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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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OBJECTIVE The primary objective of this trial was to determine if shunt entry site affects the risk of shunt failure. METHODS The authors performed a parallel-design randomized controlled trial with an equal allocation of patients who received shunt placement via the anterior entry site and patients who received shunt placement via the posterior entry site. All patients were children with symptoms or signs of hydrocephalus and ventriculomegaly. Patients were ineligible if they had a prior history of shunt insertion. Patients received a ventriculoperitoneal shunt after randomization; randomization was stratified by surgeon. The primary outcome was shunt failure. The planned minimum follow-up was 18 months. The trial was designed to achieve high power to detect a 10% or greater absolute difference in the shunt failure rate at 1 year. An independent, blinded adjudication committee determined eligibility and the primary outcome. The study was conducted by the Hydrocephalus Clinical Research Network. RESULTS The study randomized 467 pediatric patients at 14 tertiary care pediatric hospitals in North America from April 2015 to January 2019. The adjudication committee, blinded to intervention, excluded 7 patients in each group for not meeting the study inclusion criteria. For the primary analysis, there were 229 patients in the posterior group and 224 patients in the anterior group. The median patient age was 1.3 months, and the most common etiologies of hydrocephalus were postintraventricular hemorrhage secondary to prematurity (32.7%), myelomeningocele (16.8%), and aqueductal stenosis (10.8%). There was no significant difference in the time to shunt failure between the entry sites (log-rank test, stratified by age < 6 months and ≥ 6 months; p = 0.061). The hazard ratio (HR) of a posterior shunt relative to an anterior shunt was calculated using a univariable Cox regression model and was nonsignificant (HR 1.35, 95% CI, 0.98–1.85; p = 0.062). No significant difference was found between entry sites for the surgery duration, number of ventricular catheter passes, ventricular catheter location, and hospital length of stay. There were no significant differences between entry sites for intraoperative complications, postoperative CSF leaks, pseudomeningoceles, shunt infections, skull fractures, postoperative seizures, new-onset epilepsy, or intracranial hemorrhages. CONCLUSIONS This randomized controlled trial comparing the anterior and posterior shunt entry sites has demonstrated no significant difference in the time to shunt failure. Anterior and posterior entry site surgeries were found to have similar outcomes and similar complication rates.

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.

OBJECTIVE Hydrocephalus can impact all areas of health, including physical, cognitive, and social-emotional functioning. The social-emotional health of children who have had surgery for hydrocephalus is not well characterized. In this study, the authors sought to examine social-emotional functioning using the Behavior Assessment System for Children, Third Edition (BASC-3) and the Hydrocephalus Outcome Questionnaire (HOQ) in 66 children aged 5 to 17 years. METHODS Caregivers of pediatric patients with hydrocephalus completed the BASC-3 and the HOQ. BASC-3 internalizing, externalizing, and executive functioning caregiver-reported scores were compared with the BASC-3 normative sample using one-sample t-tests to evaluate overall social-emotional functioning. BASC-3 scores were correlated with the social-emotional domain of the HOQ using Pearson’s r to determine if the HOQ accurately captured the social-emotional functioning of children with hydrocephalus in a neurosurgery setting. BASC-3 and HOQ scores of children with different etiologies of hydrocephalus were compared using the Kruskal-Wallis one-way analysis of variance to determine if differences existed between the following etiologies: intraventricular hemorrhage secondary to prematurity, myelomeningocele, communicating congenital hydrocephalus, aqueductal stenosis, or other. RESULTS Children with hydrocephalus of all etiologies had more difficulties with social-emotional functioning compared with normative populations. Children with different hydrocephalus etiologies differed in executive functioning and overall HOQ scores but not in internalizing symptoms, externalizing symptoms, or social-emotional HOQ scores. The social-emotional domain of the HOQ correlated more strongly with the BASC-3 than did the physical and cognitive domains. CONCLUSIONS These results have provided evidence that children who have had surgery for hydrocephalus may be at increased risk of social-emotional and behavioral difficulties, but etiology may not be particularly helpful in predicting what kinds or degree of difficulty. The results of this study also support the convergent and divergent validity of the social-emotional domain of the HOQ.

Background and Aims Patients with inflammatory bowel disease [IBD] are often affected during their reproductive years and may have many perinatal queries that require the comprehensive perspectives of a multidisciplinary team [MDT]. The purpose of this topical review is to assess the scientific evidence and provide expert opinion related to nutritional, psychological and supportive care of women and their infants throughout the prenatal, antenatal and infant periods. Methods A consensus expert panel of a paediatrician, gastroenterologists, nurses and dietitians was convened by the European Crohn’s and Colitis Organisation. This panel critically reviewed literature related to the non-medical management of patients with IBD during preconception, pregnancy, the postnatal period and the first years of the infant’s life. Statements were developed using an e-Delphi process over two rounds and were confirmed when ≥80% of experts agreed with the statements. Results A total of 19 current practice positions were developed that cover the preconception period, pregnancy and lactation, and early-life exposures associated with risk of IBD. Development of the infant microbiome and its role in the immune system and topics including nutritional optimization, psychological support and education relating to early life were reviewed. Conclusions Patients with IBD have unique nutritional and psychosocial needs that may affect fertility and pregnancy outcomes. The early-life environment of infants born to parents with IBD may be associated with subsequent development of IBD in offspring. An MDT is the optimal setting to support and counsel patients throughout the perinatal period.

