An Improved Algorithm For Unmixing First‐Order Reversal Curve Diagrams Using Principal Component Analysis

First‐order reversal curve (FORC) diagrams of synthetic binary mixtures with single‐domain, vortex state, and multi‐domain end members (EMs) were analyzed using principal component analysis (FORC‐PCA). Mixing proportions derived from FORC‐PCA are shown to deviate systematically from the known weight percent of EMs, which is caused by the lack of reversible magnetization contributions to the FORC distribution. The error in the mixing proportions can be corrected by applying PCA to the raw FORCs, rather than to the processed FORC diagram, thereby capturing both reversible and irreversible contributions to the signal. Here we develop a new practical implementation of the FORC‐PCA method that enables quantitative unmixing to be performed routinely on suites of FORC diagrams with up to four distinct EMs. The method provides access not only to the processed FORC diagram of each EM, but also to reconstructed FORCs, which enables objective criteria to be defined that aid identification of physically realistic EMs. We illustrate FORC‐PCA with examples of quantitative unmixing of magnetic components that will have widespread applicability in paleomagnetism and environmental magnetism

A two-year participatory intervention project with owners to reduce lameness and limb abnormalities in working horses in Jaipur, India

Participatory methods are increasingly used in international human development, but scientific evaluation of their efficacy versus a control group is rare. Working horses support families in impoverished communities. Lameness and limb abnormalities are highly prevalent in these animals and a cause for welfare concern. We aimed to stimulate and evaluate improvements in lameness and limb abnormalities in horses whose owners took part in a 2-year participatory intervention project to reduce lameness (PI) versus a control group (C) in Jaipur, India.In total, 439 owners of 862 horses participated in the study. PI group owners from 21 communities were encouraged to meet regularly to discuss management and work practices influencing lameness and poor welfare and to track their own progress in improving these. Lameness examinations (41 parameters) were conducted at the start of the study (Baseline), and after 1 year and 2 years. Results were compared with control horses from a further 21 communities outside the intervention. Of the 149 horses assessed on all three occasions, PI horses showed significantly (P<0.05) greater improvement than C horses in 20 parameters, most notably overall lameness score, measures of sole pain and range of movement on limb flexion. Control horses showed slight but significantly greater improvements in four parameters, including frog quality in fore and hindlimbs.This participatory intervention succeeded in improving lameness and some limb abnormalities in working horses, by encouraging changes in management and work practices which were feasible within owners’ socioeconomic and environmental constraints. Demonstration of the potentially sustainable improvements achieved here should encourage further development of participatory intervention approaches to benefit humans and animals in other contexts

Theories of Willpower Affect Sustained Learning

Building cognitive abilities often requires sustained engagement with effortful tasks. We demonstrate that beliefs about willpower–whether willpower is viewed as a limited or non-limited resource–impact sustained learning on a strenuous mental task. As predicted, beliefs about willpower did not affect accuracy or improvement during the initial phases of learning; however, participants who were led to view willpower as non-limited showed greater sustained learning over the full duration of the task. These findings highlight the interactive nature of motivational and cognitive processes: motivational factors can substantially affect people’s ability to recruit their cognitive resources to sustain learning over time

Plasma proteomic signature predicts who will get persistent symptoms following SARS-CoV-2 infection

