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Choosing whether to exert effort to obtain rewards is fundamental to human motivated behavior. However, the neural dynamics underlying the evaluation of reward and effort in humans is poorly understood. Here, we report an exploratory investigation into this with chronic intracranial recordings from the prefrontal cortex (PFC) and basal ganglia (BG; subthalamic nuclei and globus pallidus) in people with Parkinsons disease performing a decision-making task with offers that varied in levels of reward and physical effort required. This revealed dissociable neural signatures of reward and effort, with BG beta (12 to 20 Hz) oscillations tracking effort on a single-trial basis and PFC theta (4 to 7 Hz) signaling previous trial reward, with no effects of net subjective value. Stimulation of PFC increased overall acceptance of offers and sensitivity to reward while decreasing the impact of effort on choices. This work uncovers oscillatory mechanisms that guide fundamental decisions to exert effort for reward across BG and PFC, supports a causal role of PFC for such choices, and seeds hypotheses for future studies.

Mortality disparities among persons with intellectual disability are important to guide health-care practices. The objective was to evaluate mortality patterns of persons with intellectual disability in a nationwide study from 1976 to 2020. This study establishes a Danish nationwide cohort of persons with intellectual disability and age- and sex-matched reference cohort through linkage between several registers. We established a cohort of 79,114 persons with intellectual disability. Standardized mortality ratios were increased for persons with intellectual disability, most pronounced among younger persons and among females. Life expectancies were markedly lower; among persons with intellectual disability 63.6 years among females and 59.8 years among males in 2016-2020 compared to 82.4 and 78.7 years among females and males in the reference cohort. Life expectancies decreased with severity of intellectual disability. This study reports the establishment of a nationwide Danish cohort of persons with intellectual disability.

Several closely related Myb-like activator proteins are known to have partially redundant functions within the plant circadian clock, but their specific roles are not well understood. To clarify the function of the REVEILLE 4, REVEILLE 6, and REVEILLE 8 transcriptional activators, we characterized the growth and clock phenotypes of CRISPR-Cas9-generated single, double, and triple rve mutants. We found that these genes act synergistically to regulate flowering time, redundantly to regulate leaf growth, and antagonistically to regulate hypocotyl elongation. We previously reported that increasing intensities of monochromatic blue and red light have opposite effects on the period of triple rve468 mutants. Here, we further examined light quality-specific phenotypes of rve mutants and report that rve468 mutants lack the blue light-specific increase in expression of some circadian clock genes observed in wild type. To investigate the basis of these blue light-specific circadian phenotypes, we examined RVE protein abundances and degradation rates in blue and red light and found no significant differences between these conditions. We next examined genetic interactions between RVE genes and ZEITLUPE and ELONGATED HYPOCOTYL5, two factors with blue light-specific functions in the clock. We found that the RVEs interact additively with both ZEITLUPE and ELONGATED HYPOCOTYL5 to regulate circadian period, which suggests that neither of these factors are required for the blue light-specific differences that we observed. Overall, our results suggest that the RVEs have separable functions in plant growth and circadian regulation and that they are involved in blue light-specific circadian signaling via a novel mechanism.

Inspired by Graham Harman's philosophy of human access, and within the 'flattening ontology' of Object Oriented Ontology, Ring o' Roses is speculated about as a finite object with ontological independence from humans, repertoire, song, utility, and cultural context. Ring o' Roses playfully dances us through an introduction to OOO, and on to the idea of young children's early musical play as something different from its qualities and benefits. Indeed, the reality of musical play can be speculated about as ontologically irreducible, and as having a weird and vast, yet fragile, interior which is announced by allure. Allure is composed of charm, courage, and humour, and is responsible for causation.

The transmission electron microscope (TEM) is often considered the most complete characterization tool available to scientists who study materials' microstructure, crystallography, composition, chemistry, and functional properties. Consequently, significant investments have [...]

