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The Australian SKA Pathfinder (ASKAP) offers powerful new capabilities for studying the polarised and magnetised Universe at radio wavelengths. In this paper, we introduce the Polarisation Sky Survey of the Universe’s Magnetism (POSSUM), a groundbreaking survey with three primary objectives: (1) to create a comprehensive Faraday rotation measure (RM) grid of up to one million compact extragalactic sources across the southern $\sim50$% of the sky (20,630 deg$^2$); (2) to map the intrinsic polarisation and RM properties of a wide range of discrete extragalactic and Galactic objects over the same area; and (3) to contribute interferometric data with excellent surface brightness sensitivity, which can be combined with single-dish data to study the diffuse Galactic interstellar medium. Observations for the full POSSUM survey commenced in May 2023 and are expected to conclude by mid-2028. POSSUM will achieve an RM grid density of around 30–50 RMs per square degree with a median measurement uncertainty of $\sim$1 rad m$^{-2}$. The survey operates primarily over a frequency range of 800–1088 MHz, with an angular resolution of 20” and a typical RMS sensitivity in Stokes Q or U of 18 $\mu$Jy beam$^{-1}$. Additionally, the survey will be supplemented by similar observations covering 1296–1440 MHz over 38% of the sky. POSSUM will enable the discovery and detailed investigation of magnetised phenomena in a wide range of cosmic environments, including the intergalactic medium and cosmic web, galaxy clusters and groups, active galactic nuclei and radio galaxies, the Magellanic System and other nearby galaxies, galaxy halos and the circumgalactic medium, and the magnetic structure of the Milky Way across a very wide range of scales, as well as the interplay between these components. This paper reviews the current science case developed by the POSSUM Collaboration and provides an overview of POSSUM’s observations, data processing, outputs, and its complementarity with other radio and multi-wavelength surveys, including future work with the SKA.
In natural settings, newborn calves hide for several days before joining the herd. It is unclear whether dairy calves housed indoors would show similar hiding behaviour. This study aimed to describe the use of an artificial hide provided to calves during temporary separation from the dam and assess the effect it has on lying and sleep-like behaviour, as well as heart rate variability (HRV). Twenty-eight cow-calf pairs were randomly assigned to having a hide (n = 14), or no hide (n = 14). Hide use (n = 14), as well as lying and sleep-like behaviour (n = 28), were recorded continuously via video camera during the first hour after the dam was removed for morning milking on day three to seven. Heart rate and R-R intervals were recorded using Polar equine monitors for a subsample of 12 calves (n = 6 per treatment) on day six. Descriptive statistics were calculated for hide use. Wilcoxon Signed Rank tests were used to evaluate whether having a hide affected lying and sleep-like behaviours as well as HRV. Hide use decreased over days and was highly variable between calves. Lying behaviour did not differ between treatments. Duration of sleep-like behaviour was higher for calves without a hide compared to those with a hide. Calves with a hide tended to show signs of higher HRV and parasympathetic activity compared to calves without a hide. Results suggest that providing a hiding space to young calves may be beneficial during periods when the cow is removed from the pen for milking.
Radiotherapy is an ever-changing field with constant technological advances. It is for this reason that risk management strategies are regularly updated in order to remain optimal.
Methodology:
A retrospective audit of all reported incidents and near misses in the audited department between 1 November 2020 and 30 April 2021 was performed. The root cause of each radiotherapy error (RTE), safety barrier (SB) and the causative factor (CF) would be defined by the Public Health England (PHE) coding system. The data will then be analysed to determine if there are any frequently occurring errors and if there are any existing relationships between multiple error.
Results:
670 patients were treated during the study period along with 35 reports generated. 77·1% (n = 27) were incidents, and 22·9% (n = 8) were near misses. 2·8% (n = 1) were reportable incidents. The ratio of RTEs to prescriptions was 0·052:1 (5·2%). 37% of RTEs were associated with image production. Slips and lapses were involved in 54·2%. Adherence to procedures/protocols was a factor in 48·5% (n = 17). Communication was a factor in 11·4% (n = 4).
Discussion:
The proportion of Level 1 incidents was higher in this department (2·8%) than in the PHE report (0·9%). Almost one-third, 31·4% (n = 11) of errors stemmed from one technical fault in image production. SB breaches were prevalent at the pre-treatment planning stage of the pathway. A relationship between slips/lapses and non-conformance to protocols was identified.
