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Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).
Aims
We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.
Method
Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.
Results
Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.
Conclusions
We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.
Attempts to use artificial intelligence (AI) in psychiatric disorders show moderate success, highlighting the potential of incorporating information from clinical assessments to improve the models. This study focuses on using large language models (LLMs) to detect suicide risk from medical text in psychiatric care.
Aims
To extract information about suicidality status from the admission notes in electronic health records (EHRs) using privacy-sensitive, locally hosted LLMs, specifically evaluating the efficacy of Llama-2 models.
Method
We compared the performance of several variants of the open source LLM Llama-2 in extracting suicidality status from 100 psychiatric reports against a ground truth defined by human experts, assessing accuracy, sensitivity, specificity and F1 score across different prompting strategies.
Results
A German fine-tuned Llama-2 model showed the highest accuracy (87.5%), sensitivity (83.0%) and specificity (91.8%) in identifying suicidality, with significant improvements in sensitivity and specificity across various prompt designs.
Conclusions
The study demonstrates the capability of LLMs, particularly Llama-2, in accurately extracting information on suicidality from psychiatric records while preserving data privacy. This suggests their application in surveillance systems for psychiatric emergencies and improving the clinical management of suicidality by improving systematic quality control and research.
Individuals at risk for bipolar disorder (BD) have a wide range of genetic and non-genetic risk factors, like a positive family history of BD or (sub)threshold affective symptoms. Yet, it is unclear whether these individuals at risk and those diagnosed with BD share similar gray matter brain alterations.
Methods:
In 410 male and female participants aged 17–35 years, we compared gray matter volume (3T MRI) between individuals at risk for BD (as assessed using the EPIbipolar scale; n = 208), patients with a DSM-IV-TR diagnosis of BD (n = 87), and healthy controls (n = 115) using voxel-based morphometry in SPM12/CAT12. We applied conjunction analyses to identify similarities in gray matter volume alterations in individuals at risk and BD patients, relative to healthy controls. We also performed exploratory whole-brain analyses to identify differences in gray matter volume among groups. ComBat was used to harmonize imaging data from seven sites.
Results:
Both individuals at risk and BD patients showed larger volumes in the right putamen than healthy controls. Furthermore, individuals at risk had smaller volumes in the right inferior occipital gyrus, and BD patients had larger volumes in the left precuneus, compared to healthy controls. These findings were independent of course of illness (number of lifetime manic and depressive episodes, number of hospitalizations), comorbid diagnoses (major depressive disorder, attention-deficit hyperactivity disorder, anxiety disorder, eating disorder), familial risk, current disease severity (global functioning, remission status), and current medication intake.
Conclusions:
Our findings indicate that alterations in the right putamen might constitute a vulnerability marker for BD.
We report a combined experimental and theoretical study of uranyl complexes that form on the interlayer siloxane surfaces of montmorillonite. We also consider the effect of isomorphic substitution on surface complexation since our montmorillonite sample contains charge sites in both the octahedral and tetrahedral sheets. Results are given for the two-layer hydrate with a layer spacing of 14.58 Å. Polarized-dependent X-ray absorption fine structure spectra are nearly invariant with the incident angle, indicating that the uranyl ions are oriented neither perpendicular nor parallel to the basal plane of montmorillonite. The equilibrated geometry from Monte Carlo simulations suggests that uranyl ions form outer-sphere surface complexes with the [O=U=O]2+ axis tilted at an angle of ~45° to the surface normal.
Two industrial bentonites, IBECO SEAL-80 and TIXOTON TE, have been proposed as potential backfill material in the German Asse salt dome, a test field for the disposal of low- to medium-grade active nuclear waste. Considering the unlikely but possible case of a barrier breakdown with infiltration of a highly concentrated salt brine, the physicochemical stability and material behavior of these bentonites in a saturated salt brine (predominantly MgCl2) at 25°C were studied over the time period of 150 days. The results show that no mineral transformations occurred throughout the duration of the experiments and minor dissolution was only active during the first days. Some chemical properties, namely sorption capability and swelling, were reduced during contact with the salt brine, but could be reversed by removing the salt after treatment. Despite restriction of the CEC in the presence of salt solution, interlayer cation exchange reactions are still active in this environment. The long-term chemical stability of smectite in salt brine is predicted under these low-temperature conditions, but the increased permeability during aggregate formation could lead to physical breakdown of the backfill component.
