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Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
The last meal of Tollund Man, a bog body from Early Iron Age Denmark, has been re-examined using new analyses of plant macrofossils, pollen, non-pollen palynomorphs, steroid markers and proteins found in his gut. Some 12–24 hours before he was killed, he ate a porridge containing barley, pale persicaria and flax, and probably some fish. Proteins and eggs from intestinal worms indicate that he was infected with parasites. Although the meal may reflect ordinary Iron Age fare, the inclusion of threshing waste could possibly relate to ritual practices. This re-analysis illustrates that new techniques can throw fresh light on old questions and contribute to understanding life and death in the Danish Early Iron Age.
Nonsuicidal self-injury (NSSI) is prevalent among adolescents and research is needed to clarify the mechanisms which contribute to the behavior. Here, the authors relate behavioral neurocognitive measures of impulsivity and compulsivity to repetitive and sporadic NSSI in a community sample of adolescents.
Computerized laboratory tasks (Affective Go/No-Go, Cambridge Gambling Task, and Probabilistic Reversal Task) were used to evaluate cognitive performance. Participants were adolescents aged 15 to 17 with (n = 50) and without (n = 190) NSSI history, sampled from the ROOTS project which recruited adolescents from secondary schools in Cambridgeshire, UK. NSSI was categorized as sporadic (1-3 instances per year) or repetitive (4 or more instances per year). Analyses were carried out in a series of linear and negative binomial regressions, controlling for age, gender, intelligence, and recent depressive symptoms.
Adolescents with lifetime NSSI, and repetitive NSSI specifically, made significantly more perseverative errors on the Probabilistic Reversal Task and exhibited significantly lower quality of decision making on the Cambridge Gambling Task compared to no-NSSI controls. Those with sporadic NSSI did not significantly differ from no-NSSI controls on task performance. NSSI was not associated with behavioral measures of impulsivity.
Repetitive NSSI is associated with increased behavioral compulsivity and disadvantageous decision making, but not with behavioral impulsivity. Future research should continue to investigate how neurocognitive phenotypes contribute to the onset and maintenance of NSSI, and determine whether compulsivity and addictive features of NSSI are potential targets for treatment.
This review collates the published reports that focus on microbial and viral illnesses that can be transmitted by breast milk, donor milk and powdered infant formula (PIF). In this context, we attempt to define a risk framework encompassing those hazards, exposure scenarios, vulnerability and protective factors.
A literature search was performed for reported cases of morbidity and mortality associated with different infant feeding modes.
Exclusive breast-feeding is the recommended for infant feeding under 6 months, or failing that, provision of donated human milk. However, the use of PIF remains high despite its intrinsic and extrinsic risk of microbial contamination, as well as the potential for adverse physiological effects, including infant gut dysbiosis.
Viable pathogen transmission via breast-feeding or donor milk (pasteurised and unpasteurised) is rare. However, transmission of HIV and human T-cell lymphotropic virus-1 is a concern for breast-feeding mothers, particularly for mothers undertaking a mixed feeding mode (PIF and breast-feeding). In PIF, intrinsic and extrinsic microbial contamination, such as Cronobacter and Salmonella, remain significant identifiable causes of infant morbidity and mortality.
Disease transmission through breast-feeding or donor human milk is rare, most likely owing to its complex intrinsically protective composition of human milk and protection of the infant gut lining. Contamination of PIF and the morbidity associated with this is likely underappreciated in terms of community risk. A better system of safe donor milk sharing that also establishes security of supply for non-hospitalised healthy infants in need of breast milk would reduce the reliance on PIF.
Angiostrongylus vasorum, Crenosoma vulpis and Capillaria aerophila are the most common lungworms of domestic and wild canids. We investigated the short- and long-term lungworm prevalence changes in the Swiss fox population with a focus on A. vasorum. Between 2012 and 2017, lungs and hearts of 533 foxes from north-eastern Switzerland were necropsied and blood samples tested for circulating A. vasorum antigen. Angiostrongylus vasorum prevalence increased steadily from 21.5% in 2012 to 81.8% in 2017. In contrast, C. aerophila and C. vulpis prevalences fluctuated between 41.8 and 74.7%, and 3.6 and 14.9%, respectively. Based on 3955 blood samples collected between 1986 and 2017 from three geographic areas and during four time periods, antigen seropositivity increased from 2.4 to 62.0%. In north-eastern Switzerland, seropositivity was initially low (1.9 and 1.7% in the first two time periods) but increased in the following two decades to 22.2 and 62.0%, respectively. Our findings depict the spectacular expansion of A. vasorum in the past three decades. Regionally, the prevalence in foxes increased 4-fold within 6 years in some regions. This underpins the important role of foxes as reservoir hosts, likely explaining the increasing number of cases of canine angiostrongylosis in Switzerland. Our findings are representative of central Europe and may help anticipating future developments in areas where A. vasorum is present but (still) infrequent.
