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Sleep and circadian timing shifts later during adolescence, conflicting with early school start times, and resulting in circadian misalignment. Although circadian misalignment has been linked to depression, substance use, and altered reward function, a paucity of experimental studies precludes the determination of causality. Here we tested, for the first time, whether experimentally-imposed circadian misalignment alters the neural response to monetary reward and/or response inhibition.
Healthy adolescents (n = 25, ages 13–17) completed two in-lab sleep schedules in counterbalanced order: An ‘aligned’ condition based on typical summer sleep-wake times (0000–0930) and a ‘misaligned’ condition mimicking earlier school year sleep-wake times (2000–0530). Participants completed morning and afternoon functional magnetic resonance imaging scans during each condition, including monetary reward (morning only) and response inhibition (morning and afternoon) tasks. Total sleep time and circadian phase were assessed via actigraphy and salivary melatonin, respectively.
Bilateral ventral striatal (VS) activation during reward outcome was lower during the Misaligned condition after accounting for the prior night's total sleep time. Bilateral VS activation during reward anticipation was lower during the Misaligned condition, including after accounting for covariates, but did not survive correction for multiple comparisons. Right inferior frontal gyrus activation during response inhibition was lower during the Misaligned condition, before and after accounting for total sleep time and vigilant attention, but only during the morning scan.
Our findings provide novel experimental evidence that circadian misalignment analogous to that resulting from school schedules may have measurable impacts on healthy adolescents' reward processing and inhibition of prepotent responses.
When presenting with a first episode of psychosis (FEP), migrants can have different demographic and clinical characteristics to the native-born population and this was examined in an Irish Early Intervention for Psychosis service.
All cases of treated FEP from three local mental health services within a defined catchment area were included. Psychotic disorder diagnoses were determined using the SCID and symptom and functioning domains were measured using validated and reliable measures.
From a cohort of 612 people, 21.1% were first-generation migrants and there was no difference in the demographic characteristics, diagnoses, symptoms or functioning between migrants and those born in the Republic of Ireland, except that migrants from Africa presented with less insight. Of those admitted, 48.6% of admissions for migrants were involuntary compared to 37.7% for the native-born population (p = 0.09).
First-generation migrants now make up a significant proportion of people presenting with a FEP to an Irish EI for psychosis service. Broadly the demographic and clinical characteristics of migrants and those born in the Republic of Ireland are similar, except for less insight in migrants from Africa and a trend for a higher proportion of involuntary admissions in the total migrant group.
We summarize some of the past year's most important findings within climate change-related research. New research has improved our understanding of Earth's sensitivity to carbon dioxide, finds that permafrost thaw could release more carbon emissions than expected and that the uptake of carbon in tropical ecosystems is weakening. Adverse impacts on human society include increasing water shortages and impacts on mental health. Options for solutions emerge from rethinking economic models, rights-based litigation, strengthened governance systems and a new social contract. The disruption caused by COVID-19 could be seized as an opportunity for positive change, directing economic stimulus towards sustainable investments.
A synthesis is made of ten fields within climate science where there have been significant advances since mid-2019, through an expert elicitation process with broad disciplinary scope. Findings include: (1) a better understanding of equilibrium climate sensitivity; (2) abrupt thaw as an accelerator of carbon release from permafrost; (3) changes to global and regional land carbon sinks; (4) impacts of climate change on water crises, including equity perspectives; (5) adverse effects on mental health from climate change; (6) immediate effects on climate of the COVID-19 pandemic and requirements for recovery packages to deliver on the Paris Agreement; (7) suggested long-term changes to governance and a social contract to address climate change, learning from the current pandemic, (8) updated positive cost–benefit ratio and new perspectives on the potential for green growth in the short- and long-term perspective; (9) urban electrification as a strategy to move towards low-carbon energy systems and (10) rights-based litigation as an increasingly important method to address climate change, with recent clarifications on the legal standing and representation of future generations.
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Stronger permafrost thaw, COVID-19 effects and growing mental health impacts among highlights of latest climate science.
Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.