BACKGROUND: Quality of life (QOL) is a critical factor in decision-making for advanced breast cancer (ABC). There is a need to improve how QOL and treatment-related side effects (SEs) that impact it are clinically assessed. We examined healthcare professionals (HCPs) and patients perspectives on the importance of QOL discussions and the impact of SEs on QOL in clinical settings. PATIENTS AND METHODS: A cross-sectional online survey was conducted (7/2020-5/2021) among oncologists, nurses, and patients with HR+/HER2- ABC in 7 countries. RESULTS: The survey was completed by 502 HCPs and 467 patients. Overall, 88% of oncologists and 49% of patients recalled QOL discussions at follow-up. In the first- through fourth-line (1L, 2L, 3L, and 4L) settings, respectively, 48%, 57%, 79%, and 85% of oncologists reported QOL was very important; 73% and 45% of patients receiving 1L and 2L treatment and 40% receiving 3L+ treatment indicated QOL was important. Patients reported that insomnia, anxiety, back pain, fatigue, diarrhea, hot flashes, low sexual interest, and loss of appetite had a moderate/severe impact on QOL. Of patients experiencing certain SEs, ≥64% did not discuss them with HCPs until there was a moderate/severe impact on QOL. In patients receiving a CDK4/6 inhibitor, SEs, including insomnia, diarrhea, back pain, and fatigue, had a moderate/severe impact on QOL. CONCLUSIONS: This survey discovered disconnects between HCPs and patients with ABC on the importance of QOL discussions and the impact of SEs on QOL. These data support the use of ABC-specific QOL questionnaires that closely monitor SEs impacting QOL.

Sunflowers are famous for their ability to track the sun throughout the day and then reorient at night to face east the following morning. This occurs by differential growth patterns, with the east sides of stems growing more during the day and the west sides of stems growing more at night. This process, termed heliotropism, is generally believed to be a specialized form of phototropism; however, the underlying mechanism is unknown. To better understand heliotropism, we compared gene expression patterns in plants undergoing phototropism in a controlled environment and in plants initiating and maintaining heliotropic growth in the field. We found the expected transcriptome signatures of phototropin-mediated phototropism in sunflower stems bending towards monochromatic blue light. Surprisingly, the expression patterns of these phototropism-regulated genes are quite different in heliotropic plants. Most genes rapidly induced during phototropism display only minor differences in expression across solar tracking stems. However, some genes that are both rapidly induced during phototropism and are implicated in growth responses to foliar shade are rapidly induced on the west sides of stems at the onset of heliotropism, suggesting a possible role for red light photoreceptors in solar tracking. To test the involvement of different photoreceptor signaling pathways in heliotropism, we modulated the light environment of plants initiating solar tracking. We found that depletion of either red and far-red light or blue light did not hinder the initiation or maintenance of heliotropism in the field. Together, our results suggest that the transcriptional regulation of heliotropism is distinct from phototropin-mediated phototropism and likely involves inputs from multiple light signaling pathways.

The functions of closely related Myb-like repressor and Myb-like activator proteins within the plant circadian oscillator have been well-studied as separate groups, but the genetic interactions between them are less clear. We hypothesized that these repressors and activators would interact additively to regulate both circadian and growth phenotypes. We used CRISPR-Cas9 to generate new mutant alleles and performed physiological and molecular characterization of plant mutants for five of these core Myb-like clock factors compared with a repressor mutant and an activator mutant. We first examined circadian clock function in plants likely null for both the repressor proteins, CIRCADIAN CLOCK ASSOCIATED 1 (CCA1) and LATE ELONGATED HYPOCOTYL (LHY), and the activator proteins, REVEILLE 4 (RVE4), REVEILLE (RVE6), and REVEILLE (RVE8). The rve468 triple mutant has a long period and flowers late, while cca1 lhy rve468 quintuple mutants, similarly to cca1 lhy mutants, have poor circadian rhythms and flower early. This suggests that CCA1 and LHY are epistatic to RVE4, RVE6, and RVE8 for circadian clock and flowering time function. We next examined hypocotyl elongation and rosette leaf size in these mutants. The cca1 lhy rve468 mutants have growth phenotypes intermediate between cca1 lhy and rve468 mutants, suggesting that CCA1, LHY, RVE4, RVE6, and RVE8 interact additively to regulate growth. Together, our data suggest that these five Myb-like factors interact differently in regulation of the circadian clock versus growth. More generally, the near-norm al seedling phenotypes observed in the largely arrhythmic quintuple mutant demonstrate that circadian-regulated output processes, like control of hypocotyl elongation, do not always depend upon rhythmic oscillator function.

