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Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.
To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.
This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.
The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.
Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
Dental tissues have the unique property of recording their development history as histological growth markers. Animal studies have shown that many stress events (birth, weaning, infections) can generate a chemical signature. Enamel and dentin offer a retrospective view of significant events occurring in growth but are limited in time to the end of the permanent dentition growth and development. Recent improvements in cementum histological analysis offer new perspectives for analyzing stressors and life history events throughout life. This chapter tests the hypothesis that pregnancy may disrupt acellular cementum (AC) deposits visible in the mineralized matrix, using light microscopy, Raman spectrometry, and scanning electron microscopy equipped with an EDS probe. Two human samples with known age at pregnancies demonstrated that accentuated AC increments can be identified and precisely matched to these events. In both samples, these AC variations were the most outstanding optically and chemically. This is notable since such a method’s ultimate purpose is to identify fertility events in archaeological samples blindly.
Acellular cementum anchors the root to the alveolar socket via the periodontal ligament and grows in layers continuously throughout life, unlike enamel and dentin. Increments are deposited in a biannual light-dark pattern correlated to age and season at death in transmitted light microscopy. This study investigates the still debated structure of individual acellular increments using x-ray fluorescence and x-ray diffraction mapping with synchrotron radiation microbeams on reindeer, red deer, cattle, and human samples. Results show that Ca or Zn x-ray fluorescent intensities and cAp diffracted intensity reveal cementum band structure. Average crystallographic texture (of cAp nanoplatelets’ orientation and collagen fibril orientations) is constant for each specimen. Microtextural variation is also present across individual bands, demonstrating that the overall collagen fibril orientation undergoes subtle changes with season. Patterns of “feast or famine” and concomitant changes in amount and intensity of PDL loading might produce altered collagen (and cAp) orientations between the “good” and the “bad” seasons for ungulates but maybe not for modern human populations.
Reading comprehension and fluency are crucial for successful academic learning and achievement. Yet, a rather large percentage of children still have enormous difficulties in understanding a written text at the end of primary school. In this context, the aim of our study was to investigate whether text simplification, a process of reducing text complexity while keeping its meaning unchanged, can improve reading fluency and comprehension for children learning to read. Furthermore, we were interested in finding out whether some readers would benefit more than others from text simplification as a function of their cognitive and language profile. To address these issues, we developed an iBook application for iPads, which allowed us to present normal and simplified versions of informative and narrative texts to 165 children in grade 2. Reading fluency was measured for each sentence, and text comprehension was measured for each text using multiple-choice questions. The results showed that both reading fluency and reading comprehension were significantly better for simplified than for normal texts. Results showed that poor readers and children with weaker cognitive skills (nonverbal intelligence, memory) benefitted to a greater extent from simplification than good readers and children with somewhat stronger cognitive skills.
Cardiovascular magnetic resonance serves as a useful tool in diagnosing myocarditis. Current adult protocols are yet to be validated for children; thus, it remains unclear if the methods used can be applied with sufficient image quality in children. This study assesses the use of cardiovascular magnetic resonance in children with suspected myocarditis.
Image data from clinical cardiovascular magnetic resonance studies performed in children enrolled in Mykke between June 2014 and April 2019 were collected and analysed. The quality of the data sets was evaluated using a four-point quality scale (4: excellent, 3: good, 2: moderate, 1: non-diagnostic).
A total of 102 patients from 9 centres were included with a median age (interquartile range) of 15.4(10.7-16.6) years, 137 cardiovascular magnetic resonance studies were analysed. Diagnostic image quality was found in 95%. Examination protocols were consistent with the original Lake Louise criteria in 58% and with the revised criteria in 35%. Older patients presented with better image quality, with the best picture quality in the oldest age group (13-18 years). Sedation showed a negative impact on image quality in late gadolinium enhancement and oedema sequences. No such correlation was seen in cardiac function assessment sequences. In contrast to initial scans, in follow-up examinations, the use of parametric mapping increased while late gadolinium enhancement and oedema sequences decreased.
Cardiovascular magnetic resonance protocols for the assessment of adult myocarditis can be applied to children without significant constraints in image quality. Given the lack of specific recommendations for children, cardiovascular magnetic resonance protocols should follow recent recommendations for adult cardiovascular magnetic resonance.
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.
Older adults exhibit heightened vulnerability for alcohol-related health impairments. Increases in the proportion of older adults within the European Union’s total population and prevalence rates of alcohol use disorders in this age group are being observed. This large scale international study was conducted to identify those older adults with an increased risk to engage in hazardous drinking behaviour.
Socio-demographic, socio-economic, personality characteristics (Big Five Inventory, BFI-10), and alcohol consumption patterns of 13,351 individuals from 12 different European countries, collected by the Survey of Health, Aging, and Retirement in Europe, were analyzed using regression models.