Patients with sellar masses undergoing transsphenoidal surgery (TSS) frequently develop endocrine dysfunction; therefore, in-hospital endocrinology consultation (IHEC) is recommended. However, we wondered whether routine endocrinology assessment of all TSS patients is always necessary.
We developed an IHEC Physician’s Guide to identify patients who would require peri-operative IHEC. An analysis of all patients undergoing TSS for a sellar mass over a 4-year period was conducted to assess the predictive value of the IHEC Physician’s Guide in identifying patients who required IHEC.
A total of 116 patients underwent TSS; 24 required IHEC. As expected, the risk of endocrine complications requiring peri-operative endocrine management was significantly higher in the IHEC group versus no-IHEC group (96% vs. 1%; p < 0.001). The negative predictive value of the IHEC Physician’s Guide in identifying patients who did not require IHEC was 0.99 (95% CI 0.9409–0.9997); Fisher’s exact test, p < 0.001), meaning that the IHEC Physician’s Guide successfully identified all but one patient who truly required IHEC.
Results from our study show that most patients do not need IHEC after TSS and that those patients requiring IHEC can be reliably predicted at surgery by using a simple IHEC Physician’s Guide.
The ACA shifted U.S. health policy from centering on principles of actuarial fairness toward social solidarity. Yet four legal fixtures of the health care system have prevented the achievement of social solidarity: federalism, fiscal pluralism, privatization, and individualism. Future reforms must confront these fixtures to realize social solidarity in health care, American-style.
This commentary describes limitations of mental health parity requirements in ensuring access to insurance coverage for mental health treatment and surveys regulatory options employed by states in Medicaid managed care programs as supplements to parity that can further reduce the risk of inappropriate denials of coverage.
Advanced imaging techniques are enhancing research capacity focussed on the developmental origins of adult health and disease (DOHaD) hypothesis, and consequently increasing awareness of future health risks across various subareas of DOHaD research themes. Understanding how these advanced imaging techniques in animal models and human population studies can be both additively and synergistically used alongside traditional techniques in DOHaD-focussed laboratories is therefore of great interest. Global experts in advanced imaging techniques congregated at the advanced imaging workshop at the 2019 DOHaD World Congress in Melbourne, Australia. This review summarizes the presentations of new imaging modalities and novel applications to DOHaD research and discussions had by DOHaD researchers that are currently utilizing advanced imaging techniques including MRI, hyperpolarized MRI, ultrasound, and synchrotron-based techniques to aid their DOHaD research focus.
Introduction: In 2018, Canadian postgraduate specialist Emergency Medicine (EM) programs began implementing a competency-based medical education (CBME) assessment system. To support improvement of this assessment program, we sought to evaluate its short-term educational outcomes nationally and within individual programs. Methods: Program-level data from the 2018 resident cohort were amalgamated and analyzed. The number of Entrustable Professional Activity (EPA) assessments (overall and for each EPA) and the timing of resident promotion through program stages was compared between programs and to the guidelines provided by the national EM specialty committee. Total EPA observations from each program were correlated with the number of EM and pediatric EM rotations. Results: Data from 15 of 17 (88.2%) EM programs containing 9,842 EPA observations from 68 of the 77 (88.3%) Canadian EM specialist residents in the 2018 cohort were analyzed. The average number of EPAs observed per resident in each program varied from 92.5 to 229.6 and correlated strongly with the number of blocks spent on EM and pediatric EM (r = 0.83, p < 0.001). Relative to the guidelines outlined by the specialty committee, residents were promoted later than expected and with fewer EPA observations than suggested. Conclusion: We present a new approach to the amalgamation of national and program-level assessment data. There was demonstrable variation in both EPA-based assessment numbers and promotion timelines between programs and with national guidelines. This evaluation data will inform the revision of local programs and national guidelines and serve as a starting point for further reaching outcome evaluation. This process could be replicated by other national assessment programs.