Abstract The role of serotonin in human behaviour is informed by approaches which allow in vivo modification of synaptic serotonin. However, characterising the effects of increased serotonin signalling in human models of behaviour is challenging given the limitations of available experimental probes, notably selective serotonin reuptake inhibitors. Here we use a now-accessible approach to directly increase synaptic serotonin in humans (a selective serotonin releasing agent) and examine its influence on domains of behaviour historically considered core functions of serotonin. Computational techniques, including reinforcement learning and drift diffusion modelling, explain participant behaviour at baseline and after week-long intervention. Reinforcement learning models reveal that increasing synaptic serotonin reduces sensitivity for outcomes in aversive contexts. Furthermore, increasing synaptic serotonin enhances behavioural inhibition, and shifts bias towards impulse control during exposure to aversive emotional probes. These effects are seen in the context of overall improvements in memory for neutral verbal information. Our findings highlight the direct effects of increasing synaptic serotonin on human behaviour, underlining its role in guiding decision-making within aversive and more neutral contexts, and offering implications for longstanding theories of central serotonin function.

Abstract The 5-2-1 criteria was developed to facilitate the identification and referral of patients with Parkinson’s Disease (PD) inadequately controlled by oral medications. The criterion was not developed to screen patients with PD for device-aided therapy eligibility. The robust design and validation of the 5-2-1 criteria minimizes over or inappropriate referrals, and supports physicians in the timely identification of patients with PD who may warrant further evaluation for treatment optimization. This response letter clarifies concerns raised by Moes et al.

The circadian oscillator allows organisms to synchronize their cellular and physiological activities with diurnal environmental changes. In plants, the circadian clock is primarily composed of multiple transcriptional-translational feedback loops. Regulators of post-transcriptional events, such as precursor messenger RNAs (pre-mRNA) splicing factors, are also involved in controlling the pace of the clock. However, in most cases the underlying mechanisms remain unclear. We have previously identified XAP5 CIRCADIAN TIMEKEEPER (XCT) as an Arabidopsis thaliana circadian clock regulator with uncharacterized molecular functions. Here, we report that XCT physically interacts with components of the spliceosome, including members of the Nineteen Complex (NTC). PacBio Iso-Seq data show that xct mutants have transcriptome-wide pre-mRNA splicing defects, predominantly aberrant 3' splice site selection. Expression of a genomic copy of XCT fully rescues those splicing defects, demonstrating that functional XCT is important for splicing. Dawn-expressed genes are significantly enriched among those aberrantly spliced in xct mutants, suggesting that the splicing activity of XCT may be circadian regulated. Furthermore, we show that loss-of-function mutations in PRP19A or PRP19B, 2 homologous core NTC components, suppress the short circadian period phenotype of xct-2. However, we do not see rescue of the splicing defects of core clock genes in prp19 xct mutants. Therefore, our results suggest that XCT may regulate splicing and the clock function through genetically separable pathways.

