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Agitation and aggression occur in up to half of people living with dementia over the course of the disease. Although non-pharmacological interventions are used as first-line treatment strategies, antipsychotics may be indicated in severe cases. A major adverse effect of antipsychotics in dementia is stroke; the mechanism of action of atypical antipsychotic risperidone has been linked to cardiovascular disease (CVD) biological pathways in preclinical studies.
Aims
To evaluate the risk of stroke associated with risperidone across different patient subgroups defined by stroke and CVD history.
Method
Anonymised primary care data from the UK-based Clinical Practice Research Datalink were used to identify individuals diagnosed with dementia after the age of 65 years between 2004 and 2023. Risk of stroke over 1 year was compared between individuals initiating risperidone and propensity-score-matched controls across subgroups with and without history of stroke and any CVD.
Results
In the overall cohort (28 403 risperidone users and 136 324 mtatched controls), risperidone was associated with increased risk of stroke (adjusted hazard ratio: 1.28; 95% CI: 1.20–1.37). In the risperidone user group, the incidence rate of stroke was substantially higher in those with a prior history of stroke (incidence rate: 222 per 1000 person-years) and CVD (incidence rate: 94.1 per 1000 person-years) than in the overall cohort (incidence rate: 53.3 per 1000 person-years). Relative risks related to risperidone were similar across all CVD and stroke subgroup comparisons (hazard ratios between 1.23 and 1.44).
Conclusions
People with dementia with a prior history of CVD are at a significant increased risk of stroke, and risperidone further exacerbates this risk. Moreover, risperidone increases risk of stroke in patients without a prior history of CVD. This quantification of stroke risk across subgroups with and without history of CVD may help with communication of risk and aid more judicious prescribing.
The First Large Absorption Survey in H i (FLASH) is a large-area radio survey for neutral hydrogen in and around galaxies in the intermediate redshift range $0.4\lt z\lt1.0$, using the 21-cm H i absorption line as a probe of cold neutral gas. The survey uses the ASKAP radio telescope and will cover 24,000 deg$^2$ of sky over the next five years. FLASH breaks new ground in two ways – it is the first large H i absorption survey to be carried out without any optical preselection of targets, and we use an automated Bayesian line-finding tool to search through large datasets and assign a statistical significance to potential line detections. Two Pilot Surveys, covering around 3000 deg$^2$ of sky, were carried out in 2019-22 to test and verify the strategy for the full FLASH survey. The processed data products from these Pilot Surveys (spectral-line cubes, continuum images, and catalogues) are public and available online. In this paper, we describe the FLASH spectral-line and continuum data products and discuss the quality of the H i spectra and the completeness of our automated line search. Finally, we present a set of 30 new H i absorption lines that were robustly detected in the Pilot Surveys, almost doubling the number of known H i absorption systems at $0.4\lt z\lt1$. The detected lines span a wide range in H i optical depth, including three lines with a peak optical depth $\tau\gt1$, and appear to be a mixture of intervening and associated systems. Interestingly, around two-thirds of the lines found in this untargeted sample are detected against sources with a peaked-spectrum radio continuum, which are only a minor (5–20%) fraction of the overall radio-source population. The detection rate for H i absorption lines in the Pilot Surveys (0.3 to 0.5 lines per 40 deg$^2$ ASKAP field) is a factor of two below the expected value. One possible reason for this is the presence of a range of spectral-line artefacts in the Pilot Survey data that have now been mitigated and are not expected to recur in the full FLASH survey. A future paper in this series will discuss the host galaxies of the H i absorption systems identified here.
