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Exercise has been found to be important in maintaining neurocognitive health. However, the effect of exercise intensity level remains relatively underexplored. Thus, to test the hypothesis that self-paced high-intensity exercise and cardiorespiratory fitness (peak aerobic capacity; VO2peak) increase grey matter (GM) volume, we examined the effect of a 6-month exercise intervention on frontal lobe GM regions that support the executive functions in older adults.
Ninety-eight cognitively normal participants (age = 69.06 ± 5.2 years; n = 54 female) were randomised into either a self-paced high- or moderate-intensity cycle-based exercise intervention group, or a no-intervention control group. Participants underwent magnetic resonance imaging and fitness assessment pre-intervention, immediately post-intervention, and 12-months post-intervention.
The intervention was found to increase fitness in the exercise groups, as compared with the control group (F = 9.88, p = <0.001). Changes in pre-to-post-intervention fitness were associated with increased volume in the right frontal lobe (β = 0.29, p = 0.036, r = 0.27), right supplementary motor area (β = 0.30, p = 0.031, r = 0.29), and both right (β = 0.32, p = 0.034, r = 0.30) and left gyrus rectus (β = 0.30, p = 0.037, r = 0.29) for intervention, but not control participants. No differences in volume were observed across groups.
At an aggregate level, six months of self-paced high- or moderate-intensity exercise did not increase frontal GM volume. However, experimentally-induced changes in individual cardiorespiratory fitness was positively associated with frontal GM volume in our sample of older adults. These results provide evidence of individual variability in exercise-induced fitness on brain structure.
A chloroacetamide herbicide by application timing factorial experiment was conducted in 2017 and 2018 in Mississippi to investigate chloroacetamide use in a dicamba-based Palmer amaranth management program in cotton production. Herbicides used were S-metolachlor or acetochlor, and application timings were preemergence, preemergence followed by (fb) early postemergence, preemergence fb late postemergence, early postemergence alone, late postemergence alone, and early postemergence fb late postemergence. Dicamba was included in all preemergence applications, and dicamba plus glyphosate was included with all postemergence applications. Differences in cotton and weed response due to chloroacetamide type were minimal, and cotton injury 14 d after LP application was less than 10% for all application timings. Late-season weed control was reduced up to 30 and 53% if chloroacetamide application occurred PRE or LP only, respectively. Late-season weed densities were minimized if multiple applications were used instead of a single application. Cotton height was reduced by up to 23% if a single application was made LP relative to other application timings. Chloroacetamide application at any timing except PRE alone minimized late season weed biomass. Yield was maximized by any treatment involving multiple applications or EP alone whereas applications PRE or LP alone resulted in up to 56 and 27% yield losses, respectively. While no yield loss was reported by delaying the first of sequential applications until EP, foregoing a PRE application is not advisable given the multiple factors that may delay timely POST applications such as inclement weather.
Scanning transmission electron microscopy (STEM) allows for imaging, diffraction, and spectroscopy of materials on length scales ranging from microns to atoms. By using a high-speed, direct electron detector, it is now possible to record a full two-dimensional (2D) image of the diffracted electron beam at each probe position, typically a 2D grid of probe positions. These 4D-STEM datasets are rich in information, including signatures of the local structure, orientation, deformation, electromagnetic fields, and other sample-dependent properties. However, extracting this information requires complex analysis pipelines that include data wrangling, calibration, analysis, and visualization, all while maintaining robustness against imaging distortions and artifacts. In this paper, we present py4DSTEM, an analysis toolkit for measuring material properties from 4D-STEM datasets, written in the Python language and released with an open-source license. We describe the algorithmic steps for dataset calibration and various 4D-STEM property measurements in detail and present results from several experimental datasets. We also implement a simple and universal file format appropriate for electron microscopy data in py4DSTEM, which uses the open-source HDF5 standard. We hope this tool will benefit the research community and help improve the standards for data and computational methods in electron microscopy, and we invite the community to contribute to this ongoing project.
