Sustaining attention in affective contexts during adolescence: age-related differences and association with elevated symptoms of depression and anxiety.

Sustained attention, a key cognitive skill that improves during childhood and adolescence, tends to be worse in some emotional and behavioural disorders. Sustained attention is typically studied in non-affective task contexts; here, we used a novel task to index performance in affective versus neutral contexts across adolescence (N = 465; ages 11-18). We asked whether: (i) performance would be worse in negative versus neutral task contexts; (ii) performance would improve with age; (iii) affective interference would be greater in younger adolescents; (iv) adolescents at risk for depression and higher in anxiety would show overall worse performance; and (v) would show differential performance in negative contexts. Results indicated that participants performed more poorly in negative contexts and showed age-related performance improvements. Those at risk of depression performed more poorly than those at lower risk. However, there was no difference between groups as a result of affective context. For anxiety there was no difference in performance as a function of severity. However, those with higher anxiety showed less variance in their reaction times to negative stimuli than those with lower anxiety. One interpretation is that moderate levels of emotional arousal associated with anxiety make individuals less susceptible to the distracting effects of negative stimuli.

What kind of illness is anorexia nervosa? Revisited: some preliminary thoughts to finding a cure.

Two decades have elapsed since our publication of 'What kind of illness is anorexia nervosa?'. The question remains whether our understanding of anorexia nervosa and its treatment thereof has evolved over this time. The verdict is disappointing at best. Our current gold standard treatments remain over-valued and clinical outcomes are modest at best. Those in our field are haunted by the constant reminder that anorexia nervosa carries the highest mortality rate of any psychiatric disorder. This cannot continue and demands immediate action. In this essay, we tackle the myths that bedevil our field and explore a deeper phenotyping of anorexia nervosa. We argue that we can no longer declare agnostic views of the disorder or conceive treatments that are "brainless": it is incumbent upon us to challenge the prevailing zeitgeist and reconceptualise anorexia nervosa. Here we provide a roadmap for the future.

The impact of mindfulness training in early adolescence on affective executive control, and on later mental health during the COVID-19 pandemic: a randomised controlled trial.

BACKGROUND: Previous research suggests that mindfulness training (MT) appears effective at improving mental health in young people. MT is proposed to work through improving executive control in affectively laden contexts. However, it is unclear whether MT improves such control in young people. MT appears to mitigate mental health difficulties during periods of stress, but any mitigating effects against COVID-related difficulties remain unexamined. OBJECTIVE: To evaluate whether MT (intervention) versus psychoeducation (Psy-Ed; control), implemented in after-school classes: (1) Improves affective executive control; and/or (2) Mitigates negative mental health impacts from the COVID-19 pandemic. METHODS: A parallel randomised controlled trial (RCT) was conducted (Registration: https://osf.io/d6y9q/; Funding: Wellcome (WT104908/Z/14/Z, WT107496/Z/15/Z)). 460 students aged 11-16 years were recruited and randomised 1:1 to either MT (N=235) or Psy-Ed (N=225) and assessed preintervention and postintervention on experimental tasks and self-report inventories of affective executive control. The RCT was then extended to evaluate protective functions of MT on mental health assessed after the first UK COVID-19 lockdown. FINDINGS: Results provided no evidence that the version of MT used here improved affective executive control after training or mitigated negative consequences on mental health of the COVID-19 pandemic relative to Psy-Ed. No adverse events were reported. CONCLUSIONS: There is no evidence that MT improves affective control or downstream mental health of young people during stressful periods. CLINICAL IMPLICATIONS: We need to identify interventions that can enhance affective control and thereby young people's mental health.

Chronic facial eczema in sheep: description of gross and histological changes in the liver and association with serum gamma-glutamyltransferase activity at the time of sporidesmin intoxication.

