Overexpression of BAG3 (Bcl2-associated athanogene 3) in serum and skin of patients with systemic sclerosis.

OBJECTIVES: BAG3 (Bcl2-associated athanogene3) is able to induce the transformation of cancer-associated fibroblasts to alpha smooth muscle actin (a-SMA) positive (+) myofibroblasts. In systemic sclerosis (SSc), a-SMA+ myofibroblasts also play an important role in the progression of fibrosis in the skin and involved internal organs. The aim of the study was to investigate whether BAG3 is overexpressed in SSc and may be a biomarker of fibrogenesis. METHODS: BAG3 serum levels were measured in 106 patients with SSc, 47 with the limited (lc) and 59 the diffuse (dc) SSc, and in age- and sex-matched healthy controls (HC). BAG3 levels were then compared according to their clinical subset, nailfold video-capillaroscopic (NVC) patterns, interstitial lung disease (ILD, and correlated with modified Rodnan skin score (mRSS) and global disease activity. BAG3 expression was also investigated in skin biopsies of 8 dcSSc patients. RESULTS: BAG3 serum levels were significantly higher in dcSSc (143.3 pg/mL, 95%CI 78-208.5) than in HC (0.68 pg/mL, 95%CI 0.13-1.23), and were significantly higher in patients with late NVC pattern and ILD but did not correlate with disease activity and mRSS. Of note, BAG3 was strongly expressed in the skin biopsies of dcSSc patients. CONCLUSIONS: BAG3 is overexpressed in dcSSc patients and may contribute to skin and organ fibrosis by prompting the transition of fibroblasts into myofibroblasts and increasing their survival. Thus, BAG3 may play an important role in SSc fibrotic pathogenesis and be a potential biomarker of fibrosis. Further research on its role as a therapeutic target is warranted.

How to manage adult patients with malaria in the non-endemic setting.

BACKGROUND: The diagnosis and management of malaria in non-endemic countries presents a continuing challenge. Plasmodium falciparum, which is capable to rapidly induce severe and life-threatening multiorgan disease, is the species most frequently diagnosed in Europe and North America. OBJECTIVES: To summarise the more relevant diagnostic findings and clinical features of malaria observed in non-endemic settings and to provide an up-date of the key management decision points using three illustrative clinical scenarios of uncomplicated and severe malaria. SOURCES: The discussion is based on relevant literature search spanning the last twenty years. Recommendations are based on available clinical guidelines including those of the World Health Organization (WHO), on observational studies conducted in non-endemic settings and, when available, with extrapolation from randomised studies from malaria endemic settings. CONTENT: The following topics are covered: diagnosis, including the use of molecular biology; clinical characteristics; management with specific focus on complicated (severe) and uncomplicated malaria and on areas of resistance to available antimalarial drugs. IMPLICATIONS: Malaria imported to non-endemic settings, especially Plasmodium falciparum malaria, is sometimes initially overlooked and the delayed diagnosis is responsible every year of preventable deaths. This review aims to raise awareness of malaria outside endemic countries and to provide clinicians with a practical guide for efficient diagnosis and targeted therapy to the different species involved.

The P2X7 Receptor is a Master Regulator of Microparticle and Mitochondria Exchange in Mouse Microglia.

Microparticles (MPs) are secreted by all cells, where they play a key role in intercellular communication, differentiation, inflammation, and cell energy transfer. P2X7 receptor (P2X7R) activation by extracellular ATP (eATP) causes a large MP release and affects their contents in a cell-specific fashion. We investigated MP release and functional impact in microglial cells from P2X7R-WT or P2X7R-KO mice, as well as mouse microglial cell lines characterized for high (N13-P2X7RHigh) or low (N13-P2X7RLow) P2X7R expression. P2X7R stimulation promoted release of a mixed MP population enriched with naked mitochondria. Released mitochondria were taken up and incorporated into the mitochondrial network of the recipient cells in a P2X7R-dependent fashion. NLRP3 and the P2X7R itself were also delivered to the recipient cells. Microparticle transfer increased the energy level of the recipient cells and conferred a pro-inflammatory phenotype. These data show that the P2X7R is a master regulator of intercellular organelle and MP trafficking in immune cells.

