibitor SB431542 at a concentration of 10 μM for 48h, after which total RNA was extracted and the expression levels of CDH1, CDH2, VIM and TGFBI were measured by qRT2 PCR. Expression levels are normalized to HPRT expression levels and the graph is a summary of at least three independent experiments.

Supplementary Figure 2- Phosphorylation of eIF4E is decreased in A549 and MCF-10A cells that have decreased eIF3e expression. Whole cells lysates harvested from A549 and MCF-10A cells harboring a non-silencing control shRNA (scr) or the eIF3e-targeting shRNA (205) were examined for the expression of eIF4E, phospho-eIF4E and GAPDH by Western-blot analysis.

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Background Food-related quality of life (FRQoL) encompasses the psychosocial elements of eating and drinking. The FRQoL of children and adolescents with inflammatory bowel disease has not yet been assessed. This study aimed to evaluate the utility of the validated FR-Qol-29 instrument in children with Crohn’s disease (CD). Methods Children diagnosed with CD, a shared home environment healthy sibling, and healthy control subjects 6 to 17 years of age were recruited to this single-center, prospective, cross-sectional study. Children or their parent or guardian completed the FR-QoL-29 instrument. Internal consistency was assessed by completing Cronbach’s α. Construct validity was established by correlating the CD FR-QoL-29 sum scores with the Physician Global Assessment and Pediatric Crohn Disease Activity Index scores. The discriminant validity was analyzed using a 1-way analysis of variance, and a Spearman’s correlation coefficient test was completed to identify any correlations associated with FRQoL. Results Sixty children or their parent or guardian completed the FR-QoL-29 instrument (10 children in each subgroup). The internal consistency was excellent (Cronbach’s α = 0.938). The mean FR-QoL-29 sum scores were 94.3 ± 27.6 for CD, 107.6 ± 20 for siblings, and 113.7 ± 13.8 for control subjects (P = .005). Those with higher disease activity had worse FRQoL (Physician Global Assessment P = .021 and Pediatric Crohn Disease Activity Index P = .004). Inflammatory bowel disease FR-QoL-29 sum scores correlated with weight (P = .027), height (P = .035), body mass index (P = .023), and age (P = .015). Conclusions FRQoL is impaired in children with CD. Healthy siblings also have poorer FRQoL than control subjects. Several clinical factors are associated with poorer FRQoL in children with CD including age and level of nutritional risk (weight, height, and body mass index). Further research is required validate these findings and to develop strategies for the prevention or treatment of impaired FRQoL in children with CD.

Background and aimThe identification of, and timely intervention for, patients with impaired nutritional status may reduce inflammatory bowel disease (IBD) complications. This study aimed to develop and validate an IBD-specific nutrition self-screening tool (IBD-NST) that identifies patients at nutrition risk.MethodsAn expert IBD panel was consulted to support development of an IBD-NST. The tool was assessed in different cohorts of patients attending IBD outpatient clinics for face, content and convergent validity and repeat reliability. The tool was compared with (i) the malnutrition universal screening tool to assess face validity and (ii) subjective global assessment (SGA), hand-grip strength (HGS) and mid-arm muscle circumference to assess convergent validity. Tool content was informed by agreement between assessment tools, sensitivity analysis and chi-squared tests. The IBD-NST was completed electronically twice, 1 week apart to assess repeat reliability using observed agreement and kappa statistic. Statistical significance assumed at p < 0.05.ResultsIn total, 282 IBD patients (175 with Crohn’s disease) were recruited to validate the IBD-NST. The final validated IBD-NST includes body mass index (BMI), weight loss and IBD-specific nutrition-focussed questions which were acceptable to patients. It identified patients at risk of malnutrition, moderately or severely malnourished patients and patients at nutritional risk. The IBD-NST identified 54/179 (30%) patients at moderate or high nutrition risk and had excellent repeat reliability in 85 patients [r = 0.77 (95% CI 0.669 to 0.746)].ConclusionThe IBD-NST is a self-screening tool, validated for use as either a paper or e-health version, that identifies patients at nutrition risk who are likely to benefit from dietetic assessment and intervention. Furthermore, patients with IBD symptoms who are concerned about their dietary intake can potentially access dietetic care more easily therefore encouraging greater self-management of IBD-related symptoms. The routine use of the IBD-NST as a self-screening tool would enable patient-led care in the outpatient setting and may facilitate timely access to dietetic care.

Background and aimsA low fermentable oligosaccharide, disaccharide, monosaccharide, and polyols (FODMAP) diet alleviates symptoms of irritable bowel syndrome (IBS). We aimed to investigate the relationship between habitual FODMAP intake and post-prandial bowel symptoms in adults with IBS, functional diarrhoea (FD), or constipation (FD) (functional bowel disorders), and in healthy adults (controls).Methods292 participants (173 with functional bowel disorders and 119 controls) completed a food and symptom times diary. Estimated meal portion sizes were entered into the Monash FODMAP Calculator to analyse FODMAP content. Wilcoxon and ANOVA tests were used to investigate the relationship between FODMAP intake and post-prandial bowel symptoms.ResultsIBS participants experienced more post-prandial bowel symptoms compared to participants with other functional bowel disorders or controls. Meals associated with abdominal pain contained on average increased excess fructose (0.31 g vs. 0.18 g, p < 0.05), sorbitol (0.27 g vs. 0.10 g, p < 0.01), and total FODMAP (3.46 g vs. 2.96 g, p < 0.05) compared to meals not associated with pain. Abdominal swelling was associated with increased sorbitol (0.33 g vs. 0.11 g, p < 0.01), and total FODMAP (3.26 g vs. 3.02 g, p < 0.05) consumption. Abdominal bloating was associated with increased galacto oligosaccharide consumption (0.18 g vs. 0.14 g, p < 0.05).ConclusionThese findings support the role of FODMAP in post-prandial bowel symptom onset, however, the amount and type of FODMAP triggering symptoms vary between individuals. Future research should investigate the relationship between the effect of individual FODMAP consumption on post-prandial bowel symptoms for each subtype, the interaction of FODMAP with differing functional bowel disorders and whether longitudinally symptoms and dietary intake are stable.