Age, nationality, years of education, as well as personality traits, were significantly associated with alcohol intake. For males, extraversion predicted increased alcohol intake (RR = 1.11, CI = 1.07–1.16), whereas conscientiousness (RR = 0.93, CI = 0.89–0.97), and agreeableness (RR = 0.94, CI = 0.90–0.99), were associated with a reduction. For females, openness to new experiences (RR = 1.11, CI = 1.04–1.18) predicted increased alcohol intake. Concerning excessive drinking, personality traits, nationality, and age-predicted consumption patterns for both sexes: Extraversion was identified as a risk factor for excessive drinking (OR = 1.15; CI = 1.09–1.21), whereas conscientiousness was identified as a protective factor (OR = 0.87; CI = 0.823–0.93).
Hazardous alcohol consumption in the elderly was associated with specific personality characteristics. Preventative measures, crucial in reducing deleterious health consequences, should focus on translating the knowledge of the association of certain personality traits and alcohol consumption into improved prevention and treatment.
Despite improving survival rates, people with advanced cancer face several physical and psychosocial concerns. Leisure-time physical activity (LPA) has been found to be beneficial after cancer diagnosis, but little is known about the current state of research exploring LPA in advanced cancer. Our objectives were to (a) map the literature examining LPA in people with advanced cancer, (b) report on the terms used to describe the advanced cancer population within the literature, and (c) examine how the concept of LPA is operationalized within the literature.
Our scoping review followed Arksey and O'Malley's methodological framework. We performed a search of 11 electronic databases and supplementary sources (February 2018; database search updated January 2020). Two reviewers independently reviewed and selected articles according to the inclusion criteria: English-language journal articles on original primary research studies exploring LPA in adults diagnosed with advanced cancer. Descriptive and thematic analyses were performed.
Ninety-two articles met our criteria. Most included studies were published in the last decade (80%) and used quantitative methods (77%). Many study populations included mixed (40%), breast (21%), or lung (17%) cancers. Stages 3–4 or metastatic disease were frequently indicated to describe study populations (77%). Several studies (68%) described LPA programs or interventions. Of these, 78% involved structured aerobic/resistance exercise, while 16% explored other LPA types.
Significance of results
This review demonstrates a recent surge in research exploring LPA in advanced cancer, particularly studies examining exercise interventions with traditional quantitative methods. There remains insufficient knowledge about patient experiences and perceptions toward LPA. Moreover, little is known about other leisure activities (e.g., Tai Chi, dance, and sports) for this population. To optimize the benefits of LPA in people with advanced cancer, research is needed to address the gaps in the current literature and to develop personalized, evidence-based supportive care strategies in cancer care.
The growth of judicial power globally has renewed scholarly debates about who benefits from increased judicial authority. Using original data, we examine the full universe of constitutional free expression decisions issued by three apex courts—in Colombia, India, and South Africa—across three categories of disputes that feature a diverse array of rights claimants. By so doing, we shed light on the limits of elite-driven accounts of judicial empowerment. We find that even where constitutional courts are empowered by elites seeking to advance their own interests, activist courts can develop a practice of rights-protection that benefits a diverse range of less powerful actors. Moreover, regardless of whether the speech claimants are elite or non-elite actors, these three apex courts regularly rule in favor of free expression for dissenting or unorthodox speech acts. In sum, where issues are peripheral to the governing regime’s core interests, relatively powerless actors are sometimes able to use legal processes to advance their rights and interests.
Under the Trump administration, a transatlantic trade conflict has been escalating step by step. First, it was about tariffs on steel and aluminium, then about retaliation for the French digital tax, which is suspended until the end of the year. Most recently, the US administration threatened the European Union with tariffs on cars and car parts because of Canadian seafood being subject to lower import duties. As simulations with NiGEM show, a further escalation of the transatlantic trade conflict has the potential to slow down economic growth significantly in the countries involved. This is a considerable risk given the fact that the countries have to cope with the enormous negative effects of the pandemic shock. Furthermore, the damage caused by the trade conflict depends on the extent to which the affected countries use fiscal policy to stabilise their economies.
Suicide risk in patients is markedly elevated during psychiatric inpatient care, as well as after discharge. However, it is unclear whether, and to what extent, this increased suicide risk varies between sex. Thus, the aim of this study was to analyze sex differences for suicides during and after psychiatric hospitalization in various countries.
National suicide mortality rates and inpatient-related suicide rates (three intervals: during psychiatric inpatient treatment, 1 month, and 1 year after discharge) from 12 countries for 2000–2016 were analyzed, and a logistic model was used to quantify the effect of sex.
Persons admitted to or discharged from psychiatric inpatient care exhibited significantly increased rates of suicide compared to those in the general population. Furthermore, increase of suicide risk was significantly higher for females than for males for all investigated time intervals (inpatient suicide odds ratio [OR] 1.85; suicide within 1 month after discharge—OR 1.94; suicide within 1 year after discharge—OR 2.04).
Analysis confirmed the time during and after psychiatric inpatient care to be significantly associated with an elevated risk for suicide. Further, a significant sex effect was observed, with females in this population being at a proportionally higher risk for suicide during psychiatric inpatient treatment as well as the year following discharge. Our study implicates that more effective suicide preventive measures during inpatient stay, focusing on female patients, are needed.