AIMS: To determine the gross and histological changes developing in the liver of sheep 8 months after a single period of exposure to sporidesmin and to examine associations between the severity of gross and histological changes to the liver and the activity of gamma-glutamyltransferase (GGT) measured in serum in the sheep at the time of intoxication. METHODS: A group of 50 Romney ewes grazing a mixed ryegrass/white clover pasture were accidentally exposed to sporidesmin for up to 5 weeks. Seventeen sheep showed photosensitisation and four were subject to euthanasia. The remaining sheep were moved to safer pasture and a blood sample collected and analysed for serum GGT activity. The sheep were slaughtered 8 months later. Livers were classified into grossly normal, moderately affected, or severely affected and histology performed to assess portal fibrosis, biliary hyperplasia, portal inflammation, and hepatocellular necrosis. RESULTS: Serum GGT activity ranged from 59 to 1571 IU/L (reference range 32-70 IU/L). Thirteen of the 46 sheep developed clinical signs of facial eczema. However, at slaughter all except four sheep had grossly detectable changes to the shape of the liver including atrophy of the left lobe and the lateral part of the right lobe. Hypertrophy was typically limited to the medial part of the right lobe. In severely affected sheep the liver hypertrophy formed a nodular bulging mass. Changes in the liver shape were classified as severe in 25 and moderate in 17 sheep. Severely affected livers contained significantly more fibrosis than moderately affected livers (p = 0.001, Cliff's delta (d) = 0.68). While there was significantly greater fibrosis and biliary hyperplasia in the left than right lobes, histological changes were present throughout all samples taken of affected livers. Serum GGT activity taken during acute intoxication were correlated to subsequent fibrosis and biliary hyperplasia. CONCLUSIONS: Hepatic fibrosis develops in sheep after a single episode of sporidesmin intoxication, even in sheep with only mildly elevated GGT activity at the time of intoxication. Furthermore, the severity of the subsequent hepatic fibrosis was predicted by the degree of elevation of serum GGT activity during intoxication. CLINICAL RELEVANCE: More research is required to determine how the presence and severity of hepatic fibrosis affect animal production. However, if hepatic fibrosis does decrease production, the consistent development of fibrosis after sporidesmin ingestion reinforces the importance of avoiding exposure of livestock to sporidesmin. ABBREVIATIONS: GGT: Gamma-glutamyltransferase; d: Cliff's delta.

Susceptibility to prosocial and antisocial influence in adolescence.

INTRODUCTION: Adolescents are particularly susceptible to social influence and previous studies have shown that this susceptibility decreases with age. The current study used a cross-sectional experimental paradigm to investigate the effect of age and puberty on susceptibility to both prosocial and antisocial influence. METHODS: Participants (N = 520) aged 11-18 from London and Cambridge (United Kingdom) rated how likely they would be to engage in a prosocial (e.g. "help a classmate with their work") or antisocial (e.g. "make fun of a classmate") act. They were then shown the average rating (in fact fictitious) that other adolescents had given to the same question, and were then asked to rate the same behaviour again. RESULTS: Both prosocial and antisocial influence decreased linearly with age, with younger adolescents being more socially influenced when other adolescents' ratings were more prosocial and less antisocial than their own initial rating. Both antisocial and prosocial influence significantly decreased across puberty for boys but not girls (independent of age). CONCLUSIONS: These findings suggest that social influence declines with increasing maturity across adolescence. However, the exact relationship between social influence and maturity is dependent on the nature of the social influence and gender. Understanding when adolescents are most susceptible to different types of social influence, and how this might influence their social behaviour, has important implications for understanding adolescent social development.

Development and Evaluation of a Prediction Model for Ascertaining Rheumatic Heart Disease Status in Administrative Data.

