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Neurocognitive impairments robustly predict functional outcome. However, heterogeneity in neurocognition is common within diagnostic groups, and data-driven analyses reveal homogeneous neurocognitive subgroups cutting across diagnostic boundaries.
To determine whether data-driven neurocognitive subgroups of young people with emerging mental disorders are associated with 3-year functional course.
Model-based cluster analysis was applied to neurocognitive test scores across nine domains from 629 young people accessing mental health clinics. Cluster groups were compared on demographic, clinical and substance-use measures. Mixed-effects models explored associations between cluster-group membership and socio-occupational functioning (using the Social and Occupational Functioning Assessment Scale) over 3 years, adjusted for gender, premorbid IQ, level of education, depressive, positive, negative and manic symptoms, and diagnosis of a primary psychotic disorder.
Cluster analysis of neurocognitive test scores derived three subgroups described as ‘normal range’ (n = 243, 38.6%), ‘intermediate impairment’ (n = 252, 40.1%), and ‘global impairment’ (n = 134, 21.3%). The major mental disorder categories (depressive, anxiety, bipolar, psychotic and other) were represented in each neurocognitive subgroup. The global impairment subgroup had lower functioning for 3 years of follow-up; however, neither the global impairment (B = 0.26, 95% CI −0.67 to 1.20; P = 0.581) or intermediate impairment (B = 0.46, 95% CI −0.26 to 1.19; P = 0.211) subgroups differed from the normal range subgroup in their rate of change in functioning over time.
Neurocognitive impairment may follow a continuum of severity across the major syndrome-based mental disorders, with data-driven neurocognitive subgroups predictive of functional course. Of note, the global impairment subgroup had longstanding functional impairment despite continuing engagement with clinical services.
Stenting of ostial pulmonary artery stenosis presents several unique challenges. These include difficulty in defining anatomy and need for precise stent placement in order to avoid missing the ostial stenosis or jailing either the contralateral branch pulmonary artery or the ipsilateral upper lobe branch.
A retrospective review of outcomes was conducted in 1.5 or 2-ventricle patients who underwent stent placement for ostial branch pulmonary artery stenosis. Specific catheterisation lab techniques were reviewed.
Forty-seven branch pulmonary arteries underwent stent placement for ostial stenosis in 43 patients. The median age and weight were 3.7 (0.3–18.1) years and 14.2 (5.6–70.0) kg, respectively. Three (2–8) angiographic projections were needed to profile the ostial stenosis. Open-cell stents were used in 23 and stents were modified in 5 cases. Following stent implantation, the minimum diameter improved from 3.6 (0.8–10.5) to 8.1 (4.2–16.5) mm (p < 0.001). The gradient improved from 21 (0–66) to 4 (0–27) mmHg (p < 0.001). Stent malposition occurred in eight (17%) of the stents placed. Five migrated distally causing suboptimal ostial coverage necessitating placement of a second stent in four. Three migrated proximally and partially jailed the contralateral pulmonary artery. Intentional jailing of the upper lobe branch occurred in four additional cases. At a follow-up of 2.4 (0.3–4.9) years, 15 stents underwent further dilation and 1 had a second stent placed within the exiting stent.
Ostial branch pulmonary artery stenosis may require additional angiography to accurately define the ostial stenosis. Treatment with stents is effective but carries high rates of stent malposition.
The German Twin Family Panel (TwinLife) is a German longitudinal study of monozygotic and dizygotic same-sex twin pairs and their families that was designed to investigate the development of social inequalities over the life course. The study covers an observation period from approximately 2014 to 2023. The target population of the sample are reared-together twins of four different age cohorts that were born in 2009/2010 (cohort 1), in 2003/2004 (cohort 2), in 1997/1998 (cohort 3) and between 1990 and 1993 (cohort 4). In the first wave, the study included data on 4097 twin families. Families were recruited in all parts of Germany so that the sample comprises the whole range of the educational, occupational and income structure. As of 2019, two face-to-face, at-home interviews and two telephone interviews have been conducted. Data from the first home and telephone interviews are already available free of charge as a scientific use-file from the GESIS data archive. This report aims to provide an overview of the study sample and design as well as constructs that are unique in TwinLife in comparison with previous twin studies — such as an assessment of cognitive abilities or information based on the children’s medical records and report cards. In addition, major findings based on the data already released are displayed, and future directions of the study are presented and discussed.