Using an ensemble of close- and long-range remote sensing, lake bathymetry and regional meteorological data, we present a detailed assessment of the geometric changes of El Morado Glacier in the Central Andes of Chile and its adjacent proglacial lake between 1932 and 2019. Overall, the results revealed a period of marked glacier down wasting, with a mean geodetic glacier mass balance of −0.39 ± 0.15 m w.e.a−1 observed for the entire glacier between 1955 and 2015 with an area loss of 40% between 1955 and 2019. We estimate an ice elevation change of −1.00 ± 0.17 m a−1 for the glacier tongue between 1932 and 2019. The increase in the ice thinning rates and area loss during the last decade is coincident with the severe drought in this region (2010–present), which our minimal surface mass-balance model is able to reproduce. As a result of the glacier changes observed, the proglacial lake increased in area substantially between 1955 and 2019, with bathymetry data suggesting a water volume of 3.6 million m3 in 2017. This study highlights the need for further monitoring of glacierised areas in the Central Andes. Such efforts would facilitate a better understanding of the downstream impacts of glacier downwasting.
Fecal microbiota transplantation (FMT) is an effective therapy in recurrent Clostridium difficile infection (rCDI). It is only recommended for this indication by European and American guidelines. Other indications of FMT are being studied, such as inflammatory bowel disease (IBD), and they have shown promising results.
To identify and review published FMT-related economic evaluations (EEs) to assess their quality and the economic impact of FMT in the treatment of these diseases.
The systematic literature research was conducted in both PubMed and Cochrane to identify EEs published before July 1, 2019.
Study eligibility criteria:
Articles were included if they concerned FMT (whatever the disease and its line of treatment), if they reported full or partial EEs, and if they were written in English. Articles were excluded if they did not concern FMT; if they did not report an EE; or if they were a systematic review, editorial, comment, letter to the editor, practice point, or poster.
A measurement tool, AMSTAR, was used to optimize the quality of this systematic review. Based on the CHEERS checklist, data were identified and extracted from articles. The quality of each EE was assessed using the Drummond checklist.
Overall, 9 EEs were included: all EEs were full evaluations and 8 were cost-utility analyses (CUAs). All EEs had a Drummond score ≥ 7, which indicated high quality. All CUAs related to rCDI and IBD concluded that FMT was cost-effective compared with other reference treatments, at a threshold ≤$50,000/QALY. One EE about initial CDI showed that FMT was dominated by metronidazole.
Despite a limited number of EEs, FMT seems to be a promising and cost-effective treatment for rCDI. More EE studies on other diseases like IBD are necessary to address FMT efficiency for new indications. Therefore, our systematic review provides a framework for healthcare decision making.
Black swallowwort [Vincetoxicum nigrum (L.) Moench] and pale swallowwort [Vincetoxicum rossicum (Kleopow) Barb.] are perennial vines of European origin that invade natural areas and perennial cropping systems in the northeastern United States and southeastern Canada. Both species reproduce via wind-dispersed seeds in the form of achenes with comas, but little is known about the extent of dispersal of these seeds. We studied the relationship of seed release height (0.75 m, 2 m), wind speed at the time of release, seed mass, and settling rate on distance traveled. Vincetoxicum nigrum and V. rossicum seeds traveled up to 72.1 and 79.6 m, respectively. Seeds of both species released from 2 m traveled greater distances than seeds released from 0.75 m, which fell within 20 m of the release point. Release height was the most important factor influencing long-distance dispersal events. Wind speed also strongly interacted with release height for long-distance dispersal of V. nigrum. Vincetoxicum nigrum seed mass was greater and settling rates faster than for V. rossicum. Increasing seed mass generally increased settling rate, which in turn decreased distance traveled, except in V. rossicum, for which longer distance–dispersing seeds had a faster settling rate. Our findings suggest that management efforts focus on reducing the presence of these two vines, especially if there is potential for them to climb up taller vegetation such as trees. Seeds released from these greater heights are more likely to travel far from source populations and initiate new populations. Preventing seed production in small, nonclimbing patches will also help suppress the expansion of these two vines, as seeds can still disperse up to 20 m away from parent plants.
We report on small-scale instabilities in a thermally driven rotating annulus filled with a liquid with moderate Prandtl number. The study is based on direct numerical simulations and an accompanying laboratory experiment. The computations are performed independently with two different flow solvers, that is, first, the non-oscillatory forward-in-time differencing flow solver EULAG and, second, a higher-order finite-difference compact scheme (HOC). Both branches consistently show the occurrence of small-scale patterns at both vertical sidewalls in the Stewartson layers of the annulus. Small-scale flow structures are known to exist at the inner sidewall. In contrast, short-period waves at the outer sidewall have not yet been reported. The physical mechanisms that possibly trigger these patterns are discussed. We also debate whether these small-scale structures are a gravity wave signal.