BACKGROUND: Previous research has raised substantial concerns regarding the validity of the International Statistical Classification of Diseases and Related Health Problems (ICD) codes (ICD-10 I05-I09) for rheumatic heart disease (RHD) due to likely misclassification of non-rheumatic valvular disease (non-rheumatic VHD) as RHD. There is currently no validated, quantitative approach for reliable case ascertainment of RHD in administrative hospital data. METHODS: A comprehensive dataset of validated Australian RHD cases was compiled and linked to inpatient hospital records with an RHD ICD code (2000-2018, n=7555). A prediction model was developed based on a generalized linear mixed model structure considering an extensive range of demographic and clinical variables. It was validated internally using randomly selected cross-validation samples and externally. Conditional optimal probability cutpoints were calculated, maximising discrimination separately for high-risk versus low-risk populations. RESULTS: The proposed model reduced the false-positive rate (FPR) from acute rheumatic fever (ARF) cases misclassified as RHD from 0.59 to 0.27; similarly for non-rheumatic VHD from 0.77 to 0.22. Overall, the model achieved strong discriminant capacity (AUC: 0.93) and maintained a similar robust performance during external validation (AUC: 0.88). It can also be used when only basic demographic and diagnosis data are available. CONCLUSION: This paper is the first to show that not only misclassification of non-rheumatic VHD but also of ARF as RHD yields substantial FPRs. Both sources of bias can be successfully addressed with the proposed model which provides an effective solution for reliable RHD case ascertainment from hospital data for epidemiological disease monitoring and policy evaluation.

Healthcare workers' attitudes towards hand-hygiene monitoring technology.

BACKGROUND: Automated radio-frequency identification (RFID)-based hand-hygiene monitoring technology was implemented in an infectious disease department to study healthcare workers' (HCWs') practices and to improve hand hygiene. AIM: To assess HCWs' attitudes towards this innovative monitoring device in order to anticipate resistance to change and facilitate future implementation. METHODS: In-depth interviews and an ethnographic approach. FINDINGS: From the perspective of HCWs, while they recognize the usefulness of RFID technology to prevent the transmission of infections to patients, they expressed concerns about risks related to RFID electromagnetic waves, as well as control by their superiors. Overall, HCWs' opinions oscillated between positive feelings characterized by enthusiasm for the possibility of changing their practices using technologies and research, and negative feelings marked by strong criticisms of these technologies and research. These criticisms included blaming hand-hygiene monitoring technology for decontextualizing HCWs' practices. They perceived the technologies through the prism of the local and national contexts in which they are embedded. From their point of view, technologies are primarily in the best interests of the project team. Thus, they affirm and maintain the different interests and objectives between themselves and the project team, crystallizing a conflict of professional norms and values between these two groups. The forms of resistance taken by HCWs were practical as well as oral. CONCLUSION: Innovative technologies should be developed to address HCWs' attitudes surrounding RFIDs. It is crucial to inform HCWs about the nature of these technologies, although some criticisms about monitoring systems are based on more structural causes.

Investigating associations between lamb survival to weaning and dam udder and teat scores.

Aims: To examine a range of udder and teat traits in Romney ewes and to describe the frequency with which different scores occur, and to investigate associations between lamb survival to weaning and ewe udder and teat scores. Methods: Mixed-age, mature Romney ewes (n = 1,009) were enrolled from a commercial sheep flock located in the Wellington region of New Zealand in January 2017. A range of udder and teat traits were scored in all ewes, using visual assessment and palpation, at pre-mating (February), pre-lambing (October), docking (November) and weaning (January 2018). During the lambing period each newborn lamb was matched to its dam, with lamb mortalities recorded until weaning. Associations between udder and teat scores and lamb survival to weaning were examined using multivariable models for each udder-scoring time. Results: Records from 981 ewes and 1,822 live-born lambs were included in analyses, with 252 (13.8%) lambs recorded dead between birth and weaning. Lambs born to ewes with pre-mating udder scores of lump or hard had 4.9 (95% CI = 2.6-9.6, p = 0.003) and 3.0 (95% CI = 1.5-6.1, p < 0.001) increased odds of failure to survive to weaning, respectively, compared with lambs whose dams had normal udder scores. Lambs born to ewes with mastitis at docking or weaning had 3.0 (95% CI = 1.5-5.9, p = 0.001) and 3.9 (95% CI = 1.3-11.6, p = 0.013) increased odds of failure to survive to weaning, respectively, compared with lambs whose dams did not have mastitis. Offspring of dams with asymmetrical udders at docking or weaning had 3.3 (95% CI = 2.2-4.9, p < 0.001) and 2.5 (95% CI = 1.5-4.0, p < 0.001) increased odds of failure to survive, respectively, compared with lambs whose dams had symmetrical udders. Conclusion and Clinical Relevance: Pre-mating udder palpation scores of hard or lump were associated with increased odds of lambs not surviving to weaning compared with normal scores, and could be used to identify ewes that are likely to be unsuitable for retaining in the breeding flock. Farmers could also use clinical mastitis scores and udder symmetry scores at docking or weaning to identify ewes whose lambs had greater odds of failure to survive to weaning. However these scores do not provide an indication of future performance, therefore further investigation into the impact of the present season's score on future seasons' lamb survival is required.

