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Introduction: Mental health conditions (MHC) among adolescents in low- and middle-income countries, including South Africa, are estimated to be high. Adaptive emotion regulation (ER) skills can protect against MHC among adolescents. In South Africa, there is limited adolescent mental health prevalence data as well as little understanding of the associations between MHC and ER among adolescents. This study aimed to address these gaps by describing the psychosocial characteristics of older South African adolescents from low-income settings as well as investigating associations between depression and anxiety symptoms and ER. Methods: We selected 12 schools in collaboration with two NGOs. Learners aged 15–18-years were recruited to complete a tablet-based survey. ER, depression, anxiety, and other psychosocial measures were included. Two multiple linear regression models were used to determine associations between depression symptoms, anxiety symptoms, other psychosocial factors, and ER. Results: Of the 733 participants from 12 Western Cape schools, 417 (56.90%) screened at risk for clinically significant anxiety symptoms, 423 (57.70%) participants for depression symptoms, 229 (31.40%) participants for PTSD symptoms and 263 (35.90%) for risky alcohol use. Depression and anxiety scores were found to be significantly positively correlated with ER difficulties and adolescents struggled most with identifying and utilizing adaptive ER strategies. The adjusted linear regression model reported that female gender, clinically significant depressive, anxiety, post-traumatic stress symptoms and risky-alcohol use were all significantly associated with poorer ER scores, while self-esteem was significantly associated with better ER scores. Conclusion: These findings contribute to the South African adolescent mental health literature and to the research gap on the links between depression and anxiety and ER. Future research should consider further exploration of the relationships between psychosocial factors and ER to inform the urgent development and testing of appropriate adolescent interventions in this setting.

Abstract The transcription factor MYB plays a pivotal role in haematopoietic homoeostasis and its aberrant expression is involved in the genesis and maintenance of acute myeloid leukaemia (AML). We have previously demonstrated that not all AML subtypes display the same dependency on MYB expression and that such variability is dictated by the nature of the driver mutation. However, whether this difference in MYB dependency is a general trend in AML remains to be further elucidated. Here, we investigate the role of MYB in human leukaemia by performing siRNA-mediated knock-down in cell line models of AML with different driver lesions. We show that the characteristic reduction in proliferation and the concomitant induction of myeloid differentiation that is observed in MLL-rearranged and t(8;21) leukaemias upon MYB suppression is not seen in AML cells with a complex karyotype. Transcriptome analyses revealed that MYB ablation produces consensual increase of MAFB expression in MYB-dependent cells and, interestingly, the ectopic expression of MAFB could phenocopy the effect of MYB suppression. Accordingly, in silico stratification analyses of molecular data from AML patients revealed a reciprocal relationship between MYB and MAFB expression, highlighting a novel biological interconnection between these two factors in AML and supporting new rationales of MAFB targeting in MLL-rearranged leukaemias.

Abstract Extracellular vesicles (EVs) have been shown as key mediators of extracellular small RNA transport. However, carriers of cell-free messenger RNA (cf-mRNA) in human biofluids and their association with cancer remain poorly understood. Here, we performed a transcriptomic analysis of size-fractionated plasma from lung cancer, liver cancer, multiple myeloma, and healthy donors. Morphology and size distribution analysis showed the successful separation of large and medium particles from other soluble plasma protein fractions. We developed a strategy to purify and sequence ultra-low amounts of cf-mRNA from particle and protein enriched subpopulations with the implementation of RNA spike-ins to control for technical variability and to normalize for intrinsic drastic differences in cf-mRNA amount carried in each plasma fraction. We found that the majority of cf-mRNA was enriched and protected in EVs with remarkable stability in RNase-rich environments. We observed specific enrichment patterns of cancer-associated cf-mRNA in each particle and protein enriched subpopulation. The EV-enriched differentiating genes were associated with specific biological pathways, such as immune systems, liver function, and toxic substance regulation in lung cancer, liver cancer, and multiple myeloma, respectively. Our results suggest that dissecting the complexity of EV subpopulations illuminates their biological significance and offers a promising liquid biopsy approach.