Objectives/Goals: This study assesses the feasibility of a human-to-swine lung transplant model for the evaluation of bioengineered organs. Given the critical organ shortage, this research explores bioengineered organs as a potential solution by evaluating early lung function, immune responses, and technical aspects to develop a model for bioengineered lungs. Methods/Study Population: The study employs a non-survival human-to-swine left lung transplant model in an immunosuppressed Yorkshire swine. A combination of cobra venom factor pretreated with methylprednisolone and Benadryl with scheduled dosing of tacrolimus and mycophenolate over a 24-hour period will be administered. The transplanted human lung is assessed over a 24-hour post-transplant period, with hourly pulmonary vein gas sampling and lung tissue resections. The proposed model will assess the immunological response of swine to human lung tissue as well as the efficacy of the immunosuppression model. Tissue samples are taken at intervals to evaluate for signs of rejection, cellular damage, and the overall function of the transplanted lung. All tissues are preserved in formaldehyde for subsequent immunohistology evaluation. Results/Anticipated Results: We anticipate a successful non-survival swine transplant model with pulmonary function sustained for the full 24-hour study using our proposed immunosuppression regimen. Initial testing with a standard human lung will lay the groundwork to assess the effectiveness of the human-to-swine transplant model. Hourly pulmonary vein gas analyses and tissue biopsies are expected to show minimal immune rejection, supported by the preoperative immunosuppression regimen. Early data indicate that the swine tolerates both the surgical procedure and immunosuppressive therapy well, with manageable hemodynamic stability. This model is expected to yield critical insights into lung viability and will identify areas for optimization for long-term survival studies to test the efficacy of bioengineered organs. Discussion/Significance of Impact: This non-survival swine model offers valuable insights into the acute-phase immune response and functional viability of human-to-swine lung transplant model. The findings will support the development of long-term survival models that will allow the evaluation of bioengineered organs based solely on their functionality as engineered organs.
Task-shared psychological treatments play a critical role in addressing the global mental health treatment gap, yet their integration into routine care requires further study. This study evaluated the causal association between an implementation factor of a task-shared psychological treatment and participant outcomes to strengthen the implementation-to-outcome link within global mental health. This secondary analysis utilized cohort data from the Program for Improving Mental Health Care (PRIME) implemented in Sehore, India where trained non-specialist health workers delivered treatment for depression and alcohol use disorder (AUD). Propensity scores and inverse probability of treatment weights examined the impact of mental health service users’ treatment attendance on users’ symptom severity (PHQ-9 scores for depression; AUDIT scores for AUD) at 3 and 12-month follow-ups. Among the 240 patients with depression, higher treatment session attendance led to 1.3 points lower PHQ-9 scores (vs. no attendance) and 2.4 points lower PHQ-9 scores (vs. low attendance) at 3 months, with no significant effects at 12 months. Among the 190 AUD patients, treatment session attendance did not have a significant impact on AUDIT scores. Our findings have implications for enhancing treatment session attendance among those with depression within task-shared psychological treatments.
Although the basic test for apprehended bias is now well-established in Australian law, its application continues to present difficulties. The basic test is whether a fair-minded lay observer with knowledge of the material objective facts might reasonably apprehend that the judicial or administrative decision-maker might not bring an impartial and unprejudiced mind to the resolution of the question at hand. It is equally well-established that, while the same objective test applies to judges as to tribunal members and other public decision-makers, the application and content of that test varies depending on the context, including differences in decision-making roles, functions, powers and processes.
The application of the test can be problematic and somewhat unpredictable. For example, despite the unqualified terms of the relevant parts of the High Court’s decision in Ebner, it now appears that, at least in the context of curial decision-making, the Ebner two-step test is not universal in its application.
Over the last three years the Commonwealth has enacted four statutes with the aim of overcoming some of the deficiencies which exist at common law in the reviewing of administrative action. These are the Administrative Appeals Tribunal Act 1975 (Cth), the Administrative Appeals Tribunal Amendment Act 1977 (Cth), the Ombudsman Act 1976 (Cth) and the Administrative Decisions (Judicial Review) Act 1977 (Cth). This article examines in detail the Administrative Decisions (Judicial Review) Act 1977 (Cth) in order to determine whether the common law rights and remedies have been improved.