Preclinical Pharmacokinetics in Tumors and Normal Tissues of the Antigene PNA Oligonucleotide MYCN-Inhibitor BGA002.

Although MYCN has been considered an undruggable target, MYCN alterations confer poor prognosis in many pediatric and adult cancers. The novel MYCN-specific inhibitor BGA002 is an antigene peptide nucleic acid oligonucleotide covalently bound to a nuclear localization signal peptide. In the present study, we characterized the pharmacokinetics (PK) of BGA002 after single and repeated administration to mice using a novel specific enzyme-linked immunosorbent assay. BGA002 concentrations in plasma showed linear PK, with dose proportional increase across the tested dose levels and similar exposure between male and female and between intravenous and subcutaneous route of administration. Repeated dosing resulted in no accumulation in plasma. Biodistribution up to 7 days after single subcutaneous administration of [14C]-radiolabeled BGA002 showed broad tissues and organ distribution (suggesting a potential capability to reach primary tumor and metastasis in several body sites), with high concentrations in kidney, liver, spleen, lymph nodes, adrenals, and bone marrow. Remarkably, we demonstrated that BGA002 concentrates in tumors after repeated systemic administrations in three mouse models with MYCN amplification (neuroblastoma, rhabdomyosarcoma, and small-cell lung cancer), leading to a significant reduction in tumor weight. Taking into account the available safety profile of BGA002, these data support further evaluation of BGA002 in patients with MYCN-positive tumors.

Long-Term Functional Outcomes after Hand Burns: A Monocentric Controlled Cohort Study.

Background: Hand burns are involved in 80-90% of severe burn injuries. Even though hands correspond to a small total burn surface area (TBSA) of less than 5%, the loss of their functionality has a significant impact on the patient's life. Studies that provide long-term results regarding hand functionality after hand burns are scarce. Therefore, this study aimed to investigate functional long-term results in a patient-centric approach regarding burn depth, unilateral and bilateral hand involvement, and (non-)isolated hand burns as potential influencing factors in patients with hand burns. Methods: We conducted a controlled cohort study of patients with burned hands treated at our department between 2005 and 2022. Healthy age-, sex-, and handedness-matched participants were used as controls. Data on the demographics, burn-related injuries, and treatments were collected. For a patient-centric approach, we used the Disabilities of the Arm, Shoulder, and Hand Questionnaire (Quick-DASH) and the Michigan Hand Questionnaire (MHQ) as patient-reported outcome measures for functional long-term evaluation, and the Patient and Observer Scar Assessment Scale (patient scale) for assessing long-term scar quality. Results: We enrolled 61 patients with 88 affected hands and 63 matched control participants. Up to 77.1% of the participants were male, with a mean age of 50.7 (±15.5) years and a follow-up of 8.1 (±4.7) years. The mean TBSA was 13.9% (±15.8), with 72.4% of the hands presenting with deep partial-thickness and full-thickness burns and most of the patients had only one hand affected (55.7%). The hand burn patients perceived significantly worse long-term functional scores in every domain of the MHQ as well as in the "overall function" and "work" of the Quick-DASH. Superficial hand burns negatively affected the two-handed activities of daily living (p = 0.013) and aesthetic appearance (p = 0.005) when both hands were involved. Isolated hand burns were associated with more difficulties in work performance (p = 0.03), whereas patients with bilateral hand involvement perceived more pain (p = 0.025). Conclusions: The patients with hand burns can achieve satisfactory long-term functional outcomes over time, but they do not reach the same long-term hand functionality as the healthy matched control group. Our study revealed that factors such as burn depth, unilateral or bilateral hand involvement, and (non-)isolated hand burns indeed have an impact on certain aspects of perceived long-term hand functionality.

Hospital-Based Influenza and Pneumococcal Vaccination for Cancer Patients on Active Treatment and Their Family Members during the COVID-19 Pandemic in Italy: A Single-Center Experience.