Abstract Greenspaces facilitate well‐being benefits for humans in several ways including through cognitive restoration, physical exercise and social interaction. However, some groups are under‐represented in greenspaces, including women, older people, those with health conditions, people with lower socioeconomic status and people from ethnic minority backgrounds, and so are less likely to accrue these benefits. Using thematic analysis and semi‐structured interviews with 40 individuals from under‐represented groups in Leeds, UK, we explore (1) a range of perceived barriers to greenspace access, (2) how spending time in greenspace contributes to well‐being for these groups, (3) the perceived positive and negative aspects of greenspace, (4) what impact COVID‐19 had on access to greenspace and (5) how greenspaces could be improved. We also highlight inter‐group differences and how some barriers disproportionately affect some of the groups in this study. Safety concerns were particularly important for women and people with low incomes, which included problems with anti‐social behaviour (e.g. incivilities and disorder). Cultural barriers were also evident with ethnic minority participants often citing concerns about dogs and issues with visibility and prejudice. Participants desired physical improvements to the quality of greenspaces, along with easier access and transport options, changes in policy regarding dogs and increased security and park wardens to limit anti‐social behaviour. We argue that to increase visitation for under‐represented groups, upgrades in the physical environment must be coupled with harnessing community involvement and co‐design. Some group differences and tensions in greenspaces, and problems with anti‐social behaviours and safety concerns might be limited by more considerate planning and incorporating research findings that address these tensions through intergroup contact. Read the free Plain Language Summary for this article on the Journal blog.

Abstract Background Unfortunately, many COPD patients continue to exacerbate despite good adherence to GOLD Class D recommended therapy. Acute exacerbations lead to an increase in symptoms, decline in lung function and increased mortality rate. The purpose of this review is to do a literature search for any prophylactic anti-microbial treatment trials in GOLD class D patients who ‘failed’ recommended therapy and discuss the role of COPD phenotypes, lung and gut microbiota and co-morbidities in developing a tailored approach to anti-microbial therapies for high frequency exacerbators. Main text There is a paucity of large, well-conducted studies in the published literature to date. Factors such as single-centre, study design, lack of well-defined controls, insufficient patient numbers enrolled and short follow-up periods were significant limiting factors in numerous studies. One placebo-controlled study involving more than 1000 patients, who had 2 or more moderate exacerbations in the previous year, demonstrated a non-significant reduction in exacerbations of 19% with 5 day course of moxifloxacillin repeated at 8 week intervals. In Pseudomonas aeruginosa (Pa) colonised COPD patients, inhaled antimicrobial therapy using tobramycin, colistin and gentamicin resulted in significant reductions in exacerbation frequency. Viruses were found to frequently cause acute exacerbations in COPD (AECOPD), either as the primary infecting agent or as a co-factor. However, other, than the influenza vaccination, there were no trials of anti-viral therapies that resulted in a positive effect on reducing AECOPD. Identifying clinical phenotypes and co-existing conditions that impact on exacerbation frequency and severity is essential to provide individualised treatment with targeted therapies. The role of the lung and gut microbiome is increasingly recognised and identification of pathogenic bacteria will likely play an important role in personalised antimicrobial therapies. Conclusion Antimicrobial therapeutic options in patients who continue to exacerbate despite adherence to guidelines-directed therapy are limited. Phenotyping patients, identification of co-existing conditions and assessment of the microbiome is key to individualising antimicrobial therapy. Given the impact of viruses on AECOPD, anti-viral therapeutic agents and targeted anti-viral vaccinations should be the focus of future research studies.

Greater blade lengths and higher tip speeds, coupled with a harsh environment, have caused blade leading edge erosion to develop into a significant problem for the offshore wind industry. Current protection systems do not last the lifetime of the turbine and require regular replacement. It is important to understand the characteristics of the offshore environment to model and predict leading edge erosion. The offshore precipitation environment has been characterised using up-to-date measuring techniques. Heavy and violent rain was rare and is unlikely to be the sole driver of leading edge erosion. The dataset was compared to the most widely used droplet size distribution. It was found that this distribution did not fit the offshore data and that any lifetime predictions made using it are likely to be inaccurate. A general offshore droplet size distribution has been presented that can be used to improve lifetime predictions and reduce lost power production and unexpected turbine downtime.