The Magellanic Stream (MS), a tail of diffuse gas formed from tidal and ram pressure interactions between the Small and Large Magellanic Clouds (SMC and LMC) and the Halo of the Milky Way, is primarily composed of neutral atomic hydrogen (HI). The deficiency of dust and the diffuse nature of the present gas make molecular formation rare and difficult, but if present, could lead to regions potentially suitable for star formation, thereby allowing us to probe conditions of star formation similar to those at high redshifts. We search for $\text{HCO}^{+}$, HCN, HNC, and C$_2$H using the highest sensitivity observations of molecular absorption data from the Atacama Large Millimeter Array (ALMA) to trace these regions, comparing with HI archival data from the Galactic Arecibo L-Band Feed Array (GALFA) HI Survey and the Galactic All Sky Survey (GASS) to compare these environments in the MS to the HI column density threshold for molecular formation in the Milky Way. We also compare the line of sight locations with confirmed locations of stars, molecular hydrogen, and OI detections, though at higher sensitivities than the observations presented here.
We find no detections to a 3$\sigma$ significance, despite four sightlines having column densities surpassing the threshold for molecular formation in the diffuse regions of the Milky Way. Here we present our calculations for the upper limits of the column densities of each of these molecular absorption lines, ranging from $3 \times 10^{10}$ to $1 \times 10^{13}$ cm$^{-2}$. The non-detection of $\text{HCO}^{+}$ suggests that at least one of the following is true: (i) $X_{\text{HCO}^{+}{}, \mathrm{MS}}$ is significantly lower than the Milky Way value; (ii) that the widespread diffuse molecular gas observed by Rybarczyk (2022b, ApJ, 928, 79) in the Milky Way’s diffuse interstellar medium (ISM) does not have a direct analogue in the MS; (iii) the HI-to-$\text{H}_{2}$ transition occurs in the MS at a higher surface density in the MS than in the LMC or SMC; or (iv) molecular gas exists in the MS, but only in small, dense clumps.
Evaluate knowledge and beliefs about dietary nitrate among United Kingdom (UK)-based adults.
Design:
An online questionnaire was administered to evaluate knowledge and beliefs about dietary nitrate. Overall knowledge of dietary nitrate was quantified using a twenty-one-point Nitrate Knowledge Index. Responses were compared between socio-demographic groups.
Setting:
UK.
Participants:
A nationally representative sample of 300 adults.
Results:
Only 19 % of participants had heard of dietary nitrate prior to completing the questionnaire. Most participants (∼70 %) were unsure about the effects of dietary nitrate on health parameters (e.g. blood pressure, cognitive function and cancer risk) or exercise performance. Most participants were unsure of the average population intake (78 %) and acceptable daily intake (83 %) of nitrate. Knowledge of dietary sources of nitrate was generally low, with only ∼30 % of participants correctly identifying foods with higher or lower nitrate contents. Almost none of the participants had deliberately purchased, or avoided purchasing, a food based around its nitrate content. Nitrate Knowledge Index scores were generally low (median (interquartile range (IQR)): 5 (8)), but were significantly higher in individuals who were currently employed v. unemployed (median (IQR): 5 (7) v. 4 (7); P < 0·001), in those with previous nutrition education v. no nutrition education (median (IQR): 6 (7) v. 4 (8); P = 0·012) and in individuals who had heard of nitrate prior to completing the questionnaire v. those who had not (median (IQR): 9 (8) v. 4 (7); P < 0·001).
Conclusions:
This study demonstrates low knowledge around dietary nitrate in UK-based adults. Greater education around dietary nitrate may be valuable to help individuals make more informed decisions about their consumption of this compound.
There is an increasing emphasis worldwide on breeding wheat cultivars with higher biomass and grain yield, whilst reducing excessive input of N fertilizers. Modern plant breeding has narrowed the genetic base of bread wheat, so exploring new sources of genetic variation for leaf photosynthesis traits and biomass to underpin grain yield improvement has become necessary. Our objectives were to quantify the genetic variability in a range of landrace-derived lines and elite bread wheat genotypes in flag-leaf photosynthesis traits, biomass and N-use efficiency for potential application in pre-breeding. Sixteen bread wheat genotypes including elite spring wheat cultivar Paragon × landrace crosses were tested in two field experiments in the UK. Averaging across years, pre-anthesis flag-leaf photosynthesis rate ranged amongst genotypes from 26.0 to 31.5 μmol/m2/s (P < 0.001) and post-anthesis from 14.2 to 18.6 μmol/m2/s (P < 0.001). Two landrace-derived lines had greater post-anthesis flag-leaf photosynthesis rate (P < 0.001) than their elite parent Paragon. There was a trend for a positive correlation among genotypes between post-anthesis flag-leaf photosynthesis rate and biomass (r = 0.47, P = 0.06). Two landrace derivatives showed higher post-anthesis flag-leaf stomatal conductance than Paragon. Our results indicated that introgression of traits from wider germplasm into elite UK modern wheat germplasm offers scope to raise flag-leaf photosynthetic rate and biomass.