In patients with cancer, tumor- and treatment-induced immunosuppression are responsible for a four-fold increase in morbidity and mortality caused by influenza and invasive Streptococcus pneumoniae infections compared to the general population. The main oncology societies strongly recommend vaccination in patients with cancer to prevent these infections. However, vaccine hesitancy is a main concern in this population. The aim of this study was to assess the feasibility of in-hospital vaccination for patients under anticancer treatment and their family members (FMs) against influenza and pneumococcal infections during the COVID-19 pandemic in order to increase vaccine coverage. This was a single-center, prospective, observational study conducted at the Department of Oncology of Luigi Sacco University Hospital (Milan, Italy) between October 2020 and April 2021. The main primary outcome was the incidence of influenza-like illness (ILI) and pneumococcal infections. The main secondary outcome was safety. A total of 341 subjects were enrolled, including 194 patients with cancer and 147 FMs. The incidence of ILI was higher among patients than among FMs (9% vs. 2.7%, OR 3.92, p = 0.02). Moreover, two subjects were diagnosed with pneumococcal pneumonia. The most frequent vaccine-related AEs were pain in the injection site (31%) and fatigue (8.7%). In conclusion, this hospital-based vaccination strategy was feasible during the COVID-19 pandemic, representing a potential model to maximize vaccine coverage during a public health emergency.

Factors Associated with Adverse Outcomes among SARS-CoV-2 Positive Children in a Tertiary Government COVID-19 Referral Hospital in the Philippines.

Background and Objective: Pediatric COVID-19 epidemiology and factors associated with adverse outcomes - mortality, need for invasive mechanical ventilation, and ICU admission, are largely unstudied. We described the clinico-demographic characteristics of Filipino pediatric COVID-19 patients and determined the factors associated with adverse outcomes. Methods: This is a retrospective cohort study of 180 hospitalized SARS-CoV-2-confirmed cases 0-18 years old from April 2020 to August 2021 in a tertiary COVID-19 referral hospital in Manila, National Capital Region. Crude associations were determined using chi-squared or Fisher's exact tests; and medians were compared using the Mann-Whitney test. Factors predictive of mortality were determined using Cox proportional hazards regression analysis. The survivor functions were depicted in graphs. Results: About 41.67% had mild disease, 58.33% were males, 39.4% aged 0-4 years, and 69.44% had at least one comorbidity. About 9.44% died (adjusted 9.2 persons per 1000 patient-days, 95% CI 5.5%-15.2%), 17.78% needed invasive mechanical ventilation, and 20% needed ICU admission. Independently, severe-critical COVID-19 (HRc 11.51, 95% CI 3.23, 41.06), retractions (HRc 10.30, 95% CI 3.27, 32.47), alar flaring (HRc 4.39, 95% CI 1.53, 12.58), cyanosis (HRc 4.39, 95% CI 1.72, 14.11), difficulty of breathing (HRc 7.99, 95% CI 2.25, 28.71), poor suck/appetite (HRc 4.46, 95% CI 1.59, 12.40), ferritin (HRc 1.01, 95% CI 1.00, 1.01), IL-6 (HRc 1.01, 95% CI 1.00, 1.01), aPTT (HRc 1.05, 95% CI 1.01, 1.10), IVIg (HRc 4.00, 95% CI 1.07, 14.92) and corticosteroid (HRc 6.01, 95% CI 2.04, 17.67) were significant hazards for mortality. In adjusted Cox analysis, only retractions (HRa 34.96, 95% CI 3.36, 363.79), seizure (HRa 9.98, 95% CI 1.76, 56.55), and corticosteroids (HRa 8.21, 95% CI 1.12, 60.38) were significantly associated with mortality while alar flaring appeared to be protective (HRa 0.10, 95% CI 0.01, 0.95). Several clinical characteristics were consistently associated with adverse outcomes. Conclusions: Majority of hospitalized pediatric COVID-19 patients were very young, males, had mild disease, and had at least one comorbidity. Mortality, invasive mechanical ventilation, and ICU admission were relatively low. Except for alar flaring which appeared to be protective, retractions, seizure, and use of corticosteroids were associated with adverse outcomes.

Strategic Optimization of Patient Flow and Staffing Schemes during the COVID-19 Pandemic through Operations Management in a Neonatal Intensive Care Unit.

