Current status and ongoing needs for the teaching and assessment of clinical reasoning - an international mixed-methods study from the students` and teachers` perspective.

BACKGROUND: Clinical reasoning (CR) is a crucial ability that can prevent errors in patient care. Despite its important role, CR is often not taught explicitly and, even when it is taught, typically not all aspects of this ability are addressed in health professions education. Recent research has shown the need for explicit teaching of CR for both students and teachers. To further develop the teaching and learning of CR we need to improve the understanding of students' and teachers' needs regarding content as well as teaching and assessment methods for a student and trainer CR curriculum. METHODS: Parallel mixed-methods design that used web-surveys and semi-structured interviews to gather data from both students (nsurvey = 100; ninterviews = 13) and teachers (nsurvey = 112; ninterviews = 28). The interviews and surveys contained similar questions to allow for triangulation of the results. This study was conducted as part of the EU-funded project DID-ACT ( https://did-act.eu ). RESULTS: Both the surveys and interview data emphasized the need for content in a clinical reasoning (CR) curriculum such as "gathering, interpreting and synthesizing patient information", "generating differential diagnoses", "developing a diagnostic and a treatment plan" and "collaborative and interprofessional aspects of CR". There was high agreement that case-based learning and simulations are most useful for teaching CR. Clinical and oral examinations were favored for the assessment of CR. The preferred format for a train-the-trainer (TTT)-course was blended learning. There was also some agreement between the survey and interview participants regarding contents of a TTT-course (e.g. teaching and assessment methods for CR). The interviewees placed special importance on interprofessional aspects also for the TTT-course. CONCLUSIONS: We found some consensus on needed content, teaching and assessment methods for a student and TTT-course in CR. Future research could investigate the effects of CR curricula on desired outcomes, such as patient care.

Mechanistic insights into C(sp2)-H activation in 1-Phenyl-4-vinyl-1H-1,2,3-triazole derivatives: a theoretical study with palladium acetate catalyst.

CONTEXT: The activation of C-H bonds is a fundamental process in synthetic organic chemistry, which enables their replacement by highly reactive functional groups. Coordination compounds serve as effective catalysts for this purpose, as they facilitate chemical transformations by interacting with C-H bonds. A comprehensive understanding of the mechanism of activation of this type of bond lays the foundation for the development of efficient protocols for cross-coupling reactions. We explored the activation of C(sp2)-H bonds in 1-Phenyl-4-vinyl-1H-1,2,3-triazole derivatives with CH3, OCH3, and NO2 substituents in the para position of the phenyl ring, using palladium acetate as catalyst. The studied reaction is the first step for subsequent conjugation of the triazoles with naphthoquinones in a Heck-type reaction to create a C-C bond. The basic nitrogen atoms of the 1,2,3-triazole coordinate preferentially with the cationic palladium center to form an activated species. A concerted proton transfer from the terminal vinyl carbon to one of the acetate ligands with low activation energy is the main step for the C(sp2)-H activation. This study offers significant mechanistic insights for enhancing the effectiveness of C(sp2)-H activation protocols in organic synthesis. METHODS: All calculations were performed using the Gaussian 09 software package and density functional theory (DFT). The structures of all reaction path components were fully optimized using the CAM-B3LYP functional with the Def2-SVP basis set. The optimized geometries were analyzed by computing the second-order Hessian matrix to confirm that the corresponding minimum or transition state was located. To account for solvent effects, the Polarizable Continuum Model of the Integral Equation Formalism (IEFPCM) with water as the solvent was used.

Karyotypic changes and diversification time in Epinephelidae groupers (Perciformes). Implications on reproductive isolation.