Abstract Lamotrigine is an effective mood stabiliser, largely used for the management and prevention of depression in bipolar disorder. The neuropsychological mechanisms by which lamotrigine acts to relieve symptoms as well as its neural effects on emotional processing remain unclear. The primary objective of this current study was to investigate the impact of an acute dose of lamotrigine on the neural response to a well-characterised fMRI task probing implicit emotional processing relevant to negative bias. 31 healthy participants were administered either a single dose of lamotrigine (300 mg, n = 14) or placebo (n = 17) in a randomized, double-blind design. Inside the 3 T MRI scanner, participants completed a covert emotional faces gender discrimination task. Brain activations showing significant group differences were identified using voxel-wise general linear model (GLM) nonparametric permutation testing, with threshold free cluster enhancement (TFCE) and a family wise error (FWE)-corrected cluster significance threshold of p

Abstract Lithium is an effective augmenting agent for depressed patients with inadequate response to standard antidepressant therapy, but numerous adverse effects limit its use. We previously reported that a lithium-mimetic agent, ebselen, promoted a positive emotional bias—an indicator of potential antidepressant activity in healthy participants. We therefore aimed to investigate the effects of short-term ebselen treatment on emotional processing and brain neurochemistry in depressed patients with inadequate response to standard antidepressants. We conducted a double-blind, placebo-controlled 7-day experimental medicine study in 51 patients with major depressive disorder who were currently taking antidepressants but had an inadequate response to treatment. Participants received either ebselen 600 mg twice daily for seven days or identical matching placebo. An emotional testing battery, magnetic resonance spectroscopy and depression and anxiety rating scales were conducted at baseline and after seven days of treatment. Ebselen did not increase the recognition of positive facial expressions in the depressed patient group. However, ebselen increased the response bias towards fear emotion in the signal detection measurement. In the anterior cingulate cortex, ebselen significantly reduced the concentrations of inositol and Glx (glutamate+glutamine). We found no significant differences in depression and anxiety rating scales between visits. Our study did not find any positive shift in emotional bias in depressed patients with an inadequate response to antidepressant medication. We confirmed the ability of ebselen to lower inositol and Glx in the anterior cingulate cortex. These latter effects are probably mediated through inhibition of inositol monophosphatase and glutaminase respectively.

Background: Current treatment of major depressive disorders still leave many patients with modest improvement. Attention Bias Modification (ABM) is an approach that may serve as an adjuvant therapy for subgroups of patients. We examined whether rumination, often found to be associated with a negative attentional bias, acts as a moderating variable in a computerized ABM procedure in participants with recurrent depression. Methods: A total of 301 patients were randomized to receive either active - or sham ABM twice daily for 14 days. A regression-based moderator analysis was applied to evaluate whether baseline brooding, from the Rumination Response Scale (RRS-B), moderated the effect of ABM on Hamilton Depression Rating Scale (HDRS) and Beck Depression Inventory II (BDI-II). Results: There was no significant interaction effect of ABM and RRS-B on HDRS or BDI-II at post-intervention or at 1 month follow-up. In addition, no correlation was found for pre-training attention bias and RRS-B. Limitations: : Generalizability is limited to individuals with non-clinical symptom scores. Conclusions: There was no moderator effect of brooding rumination on clinical depression scales in the largest clinical study on ABM to date.

BackgroundEfforts to develop neuroimaging-based biomarkers in major depressive disorder (MDD), at the individual level, have been limited to date. As diagnostic criteria are currently symptom-based, MDD is conceptualized as a disorder rather than a disease with a known etiology; further, neural measures are often confounded by medication status and heterogeneous symptom states.MethodsWe describe a consortium to quantify neuroanatomical and neurofunctional heterogeneity via the dimensions of novel multivariate coordinate system (COORDINATE-MDD). Utilizing imaging harmonization and machine learning methods in a large cohort of medication-free, deeply phenotyped MDD participants, patterns of brain alteration are defined in replicable and neurobiologically-based dimensions and offer the potential to predict treatment response at the individual level. International datasets are being shared from multi-ethnic community populations, first episode and recurrent MDD, which are medication-free, in a current depressive episode with prospective longitudinal treatment outcomes and in remission. Neuroimaging data consist of de-identified, individual, structural MRI and resting-state functional MRI with additional positron emission tomography (PET) data at specific sites. State-of-the-art analytic methods include automated image processing for extraction of anatomical and functional imaging variables, statistical harmonization of imaging variables to account for site and scanner variations, and semi-supervised machine learning methods that identify dominant patterns associated with MDD from neural structure and function in healthy participants.ResultsWe are applying an iterative process by defining the neural dimensions that characterise deeply phenotyped samples and then testing the dimensions in novel samples to assess specificity and reliability. Crucially, we aim to use machine learning methods to identify novel predictors of treatment response based on prospective longitudinal treatment outcome data, and we can externally validate the dimensions in fully independent sites.ConclusionWe describe the consortium, imaging protocols and analytics using preliminary results. Our findings thus far demonstrate how datasets across many sites can be harmonized and constructively pooled to enable execution of this large-scale project.

