Three linked variants have opposing regulatory effects on isovaleryl-CoA dehydrogenase gene expression.

While genome-wide association studies (GWAS) and positive selection scans identify genomic loci driving human phenotypic diversity, functional validation is required to discover the variant(s) responsible. We dissected the IVD gene locus-which encodes the isovaleryl-CoA dehydrogenase enzyme-implicated by selection statistics, multiple GWAS, and clinical genetics as important to function and fitness. We combined luciferase assays, CRISPR/Cas9 genome-editing, massively parallel reporter assays (MPRA), and a deletion tiling MPRA strategy across regulatory loci. We identified three regulatory variants, including an indel, that may underpin GWAS signals for pulmonary fibrosis and testosterone, and that are linked on a positively selected haplotype in the Japanese population. These regulatory variants exhibit synergistic and opposing effects on IVD expression experimentally. Alleles at these variants lie on a haplotype tagged by the variant most strongly associated with IVD expression and metabolites, but with no functional evidence itself. This work demonstrates how comprehensive functional investigation and multiple technologies are needed to discover the true genetic drivers of phenotypic diversity.

Organoid single-cell genomic atlas uncovers human-specific features of brain development.

The human brain has undergone substantial change since humans diverged from chimpanzees and the other great apes1,2. However, the genetic and developmental programs that underlie this divergence are not fully understood. Here we have analysed stem cell-derived cerebral organoids using single-cell transcriptomics and accessible chromatin profiling to investigate gene-regulatory changes that are specific to humans. We first analysed cell composition and reconstructed differentiation trajectories over the entire course of human cerebral organoid development from pluripotency, through neuroectoderm and neuroepithelial stages, followed by divergence into neuronal fates within the dorsal and ventral forebrain, midbrain and hindbrain regions. Brain-region composition varied in organoids from different iPSC lines, but regional gene-expression patterns remained largely reproducible across individuals. We analysed chimpanzee and macaque cerebral organoids and found that human neuronal development occurs at a slower pace relative to the other two primates. Using pseudotemporal alignment of differentiation paths, we found that human-specific gene expression resolved to distinct cell states along progenitor-to-neuron lineages in the cortex. Chromatin accessibility was dynamic during cortex development, and we identified divergence in accessibility between human and chimpanzee that correlated with human-specific gene expression and genetic change. Finally, we mapped human-specific expression in adult prefrontal cortex using single-nucleus RNA sequencing analysis and identified developmental differences that persist into adulthood, as well as cell-state-specific changes that occur exclusively in the adult brain. Our data provide a temporal cell atlas of great ape forebrain development, and illuminate dynamic gene-regulatory features that are unique to humans.

Effectiveness of nurse-home visiting in improving child and maternal outcomes prenatally to age two years: a randomised controlled trial (British Columbia Healthy Connections Project).

BACKGROUND: We investigated the effectiveness of Nurse-Family Partnership (NFP), a prenatal-to-age-two-years home-visiting programme, in British Columbia (BC), Canada. METHODS: For this randomised controlled trial, we recruited participants from 26 public health settings who were: <25 years, nulliparous, <28 weeks gestation and experiencing socioeconomic disadvantage. We randomly allocated participants (one-to-one; computer-generated) to intervention (NFP plus existing services) or comparison (existing services) groups. Prespecified outcomes were prenatal substance exposure (reported previously); child injuries (primary), language, cognition and mental health (problem behaviour) by age two years; and subsequent pregnancies by 24 months postpartum. Research interviewers were masked. We used intention-to-treat analyses. (ClinicalTrials.gov, NCT01672060.) RESULTS: From 2013 to 2016 we enrolled 739 participants (368 NFP, 371 comparison) who had 737 children. Counts for child injury healthcare encounters [rate per 1,000 person-years or RPY] were similar for NFP (223 [RPY 316.17]) and comparison (223 [RPY 305.43]; rate difference 10.74, 95% CI -46.96, 68.44; rate ratio 1.03, 95% CI 0.78, 1.38). Maternal-reported language scores (mean, M [SD]) were statistically significantly higher for NFP (313.46 [195.96]) than comparison (282.77 [188.15]; mean difference [MD] 31.33, 95% CI 0.96, 61.71). Maternal-reported problem-behaviour scores (M [SD]) were statistically significantly lower for NFP (52.18 [9.19]) than comparison (54.42 [9.02]; MD -2.19, 95% CI -3.62, -0.75). Subsequent pregnancy counts were similar (NFP 115 [RPY 230.69] and comparison 117 [RPY 227.29]; rate difference 3.40, 95% CI -55.54, 62.34; hazard ratio 1.01, 95% CI 0.79, 1.29). We observed no unanticipated adverse events. CONCLUSIONS: NFP did not reduce child injuries or subsequent maternal pregnancies but did improve maternal-reported child language and mental health (problem behaviour) at age two years. Follow-up of long-term outcomes is warranted given that further benefits may emerge across childhood and adolescence.