BACKGROUND: The majority of those infected by ancestral Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) during the UK first wave (starting March 2020) did not require hospitalisation. Most had a short-lived mild or asymptomatic infection, while others had symptoms that persisted for weeks or months. We hypothesized that the plasma proteome at the time of first infection would reflect differences in the inflammatory response that linked to symptom severity and duration. METHODS: We performed a nested longitudinal case-control study and targeted analysis of the plasma proteome of 156 healthcare workers (HCW) with and without lab confirmed SARS-CoV-2 infection. Targeted proteomic multiple-reaction monitoring analysis of 91 pre-selected proteins was undertaken in uninfected healthcare workers at baseline, and in infected healthcare workers serially, from 1 week prior to 6 weeks after their first confirmed SARS-CoV-2 infection. Symptom severity and antibody responses were also tracked. Questionnaires at 6 and 12 months collected data on persistent symptoms. FINDINGS: Within this cohort (median age 39 years, interquartile range 30-47 years), 54 healthcare workers (44% male) had PCR or antibody confirmed infection, with the remaining 102 (38% male) serving as uninfected controls. Following the first confirmed SARS-CoV-2 infection, perturbation of the plasma proteome persisted for up to 6 weeks, tracking symptom severity and antibody responses. Differentially abundant proteins were mostly coordinated around lipid, atherosclerosis and cholesterol metabolism pathways, complement and coagulation cascades, autophagy, and lysosomal function. The proteomic profile at the time of seroconversion associated with persistent symptoms out to 12 months. Data are available via ProteomeXchange with identifier PXD036590. INTERPRETATION: Our findings show that non-severe SARS-CoV-2 infection perturbs the plasma proteome for at least 6 weeks. The plasma proteomic signature at the time of seroconversion has the potential to identify which individuals are more likely to suffer from persistent symptoms related to SARS-CoV-2 infection. FUNDING INFORMATION: The COVIDsortium is supported by funding donated by individuals, charitable Trusts, and corporations including Goldman Sachs, Citadel and Citadel Securities, The Guy Foundation, GW Pharmaceuticals, Kusuma Trust, and Jagclif Charitable Trust, and enabled by Barts Charity with support from University College London Hospitals (UCLH) Charity. This work was additionally supported by the Translational Mass Spectrometry Research Group and the Biomedical Research Center (BRC) at Great Ormond Street Hospital

Implementation of chronic kidney disease guidelines for sodium-glucose co-transporter-2 inhibitor use in primary care in the UK: a cross-sectional study.

BACKGROUND: The cardiovascular and kidney benefits of sodium-glucose co-transporter-2 (SGLT2) inhibitors in people with chronic kidney disease (CKD) are well established. The implementation of updated SGLT2 inhibitor guidelines and prescribing in the real-world CKD population remains largely unknown. METHODS: A cross-sectional study of adults with CKD registered with UK primary care practices in the Oxford-Royal College of General Practitioners Research and Surveillance Centre network on the 31st December 2022 was undertaken. Pseudonymised data from electronic health records held securely within the Oxford-Royal College of General Practitioners Clinical Informatics Digital Hub (ORCHID) were extracted. An update to a previously described ontological approach was used to identify the study population, using a combination of Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT) indicating a diagnosis of CKD and laboratory confirmed CKD based on Kidney Disease: Improving Global Outcomes (KDIGO) diagnostic criteria. We examined the extent to which SGLT2 inhibitor guidelines apply to and are then implemented in adults with CKD. A logistic regression model was used to identify factors associated with SGLT2 inhibitor prescribing, reported as odds ratios (ORs) with 95% confidence intervals (CI). The four guidelines under investigation were the United Kingdom Kidney Association (UKKA) Clinical Practice Guideline SGLT2 Inhibition in Adults with Kidney Disease (October 2021), American Diabetes Association (ADA) and KDIGO Consensus Report on Diabetes Management in CKD (October 2022), National Institute for Health and Care Excellence (NICE) Guideline Type 2 Diabetes in Adults: Management (June 2022), and NICE Technology Appraisal Dapagliflozin for Treating CKD (March 2022). FINDINGS: Of 6,670,829 adults, we identified 516,491 (7.7%) with CKD, including 32.8% (n = 169,443) who had co-existing type 2 diabetes (T2D). 26.8% (n = 138,183) of the overall CKD population had a guideline directed indication for SGLT2 inhibitor treatment. A higher proportion of people with CKD and co-existing T2D were indicated for treatment, compared to those without T2D (62.8% [n = 106,468] vs. 9.1% [n = 31,715]). SGLT2 inhibitors were prescribed to 17.0% (n = 23,466) of those with an indication for treatment, and prescriptions were predominantly in those with co-existing T2D; 22.0% (n = 23,464) in those with T2D, and <0.1% (n = 2) in those without T2D. In adjusted multivariable analysis of people with CKD and T2D, females (OR 0.69, 95% CI 0.67-0.72, p <0.0001), individuals of Black ethnicity (OR 0.84, 95% CI 0.77-0.91, p <0.0001) and those of lower socio-economic status (OR 0.72, 95% CI 0.68-0.76, p <0.0001) were less likely to be prescribed an SGLT2 inhibitor. Those with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 had a lower likelihood of receiving an SGLT2 inhibitor, compared to those with an eGFR ≥60 mL/min/1.73 m2 (eGFR 45-60 mL/min/1.73 m2 OR 0.65, 95% CI 0.62-0.68, p <0.0001, eGFR 30-45 mL/min/1.73 m2 OR 0.73, 95% CI 0.69-0.78, p <0.0001, eGFR 15-30 mL/min/1.73 m2 OR 0.52, 95% CI 0.46-0.60, p <0.0001, eGFR <15 mL/min/1.73 m2 OR 0.03, 95% CI 0.00-0.23, p = 0.0037, respectively). Those with albuminuria (urine albumin-to-creatinine ratio 3-30 mg/mmol) were less likely to be prescribed an SGLT2 inhibitor, compared to those without albuminuria (OR 0.78, 95% CI 0.75-0.82, p <0.0001). INTERPRETATION: SGLT2 inhibitor guidelines in CKD have not yet been successfully implemented into clinical practice, most notably in those without co-existing T2D. Individuals at higher risk of adverse outcomes are paradoxically less likely to receive SGLT2 inhibitor treatment. The timeframe between the publication of guidelines and data extraction may have been too short to observe changes in clinical practice. Enhanced efforts to embed SGLT2 inhibitors equitably into routine care for people with CKD are urgently needed, particularly in those at highest risk of adverse outcomes and in the absence of T2D. FUNDING: None