Associations between lamb growth to weaning and dam udder and teat scores.

Aims: To investigate associations between lamb growth to weaning and dam udder and teat scores measured at pre-mating, pre-lambing, docking and weaning. Methods: Mature Romney ewes (n = 1,009) were enrolled from a commercial sheep flock located near Masterton, in the Wellington region of New Zealand in 2017. A range of udder and teat traits were scored in all ewes, using visual assessment and palpation, at pre-mating, pre-lambing, docking and weaning. During the lambing period, each newborn lamb was matched to its dam and lamb sex, birthweight and birth-rank were recorded. A rearing rank was allocated to each live-lamb at weaning, when all lambs were weighed (n = 1,570), allowing calculation of daily growth rates (g/day). Associations between udder and teat scores and lamb growth rates to weaning were examined using multivariable models for each udder-scoring time. Results: Growth rates of lambs whose dams had udder palpation scores of hard, or both teats recorded as abnormal, pre-mating were lower than lambs whose dams had normal scores (229.9 (95% CI = 213.2-246.6) vs. 254.5 (95% CI = 245.6-263.5) g/day; p = 0.011) and (227.4 (95% CI = 208.3-246.6) vs. 247.9 (95% CI = 235.7-260.2) g/day; p = 0.024), respectively. Growth rates of lambs whose dams had clinical mastitis at docking or weaning were lower than those without mastitis (215.8 (95% CI = 199.9-231.7) vs. 235.4 (95% CI = 225.4-255.0) g/day; p = 0.007) and (220.0 (95% CI = 205.2-234.8) vs. 254.7 (95% CI = 248.9-260.5) g/day; p < 0.001), respectively. Growth rates of lambs whose dams had asymmetrical udders at docking or weaning were lower than lambs whose dams had symmetrical udders (204.6 (95% CI = 189.7-219.5) vs. 240.2 (95% CI = 225.4-255.0) g/day; p < 0.001) and (223.3 (95% CI = 213.9-232.7) vs. 242.2 (95% CI = 229.4-255.0) g/day; p = 0.014), respectively. Conclusions and Clinical Relevance: Pre-mating udder palpation and teat palpation scores can be used to identify ewes whose lambs are predicted to have lower growth to weaning. Assuming a mean lamb age at weaning of 84.4 days, lambs born to ewes with a pre-mating score of hard would be expected to have a mean weaning weight that was 2.1 kg less than those whose dams had normal scores. Udder palpation, udder symmetry and clinical mastitis scores during lactation were also associated with lamb growth rates. Abbreviation: CALW: Conceptus-adjusted liveweight.

Associations between liveweight, body condition score and previous reproductive outcomes, and the risk of ewes bred at 18-months of age being dry at docking.