Comparing the reliability and validity of youth-reported checklists and standardized interviews for categorical measurement of emotional and behavioral problems.

INTRODUCTION: Self-completed checklists measuring youth mental health problems produce dimensional scale scores and can be converted to categorical classifications representing the presence/absence of psychopathology. We test whether categorical classifications from scale scores are equivalent psychometrically to categorical classifications of the same problems obtained by lay-administered standardized structured diagnostic interviews. METHODS: The sample of n = 325 youth aged 12-18 (44% male) and their parent/caregivers come from combined test-retest reliability studies conducted in Ontario, Canada, from 2011 to 2015. Ontario Child Health Study Emotional Behavioural Scales-Brief Version (OCHS-EBS-B) scores converted to categorical classifications of emotional and behavioral problems were compared with interview classifications. We test hypotheses of statistical equivalence and inferiority, using a confidence interval approach to detect if differences lie within the smallest effect size of interest of ±0.18. We compare categorical classifications on: (1) test-retest reliability (Ò¡), (2) content validity (between-instrument agreement), and (3) construct validity (strength of association with three mental health-related constructs). RESULTS: Average test-retest reliabilities were 0.695 (checklists) and 0.670 (interviews). The reliability of checklist emotional problem classifications was not inferior to interview classifications and the difference in reliability between instruments for behavioral problems was small (-0.036). Average between-instrument agreement was Ò¡ = 0.586 (observed) and Ò¡ = 0.841 (corrected for attenuation due to measurement error) indicating high content overlap. Statistical equivalence criteria were met in 5 of 6 construct validity comparisons. CONCLUSIONS: Categorical classifications of emotional and behavioral problems from youth-reported checklists are, on balance, equivalent to interview classifications. Checklists represent a simple, brief, inexpensive alternative to interviews.

Problem checklists and standardized diagnostic interviews: evidence of psychometric equivalence for classifying psychiatric disorder among children and youth in epidemiological studies.

BACKGROUND: The standard approach for classifying child/youth psychiatric disorder as present or absent in epidemiological studies is lay-administered structured, standardized diagnostic interviews (interviews) based on categorical taxonomies such as the DSM and ICD. Converting problem checklist scale scores (checklists) to binary classifications provides a simple, inexpensive alternative. METHODS: Using assessments obtained from 737 parents, we determine if child/youth behavioral, attentional, and emotional disorder classifications based on checklists are equivalent psychometrically to interview classifications. We test this hypothesis by (1) comparing their test-retest reliabilities based on kappa (κ), (2) estimating their observed agreement at times 1 and 2, and (3) in structural equation models, comparing their strength of association with clinical status and reported use of prescription medication to treat disorder. A confidence interval approach is used to determine if parameter differences lie within the smallest effect size of interest set at ±0.125. RESULTS: The test-retest reliabilities (κ) for interviews compared with checklists met criteria for statistical equivalence: behavioral, .67 and .70; attentional, .64 and .66; and emotional, .61 and .65. Observed agreement between the checklist and interviews on classifications of disorder at times 1 and 2 was, on average, κ = .61. On average, the ß coefficients estimating associations with clinical status were .59 (interviews) and .63 (checklists); and with prescription medication use, .69 (interviews) and .71 (checklists). Behavioral and attentional disorders met criteria for statistical equivalence. Emotional disorder did not, although the coefficients were stronger numerically for the checklist. CONCLUSIONS: Classifications of child/youth psychiatric disorder from parent-reported checklists and interviews are equivalent psychometrically. The practical advantages of checklists over interviews for classifying disorder (lower administration cost and respondent burden) are enhanced by their ability to measure disorder dimensionally. Checklists provide an option to interviews in epidemiological studies of common child/youth psychiatric disorders.