Chronic constipation is highly prevalent worldwide and may be managed with two green or three gold kiwifruit daily. It is unknown whether a smaller standard serve of gold kiwifruit (two daily) is as effective in constipation management. The study aimed to improve chronic constipation with two gold kiwifruit and psyllium in lieu of a placebo daily over four weeks. Adult participants (18–65 years) with functional constipation (FC, n = 11), constipation-predominant irritable bowel syndrome (IBS-C, n = 13), and healthy controls (n = 32) were block-randomized to the treatment order: gold kiwifruit (2/day) or psyllium (fiber-matched, 7.5 g/day) for four weeks, followed by four weeks washout before crossover. Outcomes included alterations of Gastrointestinal Symptom Rating Scale (GSRS) domains and weekly complete spontaneous bowel movements (CSBM) as part of a larger study. Both interventions reduced GSRS constipation domain scores in all subjects compared to baseline values (p = 0.004). All participants reported significantly more weekly CSBM (p = 0.014). Two gold kiwifruit decreased straining (p = 0.021). Two gold kiwifruit daily are as effective as fiber-matched psyllium in treating constipation in adults and should be considered as a treatment option.

Food-related quality of life (FR-QoL) is impaired in inflammatory bowel disease (IBD) and education and support on food-related issues in IBD is needed. This feasibility trial aimed to investigate the effectiveness and acceptability of a web resource in enhancing FR-QoL in newly diagnosed IBD. Patients diagnosed with Crohn’s disease or ulcerative colitis in the preceding 12 months, with an impaired FR-QoL, were recruited and randomised to either receive access to the web resource (covering IBD-specific diet concerns) or no access (control group) for 12 weeks, while receiving usual clinical care. FR-QoL, health-related quality of life, psychological outcomes, and clinical disease activity were assessed. Web resource usage was assessed, and patients’ experiences of the web resource were investigated in semi-structured interviews. Of 81 patients screened, 50 participants were randomised, 30 to the web resource and 20 to control. FR-QoL increased more in the web resource (+11.7 SD 18.2) than control group (+1.4 SD 20.4) (p = 0.067), while IBD distress reduced in the web resource (−6.8 SD 26.6) and increased in the control group (+8.3 SD 25.5) (p = 0.052), albeit not statistically significantly. End of trial Crohn’s disease clinical activity (PRO-2) was significantly lower in the web resource than control group (p = 0.046). Participants most frequently accessed web resource content discussing dietary management of gut symptoms and in semi-structured interviews, reported the website to contain relevant information. This feasibility study demonstrates potential effectiveness of the web resource on improving FR-QoL and psychological outcomes in IBD. An adequately powered effectiveness RCT is feasible to conduct and is now warranted. NCT03884686.

(1) The nutritional status of children with Crohn’s disease (CD) is rarely described. This study aimed to assess the dietary intake and blood micronutrient status of children with CD compared with their healthy, shared-environment siblings. (2) Methods: This observational study included children with CD (cases) and their shared-environment siblings (controls). The dietary nutrient intake was assessed with a four-day food/beverage diary and was compared with the recommended daily intakes (RDI). Blood micronutrient concentrations were measured using laboratory methods. The nutritional analyses were completed through a multivariate analysis of variance between groups. Between-group comparisons of single-nutrients were assessed using a Mann–Whitney U-test. Chi-squared analyses compared the proportion of children who did not meet the RDI for each nutrient. The results were significant at 0.05. (3) Results: The dietary intake was similar for most nutrients, except the controls had a lower intake of vitamins A and E, copper, zinc, iron, and selenium (p < 0.05). Children using partial enteral nutrition had significantly higher intakes of many micronutrients. It was common for both groups to not meet the RDI’s—more than 50% of cases for 9 nutrients and more than 50% of controls for 13 nutrients. (4) Conclusion: New Zealand children with CD and their shared-environment siblings did not meet the RDI for several micronutrients. Dietary education and/or micronutrient supplementation may be required.

The high cost and negative environmental impact of precious metal catalysts has led to increased demand for nonprecious alternatives for widely practiced reactions such as the Suzuki-Miyaura coupling (SMC). Ni-catalyzed versions of this reaction have failed to achieve high reactivity with Lewis-basic arylboron nucleophiles, especially pinacolboron esters. We describe the development of (PPh

Diet is a key modifier of risk of inflammatory bowel disease development and potentially a treatment option in patients with established disease. International organisations in gastroenterology and inflammatory bowel disease have published guidelines for the role of diet in disease onset and its management. Here, we discuss the major overarching themes arising from these guidelines and appraise recent literature on the role of diet for inflammatory bowel disease prevention, treatment of active disease and maintenance of remission, considering these themes. Except for exclusive enteral nutrition in active Crohn’s disease, we currently possess very little evidence to make any further dietary recommendations for the management of inflammatory bowel disease. There is also currently uncertainty on the extrapolation of epidemiological dietary signals on risk of disease development and preclinical experiments in animal models to management, once disease is established. Until high-quality evidence from clinical research becomes available, the only specific recommendations for inflammatory bowel disease we might safely give are those of healthy eating which apply for the general population for overall health and well-being.

BackgroundDual systems theories suggest that greater imbalance between higher reward sensitivity and lower cognitive control across adolescence conveys risk for behaviors such as heavy episodic drinking (HED). Prior research demonstrated that psychological analogues of these systems, sensation seeking and premeditation, change from childhood through emerging adulthood, and each has been independently linked with HED. However, few studies have assessed whether change over time in these developing analogues is prospectively associated with HED. Moreover, we know of no research that has shown whether within-person differences between higher sensation seeking and relatively lower premeditation across the adolescent period predict HED in emerging adulthood.MethodsProspective data from the National Consortium on Alcohol and NeuroDevelopment in Adolescence study (n=715) were used to examine the association of sensation seeking and premeditation with HED among adolescents ages 16 to 20years. We used novel applications of latent difference score modeling and growth curve analysis to test whether increasing sensation seeking, premeditation, and their imbalance over time are associated with HED across the study period, and whether these associations differed by sex.ResultsWhereas premeditation increased linearly from adolescence through emerging adulthood across sexes, males reported growth and females reported decline in sensation seeking. Sensation seeking in adolescence (and not premeditation) was associated with higher levels of HED by emerging adulthood. Importantly, greater imbalance between sensation seeking and premeditation was associated with higher levels of HED by emerging adulthood though we note that variability capturing this imbalance correlated highly (r=0.86) with baseline levels of sensation seeking.ConclusionsDevelopmental imbalance between higher sensation seeking and lower premeditation in late adolescence may be a risk factor for greater HED in emerging adulthood.

