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Electroconvulsive treatment (ECT) is an effective treatment option for patients with a major depressive disorder. Despite a lot of research efforts the exact mechanism of action of ECT is still not clear.
Nitric oxide (NO) is a gaseous compound, synthesized out of arginine with citrulline as concomitant product. In the endothelium NO production leads to vasodilatation and in the central nervous system it acts as neuromodulating agent. NO is increasingly thought to be related to neuropsychiatric disorders.
In 20 severely depressed, medication free patients, we measured the ratio of citrulline to arginine (Cit-Arg ratio) in plasma, before and after treatment with ECT. This ratio could be regarded as a reflection of the synthesis of NO.
The Cit-Arg ratio in the depressed patients was not different from healthy controls. After treatment a significant increase of the Cit-Arg ratio was found.
Treatment with ECT was associated with an increase of the synthesis of NO. The exact role of NO in the mechanism of action of ECT deserves further study.
The network approach to psychopathology posits that mental disorders can be conceptualized and studied as causal systems of mutually reinforcing symptoms. This approach, first posited in 2008, has grown substantially over the past decade and is now a full-fledged area of psychiatric research. In this article, we provide an overview and critical analysis of 363 articles produced in the first decade of this research program, with a focus on key theoretical, methodological, and empirical contributions. In addition, we turn our attention to the next decade of the network approach and propose critical avenues for future research in each of these domains. We argue that this program of research will be best served by working toward two overarching aims: (a) the identification of robust empirical phenomena and (b) the development of formal theories that can explain those phenomena. We recommend specific steps forward within this broad framework and argue that these steps are necessary if the network approach is to develop into a progressive program of research capable of producing a cumulative body of knowledge about how specific mental disorders operate as causal systems.
We provide an update on diagnostic methods for the detection of urogenital schistosomiasis (UGS) in men and highlight that satisfactory urine-antigen diagnostics for UGS lag much behind that for intestinal schistosomiasis, where application of a urine-based point-of-care strip assay, the circulating cathodic antigen (CCA) test, is now advocated. Making specific reference to male genital schistosomiasis (MGS), we place greater emphasis on parasitological detection methods and clinical assessment of internal genitalia with ultrasonography. Unlike the advances made in defining a clinical standard protocol for female genital schistosomiasis, MGS remains inadequately defined. Whilst urine filtration with microscopic examination for ova of Schistosoma haematobium is a convenient but error-prone proxy of MGS, we describe a novel low-cost sampling and direct visualization method for the enumeration of ova in semen. Using exemplar clinical cases of MGS from our longitudinal cohort study among fishermen along the shoreline of Lake Malawi, the portfolio of diagnostic needs is appraised including: the use of symptomatology questionnaires, urine analysis (egg count and CCA measurement), semen analysis (egg count, circulating anodic antigen measurement and real-time polymerase chain reaction analysis) alongside clinical assessment with portable ultrasonography.
Although researchers have described numerous risk factors for salmonellosis and for infection with specific common serotypes, the drivers of Salmonella serotype diversity among human populations remain poorly understood. In this retrospective observational study, we partition records of serotyped non-typhoidal Salmonella isolates from human clinical specimens reported to CDC national surveillance by demographic, geographic and seasonal characteristics and adapt sample-based rarefaction methods from the field of community ecology to study how Salmonella serotype diversity varied within and among these populations in the USA during 1996–2016. We observed substantially higher serotype richness in children <2 years old than in older children and adults and steadily increasing richness with age among older adults. Whereas seasonal and regional variation in serotype diversity was highest among infants and young children, variation by specimen source was highest in adults. Our findings suggest that the risk for infection from uncommon serotypes is associated with host and environmental factors, particularly among infants, young children and older adults. These populations may have a higher proportion of illness acquired through environmental transmission pathways than published source attribution models estimate.
Guillain Barré syndrome (GBS), which is triggered by autoantibodies produced in response to antigenic stimuli such as certain infections and vaccinations, is the most common cause of acute flaccid paralysis worldwide. Campylobacter, the most common bacterial enteric infection in the USA, is reported to be the most commonly diagnosed antecedent of GBS, yet little information is available about the risk of post-Campylobacter GBS. Data collected through active, population-based surveillance in the Emerging Infections Program during the 2009–2010 novel Influenza A (H1N1) vaccination campaign allowed us to compare confirmed and probable GBS cases to non-cases to determine whether antecedent Campylobacter infection (or a diarrhoeal illness consistent with campylobacteriosis) was more common among cases and to assess the risk of GBS following Campylobacter infection. We estimate that 8–12% of GBS cases in the USA are attributable to Campylobacter infection (or a diarrhoeal illness consistent with campylobacteriosis), with 434–650 cases of post-diarrhoeal GBS annually and about 49 cases of GBS per 100 000 Campylobacter infections. These results provide updated estimates for post-Campylobacter GBS incidence in the USA and highlight an important benefit of effective measures to prevent Campylobacter infections.