Intrauterine preeclampsia exposure affects the lifelong cardiometabolic health of the child. Our study aimed to compare the growth (from birth to 6 months) of infants exposed to either a normotensive pregnancy or preeclampsia and explore the influence of being born small for gestational age (SGA). Participants were children of women participating in the Post-partum, Physiology, Psychology and Paediatric follow-up cohort study. Birth and 6-month weight and length z-scores were calculated for term and preterm (<37 weeks) babies, and change in weight z-score, rapid weight gain (≥0.67 increase in weight z-score) and conditional weight gain z-score were calculated. Compared with normotensive exposed infants (n = 298), preeclampsia exposed infants (n = 84) were more likely to be born SGA (7% versus 23%; P < 0.001), but weight gain from birth to 6 months, by any measure, did not differ between groups. Infants born SGA, irrespective of pregnancy exposure, were more likely to have rapid weight gain and had greater increases in weight z-score compared with those not born SGA. Preeclampsia exposed infants born SGA may benefit from interventions designed to prevent future cardiometabolic disease.
Research on political representation demonstrates that the presence of historically underrepresented groups in political office (descriptive representation) can have not only a substantive impact on policies and procedures but also a symbolic impact that changes the attitudes and even behavior of those groups. The dynamics of group identity and its significance for representation, however, are complicated. Individuals often hold multiple identities, and the meanings attached to those identities may vary in relation to each other and to the particular political context. In this article, we provide an intersectional analysis of two minoritized ethno-racial groups, African Americans and Latinos/as. Using data from the 2016 Collaborative Multiracial Post-Election Survey, we explore the extent to which shared identity matters for perceptions of representation. Our findings demonstrate that while shared identity does influence perceptions of representation, the impact varies in complicated ways that are simultaneously raced and gendered.
When presenting with a first episode of psychosis (FEP), migrants can have different demographic and clinical characteristics to the native-born population and this was examined in an Irish Early Intervention for Psychosis service.
All cases of treated FEP from three local mental health services within a defined catchment area were included. Psychotic disorder diagnoses were determined using the SCID and symptom and functioning domains were measured using validated and reliable measures.
From a cohort of 612 people, 21.1% were first-generation migrants and there was no difference in the demographic characteristics, diagnoses, symptoms or functioning between migrants and those born in the Republic of Ireland, except that migrants from Africa presented with less insight. Of those admitted, 48.6% of admissions for migrants were involuntary compared to 37.7% for the native-born population (p = 0.09).
First-generation migrants now make up a significant proportion of people presenting with a FEP to an Irish EI for psychosis service. Broadly the demographic and clinical characteristics of migrants and those born in the Republic of Ireland are similar, except for less insight in migrants from Africa and a trend for a higher proportion of involuntary admissions in the total migrant group.
Platinum-based chemotherapy drugs are associated with substantial ototoxicity. The hearing of children treated with these drugs should be closely monitored.
A questionnaire was sent out to the 19 audiology departments associated with national paediatric cancer specialist centres in the UK looking at current practice in ototoxicity monitoring.
Responses were received from 17 of 19 centres (89 per cent). All offered some form of audiometric monitoring service. Extended high-frequency testing (9–20 kHz) was only utilised by 7 services (29 per cent). A majority of respondents were reluctant to consider self-test devices in paediatric ototoxicity monitoring (n = 9; 53 per cent). Provision of long-term audiological follow up is sporadic with only 4 (23 per cent) respondents keeping all children with normal hearing under review once treatment is completed.
While some good practice in paediatric ototoxicity was identified, opportunities exist to improve clinical practice and protocols, promote multidisciplinary team working and to utilise technologies such as extended high frequency and self-test audiometry.