Background: Variation in liability to cannabis use disorder has a strong genetic component (estimated twin and family heritability about 50–70%) and is associated with negative outcomes, including increased risk of psychopathology. The aim of the study was to conduct a large genome-wide association study (GWAS) to identify novel genetic variants associated with cannabis use disorder. Methods: To conduct this GWAS meta-analysis of cannabis use disorder and identify associations with genetic loci, we used samples from the Psychiatric Genomics Consortium Substance Use Disorders working group, iPSYCH, and deCODE (20 916 case samples, 363 116 control samples in total), contrasting cannabis use disorder cases with controls. To examine the genetic overlap between cannabis use disorder and 22 traits of interest (chosen because of previously published phenotypic correlations [eg, psychiatric disorders] or hypothesised associations [eg, chronotype] with cannabis use disorder), we used linkage disequilibrium score regression to calculate genetic correlations. Findings: We identified two genome-wide significant loci: a novel chromosome 7 locus (FOXP2, lead single-nucleotide polymorphism [SNP] rs7783012; odds ratio [OR] 1·11, 95% CI 1·07–1·15, p=1·84 × 10 −9) and the previously identified chromosome 8 locus (near CHRNA2 and EPHX2, lead SNP rs4732724; OR 0·89, 95% CI 0·86–0·93, p=6·46 × 10 −9). Cannabis use disorder and cannabis use were genetically correlated (r g 0·50, p=1·50 × 10 −21), but they showed significantly different genetic correlations with 12 of the 22 traits we tested, suggesting at least partially different genetic underpinnings of cannabis use and cannabis use disorder. Cannabis use disorder was positively genetically correlated with other psychopathology, including ADHD, major depression, and schizophrenia. Interpretation: These findings support the theory that cannabis use disorder has shared genetic liability with other psychopathology, and there is a distinction between genetic liability to cannabis use and cannabis use disorder. Funding: National Institute of Mental Health; National Institute on Alcohol Abuse and Alcoholism; National Institute on Drug Abuse; Center for Genomics and Personalized Medicine and the Centre for Integrative Sequencing; The European Commission, Horizon 2020; National Institute of Child Health and Human Development; Health Research Council of New Zealand; National Institute on Aging; Wellcome Trust Case Control Consortium; UK Research and Innovation Medical Research Council (UKRI MRC); The Brain & Behavior Research Foundation; National Institute on Deafness and Other Communication Disorders; Substance Abuse and Mental Health Services Administration (SAMHSA); National Institute of Biomedical Imaging and Bioengineering; National Health and Medical Research Council (NHMRC) Australia; Tobacco-Related Disease Research Program of the University of California; Families for Borderline Personality Disorder Research (Beth and Rob Elliott) 2018 NARSAD Young Investigator Grant; The National Child Health Research Foundation (Cure Kids); The Canterbury Medical Research Foundation; The New Zealand Lottery Grants Board; The University of Otago; The Carney Centre for Pharmacogenomics; The James Hume Bequest Fund; National Institutes of Health: Genes, Environment and Health Initiative; National Institutes of Health; National Cancer Institute; The William T Grant Foundation; Australian Research Council; The Virginia Tobacco Settlement Foundation; The VISN 1 and VISN 4 Mental Illness Research, Education, and Clinical Centers of the US Department of Veterans Affairs; The 5th Framework Programme (FP-5) GenomEUtwin Project; The Lundbeck Foundation; NIH-funded Shared Instrumentation Grant S10RR025141; Clinical Translational Sciences Award grants; National Institute of Neurological Disorders and Stroke; National Heart, Lung, and Blood Institute; National Institute of General Medical Sciences.

Aims To examine whether moderate adolescent cannabis use has neurocognitive effects that are unexplained by familial confounds, which prior family-controlled studies may not have identified. Design A quasi-experimental, sibling-comparison design was applied to a prospective, observational study of adolescents with moderate cannabis use. Participants were recruited from 2001 to 2006 (mean age = 17 years). A second wave of data was collected from 2008 to 2013 (mean age = 24 years). Setting Two US metropolitan communities. Participants A total of 1192 adolescents from 596 families participated in this study. Participants were primarily male (64%) and racially and ethnically diverse (non-Hispanic white = 45%). A sibling in each family was a clinical proband identified due to delinquent behaviors. Whereas prior family-controlled studies have used samples of primarily infrequent cannabis users (mean = 1-2 days/month), participants here endorsed levels of cannabis use comparable to findings from epidemiological cohort studies (mean = 7-9 days/month). Measurements Semi-structured clinical interviews assessed drug use, and a neuropsychological battery assessed cognitive abilities. Covariates included age at assessment, gender and alcohol use. Findings After correcting for multiple testing, a greater frequency and earlier onset of regular cannabis use were associated with poorer cognitive performance, specifically on tests of verbal memory. Further, after accounting for familial factors shared by siblings and alcohol use, poorer verbal memory performance was still associated with greater life-time frequency of cannabis use at wave 1 [b = -0.007 (-0.002, -0.012), adjusted P = 0.036]; earlier cannabis use at wave 2 [b = -0.12 (-0.05, -0.19), adjusted P = 0.006; b = -0.14 (-0.06, -0.23), adjusted P = 0.006]; and greater frequency of past 6 months use at wave 2 [b = -0.02 (-0.01, -0.03), adjusted P = 0.002; b = -0.02 (-0.01, -0.03), adjusted P = 0.008]. Conclusions Moderate adolescent cannabis use may have adverse effects on cognitive functioning, specifically verbal memory, that cannot be explained by familial factors.

Introduction: Although collecting faeces and blood samples are considered non-invasive methods of monitoring Crohn’s disease (CD), these methods are less preferred by some patients. This study utilized urine as an alternative to evaluate four disease biomarkers in young adults with active CD before and after exclusive enteral nutrition (EEN) therapy. Methods: Urine samples collected at baseline (W0) and after 8 weeks (W8) of EEN therapy were assayed by ELISA for levels of intestinal fatty acid-binding protein (I-FABP), liver fatty acid-binding protein (L-FABP), claudin-3, and calprotectin. Levels of each biomarker were also compared with standard clinical parameters, including disease indexes, nutrient, and inflammatory markers. Results: Of the paired urine samples from 14 patients, 10 were female and 12 were newly diagnosed with CD. Urinary I-FABP:Cr (standardized to urine Cr) levels were significantly reduced, while urinary L-FABP:Cr levels increased following EEN therapy. Urinary L-FABP:Cr correlated positively with serum insulin-like growth factor 1 (IGF-1) (r = 0.60, p = 0.02). Urinary CLND3:Cr and calprotectin:Cr levels were not significantly different after treatment. Conclusion: I-FABP is a potential urinary biomarker of disease activity in adults with CD, while urinary L-FABP may be an indirect marker of nutritional status in adults with CD. CLND3 and calprotectin do not appear to have roles as urinary biomarkers in CD. These findings warrant further investigations using a larger sample size.

