Reproducible brain-wide association studies require thousands of individuals.

Magnetic resonance imaging (MRI) has transformed our understanding of the human brain through well-replicated mapping of abilities to specific structures (for example, lesion studies) and functions1-3 (for example, task functional MRI (fMRI)). Mental health research and care have yet to realize similar advances from MRI. A primary challenge has been replicating associations between inter-individual differences in brain structure or function and complex cognitive or mental health phenotypes (brain-wide association studies (BWAS)). Such BWAS have typically relied on sample sizes appropriate for classical brain mapping4 (the median neuroimaging study sample size is about 25), but potentially too small for capturing reproducible brain-behavioural phenotype associations5,6. Here we used three of the largest neuroimaging datasets currently available-with a total sample size of around 50,000 individuals-to quantify BWAS effect sizes and reproducibility as a function of sample size. BWAS associations were smaller than previously thought, resulting in statistically underpowered studies, inflated effect sizes and replication failures at typical sample sizes. As sample sizes grew into the thousands, replication rates began to improve and effect size inflation decreased. More robust BWAS effects were detected for functional MRI (versus structural), cognitive tests (versus mental health questionnaires) and multivariate methods (versus univariate). Smaller than expected brain-phenotype associations and variability across population subsamples can explain widespread BWAS replication failures. In contrast to non-BWAS approaches with larger effects (for example, lesions, interventions and within-person), BWAS reproducibility requires samples with thousands of individuals.

Did anonymity in self-administered questionnaires improve disclosure of sensitive information during the 2022 mpox outbreak in England? An observational study.

BACKGROUND: Between May 6, 2022, and Jan 16, 2023, 3555 mpox cases were reported in England, predominantly in gay, bisexual, and other men who have sex with men. Initially, the UK Health Security agency administered questionnaires to laboratory-detected cases via telephone calls. From June, 2022, cases were requested by text or email to complete the questionnaire online, with optional anonymous completion. To inform future approaches, we assess whether anonymity improved disclosure of sensitive information. METHODS: In this observational study we analysed questionnaire data completed by people with a laboratory-detected case of mpox. We included questionnaires that were completed from May 25, 2022, to Jan 16, 2023, and restricted them to anonymous or identifiable self-completed responses. Questionnaires with forename, surname, and birth date, or an ID emailed to participants, which therefore could link to laboratory data, were considered identifiable. Questionnaires without any personal identifiable information were considered anonymous. We compared the responses to seven sensitive risk factor or exposure questions using Pearson's χ2. FINDINGS: All 3555 people diagnosed with mpox infection in England were invited to complete the questionnaire through either phone call or web link.We obtained 1075 (30%) completed questionnaires, with a response rate decreasing from 45% in May to 20% in July 2022. We included 531 self-completed questionnaires in this analysis, of which 259 (49%) were anonymous and 272 (51%) were identifiable. The median age of participants was 39 years, with 514 (97%) men, 12 (2%) women, and five (1%) other. The largest ethnic groups were white (79%; n=422) and mixed or multiple ethnic groups (9%; n=47). Results of all seven questions were similar: 98% (n=254/259) of anonymous and 97% (n=265/272) of identifiable cases answered all seven questions, 49% (n=127) and 54% (n=147) reported a sexually transmitted infection diagnosis in the past 12 months (p=0·2), 24% (n=63) and 27% (n=73) reported ten or more sexual partners in the past 3 months (p=0·8), and 15% (n=38) and 18% (n=50) reported knowing another person with mpox infection (p=0·5), respectively. INTERPRETATION: Transitioning to self-completed questionnaires resulted in reduced uptake, although optional anonymity possibly prevented a steeper drop. Anonymity did not appear to affect reporting of sensitive information, specifically of sexual behaviours or history associated with mpox risk, which reinforces results of previous literature. Our interpretation is limited, however, by relatively low questionnaire uptake, and by only analysing reported rather than true risk. The decision to implement anonymous questionnaires should therefore weigh the potential benefits of increased uptake against the disadvantage of restricted data linkage. FUNDING: None.

Segmenting hypothalamic subunits in human newborn magnetic resonance imaging data.