The Comprehensive Framework for Disaster Evaluation Typologies, developed in 2017 (CFDET 2017), aims to unify and facilitate agreement regarding the identification, structure, and relationships between various evaluation typologies found in the disaster setting. A peer-reviewed validation process sought input from international experts in the fields of disaster medicine, disaster/emergency management, humanitarian/development, and evaluation. This paper discusses the validation process, its results, and outcomes.
Previous frameworks, identified in the literature, lack validation and consistent terminology. To gain credibility and utility, this unique framework needed to be validated by international experts in the disaster setting.
A mixed methods approach was designed to validate the framework. An initial iterative process informed an online survey which used a combination of a five-point Likert scale and open-ended questions. Pre-determined consensus thresholds, informed by a targeted literature review, provided the validation criteria.
A sample of 33 experts from 11 countries responded to the validation process. Quantitative measures largely supported the elements and relationships of the framework, and strongly supported its value and usefulness for supporting, promoting, and undertaking evaluations, as well as its usefulness for teaching evaluation in the disaster setting. Qualitative input suggested opportunities to strengthen and enhance the framework. There were limited responses to better understand the barriers and enablers of undertaking disaster evaluations. A potential for self-selection bias of respondents may be a limitation of this study. The attainment of high consensus thresholds, however, provides confidence in the validity of the results.
For the first time, a framework of this nature has undergone a rigorous validation process by experts in three related disciplines at an international level. The modified framework, CFDET 2018, provides a unifying framework within which existing evaluation typologies can be structured. It gives evaluators confidence to choose an appropriate strategy for their particular evaluation in the disaster setting and facilitates consistency in reporting across the different phases of a disaster to better understand the process, outcomes, and impacts of the efficacy and efficiency of interventions. Future research could create a series of toolkits to support improved disaster evaluation processes and to evaluate the utility of the framework in the real-world setting.
Despite established clinical associations among major depression (MD), alcohol dependence (AD), and alcohol consumption (AC), the nature of the causal relationship between them is not completely understood. We leveraged genome-wide data from the Psychiatric Genomics Consortium (PGC) and UK Biobank to test for the presence of shared genetic mechanisms and causal relationships among MD, AD, and AC.
Linkage disequilibrium score regression and Mendelian randomization (MR) were performed using genome-wide data from the PGC (MD: 135 458 cases and 344 901 controls; AD: 10 206 cases and 28 480 controls) and UK Biobank (AC-frequency: 438 308 individuals; AC-quantity: 307 098 individuals).
Positive genetic correlation was observed between MD and AD (rgMD−AD = + 0.47, P = 6.6 × 10−10). AC-quantity showed positive genetic correlation with both AD (rgAD−AC quantity = + 0.75, P = 1.8 × 10−14) and MD (rgMD−AC quantity = + 0.14, P = 2.9 × 10−7), while there was negative correlation of AC-frequency with MD (rgMD−AC frequency = −0.17, P = 1.5 × 10−10) and a non-significant result with AD. MR analyses confirmed the presence of pleiotropy among these four traits. However, the MD-AD results reflect a mediated-pleiotropy mechanism (i.e. causal relationship) with an effect of MD on AD (beta = 0.28, P = 1.29 × 10−6). There was no evidence for reverse causation.
This study supports a causal role for genetic liability of MD on AD based on genetic datasets including thousands of individuals. Understanding mechanisms underlying MD-AD comorbidity addresses important public health concerns and has the potential to facilitate prevention and intervention efforts.
A 15-month-old child underwent percutaneous expansion of a Melody transcatheter pulmonary valve in the mitral position to accommodate growth after initial surgical implantation during infancy, but transiently decompensated after valvuloplasty owing to stent malformation. The Melody valve in the mitral position of small patients can be further expanded by percutaneous dilation, but there are a number of potential complications and technical improvements to consider.