AIMS Firstly, to investigate associations between liveweight and body condition score (BCS) of two-tooth ewes (18-months-old at breeding) at breeding, pregnancy diagnosis (PD) and pre-lambing and the risk of being dry at docking, on commercial New Zealand sheep farms. Secondly, to investigate the association between previous reproductive outcomes as ewe lambs, and risk of being dry at docking as two-tooth ewes. METHODS Two-tooth ewes (n=9,006) were enrolled in four cohorts from three commercial sheep farms between 2010-14. Ewes were weighed and BCS assessed immediately pre-breeding, at PD (mid-pregnancy) and pre-lambing. At PD, ewes were identified as either non-pregnant, or having single or multiple fetuses. Palpation and examination of udders at docking was used to classify each ewe as either lactating or dry at docking. RESULTS Overall, 437/8,025 (5.4%) of ewes that were diagnosed pregnant at PD were dry at docking. The risk of being dry at docking decreased with increasing pre-lambing conceptus adjusted liveweight (CALW) on all farms (p≤0.002); for 2010-born ewes from Farm A the OR=0.87 (95% CI=0.81-0.92); for Farm B the OR=0.88 (95% CI=0.83-0.92) and for Farm C the OR=0.86 (95% CI=0.79-0.95). The risk of being dry at docking also decreased with increasing CALW gain from PD to pre-lambing for all farms (p≤0.003); for 2010-born ewes from Farm A the OR=0.89 (95% CI=0.84-0.94); for Farm B the OR=0.85 (95% CI=0.81-0.89) and for Farm C the OR=0.88 (95% CI=0.80-0.96). There was no association between BCS at breeding, PD or pre-lambing and the risk of being dry at docking for 2010-born ewes from Farm A, Farm B or Farm C (p>0.05). For 2010-born ewes on Farm A, the risk of being dry at docking was greater for two-tooth ewes that were previously dry at docking as ewe lambs than those that were lactating at docking as ewe lambs (OR=1.7 (95% CI=1.1-2.8); p=0.018), but this difference was not observed for ewes on Farm B or Farm C (p>0.5). CONCLUSIONS There were negative associations between ewe CALW pre-lambing, and CALW gain between PD and pre-lambing, and risk of being dry at docking. For all cohorts, heavier ewes and those that gained CALW were less likely to be dry at docking than lighter ewes or those that lost CALW, however these relationships varied between cohorts.

Anti-fibrotic Effects of CXCR4-Targeting i-body AD-114 in Preclinical Models of Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic fibrotic lung disease that is prevalent in individuals >50 years of age, with a median survival of 3-5 years and limited therapeutic options. The disease is characterized by collagen deposition and remodeling of the lung parenchyma in a process that is thought to be driven by collagen-expressing immune and structural cells. The G-protein coupled C-X-C chemokine receptor 4, CXCR4, is a candidate therapeutic target for IPF owing to its role in the recruitment of CXCR4+ fibrocytes from the bone marrow to fibrotic lung tissue and its increased expression levels by structural cells in fibrotic lung tissue. We have engineered a novel fully human single domain antibody "i-body" called AD-114 that binds with high affinity to human CXCR4. We demonstrate here that AD-114 inhibits invasive wound healing and collagen 1 secretion by human IPF fibroblasts but not non-diseased control lung fibroblasts. Furthermore, in a murine bleomycin model of pulmonary fibrosis, AD-114 reduced the accumulation of fibrocytes (CXCR4+/Col1+/CD45+) in fibrotic murine lungs and ameliorated the degree of lung injury. Collectively, these studies demonstrate that AD-114 holds promise as a new biological therapeutic for the treatment of IPF.

Direct identification of molds by sequence analysis in fungal chronic rhinosinusitis.

Fungi are widely implicated in chronic rhinosinusitis. Direct microscopic examination (DME) is used to confirm the biological diagnosis of fungal rhinosinusitis (FRS). Diagnostic sensitivity of DME is better than culture, however DME does not allow fungal species identification. In this study, we included 54 sinus samples demonstrating hyphae on DME. Direct sequencing was compared to culture for the identification of the fungal species. Sequence analysis identified fungi in 81.5% of cases while culture was positive in only 31.5%. The most common genus was Aspergillus and the identified species belonged to section Fumigati or to section Flavi. Among other fungi identified by sequence analysis, Schizophyllum commune was present in three samples attesting to the importance of this Basidiomycetes in FRS. Our results clearly demonstrate the superiority of sequencing compared to culture when performed on specimens with hyphal elements at DME, and contributes to the epidemiological knowledge of fungi involved in FRS.