The full blood count in screening asymptomatic infants for early-onset sepsis: A cross-sectional study.

AIM: The full blood count (FBC) is commonly measured as part of a partial septic work-up in asymptomatic infants at increased risk of early-onset neonatal sepsis (EOS). To determine the impact of FBC parameters on infants' subsequent management a retrospective cross-sectional study was performed. METHODS: Infants, born at ≥34 weeks gestation, asymptomatic at birth, undergoing a partial septic work-up and receiving prophylactic antibiotics due to increased risk of EOS in a single centre over a 2-year period, were included. The primary outcome measure was frequency of FBC result impacting on duration of antibiotic therapy. Secondary outcome measures included frequency of FBC parameters outside of the reference range and incidental diagnoses. RESULTS: In total, 16 726 live-born infants were delivered during the study period. A total of 802 (4.8%) were included. Thirteen infants (1.6%) received a prolonged course of antibiotics due to suspicion for EOS. Two of these infants had elevated white cell counts. All had normal neutrophil counts. In no case did the FBC result influence the decision to prolong the antibiotic course. CONCLUSION: In a cohort of 802 infants, asymptomatic at birth and at increased risk of EOS, the FBC result did not impact on the decision to prolong the course of antibiotics for suspicion of EOS.

Hemodynamic and metabolic correspondence of resting-state voxel-based physiological metrics in healthy adults.

Voxel-based physiological (VBP) variables derived from blood oxygen level dependent (BOLD) fMRI time-course variations include: amplitude of low frequency fluctuations (ALFF), fractional amplitude of low frequency fluctuations (fALFF) and regional homogeneity (ReHo). Although these BOLD-derived variables can detect between-group (e.g. disease vs control) spatial pattern differences, physiological interpretations are not well established. The primary objective of this study was to quantify spatial correspondences between BOLD VBP variables and PET measurements of cerebral metabolic rate and hemodynamics, being well-validated physiological standards. To this end, quantitative, whole-brain PET images of metabolic rate of glucose (MRGlu; 18FDG) and oxygen (MRO2; 15OO), blood flow (BF; H215O) and blood volume (BV; C15O) were obtained in 16 healthy controls. In the same subjects, BOLD time-courses were obtained for computation of ALFF, fALFF and ReHo images. PET variables were compared pair-wise with BOLD variables. In group-averaged, across-region analyses, ALFF corresponded significantly only with BV (R = 0.64; p < 0.0001). fALFF corresponded most strongly with MRGlu (R = 0.79; p < 0.0001), but also significantly (p < 0.0001) with MRO2 (R = 0.68), BF (R = 0.68) and BV (R=0.68). ReHo performed similarly to fALFF, with significant strong correspondence (p < 0.0001) with MRGlu (R = 0.78), MRO2 (R = 0.54), and, but less strongly with BF (R = 0.50) and BV (R=0.50). Mutual information analyses further clarified these physiological interpretations. When conditioned by BV, ALFF retained no significant MRGlu, MRO2 or BF information. When conditioned by MRGlu, fALFF and ReHo retained no significant MRO2, BF or BV information. Of concern, however, the strength of PET-BOLD correspondences varied markedly by brain region, which calls for future investigation on physiological interpretations at a regional and per-subject basis.