Biological rhythms are ubiquitous. They can be generated by circadian oscillators, which produce daily rhythms in physiology and behavior, as well as by developmental oscillators such as the segmentation clock, which periodically produces modular developmental units. Here, we show that the circadian clock controls the timing of late-stage floret development, or anthesis, in domesticated sunflowers. In these plants, up to thousands of individual florets are tightly packed onto a capitulum disk. While early floret development occurs continuously across capitula to generate iconic spiral phyllotaxy, during anthesis floret development occurs in discrete ring-like pseudowhorls with up to hundreds of florets undergoing simultaneous maturation. We demonstrate circadian regulation of floral organ growth and show that the effects of light on this process are time-of-day dependent. Delays in the phase of floral anthesis delay morning visits by pollinators, while disruption of circadian rhythms in floral organ development causes loss of pseudowhorl formation and large reductions in pollinator visits. We therefore show that the sunflower circadian clock acts in concert with environmental response pathways to tightly synchronize the anthesis of hundreds of florets each day, generating spatial patterns on the developing capitulum disk. This coordinated mass release of floral rewards at predictable times of day likely promotes pollinator visits and plant reproductive success.

BackgroundA cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) + endocrine therapy is recommended as first-line treatment for hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC). Quality of life (QoL) is an important endpoint that affects treatment decisions. Understanding the relevance of CDK4/6i treatment on QoL is gaining importance given use in earlier treatment lines for ABC and an emerging role in treating early breast cancer in which QoL may be more impactful. In the absence of head-to-head trial data, a matching-adjusted indirect comparison (MAIC) permits comparative efficacy between trials.ObjectiveIn this analysis, patient-reported QoL for MONALEESA-2 [ribociclib + aromatase inhibitor (AI)] and MONARCH 3 (abemaciclib + AI) was compared using MAIC with a focus on individual domains.DesignAn anchored MAIC of QoL comparing ribociclib + AI versus abemaciclib + AI was performed using data from the European Organization for Research and Treatment of Cancer quality of life questionnaire (QLQ)-C30 and BR-23 questionnaires.MethodsIndividual patient data from MONALEESA-2 and published aggregated data from MONARCH 3 were included in this analysis. Time to sustained deterioration (TTSD) was calculated as the time from randomization to a ⩾10-point deterioration with no later improvement above this threshold.ResultsPatients from the ribociclib (n = 205) and placebo (n = 149) arms of MONALEESA-2 were matched with patients from the abemaciclib (n = 328) and placebo (n = 165) arms of MONARCH 3. After weighting, baseline patient characteristics were well balanced. TTSD significantly favored ribociclib versus abemaciclib in appetite loss [hazard ratio (HR), 0.46; 95% confidence interval (CI), 0.27-0.81], diarrhea (HR, 0.42; 95% CI, 0.23-0.79), fatigue (HR, 0.63; 95% CI, 0.41-0.96), and arm symptoms (HR, 0.49; 95% CI, 0.30-0.79). TTSD did not significantly favor abemaciclib compared with ribociclib in any functional or symptom scale of the QLQ-C30 or BR-23 questionnaires.ConclusionsThis MAIC indicates that ribociclib + AI is associated with better symptom-related QoL than abemaciclib + AI for postmenopausal patients with HR+/HER2- ABC treated in the first-line setting.Trial registrationNCT01958021 (MONALEESA-2) and NCT02246621 (MONARCH 3).