Typical enteropathogenic Escherichia coli (tEPEC) infection is a major cause of diarrhoea and contributor to mortality in children <5 years old in developing countries. Data were analysed from the Global Enteric Multicenter Study examining children <5 years old seeking care for moderate-to-severe diarrhoea (MSD) in Kenya. Stool specimens were tested for enteric pathogens, including by multiplex polymerase chain reaction for gene targets of tEPEC. Demographic, clinical and anthropometric data were collected at enrolment and ~60-days later; multivariable logistic regressions were constructed. Of 1778 MSD cases enrolled from 2008 to 2012, 135 (7.6%) children tested positive for tEPEC. In a case-to-case comparison among MSD cases, tEPEC was independently associated with presentation at enrolment with a loss of skin turgor (adjusted odds ratio (aOR) 2.08, 95% confidence interval (CI) 1.37–3.17), and convulsions (aOR 2.83, 95% CI 1.12–7.14). At follow-up, infants with tEPEC compared to those without were associated with being underweight (OR 2.2, 95% CI 1.3–3.6) and wasted (OR 2.5, 95% CI 1.3–4.6). Among MSD cases, tEPEC was associated with mortality (aOR 2.85, 95% CI 1.47–5.55). This study suggests that tEPEC contributes to morbidity and mortality in children. Interventions aimed at defining and reducing the burden of tEPEC and its sequelae should be urgently investigated, prioritised and implemented.
Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.
Individuals who experience serious mental health disorders are at an increased risk of physical illness co-morbidity and early intervention is crucial. Recommendations to embed an exercise physiologist service into a mental health service have not been fully evaluated.
This study aimed to determine (i) demographics and clinical characteristics of the young people referred to exercise physiology, (ii) adherence to metabolic monitoring, (iii) baseline physical health and (iv) level of engagement after referral.
This is a naturalistic cohort study and included all young people referred to the exercise physiology service between 2015 and 2019 at Orygen, a specialist youth mental health service in the north-western region of Melbourne.
During the study period of 45 months, 312 young people were referred to exercise physiology, and of those, 51.3% were male. The mean age was 19.8 years. In regard to primary diagnoses, 47.4% had a psychotic disorder and 33.7% an affective disorder. Baseline weight measurements were completed for 71.8% of young people. The proportion of young people who were classified as overweight or obese increased from 55.1% to 70.4% (p < 0.001). For those referred, 61.5% attended either an individual session or a group session. A total of 29.5% did not attend their appointment following referral.
As over half of young people had poor physical health at presentation, integrating an exercise physiology service into a youth mental health service is a novel and needed intervention. However, there still needs to be an emphasis on metabolic monitoring and engagement.
The radiocarbon (14C) calibration curve so far contains annually resolved data only for a short period of time. With accelerator mass spectrometry (AMS) matching the precision of decay counting, it is now possible to efficiently produce large datasets of annual resolution for calibration purposes using small amounts of wood. The radiocarbon intercomparison on single-year tree-ring samples presented here is the first to investigate specifically possible offsets between AMS laboratories at high precision. The results show that AMS laboratories are capable of measuring samples of Holocene age with an accuracy and precision that is comparable or even goes beyond what is possible with decay counting, even though they require a thousand times less wood. It also shows that not all AMS laboratories always produce results that are consistent with their stated uncertainties. The long-term benefits of studies of this kind are more accurate radiocarbon measurements with, in the future, better quantified uncertainties.
Previous genetic association studies have failed to identify loci robustly associated with sepsis, and there have been no published genetic association studies or polygenic risk score analyses of patients with septic shock, despite evidence suggesting genetic factors may be involved. We systematically collected genotype and clinical outcome data in the context of a randomized controlled trial from patients with septic shock to enrich the presence of disease-associated genetic variants. We performed genomewide association studies of susceptibility and mortality in septic shock using 493 patients with septic shock and 2442 population controls, and polygenic risk score analysis to assess genetic overlap between septic shock risk/mortality with clinically relevant traits. One variant, rs9489328, located in AL589740.1 noncoding RNA, was significantly associated with septic shock (p = 1.05 × 10–10); however, it is likely a false-positive. We were unable to replicate variants previously reported to be associated (p < 1.00 × 10–6 in previous scans) with susceptibility to and mortality from sepsis. Polygenic risk scores for hematocrit and granulocyte count were negatively associated with 28-day mortality (p = 3.04 × 10–3; p = 2.29 × 10–3), and scores for C-reactive protein levels were positively associated with susceptibility to septic shock (p = 1.44 × 10–3). Results suggest that common variants of large effect do not influence septic shock susceptibility, mortality and resolution; however, genetic predispositions to clinically relevant traits are significantly associated with increased susceptibility and mortality in septic individuals.
