The Effects of Psychosis Risk Variants on Brain Connectivity: A Review

In light of observed changes in connectivity in schizophrenia and the highly heritable nature of the disease, neural connectivity may serve as an important intermediate phenotype for schizophrenia. However, how individual variants confer altered connectivity and which measure of brain connectivity is more proximal to the underlying genetic architecture (i.e., functional or structural) has not been well delineated. In this review we consider these issues and the relative sensitivity of imaging methodologies to schizophrenia-related changes in connectivity. We searched PubMed for studies considering schizophrenia risk genes AND functional or structural connectivity. Where data was available, summary statistics were used to determine an estimate of effect size (i.e., Cohen’s d). A random-effects meta-analysis was used to consider (1) the largest effect and (2) all significant effects between functional and structural studies. Schizophrenia risk variants involved in neurotransmission, neurodevelopment and myelin function were found to be associated with altered neural connectivity. On average, schizophrenia risk genes had a large effect on functional (mean d = 0.76) and structural connectivity (mean d = 1.04). The examination of the largest effect size indicated that the outcomes of functional and structural studies were comparable (Q = 2.17, p > 0.05). Conversely, consideration of effect size estimates for all significant effects suggest that reported effect sizes in structural connectivity studies were more variable than in functional connectivity studies, and that there was a significant lack of homogeneity across the modalities (Q = 6.928, p = 0.008). Given the more variable profile of effect sizes associated with structural connectivity, these data may suggest that structural imaging methods are more sensitive to a wider range of effects, as opposed to functional studies which may only be able to determine large effects. These conclusions are limited by methodological considerations, and require further investigation involving larger samples, multiple genes, and novel analysis techniques for confirmation

Baseline brain and behavioral factors distinguish adolescent substance initiators and non-initiators at follow-up

Background Earlier substance use (SU) initiation is associated with greater risk for the development of SU disorders (SUDs), while delays in SU initiation are associated with a diminished risk for SUDs. Thus, identifying brain and behavioral factors that are markers of enhanced risk for earlier SU has major public health import. Heightened reward-sensitivity and risk-taking are two factors that confer risk for earlier SU. Materials and methods We characterized neural and behavioral factors associated with reward-sensitivity and risk-taking in substance-naïve adolescents (N = 70; 11.1–14.0 years), examining whether these factors differed as a function of subsequent SU initiation at 18- and 36-months follow-up. Adolescents completed a reward-related decision-making task while undergoing functional MRI. Measures of reward sensitivity (Behavioral Inhibition System-Behavioral Approach System; BIS-BAS), impulsive decision-making (delay discounting task), and SUD risk [Drug Use Screening Inventory, Revised (DUSI-R)] were collected. These metrics were compared for youth who did [Substance Initiators (SI); n = 27] and did not [Substance Non-initiators (SN); n = 43] initiate SU at follow-up. Results While SI and SN youth showed similar task-based risk-taking behavior, SI youth showed more variable patterns of activation in left insular cortex during high-risk selections, and left anterior cingulate cortex in response to rewarded outcomes. Groups displayed similar discounting behavior. SI participants scored higher on the DUSI-R and the BAS sub-scale. Conclusion Activation patterns in the insula and anterior cingulate cortex may serve as a biomarker for earlier SU initiation. Importantly, these brain regions are implicated in the development and experience of SUDs, suggesting differences in these regions prior to substance exposure

Cavalier King Charles Spaniels with Chiari-like malformation and Syringomyelia have increased variability of spatio-temporal gait characteristics

Abstract Background Chiari-like malformation in the Cavalier King Charles Spaniel is a herniation of the cerebellum and brainstem into or through the foramen magnum. This condition predisposes to Syringomyelia; fluid filled syrinxes within the spinal cord. The resulting pathology in spinal cord and cerebellum create neuropathic pain and changes in gait. This study aims to quantify the changes in gait for Cavalier King Charles Spaniel with Chiari-like malformation and Syringomyelia. Methods We compared Cavalier King Charles Spaniel with Chiari-like malformation with (n = 9) and without (n = 8) Syringomyelia to Border Terriers (n = 8). Two video cameras and manual tracking was used to quantify gait parameters. Results and conclusions We found a significant increase in coefficient of variation for the spatio-temporal characteristics and ipsilateral distance between paws and a wider base of support in the thoracic limbs but not in the pelvic limbs for Cavalier King Charles Spaniels compared with the border terrier