Preclinical evidence suggests that inter-individual variation in the structure of the hypothalamus at birth is associated with variation in the intrauterine environment, with downstream implications for future disease susceptibility. However, scientific advancement in humans is limited by a lack of validated methods for the automatic segmentation of the newborn hypothalamus. N = 215 healthy full-term infants with paired T1-/T2-weighted MR images across four sites were considered for primary analyses (mean postmenstrual age = 44.3 ± 3.5 weeks, nmale /nfemale = 110/106). The outputs of FreeSurfer's hypothalamic subunit segmentation tools designed for adults (segFS) were compared against those of a novel registration-based pipeline developed here (segATLAS) and against manually edited segmentations (segMAN) as reference. Comparisons were made using Dice Similarity Coefficients (DSCs) and through expected associations with postmenstrual age at scan. In addition, we aimed to demonstrate the validity of the segATLAS pipeline by testing for the stability of inter-individual variation in hypothalamic volume across the first year of life (n = 41 longitudinal datasets available). SegFS and segATLAS segmentations demonstrated a wide spread in agreement (mean DSC = 0.65 ± 0.14 SD; range = {0.03-0.80}). SegATLAS volumes were more highly correlated with postmenstrual age at scan than segFS volumes (n = 215 infants; RsegATLAS 2 = 65% vs. RsegFS 2 = 40%), and segATLAS volumes demonstrated a higher degree of agreement with segMAN reference segmentations at the whole hypothalamus (segATLAS DSC = 0.89 ± 0.06 SD; segFS DSC = 0.68 ± 0.14 SD) and subunit levels (segATLAS DSC = 0.80 ± 0.16 SD; segFS DSC = 0.40 ± 0.26 SD). In addition, segATLAS (but not segFS) volumes demonstrated stability from near birth to ~1 years age (n = 41; R2 = 25%; p < 10-3 ). These findings highlight segATLAS as a valid and publicly available (https://github.com/jerodras/neonate_hypothalamus_seg) pipeline for the segmentation of hypothalamic subunits using human newborn MRI up to 3 months of age collected at resolutions on the order of 1 mm isotropic. Because the hypothalamus is traditionally understudied due to a lack of high-quality segmentation tools during the early life period, and because the hypothalamus is of high biological relevance to human growth and development, this tool may stimulate developmental and clinical research by providing new insight into the unique role of the hypothalamus and its subunits in shaping trajectories of early life health and disease.

Network-specific selectivity of functional connections in the neonatal brain.

The adult human brain is organized into functional brain networks, groups of functionally connected segregated brain regions. A key feature of adult functional networks is long-range selectivity, the property that spatially distant regions from the same network have higher functional connectivity than spatially distant regions from different networks. Although it is critical to establish the status of functional networks and long-range selectivity during the neonatal period as a foundation for typical and atypical brain development, prior work in this area has been mixed. Although some studies report distributed adult-like networks, other studies suggest that neonatal networks are immature and consist primarily of spatially isolated regions. Using a large sample of neonates (n = 262), we demonstrate that neonates have long-range selective functional connections for the default mode, fronto-parietal, and dorsal attention networks. An adult-like pattern of functional brain networks is evident in neonates when network-detection algorithms are tuned to these long-range connections, when using surface-based registration (versus volume-based registration), and as per-subject data quantity increases. These results help clarify factors that have led to prior mixed results, establish that key adult-like functional network features are evident in neonates, and provide a foundation for studies of typical and atypical brain development.

A SARS-CoV-2 outbreak in a plastics manufacturing plant.