Conclusion:
The rate of reported radiotherapy incidents in the UK is lower when compared with this department; this could be improved with the implementation of the quality improvement plan outlined above.
Clinical trials are a vital component of translational science, providing crucial information on the efficacy and safety of new interventions and forming the basis for regulatory approval and/or clinical adoption. At the same time, they are complex to design, conduct, monitor, and report successfully. Concerns over the last two decades about the quality of the design and the lack of completion and reporting of clinical trials, characterized as a lack of “informativeness,” highlighted by the experience during the COVID-19 pandemic, have led to several initiatives to address the serious shortcomings of the United States clinical research enterprise.
Methods and Results:
Against this background, we detail the policies, procedures, and programs that we have developed in The Rockefeller University Center for Clinical and Translational Science (CCTS), supported by a Clinical and Translational Science Award (CTSA) program grant since 2006, to support the development, conduct, and reporting of informative clinical studies.
Conclusions:
We have focused on building a data-driven infrastructure to both assist individual investigators and bring translational science to each element of the clinical investigation process, with the goal of both generating new knowledge and accelerating the uptake of that knowledge into practice.
The COVID-19 pandemic substantially impacted care of patients with schizophrenia treated with long-acting injectable antipsychotics (LAIs). This study examined how clinics adapted operations to maintain a standard of care for these patients after pandemic onset.
Methods
Online surveys were completed in October-November 2020 by one principal investigator (PI) or PI-appointed designee at 35 clinics participating in OASIS (NCT03919994). Items concerned pandemic impacts on clinic operations, particularly telepsychiatry, and on the care of patients with schizophrenia treated with LAIs.
Results
All 35 clinics reported using telepsychiatry; 20 (57%) implemented telepsychiatry after pandemic onset. Telepsychiatry visits increased from 12%-15% to 45%-69% across outpatient visit types after pandemic onset; frequency of no-show and/or canceled telepsychiatry visits decreased by approximately one-third. Nearly half of clinics increased the frequency of telepsychiatry visits for patients with schizophrenia treated with LAIs. Approximately one-third of participants each reported switching patients treated with LAIs to longer injection interval LAIs or to oral antipsychotics. The most common system/clinic- and patient-related barrier for telepsychiatry visits was lower reimbursement rate and access to technology/reliable internet, respectively. Almost all participants (94%) were satisfied with telepsychiatry for maintaining care of patients with schizophrenia treated with LAIs; most predicted a hybrid of telepsychiatry and office visits post-pandemic.
Conclusions
Changes made by clinics after pandemic onset were viewed by almost all participants as satisfactory for maintaining a standard of care for patients with schizophrenia treated with LAIs. Most participants predicted continuing telepsychiatry to support patient care post-pandemic; equitable access to telepsychiatry will be important in this regard.
Clinically significant weight gain (CSWG) is associated with increased morbidity and mortality. This study describes CSWG and comorbidities observed in patients with bipolar I disorder (BD-I) and schizophrenia (SZ) after initiating select second-generation antipsychotics (SGAs).
Methods
Percent change in weight, CSWG (=7% weight increase), and incident comorbidities within 12 months of treatment were assessed among patients initiating oral SGAs of moderate-to-high weight gain risk using medical records/claims (OM1 Real-World Data Cloud; January 2013-February 2020). Oral SGAs included clozapine (SZ), iloperidone (SZ), paliperidone (SZ), olanzapine, olanzapine/fluoxetine (BD-I), quetiapine, and risperidone. Outcomes were stratified by baseline body mass index and reported descriptively.
Results
Among patients with BD-I (N = 9142) and SZ (N = 8174), approximately three-quarters were overweight/obese at baseline. During treatment (mean duration = 30 weeks), average percent weight increase was 3.7% (BD-I) and 3.3% (SZ). Average percent weight increase was highest for underweight/normal weight patients (BD-I = 5.5%; SZ = 4.8%), followed by overweight (BD-I = 3.8%; SZ = 3.4%) and obese patients (BD-I = 2.7%; SZ = 2.3%). Within 3 months of treatment, 12% of all patients experienced CSWG. A total of 11.3% (BD-I) and 14.7% (SZ) of patients developed coronary artery disease, hypertension, dyslipidemia, or type 2 diabetes within 12 months of treatment; development of comorbidities was highest among overweight/obese patients and those with CSWG.
