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Background: Tuberculin skin testing is simple and relatively inexpensive, but the specificity of PPD is affected by BCG vaccination. Objective: Determine optimal dose and specificity of recombinant ESAT-6 and CFP-10 (C-Tb) produced in Lactococcus lactis for diagnosis of M. tuberculosis infection. Methods: In a dose finding phase I trial 0.01 or 0.1 µg preserved and unpreserved C-Tb was injected by Mantoux technique in 38 patients with active tuberculosis and induration responses measured. In a phase II specificity trial in 151 uninfected, BCG vaccinated participants 0.1 µg C-Tb was compared to 2 TU PPD. Results: 0.1 µg C-Tb gave a median induration of 15 mm after 2 days. Phenol preservation did not affect the response. The specificity of C-Tb was 99.3% (95% CI 96–100%) regarding indurations ≥5 mm as a positive outcome. This was higher than the specificity of PPD (63% using a cut-off of 5 mm or 92% using a cut-off of 15 mm to adjust for non-specific BCG responses). Local adverse reactions following C-Tb injection included transient itching and discomfort as expected components of the immune response. Conclusion: C-Tb offers a simple and convenient skin test to diagnose M. tuberculosis infection using a single, universal cut-off unaffected by BCG vaccination. Trial Registration: ClinicalTrials.gov NCT01033929 and NCT01241188. [ABSTRACT FROM AUTHOR]

AMPA receptor modulation is a potential novel approach to enhance cognitive performance. CX717 is a positive allosteric modulator of the AMPA receptor that has shown efficacy in rodent and primate cognition models. CX717 (100 mg, 300 mg and 1000 mg) and placebo were studied in 16 healthy male volunteers (18–45 years) in a randomized, crossover study. Cognitive function, arousal and recovery sleep (by polysomnography) were assessed during the extended wakefulness protocol. Placebo condition was associated with significant decrements in cognition, particularly at the circadian nadir (between 03:00 and 05:00). Pre-specified primary and secondary analyses (general linear mixed modelling, GLMM) at each separate time point did not reveal consistent improvements in performance or objective alertness with any dose of CX717. Exploratory repeated measures analysis, a method used to take into account the influence of individual differences, demonstrated an improvement in attention-based task performance following the 1000 mg dose. Analysis of the recovery sleep showed that CX717 1000 mg significantly reduced stage 4 and slow-wave sleep (p ≤ 0.05) with evidence of reduced electroencephalogram (EEG) slow-wave and spindle activity. The study suggests that CX717 only at the 1000 mg dose may counteract effects of sleep deprivation on attention-based tasks and that it may interfere with subsequent recovery sleep. [ABSTRACT FROM AUTHOR]

Free recall of words has been extensively used in psychopharmacology to assess the effects of CNS-active drugs on memory functions. However, there is a relative lack of information on the impact of word frequency on the subsequent recall of words following the administration of psychoactive drugs. The present double-blind, placebo-controlled, repeated-measures experiment used lorazepam and alcohol to test the effects of word frequency on immediate and delayed word recall in 24 healthy volunteers. One half of the words contained in the lists had a high frequency (HF) of occurrence and the remainder were of low frequency (LF). The results showed that LF words were more sensitive to memory impairment than HF words. However, the more accurate recall of HF words (with respect to LF words) was eliminated when a combination of lorazepam with alcohol was administered. These findings indicate that word frequency has a significant impact on memory and, as such, is a factor to be taken into account when using memory recall tasks to assess the effects of psychoactive drugs on memory. [ABSTRACT FROM AUTHOR]

The aim of the study was to investigate the effects of continuing treatment with Ginkgo biloba extract (GBE) 120 mg/day on the activities of daily living (ADLs) and mood in healthy older volunteers who had immediately previously participated in a survey of the effects of a 4 month treatment with the drug. Following a prior postal survey investigating the effects of 4 months supplementation with GBE on ADLs and various aspects of mood and sleep, 1570 volunteers continued onto a 6 month follow-up postal survey. Subjects selected their own treatment option for the follow-up survey, which effectively created four groups: a continuation group who received GBE in the initial 4 month study and during the 6 month follow-up (GBE-GBE), a discontinuation group who received GBE in the initial study but not during the follow-up (GBE-NT), a new treatment group who did not receive GBE in the initial 4 month study but who did receive GBE during the 6 month follow-up (NT-GBE), and a no treatment group who received no treatment in either survey (NT-NT). At the end of the 6 month follow-up period each subject completed a line analogue rating scale (LARS) and a self-rating activities of daily living scale (SR-ADL). There were significant differences in the mean overall LARS and SR-ADL scores between the four treatment combination groups at the end of the follow-up period. A factor analysis of the LARS revealed two factors, 'mood' and 'alertness'. When scores from each of the treatment groups were examined over the whole 10 month period it was evident that the ratings of overall competence in the SR-ADL and both factors of the LARS were diminished on cessation of treatment with GBE, and improved when GBE treatment was initiated. The magnitude of the improvements on all scales was related to the overall duration of GBE supplementation. Significant differences between the groups of subjects treated with GBE for different periods of time (4-10 months) suggests that the extract has a demonstrable effect in improving mood and the self-assessed performance of the tasks of everyday living. Copyright © 2004 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