BACKGROUND: A SARS-CoV-2 outbreak with an attack rate of 14.3% was reported at a plastics manufacturing plant in England. METHODS: Between 23rd March and 13th May 2021, the COVID-OUT team undertook a comprehensive outbreak investigation, including environmental assessment, surface sampling, molecular and serological testing, and detailed questionnaires, to identify potential SARS-CoV-2 transmission routes, and workplace- and worker-related risk factors. RESULTS: While ventilation, indicated using real-time CO2 proxy measures, was generally adequate on-site, the technical office with the highest localized attack rate (21.4%) frequently reached peaks in CO2 of 2100ppm. SARS-CoV-2 RNA was found in low levels (Ct ≥35) in surface samples collected across the site. High noise levels (79dB) were recorded in the main production area, and study participants reported having close work contacts (73.1%) and sharing tools (75.5%). Only 20.0% of participants reported using a surgical mask and/or FFP2/FFP3 respirator at least half the time and 71.0% expressed concerns regarding potential pay decreases and/or unemployment due to self-isolation or workplace closure. CONCLUSIONS: The findings reinforce the importance of enhanced infection control measures in manufacturing sectors, including improved ventilation with possible consideration of CO2 monitoring, utilising air cleaning interventions in enclosed environments, and provision of good-quality face masks (i.e., surgical masks or FFP2/FFP3 respirators) especially when social distancing cannot be maintained. Further research on the impacts of job security-related concerns is warranted.

Synthesizing pseudo-T2w images to recapture missing data in neonatal neuroimaging with applications in rs-fMRI.

T1- and T2-weighted (T1w and T2w) images are essential for tissue classification and anatomical localization in Magnetic Resonance Imaging (MRI) analyses. However, these anatomical data can be challenging to acquire in non-sedated neonatal cohorts, which are prone to high amplitude movement and display lower tissue contrast than adults. As a result, one of these modalities may be missing or of such poor quality that they cannot be used for accurate image processing, resulting in subject loss. While recent literature attempts to overcome these issues in adult populations using synthetic imaging approaches, evaluation of the efficacy of these methods in pediatric populations and the impact of these techniques in conventional MR analyses has not been performed. In this work, we present two novel methods to generate pseudo-T2w images: the first is based in deep learning and expands upon previous models to 3D imaging without the requirement of paired data, the second is based in nonlinear multi-atlas registration providing a computationally lightweight alternative. We demonstrate the anatomical accuracy of pseudo-T2w images and their efficacy in existing MR processing pipelines in two independent neonatal cohorts. Critically, we show that implementing these pseudo-T2w methods in resting-state functional MRI analyses produces virtually identical functional connectivity results when compared to those resulting from T2w images, confirming their utility in infant MRI studies for salvaging otherwise lost subject data.

Geotemporal analysis of perinatal care changes and maternal mental health: an example from the COVID-19 pandemic.

Our primary objective was to document COVID-19 induced changes to perinatal care across the USA and examine the implication of these changes for maternal mental health. We performed an observational cross-sectional study with convenience sampling using direct patient reports from 1918 postpartum and 3868 pregnant individuals collected between April 2020 and December 2020 from 10 states across the USA. We leverage a subgroup of these participants who gave birth prior to March 2020 to estimate the pre-pandemic prevalence of specific birthing practices as a comparison. Our primary analyses describe the prevalence and timing of perinatal care changes, compare perinatal care changes depending on when and where individuals gave birth, and assess the linkage between perinatal care alterations and maternal anxiety and depressive symptoms. Seventy-eight percent of pregnant participants and 63% of postpartum participants reported at least one change to their perinatal care between March and August 2020. However, the prevalence and nature of specific perinatal care changes occurred unevenly over time and across geographic locations. The separation of infants and mothers immediately after birth and the cancelation of prenatal visits were associated with worsened depression and anxiety symptoms in mothers after controlling for sociodemographic factors, mental health history, number of pregnancy complications, and general stress about the COVID-19 pandemic. Our analyses reveal widespread changes to perinatal care across the US that fluctuated depending on where and when individuals gave birth. Disruptions to perinatal care may also exacerbate mental health concerns, so focused treatments that can mitigate the negative psychiatric sequelae of interrupted care are warranted.

Maternal Interleukin-6 Is Associated With Macaque Offspring Amygdala Development and Behavior.