Interaction between metal Fe and a variety of natural and synthetic smectite samples with contrasting crystal chemistry was studied by scanning electron microscopy and X-ray diffraction from experiments conducted at 80°C. These experiments demonstrate an important reactivity contrast as a function of smectite crystal chemistry. An XRD method involving the use of an internal standard allowed quantification of the relative proportion of smectite destabilized as a function of initial pH conditions as well as of smectite structural parameters. In mildly acidic to neutral pH conditions, a significant proportion of metal Fe is corroded to form magnetite without smectite destabilization. Under basic pH conditions, smectite and metal Fe are partly destabilized to form magnetite and newly-formed 1:1 phyllosilicate phases (odinite and crondstedtite). More specifically, systematic destabilization of both metal Fe and smectite is observed for dioctahedral smectites while trioctahedral smectites are essentially unaffected under similar experimental conditions. In addition, smectite reactivity is enhanced with increasing Fe3+ content and with the presence of Na+ cations in smectite interlayers. A conceptual model for smectite destabilization is proposed. This model involves first the release of protons from smectite structure, MeFe3+OH groups being deprotonated preferentially and metal Fe acting as proton acceptor. Corrosion of metal Fe results from its interaction with these protons. The Fe2+ cations resulting from this corrosion process sorb on the edges of smectite particles to induce the reduction of structural Fe3+ and migrate into smectite interlayers to compensate for the increased layer-charge deficit. Interlayer Fe2+ cations subsequently migrate to the octahedral sheet of smectite because of the extremely large layer-charge deficit. At low temperature, this migration is favored by the reaction time and by the absence of protons within the di-trigonal cavity. Smectite destabilization results from the inability of the tetrahedral sheets to accommodate the larger dimensions of the newly formed trioctahedral domains resulting from the migration of Fe2+ cations.
Np and Pu are two important actinides of concern for the safe long-term disposal of nuclear waste. Both actinides are, in addition, constituents of global nuclear fallout. Investigation of their environmental behavior requires ultra-sensitive analytical methods, but current methods for a concurrent determination in clay minerals are lacking. In the present study, a Pu isotope was investigated for use as a non-isotopic yield tracer for Np in extraction, purification, and mass spectrometric determination of Np and Pu isotopes in clay materials. Inductively coupled plasma mass spectrometry was used in this developmental study, but the method is intended for future ultra-trace analysis of global-fallout Np and Pu in clay-rich soil materials by the more sensitive accelerator mass spectrometry. Another field of application may be the investigation of diffusion patterns of actinides in compacted clay liners and potential host rocks for radioactive waste disposal. The analytical procedure includes the following steps: (1) extraction of Np and Pu from clay samples; (2) adjustment of Np and Pu to Np(IV) and Pu(III); (3) pre-concentration of Np and Pu by co-precipitation with iron hydroxide; (4) adjustment of Pu to Pu(IV); (5) extraction chromatographic separation of Pu and Np from iron and matrix elements; and (6) determination of Np and Pu by mass spectrometry. The analytical procedure was applied successfully to spiked montmorillonite and illite test portions of up to 1 g. High chemical yields near 90% were obtained for both Np and Pu. The suitability of Pu as a non-isotopic tracer for Np was indicated by Np/Pu chemical yield ratios close to unity. Accurate pH adjustment during the reductive co-precipitation and short processing times are vital to obtain high chemical yields and Np/Pu yield ratios close to unity.
The impact of alkaline solutions (pH = 13.2) on the clay mineralogy of the Callovo-Oxfordian formation hosting the French underground laboratory for nuclear waste disposal investigation (Meuse-Haute Marne site) has been studied experimentally. Initially, each of the four samples selected as representative of the mineralogical transition in this Callovo-Oxfordian formation consists of a mixture of three main clay phases: discrete illite, discrete smectite and a randomly interstratified mixed-layered mineral (MLM) containing ∼65% of non-expandable layers. Clay separates were altered in batch reactors at 60°C using high solution:solid ratios. The mineralogy of this clay fraction and solution chemistry were monitored as a function of reaction time. In addition, the interactions between organic matter and clay particles were investigated using scanning transmission X-ray microscopy (STXM).
The clay mineralogy is little affected even though the pH is still high after 1 y reaction time. The only significant mineralogical evolution is the partial dissolution of the discrete smectite component leading to the formation of a new randomly interstratified illite-expandable MLM. Additional mineralogical transformations lead, for one sample, to the dissolution of micro-crystalline quartz and, for another sample, to the crystallization of a tobermorite-like phase. The low reactivity of clay minerals may be attributed to the presence of organic matter in the samples. In their initial state, all outer surfaces of clay particles are indeed covered with organic matter. After 1 y reaction time, STXM studies showed the basal surfaces of clay particles to be devoid of organic matter, but their edges, which are the most reactive sites, were still protected.
Individuals with bipolar disorder are commonly correctly diagnosed a decade after symptom onset. Machine learning techniques may aid in early recognition and reduce the disease burden. As both individuals at risk and those with a manifest disease display structural brain markers, structural magnetic resonance imaging may provide relevant classification features.