Early life stress (ELS) and a Western diet (WD) promote mood and cardiovascular disorders, however, how these risks interact in disease pathogenesis is unclear. We assessed effects of ELS with or without a subsequent WD on behaviour, cardiometabolic risk factors, and cardiac function/ischaemic tolerance in male mice. Fifty-six new-born male C57BL/6J mice were randomly allocated to a control group (CON) undisturbed before weaning, or to maternal separation (3h/day) and early (postnatal day 17) weaning (MSEW). Mice consumed standard rodent chow (CON, n = 14; MSEW, n = 15) or WD chow (WD, n = 19; MSEW + WD, n = 19) from week 8 to 24. Fasted blood was sampled and open field test and elevated plus maze (EPM) tests undertaken at 7, 15, and 23 weeks of age, with hearts excised at 24 weeks for Langendorff perfusion (evaluating pre- and post-ischaemic function). MSEW alone transiently increased open field activity at 7 weeks; body weight and serum triglycerides at 4 and 7 weeks, respectively; and final blood glucose levels and insulin resistance at 23 weeks. WD increased insulin resistance and body weight gain, the latter potentiated by MSEW. MSEW + WD was anxiogenic, reducing EPM open arm activity vs. WD alone. Although MSEW had modest metabolic effects and did not influence cardiac function or ischaemic tolerance in lean mice, it exacerbated weight gain and anxiogenesis, and improved ischaemic tolerance in WD fed animals. MSEW-induced increases in body weight (obesity) in WD fed animals in the absence of changes in insulin resistance may have protected the hearts of these mice.
Estimates suggest that 1 in 100 people in the UK live with facial scarring. Despite this incidence, psychological support is limited.
Aims
The aim of this study was to strengthen the case for improving such support by determining the incidence and risk factors for anxiety and depression disorders in patients with facial scarring.
Method
A matched cohort study was performed. Patients were identified via secondary care data sources, using clinical codes for conditions resulting in facial scarring. A diagnosis of anxiety or depression was determined by linkage with the patient's primary care general practice data. Incidence was calculated per 1000 person-years at risk (PYAR). Logistic regression was used to determine risk factors.
Results
Between 2009 and 2018, 179 079 patients met the study criteria and were identified as having a facial scar, and matched to 179 079 controls. The incidence of anxiety in the facial scarring group was 10.05 per 1000 PYAR compared with 7.48 per 1000 PYAR for controls. The incidence of depression in the facial scarring group was 16.28 per 1000 PYAR compared with 9.56 per 1000 PYAR for controls. Age at the time of scarring, previous history of anxiety or depression, female gender, socioeconomic status and classification of scarring increased the risk of both anxiety disorders and depression.
Conclusions
There is a high burden of anxiety disorders and depression in this patient group. Risk of these mental health disorders is very much determined by factors apparent at the time of injury, supporting the need for psychological support.
We present the first unbiased survey of neutral hydrogen absorption in the Small Magellanic Cloud. The survey utilises pilot neutral hydrogen observations with the Australian Square Kilometre Array Pathfinder telescope as part of the Galactic Australian Square Kilometre Array Pathfinder neutral hydrogen project whose dataset has been processed with the Galactic Australian Square Kilometre Array Pathfinder-HI absorption pipeline, also described here. This dataset provides absorption spectra towards 229 continuum sources, a 275% increase in the number of continuum sources previously published in the Small Magellanic Cloud region, as well as an improvement in the quality of absorption spectra over previous surveys of the Small Magellanic Cloud. Our unbiased view, combined with the closely matched beam size between emission and absorption, reveals a lower cold gas faction (11%) than the 2019 ATCA survey of the Small Magellanic Cloud and is more representative of the Small Magellanic Cloud as a whole. We also find that the optical depth varies greatly between the Small Magellanic Cloud’s bar and wing regions. In the bar we find that the optical depth is generally low (correction factor to the optically thin column density assumption of $\mathcal{R}_{\mathrm{HI}} \sim 1.04$) but increases linearly with column density. In the wing however, there is a wide scatter in optical depth despite a tighter range of column densities.