Analysing temporal patterns in foodborne illness is important to designing and implementing effective food safety measures. The reported incidence of illness due to Salmonella in the USA. Foodborne Diseases Active Surveillance Network (FoodNet) sites has exhibited no declining trend since 1996; however, there have been significant annual trends among principal Salmonella serotypes, which may exhibit complex seasonal patterns. Data from the original FoodNet sites and penalised cubic B-spline regression are used to estimate temporal patterns in the reported incidence of illness for the top three Salmonella serotypes during 1996–2014. Our results include 95% confidence bands around the estimated annual and monthly curves for each serotype. The results show that Salmonella serotype Typhimurium exhibits a statistically significant declining annual trend and seasonality (P < 0.001) marked by peaks in late summer and early winter. Serotype Enteritidis exhibits a significant annual trend with a higher incidence in later years and seasonality (P < 0.001) marked by a peak in late summer. Serotype Newport exhibits no significant annual trend with significant seasonality (P < 0.001) marked by a peak in late summer.
Little has been reported about service provision for children with autism in low-income countries. This study explored the current service provision for children with autism and their families in Ethiopia, the existing challenges and urgent needs, and stakeholders’ views on the best approaches to further develop services.
A situational analysis was conducted based on (i) qualitative interviews with existing service providers; (ii) consultation with a wider group of stakeholders through two stakeholder workshops; and (iii) information available in the public domain. Findings were triangulated where possible.
Existing diagnostic and educational services for children with autism are scarce and largely confined to Ethiopia's capital city, with little provision in rural areas. Families of children with autism experience practical and psychosocial challenges, including severe stigma. Informants further raised the lack of culturally and contextually appropriate autism instruments as an important problem to be addressed. The study informants and local stakeholders provided several approaches for future service provision expansion, including service decentralisation, mental health training and awareness raising initiatives.
Services for children with autism in Ethiopia are extremely limited; appropriate care for these children is further impeded by stigma and lack of awareness. Ethiopia's plans to scale up mental healthcare integrated into primary care provide an opportunity to expand services for children with autism and other developmental disorders. These plans, together with the additional strategies outlined in this paper can help to address the current service provision gaps and may also inform service enhancement approaches in other low-income countries.
Schizophrenia is associated with lower intelligence and poor educational performance relative to the general population. This is, to a lesser degree, also found in first-degree relatives of schizophrenia patients. It is unclear whether bipolar disorder I (BD-I) patients and their relatives have similar lower intellectual and educational performance as that observed in schizophrenia.
This cross-sectional study investigated intelligence and educational performance in two outpatient samples [494 BD-I patients, 952 schizophrenia spectrum (SCZ) patients], 2231 relatives of BD-I and SCZ patients, 1104 healthy controls and 100 control siblings. Mixed-effects and regression models were used to compare groups on intelligence and educational performance.
BD-I patients were more likely to have completed the highest level of education (odds ratio 1.88, 95% confidence interval 1.66–2.70) despite having a lower IQ compared to controls (β = −9.09, s.e. = 1.27, p < 0.001). In contrast, SCZ patients showed both a lower IQ (β = −15.31, s.e. = 0.86, p < 0.001) and lower educational levels compared to controls. Siblings of both patient groups had significantly lower IQ than control siblings, but did not differ on educational performance. IQ scores did not differ between BD-I parents and SCZ parents, but BD-I parents had completed higher educational levels.
Although BD-I patients had a lower IQ than controls, they were more likely to have completed the highest level of education. This contrasts with SCZ patients, who showed both intellectual and educational deficits compared to healthy controls. Since relatives of BD-I patients did not demonstrate superior educational performance, our data suggest that high educational performance may be a distinctive feature of bipolar disorder patients.
To design effective food safety programmes we need to estimate how many sporadic foodborne illnesses are caused by specific food sources based on case-control studies. Logistic regression has substantive limitations for analysing structured questionnaire data with numerous exposures and missing values. We adapted random forest to analyse data of a case-control study of Salmonella enterica serotype Enteritidis illness for source attribution. For estimation of summary population attributable fractions (PAFs) of exposures grouped into transmission routes, we devised a counterfactual estimator to predict reductions in illness associated with removing grouped exposures. For the purpose of comparison, we fitted the data using logistic regression models with stepwise forward and backward variable selection. Our results show that the forward and backward variable selection of logistic regression models were not consistent for parameter estimation, with different significant exposures identified. By contrast, the random forest model produced estimated PAFs of grouped exposures consistent in rank order with results obtained from outbreak data, with egg-related exposures having the highest estimated PAF (22·1%, 95% confidence interval 8·5–31·8). Random forest might be structurally more coherent and efficient than logistic regression models for attributing Salmonella illnesses to sources involving many causal pathways.
