Search

Post-traumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 new). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (for example, GRIA1, GRM8 and CACNA1E), developmental, axon guidance and transcription factors (for example, FOXP2, EFNA5 and DCC), synaptic structure and function genes (for example, PCLO, NCAM1 and PDE4B) and endocrine or immune regulators (for example, ESR1, TRAF3 and TANK). Additional top genes influence stress, immune, fear and threat-related processes, previously hypothesized to underlie PTSD neurobiology. These findings strengthen our understanding of neurobiological systems relevant to PTSD pathophysiology, while also opening new areas for investigation.

The commercial determinants of health (CDoH) are attracting increased interest and are of great importance when discussing how trade affects health. Through a citation analysis of recent foundational CDoH documents (a Lancet paper series and an Oxford University textbook), we find that fully 71% of all citations reference the health sciences. The health sciences may be well suited to documenting the specific pathways of how commercial (by)products and practices harm human health. However, to operationalize upstream solutions for mitigating these harms, our citation analysis suggests that the field can engage political scientists, economists, sociologists, the trade law and business, as well as advocates in civil society and journalism, more so than it currently does. With CDoH explicitly referring to the interaction between commerce and health, CDoH researchers might be uniquely positioned to get health on the agenda of others, which requires that CDoH methods, datasets, evidence reviews, and proposed interventions are drawn from the widest possible range of sources.

While most research has focussed on the experiences and consequences of ethnic discrimination for students, little is known about how teachers respond to ethnic discrimination. Teachers' responses are important as they may affect the outcomes of ethnic discrimination for students. Additionally, many studies have shown that teachers find it difficult to respond or talk about these issues but we know very little about how they act or address these challenges. Using a qualitative sample of 48 teachers, 23 students and four headteachers, this study explores (1) how secondary school teachers respond to ethnic discrimination and (2) what might explain variability in their responses. We found that teachers vary in their responses to incidents of ethnic discrimination between students (or incidents in which the teacher was a third party) in comparison with accusations of ethnic discrimination (or incidents in which the teacher was a main protagonist). When teachers responded to incidents of ethnic discrimination, they generally treat it as a learning opportunity and expect students to be 'calm', 'open-minded', 'reflective', 'respectful' and 'communicative'. However, when teachers become the centre of the debate and are accused of discriminatory behaviour, they do not apply these criteria but deny or downplay the allegations. Differences in teachers' responses were related to background characteristics (years of teaching experience, school context, ethnic background, subject of teaching), role perceptions, basic needs for teaching, perceptions of students and a fear of being perceived as a racist.

Previous research shows that the lockdown of schools due to the COVID-19 pandemic increased the already existing inequalities in education but little is known about the processes underlying these outcomes. In this study we used Bourdieu's theories to explore how interactions between teachers' expectations of parents and parents' availability of cultural, social and economic capital could potentially influence educational inequalities in the context of distance education. The analysis is based on 24 qualitative interviews with parents from different social backgrounds, teachers and school coordinators, sampled from an inner-city primary school in Flanders (Belgium). The results indicate that teachers continue to have standardised expectations of the proper role that parents should perform in distance education, which were difficult for some families to meet due their availability of cultural and economic capital. However, this study suggests that teachers' exposure to familial issues can result in teachers adapting their expectations and responses so that they are more likely to respond to the needs of parents and students in the field of distance education.

Background: In the Netherlands, living in proximity to goat farms has been consistently associated with an increased incidence of community-acquired pneumonia (CAP). The cause remains largely unknown though airborne microbial agents could play a role.Objective: The aim of this study is to explore micro-organisms present in goats that can cause human pneumonia.Methods: An extensive literature review was conducted to identify all micro-organisms detected in goats that are associated with human pneumonia. Additionally, the identified micro-organisms were prioritized using a self-developed scoring system and expert opinion.Results: Through extensive literature review, 4309 references describing 302 different micro-organisms in goats or on goat farms were identified. Additional searches and reviews for human respiratory disease caused by each of these micro-organisms yielded a final list of 76 bacteria, 7 viruses, 7 fungi, and 6 protozoa. They were assigned scores based on pneumonia type, diagnosis of respiratory disease, patient immune status, and evidence strength. Based on these scores, the most likely potential causal micro-organisms included Moraxella spp. Chlamydia psittaci, Staphylococcus aureus, and Streptococcus pneumoniae. Subsequently, the list of micro-organisms was reviewed by external experts on their perceived likelihood of the organism causing this CAP.Conclusion: Results of this literature study can give insight into the possible causes of pneumonia. Nonetheless, no unambiguous conclusion on the actual cause of the increased CAP risk around goat farms can be drawn solely based on these results.