Sampling multiple life stages significantly increases estimates of marine biodiversity.

Biodiversity assessments are critical for setting conservation priorities, understanding ecosystem function and establishing a baseline to monitor change. Surveys of marine biodiversity that rely almost entirely on sampling adult organisms underestimate diversity because they tend to be limited to habitat types and individuals that can be easily surveyed. Many marine animals have planktonic larvae that can be sampled from the water column at shallow depths. This life stage often is overlooked in surveys but can be used to relatively rapidly document diversity, especially for the many species that are rare or live cryptically as adults. Using DNA barcode data from samples of nemertean worms collected in three biogeographical regions-Northeastern Pacific, the Caribbean Sea and Eastern Tropical Pacific-we found that most species were collected as either benthic adults or planktonic larvae but seldom in both stages. Randomization tests show that this deficit of operational taxonomic units collected as both adults and larvae is extremely unlikely if larvae and adults were drawn from the same pool of species. This effect persists even in well-studied faunas. These results suggest that sampling planktonic larvae offers access to a different subset of species and thus significantly increases estimates of biodiversity compared to sampling adults alone. Spanish abstract is available in the electronic supplementary material.

Biochemical testing for inborn errors of metabolism: experience from a large tertiary neonatal centre.

Inborn errors of metabolism are an individually rare but collectively significant cause of mortality and morbidity in the neonatal period. They are identified by either newborn screening programmes or clinician-initiated targeted biochemical screening. This study examines the relative contribution of these two methods to the identification of inborn errors of metabolism and describes the incidence of these conditions in a large, tertiary, neonatal unit. We also examined which factors could impact the reliability of metabolic testing in this cohort. This is a retrospective, single-site study examining infants in whom a targeted metabolic investigation was performed from January 2018 to December 2020 inclusive. Data was also provided by the national newborn screening laboratory regarding newborn screening diagnoses. Two hundred and four newborns received a clinician-initiated metabolic screen during the time period examined with 5 newborns being diagnosed with an inborn error of metabolism (IEM) (2.4%). Of the 25,240 infants born in the hospital during the period examined, a further 11 newborns had an inborn error of metabolism diagnosed on newborn screening. This produced an incidence in our unit over the time described of 6.34 per 10,000 births. This number reflects a minimum estimate, given that the conditions diagnosed refer to early-onset disorders and distinctive categories of IEM only. Efficiency of the clinician-initiated metabolic screening process was also examined. The only statistically significant variable in requiring repeat metabolic screening was early day of life (z-score = - 2.58, p = 0.0098). A total of 28.4% was missing one of three key metabolic investigation parameters of blood glucose, ammonia or lactate concentration with ammonia the most common investigation missing. While hypoglycemia was the most common clinical rationale for a clinician-initiated metabolic test, it was a poor predictor of inborn error of metabolism with no newborns of 25 screened were diagnosed with a metabolic disorder. CONCLUSION: Clinician-targeted metabolic screening had a high diagnostic yield given the relatively low prevalence of inborn errors of metabolism in the general population. Thoughts should be given to the rationale behind each targeted metabolic test and what specific metabolic disease or category of inborn error of metabolism they are concerned along with commencing targeted testing. WHAT IS KNOWN: • Inborn errors of metabolism are a rare but potentially treatable cause of newborn mortality and morbidity. • A previous study conducted in a tertiary unit in an area with limited newborn screening demonstrated a diagnostic yield of 5.4%. WHAT IS NEW: • Clinician-initiated targeted metabolic screening has a good diagnostic performance even with a more expanded newborn screening programme. • Further optimisation could be achieved by examining the best timing and also the rationale of metabolic testing in the newborn period.

