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In recent work on non-cooperative network formation star-shaped networks play an important role. In a particular theoretical model of Bala and Goyal (2000) center-sponsored stars are the only strict Nash networks. In testing this theoretical model, Falk and Kosfeld (2003) do not find experimental evidence that players select the center-sponsored star. Based on a slight modification of Bala and Goyal's model, we design a network formation experiment in which, depending on link costs, periphery-sponsored stars and the empty network are the only strict Nash networks. We observe that almost all groups not only reach a strict Nash network once but also switch the center player in periphery-sponsored stars several times. The main innovation in our experiment is to use a continuous time framework which we believe to be a more realistic setting to study behavior in network formation situations and which makes coordination on stars much easier than simultaneous strategy adaptation in discrete time.
In responding to a Chemical, Biological, Radiological, and Nuclear explosive (CBRNe) disaster, clinical leaders have important decision-making responsibilities which include implementing hospital disaster protocols or incident command systems, managing staffing, and allocating resources. Despite emergency care clinical leaders’ integral role, there is minimal literature regarding the strategies they may use during CBRNe disasters. The aim of this study was to explore emergency care clinical leaders’ strategies related to managing patients following a CBRNe disaster.
Methods
Focus groups across 5 tertiary hospitals and 1 rural hospital in Queensland, Australia. Thirty-six hospital clinical leaders from the 6 study sites crucial to hospital disaster response participated in 6 focus groups undertaken between February and May 2021 that explored strategies and decision making to optimize patient care following a CBRNe disaster.
Results
Analysis revealed the use of rehearsals, adopting new models of care, enacting current surge management processes, and applying organization lessons were facilitating strategies. Barriers to management were identified, including resource constraints and sites operating over capacity.
Conclusions
Enhanced education and training of clinical leaders, flexible models of care, and existing established processes and tested frameworks could strengthen a hospital’s response when managing patients following a CBRNe disaster.
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.
Aims
To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.
Method
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.
Results
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.
Conclusions
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.
Yarkoni's analysis clearly articulates a number of concerns limiting the generalizability and explanatory power of psychological findings, many of which are compounded in infancy research. ManyBabies addresses these concerns via a radically collaborative, large-scale and open approach to research that is grounded in theory-building, committed to diversification, and focused on understanding sources of variation.
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.
Aims
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Method
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.
Results
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.
Conclusions
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.
Patients with psychiatric disorders are exposed to high risk of COVID-19 and increased mortality. In this study, we set out to assess the clinical features and outcomes of patients with current psychiatric disorders exposed to COVID-19.
Methods
This multi-center prospective study was conducted in 22 psychiatric wards dedicated to COVID-19 inpatients between 28 February and 30 May 2020. The main outcomes were the number of patients transferred to somatic care units, the number of deaths, and the number of patients developing a confusional state. The risk factors of confusional state and transfer to somatic care units were assessed by a multivariate logistic model. The risk of death was analyzed by a univariate analysis.
Results
In total, 350 patients were included in the study. Overall, 24 (7%) were transferred to medicine units, 7 (2%) died, and 51 (15%) patients presented a confusional state. Severe respiratory symptoms predicted the transfer to a medicine unit [odds ratio (OR) 17.1; confidence interval (CI) 4.9–59.3]. Older age, an organic mental disorder, a confusional state, and severe respiratory symptoms predicted mortality in univariate analysis. Age >55 (OR 4.9; CI 2.1–11.4), an affective disorder (OR 4.1; CI 1.6–10.9), and severe respiratory symptoms (OR 4.6; CI 2.2–9.7) predicted a higher risk, whereas smoking (OR 0.3; CI 0.1–0.9) predicted a lower risk of a confusional state.
Conclusion
COVID-19 patients with severe psychiatric disorders have multiple somatic comorbidities and have a risk of developing a confusional state. These data underline the need for extreme caution given the risks of COVID-19 in patients hospitalized for psychiatric disorders.
Background: A number of small intervention studies suggested that a Mediterranean diet (MedD) and physical activity can lower the risk for breast cancer. LIBRE is the first large multicenter RCT to test the effect of these lifestyle factors on the incidence of breast cancer in women at risk because of BRCA mutations(1). LIBRE also offers to unravel underlying mechanisms such as the role of short-chain fatty acids (SCFA) for beneficial effects of such lifestyle interventions.