We explored the overall impact of foodborne disease caused by seven leading foodborne pathogens in the United States using the disability adjusted life year (DALY). We defined health states for each pathogen (acute illness and sequelae) and estimated the average annual incidence of each health state using data from public health surveillance and previously published estimates from studies in the United States, Canada and Europe. These pathogens caused about 112 000 DALYs annually due to foodborne illnesses acquired in the United States. Non-typhoidal Salmonella (32 900) and Toxoplasma (32 700) caused the most DALYs, followed by Campylobacter (22 500), norovirus (9900), Listeria monocytogenes (8800), Clostridium perfringens (4000), and Escherichia coli O157 (1200). These estimates can be used to prioritize food safety interventions. Future estimates of the burden of foodborne disease in DALYs would be improved by addressing important data gaps and by the development and validation of US-specific disability weights for foodborne diseases.
Euclid is the next ESA mission devoted to cosmology. It aims at observing most of the extragalactic sky, studying both gravitational lensing and clustering over ~15,000 square degrees. The mission is expected to be launched in year 2020 and to last six years. The sheer amount of data of different kinds, the variety of (un)known systematic effects and the complexity of measures require efforts both in sophisticated simulations and techniques of data analysis. We review the mission main characteristics, some aspects of the the survey and highlight some of the areas of interest to this meeting.
Common sources of shiga toxin-producing Escherichia coli (STEC) O157 infection have been identified by investigating outbreaks and by case-control studies of sporadic infections. We conducted an analysis to attribute STEC O157 infections ascertained in 1996 and 1999 by the Foodborne Diseases Active Surveillance Network (FoodNet) to sources. Multivariable models from two case-control studies conducted in FoodNet and outbreak investigations that occurred during the study years were used to calculate the annual number of infections attributable to six sources. Using the results of the outbreak investigations alone, 27% and 15% of infections were attributed to a source in 1996 and 1999, respectively. Combining information from both data sources, 65% of infections in 1996 and 34% of infections in 1999 were attributed. The results suggest that methods to incorporate data from multiple surveillance systems and over several years are needed to improve estimation of the number of illnesses attributable to exposure sources.
Attention deficit hyperactivity disorder (ADHD) symptoms and autistic traits often occur together. The pattern and etiology of co-occurrence are largely unknown, particularly in adults. This study investigated the co-occurrence between both traits in detail, and subsequently examined the etiology of the co-occurrence, using two independent adult population samples.
Data on ADHD traits (Inattention and Hyperactivity/Impulsivity) were collected in a population sample (S1, n = 559) of unrelated individuals. Data on Attention Problems (AP) were collected in a population-based family sample of twins and siblings (S2, n = 560). In both samples five dimensions of autistic traits were assessed (social skills, routine, attentional switching, imagination, patterns).
Hyperactive traits (S1) did not correlate substantially with the autistic trait dimensions. For Inattention (S1) and AP (S2), the correlations with the autistic trait dimensions were low, apart from a prominent correlation with the attentional switching scale (0.47 and 0.32 respectively). Analyses in the genetically informative S2 revealed that this association could be explained by a shared genetic factor.
Our findings suggest that the co-occurrence of ADHD traits and autistic traits in adults is not determined by problems with hyperactivity, social skills, imagination or routine preferences. Instead, the association between those traits is due primarily to shared attention-related problems (inattention and attentional switching capacity). As the etiology of this association is purely genetic, biological pathways involving attentional control could be a promising focus of future studies aimed at unraveling the genetic causes of these disorders.
Genes in the TGF9 signaling pathway play important roles in the regulation of ovarian follicle growth and ovulation rate. Mutations in three genes in this pathway, growth differentiation factor 9 (GDF9), bone morphogenetic protein 15 (BMP15) and the bone morphogenetic protein receptor B 1 (BMPRB1), influence dizygotic (DZ) twinning rates in sheep. To date, only variants in GDF9 and BMP15, but not their receptors transforming growth factor ß receptor 1 (TGFBR1), bone morphogenetic protein receptor 2 (BMPR2) and BMPR1B, have been investigated with respect to their roles in human DZ twinning. We screened for rare and novel variants in TGFBR1, BMPR2 and BMPR1B in mothers of dizygotic twins (MODZT) from twin-dense families, and assessed association between genotyped and imputed variants and DZ twinning in another large sample of MODZT. Three novel variants were found: a deep intronic variant in BMPR2, and one intronic and one non-synonymous exonic variant in BMPRB1 which would result in the replacement of glutamine by glutamic acid at amino acid position 294 (p.Gln294Glu). None of these variants were predicted to have major impacts on gene function. However, the p.Gln294Glu variant changes the same amino acid as a sheep BMPR1B functional variant and may have functional consequences. Six BMPR1B variants were marginally associated with DZ twinning in the larger case-control sample, but these were no longer significant once multiple testing was taken into account. Our results suggest that variation in the TGF9 signaling pathway type II receptors has limited effects on DZ twinning rates in humans.