Introduction: CAEP recently developed the acute atrial fibrillation (AF) and flutter (AFL) [AAFF] Best Practices Checklist to promote optimal care and guidance on cardioversion and rapid discharge of patients with AAFF. We sought to assess the impact of implementing the Checklist into large Canadian EDs. Methods: We conducted a pragmatic stepped-wedge cluster randomized trial in 11 large Canadian ED sites in five provinces, over 14 months. All hospitals started in the control period (usual care), and then crossed over to the intervention period in random sequence, one hospital per month. We enrolled consecutive, stable patients presenting with AAFF, where symptoms required ED management. Our intervention was informed by qualitative stakeholder interviews to identify perceived barriers and enablers for rapid discharge of AAFF patients. The many interventions included local champions, presentation of the Checklist to physicians in group sessions, an online training module, a smartphone app, and targeted audit and feedback. The primary outcome was length of stay in ED in minutes from time of arrival to time of disposition, and this was analyzed at the individual patient-level using linear mixed effects regression accounting for the stepped-wedge design. We estimated a sample size of 800 patients. Results: We enrolled 844 patients with none lost to follow-up. Those in the control (N = 316) and intervention periods (N = 528) were similar for all characteristics including mean age (61.2 vs 64.2 yrs), duration of AAFF (8.1 vs 7.7 hrs), AF (88.6% vs 82.9%), AFL (11.4% vs 17.1%), and mean initial heart rate (119.6 vs 119.9 bpm). Median lengths of stay for the control and intervention periods respectively were 413.0 vs. 354.0 minutes (P < 0.001). Comparing control to intervention, there was an increase in: use of antiarrhythmic drugs (37.4% vs 47.4%; P < 0.01), electrical cardioversion (45.1% vs 56.8%; P < 0.01), and discharge in sinus rhythm (75.3% vs. 86.7%; P < 0.001). There was a decrease in ED consultations to cardiology and medicine (49.7% vs 41.1%; P < 0.01), but a small but insignificant increase in anticoagulant prescriptions (39.6% vs 46.5%; P = 0.21). Conclusion: This multicenter implementation of the CAEP Best Practices Checklist led to a significant decrease in ED length of stay along with more ED cardioversions, fewer ED consultations, and more discharges in sinus rhythm. Widespread and rigorous adoption of the CAEP Checklist should lead to improved care of AAFF patients in all Canadian EDs.
Negative symptoms have been previously reported during the psychosis prodrome, however our understanding of their relationship with treatment-phase negative symptoms remains unclear.
We report the prevalence of psychosis prodrome onset negative symptoms (PONS) and ascertain whether these predict negative symptoms at first presentation for treatment.
Presence of expressivity or experiential negative symptom domains was established at first presentation for treatment using the Scale for Assessment of Negative Symptoms (SANS) in 373 individuals with a first episode psychosis. PONS were established using the Beiser Scale. The relationship between PONS and negative symptoms at first presentation was ascertained and regression analyses determined the relationship independent of confounding.
PONS prevalence was 50.3% in the schizophrenia spectrum group (n = 155) and 31.2% in the non-schizophrenia spectrum group (n = 218). In the schizophrenia spectrum group, PONS had a significant unadjusted (χ2 = 10.41, P < 0.001) and adjusted (OR = 2.40, 95% CI = 1.11–5.22, P = 0.027) association with first presentation experiential symptoms, however this relationship was not evident in the non-schizophrenia spectrum group. PONS did not predict expressivity symptoms in either diagnostic group.
PONS are common in schizophrenia spectrum diagnoses, and predict experiential symptoms at first presentation. Further prospective research is needed to examine whether negative symptoms commence during the psychosis prodrome.
The concept of indicated prevention has proliferated in psychiatry. Accumulating evidence suggests that it may indeed be possible to prevent or delay the onset of a First Episode of Psychosis (FEP) though adequate interventions in individuals deemed at Clinical High Risk (CHR) for such an event. However, a challenge undermining these efforts is the relatively poor predictive accuracy of clinical assessments used in practice for CHR individuals. to improve prediction by combining different types of assessments.
To improve prediction of clinical course of disease by combining biological and clinical types of assessment.
