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Abstract From 1979 to 2016, total Antarctic sea ice extent experienced a positive trend with record winter maxima in 2012 and 2014. Record summer minima followed within the period 2017-2024, raising the possibility that the Antarctic sea ice system might be changing state. Here we use a Bayesian reconstruction of Antarctic sea ice extent which extends the record back to 1899, to show that the sequence of extreme minima in summer Antarctic sea ice extent is unlikely to have happened in the 20th century. We show that they represent a structural change in the sea ice system, manifest by increased persistence in the sea ice extent anomalies and a strongly reduced tendency to return to the mean state. Further, our analysis suggests that we may no longer rely on the past, long-term, behavior of the sea ice system to predict its future state. Extreme conditions may characterize the future state of Antarctic sea ice.

Abstract Background Blood pressure (BP) control following stroke is important but currently sub-optimal. This trial aimed to determine whether self-monitoring of hypertension with telemonitoring and a treatment escalation protocol, results in lower BP than usual care in people with previous stroke or transient ischaemic attack (TIA). Methods Unblinded randomised controlled trial, comparing a BP telemonitoring-based intervention with control (usual care) for hypertension management in 12 primary care practices in England. People with previous stroke or TIA with clinic systolic BP 130–180 mmHg, taking ≤ 3 antihypertensive medications and on stable treatment for at least four weeks were randomised 1:1 using secure online system to intervention or control. The BP:Together intervention comprised self-monitoring of blood pressure with a digital behavioural intervention which supported telemonitoring of self-monitored BP with feedback to clinicians and patients regarding medication titration. The planned primary outcome was difference in clinic measured systolic BP 12 months from randomisation but was not available following early study termination due to withdrawal of funding during the COVID-19 pandemic. Instead, in addition to pre-randomised data, routinely recorded BP was extracted from electronic patient records both pre- and post-randomisation and presented descriptively only. An intention to treat approach was taken. Results From 650 postal invitations, 129 (20%) responded, of whom 95 people had been screened for eligibility prior to the pandemic (November 2019-March 2020) and 55 (58%) were randomised. Pre-randomisation routinely recorded mean BP was 145/78 mmHg in the control (n = 26) and 145/79 mmHg in the self-monitoring (n = 21) groups. Post-randomisation mean BP was 134/73 mmHg in the control (n = 19) and 130/75 mmHg in the self-monitoring (n = 25) groups. Participants randomised to self-monitoring used the intervention for ≥ 7 months in 25/27 (93%) of cases. Conclusions Recruitment of people with stroke/TIA to a trial comparing a BP self-monitoring and digital behavioural intervention to usual care was feasible prior to the COVID-19 pandemic and the vast majority of those randomised to intervention used it while the trial was running. Routinely recorded blood pressure control improved in both groups. Digital interventions including self-monitoring are feasible for people with stroke/TIA and should be definitively evaluated in future trials. Trial registration ISRCTN57946500 06/09/2019 Prospective.

Background: The purpose of this study is to evaluate survivorship and outcomes of high-activity patients compared to low-activity patients after total hip arthroplasty. Methods: A retrospective review identified 2002 patients (2532 hip) that underwent a primary total hip arthroplasty with vitamin E–infused highly crosslinked polyethylene liner. Patients were divided into 2 groups based on their University of California Los Angeles (UCLA) activity level: low activity (LA) (UCLA ≤5) and high activity (HA) (UCLA ≥6). Outcomes included Harris Hip Score, UCLA activity score, and reoperations. A multivariate nominal regression analysis was performed to evaluate the significance of postoperative activity level on survivorship. Results: The mean follow-up duration was 4.5 years (range, 0.3 to 9.9 years). HA group had significantly higher improvements in Harris Hip Score (HHS) (P < .001) and UCLA activity score (P < .001). Aseptic revisions were performed in 2.1% of the LA group and in 0.4% hips of the HA group (P < .001). After controlling for age, gender, preoperative pain, HHS, and body mass index, a higher postoperative activity level remained a significant factor for improved aseptic survivorship with an odds ratio of 4.9 (95% confidence interval, 1.1 to 21.2, P = .03). The all-cause 5-year survivorship was 99% for the HA group and 96% to for the LA group (P < .001). The aseptic 5-year survivorship was 99.6% for the HA group and 98% for the LA group (P < .001). Conclusions: This study found that a higher activity level after primary THA was not deleterious to survivorship at short to midterm follow-up with modern implants.

Reanalysis products are an invaluable tool for representing variability and long-term trends in regions with limited in situ data, and especially the Antarctic. A comparison of eight different reanalysis products shows large differences in sea level pressure and surface air temperature trends over the high-latitude Southern Ocean, with implications for studies of the atmosphere's role in driving ocean–sea ice changes. In this study, we use the established close coupling between sea ice cover and surface temperature to evaluate these reanalysis trends using the independent, 30-year sea ice record from 1980 to 2010. We demonstrate that sea ice trends are a reliable validation tool for most months of the year, although the sea ice–surface temperature coupling is weakest in summer when the surface energy budget is dominated by atmosphere-to-ocean heat fluxes. Based on our analysis, we find that surface air temperature trends in JRA55 are most consistent with satellite-observed sea ice trends over the polar waters of the Southern Ocean.