Baseline brain and behavioral factors distinguish adolescent substance initiators and non-initiators at follow-up

BackgroundEarlier substance use (SU) initiation is associated with greater risk for the development of SU disorders (SUDs), while delays in SU initiation are associated with a diminished risk for SUDs. Thus, identifying brain and behavioral factors that are markers of enhanced risk for earlier SU has major public health import. Heightened reward-sensitivity and risk-taking are two factors that confer risk for earlier SU.Materials and methodsWe characterized neural and behavioral factors associated with reward-sensitivity and risk-taking in substance-naïve adolescents (N = 70; 11.1–14.0 years), examining whether these factors differed as a function of subsequent SU initiation at 18- and 36-months follow-up. Adolescents completed a reward-related decision-making task while undergoing functional MRI. Measures of reward sensitivity (Behavioral Inhibition System-Behavioral Approach System; BIS-BAS), impulsive decision-making (delay discounting task), and SUD risk [Drug Use Screening Inventory, Revised (DUSI-R)] were collected. These metrics were compared for youth who did [Substance Initiators (SI); n = 27] and did not [Substance Non-initiators (SN); n = 43] initiate SU at follow-up.ResultsWhile SI and SN youth showed similar task-based risk-taking behavior, SI youth showed more variable patterns of activation in left insular cortex during high-risk selections, and left anterior cingulate cortex in response to rewarded outcomes. Groups displayed similar discounting behavior. SI participants scored higher on the DUSI-R and the BAS sub-scale.ConclusionActivation patterns in the insula and anterior cingulate cortex may serve as a biomarker for earlier SU initiation. Importantly, these brain regions are implicated in the development and experience of SUDs, suggesting differences in these regions prior to substance exposure

Application of Bayesian Techniques to Model the Burden of Human Salmonellosis Attributable to U.S. Food Commodities at the Point of Processing: Adaptation of a Danish Model

Mathematical models that estimate the proportion of foodborne illnesses attributable to food commodities at specific points in the food chain may be useful to risk managers and policy makers to formulate public health goals, prioritize interventions, and document the effectiveness of mitigations aimed at reducing illness. Using human surveillance data on laboratory-confirmed Salmonella infections from the Centers for Disease Control and Prevention and Salmonella testing data from U.S. Department of Agriculture Food Safety and Inspection Service's regulatory programs, we developed a point-of-processing foodborne illness attribution model by adapting the Hald Salmonella Bayesian source attribution model. Key model outputs include estimates of the relative proportions of domestically acquired sporadic human Salmonella infections resulting from contamination of raw meat, poultry, and egg products processed in the United States from 1998 through 2003. The current model estimates the relative contribution of chicken (48%), ground beef (28%), turkey (17%), egg products (6%), intact beef (1%), and pork (<1%) across 109 Salmonella serotypes found in food commodities at point of processing. While interpretation of the attribution estimates is constrained by data inputs, the adapted model shows promise and may serve as a basis for a common approach to attribution of human salmonellosis and food safety decision-making in more than one country

Keeping children safe: a multicentre programme of research to increase the evidence base for preventing unintentional injuries in the home in the under-fives