We describe an ultra-wide-bandwidth, low-frequency receiver recently installed on the Parkes radio telescope. The receiver system provides continuous frequency coverage from 704 to 4032 MHz. For much of the band (
), the system temperature is approximately 22 K and the receiver system remains in a linear regime even in the presence of strong mobile phone transmissions. We discuss the scientific and technical aspects of the new receiver, including its astronomical objectives, as well as the feed, receiver, digitiser, and signal processor design. We describe the pipeline routines that form the archive-ready data products and how those data files can be accessed from the archives. The system performance is quantified, including the system noise and linearity, beam shape, antenna efficiency, polarisation calibration, and timing stability.
There is an ongoing debate on the potential negative effect of contact sport participation on long-term neurocognitive performance due to inherent exposure to concussive and subconcussive head impacts. The aim of the present study was to investigate whether cognitive ageing is exacerbated in elite soccer players compared to the general population.
Neurocognitive performance in 6 domains was compared between 240 elite soccer players and a normative sample from the general population (n = 585) using the computerised test battery CNS Vital Signs. We used two-way factorial ANOVA to analyse the interaction between age groups (15–19, 20–29, 30–39, 40–49 years) and study population (female soccer players vs. norm sample) in their effects on neurocognitive performance.
We found no significant interaction effect of age group and study population in five of six test domains. For processing speed, the effect of age was more pronounced in female soccer players (F = 16.89, p = .002). Further, there was a clear main effect of study population on neurocognitive performance with generally better scores in soccer players.
Elite female soccer players generally performed better than the norm sample on tests of cognitive function, and further, cognitive ageing effects were similar in elite soccer players and controls in all but one domain. A lifespan approach may facilitate insightful future research regarding questions related to long-term neurocognitive health in contact sport athletes.
Previous work in an Irish cross-sectional study in adults identified three metabolic subgroups (metabotypes) of individuals using k-means cluster analysis based on four fasting clinical standard parameters (triacylglycerols, total cholesterol, HDL cholesterol and glucose). We aimed to validate these metabotypes in another large population-based study. We assigned 2221 participants aged 38–88 years from the German Cooperative Health Research in the Region of Augsburg (KORA) FF4 study (2013/2014) to the three metabotype clusters identified previously by minimizing the Euclidean distances. These clusters were characterized and compared with one another by metabolic characteristics as well as by cardiometabolic disease prevalence. Further, usual dietary intake of various foods/nutrients was estimated based on a food frequency questionnaire and multiple 24-hour food lists and was investigated across clusters. We identified three metabolically distinct clusters in the KORA FF4 study. Cluster 3 represented the group of participants with the most unfavorable metabolic characteristics (e.g. parameters of glucose and lipid metabolism, inflammatory markers), followed by clusters 2 and 1. Individuals in cluster 3 had the highest prevalence of metabolic diseases. Furthermore, they were characterized by the most unfavorable diet with significantly lowest intakes of vegetables, dairy products and fibers as well as significantly highest intakes of total, red and processed meat. Our finding of distinct metabolic subgroups in the KORA FF4 study suggest a successful validation of the metabotypes originally identified based on four commonly measured clinical parameters. Based on these metabotypes, targeted dietary recommendations may be developed for metabolic disease prevention.
Animal sterols, plant sterols and bile acids in stool samples have been suggested as biomarkers of dietary intake. It is still unknown whether they also reflect long-term habitual dietary intake and can be used in aetiological research. In a subgroup of the Cooperative Health Research in the Augsburg Region (KORA FF4) study, habitual dietary intake was estimated based on repeated 24-h food list and a FFQ. Stool samples were collected according to a standard operating procedure and those meeting the quality criteria were extracted and analysed by means of a metabolomics technique. The present study is based on data from 513 men and 495 women with a mean age of 60 and 58 years, respectively, for which faecal animal and plant sterols and bile acids concentrations and dietary intake data were available. In adjusted regression models, the associations between food intake and log-normalised metabolite concentrations were analysed. Bonferroni correction was used to account for multiple testing. In this population-based sample, associations between habitual dietary intake and faecal concentrations of animal sterols were identified, while the impact of usual diet on bile acids was limited. A habitual diet high in ‘fruits’ and ‘nuts and seeds’ is associated with lower animal faecal sterols concentrations, whereas a diet high in ‘meat and meat products’ is positively related to faecal concentrations of animal sterols. A positive association between glycocholate and fruit consumption was found. Further studies are necessary for evaluation of faecal animal sterols as biomarkers of diet. The findings need to be confirmed in other populations with diverse dietary habits.