Conclusions
Patients who were underweight/normal weight at baseline had the greatest percent change in weight during treatment. Increased comorbidities were observed within 12 months of treatment, specifically among overweight/obese patients and those with CSWG. The magnitude of weight gain and development of comorbidities were similar for patients with BD-I and SZ.
Informal carers play an essential role in the care of individuals with Parkinson’s disease (PD). This role, however, is often fraught with difficulties, including emotional, physical, and financial. Coping styles and relationship quality have been hypothesized to influence the impact of stressors. The aim of this study is to examine the relationship between carers’ coping style, relationship quality, and carer burden.
Design:
Cross-sectional.
Participants:
Thirty-nine PD patient carer dyads were included in the study.
Measurements:
Participants completed self-rated questionnaires including the Dyadic Adjustment Scale, Zarit Burden Interview, and Brief Coping Orientation to Problems Experienced Inventory.
Results:
Correlational analyses found significant and positive correlation between carer burden and all three coping styles (problem-focused, emotion-focused, and dysfunctional). There was also a moderate association between carers’ perceived relationship quality and satisfaction and carer burden. Regression analyses found that carer’s gender, severity of PD, relationship quality, emotion-focused, and dysfunctional coping styles did not predict carer burden. Conversely, problem-focused coping style predicted carer burden.
Conclusion:
The results highlight that there is no perfect way to react and care for a loved one and serves as important information for practitioners who design and implement interventions.
An open-label extension study (NCT02873208) evaluated the long-term tolerability, safety, and efficacy of combination olanzapine/samidorphan (OLZ/SAM) treatment in patients with schizophrenia. This qualitative sub study explored perceptions of benefit, burden, and satisfaction with previous medications and OLZ/SAM.
Methods
Semi-structured interviews (60 minutes; audio-recorded) were conducted. Interviewer sensitivity training, senior interviewer oversight, and a list of common medications to aid recall supported data collection. Interview transcripts were content coded and analyzed (NVivo v11.0).
Results
All 41 patients reported a lifetime burden with schizophrenia adversely impacting employment, relationships, emotional health, social activities, and daily tasks. Hospitalization for schizophrenia management was another reported aspect of disease burden. Although most (n=32) patients reported previous medication benefits, side effects affecting physical, emotional/behavioral, and cognitive functioning were reported by all (n=41). Following OLZ/SAM treatment, 39/41 patients (95%) reported improvements in symptoms including hallucinations, paranoia, depression, sleep, and concentration. Furthermore, patients described improvements in self-esteem, social activities, relationships, and daily activities. Twenty-three patients (56%) reported side effects attributed to OLZ/SAM; lack of energy (n=12 [29%]) and dry mouth (n= 5 [12%]) were most common. Twenty-four (59%) patients were “very satisfied” with OLZ/SAM; most (n=35 [85%]) preferred to continue OLZ/SAM vs switching to another medication. As most substudy patients (n=40; 98%) completed the extension study, satisfied patients may be overrepresented in this analysis.
Conclusion
This qualitative interview approach provided valuable insight into patients’ experiences with previous medications and OLZ/SAM. Overall, most patients reported treatment satisfaction and improvements in symptoms, function, and health-related quality of life with OLZ/SAM.
Among patients with schizophrenia (SZ) and bipolar I disorder (BD-I) treated with second-generation antipsychotics (SGAs), clinically-significant weight gain (CSWG) and treatment interruptions (TIs) are challenges that may result in morbidity/mortality.
CSWG and TIs were assessed among patients who initiated oral SGAs of moderate-to-high weight gain risk (no exposure to index SGAs/first-generation antipsychotics for =12 months) using medical records/claims (OM1 Data Cloud; January 2013-February 2020). Outcomes included CSWG (=7% increase in baseline weight) and TIs (switches [to SGAs of low weight gain risk/long-acting injectables] or discontinuations [no SGAs for >30 days]). Descriptive analyses included proportions of patients with CSWG and TIs, and median time to these outcomes.
Approximately three-quarters of patients were overweight/obese at baseline (SZ: N=8,174; BD-I: N=9,142). Within 3 months of SGA initiation, 12% of all patients experienced CSWG. For patients on treatment with index SGAs for >6 months (SZ: 29%; BD-I: 27%), 28% (SZ) and 30% (BD-I) experienced CSWG during follow-up. Median time to CSWG was 14 weeks. CSWG results were numerically similar among patients with SZ and BD-I.