Background: Unintentional injuries among 0- to 4-year-olds are a major public health problem incurring substantial NHS, individual and societal costs. However, evidence on the effectiveness and cost-effectiveness of preventative interventions is lacking. Aim: To increase the evidence base for thermal injury, falls and poisoning prevention for the under-fives. Methods: Six work streams comprising five multicentre case–control studies assessing risk and protective factors, a study measuring quality of life and injury costs, national surveys of children’s centres, interviews with children’s centre staff and parents, a systematic review of barriers to, and facilitators of, prevention and systematic overviews, meta-analyses and decision analyses of home safety interventions. Evidence from these studies informed the design of an injury prevention briefing (IPB) for children’s centres for preventing fire-related injuries and implementation support (training and facilitation). This was evaluated by a three-arm cluster randomised controlled trial comparing IPB and support (IPB+), IPB only (no support) and usual care. The primary outcome was parent-reported possession of a fire escape plan. Evidence from all work streams subsequently informed the design of an IPB for preventing thermal injuries, falls and poisoning. Results: Modifiable risk factors for falls, poisoning and scalds were found. Most injured children and their families incurred small to moderate health-care and non-health-care costs, with a few incurring more substantial costs. Meta-analyses and decision analyses found that home safety interventions increased the use of smoke alarms and stair gates, promoted safe hot tap water temperatures, fire escape planning and storage of medicines and household products, and reduced baby walker use. Generally, more intensive interventions were the most effective, but these were not always the most cost-effective interventions. Children’s centre and parental barriers to, and facilitators of, injury prevention were identified. Children’s centres were interested in preventing injuries, and believed that they could prevent them, but few had an evidence-based strategic approach and they needed support to develop this. The IPB was implemented by children’s centres in both intervention arms, with greater implementation in the IPB+ arm. Compared with usual care, more IPB+ arm families received advice on key safety messages, and more families in each intervention arm attended fire safety sessions. The intervention did not increase the prevalence of fire escape plans [adjusted odds ratio (AOR) IPB only vs. usual care 0.93, 95% confidence interval (CI) 0.58 to 1.49; AOR IPB+ vs. usual care 1.41, 95% CI 0.91 to 2.20] but did increase the proportion of families reporting more fire escape behaviours (AOR IPB only vs. usual care 2.56, 95% CI 1.38 to 4.76; AOR IPB+ vs. usual care 1.78, 95% CI 1.01 to 3.15). IPB-only families were less likely to report match play by children (AOR 0.27, 95% CI 0.08 to 0.94) and reported more bedtime fire safety routines (AOR for a 1-unit increase in the number of routines 1.59, 95% CI 1.09 to 2.31) than usual-care families. The IPB-only intervention was less costly and marginally more effective than usual care. The IPB+ intervention was more costly and marginally more effective than usual care. Limitations: Our case–control studies demonstrate associations between modifiable risk factors and injuries but not causality. Some injury cost estimates are imprecise because of small numbers. Systematic reviews and meta-analyses were limited by the quality of the included studies, the small numbers of studies reporting outcomes and significant heterogeneity, partly explained by differences in interventions. Network meta-analysis (NMA) categorised interventions more finely, but some variation remained. Decision analyses are likely to underestimate cost-effectiveness for a number of reasons. IPB implementation varied between children’s centres. Greater implementation may have resulted in changes in more fire safety behaviours. Conclusions: Our studies provide new evidence about the effectiveness of, as well as economic evaluation of, home safety interventions. Evidence-based resources for preventing thermal injuries, falls and scalds were developed. Providing such resources to children’s centres increases their injury prevention activity and some parental safety behaviours. Future work: Further randomised controlled trials, meta-analyses and NMAs are needed to evaluate the effectiveness and cost-effectiveness of home safety interventions. Further work is required to measure NHS, family and societal costs and utility decrements for childhood home injuries and to evaluate complex multicomponent interventions such as home safety schemes using a single analytical model. Trial registration: Current Controlled Trials ISRCTN65067450 and ClinicalTrials.gov NCT01452191. Funding: The National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 5, No. 14. See the NIHR Journals Library website for further project information

Introducing the Musical Care International Network

UIDB/00472/2020 UIDP/00472/2020In this paper we report on the inaugural meetings of the Musical Care International Network held online in 2022. The term “musical care” is defined by Spiro and Sanfilippo (2022) as “the role of music—music listening as well as music-making—in supporting any aspect of people's developmental or health needs” (pp. 2–3). Musical care takes varied forms in different cultural contexts and involves people from different disciplines and areas of expertise. Therefore, the Musical Care International Network takes an interdisciplinary and international approach and aims to better reflect the disciplinary, geographic, and cultural diversity relevant to musical care. Forty-two delegates participated in 5 inaugural meetings over 2 days, representing 24 countries and numerous disciplines and areas of practice. Based on the meetings, the aims of this paper are to (1) better understand the diverse practices, applications, contexts, and impacts of musical care around the globe and (2) introduce the Musical Care International Network. Transcriptions of the recordings, alongside notes taken by the hosts, were used to summarise the conversations. The discussions developed ideas in three areas: (a) musical care as context-dependent and social, (b) musical care's position within the broader research and practice context, and (c) debates about the impact of and evidence for musical care. We can conclude that musical care refers to context-dependent and social phenomena. The term musical care was seen as useful in talking across boundaries while not minimizing individual disciplinary and professional expertise. The use of the term was seen to help balance the importance and place of multiple disciplines, with a role to play in the development of a collective identity. This collective identity was seen as important in advocacy and in helping to shape policy. The paper closes with proposed future directions for the network and its emerging mission statement.publishersversionpublishe