Human and animal cross-sectional studies have shown that maternal levels of the inflammatory cytokine interleukin-6 (IL-6) may compromise brain phenotypes assessed at single time points. However, how maternal IL-6 associates with the trajectory of brain development remains unclear. We investigated whether maternal IL-6 levels during pregnancy relate to offspring amygdala volume development and anxiety-like behavior in Japanese macaques. Magnetic resonance imaging (MRI) was administered to 39 Japanese macaque offspring (Female: 18), providing at least one or more time points at 4, 11, 21, and 36 months of age with a behavioral assessment at 11 months of age. Increased maternal third trimester plasma IL-6 levels were associated with offspring's smaller left amygdala volume at 4 months, but with more rapid amygdala growth from 4 to 36 months. Maternal IL-6 predicted offspring anxiety-like behavior at 11 months, which was mediated by reduced amygdala volumes in the model's intercept (i.e., 4 months). The results increase our understanding of the role of maternal inflammation in the development of neurobehavioral disorders by detailing the associations of a commonly examined inflammatory indicator, IL-6, on amygdala volume growth over time, and anxiety-like behavior.

Trajectories of perinatal depressive symptoms in the context of the COVID-19 pandemic.

This study sought to advance understanding of the potential long-term consequences of the COVID-19 pandemic for child development by characterizing trajectories of maternal perinatal depression, a common and significant risk factor for adverse child outcomes. Data came from 393 women (86% White, 8% Latina; mean age = 33.51 years) recruited during pregnancy (n = 247; mean gestational age = 22.94 weeks) or during the first year postpartum (n = 146; mean child age = 4.50 months; 55% female). Rates of depression appear elevated, relative to published reports and to a pre-pandemic comparison group (N = 155). This study also provides evidence for subgroups of individuals who differ in their depressive symptom trajectories over the perinatal period. Subgroup membership was related to differences in maternal social support, but not to child birth outcomes.

Early development of negative and positive affect: Implications for ADHD symptomatology across three birth cohorts.

High levels of early emotionality (of either negative or positive valence) are hypothesized to be important precursors to early psychopathology, with attention-deficit/hyperactivity disorder (ADHD) a prime early target. The positive and negative affect domains are prime examples of Research Domain Criteria (RDoC) concepts that may enrich a multilevel mechanistic map of psychopathology risk. Utilizing both variable-centered and person-centered approaches, the current study examined whether levels and trajectories of infant negative and positive emotionality, considered either in isolation or together, predicted children's ADHD symptoms at 4 to 8 years of age. In variable-centered analyses, higher levels of infant negative affect (at as early as 3 months of age) were associated with childhood ADHD symptoms. Findings for positive affect failed to reach statistical threshold. Results from person-centered trajectory analyses suggest that additional information is gained by simultaneously considering the trajectories of positive and negative emotionality. Specifically, only when exhibiting moderate, stable or low levels of positive affect did negative affect and its trajectory relate to child ADHD symptoms. These findings add to a growing literature that suggests that infant negative emotionality is a promising early life marker of future ADHD risk and suggest secondarily that moderation by positive affectivity warrants more consideration.

Evaluation of maternal inflammation as a marker of future offspring ADHD symptoms: A prospective investigation.

Early life predictors of attention-deficit/hyperactivity disorder (ADHD) are critically needed; they could inform etiological theory and may help identify new prevention targets. The current study examined prospectively whether maternal cytokine levels during pregnancy predict offspring ADHD symptoms at age 4-6 years. Secondarily, we evaluated maternal cytokine levels as a possible common pathway through which prenatal risks exert influence on child ADHD. Data came from a sample of women recruited during the 2nd trimester of pregnancy (N = 62) and followed postnatally until children were 4-6 years old. Maternal inflammation was assessed using 3rd trimester plasma concentrations of three indicators of nuclear factor kappa B signaling: interleukin-6, tumor necrosis factor-alpha, and monocyte chemoattractant protein-1 which were combined into a latent variable. Mothers and teachers reported on child ADHD symptoms, negative affect, and externalizing behaviors at 48-72 months of age. Maternal inflammation in the 3rd trimester predicted ADHD symptoms when children were 4-6 years old (ß = 0.53, 95% CI = 0.154, 0.905, p = 0.006). Further, maternal inflammation mediated the effect of prenatal distress on child ADHD (ß = 0.21, 95% CI = 0.007, 0.419, p = 0.04). The inflammation effect on ADHD was not explained by concurrent child negative affect, externalizing behavior, or familial ADHD status. This is the first human study to prospectively link maternal pregnancy cytokine levels and offspring ADHD symptoms, suggesting that cytokine levels are a possible marker of ADHD risk. Results also provide new evidence that maternal prenatal inflammation may be one common pathway by which prenatal risk factors influence offspring mental health outcomes.