The 25-Item Ontario Child Health Study Emotional Behavioural Scales-Brief Version (OCHS-EBS-B): Test-Retest Reliability and Construct Validity When Used as Categorical Measures.

OBJECTIVE: Child and youth mental health problems are often assessed by parent self-completed checklists that produce dimensional scale scores. When converted to binary ratings of disorder, little is known about their psychometric properties in relation to classifications based on lay-administered structured diagnostic interviews. In addition to estimating agreement, our objective is to test for statistical equivalence in the test-retest reliability and construct validity of two instruments used to classify child emotional, behavioural, and attentional disorders: the 25-item, parent completed Ontario Child Health Study Emotional Behavioural Scales-Brief Version (OCHS-EBS-B) and the Mini International Neuropsychiatric Interview for Children and Adolescents-parent version (MINI-KID-P). METHODS: This study draws on independent samples (n = 452) and uses the confidence interval approach to test for statistical equivalence. Reliability is based on kappa (κ). Construct validity is based on standardized beta coefficients (ß) estimated in structural equation models. RESULTS: The average differences between the MINI-KID-P and OCHS-EBS-B in κ and ß were -0.022 and -0.020, respectively. However, in both instances, criteria for statistical equivalence were met in only 5 of 12 comparisons. Based on κ, between-instrument agreement on the classifications of disorder went from 0.481 (attentional disorder) to 0.721 (emotional disorder) but were substantially higher (0.731 to 0.895, respectively) when corrected for attenuation due to measurement error. CONCLUSIONS: Although falling short of equivalence, the results suggest on balance that the reliability and validity of the two instruments for classifying child psychiatric disorder assessed by parents are highly comparable. This conclusion is supported by the high levels of agreement between the instruments after correcting for attenuation due to measurement error.

Feeding practices and the prevalence of cow's milk protein allergy in Irish preterm infants.

BACKGROUND: The prevalence of cow's-milk protein allergy (CMPA) is between 2% and 3% and symptoms vary depending on underlying immune mechanism at play. Breast milk is the optimal nutrition for premature infants and breast milk fortifiers (BMF) are commonly used to optimise growth and nutrition. BMF are typically derived from cow's milk and, as such, preterm infants are exposed to cow's milk in the first weeks of life. Previously, preterm infants were suspected to have a higher risk of allergen development because of early antigen exposure and increased gut permeability. The primary aim of the present study was to evaluate the prevalence of CMPA among very preterm (<32 weeks) and/or very low birth weight (VLBW) infants. The secondary aim was to describe feeding practices, specifically the breastfeeding rates and specialist, non-standard formula use in this cohort over the first 6 months of life. METHODS: This was a retrospective study performed in a large tertiary maternity hospital (8500 deliveries/year and 110 very preterm infants/year) in Dublin, Ireland over a 3-year period, 2017-2020. Infants born very preterm and/or VLBW who were followed in the outpatient clinic until 6 months corrected gestational age (CGA) were included. Hospital ethical approval was obtained. RESULTS: One hundred and forty-four infants were included with a median birth weight of 1338 g. No infant had a diagnosis of CMPA when leaving the neonatal intensive care unit (NICU) but, by 6 months CGA, this increased to 1.4% (n = 2). Upon discharge from the NICU, 88 infants (61%) were receiving at least some breast milk, decreasing to 13 (9.1%) at 6 months CGA. Those who were receiving exclusive breast milk at discharge were significantly more likely to still be receiving any breast milk at three (p ≤ 0.001) and 6 months ( p ≤ 0.001) CGA compared to those combined feeding or exclusively formula feeding. At 6 months CGA, 18.9% (n = 27) were attending a dietician and 31.5% (n = 45) were using specialist, non-standard infant formula. CONCLUSIONS: The prevalence of CMPA in this cohort was 1.4%, which is similar to the reported prevalence of CMPA in the general paediatric population. Infants who were discharged from NICU exclusively breastfeeding were more likely to be receiving any breast milk at outpatient follow-up. This highlights the importance of on going dietetic and lactation support in the outpatient setting for this vulnerable cohort.