Abstract Background This study evaluates longitudinal associations between glycaemic control, measured by mean and within-patient variability of glycated haemaglobin (HbA1c) levels, and major depressive disorder (MDD) in individuals with type 2 diabetes (T2D), focusing on the timings of these diagnoses. Methods In UK Biobank, T2D was defined using self-report and linked health outcome data, then validated using polygenic scores. Repeated HbA1c measurements (mmol/mol) over the 10 years following T2D diagnosis were outcomes in mixed effects models, with disease duration included using restricted cubic splines. Four MDD exposures were considered: MDD diagnosis prior to T2D diagnosis (pre-T2D MDD), time between pre-T2D MDD diagnosis and T2D, new MDD diagnosis during follow-up (post-T2D MDD) and time since post-T2D MDD diagnosis. Models with and without covariate adjustment were considered. Results T2D diagnostic criteria were robustly associated with T2D polygenic scores. In 11,837 T2D cases (6.9 years median follow-up), pre-T2D MDD was associated with a 0.92 increase in HbA1c (95% CI: [0.00, 1.84]), but earlier pre-T2D MDD diagnosis correlated with lower HbA1c. These pre-T2D MDD effects became non-significant after covariate adjustment. Post-T2D MDD individuals demonstrated increasing HbA1c with years since MDD diagnosis ( $$\beta =0.51$$ β = 0.51 , 95% CI: [0.17, 0.86]). Retrospectively, across study follow-up, within-patient variability in HbA1c was 1.16 (95% CI: 1.13–1.19) times higher in post-T2D MDD individuals. Conclusions The timing of MDD diagnosis is important for understanding glycaemic control in T2D. Poorer control was observed in MDD diagnosed post-T2D, highlighting the importance of depression screening in T2D, and closer monitoring for individuals who develop MDD after T2D.

Thyroid hormone (TH) balance is essential for vertebrate development. Deiodinase type 1 (D1) and type 2 (D2) increase and deiodinase type 3 (D3) decreases local intracellular levels of T3, the most important active TH. The role of deiodinase-mediated TH effects in early vertebrate development is only partially understood. Therefore, we investigated the role of deiodinases during early development of zebrafish until 96 hours post fertilization at the level of the transcriptome (microarray), biochemistry, morphology and physiology using morpholino (MO) knockdown. Knockdown of D1+D2 (D1D2MO) and knockdown of D3 (D3MO) both resulted in transcriptional regulation of energy metabolism and (muscle) development in abdomen and tail, together with reduced growth, impaired swim bladder inflation, reduced protein content and reduced motility. The reduced growth and impaired swim bladder inflation in D1D2MO could be due to lower levels of T3 which is known to drive growth and development. The pronounced upregulation of a large number of transcripts coding for key proteins in ATP-producing pathways in D1D2MO could reflect a compensatory response to a decreased metabolic rate, also typically linked to hypothyroidism. Compared to D1D2MO, the effects were more pronounced or more frequent in D3MO, in which hyperthyroidism is expected. More specifically, increased heart rate, delayed hatching and increased carbohydrate content were observed only in D3MO. An increase of the metabolic rate, a decrease of the metabolic efficiency and a stimulation of gluconeogenesis using amino acids as substrates may have been involved in the observed reduced protein content, growth and motility in D3MO larvae. Furthermore, expression of transcripts involved in purine metabolism coupled to vision was decreased in both knockdown conditions, suggesting that both may impair vision. This study provides new insights, not only into the role of deiodinases, but also into the importance of a correct TH balance during vertebrate embryonic development.