Maternal Interleukin-6 concentration during pregnancy is associated with variation in frontolimbic white matter and cognitive development in early life.

Maternal inflammation during pregnancy can alter the trajectory of fetal brain development and increase risk for offspring psychiatric disorders. However, the majority of relevant research to date has been conducted in animal models. Here, in humans, we focus on the structural connectivity of frontolimbic circuitry as it is both critical for socioemotional and cognitive development, and commonly altered in a range of psychiatric disorders associated with intrauterine inflammation. Specifically, we test the hypothesis that elevated maternal concentration of the proinflammatory cytokine interleukin-6 (IL-6) during pregnancy will be associated with variation in microstructural properties of this circuitry in the neonatal period and across the first year of life. Pregnant mothers were recruited in early pregnancy and maternal blood samples were obtained for assessment of maternal IL-6 concentrations in early (12.6 ±â€¯2.8 weeks [S.D.]), mid (20.4 ±â€¯1.5 weeks [S.D.]) and late (30.3 ±â€¯1.3 weeks [S.D.]) gestation. Offspring brain MRI scans were acquired shortly after birth (N = 86, scan age = 3.7 ±â€¯1.7 weeks [S.D.]) and again at 12-mo age (N = 32, scan age = 54.0 ±â€¯3.1 weeks [S.D.]). Diffusion Tensor Imaging (DTI) was used to characterize fractional anisotropy (FA) along the left and right uncinate fasciculus (UF), representing the main frontolimbic fiber tract. In N = 30 of the infants with serial MRI data at birth and 12-mo age, cognitive and socioemotional developmental status was characterized using the Bayley Scales of Infant Development. All analyses tested for potentially confounding influences of household income, prepregnancy Body-Mass-Index, obstetric risk, smoking during pregnancy, and infant sex, and outcomes at 12-mo age were additionally adjusted for the quality of the postnatal caregiving environment. Maternal IL-6 concentration (averaged across pregnancy) was prospectively and inversely associated with FA (suggestive of reduced integrity under high inflammatory conditions) in the newborn offspring (bi-lateral, p < 0.01) in the central portion of the UF proximal to the amygdala. Furthermore, maternal IL-6 concentration was positively associated with rate of FA increase across the first year of life (bi-lateral, p < 0.05), resulting in a null association between maternal IL-6 and UF FA at 12-mo age. Maternal IL-6 was also inversely associated with offspring cognition at 12-mo age, and this association was mediated by FA growth across the first year of postnatal life. Findings from the current study support the premise that susceptibility for cognitive impairment and potentially psychiatric disorders may be affected in utero, and that maternal inflammation may constitute an intrauterine condition of particular importance in this context.

Decreased BDNF in female but not male rats after exposure to stress: a sex-sensitive rat model of stress?

The literature has consistently emphasized a relationship between chronic stress and depression as well as the involvement of brain-derived neurotrophic factor (BDNF). It is also well known that there are gender disparities with regard to depression. However, there has been a lack of biobehavioral experimental investigations of these relationships with regard to the role of BDNF in sex differences in response to stress. It was hypothesized that stress (chronic unpredictable mild stress [CUMS], shock stress [SS]) would result in greater deleterious alterations in behavior (open field activity [OFA]) and biological (serum BDNF, body weight [BW]) indices of depression for female rats as compared to male rats. Subjects consisted of 79 Sprague-Dawley rats with 11-16 rats per each condition. CUMS consisted of 14 d of stress whereby on each stress day, rats were exposed to 20-min periods of predator stress and unpredictable environmental stress. SS consisted of a 2-h per day session of immobilization and tail-shocks repeated for three consecutive days. Serum BDNF was collected via trunk blood and quantitated using commercial enzyme-linked immunosorbent assay (ELISA). There were pronounced sex differences with regard to stress-induced behavioral and biological alterations. Both stressors decreased vertical activity (VA) (i.e. increased depressive-related behavior) and SS decreased serum BDNF in female rats, but not in male rats. Findings indicate a potential relationship between depressive-like behaviors and BDNF after exposure to stress. The clear sex differences in stress responding emphasize the need for more stress research that involves male and female subjects. Lay summary Stress decreased vertical activity (VA) in female but not male rats while shock stress (SS) decreased serum BDNF in female but not male rats. VA was positively correlated with serum BDNF for female rats. These findings suggest sex differences in response to stress.