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.

Biaryl phosphorinane ligands derived from addition of biaryl primary phosphines to trans,trans-dibenzylideneacetone (AlisonPhos and AliPhos) form highly active ligands for Pd-catalyzed coupling of ...

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.

Endomyocardial biopsy (EMB) is a common procedure used to aid in the diagnosis of diffuse myocardial diseases and, less commonly, in the diagnosis of cardiac tumors. As cardiac tumors are often found in high-risk locations (ventricular free wall or atria), precision biopsy is paramount, and additional imaging, like transesophageal echocardiography is often required for guidance. The use of intracardiac echocardiography (ICE) to guide biopsy has been described, but there is no consensus on a standardized approach. We report our institutional approach with three cases of ICE-directed EMB performed with the 2.4 mm Jawz bioptome directed with an 8.5-Fr Agilis NxT steerable introducer. All cases were performed under guidance with the AcuNav ICE probe. There were no procedural complications and a definitive diagnosis was obtained in all three cases. We also review the available published cases of ICE-guided EMB in the literature-noting the different procedural approaches, complication rate, and diagnostic yield. There were only two negative biopsies reported among the published cases and no reported complications. Our review of all these cases suggests that ICE-guidance for EMB is superior to other forms of imaging in its ease of use and high definition of right-sided cardiac structures. We also feel that the use of the Agilis steerable sheath allows for more precise directing of the bioptome and is a critical component in performing a successful targeted biopsy.

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.

When taught a label for an object, and later asked whether that object or a novel object is the referent of a novel label, preschoolers favor the novel object. This article examines whether this so-called disambiguation effect may be undermined by an expectation to communicate about a discovery. This expectation may explain why 4-year-olds do not show the disambiguation effect if a sense modality shift occurs between training and test. In Study 1, 3- and 4-year-olds learned a label for a visible object, then examined two hidden objects manually and predicted which one they would be asked about. Only the older group predicted that they would be asked about the object that matched the visible object. Study 1 also included a test of the standard disambiguation effect, where both the training and test objects were visible. Both 3- and 4-year-olds showed a weaker disambiguation effect in this test when the matching object was unexpected rather than expected. In Study 2, both age groups predicted they would be asked about this object when it was unexpected. In Study 3, both age groups showed a stronger disambiguation effect when allowed to communicate about this object before deciding which object was the referent of a novel label. Metacognitive ability predicted the strength of this disambiguation effect even after controlling for age and inhibitory control. The article discusses various explanations for why only 4-year-olds abided by the pragmatics of discovery in the test of the cross-modal disambiguation effect, but both 3- and 4-year-olds abided by it in the test of the standard disambiguation effect.

Malnutrition is common in patients with Crohn's disease and negatively influences immunity and quality of life. The optimal tools for nutrition assessment in patients with Crohn's disease are not clearly defined and lead to variations in practice. With this review, we aimed to appraise the existing evidence for nutrition assessment of patients with Crohn's disease compared with healthy controls and provide a comprehensive guide with relevant measures applicable to clinical practice. A literature search using Medline, Embase, and Scopus from inception to October 1, 2018, was conducted. Forty-one articles that assessed body composition, muscle strength, micronutrient status and/or dietary intake in adults with Crohn's disease compared with an age- and sex-matched healthy individuals were included. There were heterogeneous findings on nutritional status in patients with Crohn's disease compared with healthy controls. Only one article reported a clinically significant difference for body mass index; however, significant deficits in fat mass, fat-free mass, and muscle strength were observed in patients with Crohn's disease compared with healthy controls, with more pronounced differences with increasing disease activity and length of diagnosis. Most research reported significantly lower serum micronutrients in patients with Crohn's disease compared with healthy controls. Half of studies measuring micronutrient intake reported lower intakes in patients with Crohn's disease compared with healthy controls. Fruit and vegetable intake was also lower in patients with Crohn's disease. Difficulties characterizing the type and prevalence of malnutrition exist due to the heterogeneous nature of Crohn's disease and warrants continued investigation. As a result of this review, we advocate that a nutrition assessment should include more parameters than weight and body mass index.

[ ]he tracks the text's rediscovery and reinvention over the course of the 20th century According to Rodgers, the "shining city on a hill" ultimately popularized by President Ronald Reagan bore little resemblance to the exposed and anxious city of which Winthrop wrote [ ]there is little evidence that Winthrop gave this speech on the Arbella or that he delivered the "Model" as a sermon at all [ ]very few Americans who deployed ideas or phrases like "chosen people," "city on a hill," "manifest destiny," or global "mission" in the years before World War I would, or even could, have read Winthrop's text

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.