This document is a letter to the editor of "Behavioral Sleep Medicine" discussing the need for standardization in the reporting of measures and outcomes in insomnia randomized controlled trials (RCTs). The letter emphasizes the importance of adhering to general clinical trial reporting standards and recommends pre-registering studies in clinical trial registries. The aim is to enhance consistency, facilitate comparisons, and improve scientific rigor and reproducibility in insomnia RCTs. The letter also provides a brief review of recent insomnia trials to illustrate the variability in reporting sleep continuity outcomes. [Extracted from the article]

Objective: Evidence suggests that young adults (aged 18–34) were disproportionately impacted by the COVID-19 pandemic, but little is known about their longer-term mental health changes beyond the early pandemic period. This article investigates heterogeneous trajectories of mental health among Australian young adults across 2 years of the pandemic and identifies a broad range of associated risk and protective factors. Method: Young adults (N = 653, Mage = 27.8 years) from the longitudinal Alone Together Study were surveyed biannually between July 2020 and June 2022. Measures assessed anxiety (7-item Generalised Anxiety Disorder scale) and depression (9-item Patient Health Questionnaire) symptoms at Waves 1–4, as well as demographic, psychological, adversity and COVID-19 factors at baseline. Results: Four and three distinct trajectories of anxiety and depressive symptoms, respectively, were identified through growth mixture modelling. The proportion of participants in each anxiety trajectory were Asymptomatic (45.9%), Mild Stable (17.9%), Moderate–Severe Stable (31.1%) and Initially Severe/Recovering (5.1%). For depression, Mild Stable (58.3%), Moderate–Severe Stable (30.5%) and Reactive/Recovering (11.2%). Baseline factors associated with severe symptom trajectories included a lifetime mental health disorder, pre-pandemic stressful events, identifying as LGBTQIA+ and/or female, and experiencing one or more infection-control measures. Higher household income was protective. Conclusion: Most young adults demonstrated stable trajectories of low or high symptoms during the pandemic, with smaller groups showing initially severe or reactive symptoms followed by marked improvements over time. Vulnerable subgroups (gender- or sexuality-diverse, those with prior adversity or pre-existing mental ill-health) may face ongoing impacts and require targeted psychosocial supports to assist their mental health recovery post-COVID-19 and in the event of future crises. [ABSTRACT FROM AUTHOR]

There is growing recognition that young people should be given opportunities to participate in the decisions that affect their lives, such as advisory groups, representative councils, advocacy or activism. Positive youth development theory and sociopolitical development theory propose pathways through which youth participation can influence mental health and wellbeing outcomes. However, there is limited empirical research synthesising the impact of participation on youth mental health and/or wellbeing, or the characteristics of activities that are associated with better or worse mental health and/or wellbeing outcomes. This scoping review seeks to address this gap by investigating the scope and nature of evidence detailing how youth participation initiatives can influence mental health and/or wellbeing outcomes for participants. To be eligible, literature must describe youth (aged 15–24) in participation activities and the impact of this engagement on participant mental health and/or wellbeing outcomes. A systematic scoping review of peer-reviewed and grey literature will be conducted using Scopus, PsycINFO, Embase, Medline and grey literature databases. The scoping review will apply established methodology by Arksey and O'Malley, Levac and colleagues and the Joanna Briggs Institute. Title, abstract, and full text screening will be completed by two reviewers, data will be extracted by one reviewer. Findings will be reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR), including a qualitative summary of the characteristics of youth participation and their influence on youth mental health outcomes. Youth advisory group members will be invited to deliver governance on the project from the outset; participate in, and contribute to, all stages of the review process; reflect on their own experiences of participation; and co-author the resulting publication. This scoping review will provide essential knowledge on how participation activities can be better designed to maximise beneficial psychosocial outcomes for involved youth. [ABSTRACT FROM AUTHOR]