Groupers (Epinephelidae and Serranidae) have attracted special attention to fish farming, and their species offer good opportunities for successful hybridizations. Cytogenetic data allow a better understanding of the role of karyotypic diversification in the acquisition of post-zygotic reproductive isolation (RI). Thus, chromosomal analyses were performed on E. striatus (Caribbean Sea), E. coioides and E. tauvina (Indo-Pacific Region), using standard procedures and mapping of six repetitive DNA classes by the in situ hybridization. The three species have 2n=48 chromosomes. The karyotypes of E. coioides and E. striatus are composed only of acrocentric chromosomes (FN=48), while E. tauvina has 8 submetacentric chromosomes (FN=56). Heterochromatin has a preferential centromeric distribution, and the microsatellite repeats are dispersed throughout the chromosomes of all species. The 18S and 5S rDNA sites are unique but show a colocalization arrangement in E. tauvina and E. striatus. The chromosomal organization suggests that the three species still maintain a significant amount of syntenic regions. The range of the karyotype divergence and the RI levels showed low, but goes turn proportionally greater in relation to the divergence time between the parental species. The slow acquisition of postzygotic RI is consistent with the high karyotype homogeneity presented by Epinephelidae family.

Four new records of Sipuncula (Annelida) from Northern Brazil.

There are very few taxonomic studies of Brazilian sipunculan worms, and the species occurring along the northern coasts are largely understudied. We report herein the occurrence of four shallow water species along the intertidal zones of Bahia and Pernambuco states. Antillesoma antillarum (Grbe & Oersted, 1858) occurs from underneath beach rocks or within sandstone reefs and may reach high densities. The large species Sipunculus (Sipunculus) nudus Linnaeus, 1766, Sipunculus polymyotus Fisher, 1947, and Xenosiphon branchiatus (Fischer, 1895) were collected in sandy-mud, low-energy intertidal environments. For the first time, we report that sipunculans are collected and used as fishing bait by local fishermen in the Western Atlantic. All species are fully described, including notes on their external and internal anatomy.

3D-printed electrodes using graphite/carbon nitride/polylactic acid composite material: A greener platform for detection of amaranth dye in food samples.

The production of sustainable materials with properties aimed at the additive manufacturing of electrochemical sensors has gained prestige in the scientific scenario. Here, a novel lab-made composite material using graphite (G) and carbon nitride (C3N4) embedded into polylactic acid (PLA) biopolymer is proposed to produce 3D-printed electrodes. PLA offers printability and mechanical stability in this composition, while G and C3N4 provide electrical properties and electrocatalytic sites, respectively. Characterizations by Raman and infrared spectroscopies and Energy Dispersive X-rays indicated that the G/C3N4/PLA composite was successfully obtained, while electron microscopy images revealed non-homogeneous rough surfaces. Better electrochemical properties were achieved when the G/C3N4/PLA proportion (35:5:60) was used. As a proof of concept, amaranth (AMR), a synthetic dye, was selected as an analyte, and a fast method using square wave voltammetry was developed. Utilizing the 3D-printed G/C3N4/PLA electrode, a more comprehensive linear range (0.2 to 4.2 µmol/L), a 5-fold increase in sensitivity (9.83 µmol-1 L µA), and better limits of detection (LOD = 0.06 µmol/L) and quantification (LOQ = 0.18 µmol/L) were achieved compared to the G/PLA electrode. Samples of jelly, popsicles, isotonic drinks, and food flavoring samples were analyzed, and similar results to those obtained by UV-vis spectrometry confirmed the method's reliability. Therefore, the described sensor is a simple, cost-effective alternative for assessing AMR in routine food analysis.

The impact of sleep duration on physical activity in daily life in patients with idiopathic pulmonary fibrosis.

BACKGROUND: Despite the high prevalence of sleep disturbances in idiopathic pulmonary fibrosis (IPF), the relationship between physical activity in daily life (PADL) and sleep in this population remains unclear. OBJECTIVES: Investigate the impact of sleep on different domains of PADL in IPF and characterize their PADL profile. METHODS: Sixty-seven participants (thirty-three with IPF and thirty-four healthy subjects [control group]) were included. The subjects underwent assessments of pulmonary function, exercise capacity, respiratory and peripheral muscle strength, PADL, sleep, dyspnea, and health-related quality of life. PADL and sleep measures were assessed using an activity monitor (Actigraph®, wGT3x-BT). Associations between sleep and PADL were done using correlation and regression models. RESULTS: In the IPF, sleep duration at night associated significantly with step counts, sedentary, light, and moderate-to-vigorous physical activity (MVPA) (-0.82 ≤ R ≤ 0.43; p < .05 for all). Lung function and sleep partially explained PADL variables (0.19 ≤ R2 ≤ 0.65, p < .05 for all). Compared to controls, the IPF subjects presented lower step counts, less time spent in MVPA, standing position, and more time spent in lying position (p < .05, for all). CONCLUSIONS: Sleep duration is associated with PADL in IPF. The PADL profile of patients is worse than in control subjects.