Methods
Following a pre-registered protocol, we trained linear support vector machine (SVM) to classify individuals according to their estimated risk for bipolar disorder using regional cortical thickness of help-seeking individuals from seven study sites (N = 276). We estimated the risk using three state-of-the-art assessment instruments (BPSS-P, BARS, EPIbipolar).
Results
For BPSS-P, SVM achieved a fair performance of Cohen's κ of 0.235 (95% CI 0.11–0.361) and a balanced accuracy of 63.1% (95% CI 55.9–70.3) in the 10-fold cross-validation. In the leave-one-site-out cross-validation, the model performed with a Cohen's κ of 0.128 (95% CI −0.069 to 0.325) and a balanced accuracy of 56.2% (95% CI 44.6–67.8). BARS and EPIbipolar could not be predicted. In post hoc analyses, regional surface area, subcortical volumes as well as hyperparameter optimization did not improve the performance.
Conclusions
Individuals at risk for bipolar disorder, as assessed by BPSS-P, display brain structural alterations that can be detected using machine learning. The achieved performance is comparable to previous studies which attempted to classify patients with manifest disease and healthy controls. Unlike previous studies of bipolar risk, our multicenter design permitted a leave-one-site-out cross-validation. Whole-brain cortical thickness seems to be superior to other structural brain features.
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.
Bipolar disorders are frequently not diagnosed until long after their onset, leaving patients with no or correspondingly inadequate treatment. The course of the disorder is all the more severe and the negative repercussions for those affected all the greater. Concerted research effort is therefore going into learning how to recognize bipolar disorders at an early stage. Drawing on current research results, this paper presents considerations for an integrative Early Symptom Scale with which persons at risk can be identified and timely intervention initiated. This will require prospective studies to determine the predictive power of the risk factors integrated into the scale.
Previous studies in individual countries have identified inconsistent predictors of length of stay (LoS) in psychiatric inpatient units. This may reflect methodological inconsistencies across studies or true differences of predictors. In this study we assessed predictors of LoS in five European countries and explored whether their effect varies across countries.
Methods
Prospective cohort study. All patients admitted over 14 months to 57 psychiatric inpatient units in Belgium, Germany, Italy, Poland and United Kingdom were screened. Putative predictors were collected from medical records and in face-to-face interviews and tested for their association with LoS.
Results
Average LoS varied from 17.9 days in Italy to 55.1 days in Belgium. In the overall sample being homeless, receiving benefits, social isolation, diagnosis of psychosis, greater symptom severity, substance use, history of previous admission and being involuntarily admitted predicted longer LoS. Several predictors showed significant interaction effects with countries in predicting LoS. One variable, homelessness, predicted a different LoS even in opposite directions, whilst for other predictors the direction of the association was the same, but the strength of the association with LoS varied across countries.
Conclusions
The same patient characteristics have a different impact on LoS in different contexts. Thus, although some predictor variables related to clinical severity and social dysfunction appear of generalisable relevance, national studies on LoS are required to understand the complex influence of different patient characteristics on clinical practice in the given contexts.
Patient satisfaction is a key indicator of inpatient care quality and is associated with clinical outcomes following admission. Different patient characteristics have been inconsistently linked with satisfaction. This study aims to overcome previous limitations by assessing which patient characteristics are associated with satisfaction within a large study of psychiatric inpatients conducted across five European countries.
Methods
All patients with a diagnosis of psychotic (F2), affective (F3) or anxiety/somataform (F4) disorder admitted to 57 psychiatric inpatient units in Belgium, Germany, Italy, Poland and the UK were included. Data were collected from medical records and face-to-face interviews, with patients approached within 2 days of admission. Satisfaction with inpatient care was measured on the Client Assessment of Treatment Scale.
Results
Higher satisfaction scores were associated with being older, employed, living with others, having a close friend, less severe illness and a first admission. In contrast, higher education levels, comorbid personality disorder and involuntary admission were associated with lower levels of satisfaction. Although the same patient characteristics predicted satisfaction within the five countries, there were significant differences in overall satisfaction scores across countries. Compared to other countries, patients in the UK were significantly less satisfied with their inpatient care.
Conclusions
Having a better understanding of patient satisfaction may enable services to improve the quality of care provided as well as clinical outcomes for all patients. Across countries, the same patient characteristics predict satisfaction, suggesting that similar analytical frameworks can and should be used when assessing satisfaction both nationally and internationally.
In Europe, at discharge from a psychiatric hospital, patients with severe mental illness may be exposed to one of two main care approaches: personal continuity, where one clinician is responsible for in- and outpatient care, and specialisation, where various clinicians are. Such exposure is decided through patient-clinician agreement or at the organisational level, depending on the country’s health system. Since personal continuity would be more suitable for patients with complex psychosocial needs, the aim of this study was to identify predictors of patients’ exposure to care approaches in different European countries.