Little is known about mental health problems of children and young people (CYP) involved with public and private law family court proceedings, and how these CYP fare compared to those not involved in these significant disruptions to family life.
Aims
This study examined records of depression/anxiety in CYP involved in public and private law proceedings using linked population-level data across Wales.
Method
Retrospective e-cohort study. We calculated the incidence of primary-care-recorded depression/anxiety among CYP involved in these proceedings and in a comparison group, using Poisson regression. Depression/anxiety outcomes following proceedings were evaluated using pairwise Cox regression, with age- and gender-matched controls of CYP who had no involvement with the courts.
Results
CYP in the public group had twice the risk of depression (adjusted incidence rate ratio aIRR = 2.2; 95% CI 1.9–2.6) and 20% higher risk of anxiety (aIRR = 1.2; 95% CI 1.0–1.5) relative to the comparison group. The private group had 60% higher risk of depression (aIRR = 1.6; 95% CI 1.4–1.7) and 30% higher risk of anxiety (aIRR = 1.3; 95% CI 1.2–1.4). Following private law proceedings, CYP were more likely to have depression (hazard ratio HR = 1.9; 95% CI 1.7–2.1), and anxiety (HR = 1.4; 95% CI 1.2–1.6) than the control group. Following public proceedings, CYP were more likely to have depression (HR = 2.1; 95% CI 1.7–2.5). Incidence of anxiety or depression following court proceedings was around 4%.
Conclusions
Findings highlight the vulnerability of CYP involved in family court proceedings and increased risk of depression and anxiety. Schools, health professionals, social and family support workers have a role to play in identifying needs and ensuring CYP receive appropriate support before, during and after proceedings.
To determine the impact of electronic health record (EHR)–based interventions and test restriction on Clostridioides difficile tests (CDTs) and hospital-onset C. difficile infection (HO-CDI).
Design:
Quasi-experimental study in 3 hospitals.
Setting:
957-bed academic (hospital A), 354-bed (hospital B), and 175-bed (hospital C) academic-affiliated community hospitals.
Interventions:
Three EHR-based interventions were sequentially implemented: (1) alert when ordering a CDT if laxatives administered within 24 hours (January 2018); (2) cancellation of CDT orders after 24 hours (October 2018); (3) contextual rule-driven order questions requiring justification when laxative administered or lack of EHR documentation of diarrhea (July 2019). In February 2019, hospital C implemented a gatekeeper intervention requiring approval for all CDTs after hospital day 3. The impact of the interventions on C. difficile testing and HO-CDI rates was estimated using an interrupted time-series analysis.
Results:
C. difficile testing was already declining in the preintervention period (annual change in incidence rate [IR], 0.79; 95% CI, 0.72–0.87) and did not decrease further with the EHR interventions. The laxative alert was temporally associated with a trend reduction in HO-CDI (annual change in IR from baseline, 0.85; 95% CI, 0.75–0.96) at hospitals A and B. The gatekeeper intervention at hospital C was associated with level (IRR, 0.50; 95% CI, 0.42-0.60) and trend reductions in C. difficile testing (annual change in IR, 0.91; 95% CI, 0.85–0.98) and level (IRR 0.42; 95% CI, 0.22–0.81) and trend reductions in HO-CDI (annual change in IR, 0.68; 95% CI, 0.50–0.92) relative to the baseline period.
Conclusions:
Test restriction was more effective than EHR-based clinical decision support to reduce C. difficile testing in our 3-hospital system.
To evaluate broad-spectrum intravenous antibiotic use before and after the implementation of a revised febrile neutropenia management algorithm in a population of adults with hematologic malignancies.