A review of odour impact criteria in selected countries around the world.

Exposure to environmental odour can result in annoyance, health effects and depreciation of property values. Therefore, many jurisdictions classify odour as an atmospheric pollutant and regulate emissions and/or impacts from odour generating activities at a national, state or municipal level. In this work, a critical review of odour regulations in selected jurisdictions of 28 countries is presented. Individual approaches were identified as: comparing ambient air odour concentration and individual chemicals statistics against impact criteria (maximum impact standard); using fixed and variable separation distances (separation distance standard); maximum emission rate for mixtures of odorants and individual chemical species (maximum emission standard); number of complaints received or annoyance level determined via community surveys (maximum annoyance standard); and requiring use of best available technologies (BAT) to minimize odour emissions (technology standard). The comparison of model-predicted odour concentration statistics against odour impact criteria (OIC) is identified as one of the most common tools used by regulators to evaluate the risk of odour impacts in planning stage assessments and is also used to inform assessment of odour impacts of existing facilities. Special emphasis is given to summarizing OIC (concentration percentile and threshold) and the manner in which they are applied. The way short term odour peak to model time-step mean (peak-to-mean) effects is also captured. Furthermore, the fundamentals of odorant properties, dimensions of nuisance odour, odour sampling and analysis methods and dispersion modelling guidance are provided. Common elements of mature and effective odour regulation frameworks are identified and an integrated multi-tool strategy is recommended.

Investigation of fetal loss in ewe lambs in relation to liveweight changes and progesterone concentrations in early to mid gestation.

AIMS: To investigate associations between changes in liveweight and fetal loss in ewe lambs and to determine whether fetal loss was associated with concentrations of progesterone in early and mid-gestation. METHODS: Ewe lambs on two commercial sheep farms (Flock A; n=504 and Flock B; n=460) in the southern North Island of New Zealand were weighed, and body condition score was assessed, prior to breeding and throughout pregnancy. Pregnancy diagnosis was undertaken approximately 56 (PD1), 80 (PD2) and 110 (PD3) days after the start of breeding and fetal loss determined. Blood samples were collected from a cohort of 407 ewe lambs between 45-54 and 73-84 days of gestation. Those that subsequently were diagnosed with fetal loss (n=16) were matched with ewe lambs that maintained pregnancy (n=16), and concentrations of progesterone were measured in the plasma samples from these animals. RESULTS: Fetal loss was diagnosed in 55/472 (11.7%) pregnant ewes from Flock A and 14/378 (3.7%) from Flock B. In both flocks the change in conceptus-free liveweight (CFLW) between PD1 and PD2 differed between ewe lambs with and without fetal loss; in Flock A the mean change was -59.9 (95% CI=-80.1 to -39.7) g/day vs. -3.43 (95% CI=-9.8 to 3.0) g/day (p<0.001), and in Flock B the change was -38.5 (95% CI=-78.9 to 1.94) g/day vs. 79.5 (95% CI=72.6-86.4) g/day (p<0.001). Similarly in Flock A the mean increase in CFLW between PD2 and PD3 was lower in ewe lambs with fetal loss than in those that maintained pregnancy (25.8 (95% CI=-13.8 to 65.4) g/day vs. 181.9 (95% CI=175.1-188.7) g/day) (p<0.001). There was no difference (p>0.05) in early and mid-gestation mean concentrations of progesterone in plasma between ewe lambs that had fetal loss compared with those that maintained pregnancy. CONCLUSIONS: Ewe lambs with fetal loss had a marked reduction in CFLW in the 24-30 days leading up to the identification of the fetal loss compared with those that maintained pregnancy. Early and mid-gestation concentrations of progesterone in plasma were similar between ewe lambs who went on to have fetal loss and those that maintained pregnancy.