Background: The COVID-19 pandemic posed challenges in making time-bound hospital management decisions. The University of the Philippines -Philippine General Hospital (UP-PGH) is a tertiary COVID-19 referral center located in Manila, Philippines. The mismatch of increasing suspected or confirmed COVID-19 infected mothers with few documented cases of infected infants has caused significant patient overflow and manpower shortage in its NICU. Objective: We present an evaluated scheme for NICU bed reallocation to maximize capacity performance, staff rostering, and resource conservation, while preserving COVID-19 infection prevention and control measures. Methods: Existing process workflows translated into operational models helped create a solution that modified cohorting and testing schemes. Staffing models were transitioned to meet patient flow. Outcome measurements were obtained, and feedback was monitored during the implementation phase. Results: The scheme evaluation demonstrated benefits in (a) achieving shorter COVID-19 subunit length of stay; (b) better occupancy rates with minimal overflows; (c) workforce shortage mitigation with increased non-COVID workforce pool; (d) reduced personal protective equipment requirements; and (e) zero true SARS-CoV-2 infections. Conclusion: Designed for hospital operations leaders and stakeholders, this operations process can aid in hospital policy formulation in modifying cohorting schemes to maintain quality NICU care and service during the COVID-19 pandemic.

Impact dynamics of granular debris flows based on a small-scale physical model.

The peak pressure of a granular debris flow at low Froude conditions can be calculated with knowledge of the stress anisotropy and the bulk density as well as the run-up height at impact. Based on a small-scale physical model, measurements of stress anisotropy and flow density values at impact are presented and applied to existing run-up prediction models, and further compared with back-calculated run-up coefficients from measured maximum impact pressures. For this purpose, we conducted 17 experiments with impact measurements and six experiments without impact measurements at Froude numbers, ranging from 0.84 to 2.41. Our results indicate that run-up heights are best reproduced by predictive models, either based on energy or mass and moment conservation, when anisotropic stress conditions, found in this study to range from 1.2 to 5.0, and bulk density variations due to impact, ranging in this study from 0.8 to 2.3, are considered. The influence of stress anisotropy and density variation on the run-up prediction differs, depending on the modelling approach. For the calculation of run-up heights based on the energy conservation concept, the influence of stress anisotropy becomes more significant with increasing Froude number, whereas for models based on mass and momentum conservation, bulk density variations have a greater influence on the estimation of the potential run-up.

Establishing targets for goal-directed anesthesia in renal transplantation: A cohort analysis of high-saliency surgical time courses.

Delayed graft function (DGF) increases morbidity and mortality in kidney transplant recipients. Operative parameters, including hemodynamic manipulation through vasopressors and fluids, can impact perfusion to the newly transplanted kidney and influence DGF incidence. We analyzed intraoperative time-series data in 5-minute intervals from kidney transplant recipient operations (N = 545) in conjunction with pretransplant characteristics and postsurgical outcomes, including DGF incidence, 60-day creatinine, and graft survival. Of the operations, 127 DGF events were captured in our cohort from a single academic transplant center (57/278 donations after brainstem death [DBDs], 65/150 donations after circulatory/cardiac death [DCDs], 5/117 live donations). In multiple regression, postanastomosis hypotension defined as mean arterial pressure (MAP) <75 mmHg was a risk factor for DGF independent of conventional predictors of DGF in DCD and DBD kidneys. DCD recipients with DGF had lower average postanastomosis MAP (DGF: 80.1 ± 8.1 mmHg vs no DGF: 76.4 ± 6.7 mmHg, P = .004). Interaction analysis demonstrated above-average doses of vasopressors and crystalloids were associated with improved outcomes when used at MAPs ≤75 mmHg, but they were associated with increased DGF at MAPs >75 mmHg, suggesting that the incidence of DGF can be highly influenced by intraoperative hemodynamic controls. This analysis of surgical time courses has identified potential new strategies for goal-directed anesthesia in renal transplantation.

Impact of inadequate bowel cleansing in sigmoidoscopy screening.