Objective: To investigate the genetic architecture of internalizing symptoms in childhood and adolescence. Method: In 22 cohorts, multiple univariate genome-wide association studies (GWASs) were performed using repeated assessments of internalizing symptoms, in a total of 64,561 children and adolescents between 3 and 18 years of age. Results were aggregated in meta-analyses that accounted for sample overlap, first using all available data, and then using subsets of measurements grouped by rater, age, and instrument. Results: The meta-analysis of overall internalizing symptoms (INToverall) detected no genome-wide significant hits and showed low single nucleotide polymorphism (SNP) heritability (1.66%, 95% CI = 0.84-2.48%, neffective = 132,260). Stratified analyses indicated rater-based heterogeneity in genetic effects, with self-reported internalizing symptoms showing the highest heritability (5.63%, 95% CI = 3.08%-8.18%). The contribution of additive genetic effects on internalizing symptoms appeared to be stable over age, with overlapping estimates of SNP heritability from early childhood to adolescence. Genetic correlations were observed with adult anxiety, depression, and the well-being spectrum (|rg| > 0.70), as well as with insomnia, loneliness, attention-deficit/hyperactivity disorder, autism, and childhood aggression (range |rg| = 0.42-0.60), whereas there were no robust associations with schizophrenia, bipolar disorder, obsessive-compulsive disorder, or anorexia nervosa. Conclusion: Genetic correlations indicate that childhood and adolescent internalizing symptoms share substantial genetic vulnerabilities with adult internalizing disorders and other childhood psychiatric traits, which could partially explain both the persistence of internalizing symptoms over time and the high comorbidity among childhood psychiatric traits. Reducing phenotypic heterogeneity in childhood samples will be key in paving the way to future GWAS success. Dr. Border has received support from the National Institutes of Health (NIH; MH100141 and MH016880 ). Dr. Peterson has received support from NIH (K01MH113848) and the Brain & Behavior Research Foundation Young Investigator Grant (28632). Drs. Sallis and Munafò have served as members of the MRC Integrative Epidemiology Unit at the University of Bristol (MC_UU_00011/7). Dr. Shabalin has received support from a NARSAD Young Investigator Award. Dr. Vilor-Tejedor has received support from a post-doctoral grant, Juan de la Cierva Programme (FJC2018-038085-I), Ministerio de Ciencia, Innovación y Universidades – Spanish State Research Agency. Her research has received additional support of “la Caixa” Foundation (LCF/PR/GN17/10300004) and the Health Department of the Catalan Government (Health Research and Innovation Strategic Plan (PERIS) 2016-2020 grant# SLT002/16/00201). She has acknowledged the support of the Spanish Ministry of Science, Innovation and Universities to the EMBL partnership, the Centro de Excelencia Severo Ochoa, and the CERCA Programme/Generalitat de Catalunya. Dr. Alemany has received support from a Juan de la Cierva – Incorporación Postdoctoral Contract from Ministerio de Economía, Industria y Competitividad (IJCI-2017-34068). Dr. Corley has received support from NIH (DA011015, AG046938, and DA035804). Dr. Evans has received support from NIH (MH100141, DA044283, and AG046938). Dr. Havdahl has received support from the South-Eastern Norway Regional Health Authority (2018059) at Nic Waals Institute, Lovisenberg Diaconal Hospital. Dr. Rimfeld has received support from a Sir Henry Wellcome Postdoctoral Fellowship. Dr. Andreassen has served as a consultant to HealthLytix and has received funding from the Research Council of Norway (223273 and 273291) and KG Jebsen Stiftelsen. Dr. Boomsma has received support from the Royal Netherlands Academy of Science Professor Award (PAH/5535). Dr. Brown has received support from NIH (DA035804). Dr. Copeland has received support from NIH (MH117559 and HD093651). Dr. Dick has received support from a mid-career award NIH K02 AA018755, NIH R01 AA015416 (Finnish Twin Study), P50 AA022537 (Alcohol Research Center), R25 AA027402 (VCU GREAT), and U10 AA008401 (COGA) from the National Institute on Alcohol Abuse and Alcoholism. Drs. Hewitt, Krauter, Smolen, and Stallings have received support from NIH (DA011015 and DA035804). Dr. Hopfer has received support from NIH (DA042755, DA035804, and DA032555). Dr. Kaprio has received support from the Academy of Finland (grants 308248 and 312073). Dr. Larsson has served as a speaker for Evolan Pharma and Shire/Takeda and has received research grants from Shire/Takeda, all outside the submitted work. Dr. Lichtenstein has received support from the Swedish Research Council for Health, Working Life and Welfare (project 2012-1678) and the Swedish Research Council (2016-1989). Dr. Lundström has received support from the Swedish Research Council ( 2017-02552 ). Dr. Magnus has received support from the Research Council of Norway through its Centers of Excellence scheme, project no 262700. Dr. Njølstad has received support from the European Research Council (AdG #293574). Stiftelsen Kristian Gerhard Jebsen has received support from the Research Council of Norway (FRIPRO 240413), the Western Norway Regional Health Authority (Strategic Fund “Personalized Medicine for Children and Adults”) and the Novo Nordisk Foundation (54741). Dr. Plomin has received support from a MRC Professorship award (G19/2). Dr. Reichborn-Kjennerud has received support from the Research Council of Norway grant 274611 . Drs. Reynolds and Wadsworth have received support from NIH (AG046938). Dr. Rose has received support from a NIH Research Scientist Award (AA-000145). Dr. Wall has received support from NIH (DA03580 and DA021905). Dr. Whitehouse has received support from an Investigator Grant from the National Health and Medical Research Council. Dr. Ystrøm has received support from the Research Council of Norway (262177 and 288083). Dr. Nivard has received support from ZonMW (849200011), the Netherlands Organisation for Health Research and Development (531003014 937), a Jacobs Foundation Research Fellowship, and a VENI grant awarded by NWO (VI.Veni.191G.030). Dr. Bartels has received support from an ERC Consolidator Grant (WELL-BEING 771057). Ms. Hagenbeek and Mr. Ip have received support from the Aggression in Children: Unraveling gene-environment interplay to inform Treatment and Intervention strategies project (ACTION). ACTION received funding from the European Union Seventh Framework Program (FP7/2007-2013) under grant agreement no 602768