Over 96% of patients had TIs during follow-up (median time of 12 [SZ] and 13 [BD-I] weeks). Among patients with CSWG and subsequent TIs and weight measurements, 74% did not return to baseline weight after interrupting treatment; the remainder returned to baseline weight with median times of 38 (SZ) and 39 (BD-I) weeks. Results suggest that most patients with CSWG do not return to baseline weight after stopping treatment with oral SGAs of moderate-to-high weight gain risk.
We present the first Faraday rotation measure (RM) grid study of an individual low-mass cluster—the Fornax cluster—which is presently undergoing a series of mergers. Exploiting commissioning data for the POlarisation Sky Survey of the Universe’s Magnetism (POSSUM) covering a ${\sim}34$ square degree sky area using the Australian Square Kilometre Array Pathfinder (ASKAP), we achieve an RM grid density of ${\sim}25$ RMs per square degree from a 280-MHz band centred at 887 MHz, which is similar to expectations for forthcoming GHz-frequency ${\sim}3\pi$-steradian sky surveys. These data allow us to probe the extended magnetoionic structure of the cluster and its surroundings in unprecedented detail. We find that the scatter in the Faraday RM of confirmed background sources is increased by $16.8\pm2.4$ rad m−2 within 1$^\circ$ (360 kpc) projected distance to the cluster centre, which is 2–4 times larger than the spatial extent of the presently detectable X-ray-emitting intracluster medium (ICM). The mass of the Faraday-active plasma is larger than that of the X-ray-emitting ICM and exists in a density regime that broadly matches expectations for moderately dense components of the Warm-Hot Intergalactic Medium. We argue that forthcoming RM grids from both targeted and survey observations may be a singular probe of cosmic plasma in this regime. The morphology of the global Faraday depth enhancement is not uniform and isotropic but rather exhibits the classic morphology of an astrophysical bow shock on the southwest side of the main Fornax cluster, and an extended, swept-back wake on the northeastern side. Our favoured explanation for these phenomena is an ongoing merger between the main cluster and a subcluster to the southwest. The shock’s Mach angle and stand-off distance lead to a self-consistent transonic merger speed with Mach 1.06. The region hosting the Faraday depth enhancement also appears to show a decrement in both total and polarised radio emission compared to the broader field. We evaluate cosmic variance and free-free absorption by a pervasive cold dense gas surrounding NGC 1399 as possible causes but find both explanations unsatisfactory, warranting further observations. Generally, our study illustrates the scientific returns that can be expected from all-sky grids of discrete sources generated by forthcoming all-sky radio surveys.
Diet has a major influence on the composition and metabolic output of the gut microbiome. Higher-protein diets are often recommended for older consumers; however, the effect of high-protein diets on the gut microbiota and faecal volatile organic compounds (VOC) of elderly participants is unknown. The purpose of the study was to establish if the faecal microbiota composition and VOC in older men are different after a diet containing the recommended dietary intake (RDA) of protein compared with a diet containing twice the RDA (2RDA). Healthy males (74⋅2 (sd 3⋅6) years; n 28) were randomised to consume the RDA of protein (0⋅8 g protein/kg body weight per d) or 2RDA, for 10 weeks. Dietary protein was provided via whole foods rather than supplementation or fortification. The diets were matched for dietary fibre from fruit and vegetables. Faecal samples were collected pre- and post-intervention for microbiota profiling by 16S ribosomal RNA amplicon sequencing and VOC analysis by head space/solid-phase microextraction/GC-MS. After correcting for multiple comparisons, no significant differences in the abundance of faecal microbiota or VOC associated with protein fermentation were evident between the RDA and 2RDA diets. Therefore, in the present study, a twofold difference in dietary protein intake did not alter gut microbiota or VOC indicative of altered protein fermentation.