Are adolescents more vulnerable to the harmful effects of cannabis than adults? A placebo-controlled study in human males.

Preclinical research demonstrates that cannabinoids have differing effects in adolescent and adult animals. Whether these findings translate to humans has not yet been investigated. Here we believe we conducted the first study to compare the acute effects of cannabis in human adolescent (n=20; 16-17 years old) and adult (n=20; 24-28 years old) male cannabis users, in a placebo-controlled, double-blind cross-over design. After inhaling vaporized active or placebo cannabis, participants completed tasks assessing spatial working memory, episodic memory and response inhibition, alongside measures of blood pressure and heart rate, psychotomimetic symptoms and subjective drug effects (for example, 'stoned', 'want to have cannabis'). Results showed that on active cannabis, adolescents felt less stoned and reported fewer psychotomimetic symptoms than adults. Further, adults but not adolescents were more anxious and less alert during the active cannabis session (both pre- and post-drug administration). Following cannabis, cognitive impairment (reaction time on spatial working memory and prose recall following a delay) was greater in adults than adolescents. By contrast, cannabis impaired response inhibition accuracy in adolescents but not in adults. Moreover, following drug administration, the adolescents did not show satiety; instead they wanted more cannabis regardless of whether they had taken active or placebo cannabis, while the opposite was seen for adults. These contrasting profiles of adolescent resilience (blunted subjective, memory, physiological and psychotomimetic effects) and vulnerability (lack of satiety, impaired inhibitory processes) show some degree of translation from preclinical findings, and may contribute to escalated cannabis use by human adolescents.

Altered gray matter organization in children and adolescents with ADHD: a structural covariance connectome study.

Although multiple studies have reported structural deficits in multiple brain regions in attention-deficit hyperactivity disorder (ADHD), we do not yet know if these deficits reflect a more systematic disruption to the anatomical organization of large-scale brain networks. Here we used a graph theoretical approach to quantify anatomical organization in children and adolescents with ADHD. We generated anatomical networks based on covariance of gray matter volumes from 92 regions across the brain in children and adolescents with ADHD (n=34) and age- and sex-matched healthy controls (n=28). Using graph theory, we computed metrics that characterize both the global organization of anatomical networks (interconnectivity (clustering), integration (path length) and balance of global integration and localized segregation (small-worldness)) and their local nodal measures (participation (degree) and interaction (betweenness) within a network). Relative to Controls, ADHD participants exhibited altered global organization reflected in more clustering or network segregation. Locally, nodal degree and betweenness were increased in the subcortical amygdalae in ADHD, but reduced in cortical nodes in the anterior cingulate, posterior cingulate, mid temporal pole and rolandic operculum. In ADHD, anatomical networks were disrupted and reflected an emphasis on subcortical local connections centered around the amygdala, at the expense of cortical organization. Brains of children and adolescents with ADHD may be anatomically configured to respond impulsively to the automatic significance of stimulus input without having the neural organization to regulate and inhibit these responses. These findings provide a novel addition to our current understanding of the ADHD connectome.

Psychometric Properties of the Dutch Depression Stigma Scale (DSS) and Associations with Personal and Perceived Stigma in a Depressed and Community Sample.