3D printed graphite-based electrode coupled with batch injection analysis: An affordable high-throughput strategy for atorvastatin determination.

This work integrated a lab-made conductive graphite/polylactic acid (Grp/PLA, 40:60% w/w) filament into a 3D pen to print customized electrodes (cylindrical design). Thermogravimetric analysis validated the incorporation of graphite into the PLA matrix, while Raman spectroscopy and scanning electron microscopy images indicated a graphitic structure with the presence of defects and highly porous, respectively. The electrochemical features of the 3D-printed Gpt/PLA electrode were systematically compared to that achieved using commercial carbon black/polylactic acid (CB/PLA, from Protopasta®) filament. The 3D printed Gpt/PLA electrode "in the native form" provided lower charge transfer resistance (Rct = 880 Ω) and a more kinetically favored reaction (K0 = 1.48 × 10-3 cm s-1) compared to the 3D printed CB/PLA electrode (chemically/electrochemically treated). Moreover, a method by batch injection analysis with amperometric detection (BIA-AD) was developed to determine atorvastatin (ATR) in pharmaceutical and water samples. Using the 3D printed Gpt/PLA electrode, a wider linear range (1-200 µmol L-1), sensitivity (3-times higher), and lower detection limit (LOD = 0.13 µmol L-1) were achieved when compared to the CB/PLA electrode. Repeatability studies (n = 15, RSD <7.3%) attested to the precision of the electrochemical measurements, and recovery percentages between 83 and 108% confirmed the accuracy of the method. Remarkably, this is the first time that ATR has been determined by the BIA-AD system and a low-cost 3D-printed device. This approach is promising to be implemented in research laboratories for quality control of pharmaceuticals and can also be useful for on-site environmental analysis.

Under-reporting of forensic findings: craniocervical emergency imaging in cases of survived hanging.

To determine the diagnostic bias between clinical and forensic radiology in cases of nonfatal hanging and determine and describe typical underreported imaging findings. In a retrospective, single-center study, all patients admitted for attempted suicide with near-hanging or fatal hanging between January 2008 and December 2020 who received CT or MRI of head and neck were reviewed and missed findings in the original report were documented. A binary regression with disagreement as dependent variable was fitted for the imaging modality, fatality, age, and sex. A total of 123 hanging incidents were retrospectively analyzed. The vast majority (n = 108; 87.8%) had attempted suicide with a nonfatal outcome. Fatal outcome occurred in 15 (12.0%). The extra- and intracranial injuries documented on CT and MRI scans were laryngeal (n = 8; 6.5%), soft tissue (n = 42; 34.1%), and vascular injuries (n = 1; 0.8%). Intracranial pathology was evident on 18 (14.6%) scans. Disagreement occurred in 36 (29.3%) cases and represented 52 (69.2%) of all cases with a radiological finding. Disagreement was strongly associated with fatality (OR: 2.7-44.9.4, p = 0.0012). In most cases, nonfatal hangings cause no or only minor injuries. Fatal cases are associated with a greater probability of missed minor imaging findings. This suggests that findings deemed clinically irrelevant are probably not reported in such severe emergency cases. This association indicates that minor abnormalities are underreported when major pathologies are evident on imaging in victims of strangulation.

Preliminary Assessment of the First-Order Density Matrix in Quantum Monte Carlo from Density Matrix Theory.