Imputation of canine genotype array data using 365 whole-genome sequences improves power of genome-wide association studies.

Genomic resources for the domestic dog have improved with the widespread adoption of a 173k SNP array platform and updated reference genome. SNP arrays of this density are sufficient for detecting genetic associations within breeds but are underpowered for finding associations across multiple breeds or in mixed-breed dogs, where linkage disequilibrium rapidly decays between markers, even though such studies would hold particular promise for mapping complex diseases and traits. Here we introduce an imputation reference panel, consisting of 365 diverse, whole-genome sequenced dogs and wolves, which increases the number of markers that can be queried in genome-wide association studies approximately 130-fold. Using previously genotyped dogs, we show the utility of this reference panel in identifying potentially novel associations, including a locus on CFA20 significantly associated with cranial cruciate ligament disease, and fine-mapping for canine body size and blood phenotypes, even when causal loci are not in strong linkage disequilibrium with any single array marker. This reference panel resource will improve future genome-wide association studies for canine complex diseases and other phenotypes.

Infectious Complications of Biological and Small Molecule Targeted Immunomodulatory Therapies.

The past 2 decades have seen a revolution in our approach to therapeutic immunosuppression. We have moved from relying on broadly active traditional medications, such as prednisolone or methotrexate, toward more specific agents that often target a single receptor, cytokine, or cell type, using monoclonal antibodies, fusion proteins, or targeted small molecules. This change has transformed the treatment of many conditions, including rheumatoid arthritis, cancers, asthma, and inflammatory bowel disease, but along with the benefits have come risks. Contrary to the hope that these more specific agents would have minimal and predictable infectious sequelae, infectious complications have emerged as a major stumbling block for many of these agents. Furthermore, the growing number and complexity of available biologic agents makes it difficult for clinicians to maintain current knowledge, and most review articles focus on a particular target disease or class of agent. In this article, we review the current state of knowledge about infectious complications of biologic and small molecule immunomodulatory agents, aiming to create a single resource relevant to a broad range of clinicians and researchers. For each of 19 classes of agent, we discuss the mechanism of action, the risk and types of infectious complications, and recommendations for prevention of infection.

Review of flipped learning in engineering education: Scientific mapping and research horizon.

The COVID-19 pandemic makes flipped learning more relevant to address the challenges of remote learning. Therefore, renewed attention is warranted in critically appraising the implications on which flipped learning is built. Though several studies have reviewed the flipped learning research in the past, the majority has qualitatively synthesized the flipped learning literature, thus, lacking the overall perspective provided quantitatively for appraising the existing state of affairs of flipped learning research in engineering education. This study addresses this gap by objectively mapping the conceptual, intellectual, and social structure of research development in flipped learning using a bibliometric review method. Findings reveal that flipped learning in engineering education is a relatively new field of research and in recent time it has entered into the stage of exponential growth. Findings also show the effectiveness of the flipped learning model to address the challenges of complex pedagogical applications in different fields of engineering education. This study provides a quantitative synopsis of the flipped learning literature which can be used as an anchor for future study.

Validation of T2 -based oxygen extraction fraction measurement with 15 O positron emission tomography.