Introduction It is recommended that pediatric patients be released from the post-anesthesia recovery area once they are no longer at risk for cardiorespiratory depression. However, these guidelines do not specify how a provider is to monitor recovery of neurocognitive status. Previous studies have evaluated the utility of psychomo- tor tests to measure anesthetic recovery; however, most of these tests are time consuming and are rarely used in the post-anesthesia recovery area. The Trieger Dot Test (TDT) is one of these tests and is a well validated meas- ure of anesthetic recovery. The King Devick Test (KDT) has emerged as a scientifically valid test for a multitude of neurological medical conditions. The test uses a system of Rapid Number Naming which assesses the subject’s ability to read aloud a series of numbers and determines their ability to discern levels of contrast. This test detects impairments of eye move- ments, language, attention, and overall neurological func- tion and is validated down to an age of 5 years. Null Hypothesis: There is no measured difference in the return to baseline between the King Devick Test and the Trieger Dot Test in determining sedation recovery in non-neurological pe- diatric patients. Material and methods Subjects were recruited from the University of Iowa pe- diatric sedation clinic. The recruited subjects were chil- dren and adolescents between the ages of 6-17. No pa- tients with a neurologic diagnosis were included in the study. Each patient performed both the KDT and TDT pre-sedation to establish a baseline. These tests were re- peated once when the patient woke up (Post1) and again 20 minutes later (Post2). These tests did not interfere with clinical care, and the discharging physician was blinded to the results. After discharge, the family repeated both tests on the subject at home 24 hours post-sedation. Results A total of 41 patients were recruited for the study. Extra- neous deviations for the TDT were compared to a total score for the KDT which summed the time and errors from all three cards. Baseline was established as baseline +/- 1/5(median change in score after sedation) to account for natural random variation. The results of the paired t- tests for KDT show that there is a highly significant dif- ference between scores at baseline, Post1, and Post2 (p < 0.001). The p-values for the same tests for TDT were also all significant at the 5% level, however the difference be- tween deviations at the Post2 after sedation is much less significant (p = 0.04). The results of McNemar’s statisti- cal test show no difference between the two assessmentsat Post1 (p = 0.31), but a significant difference between the assessments at Post2 (p = 0.04). 0.018). Conclusions The paired t-test results show that the KDT, like the TDT, can measure differences in a patient’s cognitive ability during recovery from sedation. Furthermore, McNemar’s statistical test shows that at Post2 the TDT significantly classified more patients at baseline than the KDT. This corresponds with the results of the paired t-tests, in that more patients were close to baseline at Post2 for the TDT, than for the KDT. Overall, we can conclude that there is evidence that the KDT is more sensitive to impairment than the TDT, and if it were used in place of the TDT it would take more time for children to return to baseline after sedation.

Background: Person-centred services are inherently related to patients/caregivers' needs. However, the extent to which dysphagia services within Singapore meet consumer needs is largely unknown. Involving patients/caregivers in service evaluation/redesign deepens the understanding of consumer needs. This process also increases the success of implementing service enhancements through relevant and meaningful change. Aim: This study aimed to identify aspects of dysphagia services, within acute and subacute settings in Singapore, perceived as highly important and easy to change by patients/caregivers. Methods & Procedures: Using concept mapping methodology, 5 patients and 11 caregivers reflected on their experiences of receiving dysphagia care and proposed 59 unique suggestions to improve dysphagia services within Singapore. Then, each individual sorted the suggestions into groups based on similarity and rated each statement for its perceived importance and changeability for service enhancement. Data were analysed using multidimensional scaling, hierarchical cluster analysis, and bivariate analysis to generate clusters of conceptually similar suggestions and a prioritised list of suggestions for service enhancement. Results: Twelve clusters were identified, with most rated as more important than changeable for service improvement. Participants prioritised 23 (39%) of the suggestions as highly important and easy to change, and these focused on ensuring effective communication among consumers and healthcare team, enhancing patients and carers' access to support at home, increasing patients and carers' access to educational resources, and improving service quality and access through technology. Conclusion: These findings provide future directions on how to develop and implement dysphagia services in Singapore to better meet the needs of patients/caregivers.