Abstract Background Excess weight and unexpected weight loss are associated with multiple disease states and increased morbidity and mortality, but weight measurement is not routine in many primary care settings. The aim of this study was to characterise who has had their weight recorded in UK primary care, how frequently, by whom and in relation to which clinical events, symptoms and diagnoses. Methods A longitudinal analysis of UK primary care electronic health records (EHR) data from 2000 to 2017. Descriptive statistics were used to summarise weight recording in terms of patient sociodemographic characteristics, health professional encounters, clinical events, symptoms and diagnoses. Negative binomial regression was used to model the likelihood of having a weight record each year, and Cox regression to the likelihood of repeated weight recording. Results A total of 14,049,871 weight records were identified in the EHR of 4,918,746 patients during the study period, representing 26,998,591 person-years of observation. Around a third of patients had a weight record each year. Forty-nine percent of weight records were repeated within a year with an average time to a repeat weight record of 1.92 years. Weight records were most often taken by nursing staff (38–42%) and GPs (37–39%) as part of a routine clinical care, such as chronic disease reviews (16%), medication reviews (6–8%) and health checks (6–7%), or were associated with consultations for contraception (5–8%), respiratory disease (5%) and obesity (1%). Patient characteristics independently associated with an increased likelihood of weight recording were as follows: female sex, younger and older adults, non-drinkers, ex-smokers, low or high BMI, being more deprived, diagnosed with a greater number of comorbidities and consulting more frequently. The effect of policy-level incentives to record weight did not appear to be sustained after they were removed. Conclusion Weight recording is not a routine activity in UK primary care. It is recorded for around a third of patients each year and is repeated on average every 2 years for these patients. It is more common in females with higher BMI and in those with comorbidity. Incentive payments and their removal appear to be associated with increases and decreases in weight recording.

Aims: Veterans from the 1990–91 Gulf War were exposed to acetylcholinesterase inhibitors (AChEIs), and, following service, an estimated one-third began suffering from a medically unexplained, multi-symptom illness termed Gulf War Illness (GWI). Previous research has developed validated rodent models that include exposure to exogenous corticosterone (CORT) and AChEIs to simulate high stress and chemical exposures encountered in theater. This combination of exposures in mice resulted in a marked increase in neuroinflammation, which is a common symptom of veterans suffering from GWI. To further elucidate the mechanisms associated with these mouse models of GWI, an investigation into intracellular responses in the cortex were performed to characterize the early cellular signaling changes associated with this exposure-initiated neuroinflammation. Main methods: Adult male C57BL/6J mice were exposed to CORT in the drinking water (200 μg/mL) for 7 days followed by a single intraperitoneal injection of diisopropyl fluorophosphate (DFP; 4.0 mg/kg) or chlorpyrifos oxon (CPO; 8.0 mg/kg), on day 8 and euthanized 0.5, 2, and 24 h post-injection. Eleven post-translationally modified protein targets were measured using a multiplexed ELISA. Key findings: Phosphoprotein responses were found to be exposure specific following AChEI insult, with and without CORT. Specifically, CORT + CPO exposure was found to sequentially activate several phosphoproteins involved in mitogen activated protein kinase signaling (p-MEK1/2, p-ERK1/2, and p-JNK). DFP alone similarly increased proteins in this pathway (p-RPS6, and p-JNK), but the addition of CORT ameliorated these affects. Significance: The results of this study provide insight into differentially activated pathways depending on AChEI in these GWI models.

Abstract Background A structured approach to perioperative patient management based on an enhanced recovery pathway protocol facilitates early recovery and reduces morbidity in high income countries. However, in low- and middle-income countries (LMICs), the feasibility of implementing enhanced recovery pathways and its influence on patient outcomes is scarcely investigated. To inform similar practice in LMICs for total hip and knee arthroplasty, it is necessary to identify potential factors for inclusion in such a programme, appropriate for LMICs. Methods Applying a Delphi method, 33 stakeholders (13 arthroplasty surgeons, 12 anaesthetists and 8 physiotherapists) from 10 state hospitals representing 4 South African provinces identified and prioritised i) risk factors associated with poor outcomes, ii) perioperative interventions to improve outcomes and iii) patient and clinical outcomes necessary to benchmark practice for patients scheduled for primary elective unilateral total hip and knee arthroplasty. Results Thirty of the thirty-three stakeholders completed the 3 months Delphi study. The first round yielded i) 36 suggestions to preoperative risk factors, ii) 14 (preoperative), 18 (intraoperative) and 23 (postoperative) suggestions to best practices for perioperative interventions to improve outcomes and iii) 25 suggestions to important postsurgical outcomes. These items were prioritised by the group in the consecutive rounds and consensus was reached for the top ten priorities for each category. Conclusion The consensus derived risk factors, perioperative interventions and important outcomes will inform the development of a structured, perioperative multidisciplinary enhanced patient care protocol for total hip and knee arthroplasty. It is anticipated that this study will provide the construct necessary for developing pragmatic enhanced care pathways aimed at improving patient outcomes after arthroplasty in LMICs.