According to the hopelessness theory of depression, some individuals have a cognitive vulnerability (i.e., negative cognitive style) that interacts with stressful life events to produce depression. A negative cognitive style is associated with a maladaptive cognitive response to stress (i.e., increased negative attributions); however, no study has assessed whether this cognitive vulnerability is also associated with a maladaptive endocrine (e.g., cortisol) response to stress. If shown to be related, individual differences in cognitive style may potentially explain why the literature on the association between cortisol stress reactivity and depression is mixed, as cortisol responses to stress may vary as a function of attributional style. The aim of the present study was to provide a preliminary test of whether cognitive vulnerability was related to cortisol reactivity to an acute laboratory stressor among a sample of young adults (n = 20; Mage = 23.1 years; 10 females). Negative cognitive style and depressive symptoms were assessed via the Cognitive Style Questionnaire and the Patient Health Questionnaire, respectively. All participants also completed the Trier Social Stress Test (TSST). Salivary cortisol was collected before, during, and after the TSST. Results showed a significant association between negative cognitive style and cortisol stress reactivity, such that a greater negative cognitive style was related to a larger cortisol response to the TSST. Post hoc analyses revealed that this association was moderated by gender (i.e., effect observed in males only). Cortisol responses to the TSST, in general, were lower among females, but this relationship was not moderated by cognitive style. These findings may be related to underlying gender differences in stress vulnerability, which may have clinical implications for understanding the interactive effect of cognitive and neuroendocrine processes on vulnerability and resiliency to depression. [ABSTRACT FROM AUTHOR]

Background: Pediatric long COVID remains incompletely understood with scant Australian data available. We aimed to assess the impacts of the 2021 Delta variant of SARS-CoV-2 outbreak on symptoms and functioning 12 weeks post-acute infection in a cohort of children and adolescents., Methods: The parents/carers of 11,864 patients with PCR-confirmed SARS-CoV-2 were invited, via email or text message, to complete an online survey assessing symptoms and functional impairment., Findings: 1731 (17.6%) responded to the survey. 203 (11.7%) reported continued symptoms and/or functional impairment which were flagged for clinical review, all others reported recovery. Of the 169 subsequently clinically reviewed, 63 had already recovered (37.3%) and 17 had exacerbation of pre-existing condition(s) (10.1%); 63 (37.3%) were diagnosed with a Post COVID Condition (PCC). Of these, 21 (12.4%) were considered to have features compatible with the United Kingdom consensus cases definition for Long COVID., Interpretation: During an outbreak of SARS-CoV-2 an online questionnaire with subsequent clinical review revealed self-reported non-recovery at 12 weeks in a minority of cases, with a spectrum of features. Long COVID comprised only a subset of cases with self-reported non-recovery, and is infrequent in children and adolescents, but still comprises a likely significant burden that warrants attention., Impact: Our study provides the only comprehensive estimate of the frequency and spectrum of post-COVID conditions in children from Australia. The high frequency of self-reported recovery, and low frequency of Long COVID compatible illness adds to the literature from other settings. Risk factors for post-COVID conditions in children are identified and include: age >11 year, and previous medical co-morbidity., (© 2024. The Author(s).)

Host-associated microbiomes are shaped by both their environment and host genetics, and often impact host performance. The scale of host genetic variation important to microbes is largely unknown yet fundamental to the community assembly of host-associated microbiomes, with implications for the eco-evolutionary dynamics of microbes and hosts. Using Ipomoea hederacea , ivyleaf morning glory, we generated matrilines differing in quantitative genetic variation and leaf shape, which is controlled by a single Mendelian locus. We then investigated the relative roles of Mendelian and quantitative genetic variation in structuring the leaf microbiome and how these two sources of genetic variation contributed to microbe heritability. We found that despite large effects of the environment, both Mendelian and quantitative genetic host variation contribute to microbe heritability and that the cumulative small effect genomic differences due to matriline explained as much or more microbial variation than a single large effect Mendelian locus. Furthermore, our results are the first to suggest that leaf shape itself contributes to variation in the abundances of some phyllosphere microbes.IMPORTANCEWe investigated how host genetic variation affects the assembly of Ipomoea hederacea 's natural microbiome. We found that the genetic architecture of leaf-associated microbiomes involves both quantitative genetic variation and Mendelian traits, with similar contributions to microbe heritability. The existence of Mendelian and quantitative genetic variation for host-associated microbes means that plant evolution at the leaf shape locus or other quantitative genetic loci has the potential to shape microbial abundance and community composition., Competing Interests: The authors declare no conflict of interest.