Methods: We examined the effect of the lifestyle intervention on the production of SCFA measured in feces by gas chromatography. From the ongoing LIBRE trial we included all complete datasets (171 women; mean age 44 ± 11 years). Both women with and without previous breast cancer diagnosis were recruited (diseased; non-diseased). The participants were randomized into an intervention group (IG) trained for MedD and physical activity, and a usual care control group (CG). Adherence to the MedD was assessed at baseline and after 3 months (V1) using the validated Mediterranean Diet Adherence Screener (MEDAS) and the EPIC food frequency questionnaire (FFQ).
Results: At baseline there was no difference in SCFA levels between the groups. In the IG the MEDAS score increased substantially by 2.5 points (p < 0.001), in the CG only mildly by 0.4 points (p < 0.05). Correspondingly, the intake of fibers increased solely in the IG. In the course of the study the amount of caproic acid decreased in the control group (p < 0.001). At V1 non-diseased women showed higher amounts of acetic acid (p = 0.042), n-butyric acid (p = 0.023), n-valeric acid (p = 0.018) and iso-valeric acid (p = 0.031). There were several correlations between the intake of different fibers and fecal SCFA. For example, the sum of poly- and oligosaccharides correlated with acetic acid (p = 0.001; r = 0.316), propionic acid (p = 0.034; r = 0,251), n-butyric acid (p = 0.010; r = 0.316) and iso-valeric acid (p = 0.012; r = 0.306). There was no correlation between the MEDAS and SCFA.
Discussion: A lifestyle change towards a MedD and increased physical activity did not change the levels of SCFA in feces, although an increase of fiber intake was documented in the IG. To further analyze SCFA metabolism in this target population, gut microbiota composition and function (metabolites) are currently analyzed.
Restrictive food intake in anorexia nervosa (AN) has been related to an overactive cognitive control network inhibiting intuitive motivational responses to food stimuli. However, the influence of short-term homeostatic signaling on the neural regulation of cue-induced food craving in AN is still unclear.
Methods
Twenty-five women with AN and 25 matched normal-weight women were examined on two occasions after receiving either glucose or water directly into their stomach using a nasogastric tube. Participants were blinded to the type of infusion. An event-related functional magnetic resonance imaging paradigm was used to investigate the effect of intestinal glucose load on neural processing during either simple viewing or distraction from food stimuli.
Results
Neural differences between patients with AN and normal-weight participants were found during the distraction from food stimuli, but not during the viewing condition. When compared to controls, patients with AN displayed increased activation during food distraction in the left parietal lobule/precuneus and fusiform gyrus after water infusion and decreased activation in ventromedial prefrontal and cingulate regions after intestinal glucose load.
Conclusions
Independent of the cephalic phase and the awareness of caloric intake, homeostatic influences trigger disorder-specific reactions in AN. Food distraction in patients with AN is associated with either excessive higher-order cognitive control during physiological hunger or decreased internally directed attention after intestinal glucose load. These findings suggest that food distraction plays an important role in the psychopathology of AN. This study was registered on clinicaltrials.gov with identifier: NCT03075371.
To examine the impact of determinants of incident dementia in three different old age groups (75–79, 80–84, 85+years) in Germany.
Design:
Multicenter prospective AgeCoDe/AgeQualiDe cohort study with baseline and nine follow-up assessments at 1.5-year intervals.
Setting:
Primary care medical record registry sample.
Participants:
General practitioners’ (GPs) patients aged 75+years at baseline.
Measurements:
Conduction of standardized interviews including neuropsychological assessment and collection of GP information at each assessment wave. We used age-stratified competing risk regression models (accounting for the competing event of mortality) to assess determinants of incident dementia and age-stratified ordinary least square regressions to quantify the impact of identified determinants on the age at dementia onset.
Results:
Among 3027 dementia-free GP patients, n = 704 (23.3%) developed dementia during the 13-year study period. Worse cognitive performance and subjective memory decline with related worries at baseline, and the APOE ε4 allele were associated independently with increased dementia risk in all three old age groups. Worse cognitive performance at baseline was also associated with younger age at dementia onset in all three age groups. Other well-known determinants were associated with dementia risk and age at dementia onset only in some or in none of the three old age groups.
Conclusions:
This study provides further evidence for the age-specific importance of determinants of incident dementia in old age. Such specifics have to be considered more strongly particularly with regard to potential approaches of early detection and prevention of dementia.