The trial wave function commonly used in the quantum Monte Carlo method consists of the product of up-spin and down-spin Slater determinants, allowing accurate calculations of multielectronic properties, although it is not antisymmetric under the exchange of electrons with opposite spins. An alternative description that overcomes these limitations using the Nth-order density matrix was already presented. This study introduces two new strategies based on the Dirac-Fock density matrix for QMC that still fully preserve antisymmetry and electron indistinguishability. Simulations are performed for the ground and excited states of He, Li, and Be showing that the present formulation and the conventional separation of spins are appropriate for a correct description of these systems, except for singlet excited states of the He and Be atoms, and that a part of the antisymmetry (antiparallel spins) can be neglected.

Application of Lipidomics in Psychiatry: Plasma-Based Potential Biomarkers in Schizophrenia and Bipolar Disorder.

In this study, we obtained a lipidomic profile of plasma samples from drug-naïve patients with schizophrenia (SZ) and bipolar disorder (BD) in comparison to healthy controls. The sample cohort consisted of 30 BD and 30 SZ patients and 30 control individuals. An untargeted lipidomics strategy using liquid chromatography coupled with high-resolution mass spectrometry was employed to obtain the lipid profiles. Data were preprocessed, then univariate (t-test) and multivariate (principal component analysis and orthogonal partial least squares discriminant analysis) statistical tools were applied to select differential lipids, which were putatively identified. Afterward, multivariate receiver operating characteristic tests were performed, and metabolic pathway networks were constructed, considering the differential lipids. Our results demonstrate alterations in distinct lipid pathways, especially in glycerophospholipids, sphingolipids and glycerolipids, between SZ and BD patients. The results obtained in this study may serve as a basis for differential diagnosis, which is crucial for effective treatment and improving the quality of life of patients with psychotic disorders.

Inflammatory cytokines and white matter microstructure in the acute phase of first-episode psychosis: A longitudinal study.

OBJECTIVES: Schizophrenia-related psychosis is associated with abnormalities in white matter (WM) microstructure and structural brain dysconnectivity. However, the pathological process underlying such changes is unknown. We sought to investigate the potential association between peripheral cytokine levels and WM microstructure during the acute phase of first-episode psychosis (FEP) in a cohort of drug-naïve patients. METHODS: Twenty-five non-affective FEP patients and 69 healthy controls underwent MRI scanning and blood collection at study entry. After achieving clinical remission, 21 FEP were reassessed; 38 age and biological sex-matched controls also had a second assessment. We measured fractional anisotropy (FA) of selected WM regions-of-interest (ROIs) and plasma levels of four cytokines (IL-6, IL-10, IFN-γ, and TNF-α). RESULTS: At baseline (acute psychosis), the FEP group showed reduced FA relative to controls in half the examined ROIs. Within the FEP group, IL-6 levels were negatively correlated with FA values. Longitudinally, patients showed increments of FA in several ROIs affected at baseline, and such changes were associated with reductions in IL-6 levels. CONCLUSIONS: A state-dependent process involving an interplay between a pro-inflammatory cytokine and brain WM might be associated with the clinical manifestation of FEP. This association suggests a deleterious effect of IL-6 on WM tracts during the acute phase of psychosis.

[Trauma team activation-Who should be alerted for which patients?] / Schockraumaktivierung ­ Bei welchen Patienten alarmieren wir wen?

INTRODUCTION: It is estimated that in total almost 10 million people are injured in accidents in Germany every year, most of which are in the household milieu and leisure sector. It is estimated that of these more than 32,000 seriously injured patients are admitted to the emergency room every year. It is recommended that the decision of the prehospital treatment team or the first examiner in the hospital as to whether a potentially severely injured patient should be admitted via the emergency room of the hospital should be based on a catalogue of criteria. MATERIAL AND METHOD: Against the background of the update of the S3 guidelines on the treatment of multiple trauma/severely injured patients and on the basis of the current literature, an overview with respect to the composition of the team and the criteria for which an emergency room team is or should be activated is given. RESULTS: Alerting the emergency room team is still recommended if a certain injury pattern is present or if a prehospital intervention is necessary. The B­criteria based on the course of the accident or mechanism, which have recently been the subject of increasing criticism, have been adapted. Recommendations for geriatric patients could also be formulated. DISCUSSION: Compared to the S3 guidelines from 2016 the emergency room alarm criteria could be revised on the basis of new literature and have been included in the revised guidelines. There is no doubt that further optimization. e.g., based on prehospital algorithms or using point of care diagnostics, are possible and desirable in the future.