To present a probabilistic prediction model containing clinical and biological data for the transition to first episode psychosis.
Using data from published studies, and employing predictive models based on the odds ratio form of Bayes’ rule, we simulated scenarios where clinical interview, neurocognitive testing, structural magnetic resonance imaging (MRI) and electrophysiology are part of the initial assessment process of a CHR individual (Extended Diagnostic Approach).
Our findings indicate that for most at-risk patients, at least three types of assessments are necessary to arrive at a clinically meaningful differentiation into high- intermediate-, and low-risk groups. In particular, patients with equivocal results in the initial assessments require additional diagnostic testing to produce an accurate risk profile forming part of the comprehensive initial assessment.
The findings may inform future research into reliable identification and personalized therapeutic targeting of CHR patients, to prevent transition to full-blown psychosis and to inform decision in intervention.
Predicting transition from clinical high risk (CHR) to first episode psychosis has proven difficult. Assessment of oxidative stress biomarkers and the niacin skin flush response (NSFR) may improve prediction accuracy.
To predict transition to psychosis based on combined clinical and blood biomarker.
To analyse data from patients in placebo group of a 12-week trial of omega-3 fatty acid supplementation in CHR. Transition likelihood ratios (LRs) for baseline historical risks, clinical assessments (PANSS subscales and total, GAF), NSFR and blood markers (nervonic acid, superoxide dismutase, glutathione) were calculated. Variables with the highest positive and lowest negative LRs were included in an odds ratio form of Bayes’ rule transition prediction models. Model accuracy was calculated by area under the receiver operating curves (AUROC) of each model.
1-year transition to psychosis was 28% (n=40). Historical data showed no predictability (sensitivity 30%, specificity 100% (AUROC)=0.688, p=0.085). Clinical assessments alone produced a sensitivity of 30% at a specificity of 95% (AUROC=0.83, p<0.0001). The biomarker panel alone predicted transition with 40% sensitivity and 100% specificity (AUROC=0.73, p=0.03). Combining history and clinical assessment provided no improvement above clinical data alone (sensitivity = 30%, specificity = 100%, AUROC=0.85, p< 0.0001). The combination of history, clinical assessment and biomarkers identified transition with a sensitivity of 60% and specificity of 100% (AUROC=0.87, p< 0.0001).
Probabilistic models combining biomarkers and clinical data are able to target high-risk subgroups within CHR and may help to personalise treatment.
The comparative effectiveness of antidepressant medication and cognitive-behaviour therapy for the acute treatment of depression is contentious.
To compare the acute outcomes of antidepressant medication, cognitive-behaviour therapy (CBT), and the combination of the two, in adult, depressed patients.
Sixteen electronic databases together with reference lists were searched for randomised and other clinical trials that compared CBT, antidepressants, or their combination.
In the comparison between CBT and antidepressants, 8 studies met inclusion criteria. Five studies met the inclusion criteria for the second comparison between single therapy and combination therapy. In the antidepressant and CBT comparison, effect sizes favoured CBT over antidepressants with a significant advantage for CBT on some outcome measures. Combined treatment appeared more effective than antidepressants. However, combined treatment did not emerge more effective than CBT.
Antidepressants may not be considered more efficacious than CBT for the acute treatment of depressed patients nor can combination therapy be regarded as more effective than CBT alone.
The purpose of this paper was to examine national differences in the desire to participate in decision-making of people with severe mental illness in six European countries.
The data was taken from a European longitudinal observational study (CEDAR; ISRCTN75841675). A sample of 514 patients with severe mental illness from the study centers in Ulm, Germany, London, England, Naples, Italy, Debrecen, Hungary, Aalborg, Denmark and Zurich, Switzerland were assessed as to desire to participate in medical decision-making. Associations between desire for participation in decision-making and center location were analyzed with generalized estimating equations.