This paper addresses three control implementation issues for trajectory tracking of robotic manipulators: unmodeled dynamics, unknown input saturation and peaking effects during the transient phase. A model-free first-order robust-adaptive control method is used to deal with the unmodeled dynamics. Robust optimality and stability of the controller are proved using the 𝓗∞ technique and the game-algebraic Riccati equation. An intuitive approach is devised to incorporate the unknown input saturation by modifying the speed of the desired trajectory. The trajectory scaling is performed by using only the state errors. Furthermore, two different techniques are utilized to suppress peaking during the transient response of the trajectory tracking. The first method adds an extra term in the input while the second method uses variable gain to improve the transient response. A systematic procedure for finding the controller parameters is formulated using features, such as rise time and settling time. A three-degree-of-freedom robot manipulator is used for the validation of the proposed controller in simulations and experiments.
King George Island is the largest of the South Shetland Islands, close to the tip of the Antarctic Peninsula. The annual mean temperature on the island has increased by 1°C during the past three decades, and the ice cap that covers the majority of the island is sensitive to climatic change. We present data from two field campaigns (1997 and 2007): 700 km of global positioning system (GPS) and ground-penetrating radar (GPR) profiles were collected on Arctowski Icefield and on the adjacent central part. The data were analysed to determine the surface and bed topography and the thermal regime of the ice. Average ice thickness is 250 m and maximum thickness is 420 m. The GPR profiles show isochrones throughout the ice cap which depict the uparching of Raymond bumps beneath or close to the ice divides. A water table from percolation of meltwater in the snowpack shows the firn-ice boundary at ∼ 3 5 m depth. The firn layer may be temperate due to the release of latent heat. In the area below 400ma.s.l., backscatter by water inclusions is abundant for ice depths below the water table. We interpret this as evidence for temperate ice. Scatter decreases significantly above 400 m. Ice temperatures below the water table in this part of the ice cap are subject to further field and modelling investigations.
Most of the previous studies attempted to disentangle the relationship between disability and depressive symptoms were limited to observation periods of only few years. Moreover, evidence is missing regarding the complex co-occurrence of disability and depressive symptoms in old age in Germany. In order to close the research gap, we aimed at disentangling the complex co-occurrence of disability and depressive symptoms in old age in Germany over a longer time frame.
Methods:
Based on data from a representative survey of the German general population aged 75 years and older, the course of disability as well as depressive symptoms was observed every 1.5 years over six waves. While disability was quantified by the Lawton and Brody Instrumental Activities of Daily Living scale, the Geriatric Depression Scale was used to measure depressive symptoms. Taking into account the complex co-occurrence of depressive symptoms and disability, a panel vector autoregressive model was used. By taking the first differences, unobserved heterogeneity was taken into account.
Results:
In the total sample and in both sexes, we revealed a robust positive association between an initial change in depressive symptoms and subsequent changes in disability. No robust association between an initial change in disability and a subsequent change in depressive symptoms was detected.
Conclusion:
Our findings highlight the importance of changes in depressive symptoms for future changes in disability in old age.
The German twin family study ‘TwinLife’ was designed to enhance our understanding of the development of social inequalities over the life course. The interdisciplinary project investigates mechanisms of social inequalities across the lifespan by taking into account psychological as well as social mechanisms, and their genetic origin as well as the interaction and covariation between these factors. Main characteristics of the study are: (1) a multidimensional perspective on social inequalities, (2) the assessment of developmental trajectories in childhood, adolescence, and young adulthood in a longitudinal design by using (3) a combination of a multi-cohort cross-sequential and an extended twin family design, while (4) capturing a large variation of behavioral and environmental factors in a representative sample of about 4,000 German twin families. In the present article, we first introduce the theoretical and empirical background of the TwinLife study, and second, describe the design, content, and implementation of TwinLife. Since the data will be made available as scientific use file, we also illustrate research possibilities provided by this project to the scientific community.