Introduction: Insomnia symptoms are associated with poor physical and mental health. Exercise is associated with good sleep while sedentary behavior is associated with poor sleep. This study investigated the longitudinal, dynamic associations among exercise, sedentary behavior, and insomnia symptoms., Methods: Seven hundred and fifty-six adults (M age =47.2years, 54.9% female) took part in an online longitudinal study investigating sleep and health across the lifespan. Participants reported duration of moderate-to-strenuous exercise, percentage of day spent sitting, and insomnia symptoms (Insomnia Severity Index [ISI]). The ISI was scored as a total score and two-factor scores: (1) Sleep Disturbance (items 1, 2, 3) and (2) Daytime Dysfunction (items 4, 5, 6, 7). Multilevel modeling was used to examine the typical (i.e., between-persons) and individual (i.e., within-persons) associations among sedentary behavior, exercise, and insomnia symptoms., Results: Sedentary behavior was significantly associated with total ISI scores at both the between-person and within-person levels (β = 0.036, t = 3.23, p = .001; β = 0.014, t = 1.99, p = .048). Both between-persons and within-person levels of sedentary behavior were associated with Daytime Dysfunction (β = 0.028, t = 3.79, p < .001; β = 0.009, t = 2.08, p = .039). Exercise was associated with total ISI and Daytime Dysfunction scores at the between-persons level but not at the within-persons level (β = 0.028, t = 2.57, p = .01; β = -0.002, t = -3.02, p = .003)., Conclusions: Sedentary behavior was a more consistent and robust predictor of insomnia symptoms than exercise. The association between sedentary behavior and insomnia symptoms was dynamic in that when an individual reported being more sedentary than their norm, they also reported more insomnia symptoms. Future analyses should examine potential moderator variables and comorbid conditions., Competing Interests: Declaration of conflicts of interest Joseph Dzierzewski served on an advisory panel for Eisai Pharmaceuticals and received an honorarium for a presentation given for the Nevada Psychological Association. Some material within this manuscript is the result of work supported with resources and use of facilities as VA Boston Healthcare System. The contents do not represent the views of the National Sleep Foundation, U.S. Department of Veterans Affairs, or the United States Government. All other co-authors have no interests to disclose., (Copyright © 2024 National Sleep Foundation. All rights reserved.)

Background: The CSC study found that the universal delivery of a school-based, online programme for the prevention of mental health and substance use disorders among adolescents resulted in improvements in mental health and substance use outcomes at 30-month follow-up. We aimed to compare the long-term effects of four interventions-Climate Schools Combined (CSC) mental health and substance use, Climate Schools Substance Use (CSSU) alone, Climate Schools Mental Health (CSMH) alone, and standard health education-on mental health and substance use outcomes among adolescents at 72-month follow-up into early adulthood., Methods: This long-term study followed up adolescents from a multicentre, cluster-randomised trial conducted across three states in Australia (New South Wales, Queensland, and Western Australia) enrolled between Sept 1, 2013, and Feb 28, 2014, for up to 72 months after baseline assessment. Adolescents (aged 18-20 years) from the original CSC study who accepted contact at 30-month follow-up and provided informed consent at 60-month follow-up were eligible. The interventions were delivered in school classrooms through an online delivery format and used a mixture of peer cartoon storyboards and classroom activities that were focused on alcohol, cannabis, anxiety, and depression. Participants took part in two web-based assessments at 60-month and 72-month follow-up. Primary outcomes were alcohol use, cannabis use, anxiety, and depression, measured by self-reported surveys and analysed by intention to treat (ie, in all students who were eligible at baseline). This trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12613000723785), including the extended follow-up study., Findings: Of 6386 students enrolled from 71 schools, 1556 (24·4%) were randomly assigned to education as usual, 1739 (27·2%) to CSSU, 1594 (25·0%) to CSMH, and 1497 (23·4%) to CSC. 311 (22·2%) of 1401 participants in the control group, 394 (26·4%) of 1495 in the CSSU group, 477 (37·%) of 1289 in the CSMH group, and 400 (32·5%) of 1232 in the CSC group completed follow-up at 72 months. Adolescents in the CSC group reported slower year-by-year increases in weekly alcohol use (odds ratio 0·78 [95% CI 0·66-0·92]; p=0·0028) and heavy episodic drinking (0·69 [0·58-0·81]; p<0·0001) than did the control group. However, significant baseline differences between groups for drinking outcomes, and no difference in the predicted probability of weekly or heavy episodic drinking between groups were observed at 72 months. Sensitivity analyses increased uncertainty around estimates. No significant long-term differences were observed in relation to alcohol use disorder, cannabis use, cannabis use disorder, anxiety, or depression. No adverse events were reported during the trial., Interpretation: We found some evidence that a universal online programme for the prevention of anxiety, depression, and substance use delivered in early adolescence is effective in reducing the use and harmful use of alcohol into early adulthood. However, confidence in these findings is reduced due to baseline differences, and we did not see a difference in the predicted probability of drinking between groups at 72-month follow-up. These findings suggest that a universal prevention programme in adolescence is not sufficient to have lasting effects on mental health and substance use disorders in the long term. In addition to baseline differences, substantial attrition warrants caution in interpretation and the latter factor highlights the need for future long-term follow-up studies to invest in strategies to increase engagement., Funding: Australian National Health and Medical Research Council., Competing Interests: Declaration of interests MT and NCN are two of the developers of the OurFutures programmes (formerly Climate Schools) and are members of the OurFutures Institute, a not-for-profit charity that distributes the OurFutures programmes to maximise social wellbeing. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