We found large cross-national differences in patients’ desire to participate in decision-making, with the center explaining 47.2% of total variance in the desire for participation (P < 0.001). Averaged over time and independent of patient characteristics, London (mean = 2.27), Ulm (mean = 2.13) and Zurich (mean = 2.14) showed significantly higher scores in desire for participation, followed by Aalborg (mean = 1.97), where scores were in turn significantly higher than in Debrecen (mean = 1.56). The lowest scores were reported in Naples (mean = 1.14). Over time, the desire for participation in decision-making increased significantly in Zurich (b = 0.23) and decreased in Naples (b = −0.14). In all other centers, values remained stable.
This study demonstrates that patients’ desire for participation in decision-making varies by location. We suggest that more research attention be focused on identifying specific cultural and social factors in each country to further explain observed differences across Europe.
Correlation of Rodinian and Gondwanan crustal domains relies on a thorough knowledge of those vestiges preserved today. The Bunger Hills hold a critical place in East Antarctica, recording the Mesoproterozoic assembly of Australo-Antarctica in Rodinia and the Neoproterozoic–Cambrian amalgamation of Indo- and Australo-Antarctica in Gondwana. It is situated in a region of disputed overlap between the different components of Rodinia and Gondwana, where there is little consensus on the location of sutures in this region and thus often speculative geological interpretations. The Bunger Hills therefore provide an opportunity to better understand the tectonic setting and palaeogeography during the assembly of these supercontinents. Recent work has confirmed that the Bunger Hills are one of few rare outcrops in Wilkes Land, East Antarctica that can be directly correlated with the broader Musgrave–Albany–Fraser–Wilkes Orogen (MAFWO). Whilst other constituent terranes of the MAFWO have been intensely studied, our geological knowledge of the Bunger Hills was comparatively limited until recently. In light of recent geological and geophysical developments, this contribution serves as an updated and concise standalone reference for the present state of knowledge of the Neoarchean–Cambrian evolution of the Bunger Hills region.
Studies suggest that alcohol consumption and alcohol use disorders have distinct genetic backgrounds.
We examined whether polygenic risk scores (PRS) for consumption and problem subscales of the Alcohol Use Disorders Identification Test (AUDIT-C, AUDIT-P) in the UK Biobank (UKB; N = 121 630) correlate with alcohol outcomes in four independent samples: an ascertained cohort, the Collaborative Study on the Genetics of Alcoholism (COGA; N = 6850), and population-based cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC; N = 5911), Generation Scotland (GS; N = 17 461), and an independent subset of UKB (N = 245 947). Regression models and survival analyses tested whether the PRS were associated with the alcohol-related outcomes.
In COGA, AUDIT-P PRS was associated with alcohol dependence, AUD symptom count, maximum drinks (R2 = 0.47–0.68%, p = 2.0 × 10−8–1.0 × 10−10), and increased likelihood of onset of alcohol dependence (hazard ratio = 1.15, p = 4.7 × 10−8); AUDIT-C PRS was not an independent predictor of any phenotype. In ALSPAC, the AUDIT-C PRS was associated with alcohol dependence (R2 = 0.96%, p = 4.8 × 10−6). In GS, AUDIT-C PRS was a better predictor of weekly alcohol use (R2 = 0.27%, p = 5.5 × 10−11), while AUDIT-P PRS was more associated with problem drinking (R2 = 0.40%, p = 9.0 × 10−7). Lastly, AUDIT-P PRS was associated with ICD-based alcohol-related disorders in the UKB subset (R2 = 0.18%, p < 2.0 × 10−16).
AUDIT-P PRS was associated with a range of alcohol-related phenotypes across population-based and ascertained cohorts, while AUDIT-C PRS showed less utility in the ascertained cohort. We show that AUDIT-P is genetically correlated with both use and misuse and demonstrate the influence of ascertainment schemes on PRS analyses.
Emerging cybertechnologies, such as social digibots, bend epistemological conventions of life and culture already complicated by human and animal relationships. Virtually-augmented niches of machines and organic life promise new free-energy-governed selection of intelligent digital life. These provocative eco-evolutionary contexts demand a theory of (natural and artificial) minds to characterize and validate the immersive social phenomena universally-shaping cultural affordances.