Aquatic larval habitat conditions influence the development, fitness and vectorial capacity of mosquitoes. In turn, human activities can influence these conditions and shape mosquito vector distribution, thus affecting pathogen circulation and transmission. We measured environmental factors (chemical and microbial) in mosquito larval habitats and evaluated their potential as predictors for the occurrence of different mosquito species in an arbovirus and malaria endemic region of western Kenya. We found significantly greater proportions of Aedes aegypti mosquito larvae in ammonium and phosphate rich habitats, suggesting that fertilizer usage could potentially increase aquatic habitat suitability and Aedes vectored disease transmission. Anopheles gambiae larval habitats correlated significantly with higher temperatures. However, none of the Culex species’ habitats correlated with investigated variables, indicating greater larval plasticity compared to Aedes or Anopheles. Profiling of bacterial communities by 16S rRNA pyrosequencing revealed Proteobacteria, Bacterioidetes and Firmicutes as the major bacteria phyla present in mosquito aquatic microhabitats. Although there were no correlations between microbiota composition or diversity and larval species abundance, the dominant genera of microbes detected in larval habitats were reported in larval and adult mid-guts, suggesting that bacteria acquired from the larval habitats are transmitted to adult stages. This study identified the chemical and bacterial composition of aquatic microhabitats that are conducive to the development of different mosquito vectors in western Kenya. This information can inform potential vector control strategies by assessing management of breeding sites based on likely exposure to fertilizer, light and bacterial fauna.
Bipolar disorder is a highly heritable polygenic disorder. Recent enrichment analyses suggest that there may be true risk variants for bipolar disorder in the expression quantitative trait loci (eQTL) in the brain.
Aims
We sought to assess the impact of eQTL variants on bipolar disorder risk by combining data from both bipolar disorder genome-wide association studies (GWAS) and brain eQTL.
Method
To detect single nucleotide polymorphisms (SNPs) that influence expression levels of genes associated with bipolar disorder, we jointly analysed data from a bipolar disorder GWAS (7481 cases and 9250 controls) and a genome-wide brain (cortical) eQTL (193 healthy controls) using a Bayesian statistical method, with independent follow-up replications. The identified risk SNP was then further tested for association with hippocampal volume (n = 5775) and cognitive performance(n = 342) among healthy individuals.
Results
Integrative analysis revealed a significant association between a brain eQTL rs6088662 on chromosome 20q11.22 and bipolar disorder (log Bayes factor = 5.48; bipolar disorder P = 5.85×10–5). Follow-up studies across multiple independent samples confirmed the association of the risk SNP (rs6088662) with gene expression and bipolar disorder susceptibility (P =3.54×10–8). Further exploratory analysis revealed that rs6088662 is also associated with hippocampal volume and cognitive performance in healthy individuals.
Conclusions
Our findings suggest that 20q11.22 is likely a risk region for bipolar disorder; they also highlight the informative value of integrating functional annotation of genetic variants for gene expression in advancing our understanding of the biological basis underlying complex disorders, such as bipolar disorder.
To determine the sensitivity and specificity of clinical and laboratory signs for the diagnosis of septic arthritis (SA).
Patients and methods
This prospective study included all adult patients with suspected SA seen in the emergency department or rheumatology department at the University Hospital, Clermont-Ferrand, France, over a period of 18 months.
Results
In total, 105 patients with suspected SA were included, 38 (36%) presenting with SA (29 [28%] with bacteriologically documented SA). In the univariate analysis, chills (p=0.015), gradual onset (p=0.04), local redness (p=0.01), as well as an entry site for infection (p=0.01) were most often identified in SA. A history of crystal-induced arthritis (p=0.004) was more frequent in non-SA cases. An erythrocyte sedimentation rate (ESR)>50 mm (p=0.005), a C-reactive protein (CRP) level >100 mg/L (p=0.019), and radiological signs suggestive of SA (p=0.001) were more frequent in the SA cases. Synovial fluid appearance: purulent (p<0.001) and clear (p=0.007), synovial white blood cell (WBC) count >50,000/μL (p < 0.001), differentiated between SA and non-SA.
In multivariate analysis, only chills (odds ration [OR]=4.7, 95% confidence interval [CI] 1.3–17.1), a history of crystal-induced arthritis (OR=0.09, 95% CI 0.01–0.9), purulent appearance of the joint fluid (OR=8.4, 95% CI 2.4–28.5), synovial WBC count >50,000/mm3 (OR=6.8, 95% CI 1.3–36), and radiological findings (OR=7.1, 95% CI 13–37.9) remained significant.
Conclusion
No clinical sign or laboratory test (excluding bacteriological test), taken alone, is conclusive for the differentiation between SA and non-SA, but the association of several signs, notably chills, history of crystal-induced arthritis, radiological findings, and the appearance and cellularity of joint fluid may be suggestive.