BACKGROUND AND STUDY AIMS: Long-time follow-up of sigmoidoscopy screening trials has shown reduced incidence and mortality of colorectal cancer (CRC), but inadequate bowel cleansing may hamper efficacy. The aim of this study was to assess the impact of bowel cleansing quality in sigmoidoscopy screening. PATIENTS AND METHODS: Individuals 50 to 74 years old who had a screening sigmoidoscopy in a population-based Norwegian, randomized trial between 2012 and 2019, were included in this cross-sectional study. The bowel cleansing quality was categorised as excellent, good, partly poor, or poor. The effect of bowel cleansing quality on adenoma detection rate (ADR) and referral to colonoscopy was evaluated by fitting multivariable logistic regression models. RESULTS: 35,710 individuals were included. The bowel cleansing at sigmoidoscopy was excellent in 20,934 (58.6%) individuals, good in 6580 (18.4%), partly poor in 7097 (19.9%) and poor in 1099 (3.1%). The corresponding ADRs were 17.0%, 16.6%, 14.5%, and 13.0%. Compared to participants with excellent bowel cleansing, those with poor bowel cleansing had an odds ratio for adenoma detection of 0.66 (95% confidence interval 0.55-0.79). We found substantial differences in the assessment of bowel cleansing quality among endoscopists. CONCLUSIONS: Inadequate bowel cleansing reduces the efficacy of sigmoidoscopy screening, by lowering ADR. A validated rating scale and improved bowel preparation are needed to make sigmoidoscopy an appropriate screening method.Trial registration Clinicaltrials.gov (NCT01538550).

Palliative psychiatry: research, clinical, and educational priorities.

BACKGROUND: Palliative psychiatry has been proposed as a new clinical construct within mental health care and aims to improve quality of life (QoL) for individuals experiencing severe and persistent mental illness (SPMI). To date, explorations of palliative psychiatry have been largely theoretical, and more work is needed to develop its approaches into tangible clinical practice. METHODS: In this paper, we synthesize existing literature with discussions held at a one-day knowledge user meeting titled "A Community of Practice for Palliative Psychiatry" to generate priorities for research, clinical practice, and education that will help advance the development of palliative psychiatry. RESULTS: Palliative psychiatry will benefit from research that is co-produced by people with lived experience (PWLE) of mental illness, that clarifies contested concepts within mental health care and wider medicine, and that adapts existing interventions that have the potential to improve the QoL of individuals experiencing SPMI into the mental health care context. Specific methods and tools might be developed for use in clinical spaces taking a palliative psychiatry approach. More work must be done to understand the populations that might benefit from palliative psychiatry, and to mitigate mental health care providers' (MHCPs') anxieties about using these approaches in their work. As palliative psychiatry is developed, current MHCPs, trainees, individuals experiencing SPMI, and their loved ones will all require education about and orientation to this novel approach within mental health care. CONCLUSIONS: There are several priorities in research, clinical practice, and education that can help advance the development of palliative psychiatry. All future work must be considered through a human rights-based, anti-oppressive lens. Research projects, clinical models, and educational initiatives should all be developed in co-production with PWLE to mitigate the epistemic injustices common in mental health care.

Management of the Drug-Drug Interactions Between Valproic Acid and Dolutegravir-A Case Study.

OBJECTIVE: Preliminary evidence shows that concomitant administration of valproic acid can reduce the exposure to dolutegravir with limited clinical impacts. Here, we describe a male living with HIV who experienced a drastic reduction in dolutegravir trough concentrations a few weeks after starting valproic acid treatment as identified by therapeutic drug monitoring. Concomitantly, pharmacists recommended a supplementation of magnesium to improve insomnia. CASE REPORT: A 62-year-old man with HIV on antiretroviral therapy with dolutegravir and lamivudine recently added valproic acid to clonazepam and sertraline to treat severe sleep disturbances. An 84% reduction in dolutegravir trough concentrations was observed compared with the previous outpatient visit (418 versus 2714 ng/mL), with values close to the minimum effective drug concentration (300 ng/mL). Considering this, we strongly discourage the use of magnesium. CONCLUSIONS: We are confident that our findings can contribute to a better understanding of the clinical problems that infectious disease physicians encounter in their daily management of people with HIV and how therapeutic drug monitoring may add value in this context. This case also highlights the importance of multidisciplinary services for the optimal management of polypharmacy in people with HIV.

Kinematic Effects of Derotational Osteotomy of the Humerus in Patients with Internal Shoulder Contracture Secondary to Erb's Palsy-A Retrospective Cohort Study.