We demonstrate the use of matrix product state (MPS) models for discriminating quantum data on quantum computers using holographic algorithms, focusing on classifying a translationally invariant quantum state based on $L$ qubits of quantum data extracted from it. We detail a process in which data from single-shot experimental measurements are used to optimize an isometric tensor network, the tensors are compiled into unitary quantum operations using greedy compilation heuristics, parameter optimization on the resulting quantum circuit model removes the post-selection requirements of the isometric tensor model, and the resulting quantum model is inferenced on either product state or entangled quantum data. We demonstrate our training and inference architecture on a synthetic dataset of six-site single-shot measurements from the bulk of a one-dimensional transverse field Ising model (TFIM) deep in its antiferromagnetic and paramagnetic phases. We experimentally evaluate models on Quantinuum's H1-2 trapped ion quantum computer using entangled input data modeled as translationally invariant, bond dimension 4 MPSs across the known quantum phase transition of the TFIM. Using linear regression on the experimental data near the transition point, we find predictions for the critical transverse field of $h=0.962$ and $0.994$ for tensor network discriminators of bond dimension $\chi=2$ and $\chi=4$, respectively. These predictions compare favorably with the known transition location of $h=1$ despite training on data far from the transition point. Our techniques identify families of short-depth variational quantum circuits in a data-driven and hardware-aware fashion and robust classical techniques to precondition the model parameters, and can be adapted beyond machine learning to myriad applications of tensor networks on quantum computers, such as quantum simulation and error correction., Comment: 19 pages, 9 figures. Abstract shortened compared to uploaded version to meet arXiv requirements

Despite increased awareness of diet and nutrition being integral to the management of patients with inflammatory bowel disease (IBD), there are gaps in the knowledge of IBD healthcare providers regarding nutrition. Furthermore, high quality evidence on nutritional assessment and dietary management of IBD is limited. A Delphi consensus from a panel of experts allows for best-practice guidelines to be developed, especially where high quality evidence is limited. The aim was to develop guidelines for the nutritional assessment and dietary management of IBD using an eDelphi online consensus agreement platform.Seventeen research topics related to IBD and nutrition were systematically reviewed. Searches in Cochrane, Embase®, Medline® and Scopus® electronic databases were performed. GRADE was used to develop recommendations. Experts from the IBD community (healthcare professionals and patients with IBD) were invited to vote anonymously on the recommendations in a custom-built online platform. Three rounds of voting were carried out with updated iterations of the recommendations and evaluative text based on feedback from the previous round.From 23,824 non-duplicated papers, 167 were critically appraised. Fifty-five participants completed three rounds of voting and 14 GRADE statements and 42 practice statements achieved 80% consensus. Comprehensive guidance related to nutrition assessment, nutrition screening and dietary management is provided.Guidelines on the nutritional assessment and dietary management of IBD have been developed using evidence-based consensus to improve equality of care. The statements and practice statements developed demonstrate the level of agreement and the quality and strength of the guidelines.

Introduction: Diabetes mellitus is a significant cause of morbidity and mortality. Foot-related complications affect 2–2.5% of people with diabetes. There is significant variation in outcomes for patients with diabetic foot disease within the UK. The multidisciplinary approach to diabetic foot disease is well publicised and protocols, guidance and consensus approaches exist for most components of the management of diabetic foot disease. Antimicrobial therapy to treat diabetic foot infections based on microbiological sampling and culture is well documented, but no consensus exists on how these samples should be obtained, processed and reported. Methods: A literature review was undertaken to establish the reporting of techniques used in obtaining and processing microbiological samples in diabetic foot disease to establish if consensus exists in the methodologies used with a view to develop best practice guidelines. Results: Six out of 102 papers reported all processes in obtaining and processing microbiological samples. Conclusion: No gold standard consensus exists for microbiological sampling of diabetic foot infections, preventing optimisation of this aspect of management of diabetic foot disease and ultimately potentially adversely affecting the outcomes of this growing patient cohort.

The genetic architecture of numerous smoking behaviors is highly polygenic, but these genetic effects are heterogeneous and depend on moderating factors. Here, we used common SNPs from the UK Biobank to investigate heterogeneous genetic effects for smoking heaviness using cigarettes per day (CPD) records, smoking initiation (SI), and smoking cessation (SC). We assessed heterogeneous effects across levels of sex, age of smoking initiation, major depressive disorder (MDD) DSM-V-like diagnosis, generalized anxiety disorder (GAD) DSM-V-like diagnosis, and whether an individual has seen a psychiatrist for nerves, anxiety, tension, or depression. We observed suggestive evidence of heterogeneous genetic effects for CPD and SC, moderated by MDD and GAD, respectively [ (SE = 0.15) between MDD cases and controls, and (SE = 0.28) between GAD cases and controls, p < 0.05]. We detected 5 SNPs with genome-wide significant evidence of heterogeneous effects moderated by either MDD or GAD (p-value < 5×10-8) for CPD and SC. We also observed strong evidence for heterogeneous genetic effects for SI between sexes (between-sex , SE = 0.02). While we detected no individual SNPs that were moderated by sex at genome-wide significance (all p-value > 5×10-8), we observed evidence of novel genome-wide significant SI-SNP associations using sex-stratified GWAS; six loci were discovered in either men or women separately that were not identified in a previous smoking meta-analysis that had a 6-fold larger, sex-combined sample. Furthermore, using several independent testing samples, there was suggestive evidence that the prediction ability of a polygenic risk score (PRS) for smoking initiation improved through the utilization of sex-specific SNP effects. This work suggests that a more nuanced approach to GWAS analyses is warranted, as potential heterogeneous effects can complicate variant discovery and polygenic risk score accuracy.Author SummarySmoking imposes a heavy health burden and is highly polygenic in architecture. Consistent with most complex traits, many causal loci have yet to be identified, even when using the largest available samples. One possible reason for the difficulty in inferring genetic variants associated with such complex traits is that common genetic variants possess context-dependent (or heterogeneous) effects. Utilizing the UK Biobank, we find evidence for heterogeneous SNP effects on smoking initiation, heaviness, and cessation among psychiatric disorder cases and controls and between sexes. Failure to model such heterogeneity (when accounting for sample size) resulted in lower independent sample predictive ability. This work encourages a more nuanced approach to GWAS and polygenic risk prediction. The assumption that all genetic effects are homogeneous limits our understanding of complex traits when heterogeneous effects are present.

Tropical forest ecosystems are the most species-rich in the world and face intense pressures from land conversion. If done well, selective logging can be an important way of supporting local economies while minimally impacting wildlife. However, most studies on how selective logging affects wildlife come from sites that have been logged some time ago, often a decade or more. Here we assess how logging affects species assemblages in the very short term, immediately after the cessation of timber operations. We estimated overall mammal species richness in unlogged forest, previously logged forest, and an active logging concession in Indonesian Borneo using rarefaction-extrapolation-based diversity estimators. We found that estimated species richness did not differ significantly between unlogged forest (15.5 ± 2.82 species), previously logged forest (14.5 ± 2.10), or recently logged sites (14.2 ± 1.45) sites. Our findings suggest that the short-term impacts of properly managed selective logging are on par with the longer-term impacts that have been assessed in many prior studies.

