155 research outputs found
Problem Management Plus (PM plus ): pilot trial of a WHO transdiagnostic psychological intervention in conflict-affected Pakistan
Problem Management Plus (PM+) for common mental disorders in a humanitarian setting in Pakistan; study protocol for a randomised controlled trial (RCT)
The Gemini Planet Imager Exoplanet Survey: Giant Planet and Brown Dwarf Demographics From 10-100 AU
We present a statistical analysis of the first 300 stars observed by the
Gemini Planet Imager Exoplanet Survey (GPIES). This subsample includes six
detected planets and three brown dwarfs; from these detections and our contrast
curves we infer the underlying distributions of substellar companions with
respect to their mass, semi-major axis, and host stellar mass. We uncover a
strong correlation between planet occurrence rate and host star mass, with
stars M 1.5 more likely to host planets with masses between 2-13
M and semi-major axes of 3-100 au at 99.92% confidence. We fit a
double power-law model in planet mass (m) and semi-major axis (a) for planet
populations around high-mass stars (M 1.5M) of the form , finding = -2.4 0.8 and
= -2.0 0.5, and an integrated occurrence rate of %
between 5-13 M and 10-100 au. A significantly lower occurrence rate
is obtained for brown dwarfs around all stars, with 0.8% of
stars hosting a brown dwarf companion between 13-80 M and 10-100
au. Brown dwarfs also appear to be distributed differently in mass and
semi-major axis compared to giant planets; whereas giant planets follow a
bottom-heavy mass distribution and favor smaller semi-major axes, brown dwarfs
exhibit just the opposite behaviors. Comparing to studies of short-period giant
planets from the RV method, our results are consistent with a peak in
occurrence of giant planets between ~1-10 au. We discuss how these trends,
including the preference of giant planets for high-mass host stars, point to
formation of giant planets by core/pebble accretion, and formation of brown
dwarfs by gravitational instability.Comment: 52 pages, 18 figures. AJ in pres
Targeting enhancer switching overcomes non-genetic drug resistance in acute myeloid leukaemia.
Non-genetic drug resistance is increasingly recognised in various cancers. Molecular insights into this process are lacking and it is unknown whether stable non-genetic resistance can be overcome. Using single cell RNA-sequencing of paired drug naĂŻve and resistant AML patient samples and cellular barcoding in a unique mouse model of non-genetic resistance, here we demonstrate that transcriptional plasticity drives stable epigenetic resistance. With a CRISPR-Cas9 screen we identify regulators of enhancer function as important modulators of the resistant cell state. We show that inhibition of Lsd1 (Kdm1a) is able to overcome stable epigenetic resistance by facilitating the binding of the pioneer factor, Pu.1 and cofactor, Irf8, to nucleate new enhancers that regulate the expression of key survival genes. This enhancer switching results in the re-distribution of transcriptional co-activators, including Brd4, and provides the opportunity to disable their activity and overcome epigenetic resistance. Together these findings highlight key principles to help counteract non-genetic drug resistance
Peer-provided psychological intervention for Syrian refugees: results of a randomised controlled trial on the effectiveness of Problem Management Plus
Background The mental health burden among refugees in high-income countries (HICs) is high, whereas access to mental healthcare can be limited. Objective To examine the effectiveness of a peer-provided psychological intervention (Problem Management Plus; PM+) in reducing symptoms of common mental disorders (CMDs) among Syrian refugees in the Netherlands. Methods We conducted a single-blind, randomised controlled trial among adult Syrian refugees recruited in March 2019âDecember 2021 (No. NTR7552). Individuals with psychological distress (Kessler Psychological Distress Scale (K10) >15) and functional impairment (WHO Disability Assessment Schedule (WHODAS 2.0) >16) were allocated to PM+ in addition to care as usual (PM+/CAU) or