Heterologous infection and vaccination shapes immunity against SARS-CoV-2 variants

[Figure: see text].The impact of initial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infecting strain on downstream immunity to heterologous variants of concern (VOC) is unknown. Studying a longitudinal healthcare worker cohort, we found that after three antigen exposures (infection+two vaccine doses), S1 antibody, memory B cells and heterologous neutralization of B.1.351, P.1 and B.1.617.2 plateaued, while B.1.1.7 neutralization and spike T cell responses increased. Serology using Wuhan Hu-1 spike receptor binding domain poorly predicted neutralizing immunity against VOCs. Neutralization potency against VOCs changed with heterologous virus encounter and number of antigen exposures. Neutralization potency fell differentially depending on targeted VOCs over 5-months from the second vaccine dose. Heterologous combinations of spike encountered during infection and vaccination shape subsequent cross-protection against VOC, with implications for future-proof next-generation vaccines

Magnetic and electronic phase transitions probed by nanomechanical resonators

The reduced dimensionality of two-dimensional (2D) materials results in characteristic types of magnetically and electronically ordered phases. However, only few methods are available to study this order, in particular in ultrathin insulating antiferromagnets that couple weakly to magnetic and electronic probes. Here, we demonstrate that phase transitions in thin membranes of 2D antiferromagnetic FePS3, MnPS3 and NiPS3 can be probed mechanically via the temperature-dependent resonance frequency and quality factor. The observed relation between mechanical motion and antiferromagnetic order is shown to be mediated by the specific heat and reveals a strong dependence of the Néel temperature of FePS3 on electrostatically induced strain. The methodology is not restricted to magnetic order, as we demonstrate by probing an electronic charge-density-wave phase in 2H-TaS2. It thus offers the potential to characterize phase transitions in a wide variety of materials, including those that are antiferromagnetic, insulating or so thin that conventional bulk characterization methods become unsuitable

The accuracy of the report of hepatic steatosis on ultrasonography in patients infected with hepatitis C in a clinical setting: A retrospective observational study