Abstract Human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) represent an in vitro model of cardiac function. Isolated iPSC-CMs, however, exhibit electrophysiological heterogeneity which hinders their utility in the study of certain cardiac currents. In the healthy adult heart, the current mediated by small conductance, calcium-activated potassium (SK) channels (ISK) is atrial-selective. Functional expression of ISK within atrial-like iPSC-CMs has not been explored thoroughly. The present study therefore aimed to investigate atrial-like iPSC-CMs as a model system for the study of ISK. iPSCs were differentiated using retinoic acid (RA) to produce iPSC-CMs which exhibited an atrial-like phenotype (RA-iPSC-CMs). Only 18% of isolated RA-iPSC-CMs responded to SK channel inhibition by UCL1684 and isolated iPSC-CMs exhibited substantial cell-to-cell electrophysiological heterogeneity. This variability was significantly reduced by patch clamp of RA-iPSC-CMs in situ as a monolayer (iPSC-ML). A novel method of electrical stimulation was developed to facilitate recording from iPSC-MLs via In situ Monolayer Patch clamp of Acutely Stimulated iPSC-CMs (IMPASC). Using IMPASC, > 95% of iPSC-MLs could be paced at a 1 Hz. In contrast to isolated RA-iPSC-CMs, 100% of RA-iPSC-MLs responded to UCL1684, with APD50 being prolonged by 16.0 ± 2.0 ms (p

Abstract Diazotrophic cyanobacteria such as Trichodesmium play a crucial role in the nitrogen budget of the oceans due to their capability to bind atmospheric nitrogen. Little is known about their interoceanic transport pathways and their distribution in upwelling regions. Trichodesmium has been detected using a Video Plankton Recorder (VPR) mounted on a remotely operated towed vehicle (TRIAXUS) in the southern and northern Benguela Upwelling System (BUS) in austral autumn, Feb/Mar 2019. The TRIAXUS, equipped with a CTD as well as fluorescence and nitrogen sensors, was towed at a speed of 8 kn on two onshore–offshore transects undulating between 5 and 200 m over distances of 249 km and 372 km, respectively. Trichodesmium was not detected near the coast in areas of freshly upwelled waters but was found in higher abundances offshore on both transects, mainly in subsurface water layers down to 80 m depth with elevated salinities. These salinity lenses can be related to northward moving eddies that most probably have been detached from the warm and salty Agulhas Current. Testing for interaction and species-habitat associations of Trichodesmium colonies with salinity yielded significant results, indicating that Trichodesmium may be transported with Agulhas Rings from the Indian Ocean into the Atlantic Ocean.

Abstract Immunotherapies targeting PD-1/PD-L1 are now widely used in the clinic to treat a variety of malignancies. While most of the research on T cell exhaustion and PD-1 blockade has been focused on conventional αβ T cells, the contribution of innate-like T cells such as γδ T cells to anti-PD-1/PD-L1 mediated therapy is limited. Here we show that tumor reactive γδ T cells respond to PD-1 blockade in a Merkel cell carcinoma (MCC) patient experiencing a complete response to therapy. We find clonally expanded γδ T cells in the blood and tumor after pembrolizumab treatment, and this Vγ2Vδ1 clonotype recognizes Merkel cancer cells in a TCR-dependent manner. Notably, the intra-tumoral γδ T cells in the MCC patient are characterized by higher expression of PD-1 and TIGIT, relative to conventional CD4 and CD8 T cells. Our results demonstrate that innate-like T cells could also contribute to an anti-tumor response after PD-1 blockade.