CAU only. Participants were reassessed at 1-week and 3-month follow-up. Primary outcome was depression/anxiety combined (Hopkins Symptom Checklist; HSCL-25) at 3-month follow-up. Secondary outcomes included depression (HSCL-25), anxiety (HSCL-25), post-traumatic stress disorder (PTSD) symptoms (PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition; PCL-5), impairment (WHODAS 2.0) and self-identified problems (PSYCHLOPS; Psychological Outcomes Profiles). Primary analysis was intention-to-treat. Findings Participants (n=206; mean age=37âyears, 62% men) were randomised into PM+/CAU (n=103) or CAU (n=103). At 3-month follow-up, PM+/CAU had greater reductions on depression/anxiety relative to CAU (mean difference â0.25; 95%âCI â0.385 to â0.122; p=0.0001, Cohenâs d=0.41). PM+/CAU also showed greater reductions on depression (p=0.0002, Cohenâs d=0.42), anxiety (p=0.001, Cohenâs d=0.27), PTSD symptoms (p=0.0005, Cohenâs d=0.39) and self-identified problems (p=0.03, Cohenâs d=0.26), but not on impairment (p=0.084, Cohenâs d=0.21). Conclusions PM+ effectively reduces symptoms of CMDs among Syrian refugees. A strength was high retention at follow-up. Generalisability is limited by predominantly including refugees with a resident permit. Clinical implications Peer-provided psychological interventions should be considered for scale-up in HICs
Peer-provided psychological intervention for Syrian refugees: results of a randomised controlled trial on the effectiveness of Problem Management Plus
Background: The mental health burden among refugees in high-income countries (HICs) is high, whereas access to mental healthcare can be limited.
Objective: To examine the effectiveness of a peer-provided psychological intervention (Problem Management Plus; PM+) in reducing symptoms of common mental disorders (CMDs) among Syrian refugees in the Netherlands.
Methods: We conducted a single-blind, randomised controlled trial among adult Syrian refugees recruited in March 2019-December 2021 (No. NTR7552). Individuals with psychological distress (Kessler Psychological Distress Scale (K10) >15) and functional impairment (WHO Disability Assessment Schedule (WHODAS 2.0) >16) were allocated to PM+ in addition to care as usual (PM+/CAU) or CAU only. Participants were reassessed at 1-week and 3-month follow-up. Primary outcome was depression/anxiety combined (Hopkins Symptom Checklist; HSCL-25) at 3-month follow-up. Secondary outcomes included depression (HSCL-25), anxiety (HSCL-25), post-traumatic stress disorder (PTSD) symptoms (PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition; PCL-5), impairment (WHODAS 2.0) and self-identified problems (PSYCHLOPS; Psychological Outcomes Profiles). Primary analysis was intention-to-treat.
Findings: Participants (n=206; mean age=37 years, 62% men) were randomised into PM+/CAU (n=103) or CAU (n=103). At 3-month follow-up, PM+/CAU had greater reductions on depression/anxiety relative to CAU (mean difference -0.25; 95% CI -0.385 to -0.122; p=0.0001, Cohen's d=0.41). PM+/CAU also showed greater reductions on depression (p=0.0002, Cohen's d=0.42), anxiety (p=0.001, Cohen's d=0.27), PTSD symptoms (p=0.0005, Cohen's d=0.39) and self-identified problems (p=0.03, Cohen's d=0.26), but not on impairment (p=0.084, Cohen's d=0.21).
Conclusions: PM+ effectively reduces symptoms of CMDs among Syrian refugees. A strength was high retention at follow-up. Generalisability is limited by predominantly including refugees with a resident permit.
Clinical implications: Peer-provided psychological interventions should be considered for scale-up in HICs
Efficacy and moderators of efficacy of cognitive behavioural therapies with a trauma focus in children and adolescents: an individual participant data meta-analysis of randomised trials
Background: Existing clinical trials of cognitive behavioural therapies with a trauma focus (CBTs-TF) are underpowered to examine key variables that might moderate treatment effects. We aimed to determine the efficacy of CBTs-TF for young people, relative to passive and active control conditions, and elucidate putative individual-level and treatment-level moderators.