Methods:
Data were collected on 7302 psychiatric hospitalised patients in 2015 in Germany, Poland, and Belgium (patient-level exposure); and in the UK and Italy (organisational-level exposure). At discharge, patients were exposed to one of the care approaches according to usual practice. Putative predictors of exposure at patients’ discharge were assessed in both groups of countries.
Results:
Socially disadvantaged patients were significantly more exposed to personal continuity. In all countries, the main predictor of exposure was the admission hospital, except in Germany, where having a diagnosis of psychosis and a higher education status were predictors of exposure to personal continuity. In the UK, hospitals practising personal continuity had a more socially disadvantaged patient population.
Conclusion:
Even in countries where exposure is decided through patient-clinician agreement, it was the admission hospital, not patient characteristics, that predicted exposure to care approaches. Nevertheless, organisational decisions in hospitals tend to expose socially disadvantaged patients to personal continuity.
Jarosite, a hydrous potassium iron sulphate mineral, has been found as the product of weathering in a silicic chalk building stone of a 13th century abbey at Fontevrault (Maine-et-Loire, France). Destabilization of pyrite and glauconite dispersed in the calcareous stone results in the formation of jarosite. The alteration process is probably of very local origin, within the zone in the building stone at its surface where oxidation occurs during wetting and drying on a cyclical basis. The problem of the incompatibility of highly acidic solutions needed to stabilise jarosite (2.5 < pH) within the highly porous, calcareous silicate rock is not explained at present.
Evaluate antimicrobial stewardship interventions targeted to reduce highly active antiretroviral therapy (HAART)– or opportunistic infection (Ol)–related medication errors and increase error resolution.
Design.
Retrospective before-after study.
Setting.
Academic medical center.
Patients.
Inpatients who were prescribed antiretroviral therapy before the intervention (January 1, 2011, to October 31, 2011) and after the intervention (July 1, 2012, to December 31, 2012). Patients treated with lamivudine or tenofovir monotherapy for hepatitis B were excluded.
Methods.
Antimicrobial stewardship interventions included education, modification of electronic medication records, collaboration with the infectious diseases (ID) department, and prospective audit and review of HAART and OI regimens by an ID clinical pharmacist.
Results.
Data for 162 admissions from the preintervention period and 110 admissions from the postintervention period were included. The number of admissions with a medication error was significantly reduced after the intervention (81 [50%] of 162 admissions vs 37 (34%) of 110 admissions; P < .00)1. A total of 124 errors occurred in the preintervention group (mean no. of errors, 1.5 per admission), and 43 errors occurred in the postintervention group (mean no. of errors, 1.2 per admission). The most common error types were major drug interactions and dosing in the preintervention group and renal adjustment and OI-related errors in the postintervention group. A significantly higher error resolution rate was observed in the postintervention group (36% vs 74%; P < .001). After adjustment for potential confounders with logistic regression, admission in the postintervention group was independently associated with fewer medication errors (odds ratio, 0.4 [95% confidence interval, 0.24-0.77]; P = .005). Overall, presence of an ID consultant demonstrated a higher error resolution rate (32% without a consultation vs 68% with a consultation; P = .002).
Conclusions.
Multifaceted, multidisciplinary stewardship efforts reduced the rate and increased the overall resolution of HAART-related medication errors.
We have studied Cu2S absorber layers prepared by physical vapor deposition (PVD) by calibrated spectral photoluminescence (PL) and by confocal PL as function of temperature T and excitation fluxes to obtain the absolute PL-yield at an excitation flux equivalent to the AM1.5 spectrum and to calculate the splitting of the quasi-Fermi levels (QFL) µ = Ef,n-Ef,p and the absorption coefficient α(E), both in the temperature range 20 K ≤ T ≤ 400 K. The PL-spectra reveal two peaks at E1 = 1.17 eV and E2 = 1.3 eV, of which the low energy peak is only detectable at temperatures T < 200 K. The samples show an impressive QFL-splitting of µ > 700 meV at 300 K associated with a pseudo band gap of Eg = 1.25 eV. The high energy peak shows an unexpected temperature behavior, namely an increase of the PL-yield with rising temperature at variance with the behavior of QFL-splitting that decreases with rising T from extrapolated T = 0K value of µ = 1.3 eV. The PL-yield versus temperature will be discussed in terms of different defect states in the band gap. Our observations indicate that, contrary to common believe, it is not the PL-yield, but rather the QFL-splitting that is the comprehensive indicator of the quality of the excited state in an illuminated semiconductor. A further examination of the lateral variation of the opto-electronic properties by confocal PL shows a strong correlation between the QFL-splitting, the Urbach energy EU and the optical band gap Eopt, respectively.