As the population grows, the incidence of dementia will increase. A common occurrence in people with dementia is behavioral and psychological symptoms of dementia (BPSD). BPSD can include apathy, aggression, resistance to care, and agitation. BPSD can start or worsen during an acute hospitalization, but these units are not well-equipped to handle BPSD, often relying on pharmacological interventions to address distress behaviors. One known behavioral intervention for BPSD is STAR-VA, an interdisciplinary approach to managing these behaviors. However, this intervention has not been utilized in acute care. Our team implemented STAR-VA in acute care at a Veterans Affairs hospital in the northeastern United States. Using the VA's Quality Enhancement Research Initiative (QUERI) implementation roadmap to guide our work, we first outlined the problem, completed a needs assessment with staff, and began implementation. Results from this quality improvement project demonstrated the feasibility and efficacy of STAR-VA in an acute care setting., Competing Interests: Declaration of competing interest None, (Published by Elsevier Inc.)

Objectives: Evaluate insomnia symptoms and environmental disruptors at admission and discharge in a subacute rehabilitation care setting., Methods: Veterans (age ≥50) admitted to a Veterans Health Administration (VA) Hospital subacute rehabilitation between March and August 2022 completed baseline ( N  = 46) and follow up ( N  = 33) assessments with the Insomnia Severity Index (ISI), Sleep Need Questionnaire (SNQ), Epworth Sleepiness Scale (ESS), and an assessment of environmental sleep disruptors. Veterans were offered sleep resources after admission evaluations and outpatient referrals after discharge evaluations. Pearson correlation determined associations between length of stay (LOS), ISI, SNQ, and ESS scores at admission and discharge; chi-square and Wilcoxon Signed Rank Tests compared insomnia at admission and discharge., Results: One-half of participants reported clinically meaningful insomnia symptoms and sleep needs at baseline with no significant change at discharge. Almost all (89.1%) Veterans reported sleep was disturbed by environmental factors, primarily staff awakenings. LOS was correlated with ESS scores at discharge ( r  = .52, p  = .002)., Conclusions: Environmental sleep disruption was common during a subacute rehabilitation admission and were not adequately addressed through sleep resources and treatment due to low uptake., Clinical Implications: Providers should assess sleep at admission and lessen environmental sleep disruptors by reducing noise, light, and non-essential awakenings at night.

Study Objectives: The 3P and 4P models represent illness severity over the course of insomnia disorder. The 3P model suggests that illness severity is worst during acute onset. The 4P model suggests that illness severity crescendos with chronicity. The present analysis from an archival dataset assesses illness severity with new onset illness (i.e. from good sleep [GS] to acute insomnia [AI] to chronic insomnia [CI]). Illness severity is quantified in terms of total wake time (TWT)., Methods: GSs (N = 934) were followed up to 1 year with digital sleep diaries, and classified as GS, AI, or CI. Data for CIs were anchored to the first of 14 days with insomnia so that day-to-day TWT was represented prior to and following AI onset. A similar graphic (+/-acute onset) was constructed for number of days per week with insomnia. GS data were temporally matched to CI data. Segmented linear mixed regression models were applied to examine the change in slopes in the AI-to-CI period compared to GS-to-AI period., Results: Twenty-three individuals transitioned to AI and then CI. Average TWT rose during the first 2 weeks of AI onset (b = 1.8, SE = 0.57, p = 0.001) and was then stable for 3 months (b = -0.02, SE = 0.04, p = 0.53). Average number of affected days was stable from AI to CI (b = 0.0005, SE = 0.002, p = 0.81). That is, while there was week-to-week variability in the number of days affected, no linear trend was evident., Conclusions: In our sample of CIs, primarily with middle insomnia, the average severity and number of affected days were worst with the onset of AI (worst is first) and stable thereafter., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Cognitive behavioral therapy for insomnia (CBT-I) is an empirically supported intervention for insomnia. Given the strong, consistent support of its efficacy, scholars have become increasingly interested in the behavioral and cognitive mechanisms targeted during CBT-I. The purpose of the systematic review was to synthesize findings from the literature regarding the associations among maladaptive sleep beliefs, a cognitive mechanism implicated in maintaining insomnia, and treatment outcomes following CBT-I. The systematic review was completed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Seventeen studies were included in the final sample of reviewed articles and a study quality assessment was performed for all studies included in the review. The results suggested that reductions in maladaptive sleep beliefs were associated with improved insomnia severity; however, reductions in maladaptive beliefs were not associated with changes in sleep efficiency or other sleep parameters. Moreover, in some cases, improved sleep parameters preceded reductions in maladaptive beliefs. Maladaptive sleep beliefs may be an important target for improving insomnia. Targeting maladaptive sleep beliefs may initiate a trickle-down process that limits the influence of other cognitive and behavioral processes maintaining insomnia. Additional investigation is needed to evaluate the directional relationship between improved insomnia symptoms and reduced maladaptive beliefs., Competing Interests: Declaration of competing interest Joseph Dzierzewski served on an advisory panel for Eisai Pharmaceuticals and received an honorarium for a presentation given for the Nevada Psychological Association. Some material within this manuscript is the result of work supported with resources and use of facilities as VA Boston Healthcare System. The contents do not represent the views of the National Sleep Foundation, U.S. Department of Veterans Affairs, or the United States Government. All other co-authors have no interests to disclose., (Copyright © 2023. Published by Elsevier Ltd.)