The discovery via gravitational waves of binary black hole systems with total masses greater than 60Mʘ has raised interesting questions for stellar evolution theory. Among the most promising formation channels for these systems is one involving a common envelope binary containing a low metallicity, core helium burning star with mass ⁓30 – 40Mʘ and a black hole with mass ⁓30 – 40Mʘ. For this channel to be viable, the common envelope binary must eject more than half the giant star’s mass and reduce its orbital separation by as much as a factor of 80. We discuss issues faced in numerically simulating the common envelope evolution of such systems and present a 3D AMR simulation of the dynamical inspiral of a low-metallicity red supergiant with a massive black hole companion.
One indication for intervention in coarctation of the aorta is a peak-to-peak gradient >20 mmHg. Gradients may be masked in patients under general anaesthesia and may be higher during exercise. Isoproterenol was given during cardiac catheterisation to simulate a more active physiologic state.
We aimed to describe the haemodynamic effects of isoproterenol in patients with coarctation and the impact of intervention on the elicited gradients.
A retrospective study was performed on two-ventricle patients who underwent cardiac catheterisation for coarctation with isoproterenol testing.
25 patients received isoproterenol before and after intervention. With isoproterenol, the mean diastolic (p=0.0015) and mean arterial (p=0.0065) blood pressures proximal to the coarctation decreased significantly. The mean systolic, diastolic, and mean arterial blood pressures distal to the coarctation decreased significantly (p<0.0001). In patients with a baseline gradient ⩽20 mmHg (n=17) at catheterisation, the median gradient increased from 10 (0–20) to 30 (15–50) mmHg (p<0.0001) with isoproterenol. Of these, 15 patients developed a gradient >20 mmHg. Post intervention, the median gradient decreased to 2 (0–29) mmHg, versus baseline, p=0.005, and with isoproterenol it decreased to 8 (0–27) mmHg, versus pre-intervention isoproterenol, p<0.0001. There were significant improvements in the gradients by Doppler (<0.0001) and by blood pressure cuff (p=0.0313). The gradients on isoproterenol best correlated with gradients by blood pressure cuff in the awake state (R2=0.76, p<0.0001).
Isoproterenol can be a useful tool to assess the significance of a coarctation and the effectiveness of an intervention. Percutaneous interventions can effectively reduce the gradients elicited by isoproterenol.
The frequency of disasters is increasing around the world with more people being at risk. There is a moral imperative to improve the way in which disaster evaluations are undertaken and reported with the aim of reducing preventable mortality and morbidity in future events. Disasters are complex events and undertaking disaster evaluations is a specialized area of study at an international level.
While some frameworks have been developed to support consistent disaster research and evaluation, they lack validation, consistent terminology, and standards for reporting across the different phases of a disaster. There is yet to be an agreed, comprehensive framework to structure disaster evaluation typologies.
The aim of this paper is to outline an evolving comprehensive framework for disaster evaluation typologies. It is anticipated that this new framework will facilitate an agreement on identifying, structuring, and relating the various evaluations found in the disaster setting with a view to better understand the process, outcomes, and impacts of the effectiveness and efficiency of interventions.
Research was undertaken in two phases: (1) a scoping literature review (peer-reviewed and “grey literature”) was undertaken to identify current evaluation frameworks and typologies used in the disaster setting; and (2) a structure was developed that included the range of typologies identified in Phase One and suggests possible relationships in the disaster setting.
No core, unifying framework to structure disaster evaluation and research was identified in the literature. The authors propose a “Comprehensive Framework for Disaster Evaluation Typologies” that identifies, structures, and suggests relationships for the various typologies detected.
The proposed Comprehensive Framework for Disaster Evaluation Typologies outlines the different typologies of disaster evaluations that were identified in this study and brings them together into a single framework. This unique, unifying framework has relevance at an international level and is expected to benefit the disaster, humanitarian, and development sectors. The next step is to undertake a validation process that will include international leaders with experience in evaluation, in general, and disasters specifically. This work promotes an environment for constructive dialogue on evaluations in the disaster setting to strengthen the evidence base for interventions across the disaster spectrum. It remains a work in progress.