Design:
Quasi-experimental study.
Setting and population:
Patients admitted between 2014 and 2018 to the Adult Malignant Hematology service of an acute-care hospital in the United States.
Methods:
Aggregate data for adult malignant hematology service were obtained for population-level antibiotic use: days of therapy (DOT), C. difficile infections, bacterial bloodstream infections, intensive care unit (ICU) length of stay, and in-hospital mortality. All rates are reported per 1,000 patient days before the implementation of an febrile neutropenia management algorithm (July 2014–May 2016) and after the intervention (June 2016–December 2018). These data were compared using interrupted time series analysis.
Results:
In total, 2,014 patients comprised 6,788 encounters and 89,612 patient days during the study period. Broad-spectrum intravenous (IV) antibiotic use decreased by 5.7% with immediate reductions in meropenem and vancomycin use by 22 (P = .02) and 15 (P = .001) DOT per 1,000 patient days, respectively. Bacterial bloodstream infection rates significantly increased following algorithm implementation. No differences were observed in the use of other antibiotics or safety outcomes including C. difficile infection, ICU length of stay, and in-hospital mortality.
Conclusions:
Reductions in vancomycin and meropenem were observed following the implementation of a more stringent febrile neutropenia management algorithm, without evidence of adverse outcomes. Successful implementation occurred through a collaborative effort and continues to be a core reinforcement strategy at our institution. Future studies evaluating patient-level data may identify further stewardship opportunities in this population.
The Rapid ASKAP Continuum Survey (RACS) is the first large-area survey to be conducted with the full 36-antenna Australian Square Kilometre Array Pathfinder (ASKAP) telescope. RACS will provide a shallow model of the ASKAP sky that will aid the calibration of future deep ASKAP surveys. RACS will cover the whole sky visible from the ASKAP site in Western Australia and will cover the full ASKAP band of 700–1800 MHz. The RACS images are generally deeper than the existing NRAO VLA Sky Survey and Sydney University Molonglo Sky Survey radio surveys and have better spatial resolution. All RACS survey products will be public, including radio images (with $\sim$ 15 arcsec resolution) and catalogues of about three million source components with spectral index and polarisation information. In this paper, we present a description of the RACS survey and the first data release of 903 images covering the sky south of declination $+41^\circ$ made over a 288-MHz band centred at 887.5 MHz.
This work investigated the photophysical pathways for light absorption, charge generation, and charge separation in donor–acceptor nanoparticle blends of poly(3-hexylthiophene) and indene-C60-bisadduct. Optical modeling combined with steady-state and time-resolved optoelectronic characterization revealed that the nanoparticle blends experience a photocurrent limited to 60% of a bulk solution mixture. This discrepancy resulted from imperfect free charge generation inside the nanoparticles. High-resolution transmission electron microscopy and chemically resolved X-ray mapping showed that enhanced miscibility of materials did improve the donor–acceptor blending at the center of the nanoparticles; however, a residual shell of almost pure donor still restricted energy generation from these nanoparticles.
Across the globe, there has been a marked increase in longevity, but significant inequalities remain. These are exacerbated by inadequate access to proper nutrition and health care services and to reliable information to make the decisions related to nutrition and health care. Many in economically developing as well as developed societies are plagued with the double-burden of energy excess and undernutrition. This has resulted in mental and physical deterioration, increased non-communicable disease rates, lost productivity, increased medical costs and reduced quality of life. While adequate nutrition is fundamental to good health at all stages of the life course, the impact of diet on prolonging good quality of life during ageing remains unclear. For progress to continue, there is need for new and/or innovative approaches to promoting health as individuals age, as well as qualitative and quantitative biomarkers and other accepted tools that can measure improvements in physiological integrity throughout life. A framework for progress has been proposed by the World Health Organization in their Global Strategy and Action Plan on Ageing and Health. Here, we focused on the impact of nutrition within this framework, which takes a broad, person-centred emphasis on healthy ageing, stressing the need to better understand each individual's intrinsic capacity, their functional abilities at various life stages, and the impact of their mental, and physical health, as well as the environments they inhabit.