Abstract Background Thrice-daily physiotherapy immediately following surgical repair of hip fracture has been shown to be safe and to reduce total hospital length of stay. However, implementing this is challenging with respect to health service funding and staffing. A novel approach may be to utilize an alternative workforce (allied health staff and student physiotherapists) to deliver two of the three daily treatments. However, how patients and staff may view such an approach is unknown. Thus, the aim of this qualitative study was to explore the views of inpatients with surgical repair of a hip fracture, their carers, health care professionals, and physiotherapy students about the implementation and acceptability of thrice-daily physiotherapy, with two sessions delivered by the alternative workforce (the BOOST study). Methods Semi-structured interviews and focus groups with patients, carers, health professionals and physiotherapy students. All interviews were digitally recorded and transcribed via verbatim. The transcripts were coded, and the data analysed via inductive thematic analysis. Results A total of 37 interviews (32 one-to-one interviews and five focus group interviews) were analysed. Five main themes were identified: (1) individual perceptions of the intervention: inpatients/carer/staff/student, (2) implementation within the service and organisational context, (3) implementation strategies that were effective, (4) improvements to implementation strategies/barriers to implementation/unsuccessful strategies and (5) future directions of BOOST. Conclusions The qualitative data revealed that higher frequency physiotherapy was well-received by inpatients and that staff/students involved in providing care perceived it as a safe, acceptable and valuable practice. Implementation of higher daily frequency of physiotherapy using an alternative workforce may feasibly be adopted for inpatients following hip fracture surgery. Trial registration This study was approved by the Human Research Ethics Committee (HREC) of the Western Sydney Local Health District (2020/ETH02718). Mutual recognition of approval was subsequently obtained from Northern Sydney Local Health District HREC.

Abstract Background Hip fracture has a devastating impact on individuals and is an increasing burden for health systems and society. Compared to usual care, increased physiotherapy provision has demonstrated efficacy in improving patient and health service outcomes in this population. However, physiotherapy workforce challenges prevent sustained implementation. Methods Our aim was to evaluate the safety, feasibility, acceptability, effectiveness and implementation cost of thrice daily physiotherapy for patients in the acute care setting after hip fracture at two public hospitals. We added twice-daily exercise implemented by an alternative workforce, to usual care consisting of daily mobility practice by a physiotherapist. Sites identified their preferred alternative workforce, with pre-registration physiotherapy students and allied health assistants chosen. We used a mixed methods approach, using the Consolidated Framework for Implementation Research (CFIR) as a determinant framework to guide implementation planning and data collection. We compared hospital length of stay data to a reference cohort. Results We recruited 25 patients during the study period. Acute care hospital length of stay decreased from 11 days in the reference cohort to 8 days in the BOOST cohort (mean difference − 3.3 days, 95%CI -5.4 to -1.2 days, p = 0.003). Intervention fidelity was 72% indicating feasibility, no safety concerns were attributed to the intervention, and uptake was 96% of all eligible patients. The intervention was acceptable to patients, carers and healthcare providers. This intervention was cost-effective from the acute orthopaedic service perspective. Conclusion Higher daily frequency of physiotherapy can be safely, feasibly and effectively implemented by an alternative workforce for patients in the acute care setting following hip fracture surgery.

This study produced a high-accuracy remotely piloted aircraft system (RPAS) imagery classification method for identifying the invasive reed Phragmites australis (Cav.) Trin. Ex Steud subsp. australis using random forest (RF) machine learning. RPAS imagery was collected in the spring and fall of 2019 using a fixed-wing RPAS equipped with a visible spectrum camera (eBee X, S.O.D.A. 3D; senseFly) in Long Point, Ontario, Canada. Imagery was used to produce separate early and late season classifications and a bi-temporal classification which used imagery from both dates. The overall accuracy achieved for each was 97%, 96%, and 91%, respectively. Digital surface models (DSMs) were the most important variable for identifying Phragmites in all classifications due to their greater height when compared to surrounding herbaceous vegetation. The bi-temporal classification, which utilized change in DSM value during the growing season, resulted in an estimated 47.8% new growth of Phragmites and appeared to capture sparse growth better than traditional classification differencing alone. This study highlights the promising use of high-resolution DSMs produced from RPAS imagery to classify invasive Phragmites and monitor within-year patch expansions.