Introduction: Speech Language Therapy First Point of Contact Clinic (SLT-FPOCC) models can assist assessment of low-risk patient populations referred to ear, nose and throat (ENT) services. To further improve ENT waitlist management and compliance with best-practice care, consideration of other low-risk populations that could be safely managed through this service model is needed. The aims of this paper are to evaluate the clinical and service outcomes of completing vocal cord check (VCC) assessments for patients' pre and post thyroid/parathyroid surgery within an SLT-FPOCC model and examine consumer perceptions. Methods & Procedures: The service followed existing SLT-FPOCC procedures, with ENT triaging referrals, then SLT completing pre- and postoperative VCC assessment (interview, perceptual assessment, flexible nasendoscopy), with assessment data later reviewed by ENT to diagnose laryngeal pathology. Clinical and service outcomes were collected prospectively. Patients completed an anonymous post-service satisfaction survey. Results: Of the first 100 patients referred for preoperative VCCs, SLT assessment identified 42 with dysphonia and 30 reporting dysphagia, while ENT confirmed 9 with significant preoperative anatomical findings. Eighty-three underwent surgery, with 63 (95 nerves at surgical risk) returning for a postoperative VCC. Postoperative VCC identified three temporary neuropraxias (3.2%) and three unilateral vocal fold paresis (3.2%). Patients were highly satisfied with the service. All 163 pre-/postoperative VCCs were completed with no adverse events. Conclusion & Implications: The current data support SLT-FPOCC service expansion to include pre and post thyroid/parathyroid surgery VCC checks, with positive consumer perception. The model supports delivery of best practice management (i.e., pre- and postoperative VCC) for patients receiving surgery for thyroid/parathyroid dysfunction, and associated efficiencies for ENT services.

Sandwich panels are used in many industries for the advantageous properties of high stiffness, good strength to weight ratio, and impact resistance. This paper investigates properties of thin-walled cores manufactured through Fused Deposition Modeling (FDM); a process which, through a wider design space, could improve the functionality of sandwich panels. The bond strength between the layers of thin walls manufactured through FDM was evaluated through tensile testing. To measure the effect of modified manufacturing speeds, wall thicknesses were varied through the flow rate and nozzle speed. Honeycomb cores using FDM were produced with different toolpaths, and compared with an example of an industry standard Nomex honeycomb core. During tensile testing, thick-walled FDM components exhibited a more ductile failure with a lower yield point when compared to thinner specimens. The ultimate tensile stress remained constant across samples within each of the tested ABS and PLA polymers used. Honeycomb cores produced using FDM were found to have a higher compressive failure force than Nomex honeycomb, and a lower specific strength. The force–displacement curves of compressive failure show a ductile response for thick specimens, consistent with the previous result. These results, combined with the increased flexibility of additive manufacture technologies, could provide a method of manufacturing high strength cores with complex geometry.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Forgiveness is important for repairing relationships that have been damaged by transgressions. In this research we explored the notion that the mode of physical exercise that victims of transgressions engage in and their capacity to override grudges are important in the process of forgiveness. Two exploratory studies that varied in samples (community non-student adults, undergraduate students) and research methods (non-experimental, experimental) were used to test these predictions. Findings showed that, compared to anaerobic or no exercise, aerobic and flexibility exercise facilitated self-control over grudges and forgiveness (Studies 1 and 2), and self-control over grudges explained the relation between exercise and forgiveness (Study 2). Possible mechanisms for future research are discussed.

The airways are poorly protected from potentially damaging agents contained within gastric contents. While digestive factors are obvious damaging agents, gastric aspiration may also deliver microbial agents, cytokines or food antigens to airway tissues. Direct damage or the triggering of the inflammatory cascade by gastric aspiration is believed to drive airways disease onset and/or progression. Evidence exists from experimental models demonstrating direct instillation of damaging factors to a range of airways epithelia causes damage and/or an inflammatory response. Clinical longitudinal studies have also noted an association between the presence of biomarkers of reflux in airways samples and disease progression. A shared pathophysiology of many chronic airways diseases is a more negative intrathoracic pressure. Such changes would drive an increased abdominothoracic pressure gradient. These changes in respiratory mechanics mean that chronic lung disease patients may be predisposed to reflux and subsequent aspiration. Therefore, it appears that gastric aspiration and airways disease progression may be linked not solely as cause and effect, but seemingly within a vicious cycle. A range of physiological factors govern both occurrence of gastric reflux into the pharynx/larynx and could also increase the susceptibility of certain individuals to disease progression. A range of long-term surgical and pharmacological intervention studies are necessary to test the benefit of such therapies in reducing disease progression or driving symptom improvement. Such studies may be hampered by the reliability of available therapies in halting gastric aspiration and the difficulty in the clinical or biochemical assessment of gastric aspiration.