Alcohol biosensor devices have been developed to unobtrusively measure transdermal alcohol concentration (TAC), the amount of ethanol diffusing through the skin, in nearly continuous fashion in naturalistic settings. Because TAC data are affected by physiological and environmental factors that vary across individuals and drinking episodes, there is not an elementary formula to convert TAC into easily interpretable metrics such as blood and breath alcohol concentrations (BAC/BrAC). In our prior work, we addressed this conversion problem in a deterministic way by developing physics/physiological-based models to convert TAC to estimated BrAC (eBrAC), in which the model parameter values were individually determined for each person wearing a specific transdermal sensor using simultaneously collected TAC (via a biosensor) and BrAC (via a breath analyzer) during a calibration episode. We found these individualized parameter values produced relatively good eBrAC curves for subsequent drinking episodes, but our results also indicated the models were not fully capturing the dynamics of the system and variations across drinking episodes. Here, we report on a novel mathematical framework to improve our ability to model eBrAC from TAC data that uses aggregate population data instead of individualized calibration data to determine model parameter values via a random diffusion equation. We first provide the theoretical mathematical basis for our approach, and then test the efficacy of this method using datasets of contemporaneous BrAC/TAC measurements obtained by a) a single subject during multiple drinking episodes and b) multiple subjects during single drinking episodes. For each dataset, we used a set of drinking episodes to construct the population model, and then ran the model with another set of randomly selected test episodes. We compared raw TAC data to model-simulated TAC curve, breath analyzer BrAC data to model eBrAC curve with 75% credible bands, episode summary scores of peak BrAC, times of peak BrAC, and area under the drinking curve also with 75% credible intervals, and report the percent of the raw BrAC captured within the eBrAC curve credible bands. We also display results when stratifying the data based on the relationship between the raw BrAC and TAC data. Results indicate the population-based model is promising, with better fit within a single participant when stratifying episodes. This study provides initial proof-of-concept for constructing, fitting, and using a population-based model to obtain estimates and error bands for BrAC from TAC. The advancements in this study, including new applications of math, the development of a population-based model with error bars, and the production of corresponding MATLAB codes, represent a major step forward in our ability to produce quantitatively- and temporally-accurate estimates of BrAC from TAC biosensor data.

The beneficial effects of exercise on cognition are well established; however specific exercise parameters regarding the frequency and duration of physical activity that provide optimal cognitive health have not been well defined. Here, we explore the effects of the duration of exercise and sedentary periods on long-term object location memory (OLM) in mice. We use a weak object location training paradigm that is subthreshold for long-term memory formation in sedentary controls, and demonstrate that exercise enables long-term memories to form. We show that 14- and 21-d of running wheel access enables mice to discriminate between familiar and novel object locations after a 24 h delay, while 2- or 7-d running wheel access provides insufficient exercise for such memory enhancement using the subthreshold learning paradigm. After 14- and 21-d of wheel running, exercise-induced cognitive enhancement then decays back to baseline performance following 3-d of sedentary activity. However, exercise-induced cognitive enhancement can be reactivated by an additional period of just 2 d exercise, previously shown to be insufficient to induce cognitive enhancement on its own. The reactivating period of exercise is capable of enhancing memory after three- or seven-sedentary days, but not 14-d. These data suggest a type of “molecular memory” for the exercise stimulus, in that once exercise duration reaches a certain threshold, it establishes a temporal window during which subsequent low-level exercise can capitalize on the neurobiological adaptations induced by the initial period of exercise, enabling it to maintain the benefits on cognitive function. These findings provide new information that may help to guide future clinical studies in exercise.

AIMS: The current meta-analysis tested independent and composite associations of three commonly studied alcohol metabolism alleles with alcohol use disorder (AUD) within East Asians as well as characterized potential moderating factors in these associations. METHODS: For meta-analysis, 32 articles were selected that investigated ALDH2 (n = 17,755), ADH1B (n = 13,591) and ADH1C (n = 4,093) associations with AUD in East Asians. RESULTS AND CONCLUSIONS: All three variants were associated with AUD across allelic and genotypic models: ALDH2, ORs = 0.25, P < 0.001; ADH1B, ORs = 0.22–0.49, P < 0.001; ADH1C, ORs = 0.26–0.46, P < 0.001. Composite analyses suggested genetic associations did not differ across ALDH2*2 and ADH1B*2, correcting for multiple comparisons. Moderation analyses suggested ADH1B was more strongly associated with AUD among samples with cases recruited from treatment than the community. Also, strength of ALDH2 and/or ADH1B associations varied with mean age and proportion of men in cases and controls. Findings support medium to large and unique associations of ALDH2, ADH1B, and ADH1C with AUD in East Asians. Results also identified novel methodological and sample characteristics that may modulate strength of these associations.

On February 27 to 28, 2018, the Produce Safety Alliance convened a national water summit in Covington, KY to discuss the requirements of the United States Food and Drug Administration's (FDA) Food Safety Modernization Act Standards for the Growing, Harvesting, Packing, and Holding of Produce for Human Consumption (Produce Safety Rule [PSR]). The goals of the meeting were to better understand the challenges growers face in implementing the requirements in Subpart E-Agricultural Water and work collaboratively to develop practical solutions to meet fruit and vegetable production needs while protecting public health. To meet these goals, the summit engaged a diverse group of stakeholders including growers, researchers, extension educators, produce industry members, and regulatory personnel. Key outcomes included defining implementation barriers due to diversity in water sources, distribution systems, commodity types, climates, farm size, and production activities. There was an articulated need for science-based solutions, such as the use of agricultural water system assessments and sharing of federal, state, and regional water quality data, to ensure qualitative and quantitative standards reduce microbial risks. These identified challenges and needs resulted in significant debate about whether reopening the PSR-Subpart E for modification or attempting to address concerns through guidance would provide the best mechanism for alleviating concerns. In addition, training, outreach, and technical assistance were identified as vital priorities once the concerns are formally addressed by FDA. The water summit highlighted the critical need for transparency of FDA's progress on reevaluating the Subpart E requirements to help guide growers' decisions regarding the use of agricultural water.