This article is personal and rather anecdotal as it is an attempt to sum up my experience of 30 years of Ofsted inspections. The key questions remain what they always were. How do you deal with the sometimes conflicting requirements of support and accountability, objectivity and impartiality, styles of inspection, reporting and grading? Perhaps most importantly, how do you try to ensure that inspection leads to improvement?

Abstract Physical activity (PA) is understood to be important for the prevention and treatment of depression, however, less is known about the effects of withdrawal from PA on mood. Here we consider evidence published since the outbreak of the SARS‐CoV‐2 virus to assess the impact of the COVID‐19 pandemic on PA patterns and to evaluate whether engagement in PA in the context of the pandemic had an impact on depression vulnerability. During the initial stages of the pandemic and consequent lockdowns, there were global decreases in PA, with women, ethnic minorities, lower‐education, lower‐income, younger, and elderly people displaying more marked reductions in PA. Less PA was associated with a higher risk of experiencing moderate‐to‐severe depression symptoms, particularly for those who decreased their PA levels compared to pre‐pandemic. Both PA and sedentary behavior were independently associated with depression, such that low activity and high amounts of sitting both increased the likelihood of clinically significant symptoms. We also consider the role social connection during movement; while both in‐person and online PA can foster a sense of belonging, there is some evidence that socially distant, pandemic‐safe movement might disincentivise certain groups such as older adults and experienced exercisers from participating in PA. We conclude with several implications for prospective public health communications regarding PA, especially in the event of another global pandemic.

Abstract Across the fields of psychology, neuroscience, and psychiatry, dance—broadly and heterogeneously defined across cultures and movement styles—has been investigated for a range of potential benefits in healthy and clinical populations. There is a growing body of literature investigating the potential for dance, and in particular social forms of dance, to have a positive impact on mental health and well‐being. Given widespread availability through community providers, social dance and movement could be an accessible, non‐invasive, and affordable approach to the prevention and treatment of mood disorders, including depression. However, the existing literature is heterogenous, and there is a lack of methodological cohesiveness and systematization in the field of dance for mental health research. In this narrative review, we propose a novel classification system for social dance mental health research, which encompasses solo dance, partner dance, group dance, dance movement therapy, and cooperative movement. We review the existing literature examining the effects of social dance and movement in the context of low mood and depression and identify future research directions for building a solid evidence base for the application of social dance and movement in the prevention and treatment of mood disorders.

Background New National Institute for Health and Care Excellence (NICE) guidance endorses the prescription of statins in larger population groups for the prevention of cardiovascular and cerebrovascular morbidity and mortality, especially in people with severe mental illness. However, the evidence base for their safety and risk/benefit balance in depression is not established.Objectives This study aims to assess the real-world mortality and adverse events of statins in depressive disorders.Methods Population-based, nationwide (England), between-subject, cohort study. We used electronic health records (QResearch database) of people aged 18–100 years with first-episode depression, registered with English primary care practices over January 1998–August 2020 for 12(+) months, divided into statin users versus non-users.Primary safety outcomes included all-cause mortality and any adverse event measured at 2, 6 and 12 months. Multivariable logistic regression was employed to control for several potential confounders and calculate adjusted ORs (aORs) with 99% CIs.Findings From over 1 050 105 patients with depression (42.64% males, mean age 43.23±18.32 years), 21 384 (2.04%) died, while 707 111 (67.34%) experienced at least one adverse event during the 12-month follow-up. Statin use was associated with lower mortality over 12 months (range aOR2–12months 0.66–0.67, range 99% CI 0.60 to 0.73) and with lower adverse events over 6 months (range aOR2–6months 0.90–0.96, range 99% CI 0.91 to 0.99), but not at 1 year (aOR12months 0.99, 99% CI 0.96 to 1.03). No association with any other individual outcome measure (ie, any other neuropsychiatric symptoms) was identified.Conclusions We found no evidence that statin use among people with depression increases mortality or other adverse events.Clinical implications Our findings support the safety of updated NICE guidelines for prescribing statins in people with depressive disorders.