Control diet in a high-fat diet study in mice: Regular chow and purified low-fat diet have similar effects on phenotypic, metabolic, and behavioral outcomes.

BACKGROUND: Differences in the composition of control diets may confound outcomes in studies investigating dietary effects. OBJECTIVE: We compared the effects of two control diets commonly used in mice studies, chow (SD) and a purified low-fat diet (LFD), in relation to a chronic high-fat diet (HFD). We hypothesized that SD and LFD will have similar effects on phenotypic, metabolic, and behavioral outcomes. METHODS: Fifty-four 5-week-old male C57BL/6J mice were randomly assigned to one of the three dietary interventions (SD, LFD, or HFD) for 18 weeks. At week 16, mice were tested for behavioral changes. Glucose tolerance testing was conducted at week 17 and terminal blood collection at week 18. RESULTS: SD and LFD mice exhibited no differences in cognitive performance on the Y-maze test and comparable anxiety-like behavior in the open-field and elevated zero maze tests. Significant declines in cognitive function and greater anxiety-like behavior were observed in the HFD group compared to both SD and LFD. Areas under the glucose tolerance curve were similar for SD and LFD, as were levels of high-density lipoprotein, triglycerides, cytokines, and adipocytokines. Only total cholesterol was significantly higher in LFD mice compared to SD mice. All measures were significantly higher in the HFD group. DISCUSSION: Our data demonstrate that young mice develop similar phenotypic, metabolic, and behavioral profiles when fed SD vs. LFD. The two diets may thus be equally appropriate as controls for an HFD, although some studies may want to consider differences in effects on cholesterol levels.

Effects of a school readiness intervention on hypothalamus-pituitary-adrenal axis functioning and school adjustment for children in foster care.

Maltreated children in foster care are at high risk for dysregulated hypothalamus-pituitary-adrenal (HPA) axis functioning and educational difficulties. The present study examined the effects of a short-term school readiness intervention on HPA axis functioning in response to the start of kindergarten, a critical transition marking entry to formal schooling, and whether altered HPA axis functioning influenced children's school adjustment. Compared to a foster care comparison group, children in the intervention group showed a steeper diurnal cortisol slope on the first day of school, a pattern previously observed among nonmaltreated children. A steeper first day of school diurnal cortisol slope predicted teacher ratings of better school adjustment (i.e., academic performance, appropriate classroom behaviors, and engagement in learning) in the fall of kindergarten. Furthermore, the children's HPA axis response to the start of school mediated the effect of the intervention on school adjustment. These findings support the potential for ameliorative effects of interventions targeting critical transitional periods, such as the transition of formal schooling. This school readiness intervention appears to influence stress neurobiology, which in turn facilitates positive engagement with the school environment and better school adjustment in children who have experienced significant early adversity.

The Stem Cell Club: a model for unrelated stem cell donor recruitment.