The common C677T polymorphism in the MTHFR gene encoding the folate-metabolising enzyme methylenetetrahydrofolate reductase is implicated in hypertension and hypertension in pregnancy. Hypertension affects up to 15% of all pregnancies and has been identified as a leading cause of maternal and neonatal morbidity and mortality worldwide. We previously reported higher systolic and diastolic blood pressure (BP) in non-pregnant women with the variant MTHFR 677TT genotype compared to CT/CC genotypes. In addition, randomised controlled trials (RCTs) in non-pregnant hypertensive adults from our Centre demonstrated that supplemental riboflavin (co-factor for MTHFR) lowers BP specifically in those with the TT genotype. However, the role of this common folate polymorphism and its interaction with riboflavin during pregnancy remains unclear. The aim of this study was to investigate the impact of MTHFR genotype and riboflavin status on BP in pregnancy. Data were generated from the ongoing Optimal Nutrition for the Prevention of Hypertension (OptiPREG) project. Pregnant women were recruited at the end of the first trimester from antenatal clinics in Northern Ireland and in the Republic of Ireland. Participants were screened for MTHFR genotype and BP was measured according to current clinical guidelines. Biomarker status of riboflavin was determined using the erythrocyte glutathione reductase activation coefficient (EGRac), a functional assay with higher EGRac values representing a lower status. Overall, 117 (11.6%) participants were identified with the variant MTHFR 677TT genotype. Both systolic and diastolic BP decreased from 8th to 16th gestational week (GW), however, this typical BP pattern was not observed in the TT genotype group. After adjusting for maternal age, GW and body mass index, women with the TT genotype at 12th GW had higher mean systolic (P 0.035) and diastolic (P 0.034) BP. When the results at the 12th GW were stratified by riboflavin status, the BP phenotype owing to this polymorphism was evident only among women with lower status (i.e. EGRac > 1.30), with mean (SEM) systolic BP of 120.4 (3.1) mmHg compared to 112.6 (2.5) mmHg in those with higher status (EGRac ≤ 1.30) within the TT genotype group; in contrast, low versus high riboflavin status had no impact on BP in CT/CC genotype groups. These results suggest that MTHFR genotype influences BP during pregnancy and that riboflavin can exert an important modulating effect on BP in women with TT genotype. An RCT is required to fully investigate the role of MTHFR genotype and its interactive effect with riboflavin in BP during pregnancy.
Stigma and social exclusion related to mental health are of substantial public health importance for Europe. As part of ROAMER (ROAdmap for MEntal health Research in Europe), we used systematic mapping techniques to describe the current state of research on stigma and social exclusion across Europe. Findings demonstrate growing interest in this field between 2007 and 2012. Most studies were descriptive (60%), focused on adults of working age (60%) and were performed in Northwest Europe—primarily in the UK (32%), Finland (8%), Sweden (8%) and Germany (7%). In terms of mental health characteristics, the largest proportion of studies investigated general mental health (20%), common mental disorders (16%), schizophrenia (16%) or depression (14%). There is a paucity of research looking at mechanisms to reduce stigma and promote social inclusion, or at factors that might promote resilience or protect against stigma/social exclusion across the life course. Evidence is also limited in relation to evaluations of interventions. Increasing incentives for cross-country research collaborations, especially with new EU Member States and collaboration across European professional organizations and disciplines, could improve understanding of the range of underpinning social and cultural factors which promote inclusion or contribute toward lower levels of stigma, especially during times of hardship.
Current techniques for measuring the dry matter intake (DMI) of grazing lactating beef cows are invasive, time consuming and expensive making them impractical for use on commercial farms. This study was undertaken to explore the potential to develop and validate a model to predict DMI of grazing lactating beef cows, which could be applied in a commercial farm setting, using non-invasive animal measurements. The calibration dataset used to develop the model was comprised of 94 measurements recorded on 106 beef or beef–dairy crossbred cows (maternal origin). The potential of body measurements, linear type scoring, grazing behaviour and thermal imaging to predict DMI in combination with known biologically plausible adjustment variables and energy sinks was investigated. Multivariable regression models were constructed for each independent variable using SAS PROC REG and contained milk yield, BW, parity, calving day and maternal origin (dairy or beef). Of the 94 variables tested, 32 showed an association with DMI (P < 0.25) upon multivariable analysis. These variables were incorporated into a backwards linear regression model using SAS PROC REG. Variables were retained in this model if P < 0.05. Five variables; width at pins, full body depth, ruminating mastications, central ligament and rump width score, were retained in the model in addition to milk yield, BW, parity, calving day and maternal origin. The inclusion of these variables in the model increased the predictability of DMI by 0.23 (R2 = 0.68) when compared to a model containing milk yield, BW, parity, calving day and maternal origin only. This model was applied to data recorded on an independent dataset; a herd of 60 lactating beef cows two years after the calibration study. The R2 for the validation was 0.59. Estimates of DMI are required for measuring feed efficiency. While acknowledging challenges in applicability, the findings suggest a model such as that developed in this study may be used as a tool to more easily and less invasively estimate DMI on large populations of commercial beef cows, and therefore measure feed efficiency.