Autism is associated with intellectual disability. The strength and origin of this association is unclear.
To investigate the association between extreme autistic traits and intellectual disability in children from a community-based sample and to examine whether the association can be explained by genetic factors.
Children scoring in the extreme 5% on measures of autistic traits, IQ and academic achievement were selected from 7965 7/8-year-old and 3687 9-year-old twin pairs. Phenotypic associations between extreme autistic traits and intellectual disability were compared with associations among the full-range scores. Genetic correlations were estimated using bivariate DeFries–Fulker extremes analyses.
Extreme autistic traits were modestly related to intellectual disability; this association was driven by communication problems characteristic of autism. Although this association was largely explained by genetic factors, the genetic correlation between autistic traits and intellectual disability was only modest.
Extreme autistic traits are substantially genetically independent of intellectual disability.
The incidence of gastrointestinal diseases was studied in a community-based study in four regions of The Netherlands. Two grades of severity were distinguished − 1: diarrhoea or vomiting and at least 2 additional symptoms within the period of 1 week, and 2: diarrhoea or vomiting and at least 2 additional symptoms occurring on the same day lasting at least 2 days within the period of 1 week. The incidence of gastrointestinal episodes was calculated to be 630 for grade 1 and 180 for grade 2 disease per 1000 person-years, after correction for age and sex. The incidence was higher for women than for men (relative risk 1·25) and lower for those in the 19–64-year-old age group when compared to those younger or older (relative risk 0·75 and 0·40. respectively). Independent of the degree of severity of the symptoms, about 20% of the patients had consulted a general practitioner, about half in person and half by telephone. It is concluded that community studies are essential to assess the real incidence of gastrointestinal diseases in the population.
The lack of robustness of models of the maintenance of polymorphism in a heterogeneous environment which has been pointed out by Maynard Smith & Hoekstra (1980), applies also to models based on habitat selection, on temporal variation and on density-regulated selection. Only if (partial) dominance ‘switches’ between environments such that the fitness of the heterozygote is always close to the favoured homozygote, is there reasonable robustness. This is true for all models considered. It is argued that there are good reasons for supposing that the favourable allele at a locus may show dominance, although the experimental evidence is still scanty.
This paper shows that a number of models of the maintenance of polymorphism in a heterogeneous environment, including those of Levene and Dempster, can be derived from a simple assumption about the way in which the numbers and kinds of individuals emerging from a niche depend on the number of eggs laid in it. It is shown that for such models, unless selective advantages per locus are large, protected polymorphism requires that the relative niche sizes lie in a narrow range. This lack of robustness applies also to models of stable polymorphism proposed by Clarke and by Stewart & Levin. Excluding models relaying on habitat selection or restricted migration, the only models which may escape this criticism are diploid models with partial dominance with respect to fitness, such as one proposed by Gillespie, in which in all niches the fitness of heterozygotes is higher than the arithmetic mean of the homozygotes.
Many crop genetic resources collections have been established without a clearly defined conservation goal or mandate, which has resulted in collections of considerable size, unbalanced composition and high levels of duplication. Attempts to improve the composition of collections are hampered by the fact that conceptual views to optimize collection composition are very rare. An optimization strategy is proposed herein, which largely builds on the concepts of core collection and core selection. The proposed strategy relies on hierarchically structuring the crop gene pool and assigning a relative importance to each of its different components. Comparison of the resulting optimized distribution of the number of accessions with the actual distribution allows identification of under- and over-representation within a collection. Application of this strategy is illustrated by an example using potato. The proposed optimization strategy is applicable not only to individual genebanks, but also to consortia of cooperating genebanks, which makes it relevant for ongoing activities within projects that aim at sharing responsibilities among institutions on the basis of rational conservation, such as a European genebank integrated system and the global cacao genetic resources network CacaoNet.
Use of well persons as the comparison group for laboratory-confirmed cases of sporadic salmonellosis may introduce ascertainment bias into case-control studies. Data from the 1996–1997 FoodNet case-control study of laboratory-confirmed Salmonella serogroups B and D infection were used to estimate the effect of specific behaviours and foods on infection with Salmonella serotype Enteritidis (SE). Persons with laboratory-confirmed Salmonella of other serotypes acted as the comparison group. The analysis included 173 SE cases and 268 non-SE controls. SE was associated with international travel, consumption of chicken prepared outside the home, and consumption of undercooked eggs prepared outside the home in the 5 days prior to diarrhoea onset. SE phage type 4 was associated with international travel and consumption of undercooked eggs prepared outside the home. The use of ill controls can be a useful tool in identifying risk factors for sporadic cases of Salmonella.