Abstract The commercial determinants of health (CDoH) are attracting increased interest and are of great importance when discussing how trade affects health. Through a citation analysis of recent foundational CDoH documents (a Lancet paper series and an Oxford University textbook), we find that fully 71% of all citations reference the health sciences. The health sciences may be well suited to documenting the specific pathways of how commercial (by)products and practices harm human health. However, to operationalize upstream solutions for mitigating these harms, our citation analysis suggests that the field can engage political scientists, economists, sociologists, the trade law and business, as well as advocates in civil society and journalism, more so than it currently does. With CDoH explicitly referring to the interaction between commerce and health, CDoH researchers might be uniquely positioned to get health on the agenda of others, which requires that CDoH methods, datasets, evidence reviews, and proposed interventions are drawn from the widest possible range of sources.

As most studies focus on the outcomes of multiculturalism, assimilation and colourblindness (MAC) for students, little is known about why schools vary in the diversity approaches that they adopt and the role of the teacher in this process. This study explores how teachers implement MAC diversity approaches and what drives them in doing so. Based on a cluster analysis of 38 schools, three extreme cases were selected that either valued (multiculturalism), rejected (assimilation) or ignored (colourblindness) ethnic diversity. In these schools observations and in-depth interviews were conducted with 39 teachers, 23 students and 3 headteachers. Our results indicate that teachers varied in their implementation of MAC diversity approaches according to four diversity domains: 1) multilingualism, 2) religious diversity, 3) ethnic discrimination and 4) diversity curriculum. Teachers' beliefs and attitudes (individual-level) and their preconditions for teaching (micro-level) appeared as the most important motivators for adopting a particular diversity approach.

Abstract Although most infections are transmitted through the environment, the processes underlying the environmental stage of transmission are still poorly understood for most systems. Improved understanding of the environmental transmission dynamics is important for effective non-pharmaceutical intervention strategies. To study the mechanisms underlying environmental transmission we formulated a parsimonious modelling framework including hypothesised mechanisms of pathogen dispersion and decay. To calibrate and validate the model, we conducted a series of experiments studying distance-dependent transmission of Campylobacter jejuni in broilers. We obtained informative simultaneous estimates for all three model parameters: the parameter of C. jejuni inactivation, the diffusion coefficient describing pathogen dispersion, and the transmission rate parameter. The time and distance dependence of transmission in the fitted model is quantitatively consistent with marked spatiotemporal patterns in the experimental observations. These results, for C. jejuni in broilers, show that the application of our modelling framework to suitable transmission data can provide mechanistic insight in environmental pathogen transmission.

Human salmonellosis cases are often caused by Salmonella serovars Enteritidis and Typhimurium and associated with the consumption of eggs and egg products. Many countries therefore implemented general surveillance programmes on pullet and layer farms. The identification of risk factors for Salmonella infection may be used to improve the performance of these surveillance programmes. The aims of this study were therefore to determine 1) whether local farm density is a risk factor for the infection of pullet and layer farms by Salmonella Enteritidis and Typhimurium and 2) whether the sampling effort of surveillance programmes can be reduced by accounting for this risk factor, while still providing sufficient control of these serovars. We assessed the importance of local farm density as a risk factor by fitting transmission kernels to Israeli surveillance data during the period from June 2017 to April 2019. The analysis shows that the risk of infection by serovars Enteritidis and Typhimurium significantly increased if infected farms were present within a radius of approximately 4 km and 0.3 km, respectively. We subsequently optimized a surveillance programme that subdivided layer farms into low and high risk groups based on the local farm density with and allowed the sampling frequency to vary between these groups. In this design, the pullet farms were always sampled one week prior to pullet distribution. Our analysis shows that the risk-based surveillance programme is able to keep the between-farm R0 of serovars Enteritidis and Typhimurium below 1 for all pullet and layer farms, while reducing the sampling effort by 32% compared to the currently implemented surveillance programme in Israel. The results of our study therefore indicate that local farm density is an important risk factor for infection of pullet and layer farms by Salmonella Enteritidis and Typhimurium and can be used to improve the performance of surveillance programmes.