Type 2 diabetes mellitus (T2DM) is a global public health epidemic. Diet and lifestyle changes have been demonstrated as effective measures in managing T2DM and preventing or delaying the progression from prediabetes to diabetes, yet the relationship between diet, prediabetes and diabetes is still not entirely clear. The present study aimed to further elucidate the relationship between diet, diabetes and especially prediabetes. A total of 1542 participants of the cross-sectional, population-based Cooperative Health Research in the Region of Augsburg (KORA) FF4 study (2013/2014) were included in this analysis. Dietary intake was derived using a method combining information from a FFQ and repeated 24-h food lists. Glucose tolerance status was assessed via oral glucose tolerance tests in all participants without a previous physician-confirmed diagnosis of T2DM, and was classified according to the 2003 American Diabetes Association criteria. Crude and fully adjusted multinomial logistic regression models were fitted to examine associations between diet and prediabetes, undetected diabetes mellitus (UDM) and prevalent T2DM. After adjusting for major covariates, fruit was significantly inversely and total meat, processed meat, sugar-sweetened beverages and moderate alcohol significantly associated with UDM and/or prevalent diabetes. Sex-specific analyses showed that in men, coffee was significantly inversely (OR 0·80; 95 % CI 0·67, 0·96) and heavy alcohol significantly (OR 1·84; 95 % CI 1·14, 2·95) associated with prediabetes. Our findings on diet and T2DM are consistent with current literature, while our results regarding coffee, heavy alcohol consumption and prediabetes highlight new possible targets for primary prevention of the derangement of glucose homeostasis.
Background: Based on the vulnerability model, several studies indicate that low self-esteem seems to contribute to depressive symptoms. Aims: The aim of this study was to treat depressive symptoms in a cognitive behavioural group therapy, focusing on the enhancement of self-esteem, and to explore co-variation in depressive symptoms and the level of self-esteem. Method: The Multidimensional Self-esteem Scale (MSWS) and the Beck Depression Inventory (BDI) were administered to 147 psychiatric in-patients with current depressive symptoms due to an affective disorder (major depression, bipolar I, dysthymia). Self-esteem was measured pre-treatment (t0) and post-treatment (t4, after 5 weeks of eight group sessions); the BDI was applied weekly. A linear mixed growth analysis was conducted to estimate the change in depressive symptoms including interactions with self-esteem. Results: Within the 5 weeks of group therapy, depressive symptoms showed a linear decline, which was stronger for patients with higher gains in self-esteem between t0 and t4. Self-esteem at t0 was unrelated to the change in depression but predicted self-esteem at t4. Conclusions: Treating depressive symptoms in a cognitive behavioural group therapy in a naturalistic setting might have a positive effect on the process of recovery. Moreover, depressive symptoms and level of self-esteem seemed to co-vary.
The appropriate medical treatment test (ATT), included in the Mental Health Act (MHA) (1983, as amended 2007), aims to ensure that detention only occurs when treatment with the purpose of alleviating a mental disorder is available.
As part of the Assessing the Impact of the Mental Health Act (AMEND) project, this qualitative study aimed to assess professionals' understanding of the ATT, and its impact on clinical practice.
Forty-one professionals from a variety of mental health subspecialties were interviewed. Interviews were coded related to project aims, and themes were generated in an inductive process.
We found that clinicians are often wholly relied upon for the ATT. Considered treatment varied depending on the patient's age rather than diagnosis. The ATT has had little impact on clinical practice.
Our findings suggest the need to review training and support for professionals involved in MHA assessments, with better-defined roles. This may enable professionals to implement the ATT as its designers intended.
Information on the occurrence, spatial distribution and morphometric characteristics of Antarctic icebergs is needed in a large number of applications including navigation, heat and freshwater balance calculations, biochemistry of the ocean and climatology. Using over 60 000 ship observations of icebergs in the Southern Ocean collected since the end of the 1940s we have produced a detailed map of the distribution of Antarctic icebergs as well as maps of related statistics including the standard deviation, minimum and maximum values of the iceberg concentration and the probability of iceberg-free observations. The study incorporated small and medium-sized icebergs with a length of <10 nautical miles. Most observations were taken during the warm period of the year, from December to April. It is shown that the iceberg distribution across the Southern Ocean is determined by the location of calving regions and peculiarities of the atmospheric circulation and ocean currents. Iceberg concentration data combined with information on the iceberg size and shape distribution have been used to evaluate the area-integrated characteristics of Antarctic icebergs. The instantaneous number of icebergs in the Southern Ocean was estimated as 132 269 with an uncertainty of 7%. The area and volume of icebergs were equal correspondingly to 55 805 km2 and 16 893 km3 with uncertainties of 32–33%.