A new class of peptides from wasp venom: a pathway to antiepileptic/neuroprotective drugs.

The ability of venom-derived peptides to disrupt physiological processes in mammals provides an exciting source for pharmacological development. Our research group has identified a new class of neuroactive peptides from the venom of a Brazilian social wasp, Polybia occidentalis, with the potential pharmacological profile to treat epilepsies. The study was divided into five phases: Phase 1 concerned the extraction, isolation and purification of Occidentalin-1202(n) from the crude venom, followed by the synthesis of an identical analogue peptide, named Occidentalin-1202(s). In Phase 2, we described the effects of both peptides in two acute models of epilepsy-kainic acid and pentylenetetrazole-induced model of seizures-and measured estimated ED50 and therapeutic index values, electroencephalographic studies and C-fos evaluation. Phase 3 was a compilation of advanced tests performed with Occidentalin-1202(s) only, reporting histopathological features and its performance in the pilocarpine-induced status epilepticus. After the determination of the antiepileptic activity of Occidentalin-1202(s), Phase 4 consisted of evaluating its potential adverse effects, after chronic administration, on motor coordination (Rotarod) and cognitive impairment (Morris water maze) tests. Finally, in Phase 5, we proposed a mechanism of action using computational models with kainate receptors. The new peptide was able to cross the blood-brain barrier and showed potent antiseizure effects in acute (kainic acid and pentylenetetrazole) and chronic (temporal lobe epilepsy model induced by pilocarpine) models. Motor and cognitive behaviour were not adversely affected, and a potential neuroprotective effect was observed. Occidentalin-1202 can be a potent blocker of the kainate receptor, as assessed by computational analysis, preventing glutamate and kainic acid from binding to the receptor's active site. Occidentalin-1202 is a peptide with promising applicability to treat epilepsy and can be considered an interesting drug model for the development of new medicines.

[Radiation exposure of the eye lens in orthopedics and trauma surgery : A pilot study]. / Strahlenbelastung der Augenlinse in O&U : Eine Pilotstudie.

BACKGROUND: On 27 June 2017 the Act on new regulation of the law for the protection against the harmful effects of ionizing radiation was passed. One of the main innovations in daily surgical practice in the now legally stipulated provisions is the lowering of the eye lens dose to 20 mSv/year (§§ 78, 212 Radiation Protection Act, StrlSchG). MATERIAL AND METHODS: To estimate the level of exposure of the eye lens to ionizing radiation that is to be expected in the course of surgical interventions, the dose that surgeons receive during surgery was determined. For this, the radiation exposure adjacent to the eye lens was measured using a forehead dosimeter while performing surgical interventions over a period of 8 weeks in 2 different operating rooms. RESULTS: As a result, a mean estimated eye lens radiation dose Hp (3) of 190 µSv could be determined during the 2­month study period. Thus, the estimated cumulative radiation dose in 1 year of approximately 1.2 mSv was significantly below the threshold of 20 mSv/year. CONCLUSION: By complying with the common radiation protection measures in the context of operative interventions in orthopedics and trauma surgery, the legal limit value of 20 mSv/year is generally not expected to be exceeded.

BDNF blood levels after electroconvulsive therapy in patients with mood disorders: An updated systematic review and meta-analysis.