WongDF, SpencerC, BoydL, BurkleFMJr., ArcherF. Disaster Metrics: A Comprehensive Framework for Disaster Evaluation Typologies. Prehosp Disaster Med. 2017;32(5):501–514.
The parent–child attachment relationship plays an important role in the development of the infant's stress regulation system. However, genetic and epigenetic factors such as FK506 binding protein 51 (FKBP5) genotype and DNA methylation have also been associated with hypothalamus–pituitary–adrenal axis functioning. In the current study, we examined how parent–child dyadic regulation works in concert with genetic and epigenetic aspects of stress regulation. We study the associations of attachment, extreme maternal insensitivity, FKBP5 single nucleotide polymorphism 1360780, and FKBP5 methylation, with cortisol reactivity to the Strange Situation Procedure in 298 14-month-old infants. The results indicate that FKBP5 methylation moderates the associations of FKBP5 genotype and resistant attachment with cortisol reactivity. We conclude that the inclusion of epigenetics in the field of developmental psychopathology may lead to a more precise picture of the interplay between genetic makeup and parenting in shaping stress reactivity.
Epidemiological evidence indicates that high consumption of tomatoes and tomato-based products reduces the risk of chronic diseases such as CVD and cancer. Such potential benefits are often ascribed to high concentrations of lycopene present in tomato products. Mainly from the results of in vitro studies, potential biological mechanisms by which carotenoids could protect against heart disease and cancer have been suggested. These include cholesterol reduction, inhibition of oxidation processes, modulation of inflammatory markers, enhanced intercellular communication, inhibition of tumourigenesis and induction of apoptosis, metabolism to retinoids and antiangiogenic effects. However, with regard to CVD, results from intervention studies gave mixed results. Over fifty human intervention trials with lycopene supplements or tomato-based products have been conducted to date, the majority being underpowered. Many showed some beneficial effects but mostly on non-established cardiovascular risk markers such as lipid peroxidation, DNA oxidative damage, platelet activation and inflammatory markers. Only a few studies showed improvement in lipid profiles, C reactive protein and blood pressure. However, recent findings indicate that lycopene could exert cardiovascular protection by lowering HDL-associated inflammation, as well as by modulating HDL functionality towards an antiatherogenic phenotype. Furthermore, in vitro studies indicate that lycopene could modulate T lymphocyte activity, which would also inhibit atherogenic processes and confer cardiovascular protection. These findings also suggest that HDL functionality deserves further consideration as a potential early marker for CVD risk, modifiable by dietary factors such as lycopene.
Pathological gambling is a behavioural addiction with negative economic, social, and psychological consequences. Identification of contributing genes and pathways may improve understanding of aetiology and facilitate therapy and prevention. Here, we report the first genome-wide association study of pathological gambling. Our aims were to identify pathways involved in pathological gambling, and examine whether there is a genetic overlap between pathological gambling and alcohol dependence.
Four hundred and forty-five individuals with a diagnosis of pathological gambling according to the Diagnostic and Statistical Manual of Mental Disorders were recruited in Germany, and 986 controls were drawn from a German general population sample. A genome-wide association study of pathological gambling comprising single marker, gene-based, and pathway analyses, was performed. Polygenic risk scores were generated using data from a German genome-wide association study of alcohol dependence.
No genome-wide significant association with pathological gambling was found for single markers or genes. Pathways for Huntington's disease (P-value = 6.63 × 10−3); 5′-adenosine monophosphate-activated protein kinase signalling (P-value = 9.57 × 10−3); and apoptosis (P-value = 1.75 × 10−2) were significant. Polygenic risk score analysis of the alcohol dependence dataset yielded a one-sided nominal significant P-value in subjects with pathological gambling, irrespective of comorbid alcohol dependence status.
The present results accord with previous quantitative formal genetic studies which showed genetic overlap between non-substance- and substance-related addictions. Furthermore, pathway analysis suggests shared pathology between Huntington's disease and pathological gambling. This finding is consistent with previous imaging studies.
