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Background: Schizophrenia is a severe psychiatric disorder with periods of remission and relapse. As discontinuation of antipsychotic medication is the most important reason for relapse, long-term maintenance treatment is key. Whether intramuscular long-acting (depot) antipsychotics are more efficacious than oral medication in preventing medication discontinuation is still unresolved. We aimed to compare time to all-cause discontinuation in patients randomly allocated to long-acting injectable (LAI) versus oral medication. Methods: EULAST was a pragmatic, randomised, open-label trial conducted at 50 general hospitals and psychiatric specialty clinics in 15 European countries and Israel. Patients aged 18 years and older, with DSM-IV schizophrenia (as confirmed by the Mini International Neuropsychiatric Interview 5 plus) and having experienced their first psychotic episode from 6 months to 7 years before screening, were randomly allocated (1:1:1:1) using block randomisation to LAI paliperidone, LAI aripiprazole, or the respective oral formulations of these antipsychotics. Randomisation was stratified by country and duration of illness (6 months up to 3 years vs 4 to 7 years). Patients were followed up for up to 19 months. The primary endpoint was discontinuation, regardless of the reason, during 19 months of treatment. We used survival analysis to assess the time until all-cause discontinuation in the intention-to-treat (ITT) group, and per protocol analyses were also done. This trial is registered with ClinicalTrials.gov, NCT02146547, and is complete. Findings: Between Feb 24, 2015, and Dec 15, 2018, 533 individuals were recruited and assessed for eligibility. The ITT population included 511 participants, with 171 (33%) women and 340 (67%) men, and a mean age of 30·5 (SD 9·6) years. 410 (80%) of 511 participants were White, 35 (7%) were Black, 20 (4%) were Asian, and 46 (9%) were other ethnicity. In the combined oral antipsychotics treatment group of 247 patients, 72

We investigated food supply mechanisms to a cold-water coral (CWC) reef at 260 m depth on the Norwegian continental shelf using data from a cabled ocean observatory equipped with Acoustic Doppler Current Profilers (ADCPs), an echosounder, and sensors for chlorophyll, turbidity and hydrography in the benthic boundary layer (BBL). Tidal currents of up to tens of cm s−1 dominated BBL hydrodynamics while residual currents were weak (∼10 cm s−1), emphasizing a supply and high retention of locally produced phytodetritus within the trough. A direct connection between the reefs and surface organic matter (OM) was established by turbulent mixing and passive particle settling, but relative contributions varied seasonally. Fresh OM from a spring-bloom was quickly mixed into the BBL, but temperature stratification in summer reduced the surface-to-bottom connectivity and reduced the phytodetritus supply. A qualitative comparison among acoustic backscatter in the ADCPs (600 kHz, 190 kHz) and echosounder (70 kHz) suggests that vertically migrating zooplankton may present an alternative food source in summer. Nocturnal feeding by zooplankton in the upper water column sustains downward OM transport independent from water column mixing and may dominate as food supply pathway over sedimentation of the phytodetritus, especially during stratified conditions. In addition, it could present a concentrating mechanism for nutritional components as compensation for the deteriorating phytodetritus quality. Overall, the observed patterns suggest seasonal changes in the food supply pathways to the reef communities. The moderating role of temperature stratification in phytodetritus transport suggests stronger dependence of the cold-water corals on zooplankton for their dietary requirements with increased stratification under future climate scenarios. This study demonstrates the added value of permanent ocean observatories to research based on dedicated campaigns and regular monitoring.

We investigated food supply mechanisms to a cold-water coral (CWC) reef at 260 m depth on the Norwegian continental shelf using data from a cabled ocean observatory equipped with Acoustic Doppler Current Profilers (ADCPs), an echosounder, and sensors for chlorophyll, turbidity and hydrography in the benthic boundary layer (BBL). Tidal currents of up to tens of cm s−1 dominated BBL hydrodynamics while residual currents were weak (∼10 cm s−1), emphasizing a supply and high retention of locally produced phytodetritus within the trough. A direct connection between the reefs and surface organic matter (OM) was established by turbulent mixing and passive particle settling, but relative contributions varied seasonally. Fresh OM from a spring-bloom was quickly mixed into the BBL, but temperature stratification in summer reduced the surface-to-bottom connectivity and reduced the phytodetritus supply. A qualitative comparison among acoustic backscatter in the ADCPs (600 kHz, 190 kHz) and echosounder (70 kHz) suggests that vertically migrating zooplankton may present an alternative food source in summer. Nocturnal feeding by zooplankton in the upper water column sustains downward OM transport independent from water column mixing and may dominate as food supply pathway over sedimentation of the phytodetritus, especially during stratified conditions. In addition, it could present a concentrating mechanism for nutritional components as compensation for the deteriorating phytodetritus quality. Overall, the observed patterns suggest seasonal changes in the food supply pathways to the reef communities. The moderating role of temperature stratification in phytodetritus transport suggests stronger dependence of the cold-water corals on zooplankton for their dietary requirements with increased stratification under future climate scenarios. This study demonstrates the added value of permanent ocean observatories to research based on dedicated campaigns and regular monitoring.