Since the Last Glacial Maximum, ice has retreated through the fjords of the South Shetland Islands leaving a valuable record of submarine landforms behind. In this study, glacial landforms and sub-bottom characteristics have been mapped to investigate the late Holocene retreat behaviour of the Fourcade Glacier and to delineate past environmental processes in Potter Cove, King George Island. The comprehensive datasets include high-resolution swath bathymetry, shallow seismic profiling and one sediment core. Moraines, moraine incisions and glacial lineations were mapped on the sea floor in the inner part of the cove, whereas pockmarks, ice scour marks and channel structures were identified in the outer part. Sub-bottom characteristics have been assigned to different acoustic facies types indicating different depositional settings. The results reveal glacial recessions as well as stillstands and potential readvances during the late Holocene. Furthermore, the sediment record indicates that the Fourcade Glacier was situated inside the inner cove during the Little Ice Age (500–100 cal yr bp).
The present research examined the perceptions of Australian employees on dimensions of workplace stress. The sample included 664 male (n = 234) and female (n = 430) workers from the public (n = 559) and private (n = 105) sectors. Participants completed the Health and Safety Executive Indicator Tool as a measure of workplace stress. Results indicated that private sector employees rated their employers as being more effective in managing workplace stress, while employees in both sectors rated their employers as less effective in managing Job Content stressors than Job Context stressors. Compared with normative benchmarks, employees overall also reported risks of stress associated with Relationships and Role. Implications of these findings and suggestions for future research were discussed.
Dietary patterns, which represent a broader picture of food and nutrient consumption, have gained increasing interest over the last decades. In a cohort design, we followed 27 544 women aged 29–49 years from baseline in 1991–1992. We collected data from an FFQ at baseline and body weight (BW) and waist circumference (WC) data both at baseline and at follow-up in 2003. We calculated the Mediterranean diet score (MDS, ranging from 0 to 9) and the Nordic diet score (NDS, ranging from 0 to 6). We used linear regression to examine the association between MDS and NDS (exposures) with subsequent BW change (ΔBW) and WC change (ΔWC) (outcomes) both continuously and categorically. Higher adherence to the MDS or NDS was not associated with ΔBW. The multivariable population average increment in BW was 0·03 kg (95 % CI −0·03, 0·09) per 1-point increase in MDS and 0·04 kg (95 % CI −0·02, 0·10) per 1-point increase in NDS. In addition, higher adherence to the MDS was not associated with ΔWC, with the multivariable population average increment per 1-point increase in MDS being 0·05 cm (95 % CI −0·03, 0·13). Higher adherence to the NDS was not significantly associated with gain in WC when adjusted for concurrent ΔBW. In conclusion, a higher adherence to the MDS or NDS was not associated with changes in average BW or WC in the present cohort followed for 12 years.
Detailed imaging and spectroscopic analysis of the centers of nearby S0 and spiral galaxies shows the existence of “composite bulges”, where both classical bulges and disky pseudobulges coexist in the same galaxy. As part of a search for supermassive black holes in nearby galaxy nuclei, we obtained VLT-SINFONI observations in adaptive-optics mode of several of these galaxies. Schwarzschild dynamical modeling enables us to disentangle the stellar orbital structure of the different central components, and to distinguish the differing contributions of kinematically hot (classical bulge) and kinematically cool (pseudobulge) components in the same galaxy.
High purity anatase titanium dioxide (TiO2) and iron (Fe)-doped TiO2 nanocrystals were prepared by a continuous flow synthesis method using isopropanol-water mixtures as solvent in supercritical or near-critical conditions. The method allows complete control of size (5–20 nm) and crystallinity (10–100%) of the nanoparticles and provides quick synthesis with a residence time of ∼10 s that can be scaled up to commercial production. It is found that the average crystallite size can be easily controlled by adjusting the ratio between isopropanol and water in the solvent, whereas the crystallinity is mainly controlled by the reaction temperature. As-prepared Fe-doped TiO2 nanoparticles appear to be single phase, but Fe3+ ions most likely do not occupy the Ti4+ sites in the anatase TiO2 crystal structure.