Programmable photonic integrated circuits (PICs) are emerging as powerful tools for control of light, with applications in quantum information processing, optical range finding, and artificial intelligence. Low-power implementations of these PICs involve micromechanical structures driven capacitively or piezoelectrically but are often limited in modulation bandwidth by mechanical resonances and high operating voltages. Here we introduce a synchronous, micromechanically resonant design architecture for programmable PICs and a proof-of-principle 1×8 photonic switch using piezoelectric optical phase shifters. Our design purposefully exploits high-frequency mechanical resonances and optically broadband components for larger modulation responses on the order of the mechanical quality factor Q m while maintaining fast switching speeds. We experimentally show switching cycles of all 8 channels spaced by approximately 11 ns and operating at 4.6 dB average modulation enhancement. Future advances in micromechanical devices with high Q m , which can exceed 10000, should enable an improved series of low-voltage and high-speed programmable PICs., (© 2023. The MITRE Corporation and The Author(s).)

Background: Multiple myeloma remains incurable, and heavily pretreated patients with relapsed or refractory disease have few good treatment options. Belantamab mafodotin showed promising results in a phase 2 study of patients with relapsed or refractory multiple myeloma at second or later relapse and a manageable adverse event profile. We aimed to assess the safety and efficacy of belantamab mafodotin in a phase 3 setting., Methods: In the DREAMM-3 open-label phase 3 study, conducted at 108 sites across 18 countries, adult patients were enrolled who had confirmed multiple myeloma (International Myeloma Working Group criteria), ECOG performance status of 0-2, had received two or more previous lines of therapy, including two or more consecutive cycles of both lenalidomide and a proteasome inhibitor, and progressed on, or within, 60 days of completion of the previous treatment. Participants were randomly allocated using a central interactive response technology system (2:1) to receive belantamab mafodotin 2·5 mg/kg intravenously every 21 days, or oral pomalidomide 4·0 mg daily (days 1-21) and dexamethasone 40·0 mg (20·0 mg if >75 years) weekly in a 28-day cycle. Randomisation was stratified by previous anti-CD38 therapy, International Staging System stage, and number of previous therapies. The primary endpoint was progression-free survival in all patients who were randomly allocated. The safety population included all randomly allocated patients who received one or more doses of study treatment. This trial is registered with ClinicalTrials.gov, NCT04162210, and is ongoing. Data cutoff for this analysis was Sept 12, 2022., Findings: Patients were recruited between April 2, 2020, and April 18, 2022. As of September, 2022, 325 patients were randomly allocated (218 to the belantamab mafodotin group and 107 to the pomalidomide-dexamethasone group); 184 (57%) of 325 were male and 141 (43%) of 325 were female, 246 (78%) of 316 were White. Median age was 68 years (IQR 60-74). Median follow-up was 11·5 months (5·5-17·6) for belantamab mafodotin and 10·8 months (5·6-17·1) for pomalidomide-dexamethasone. Median progression-free survival was 11·2 months (95% CI 6·4-14·5) for belantamab mafodotin and 7·0 months (4·6-10·6) for pomalidomide-dexamethasone (hazard ratio 1·03 [0·72-1·47]; p=0·56). Most common grade 3-4 adverse events were thrombocytopenia (49 [23%] of 217) and anaemia (35 [16%]) for belantamab mafodotin, and neutropenia (34 [33%] of 102) and anaemia (18[18%]) for pomalidomide-dexamethasone. Serious adverse events occurred in 94 (43%) of 217 and 40 (39%) of 102 patients, respectively. There were no treatment-related deaths in the belantamab mafodotin group and one (1%) in the pomalidomide-dexamethasone group due to sepsis., Interpretation: Belantamab mafodotin was not associated with statistically improved progression-free survival compared with standard-of-care, but there were no new safety signals associated with its use. Belantamab mafodotin is being tested in combination regimens for relapsed or refractory multiple myeloma., Funding: GSK (study number 207495)., Competing Interests: Declaration of interests MAD has received fees from speaker's bureau participation