Climbing bean is the key staple legume crop in the highlands of East and Central Africa. We assessed the impact of interactions between soil fertility characteristics, crop management and socio-economic factors, such as household resource endowment and gender of the farmer, on climbing bean productivity and yield responses to basal P fertiliser in northern Rwanda. Through a combination of detailed characterisations of 12 farms and on-farm demonstration trials at 110 sites, we evaluated variability in grain yields and responses to fertiliser. Grain yields varied between 0.14 and 6.9 t ha−1 with an overall average of 1.69 t ha−1. Household resource endowment and gender of the farmer was strongly associated with climbing bean yield, even though these were partly confounded with Sector. Poorer households and women farmers achieved lower yields than wealthier households and male farmers. Household resource endowment and gender were likely to act as proxies for a range of agronomic and crop management factors that determine crop productivity, such as soil fertility, current and past access to organic manure and mineral fertiliser, access to sufficient quality staking material, ability to conduct crop management operation on time, but we found evidence for only some of these relationships. Poorer households and female farmers grew beans on soils with poorer soil fertility. Moreover, poorer households had a lower density of stakes, while stake density was strongly correlated with yield. Diammonium phosphate (DAP) fertiliser application led to a substantial increase in the average grain yield (0.66 t ha−1), but a large variability in responses implied that its use would be economically worthwhile for roughly half of the farmers. For the sake of targeting agricultural innovations to those households that are most likely to adopt, the Ubudehe household typology – a Rwandan government system of wealth categorisation – could be a useful and easily available tool to structure rural households within regions of Rwanda that are relatively uniform in agro-ecology.
We analyzed birth order differences in means and variances of height and body mass index (BMI) in monozygotic (MZ) and dizygotic (DZ) twins from infancy to old age. The data were derived from the international CODATwins database. The total number of height and BMI measures from 0.5 to 79.5 years of age was 397,466. As expected, first-born twins had greater birth weight than second-born twins. With respect to height, first-born twins were slightly taller than second-born twins in childhood. After adjusting the results for birth weight, the birth order differences decreased and were no longer statistically significant. First-born twins had greater BMI than the second-born twins over childhood and adolescence. After adjusting the results for birth weight, birth order was still associated with BMI until 12 years of age. No interaction effect between birth order and zygosity was found. Only limited evidence was found that birth order influenced variances of height or BMI. The results were similar among boys and girls and also in MZ and DZ twins. Overall, the differences in height and BMI between first- and second-born twins were modest even in early childhood, while adjustment for birth weight reduced the birth order differences but did not remove them for BMI.
The development and maintenance of an alcohol addiction is a complex interaction between genetic and environmental factors. Genetic effects seem to contribute substantially to the risk of developing an addiction, but also to its course and patients’ responses to different treatments. Recent studies identified associations between polymorphisms in the genes of glutamate and μ-opioid receptors and addiction risk. Those receptors are of special interest, because they are targets of therapeutic agents, such as acamprosate and topiramate.
Objectives and aims
Several studies were conducted, in order to further determine the effects of genetic polymorphisms in glutamate and opioid receptor genes on addictive behavior, neural response to alcohol cues and relapse risk.
Genetic effects were investigated in samples of alcohol-dependent patients using functional imaging techniques, neuropsychological tests and follow-up investigation after standard clinical treatment. Data on clinical parameters, neuronal response to alcohol cues, functional neuronal connectivity and relapse risk were collected and analyzed.
Results demonstrate effects of genetic polymorphisms in glutamate and opioid receptors on neuronal response to alcohol cues in frontal and mesolimbic brain areas, subjective craving and time to first relapse. Current findings will be discussed in the light of existing evidence on the contribution of genetic effects to treatment outcome and patient stratification.