Methods: This was an individual participant data meta-analysis of published and unpublished randomised studies in young people aged 6-18 years exposed to trauma. We included studies identified by the latest UK National Institute of Health and Care Excellence guidelines (completed on Jan 29, 2018) and updated their search. The search strategy included database searches restricted to publications between Jan 1, 2018, and Nov 12, 2019; grey literature search of trial registries ClinicalTrials.gov and ISRCTN; preprint archives PsyArXiv and bioRxiv; and use of social media and emails to key authors to identify any unpublished datasets. The primary outcome was post-traumatic stress symptoms after treatment (<1 month after the final session). Predominantly, one-stage random-effects models were fitted. This study is registered with PROSPERO, CRD42019151954.
Findings: We identified 38 studies; 25 studies provided individual participant data, comprising 1686 young people (mean age 13·65 years [SD 3·01]), with 802 receiving CBTs-TF and 884 a control condition. The risk-of-bias assessment indicated five studies as low risk and 20 studies with some concerns. Participants who received CBTs-TF had lower mean post-traumatic stress symptoms after treatment than those who received the control conditions, after adjusting for post-traumatic stress symptoms before treatment (b=-13·17, 95% CI -17·84 to -8·50, p<0·001, Ï2=103·72). Moderation analysis indicated that this effect of CBTs-TF on post-traumatic stress symptoms post-treatment increased by 0·15 units (b=-0·15, 95% CI -0·29 to -0·01, p=0·041, Ï2=0·03) for each unit increase in pre-treatment post-traumatic stress symptoms.
Interpretation: This is the first individual participant data meta-analysis of young people exposed to trauma. Our findings support CBTs-TF as the first-line treatment, irrespective of age, gender, trauma characteristics, or carer involvement in treatment, with particular benefits for those with higher initial distress
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Lack of privileged access to awareness for rewarding social scenes in Autism Spectrum Disorder
Reduced social motivation is hypothesised to underlie social behavioural symptoms of Autism Spectrum Disorder (ASD). The extent to which rewarding social stimuli are granted privileged access to awareness in ASD is currently unknown. We use continuous flash suppression to investigate whether individuals with and without ASD show privileged access to awareness for social over nonsocial rewarding scenes that are closely matched for stimulus features. Strong evidence for a privileged access to awareness for rewarding social over nonsocial scenes was observed in neurotypical adults. No such privileged access was seen in ASD individuals, and moderate support for the null model was noted. These results suggest that the purported deficits in social motivation in ASD may extend to early processing mechanisms
A dynamic leaf gas-exchange strategy is conserved in woody plants under changing ambient CO2: evidence from carbon isotope discrimination in paleo and CO2 enrichment studies
Rising atmospheric [CO2 ], ca , is expected to affect stomatal regulation of leaf gas-exchange of woody plants, thus influencing energy fluxes as well as carbon (C), water and nutrient cycling of forests. Researchers have proposed various strategies for stomatal regulation of leaf gas-exchange that include maintaining a constant leaf internal [CO2 ], ci , a constant drawdown in CO2 (ca - ci ), and a constant ci /ca . These strategies can result in drastically different consequences for leaf gas-exchange. The accuracy of Earth systems models depends in part on assumptions about generalizable patterns in leaf gas-exchange responses to varying ca . The concept of optimal stomatal behavior, exemplified by woody plants shifting along a continuum of these strategies, provides a unifying framework for understanding leaf gas-exchange responses to ca . To assess leaf gas-exchange regulation strategies, we analyzed patterns in ci inferred from studies reporting C stable isotope ratios (ÎŽ(13) C) or photosynthetic discrimination (â) in woody angiosperms and gymnosperms that grew across a range of ca spanning at least 100 ppm. Our results suggest that much of the ca -induced changes in ci /ca occurred across ca spanning 200 to 400 ppm. These patterns imply that ca - ci will eventually approach a constant level at high ca because assimilation rates will reach a maximum and