Raw milk cheeses are commonly consumed in France and are also a common source of foodborne outbreaks (FBOs). Both an FBO surveillance system and a laboratory-based surveillance system aim to detect Salmonella outbreaks. In early August 2018, five familial FBOs due to Salmonella spp. were reported to a regional health authority. Investigation identified common exposure to a raw goats' milk cheese, from which Salmonella spp. were also isolated, leading to an international product recall. Three weeks later, on 22 August, a national increase in Salmonella Newport ST118 was detected through laboratory surveillance. Concomitantly isolates from the earlier familial clusters were confirmed as S. Newport ST118. Interviews with a selection of the laboratory-identified cases revealed exposure to the same cheese, including exposure to batches not included in the previous recall, leading to an expansion of the recall. The outbreak affected 153 cases, including six cases in Scotland. S. Newport was detected in the cheese and in the milk of one of the producer's goats. The difference in the two alerts generated by this outbreak highlight the timeliness of the FBO system and the precision of the laboratory-based surveillance system. It is also a reminder of the risks associated with raw milk cheeses.
Introduction: For rhythm control of acute atrial flutter (AAFL) in the emergency department (ED), choices include initial drug therapy or initial electrical cardioversion (ECV). We compared the strategies of pharmacological cardioversion followed by ECV if necessary (Drug-Shock), and ECV alone (Shock Only). Methods: We conducted a randomized, blinded, placebo-controlled trial (1:1 allocation) comparing two rhythm control strategies at 11 academic EDs. We included stable adult patients with AAFL, where onset of symptoms was <48 hours. Patients underwent central web-based randomization stratified by site. The Drug-Shock group received an infusion of procainamide (15mg/kg over 30 minutes) followed 30 minutes later, if necessary, by ECV at 200 joules x 3 shocks. The Shock Only group received an infusion of saline followed, if necessary, by ECV x 3 shocks. The primary outcome was conversion to sinus rhythm for ≥30 minutes at any time following onset of infusion. Patients were followed for 14 days. The primary outcome was evaluated on an intention-to-treat basis. Statistical significance was assessed using chi-squared tests and multivariable logistic regression. Results: We randomized 76 patients, and none was lost to follow-up. The Drug-Shock (N = 33) and Shock Only (N = 43) groups were similar for all characteristics including mean age (66.3 vs 63.4 yrs), duration of AAFL (30.1 vs 24.5 hrs), previous AAFL (72.7% vs 69.8%), median CHADS2 score (1 vs 1), and mean initial heart rate (128.9 vs 126.0 bpm). The Drug-Shock and Shock only groups were similar for the primary outcome of conversion (100% vs 93%; absolute difference 7.0%, 95% CI -0.6;14.6; P = 0.25). The multivariable analyses confirmed the similarity of the two strategies (P = 0.19). In the Drug-Shock group 21.2% of patients converted with the infusion. There were no statistically significant differences for time to conversion (84.2 vs 97.6 minutes), total ED length of stay (9.4 vs 7.5 hours), disposition home (100% vs 95.3%), and stroke within 14 days (0 vs 0). Premature discontinuation of infusion (usually for transient hypotension) was more common in the Drug-Shock group (9.1% vs 0.0%) but there were no serious adverse events. Conclusion: Both the Drug-Shock and Shock Only strategies were highly effective and safe in allowing AAFL patients to go home in sinus rhythm. IV procainamide alone was effective in only one fifth of patients, much less than for acute AF.