from Amgen, Beigene, BMS, Janssen, and Takeda. VTMH has received fees for consulting from AbbVie, Amgen, BMS, Celgene, Janssen, Sanofi, and Takeda. AR has received honoraria from Roche, Pfizer, AbbVie, Swixx, SOBI, and Novartis; consulting or advisory fees from Roche, Swixx, SOBI. SD has received honoraria from Amgen, GSK, Janssen, and Takeda. GM has received honoraria from AbbVie, Amgen, Celgene, Janssen, BMS, Takeda, Roche, and Richter; has received consulting or advisory fees from AbbVie, Amgen, Celgene, Janssen, BMS, Takeda, Roche; research funding from AbbVie; and fees for travel, accommodations, and expenses from BMS, Janssen, and Takeda. TM has received fees for participation on a Data Safety Monitoring Board or Advisory Board from AbbVie, BMS, Janssen, Novartis, Pfizer, and Takeda. MC has received speaker's bureau participation fees from Sanofi, BMS, and Janssen; and fees for travel, accommodations, and expenses Sanofi, BMS, and Janssen. AM reports honoraria from Amgen, BMS, Janssen, Sanofi, and Takeda. VP reports research funding from Genesis Pharma SA. XL has received honoraria from Amgen, BMS/Celgene, Janssen, Takeda, Novartis, Sanofi, Merck, Oncopeptide, Karyopharm, Roche, AbbVie, Carsgen, GSK, and Harpoon Therapeutics. NS is an employee of GSK and holds stocks and shares in GSK, Pfizer, and BMS. MaL is an employee of GSK and holds stocks and shares in GSK and Astra Zeneca. AMK is an employee of, and holds stocks and shares in GSK, AstraZeneca, and Novartis. WH was an employee of GSK at the time this analysis was completed, and holds stocks and shares in GSK. SB, BC, SP, JB, and SR-G are all employees of and hold stocks and shares in GSK. JO is an employee of and holds stocks, patents, and shares in GSK. KW has received honoraria from AbbVie, Amgen, Adaptive Biotech, Astra Zeneca, BMS/Celgene, Janssen, GSK, Karyopharm, Novartis, Oncopeptides, Pfizer, Roche Pharma, Sanofi, Stemline, and Takeda; consulting or advisory fees from AbbVie, Amgen, Adaptive Biotech, BMS/Celgene, Janssen, GSK, Karyopharm, Oncopeptides, Pfizer, Roche Pharma, Sanofi, and Takeda; and research funding from AbbVie, Amgen, BMS/Celgene, Janssen, GSK, and Sanofi. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Emerging data suggests that COVID-19 is associated with fatigue well beyond the acute illness period. The present analysis aimed to: (1) characterize the prevalence and incidence of high fatigue at baseline and follow-up; (2) examine the impact of COVID-19 diagnosis on fatigue level following acute illness; and (3) examine the impact of acute COVID-19 symptom severity and duration on fatigue at follow-up. Subjects ( n = 1417; 81.0% female; 83.3% White; X¯ age = 43.6 years) completed the PROMIS-Fatigue during the initial wave of the pandemic at baseline (April-June 2020) and 9-month follow-up (January-March 2021). A generalized linear model (binomial distribution) was used to examine whether COVID-19 positivity, severity, and duration were associated with higher fatigue level at follow-up. Prevalence of high fatigue at baseline was 21.88% and 22.16% at follow-up, with 8.12% new cases at follow-up. Testing positive for COVID-19 was significantly associated with higher fatigue at follow-up. COVID-19 symptom duration and severity were significantly associated with increased fatigue at follow-up. COVID-19 symptom duration and severity during acute illness may precipitate longer-term fatigue, which could have implications for treatment planning and future research. Future studies should further evaluate the relationship between symptom severity, duration, and fatigue.

Background: Pharmacists are well trained, readily accessible health care professionals (HCPs) who practice in a variety of inpatient and outpatient mental health settings., Observations: As part of the interdisciplinary team, pharmacists can help address HCP shortages. Pharmacists currently are providing mental health collaborative practice services at US Department of Veterans Affairs (VA) facilities., Conclusions: Collaborative practice services can be expanded within and outside the VA by using pharmacists to increase access to care and improve outcomes., Competing Interests: Author disclosures The authors report no actual or potential conflicts of interest or outside sources of funding with regard to this article., (Copyright © 2022 Frontline Medical Communications Inc., Parsippany, NJ, USA.)