stomatal conductance of each species should be constrained to some minimum level. These analyses are not consistent with canalization towards any single strategy, particularly maintaining a constant ci . Rather, the results are consistent with the existence of a broadly conserved pattern of stomatal optimization in woody angiosperms and gymnosperms. This results in trees being profligate water users at low ca , when additional water loss is small for each unit of C gain, and increasingly water-conservative at high ca , when photosystems are saturated and water loss is large for each unit C gain. This article is protected by copyright. All rights reserved.Rising atmospheric [CO2], c(a), is expected to affect stomatal regulation of leaf gas-exchange of woody plants, thus influencing energy fluxes as well as carbon (C), water, and nutrient cycling of forests. Researchers have proposed various strategies for stomatal regulation of leaf gas-exchange that include maintaining a constant leaf internal [CO2], c(i), a constant drawdown in CO2 (c(a)-c(i)), and a constant c(i)/c(a). These strategies can result in drastically different consequences for leaf gas-exchange. The accuracy of Earth systems models depends in part on assumptions about generalizable patterns in leaf gas-exchange responses to varying c(a). The concept of optimal stomatal behavior, exemplified by woody plants shifting along a continuum of these strategies, provides a unifying framework for understanding leaf gas-exchange responses to c(a). To assess leaf gas-exchange regulation strategies, we analyzed patterns in c(i) inferred from studies reporting C stable isotope ratios (C-13) or photosynthetic discrimination () in woody angiosperms and gymnosperms that grew across a range of c(a) spanning at least 100ppm. Our results suggest that much of the c(a)-induced changes in c(i)/c(a) occurred across c(a) spanning 200 to 400ppm. These patterns imply that c(a)-c(i) will eventually approach a constant level at high c(a) because assimilation rates will reach a maximum and stomatal conductance of each species should be constrained to some minimum level. These analyses are not consistent with canalization toward any single strategy, particularly maintaining a constant c(i). Rather, the results are consistent with the existence of a broadly conserved pattern of stomatal optimization in woody angiosperms and gymnosperms. This results in trees being profligate water users at low c(a), when additional water loss is small for each unit of C gain, and increasingly water-conservative at high c(a), when photosystems are saturated and water loss is large for each unit C gain
The Gemini Planet Imager Exoplanet Survey : giant planet and brown dwarf demographics from 10 to 100 au
We present a statistical analysis of the first 300 stars observed by the Gemini Planet Imager Exoplanet Survey. This subsample includes six detected planets and three brown dwarfs; from these detections and our contrast curves we infer the underlying distributions of substellar companions with respect to their mass, semimajor axis, and host stellar mass. We uncover a strong correlation between planet occurrence rate and host star mass, with stars M* > 1.5 Mâ more likely to host planets with masses between 2 and 13MJup and semimajor axes of 3â100 au at 99.92% confidence. We fit a double power-law model in planet mass (m) and semimajor axis (a) for planet populations around high-mass stars (M* > 1.5 Mâ) of the form d2N/(dm da) â mα aÎČ, finding α = â2.4 ± 0.8 and ÎČ = â2.0 ± 0.5, and an integrated occurrence rate of 9+5-4% between 5â13MJup and 10â100 au. A significantly lower occurrence rate is obtained for brown dwarfs around all stars, with 0.8+0.8-0.5% of stars hosting a brown dwarf companion between 13â80MJup and 10â100 au. Brown dwarfs also appear to be distributed differently in mass and semimajor axis compared to giant planets; whereas giant planets follow a bottom-heavy mass distribution and favor smaller semimajor axes, brown dwarfs exhibit just the opposite behaviors. Comparing to studies of short-period giant planets from the radial velocity method, our results are consistent with a peak in occurrence of giant planets between âŒ1 and 10 au. We discuss how these trends, including the preference of giant planets for high-mass host stars, point to formation of giant planets by core/pebble accretion, and formation of brown dwarfs by gravitational instability.Peer reviewe
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