OBJECTIVES: Studies have suggested Brain-Derived Neurotrophic Factors (BDNF) increase after electroconvulsive therapy (ECT) although they were methodologically limited and enrolled small sample sizes. We aimed at updating a systematic review and meta-analysis to explore BDNF changes after ECT for the treatment of depression. METHODS: PubMed, PsycInfo, Embase and Global health were searched (March, 2021). Clinical trials that measured BDNF in the blood before and after ECT in adults (≥ 18 years old) with depression (major depressive disorder or bipolar disorder) were eligible. Data were pooled through random-effects meta-analyses. RESULTS: Twenty-eight studies involving 778 participants were included. Meta-analysis showed a significant increase in BDNF levels after ECT (Hedges' g = 0.28; 95% CI: 0.10, 0.46) while there was evidence of significant heterogeneity (I2 = 67.64%) but not publication bias/small-study effect. Subgroup analyses and meta-regressions were underpowered to detect significant differences. Meta-analysis of depression severity scores demonstrated a considerable larger treatment effect in reducing depressive symptoms after ECT (Hedge's g = -3.72 95% CI: -4.23, -3.21). CONCLUSION: This updated review showed that BDNF blood levels increased after ECT treatment. However, there was still evidence of substantial heterogeneity and there were limited sample sizes to investigate factors driving the variability of effects across studies. Importantly, the increase in BDNF levels was substantially smaller than the observed in depressive symptomatology, which could be indicative that the former was independent than the latter. Additional studies with larger sample sizes are currently required.

The relationship between depression symptoms and academic performance among first-year undergraduate students at a South African university: a cross-sectional study.

BACKGROUND: South African universities face a challenge of low throughput rates, with most students failing to complete their studies within the minimum regulatory time. Literature has begun to investigate the contribution of well-being, including mental health, with depression among students being one of the most common mental disorders explored. However, locally relevant research exploring associations between depression and academic performance has been limited. This research hypothesizes that the presence of depression symptoms, when controlling for key socio-demographic factors, has an adverse impact on student academic outcomes and contributes to the delay in the academic progression of students. METHODS: The study used a cross-sectional design. Data were collected in 2019 from first-time, first-year undergraduate students using a self-administered online questionnaire. In total, 1,642 students completed the survey. The Patient Health Questionnaire-9 (PHQ-9) was used to screen for depression symptoms. Data on students' academic performance were obtained from institutional records. Bivariate and multivariate regression analyses were used to examine associations between depression symptoms and academic performance. RESULTS: Most participants (76%) successfully progressed (meeting the requirements to proceed to the second year of university study). Of the participants, 10% displayed symptoms of severe depression. The likelihood of progression delay (not meeting the academic requirements to proceed to the second year of university study) increased with the severity of depression symptoms. Moderate depression symptoms nearly doubled the adjusted odds of progression delay (aOR = 1.98, 95% CI: 1.30-3.00, p = 0.001). The likelihood of progression delay was nearly tripled by moderate severe depression symptoms (aOR = 2.70, 95% CI:1.70-4.36, p < 0.001) and severe depression symptoms (aOR = 2.59, 95% CI:1.54-4.36, p < 0.001). The model controlled for field of study, financial aid support as well as sex and race. CONCLUSION: Higher levels of depression symptoms among first-year university students are associated with a greater likelihood of progression delay and may contribute to the low throughput rates currently seen in South African universities. It is important for students, universities and government departments to recognize student mental wellness needs and how these can be met.

Two new deep-sea species of Capitella (Annelida: Capitellidae) from sunken wood in the Northeast Pacific.

Natural and experimental wood falls harbor a rich and abundant macrofaunal community in the deep-sea. Two undescribed capitellids have been collected from wood species bundles deployed at 3,100 m at the Deadwood 2 site in Monterey Bay and several other locations in the northeastern Pacific. Capitella blakei sp. nov. is a widely distributed deep-sea capitellid in the northeastern Pacific occurring from the Monterey canyon north to the Endeavour segment of the San Juan de Fuca Ridge, a range of almost 1,400 km. It belongs to a group of Capitella species having only individuals with male external characteristics, chaetigers 17 with notopodial and neuropodial capillaries and is readily distinguished from its congeners by the presence of a peristomium clearly separated from prostomium, deep lateral and ventral grooves, and methyl green staining pattern. Capitella multibranchiata sp. nov. is unique in the genus by the presence of branchiae on abdominal notopodial and neuropodial segments. The adult morphology of both species is described and compared to their most apparently related congeners. Our results have shown a greater diversity of deep-sea Capitella than previously known. The wide geographical distribution of C. blakei sp. nov. on wood habitats indicates that these wood falls may be functioning as ecological and evolutionary stepping-stones between the enriched sediments of vents and seeps.