Priority effects occur when the order of species arrival affects the final community structure. Mutualists often interact with multiple partners in different orders, but if or how priority effects alter interaction outcomes is an open question. In the field, we paired the legume Medicago lupulina with two nodulating strains of Ensifer bacteria that vary in nitrogen-fixing ability. We inoculated plants with strains in different orders and measured interaction outcomes. The first strain to arrive primarily determined plant performance and final relative abundances of rhizobia on roots. Plants that received effective microbes first and ineffective microbes second grew larger than plants inoculated with the same microbes in the opposite order. Our results show that mutualism outcomes can be influenced not just by partner identity, but by the interaction order. Furthermore, hosts receiving high-quality mutualists early can better tolerate low-quality symbionts later, indicating that priority effects may help explain the persistence of ineffective symbionts.

Mental disorders and problematic alcohol use are common, co-occurring and cause significant harm to individuals and society. It is critical to intervene early to prevent chronic and debilitating trajectories. Existing prevention programs among adolescents are limited in effectiveness and implementation. This Australian-first study will examine the effectiveness and feasibility of a personality-targeted program called Preventure, in preventing the onset or escalation of alcohol use, internalising problems and externalising problems among young Australians, when delivered by school staff. A cluster randomised controlled trial (RCT) of effectiveness will be conducted from 2020 to 2022 with 12 schools in Sydney, Australia, with students aged 13 years at baseline. Schools will be randomly allocated to the Preventure intervention or a control condition who will receive their usual Health Education curriculum. Schools allocated to the intervention will deliver Preventure to students scoring one standard deviation above the population mean on one of four personality traits. Preventure consists of two 90-minute group sessions that incorporate cognitive-behavioural therapy and motivational interviewing to promote coping skills. Students will be invited to complete surveys at baseline, 6- and 12-months following the intervention. Primary outcomes include student alcohol use, internalising problems, and externalising problems. Implementation fidelity, feasibility and acceptability will also be examined through surveys with school staff and students. Ethical approval has been obtained from the University of Sydney Human Research Ethics Committee, and the State Education Research Applications Process for research in public schools in NSW. This trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12620000790943)., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Author(s).)

Introduction: Opioid-related overdoses have risen despite extensive media coverage and apparent awareness of this public health crisis. Emergency department visits related to opioid use nearly tripled from 2004 to 2011. Patients with mental illness are more likely to be prescribed opioids and have higher rates of overdose. This retrospective chart review sought to determine if opioid represcribing occurred after patients were treated for a nonfatal opioid overdose (NFO) at a Veterans Affairs hospital., Methods: Patients who experienced an NFO between 2009 and 2013 were included and charts reviewed until January 1, 2016. Review of the electronic medical record (EMR) was performed to determine if and when opioids were again prescribed after NFO., Results: Fifty-six veterans met the inclusion criteria. A new opioid prescription was issued to 82% of patients within 3 months following the index NFO date. The average daily morphine equivalent dose prescribed before (122 mg) and after (120 mg) NFO did not differ. A subsequent opioid overdose event occurred in 25% of patients, and there was 1 fatal event. Only 1 patient had medication overdose on the problem list of their EMR., Discussion: Despite experiencing NFO, veterans continued to be prescribed opioids without significant changes in the drug or dose; some experienced repeated overdose events, possibly due to poor communication and documentation of NFO. Pharmacists can play a key role in clinical interventions and education of patients and prescribers., Competing Interests: Disclosures: The authors have nothing to disclose.

Next-day residual effects of single evening doses of 3 mg of eszopiclone, 7.5 mg of zopiclone, and placebo were assessed in a randomized, double-blind, placebo-controlled, 3-way crossover study that used a mild sleep restriction protocol (sleep duration, 7 hours). During each period, 91 healthy volunteers spent 2 consecutive nights in the laboratory with time in bed restricted to 7 hours. Volunteers completed the Continuous Tracking Test, Critical Flicker Fusion task, Digit Symbol Substitution Test, N-back tasks, and Linear Analogue Rating Scales every half-hour from 7.5 to 11.5 hours after dose, commencing 15 minutes after awakening. Nighttime dosing of both eszopiclone (3 mg) and racemic zopiclone (7.5 mg) was associated with next-day performance impairment, and these residual effects dissipated over time. Eszopiclone did not differ from zopiclone on the primary end point, mean Continuous Tracking Test tracking error averaged from 7.5 to 9.5 hours after dose; however, a prespecified post hoc parametric analysis of reciprocal-transformed data favored eszopiclone over racemic zopiclone (P = 0.026).

It is now believed that up to 43% of children can experience a sleep problem at some stage during their development. Reduced quality of sleep can have important implications for the developing child as it can impair growth, learning and emotional development. It is important for health professionals to understand the significance of sleep and the ways to alleviate problems so that these can be tackled at an early age. By educating people in how to get a good night's sleep we shall hopefully move towards a more happy, healthy and capable child population.