Background: Internal rotation contractures of the shoulder are common sequelae of conservatively treated obstetric brachial plexus palsy (OBPP) with incomplete spontaneous neurological recovery. Humerus derotation osteotomy has been suggested as a possible treatment option to improve arm positioning. However, consensus as to whether humerus derotation osteotomy can successfully restore limb function is missing. Methods: In the present controlled cohort study, we aimed at analyzing global upper extremity kinematics with a 3D-video analysis system in children with shoulder internal rotation contractures secondary to OBPP before, and one year after, humerus derotation osteotomy. Patients under 18 years of age that presented to our center with conservatively treated internal rotation contractures of the shoulder and subsequently underwent humerus derotation osteotomy were included. The unimpaired arm served as a respective control. Results: Pre-operatively, all patients showed severe internal rotation contractures of the shoulder of almost 60° at rest. At the follow-up, the position of the shoulder at rest was greatly shifted to 9° of internal rotation. The patients showed statistically significant improvement in maximum external rotation and abduction of the shoulder, as well as in maximum flexion of the elbow, and the range of motion of pro/supination. The maximum internal rotation of the shoulder, however, was diminished after the osteotomy. Conclusions: Our data indicated that derotational osteotomy is a promising procedure which can be used to correct for internal rotation contractures secondary to OBPP. Moreover, 3D-video analysis proved to be a useful tool that supplies the surgeon with both precise information about the degree of distortion pre-operatively, thus helping to decide on the amount of correction, and secondly, a measurement of the post-operative gain in upper extremity function.

Major Bleeding Events in Hospitalized COVID-19 Patients: A Retrospective Observational Study.

Thromboprophylaxis/anticoagulation treatment is often required in hospitalized COVID-19 patients. We aimed to estimate the prevalence of major bleeding events in hospitalized COVID-19 patients. This was a retrospective observational study including all COVID-19 hospitalized patients ≥18 years of age at one reference center in northern Italy. The crude prevalence (between February 2020-2022) of major bleeding events was estimated as the number of major bleeding episodes divided by patients at risk. Uni- and multivariable Cox models were built to assess factors potentially associated with major bleeding events. Twenty-nine (0.98%) out of 2,945 COVID-19 patients experienced a major bleeding event [prevalence of 0.55% (95%CI 0.37-0.79)], of which five were fatal. Patients who experienced a major bleeding event were older [78 years (72-84 IQR) vs. 67 years (55-78 IQR), p-value < 0.001] and more frequently exposed to anti-aggregating therapy (44.8% vs. 20.0%, p-value 0.002) when compared to those who did not. In the multivariable Cox model, age [per 1 year more AHR 1.05 (CI95% 1.02-1.09)] was independently associated with an increased risk of major bleeding events. A strict monitoring of older hospitalized COVID-19 patients is warranted due to the risk of major bleeding events.

Ceramic Dressings-A New Non-Pharmacological Therapeutic Option in the Management of Chronic Wounds?

A new ceramic dressing, free from active antimicrobial or pharmaceutical agents, uses physical binding mechanisms for its absorption capacities and bacterial-binding properties. The purpose of this study was to evaluate wound healing, bacterial-related retention, and diagnostic properties of ceramic dressings in patients with stagnated chronic wounds. METHODS: In this monocentric, intra-individually controlled, prospective study, patients with conservatively treated refractory chronic wounds were enrolled. One week before the start of the application with ceramic dressing, it was ensured during a screening phase that chronic wounds showed less than a 10% reduction in wound size. During the 4-week ceramic dressing treatment wound size measurements, wound scoring, measurement of wound exudate amount, wound swabs, and ceramic dressing sonication (low-intensity ultrasound) were carried out. The sonication fluid of the removed ceramic dressing was used for analysis of bacterial retention and compared to wound swabs. RESULTS: A total of 20 patients with a mean age of 64.6 years (±26.2) and 21 chronic wounds were included in this study. After a 4-week treatment, a significant reduction of median wound size from 1178 mm2 (range 104-6300) to 751.5 mm2 (range 16-4819) and better total wound scores were observed (p < 0.001). The sensitivity of bacteria detection was 90.7% in the sonication fluid from the ceramic dressings, while only 76.9% in the conventional wound swabs. CONCLUSION: The new ceramic dressing seems to have a positive impact on wound healing in chronic wounds. Bacteria-binding characteristics of the investigated ceramic dressing, in combination with its debridement, absorption, and detoxification properties, could contribute to its healing abilities. Based on those results, the investigated ceramic dressing seems to be a promising new treatment option for chronic wounds without the use of any active antimicrobial or pharmacological agents. Moreover, ceramic dressings can also be considered for microbiological diagnostic purposes.