Abstract Objective: Food taxation can improve diets by making unhealthy foods more expensive and by making healthy foods cheaper. In the Netherlands, a political window of opportunity arose in December 2021 to reduce the value-added tax (VAT) on fruits and vegetables to zero percent. The policy is now facing institutional friction along several fronts, however, delaying and potentially averting its implementation. We analysed this institutional friction to inform future food tax policies. Design: We qualitatively analysed open-access fiscal and health experts’ position papers about benefits and downsides of the zero-rate that were discussed with members of parliament in June 2023. Setting: The Netherlands. Participants: Not applicable. Results: Health and fiscal experts expressed noticeably different viewpoints towards the utility of the zero-rate. One important argument fiscal experts based their negative advice upon pertained to the legal restrictions for distinguishing between healthier and unhealthier forms of fruits and vegetables (i.e. the principle of neutrality). A zero-rate VAT on unhealthier forms of fruits and vegetables, e.g. processed cucumber, mixed with salt and sugar, would be undesirable, but differentiating between raw and processed cucumber would offend the neutrality principle. Conclusions: The Dutch attempt to give fruits and vegetables a tax break highlights the need for crystal-clear food classifications when designing food tax policies. Public health nutritionists should combine classifications based on caloric density, palatability, degree of processing and nutrient content to provide a database for evidence-informed tax differentiation according to food item healthfulness.

Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies.

A devastating bluetongue (BT) epidemic caused by bluetongue virus serotype 3 (BTV-3) has spread throughout most of the Netherlands within two months since the first infection was officially confirmed in the beginning of September 2023. The epidemic comes with unusually strong suffering of infected cattle through severe lameness, often resulting in mortality or euthanisation for welfare reasons. In total, tens of thousands of sheep have died or had to be euthanised. By October 2023, more than 2200 locations with ruminant livestock were officially identified to be infected with BTV-3, and additionally, ruminants from 1300 locations were showing BTV-associated clinical symptoms (but not laboratory-confirmed BT). Here, we report on the spatial spread and dynamics of this BT epidemic. More specifically, we characterized the distance-dependent intensity of the between-holding transmission by estimating the spatial transmission kernel and by comparing it to transmission kernels estimated earlier for BTV-8 transmission in Northwestern Europe in 2006 and 2007. The 2023 BTV-3 kernel parameters are in line with those of the transmission kernel estimated previously for the between-holding spread of BTV-8 in Europe in 2007. The 2023 BTV-3 transmission kernel has a long-distance spatial range (across tens of kilometres), evidencing that in addition to short-distance dispersal of infected midges, other transmission routes such as livestock transports probably played an important role.

Background. In The Netherlands, 60% of deceased-donor kidney offers are after donation after circulatory death. Cold and warm ischemia times are known risk factors for delayed graft function (DGF) and inferior allograft survival. Extraction time is a relatively new ischemia time. During procurement, cooling of the kidneys is suboptimal with ongoing ischemia. However, evidence is lacking on whether extraction time has an impact on DGF if all ischemic periods are included. Methods. Between 2012 and 2018, 1524 donation after circulatory death kidneys were procured and transplanted in The Netherlands. Donation and transplantation-related data were obtained from the database of the Dutch Transplant Foundation. The primary outcome parameter was the incidence of DGF. Results. In our cohort, extraction time ranged from 14 to 237 min, with a mean of 62 min (SD 32). In multivariate logistic regression analysis, extraction time was an independent risk factor for incidence of DGF (odds ratio per minute increase 1.008; 95% confidence interval, 1.003-1.013; P = 0.001). The agonal phase, hypoperfusion time, and anastomosis time were not independent risk factors for incidence of DGF. Conclusions. Considering all known ischemic periods during the donation after the circulatory death process, prolonged kidney extraction time increased the risk of DGF after kidney transplantation.

White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.

Abstract The risk of epidemic spread of diseases in livestock poses a threat to animal and often also human health. Important for the assessment of the effect of control measures is a statistical model quantification of between-farm transmission during epidemics. In particular, quantification of the between-farm transmission kernel has proven its importance for a range of different diseases in livestock. In this paper we explore if a comparison of the different transmission kernels yields further insight. Our comparison identifies common features that connect across the different pathogen-host combinations analyzed. We conjecture that these features are universal and thereby provide generic insights. Comparison of the shape of the spatial transmission kernel suggests that, in absence of animal movement bans, the distance dependence of transmission has a universal shape analogous to Lévy-walk model descriptions of human movement patterns. Also, our analysis suggests that interventions such as movement bans and zoning, through their impact on these movement patterns, change the shape of the kernel in a universal fashion. We discuss how the generic insights suggested can be of practical use for assessing risks of spread and optimizing control measures, in particular when outbreak data is scarce.