Contains fulltext : 136093.pdf (publisher's version ) (Closed access), There is recognition that biomedical research into the causes of mental disorders and their treatment needs to adopt new approaches to research. Novel biomedical techniques have advanced our understanding of how the brain develops and is shaped by behaviour and environment. This has led to the advent of stratified medicine, which translates advances in basic research by targeting aetiological mechanisms underlying mental disorder. The resulting increase in diagnostic precision and targeted treatments may provide a window of opportunity to address the large public health burden, and individual suffering associated with mental disorders. While mental health and mental disorders have significant representation in the "health, demographic change and wellbeing" challenge identified in Horizon 2020, the framework programme for research and innovation of the European Commission (2014-2020), and in national funding agencies, clear advice on a potential strategy for mental health research investment is needed. The development of such a strategy is supported by the EC-funded "Roadmap for Mental Health Research" (ROAMER) which will provide recommendations for a European mental health research strategy integrating the areas of biomedicine, psychology, public health well being, research integration and structuring, and stakeholder participation. Leading experts on biomedical research on mental disorders have provided an assessment of the state of the art in core psychopathological domains, including arousal and stress regulation, affect, cognition social processes, comorbidity and pharmacotherapy. They have identified major advances and promising methods and pointed out gaps to be addressed in order to achieve the promise of a stratified medicine for mental disorders.

Contains fulltext : 136093.pdf (publisher's version ) (Closed access), There is recognition that biomedical research into the causes of mental disorders and their treatment needs to adopt new approaches to research. Novel biomedical techniques have advanced our understanding of how the brain develops and is shaped by behaviour and environment. This has led to the advent of stratified medicine, which translates advances in basic research by targeting aetiological mechanisms underlying mental disorder. The resulting increase in diagnostic precision and targeted treatments may provide a window of opportunity to address the large public health burden, and individual suffering associated with mental disorders. While mental health and mental disorders have significant representation in the "health, demographic change and wellbeing" challenge identified in Horizon 2020, the framework programme for research and innovation of the European Commission (2014-2020), and in national funding agencies, clear advice on a potential strategy for mental health research investment is needed. The development of such a strategy is supported by the EC-funded "Roadmap for Mental Health Research" (ROAMER) which will provide recommendations for a European mental health research strategy integrating the areas of biomedicine, psychology, public health well being, research integration and structuring, and stakeholder participation. Leading experts on biomedical research on mental disorders have provided an assessment of the state of the art in core psychopathological domains, including arousal and stress regulation, affect, cognition social processes, comorbidity and pharmacotherapy. They have identified major advances and promising methods and pointed out gaps to be addressed in order to achieve the promise of a stratified medicine for mental disorders.

Contains fulltext : 136093.pdf (publisher's version ) (Closed access), There is recognition that biomedical research into the causes of mental disorders and their treatment needs to adopt new approaches to research. Novel biomedical techniques have advanced our understanding of how the brain develops and is shaped by behaviour and environment. This has led to the advent of stratified medicine, which translates advances in basic research by targeting aetiological mechanisms underlying mental disorder. The resulting increase in diagnostic precision and targeted treatments may provide a window of opportunity to address the large public health burden, and individual suffering associated with mental disorders. While mental health and mental disorders have significant representation in the "health, demographic change and wellbeing" challenge identified in Horizon 2020, the framework programme for research and innovation of the European Commission (2014-2020), and in national funding agencies, clear advice on a potential strategy for mental health research investment is needed. The development of such a strategy is supported by the EC-funded "Roadmap for Mental Health Research" (ROAMER) which will provide recommendations for a European mental health research strategy integrating the areas of biomedicine, psychology, public health well being, research integration and structuring, and stakeholder participation. Leading experts on biomedical research on mental disorders have provided an assessment of the state of the art in core psychopathological domains, including arousal and stress regulation, affect, cognition social processes, comorbidity and pharmacotherapy. They have identified major advances and promising methods and pointed out gaps to be addressed in order to achieve the promise of a stratified medicine for mental disorders.

There is recognition that biomedical research into the causes of mental disorders and their treatment needs to adopt new approaches to research. Novel biomedical techniques have advanced our understanding of how the brain develops and is shaped by behaviour and environment. This has led to the advent of stratified medicine, which translates advances in basic research by targeting aetiological mechanisms underlying mental disorder. The resulting increase in diagnostic precision and targeted treatments may provide a window of opportunity to address the large public health burden, and individual suffering associated with mental disorders. While mental health and mental disorders have significant representation in the "health, demographic change and wellbeing" challenge identified in Horizon 2020, the framework programme for research and innovation of the European Commission (2014-2020), and in national funding agencies, clear advice on a potential strategy for mental health research investment is needed. The development of such a strategy is supported by the EC-funded "Roadmap for Mental Health Research" (ROAMER) which will provide recommendations for a European mental health research strategy integrating the areas of biomedicine, psychology, public health well being, research integration and structuring, and stakeholder participation. Leading experts on biomedical research on mental disorders have provided an assessment of the state of the art in core psychopathological domains, including arousal and stress regulation, affect, cognition social processes, comorbidity and pharmacotherapy. They have identified major advances and promising methods and pointed out gaps to be addressed in order to achieve the promise of a stratified medicine for mental disorders.

Fragile-X mental retardation (FRAX-MR) is one of the more common X-linked disorders affecting 1 in 1,500 newborn males. This disease is characterized by the expression of fragile site in the region q27.3 of the X-chromosome of affected boys when their lymphocytes are cultured in folate deficient medium. In most patients there is macroorchidism postpubertally. The clinical diagnosis of carrier females based on the expression of fragile site in Xq27.3 is usually difficult and sometimes impossible. About half of the carrier females escape diagnosis by this method. Furthermore, prenatal diagnosis is not always feasible. Using Restriction Fragment Length Polymorphism (RFLP) and cloned DNA segments from the region Xq27-Xqter as probes, we have investigated Swedish families with FRAX-MR in three generations. Interesting observations, previously unreported to our knowledge, have been made in some patients and carrier mothers, using one of the probes which is localized to the distal end of Xq. The significance of these findings and the linkage of the disease locus to the different probes used in this study is presented.