BACKGROUND: Patients with blood, immune, or metabolic diseases may require a stem cell transplant as part of their treatment. However, 70% of patients do not have a suitable human leukocyte antigen match in their family, and need an unrelated donor. Individuals can register as potential donors at stem cell drives, where they provide consent and a tissue sample for human leukocyte antigen typing. The ideal donors are young, male, and from a diversity of ethnic backgrounds. However, in Canada, non-Caucasian males ages 17 to 35 years represent only 8.8% of listed donors. STUDY DESIGN AND METHODS: The Stem Cell Club is a non-profit organization founded in 2011 in Canada that aims to augment recruitment of the most needed donors. The initiative published a recruitment toolkit online (www.stemcellclub.ca). Currently, there are 12 chapters at universities across Canada. RESULTS: To date, the Stem Cell Club has recruited 6585 potential registrants, representing 1.63% of donors on Canada's donor-database. Of the recruited registrants, 58.3% were male; 60.3% of males self-reported as non-Caucasian, and 78.5% were ages 17 to 25 years. From 2015 to 2016, the initiative recruited 13.7% of all ethnically diverse males ages 17 to 35 years listed in Canada's donor database. Data from this initiative demonstrate sustainability and performance on key indicators of stem cell drive quality. CONCLUSION: The Stem Cell Club has developed a capacity to recruit 2600 donors annually, with the majority being males with a high degree of ethnic diversity. The initiative enhances the quality of Canada's unrelated donor-database, improving the chances that patients in need of an unrelated donor will find a match for transplant. The Stem Cell Club is a model relevant to recruitment organizations around the world.

Early life stress is associated with default system integrity and emotionality during infancy.

BACKGROUND: Extensive animal research has demonstrated the vulnerability of the brain to early life stress (ELS) with consequences for emotional development and mental health. However, the influence of moderate and common forms of stress on early human brain development is less well-understood and precisely characterized. To date, most work has focused on severe forms of stress, and/or on brain functioning years after stress exposure. METHODS: In this report we focused on conflict between parents (interparental conflict), a common and relatively moderate form of ELS that is highly relevant for children's mental health outcomes. We used resting state functional connectivity MRI to examine the coordinated functioning of the infant brain (N = 23; 6-12-months-of-age) in the context of interparental conflict. We focused on the default mode network (DMN) due to its well-characterized developmental trajectory and implications for mental health. We further examined DMN strength as a mediator between conflict and infants' negative emotionality. RESULTS: Higher interparental conflict since birth was associated with infants showing stronger connectivity between two core DMN regions, the posterior cingulate cortex (PCC) and the anterior medial prefrontal cortex (aMPFC). PCC to amygdala connectivity was also increased. Stronger PCC-aMPFC connectivity mediated between higher conflict and higher negative infant emotionality. CONCLUSIONS: The developing DMN may be an important marker for effects of ELS with relevance for emotional development and subsequent mental health. Increasing understanding of the associations between common forms of family stress and emerging functional brain networks has potential to inform intervention efforts to improve mental health outcomes.

A decade of Campylobacter and Campylobacter bacteraemias in a district general hospital and the surrounding London and South East region, England.

BACKGROUND: Campylobacter bacteraemia is a rare complication of the most common bacterial gastrointestinal infection but is associated with significant morbidity and mortality. There is limited data describing current trends in surveillance and antimicrobial resistance for the Campylobacter strains involved. At the Epsom and St Helier's University Hospital (ESTH), we noted a marked increase in Campylobacter bacteraemia infections in 2021. METHODS: We extracted Campylobacter reports using the UK Health Security Agency's (UKHSA) Second Generation Surveillance System (laboratory reporting system) between 1st January 2012 and 31st December 2021. We reviewed patient records of patients with Campylobacter bacteraemia for details including presentation, past medical history, duration of hospital stay, and antibiotic use. RESULTS: Between 2012 and 2021, ESTH reported a total of 34 cases of Campylobacter bacteraemia. In 2021, the estimated incidence was 6.8 cases per 100,000 population and in the surrounding area, the incidence was 0.4 per 100,000 population. The incidence rate of Campylobacter bacteraemia in London and the South East region was significantly lower than ESTH (RR = 0.17, p < 0.0001). Campylobacter bacteraemia cases at ESTH reported a high number of co-morbidities (average number of comorbidities = 2.3) and had a duration of stay in hospital of a median of 7 days (IQR = 4-10 days). Campylobacter jejuni was the most commonly reported species for stool and blood Campylobacter in ESTH, London, and South East England. CONCLUSION: Campylobacter bacteraemia reports at ESTH were significantly (p < 0.001) higher than the surrounding London and South East region. While no common cause for the exceedance of Campylobacter bacteraemia has been identified, common risk factors for Campylobacter bacteraemia infection include underlying health conditions, being older, and male.