Abstract Background Unexpected weight loss is a symptom of serious disease in primary care, for example between 1 in 200 and 1 in 30 patients with unexpected weight loss go on to develop cancer. However, it remains unclear how and when general practitioners (GPs) should investigate unexpected weight loss. Without clarification, GPs may wait too long before referring (choosing to watch and wait and potentially missing a diagnosis) or not long enough (overburdening hospital services and exposing patients to the risks of investigation). The overall aim of this study is to provide the evidence necessary to allow GPs to more effectively manage patients with unexpected weight loss. Methods A retrospective cohort analysis of UK Clinical Practice Research Datalink (CPRD) data to: (1) describe how often in UK primary care the symptom of reported weight loss is coded, when weight is measured, and how GPs respond to a patient attending with unexpected weight loss; (2) identify the predictive value of recorded weight loss for cancer and serious disease in primary care, using cumulative incidence plots to compare outcomes between subgroups and Cox regression to explore and adjust for covariates. Preliminary work in CPRD estimates that weight loss as a symptom is recorded for approximately 148,000 eligible patients > 18 years and is distributed evenly across decades of age, providing adequate statistical power and precision in relation to cancer overall and common cancers individually. Further stratification by cancer stage will be attempted but may not be possible as not all practices within CPRD are eligible for cancer registry linkage, and staging information is often incomplete. The feasibility of using multiple imputation to address missing covariate values will be explored. Discussion This will be the largest reported retrospective cohort of primary care patients with weight measurements and unexpected weight loss codes used to understand the association between weight measurement, unexpected weight loss, and serious disease including cancer. Our findings will directly inform international guidelines for the management of unexpected weight loss in primary care populations.

Working with individuals with intellectual disabilities presents unique opportunities and challenges. In addition to challenges presented by having a disability (e.g., communicating with others), is the obscurity of coordination of services within an often fragmented service delivery system. One response has been to create a system that brings together various professionals responsible for an individual's care and identify possible courses of action to address identified concerns, both medical and behavioral. In this paper, we discuss development of the team, describe changes that have resulted in improved processes, and highlight some of the successful outcomes. We also discuss implications for policies and practices related to working via such an approach and its benefits.

BACKGROUND:Perfluoroalkyl substances (PFASs) have been associated with decreased immunity to childhood tetanus and diphtheria immunizations. If these vaccinations are vulnerable to influence from PFASs, questions arise about associations with other common inoculations. OBJECTIVE:To examine whether serum PFASs were associated with reduced immunity to rubella immunization, and whether interactions with sex or ethnicity warranted analytic stratification. Usually, toxicology analyses are calculated controlling for race and sex. However, sex differences in immune function have been reported and a reduction of immunity to rubella in women could pose risks such miscarriage. METHODS:We analyzed a nationally representative sample of individuals ≥ 12 years from the National Health and Nutrition Examination Survey (NHANES) for years 1999-2000 and 2003-2004 for whom PFAS measures were available. Our analytic strategy was to start with separate analyses for youth and adults controlling for several covariates including ethnicity and sex, as well as the interaction of these terms with PFASs. If there was a main effect of PFASs and an interaction term, we would stratify analyses of effect size. The outcome variable was Rubella IgG titers by quartile of perfluoroalkyl substances. RESULTS:After exclusion for missing data, the analyzed sample contained 581 adult women, 621 adult men, and 1012 youth. There was no significant effect of PFASs on immunity in youths but a significant effect of both PFOA and PFOS in adults, as well as a significant interaction of PFOA x sex and a borderline significant interaction of PFOS x sex. When effect size analyses were stratified by sex, a significant association between rubella titres and PFOA was found in men but not women and PFOS was not significant in either sex. CONCLUSIONS:These results support our earlier studies showing sex specific responses to PFASs and indicate the importance of thinking carefully about analytic strategies in population based toxicology research.

Between 1940 and 2005, in the United States, the rate of unnatural death declined about 75 percent in infant and young child boys and girls; a remarkable indicator of successful child protection. During this same period, the rate of reported homicide in infant boys increased 64.0 percent, in infant girls increased 43.5 percent, in young child boys increased 333.3 percent, and in young child girls increased 300.0 percent, a dismal and disturbing indicator of failed child protection. Can these simultaneously encouraging and discouraging observations be reconciled? The four categories of unnatural death, homicide, suicide, motor vehicle accident (MVA), and non-MVA, are mutually exclusive classifications. Correlations between the four categories of unnatural death among U.S. men and woman in all age groups for the years 1940 through 2005 were calculated. A negative correlation between homicide and non-MVA death rates was shown for all age groups, encompassing the entire human lifespan, in both genders. This consistently observed negative correlation was only observed between homicide and non-MVA death rates, and was not demonstrated between other causes of unnatural deaths. Moreover, this negative correlation was strongest (less than −0.7) in infants and young children. These observations are consistent with the suggestion that as the rate of unnatural death in infants and young children dramatically declined, society gave greater scrutiny to those fewer occurring unnatural deaths and demonstrated an increasing propensity to assign blame for those fewer deaths.