BACKGROUND: High-dose oral vitamin D (stoss) is a novel treatment in children with inflammatory bowel disease (IBD). Vitamin D supplementation may have benefits in IBD beyond bone health including reduced disease activity and improvements in inflammatory markers. The aim of this study was to retrospectively assess the efficacy, safety and impact on disease activity of single oral high-dose vitamin D3 therapy in New Zealand (NZ) children with IBD and vitamin D deficiency. METHODS: In this retrospective chart review, children with IBD and vitamin D deficiency [serum 25-OH vitamin D level (25-OHD) 75 nmol/L. One child had a serum calcium of 2.7 (normal range, 2.2 to 2.6 mmol/L) 2 weeks after treatment, which normalized on repeat testing 10 days later. PCDAI scores, mean platelet count, erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) all reduced significantly from baseline to 3 months following stoss therapy. CONCLUSIONS: Single high-dose oral vitamin D therapy was used successfully and safely to manage vitamin D deficiency in these children with IBD. An improvement in inflammatory markers and disease activity scores also occurred following stoss therapy.

Noisy, intermediate-scale quantum (NISQ) computing devices have become an industrial reality in the last few years, and cloud-based interfaces to these devices are enabling exploration of near-term quantum computing on a range of problems. As NISQ devices are too noisy for many of the algorithms with a known quantum advantage, discovering impactful applications for near-term devices is the subject of intense research interest. We explore quantum-assisted machine learning (QAML) on NISQ devices through the perspective of tensor networks (TNs), which offer a robust platform for designing resource-efficient and expressive machine learning models to be dispatched on quantum devices. In particular, we lay out a framework for designing and optimizing TN-based QAML models using classical techniques, and then compiling these models to be run on quantum hardware, with demonstrations for generative matrix product state (MPS) models. We put forth a generalized canonical form for MPS models that aids in compilation to quantum devices, and demonstrate greedy heuristics for compiling with a given topology and gate set that outperforms known generic methods in terms of the number of entangling gates, e.g., CNOTs, in some cases by an order of magnitude. We present an exactly solvable benchmark problem for assessing the performance of MPS QAML models, and also present an application for the canonical MNIST handwritten digit dataset. The impacts of hardware topology and day-to-day experimental noise fluctuations on model performance are explored by analyzing both raw experimental counts and statistical divergences of inferred distributions. We also present parametric studies of depolarization and readout noise impacts on model performance using hardware simulators., 31 pages. 18+49 figures

We describe a quantum-assisted machine learning (QAML) method in which multivariate data is encoded into quantum states in a Hilbert space whose dimension is exponentially large in the length of the data vector. Learning in this space occurs through applying a low-depth quantum circuit with a tree tensor network (TTN) topology, which acts as an unsupervised feature extractor to identify the most relevant quantum states in a data-driven fashion. This unsupervised feature extractor then feeds a supervised linear classifier and encodes the output in a small-dimensional quantum register. In contrast to previous work on \emph{quantum-inspired} TTN classifiers, in which the embedding map and class decision weights did not map the data to well-defined quantum states, we present an approach that can be implemented on gate-based quantum computing devices. In particular, we identify an embedding map with accuracy similar to exponential machines (Novikov \emph{et al.}, arXiv:1605.03795), but which produces valid quantum states from classical data vectors, and utilize manifold-based gradient optimization schemes to produce isometric operations mapping quantum states to a register of qubits defining a class decision. We detail methods for efficiently obtaining one- and two-point correlation functions of the decision boundary vectors of the quantum model, which can be used for model interpretability, as well as methods for obtaining classifications from partial data vectors. Further, we show that the use of isometric tensors can significantly aid in the human interpretability of the correlation functions extracted from the decision weights, and may produce models that are less susceptible to adversarial perturbations. We demonstrate our methodologies in applications utilizing the MNIST handwritten digit dataset and a multivariate timeseries dataset of human activity recognition., Comment: 20 pages, 15 figures. Abstract slightly shortened to fit arXiv requirements

Childhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association meta-analysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis (AGGoverall) was 3.31% (SE = 0.0038). We found no genome-wide significant SNPs for AGGoverall. The gene-based analysis returned three significant genes: ST3GAL3 (P = 1.6E–06), PCDH7 (P = 2.0E–06), and IPO13 (P = 2.5E–06). All three genes have previously been associated with educational traits. Polygenic scores based on our GWAMA significantly predicted aggression in a holdout sample of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations (rg) among rater-specific assessment of AGG ranged from rg = 0.46 between self- and teacher-assessment to rg = 0.81 between mother- and teacher-assessment. We obtained moderate-to-strong rgs with selected phenotypes from multiple domains, but hardly with any of the classical biomarkers thought to be associated with AGG. Significant genetic correlations were observed with most psychiatric and psychological traits (range $$\left| {r_g} \right|$$ r g : 0.19–1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (rg = ~−0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range $$\left| {r_g} \right|$$ r g : 0.46–0.60). The genetic correlations between aggression and psychiatric disorders were weaker for teacher-reported AGG than for mother- and self-reported AGG. The current GWAMA of childhood aggression provides a powerful tool to interrogate the rater-specific genetic etiology of AGG.

The KArlsruhe TRItium Neutrino (KATRIN) experiment, which aims to make a direct and model-independent determination of the absolute neutrino mass scale, is a complex experiment with many components. More than 15 years ago, we published a technical design report (TDR) [https://publikationen.bibliothek.kit.edu/270060419] to describe the hardware design and requirements to achieve our sensitivity goal of 0.2 eV at 90% C.L. on the neutrino mass. Since then there has been considerable progress, culminating in the publication of first neutrino mass results with the entire beamline operating [arXiv:1909.06048]. In this paper, we document the current state of all completed beamline components (as of the first neutrino mass measurement campaign), demonstrate our ability to reliably and stably control them over long times, and present details on their respective commissioning campaigns., Comment: Added missing acknowledgement, corrected performance statement in chapter 4.2.5, updated author list and references

Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa (BN) and problem alcohol use (genetic correlation [rg], twin-based=0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge-eating, AN without binge-eating, and a BN factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder (MDD). Total sample sizes per phenotype ranged from ~2,400 to ~537,000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (rg=0.18; false discovery rate q=0.0006), cannabis initiation and AN (rg=0.23; qwith binge-eating (rg=0.27; q=0.0016). Conversely, significant negative genetic correlations were observed between three non-diagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge-eating (rgs=-0.19 to −0.23; qs