Lithium increases cortical and subcortical volumes in subjects with bipolar disorder.

Bipolar disorder (BD) is a highly variable and burdensome disease for patients and caregivers. A BD diagnosis almost triples the likelihood of developing dementia as the disease progresses. Neurocognitive reserve appears to be one of the most important influences on lifelong functional outcomes and quality of life in BD. Though several prior studies have assessed the effects of lithium on regional gray and white matter volumes in this population, representative cohorts are typically middle-aged, have a more severe pathology, and are not as commonly assessed in the depressive phase (which represents the majority of most patients' lifespans outside of remission). Here we have shown that positive adaptations with lithium can be observed throughout the brain after only six weeks of monotherapy at low-therapeutic serum levels. Importantly, these results remove some confounders seen in prior studies (patients were treatment free at time of enrollment and mostly treatment naïve). This cohort also includes underrepresented demographics in the literature (young adult patients, mostly bipolar II, and exclusively in the depressed phase). These findings bolster the extensive body of evidence in support of long-term lithium therapy in BD, furthering the possibility of its expanded use to wider demographics.

The role of lithium treatment on comorbid anxiety symptoms in patients with bipolar depression.

BACKGROUND: Comorbid anxiety is pervasive and carries an immense psychosocial burden for patients with bipolar disorder. Despite this, trials reporting anxiety-related outcomes in this population are uncommon, particularly with regards to monotherapies. METHODS: Patients (n = 31) with both bipolar I or II disorder in current depressive episodes were enrolled in a six-week, open-label, single-center trial assessing the efficacy of lithium monotherapy in treating symptoms depression and comorbid anxiety. Patients were mostly medication-free and lithium-naïve at baseline. RESULTS: Significant improvements in depression (HAMD) and anxiety (HAM-A) were observed at the six-week endpoint, with remission and response rates greater than 50%. There was a positive correlation between endpoint HAM-A scores and HAM-D scores, r = 0.80, (p < 0.01). Improvements were realized at low serum lithium concentrations (0.49 ± 0.20 mEq/L). LIMITATIONS: Lack of placebo control and small sample size warrants validation in larger randomized studies. CONCLUSIONS: Taken in the context of prior evidence, lithium may have an important role in treating comorbid anxiety in bipolar disorder, both as adjunct and monotherapy. Lower doses of lithium may provide equivalent efficacy and enhance tolerability and compliance.

Simulation-based design study for the passive shielding of the COSINUS dark matter experiment.

The COSINUS (Cryogenic Observatory for SIgnatures seen in Next-generation Underground Searches) experiment aims at the detection of dark matter-induced recoils in sodium iodide (NaI) crystals operated as scintillating cryogenic calorimeters. The detection of both scintillation light and phonons allows performing an event-by-event signal to background discrimination, thus enhancing the sensitivity of the experiment. The choice of using NaI crystals is motivated by the goal of probing the long-standing DAMA/LIBRA results using the same target material. The construction of the experimental facility is foreseen to start by 2021 at the INFN Gran Sasso National Laboratory (LNGS) in Italy. It consists of a cryostat housing the target crystals shielded from the external radioactivity by a water tank acting, at the same time, as an active veto against cosmic ray-induced events. Taking into account both environmental radioactivity and intrinsic contamination of materials used for cryostat, shielding and infrastructure, we performed a careful background budget estimation. The goal is to evaluate the number of events that could mimic or interfere with signal detection while optimising the geometry of the experimental setup. In this paper we present the results of the detailed Monte Carlo simulations we performed, together with the final design of the setup that minimises the residual amount of background particles reaching the detector volume.