BACKGROUND: Research on depression stigma is needed to gain more insight into the underlying construct and to reduce the level of stigma in the community. However, few validated measurements of depression stigma are available in the Netherlands. Therefore, this study first sought to examine the psychometric properties of the Dutch translation of the Depression Stigma Scale (DSS). Second, we examined which demographic (gender, age, education, partner status) and other variables (anxiety and knowledge of depression) are associated with personal and perceived stigma within these samples. METHODS: The study population consisted of an adult convenience sample (n = 253) (study 1) and a community adult sample with elevated depressive symptoms (n = 264) (study 2). Factor structure, internal consistency, and validity were assessed. The associations between stigma, demographic variables and anxiety level were examined with regression analyses. RESULTS: Confirmatory factor analysis supported the validity and internal consistency of the DSS personal stigma scale. Internal consistency was sufficient (Cronbach's alpha = .70 (study 1) and .77 (study 2)). The results regarding the perceived stigma scale revealed no clear factor structure. Regression analyses showed that personal stigma was higher in younger people, those with no experience with depression, and those with lower education. CONCLUSIONS: This study established the validity and internal consistency of the DSS personal scale in the Netherlands, in a community sample and in people with elevated depressive symptoms. However, additional research is needed to examine the factor structure of the DSS perceived scale and its use in other samples.

A novel corrective approach to achieve satisfactory function of a 'sunk' colostomy.

INTRODUCTION: Creation of gastrointestinal stomas is a common colorectal procedure associated with early or late complications, some of which demand advanced technical skills and expertise for optimal management. CASE HISTORY: A 63-year-old male underwent a defunctioning loop colostomy for locally advanced rectal cancer with liver metastasis. Three months later, he had developed a skinfold over his stoma that resulted in a horizontal skin crease traversing through the stoma, causing the stoma to 'sink' leading to obliteration of the stomal opening. This scenario led to ineffective attachment of a stoma appliance, resulting in painful peristomal ulcers. After excision of the anterior abdominal wall, assessment of colostomy opening was carried out, followed by closure of the subcutaneous tissues and drain fixation. An elevated colostomy with an adequate functional opening was seen after wound closure. The patient made an uneventful recovery and was discharged home. After 3 weeks, he had a fully opened, normally functioning colostomy and peristomal ulcers were almost healed. CONCLUSIONS: This case highlights the challenges of stoma management, its related risks, avoidance of delay in chemotherapy, a patient wish for early return to work, and the novel approach we adopted to deal with these issues.

Repetition rate after non-fatal self-poisoning in Sri-Lanka: a one year prospective longitudinal study

Introduction: Attempted or non-fatal self-poisoning is an important public health problem in Sri Lanka. Current evidence from Sri Lanka suggests that this phenomenon is more common among young people, and females, and is associated with a recent interpersonal conflict. International studies indicate that recent non-fatal selfharm is associated with an increased risk of repetition and completed suicide. Prospective follow-up data regarding rates of repetition of self-harm in Sri Lanka is limited. Objectives: The aim of this study was to describe the rate of repetition, and rate of suicidal ideation, at one-year follow up among those who have survived an act of selfpoisoning. Methods: Participants who presented to the toxicology unit, Teaching Hospital Peradeniya over a 14-month period, for medical management of non-fatal self-poisoning, were contacted by telephone one-year following the initial presentation. Results: A total of 949 persons were included in the study, of which 35.3% (n=335) were contactable at one-year follow-up. The rate of repetition of self-harm after one year was 2.5% and 2.7% of participants had suicidal ideation at one-year follow-up. Conclusions: The rate of repetition of self-harm in Sri Lanka is lower than the rate reported in the West (15%).

Improvement of BCG protective efficacy with a novel chimpanzee adenovirus and a modified vaccinia Ankara virus both expressing Ag85A.

A replication-deficient chimpanzee adenovirus expressing Ag85A (ChAdOx1.85A) was assessed, both alone and in combination with modified vaccinia Ankara also expressing Ag85A (MVA85A), for its immunogenicity and protective efficacy against a Mycobacterium tuberculosis (M.tb) challenge in mice. Naïve and BCG-primed mice were vaccinated or boosted with ChAdOx1.85A and MVA85A in different combinations. Although intranasally administered ChAdOx1.85A induced strong immune responses in the lungs, it failed to consistently protect against aerosol M.tb challenge. In contrast, ChAdOx1.85A followed by MVA85A administered either mucosally or systemically, induced strong immune responses and was able to improve the protective efficacy of BCG. This vaccination regime has consistently shown superior protection over BCG alone and should be evaluated further.