The climate of the early nineteenth century is likely to have been significantly cooler than that of today, as it was a period of low solar activity (the Dalton minimum) and followed a series of large volcanic eruptions. Proxy reconstructions of the temperature of the period do not agree well on the size of the temperature change, so other observational records from the period are particularly valuable. Weather observations have been extracted from the reports of the noted whaling captain William Scoresby Jr., and from the records of a series of Royal Navy expeditions to the Arctic, preserved in the UK National Archives. They demonstrate that marine climate in 1810–1825 was marked by consistently cold summers, with abundant sea-ice. But although the period was significantly colder than the modern average, there was considerable variability: in the Greenland Sea the summers following the Tambora eruption (1816 and 1817) were noticeably warmer, and had less sea-ice coverage, than the years immediately preceding them; and the sea-ice coverage in Lancaster Sound in 1819 and 1820 was low even by modern standards.

This investigation introduces a novel tool for identifying conscientious responders (CRs) and random responders (RRs) in psychological inventory data. The Conscientious Responders Scale (CRS) is a five-item validity measure that uses instructional items to identify responders. Because each item instructs responders exactly how to answer that particular item, each response can be scored as either correct or incorrect. Given the long odds of answering a CRS item correctly by chance alone on a 7-point scale (14.29%), we reasoned that RRs would answer most items incorrectly, whereas CRs would answer them correctly. This rationale was evaluated in two experiments in which CRs’ CRS scores were compared against RRs’ scores. As predicted, results showed large differences in CRS scores across responder groups. Moreover, the CRS correctly classified responders as either conscientious or random with greater than 93% accuracy. Implications for the reliability and effectiveness of the CRS are discussed.

Low adhesion in the wheel/rail contact or the ‘leaves on the line’ problem is a large operational issue for the railway industry. There is currently a shortage of up to date information about the running conditions of rails with respect to short term adhesion trends (over a daily period) and macro trends (across seasons). This can lead to costly over application of mitigation actions such as rail head cleaning to combat the problem. The generally established methods of assessing areas of low adhesion involve mapping activations of wheel slide and wheel slip protection events to track locations. These methods are reactive and rely upon a slip/slide event to be initiated by the application of traction or braking. The RSSB managed project T959 is forwarding previous fundamental research into methods of low adhesion detection (LAD) in real time using 'modest cost' inertial sensors mounted to in service vehicles. The LAD system proposes that the motions of a railway vehicle (in both lateral and yaw movements) vary as the adhesion conditions under the vehicle change. If the changes in the running dynamics as a result of low adhesion can be observed and interpreted, they can infer the adhesion at all points across a network and not just when slip/slide events are triggered. The main focus of the research has been to use a linearised model of a rail vehicle suspension system to define a Kalman-Bucy filter. The creep forces, that are unable to be measured directly, are outputted from this filter as augmented states. By comparing the estimated values of creep forces against measurablevehicle dynamics, an estimation of adhesion level can be realised. This approach has been verified against rail vehicle simulations performed by DeltaRail using the multi-body physics software VAMPIRE®.

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and phenocopies a muscle precursor that fails to undergo terminal differentiation. The alveolar subtype (ARMS) has the poorest prognosis and represents the greatest unmet medical need for RMS. Emerging evidence supports the role of epigenetic dysregulation in RMS. Here we show that SMARCA4/BRG1, an ATP-dependent chromatin remodeling enzyme of the SWI/SNF complex, is prominently expressed in primary tumors from ARMS patients and cell cultures. Our validation studies for a CRISPR screen of 400 epigenetic targets identified SMARCA4 as a unique factor for long-term (but not short-term) tumor cell survival in ARMS. A SMARCA4/SMARCA2 protein degrader (ACBI-1) demonstrated similar long-term tumor cell dependence in vitro and in vivo. These results credential SMARCA4 as a tumor cell dependency factor and a therapeutic target in ARMS.