BACKGROUND: Steatosis is occasionally reported during screening ultrasonography in patients with hepatitis C virus (HCV). We conducted a retrospective observational study to assess the factors associated with steatosis on ultrasonography and the relationship between steatosis on ultrasound versus biopsy in patients infected with HCV in a clinical setting. Our hypothesis was ultrasonography would perform poorly for the detection of steatosis outside of the context of a controlled study, primarily due to false-positive results caused by hepatic fibrosis and inflammation. METHODS: A retrospective review of ultrasound reports was conducted on patients infected with HCV in a tertiary care gastroenterology clinic. Reports were reviewed for the specific documentation of the presence of steatosis. Baseline clinical and histologic parameters were recorded, and compared for patients with vs. without steatosis. Multiple logistic regression analysis was performed on these baseline variables. Liver biopsies were reviewed by two pathologists, and graded for steatosis. Steatosis on biopsy was compared to steatosis on ultrasound report, and the performance characteristics of ultrasonography were calculated, using biopsy as the gold standard. RESULTS: Ultrasound reports were available on 164 patients. Patients with steatosis on ultrasound had a higher incidence of the following parameters compared to patients without steatosis: diabetes (12/49 [24%] vs. 7/115 [6%], p < 0.001), fibrosis stage >2 (15/48 [31%] vs. 16/110 [15%], p = 0.02), histologic grade >2 (19/48 [40%] vs. 17/103 [17%], p = 0.002), and ALT (129.5 ± 89.0 IU/L vs. 94.3 ± 87.0 IU/L, p = 0.01). Histologic grade was the only factor independently associated with steatosis with multivariate analysis. When compared to the histologic diagnosis of steatosis (n = 122), ultrasonography had a substantial number of false-positive and false-negative results. In patients with a normal ultrasound, 8/82 (10%) had >30% steatosis on biopsy. Among patients with steatosis reported on ultrasound, only 12/40 (30%) had >30% steatosis on biopsy review. CONCLUSION: Steatosis on ultrasound is associated with markers of inflammation and fibrosis in HCV-infected patients, but does not consistently correlate with steatosis on biopsy outside of the context of a controlled study. Clinicians should be skeptical of the definitive diagnosis of steatosis on hepatic ultrasonography

A Comparison of Sodium-Glucose Co-Transporter 2 Inhibitor Kidney Outcome Trial Participants with a Real-World Chronic Kidney Disease Primary Care Population.

BACKGROUND/HYPOTHESIS: Observational studies suggest sodium-glucose co-transporter-2 (SGLT2) inhibitor kidney outcome trials are not representative of the broader population of people with chronic kidney disease (CKD). However, there are limited data on the generalisability to those without co-existing type 2 diabetes (T2D), and the representativeness of the EMPA-KIDNEY trial has not been adequately explored. We hypothesised that SGLT2 inhibitor kidney outcome trials are more representative of people with co-existing T2D than those without, and that EMPA-KIDNEY is more representative than previous trials. METHODS: A cross-sectional analysis of adults with CKD in English primary care was conducted using the Oxford-Royal College of General Practitioners Clinical Information Digital Hub. The proportions that met the eligibility criteria of SGLT2 inhibitor kidney outcome trials were determined, and their characteristics described. Logistic regression analyses were performed to identify factors associated with trial eligibility. RESULTS: Of 6,670,829 adults, 516,491 (7.7%) with CKD were identified. In the real-world CKD population, 0.9%, 2.2%, and 8.0% met the CREDENCE, DAPA-CKD, and EMPA-KIDNEY eligibility criteria, respectively. All trials were more representative of people with co-existing T2D than those without T2D. Trial participants were 9-14 years younger than the real-world CKD population, and had more advanced CKD, including higher levels of albuminuria. A higher proportion of the CREDENCE (100%), DAPA-CKD (67.6%) and EMPA-KIDNEY (44.5%) trial participants had T2D compared to the real-world CKD population (32.8%). Renin-angiotensin system inhibitors were prescribed in almost all trial participants, compared to less than half of the real-world CKD population. Females were under-represented and less likely to be eligible for the trials. CONCLUSION: SGLT2 inhibitor kidney outcome trials represent a sub-group of people with CKD at high risk of adverse kidney events. Out study highlights the importance of complementing trials with real-world studies, exploring the effectiveness of SGLT2 inhibitors in the broader population of people with CKD