The investigation of genetic risk factors and mechanisms by which they affect addiction related phenotypes seems to be a promising tool to identify molecular treatment targets and predictors for successful treatment strategies.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
In September 2011, a patient cluster with a rare Salmonella serotype – Strathcona – was identified in Denmark. An outbreak investigation was initiated to reveal the source in order to stop the outbreak. In addition to hypothesis-generating interviews, comparable analyses of patients’ household shopping receipts were conducted. A matched case-control study with 25 cases and 56 population register controls was conducted to test the findings of the hypothesis-generating investigation. In total, 43 cases of Salmonella Strathcona were reported in Denmark. Additionally, 28 cases were reported from Germany, Italy, Austria and Belgium. The results of the investigation in Denmark showed that 8/10 cases had bought datterino tomatoes prior to disease onset. Illness was associated with a specific supermarket chain [matched odds ratio (mOR) 16·9, 95% confidence interval (CI) 2·2–130], and having consumed elongated small tomatoes (OR 28·1, 95% CI 2·6–302). Traceback investigation showed that the tomatoes came from an Italian producer. This outbreak, linked to tomatoes, underpins the growing recognition of the broad source range of Salmonella and the ability of fresh produce to cause multi-country outbreaks. It is important to strengthen the international cooperation between public-health and food-safety authorities in the European Union to investigate future multi-country outbreaks in order to prevent illness from ready-to-eat produce.
The aim of the present study was to determine the outcomes of using the Valeo stent (Bard Peripheral Vascular, Tempe, Arizona, United States of America) in small children with CHD.
Stenting vascular stenoses is safe and effective in adults and older children with CHD but is limited in smaller children. The design of the Valeo stent addresses these limitations but has not been extensively described.
Bench testing was conducted to determine the maximum diameter of the stent, foreshortening, and side-cell diameter. A retrospective analysis of Valeo stents implanted between October, 2012 and October, 2014 was performed. Patient profile, pre-implant/post-implant catheterization data, and stent geometry were reviewed.
Bench testing: medium and large Valeo stents can be dilated up to 13 mm and 20 mm diameters, respectively. Side-cells are dilatable up to 12 mm. Valeo stents are of low profile – delivered through 6- or 7-Fr sheaths – and show minimal foreshortening. Retrospective analysis: a total of 81 stents were implanted in 61 patients with CHD. The median weight was 15.3 kg, and the median age was 58.9 months. Stents were implanted in the pulmonary artery, systemic vein, aorta, and pulmonary vein. Overall, mean vessel diameters increased from 4.1 to 7.7 mm (121.7%). There was effective mean gradient reduction: 3.7–0.5 mmHg (63%) in the venous systems, 28.2–12.5 mmHg (63.7%) in the pulmonary arteries, and 17.4–4 mmHg (77.1%) in the aorta. The mean stent foreshortening was 2.5%, and the mean recoil was 5.9%. Side-cells that crossed other vessels were dilated in four cases, and stents were re-mounted onto different-sized balloons in seven cases.
The features of the Valeo stent, such as low profile, large maximum diameter, open-cell design, minimal foreshortening, and recoil, make it suitable for treating vascular stenoses in small children with CHD.
The effects of fish oil (FO) supplementation on glycaemic control are unclear, and positive effects may occur only when the phospholipid content of tissue membranes exceeds 14 % as n-3 PUFA. Subjects (n 36, thirty-three completed) were paired based on metabolic parameters and allocated into a parallel double-blind randomised trial with one of each pair offered daily either 6 g of FO (3·9 g n-3 PUFA) or 6 g of maize oil (MO) for 9 months. Hyperinsulinaemic–euglycaemic–euaminoacidaemic (HIEGEAA) clamps (with [6,6 2H2 glucose]) were performed at the start and end of the intervention. Endogenous glucose production (EGP) and whole-body protein turnover (WBPT) were each measured after an overnight fast. The primary outcome involved the effect of oil type on insulin sensitivity related to glycaemic control. The secondary outcome involved the effect of oil type on WBPT. Subjects on FO (n 16) had increased erythrocyte n-3 PUFA concentrations >14 %, whereas subjects on MO (n 17) had unaltered n-3 PUFA concentrations at 9 %. Type of oil had no effect on fasting EGP, insulin sensitivity or total glucose disposal during the HIEGEAA clamp. In contrast, under insulin-stimulated conditions, total protein disposal (P=0·007) and endogenous WBPT (P=0·001) were both increased with FO. In an associated pilot study (n 4, three completed), although n-3 PUFA in erythrocyte membranes increased to >14 % with the FO supplement, the enrichment in muscle membranes remained lower (8 %; P<0·001). In conclusion, long-term supplementation with FO, at amounts near the safety limits set by regulatory authorities in Europe and the USA, did not alter glycaemic control but did have an impact on WBPT.