Introduction: CAEP recently developed the acute atrial fibrillation (AF) and flutter (AFL) [AAFF] Best Practices Checklist to promote optimal care and guidance on cardioversion and rapid discharge of patients with AAFF. We sought to assess the impact of implementing the Checklist into large Canadian EDs. Methods: We conducted a pragmatic stepped-wedge cluster randomized trial in 11 large Canadian ED sites in five provinces, over 14 months. All hospitals started in the control period (usual care), and then crossed over to the intervention period in random sequence, one hospital per month. We enrolled consecutive, stable patients presenting with AAFF, where symptoms required ED management. Our intervention was informed by qualitative stakeholder interviews to identify perceived barriers and enablers for rapid discharge of AAFF patients. The many interventions included local champions, presentation of the Checklist to physicians in group sessions, an online training module, a smartphone app, and targeted audit and feedback. The primary outcome was length of stay in ED in minutes from time of arrival to time of disposition, and this was analyzed at the individual patient-level using linear mixed effects regression accounting for the stepped-wedge design. We estimated a sample size of 800 patients. Results: We enrolled 844 patients with none lost to follow-up. Those in the control (N = 316) and intervention periods (N = 528) were similar for all characteristics including mean age (61.2 vs 64.2 yrs), duration of AAFF (8.1 vs 7.7 hrs), AF (88.6% vs 82.9%), AFL (11.4% vs 17.1%), and mean initial heart rate (119.6 vs 119.9 bpm). Median lengths of stay for the control and intervention periods respectively were 413.0 vs. 354.0 minutes (P < 0.001). Comparing control to intervention, there was an increase in: use of antiarrhythmic drugs (37.4% vs 47.4%; P < 0.01), electrical cardioversion (45.1% vs 56.8%; P < 0.01), and discharge in sinus rhythm (75.3% vs. 86.7%; P < 0.001). There was a decrease in ED consultations to cardiology and medicine (49.7% vs 41.1%; P < 0.01), but a small but insignificant increase in anticoagulant prescriptions (39.6% vs 46.5%; P = 0.21). Conclusion: This multicenter implementation of the CAEP Best Practices Checklist led to a significant decrease in ED length of stay along with more ED cardioversions, fewer ED consultations, and more discharges in sinus rhythm. Widespread and rigorous adoption of the CAEP Checklist should lead to improved care of AAFF patients in all Canadian EDs.
Introduction: Acute heart failure (AHF) is a common emergency department (ED) presentation and may be associated with poor outcomes. Conversely, many patients rapidly improve with ED treatment and may not need hospital admission. Because there is little evidence to guide disposition decisions by ED and admitting physicians, we sought to create a risk score for predicting short-term serious outcomes (SSO) in patients with AHF. Methods: We conducted prospective cohort studies at 9 tertiary care hospital EDs from 2007 to 2019, and enrolled adult patients who required treatment for AHF. Each patient was assessed for standardized real-time clinical and laboratory variables, as well as for SSO (defined as death within 30 days or intubation, non-invasive ventilation (NIV), myocardial infarction, coronary bypass surgery, or new hemodialysis after admission). The fully pre-specified, logistic regression model with 13 predictors (age, pCO2, and SaO2 were modeled using spline functions with 3 knots and heart rate and creatinine with 5 knots) was fitted to the 10 multiple imputation datasets. Harrell's fast stepdown procedure reduced the number of variables. We calculated the potential impact on sensitivity (95% CI) for SSO and hospital admissions and estimated a sample size of 170 SSOs. Results: The 2,246 patients had mean age 77.4 years, male sex 54.5%, EMS arrival 41.1%, IV NTG 3.1%, ED NIV 5.2%, admission on initial visit 48.6%. Overall there were 174 (7.8%) SSOs including 70 deaths (3.1%). The final risk scale is comprised of five variables (points) and had c-statistic of 0.76 (95% CI: 0.73-0.80): 1.Valvular heart disease (1) 2.ED non-invasive ventilation (2) 3.Creatinine 150-300 (1) ≥300 (2) 4.Troponin 2x-4x URL (1) ≥5x URL (2) 5.Walk test failed (2) The probability of SSO ranged from 2.0% for a total score of 0 to 90.2% for a score of 10, showing good calibration. The model was stable over 1,000 bootstrap samples. Choosing a risk model total point admission threshold of >2 would yield a sensitivity of 80.5% (95% CI 73.9-86.1) for SSO with no change in admissions from current practice (48.6% vs 48.7%). Conclusion: Using a large prospectively collected dataset, we created a concise and sensitive risk scale to assist with admission decisions for patients with AHF in the ED. Implementation of this risk scoring scale should lead to safer and more efficient disposition decisions, with more high-risk patients being admitted and more low-risk patients being discharged.