A search has been performed for neutrinos from two sources, the $hep$ reaction in the solar $pp$ fusion chain and the $��_e$ component of the diffuse supernova neutrino background (DSNB), using the full dataset of the Sudbury Neutrino Observatory with a total exposure of 2.47 kton-years after fiducialization. The $hep$ search is performed using both a single-bin counting analysis and a likelihood fit. We find a best-fit flux that is compatible with solar model predictions while remaining consistent with zero flux, and set a one-sided upper limit of $��_{hep} < 30\times10^{3}~\mathrm{cm}^{-2}~\mathrm{s}^{-1}$ [90% credible interval (CI)]. No events are observed in the DSNB search region, and we set an improved upper bound on the $��_e$ component of the DSNB flux of $��^\mathrm{DSNB}_{��_e} < 19~\textrm{cm}^{-2}~\textrm{s}^{-1}$ (90% CI) in the energy range $22.9 < E_��< 36.9$~MeV., 11 pages, 6 figures

Despite the many barriers to receiving care, children with asthma must have access to regular care and frequent follow-up visits. The usual barriers to the provision of asthma care have been made even more complicated by the current COVID-19 pandemic. To minimize the disruption of care due to the necessary constraints dictated by COVID-19, the televisit provides a practical solution that can assess the child’s current level of symptom control, reinforce asthma education, and determine treatment options. This article provides the tools and guidelines to facilitate the implementation of successful televisits to provide uninterrupted care for children with asthma., Highlights • Televisits are the work-around that mitigates the disruption to usual care appointments for children with asthma during COVID-19 and after. • Televisit sessions provide families with the continued reinforcement necessary for maintaining the course for good asthma control • Televisits address medical, pharmaceutical and administrative issues in real time • Televisits moved into usual care has the potential to reduce the low follow up rate common to children with asthma

Internalising symptoms in childhood and adolescence are as heritable as adult depression and anxiety, yet little is known of their molecular basis. This genome-wide association meta-analysis of internalising symptoms included repeated observations from 64,641 individuals, aged between 3 and 18. The N-weighted meta-analysis of overall internalising symptoms (INToverall) detected no genome-wide significant hits and showed low SNP heritability (1.66%, 95% confidence intervals 0.84-2.48%, Neffective=132,260). Stratified analyses indicated rater-based heterogeneity in genetic effects, with self-reported internalising symptoms showing the highest heritability (5.63%, 95% confidence intervals 3.08-8.18%). Additive genetic effects on internalising symptoms appeared stable over age, with overlapping estimates of SNP heritability from early-childhood to adolescence. Genetic correlations were observed with adult anxiety, depression, and the wellbeing spectrum (|rg|> 0.70), as well as with insomnia, loneliness, attention-deficit hyperactivity disorder, autism, and childhood aggression (range |rg|=0.42-0.60), whereas there were no robust associations with schizophrenia, bipolar disorder, obsessive-compulsive disorder, or anorexia nervosa. The pattern of genetic correlations suggests that childhood and adolescent internalising symptoms share substantial genetic vulnerabilities with adult internalising disorders and other childhood psychiatric traits, which could partially explain both the persistence of internalising symptoms over time and the high comorbidity amongst childhood psychiatric traits. Reducing phenotypic heterogeneity in childhood samples will be key in paving the way to future GWAS success.

We study spin-1/2 fermions in spin dependent potentials under the \emph{spin model approximation}, in which interatomic collisions that change the total occupation of single-particle modes are ignored. The spin model approximation maps the interacting fermion problem to an ensemble of lattice spin models in energy space, where spin-spin interactions are long-ranged and spin-anisotropic. We show that the spin model approximation is accurate for weak interactions compared to the harmonic oscillator frequency, and captures the collective spin dynamics to timescales much longer than would be expected from perturbation theory. We explore corrections to the spin model, and the relative importance of corrections when realistic anharmonic potential corrections are taken into account. Additionally, we present numerical techniques that are useful for analysis of spin models on an energy lattice, including enacting a change of single-particle basis on a many-body state as an effective time evolution, and fitting of spatially inhomogeneous long-range interactions with exponentials. This latter technique is useful for constructing matrix product operators for use in DMRG analyses, and may have broader applicability within the tensor network community., Comment: 16 pages, 13 figures

Good Agricultural Practices (GAPs) training programs were developed to provide guidance to fruit and vegetable growers on how to reduce food safety risks on the farm. These programs have been enhanced over the years due, in part, to increasing buyer and regulatory requirements. However, the costs of implementing additional food safety practices has been identified as a primary barrier to long-term farm financial feasibility, particularly for smaller scale producers. A survey of past participants in New York State revealed that increasing food safety improvements facilitated by GAPs have not significantly impacted the size of farm operations or the types of crops grown. In terms of farm size, we show that both the financial costs and financial benefits of food safety improvements increase with farm size, but at decreasing rates. In so doing, relatively higher market sales gains per acre by smaller farms from additional food safety investments offset the relatively higher costs to them of their implementation. We also demonstrate that benefits of food safety improvements were significantly higher for farms that had third-party food safety audits and for those that market primarily through wholesale channels. The results should prove welcome by educators as they encourage participation by all scales of producers in GAPs trainings and for growers in understanding that food safety investments can support both reduced microbial risks and sales growth.

Background and AimsThe incidence of inflammatory bowel disease [IBD] is rising worldwide and no cure is available. Many patients require surgery and they often present with nutritional deficiencies. Although randomised controlled trials of dietary therapy are lacking, expert IBD centres have long-established interdisciplinary care, including tailored nutritional therapy, to optimise clinical outcomes and resource utilisation. This topical review aims to share expertise and offers current practice recommendations to optimise outcomes of IBD patients who undergo surgery.MethodsA consensus expert panel consisting of dietitians, surgeons, and gastroenterologists, convened by the European Crohn’s and Colitis Organisation, performed a systematic literature review. Nutritional evaluation and dietary needs, perioperative optimis ation, surgical complications, long-term needs, and special situations were critically appraised. Statements were developed using a Delphi methodology incorporating three successive rounds. Current practice positions were set when ≥80% of participants agreed on a recommendation.ResultsA total of 26 current practice positions were formulated which address the needs of IBD patients perioperatively and in the long term following surgery. Routine screening, perioperative optimisation by oral, enteral, or parenteral nutrition, dietary fibre, and supplements were reviewed. IBD-specific situations, including management of patients with a restorative proctocolectomy, an ostomy, strictures, or short-bowel syndrome, were addressed.ConclusionsPerioperative dietary therapy improves the outcomes of IBD patients who undergo a surgical procedure. This topical review shares interdisciplinary expertise and provides guidance to optimise the outcomes of patients with Crohn’s disease and ulcerative colitis. taking advantage of contemporary nutrition science.