PURPOSE: To evaluate the accuracy of T2 -based whole-brain oxygen extraction fraction (OEF) estimation by comparing it with gold standard 15 O-PET measurements. METHODS: Sixteen healthy adult subjects underwent MRI and 15 O-PET OEF measurements on the same day. On MRI, whole-brain OEF was quantified by T2 -relaxation-under-spin-tagging (TRUST) MRI, based on subject-specific hematocrit. The TRUST OEF was compared to the whole-brain averaged OEF produced by 15 O-PET. Agreement between TRUST and 15 O-PET whole-brain OEF measurements was examined in terms of intraclass correlation coefficient (ICC) and in absolute OEF values. In a subset of 10 subjects, test-retest reproducibility of whole-brain OEF was also evaluated and compared between the two modalities. RESULTS: Across the 16 subjects, the mean whole-brain OEF of TRUST and 15 O-PET were 36.44 ± 4.07% and 36.45 ± 3.65%, respectively, showing no difference between the two modalities (P = .99). TRUST whole-brain OEF strongly correlated with that of 15 O-PET (N = 16, ICC = 0.90, P = 4 × 10-7 ). The coefficient-of-variation of TRUST and 15 O-PET whole-brain OEF measurements were 1.79 ± 0.67% and 2.06 ± 1.55%, respectively, showing no difference between the two modalities (N = 10, P = .64). Further analyses on the effect of hematocrit revealed that correlation between PET OEF and TRUST OEF with assumed hematocrit remained significant (ICC = 0.8, P < 2 × 10-5 ). CONCLUSION: Whole-brain OEF measured by TRUST was in excellent agreement with gold standard 15 O-PET, with highly comparable accuracy and reproducibility. These findings suggest that TRUST MRI can provide accurate quantification of whole-brain OEF noninvasively.

Nurse-Family Partnership nurses' attitudes and confidence in identifying and responding to intimate partner violence: An explanatory sequential mixed methods evaluation.

AIMS: To evaluate the effect of an intimate partner violence intervention education component on nurses' attitudes in addressing intimate partner violence; complementary aims included understanding nurses' perceptions of the education and how it influenced their attitudes and confidence to address intimate partner violence in practice. DESIGN: An explanatory sequential mixed methods design embedded within a 15-site cluster randomized clinical trial that evaluated an intimate partner violence intervention within the Nurse-Family Partnership programme. METHODS: Data were collected between February 2011 and September 2016. Quantitative assessment of nurses' attitudes about addressing intimate partner violence was completed by nurses in the intervention (n = 77) and control groups (n = 101) at baseline, 12 months and at study closure using the Public Health Nurses' Responses to Women Who Are Abused Scale. Qualitative data were collected from nurses in the intervention group at two timepoints (n = 14 focus groups) and focused on their perceptions of the education component. Data were analysed using content analysis. RESULTS: Nurses in the intervention group reported large improvements in their thoughts, feelings and perceived behaviours related to addressing intimate partner violence; a strong effect of the education was found from baseline to 12 months and baseline to study closure timepoints. Nurses reported that the education component was acceptable and increased their confidence to address intimate partner violence. CONCLUSION: Nurses reported improved attitudes about and confidence in addressing intimate partner violence after receiving the education component. However, these findings need to be considered together with trial results showing no main effects for clients, and a low level of intervention fidelity. IMPACT: These evaluation findings underscore that improvement in nurses' self-reported educational outcomes about addressing intimate partner violence cannot be assumed to result in adherence to intervention implementation or improvement in client outcomes. These are important considerations for developing nurse education on intimate partner violence.

Emotional memory processing in post-traumatic stress disorder affected Colombian youth.

Post-traumatic stress disorder (PTSD) is a neuropsychological condition caused by exposure to chronic stressors and extreme trauma. In past decades, Colombia (South America) has experienced high levels of armed conflict, which created an environment of chronic stress, resulting in an increased incidence of PTSD in children. Limited research exists on the effects of PTSD on emotional memory functioning of these Colombian youth living in chronically stressful environments. In the present study, 23 PTSD affected youth and 26 controls were asked to recall items from a memorised word list, as well as remembering details from a short emotional story. Although no significant differences were found for word list memory, deficits for emotional story content were found in the PTSD youth, particularly for facts involving negative emotional details. The latter may suggest a deficit in executive functioning for the integration of emotionally laden stimuli, perhaps induced as a by-product of their traumatic experiences.

Detecting ancient positive selection in humans using extended lineage sorting.