Introduction: An important challenge physicians face when treating acute heart failure (AHF) patients in the emergency department (ED) is deciding whether to admit or discharge, with or without early follow-up. The overall goal of our project was to improve care for AHF patients seen in the ED while avoiding unnecessary hospital admissions. The specific goal was to introduce hospital rapid referral clinics to ensure AHF patients were seen within 7 days of ED discharge. Methods: This prospective before-after study was conducted at two campuses of a large tertiary care hospital, including the EDs and specialty outpatient clinics. We enrolled AHF patients ≥50 years who presented to the ED with shortness of breath (<7 days). The 12-month before (control) period was separated from the 12-month after (intervention) period by a 3-month implementation period. Implementation included creation of rapid access AHF clinics staffed by cardiology and internal medicine, and development of referral procedures. There was extensive in-servicing of all ED staff. The primary outcome measure was hospital admission at the index visit or within 30 days. Secondary outcomes included mortality and actual access to rapid follow-up. We used segmented autoregression analysis of the monthly proportions to determine whether there was a change in admissions coinciding with the introduction of the intervention and estimated a sample size of 700 patients. Results: The patients in the before period (N = 355) and the after period (N = 374) were similar for age (77.8 vs. 78.1 years), arrival by ambulance (48.7% vs 51.1%), comorbidities, current medications, and need for non-invasive ventilation (10.4% vs. 6.7%). Comparing the before to the after periods, we observed a decrease in hospital admissions on index visit (from 57.7% to 42.0%; P <0.01), as well as all admissions within 30 days (from 65.1% to 53.5% (P < 0.01). The autoregression analysis, however, demonstrated a pre-existing trend to fewer admissions and could not attribute this to the intervention (P = 0.91). Attendance at a specialty clinic, amongst those discharged increased from 17.8% to 42.1% (P < 0.01) and the median days to clinic decreased from 13 to 6 days (P < 0.01). 30-day mortality did not change (4.5% vs. 4.0%; P = 0.76). Conclusion: Implementation of rapid-access dedicated AHF clinics led to considerably increased access to specialist care, much reduced follow-up times, and possible reduction in hospital admissions. Widespread use of this approach can improve AHF care in Canada.
Tobacco smoking is a leading cause of preventable death and disease worldwide. Adults with mental ill-health smoke tobacco at substantially higher rates than other adults, with public health approaches effective in the population overall having less impact on those with mental ill-health. However, less is known about the tobacco smoking behaviours, attitudes and knowledge of young people with mental ill-health, despite this being the peak period of onset for both mental illness and cigarette smoking.
Young people attending a youth mental health centre (providing both primary and specialist care) in Melbourne, Australia were approached by youth peer researchers and asked to complete a survey about smoking behaviours, attitudes and knowledge. We examined smoking and associated attitudes in the sample overall, and as a function of the services accessed.
In total, 114 young people completed the survey, with 56.3% reporting lifetime cigarette smoking, 42.0% smoking in the last 12 months and 28.6% in the past week. Of current regular smokers, 75.0% acknowledged they should quit in the future; however, only 23.5% planned to do so in the next month, with 44.4% confident that they could quit. Participants lacked knowledge about interactions between tobacco smoking, mental and physical health.
Youth presenting for mental ill-health had high rates of cigarette smoking relative to population rates. Presentation at youth mental health services may represent a critical window for early intervention to reduce the lifetime impacts of cigarette smoking in mental ill-health. Interventions to support smoking cessation in this group are urgently needed.