Unlocking the secret life of blue mussels: Exploring connectivity in the Skagerrak through biophysical modeling and population genomics.

Knowledge of functional dispersal barriers in the marine environment can be used to inform a wide variety of management actions, such as marine spatial planning, restoration efforts, fisheries regulations, and invasive species management. Locations and causes of dispersal barriers can be studied through various methods, including movement tracking, biophysical modeling, demographic models, and genetics. Combining methods illustrating potential dispersal, such as biophysical modeling, with realized dispersal through, e.g., genetic connectivity estimates, provides particularly useful information for teasing apart potential causes of observed barriers. In this study, we focus on blue mussels (Mytilus edulis) in the Skagerrak-a marginal sea connected to the North Sea in Northern Europe-and combine biophysical models of larval dispersal with genomic data to infer locations and causes of dispersal barriers in the area. Results from both methods agree; patterns of ocean currents are a major structuring factor in the area. We find a complex pattern of source-sink dynamics with several dispersal barriers and show that some areas can be isolated despite an overall high dispersal capability. Finally, we translate our finding into management advice that can be used to sustainably manage this ecologically and economically important species in the future.

Comparing attitudes towards compulsory interventions in severe and persistent mental illness among psychiatrists in India and Switzerland.

BACKGROUND: Psychiatrists face a major ethical challenge when deciding whether to make use of coercive measures in the treatment process of patients suffering from severe and persistent mental illness (SPMI). As India and Switzerland show major cultural, political and financial differences, it is hypothesized that attitudes towards coercive measures among Indian and Swiss psychiatrists will vary too. Exploring differences in attitudes between cultures strengthens the critical reflection on one's own stances and in consequence, on our way of action. Especially when it comes to situations involving power imbalances between patients and health practitioners, self-reflection is essential to prevent ethically inappropriate behavior. METHODS: An online survey on aspects of care for patients with SPMI was sent to 3'056 members of the Indian Psychiatric Society between April and June 2020 and to 1'311 members of the Swiss Society for Psychiatry and Psychotherapy between February and March 2016. The respondents' answers were compared. This article deals with the questionnaire's items on autonomous decision making and the implementation of coercive measures in clinical practice. More precisely, participating psychiatrists were asked to rate the importance of patient's autonomy in general and their willingness to apply coercive measures regarding two specific case vignettes depicting a patient with schizophrenia and one with depression. The statistical analysis, namely descriptive data analysis and calculation of arithmetic means, Shapiro Wilks tests and Mann-Whitney U tests, was carried out using IBM SPSS Statistics version 27. RESULTS: Answers were received from 206 psychiatrists in India and 457 psychiatrists in Switzerland. Indian participants tended to value autonomous decision making as slightly less important than Swiss participants (62.2% vs. 91%, p =.01). Regarding a case of severe and persistent depression, psychiatrists in the Indian group were on average more in favor of acting against the wishes of the patient (55% vs. 34.1%, p <.0001) as well as of accepting a temporary decrease in quality of life due to coercion (40% vs. 23%, p =.008). Answers concerning a case of schizophrenia revealed that Indian participants were more in favor of acting against the patient's wishes than Swiss participants (39% vs. 37%, p =.007), whereas the comparison whether to accept a temporary decrease in quality of life regarding this case showed no significant difference (p =.328). CONCLUSIONS: The significant difference in attitudes towards coercive measures among Indian compared to Swiss psychiatrists found in this study might arise from a predominantly more collectivist society in India compared to Switzerland. Moreover, differences in financial resources, the organization of the health care system, and the historical background might have an influence. Continuous and critical reflection on one's own views and behavior is essential, especially if ethical principles and individual rights could be violated through a power imbalance, as in the case of coercive measures.