Natural selection that affected modern humans early in their evolution has likely shaped some of the traits that set present-day humans apart from their closest extinct and living relatives. The ability to detect ancient natural selection in the human genome could provide insights into the molecular basis for these human-specific traits. Here, we introduce a method for detecting ancient selective sweeps by scanning for extended genomic regions where our closest extinct relatives, Neandertals and Denisovans, fall outside of the present-day human variation. Regions that are unusually long indicate the presence of lineages that reached fixation in the human population faster than expected under neutral evolution. Using simulations, we show that the method is able to detect ancient events of positive selection and that it can differentiate those from background selection. Applying our method to the 1000 Genomes data set, we find evidence for ancient selective sweeps favoring regulatory changes and present a list of genomic regions that are predicted to underlie positively selected human specific traits.

Temporal Changes in the Cross-Sectional Associations between Cannabis Use, Suicidal Ideation, and Depression in a Nationally Representative Sample of Canadian Adults in 2012 Compared to 2002.

BACKGROUND: With the recent legalization of nonmedical cannabis in Canada, it is important to document previous associations between cannabis use and major depressive episode and suicidal ideation, as well as the extent to which these associations have changed over time. METHODS: This study uses pooled data from the 2002 and 2012 Canadian Community Health Survey's Mental Health Component, which are repeated cross-sectional surveys of nationally representative samples of Canadians 15 to 60 years of age (n = 43,466). Binary logistic regression was performed, applying weighting and bootstrapping, to examine the association between at least monthly use of cannabis and past 12-month suicidal ideation and major depressive episode (MDE). RESULTS: At least monthly nonmedical cannabis use was associated with an increased odds of MDE and suicidal ideation, and both associations strengthened in 2012 compared to 2002. Canadians using cannabis at least once a month in 2012 had 1.59 (95% confidence interval [CI], 1.11 to 2.27) times the odds of experiencing suicidal ideation and 1.55 (95% CI, 1.12 to 2.13) times the odds of experiencing MDE compared to those who used cannabis at least once a month in 2002. This temporal change remained after controlling for other substance use. CONCLUSIONS: Monthly cannabis use was consistently related to both suicidal ideation and MDE, and these associations were stronger in 2012 compared to 2002. The findings of this study provide a baseline for the association between cannabis use and suicide and depression in the Canadian population that should be reevaluated now that nonmedical cannabis has been legalized.

Differential associations between passive and active forms of screen time and adolescent mood and anxiety disorders.

OBJECTIVES: To quantify the strength of association between passive and active forms of screen time and adolescent major depressive episode and anxiety disorders. METHODS: Data from the 2014 Ontario Child Health Study, a representative sample of 2,320 adolescents aged 12-17 years in Ontario (mean age = 14.58, male = 50.7%) were used. Screen time was measured using adolescent self-report on time spent on screen-based activities. Past 6-month occurrence of DSM-IV-TR defined major depressive episode, social phobia, generalized anxiety disorder, and specific phobia which were assessed using the Mini International Neuropsychiatric Interview for Children and Adolescents. RESULT: Adolescents reporting 4 or more hours of passive screen time per day, compared to those reporting less than 2 h, were three times more likely to meet the DSM-IV-TR criteria for major depressive episode [OR = 3.28(95% CI = 1.71-6.28)], social phobia [OR = 3.15 (95% CI = 1.57-6.30)] and generalized anxiety disorder [OR = 2.92 (95% CI = 1.64-5.20)]. Passive screen time continued to be significantly associated with increased odds of disorders, after adjusting for age, sex, low income, active screen time use, sleep and physical activity. A small-to-moderate attenuation of the estimated ORs was observed in the fully adjusted model. In contrast, associations between active screen time use and depression and anxiety disorders were smaller in magnitude and failed to reach statistical significance. CONCLUSIONS: Passive screen time use was associated with mood and anxiety disorders, whereas active screen time was not. Further research is needed to better understand the underlying processes contributing to differential risk associated with passive versus active screen time use and adolescent mood and anxiety disorders.