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Abstract Background Peripartum cardiomyopathy (PPCM) is a form of heart failure occurring towards the end of pregnancy or in the months following delivery. Concerns regarding the role of prolactin (the polypeptide hormone responsible for lactation) driving the pathogenesis of PPCM have led experts to discourage patients from breastfeeding; however, limited clinical data exist. We sought to (1) determine whether lactation was associated with less cardiac recovery and (2) assess the counseling about breastfeeding given to patients at the time of their initial diagnosis. Methods Patients diagnosed with PPCM from 1999 to 2019 were identified through detailed chart review and demographic characteristics, comorbidities, outcomes, and lactation status were collected. Cardiac recovery was defined as left ventricular ejection fraction (LVEF) 55% or higher. A survey about breastfeeding and patient experience was administered by mail. Patients were only included in this analysis if definitive information about lactation status was documented. Results Of 220 patients with confirmed PPCM, lactation status was known definitively in 54 patients; of these, 18 (33%) had breastfed for at least 6 weeks and 36 (67%) did not breastfeed. There were no significant differences in the breastfeeding and non-breastfeeding groups related to baseline LVEF, age, race, gestational diabetes, smoking, hypertensive disorders of pregnancy, and medication treatments. Despite similar baseline LVEF at the time of diagnosis, there was no statistically significant difference in cardiac recovery based on lactation status. In a subset of patients with severe cardiac dysfunction at the time of diagnosis, there remained no significant differences in recovery based on lactation status. Of the 34 survey respondents, 62% were told not to breastfeed due to their diagnosis or concerns regarding safety of medications, and none were encouraged to breastfeed. Conclusion In this retrospective cohort, lactation was not associated with lower rates of myocardial recovery. Importantly, a majority of patients had received counseling that they should not breastfeed. Future studies of the role of lactation in PPCM are needed in order to better understand the impact of breastfeeding and improve patient counseling.

Objective To assess the effect of goal-directed mobilisation (GDM) on physical functioning in medical inpatients.Design Randomised, controlled, single-centre, parallel, superiority trial with a 3-month follow-up and blinded outcome assessment.Setting General internal medicine wards of a Swiss tertiary acute hospital, September 2021 to April 2023.Participants Adults with expected hospitalisation of ≥5 days, physiotherapy prescription and ability to follow study procedures.Intervention GDM during hospitalisation, which includes personal goal setting and a short session of patient education through a physiotherapist (experimental group), versus standard care (control group).Outcome measures The primary outcome was the change in physical activity between baseline and day 5 (De Morton Mobility Index (DEMMI)). Secondary outcomes included in-hospital accelerometer-measured mobilisation time; in-hospital falls; delirium; length of stay; change in independence in activities of daily living, concerns of falling and quality of life; falls, readmission and mortality within 3 months.Results The study was completed by 123 of 162 (76%) patients enrolled, with the primary outcome collected at day 5 in 126 (78%) participants. DEMMI Score improved by 8.2 (SD 15.1) points in the control group and 9.4 (SD 14.2) in the intervention group, with a mean difference of 0.3 (adjusted for the stratification factors age and initial DEMMI Score, 95% CI −4.1 to 4.8, p=0.88). We did not observe a statistically significant difference in effects of the interventions on any secondary outcome.Conclusions The patient’s physical functioning improved during hospitalisation, but the improvement was similar for GDM and standard of care. Improving physical activity during an acute medical hospitalisation remains challenging. Future interventions should target additional barriers that can be implemented without augmenting resources.Trial registration number NCT04760392.

IntroductionThe study demonstrated the feasibility of incorporating RNA biomarkers, specifically 5-aminolevulinic acid synthase (ALAS2) and carbonic anhydrase 1 (CA1), to improve the hematological module of the Athlete Biological Passport (ABP) in routine antidoping context.ObjectiveThe aim was to investigate the implementation of reticulocyte (RET) related biomarkers, specifically ALAS2 and CA1, using quantitative reverse transcription polymerase chain reaction (RT-qPCR) on dried blood spots (DBS) from elite athletes. Hemoglobin changes over time in DBS samples was measured as well. Combining hemoglobin and messenger RNA (mRNA) analyses allowed to monitor alterations of the established marker, “DBS OFF-score”.MethodologyTen athletes were selected for sampling by the Swiss national antidoping organization, Swiss Sports Integrity (SSI). Samples were collected, transported and analyzed for ABP following the World Anti-Doping Agency (WADA) procedures and spotted onto Protein Saver DBS cards.ResultsMost athletes exhibited stable biomarker levels, except for one individual involved in ski mountaineering, who demonstrated a sustained increase in ALAS2 compared to the individual baseline. This elevation could be due to blood withdrawal or other factors, such as doping with substances outside the targeted test menu.ConclusionIn this study, RNA-biomarkers were successfully analyzed in routine blood samples, and the project demonstrated promising results for the implementation of ALAS2 and CA1 in routine analysis to complement the ABP.

IntroductionThe acute respiratory distress syndrome (ARDS) is a common complication of severe COVID-19 and contributes to patient morbidity and mortality. ARDS is a heterogeneous syndrome caused by various insults, and results in acute hypoxemic respiratory failure. Patients with ARDS from COVID-19 may represent a subgroup of ARDS patients with distinct molecular profiles that drive disease outcomes. Here, we hypothesized that longitudinal transcriptomic analysis may identify distinct dynamic pathobiological pathways during COVID-19 ARDS.MethodsWe identified a patient cohort from an existing ICU biorepository and established three groups for comparison: 1) patients with COVID-19 ARDS that survived hospitalization (COVID survivors, n = 4), 2) patients with COVID-19 ARDS that did not survive hospitalization (COVID non-survivors, n = 5), and 3) patients with ARDS from other causes as a control group (ARDS controls, n = 4). RNA was isolated from peripheral blood mononuclear cells (PBMCs) at 4 time points (Days 1, 3, 7, and 10 following ICU admission) and analyzed by bulk RNA sequencing.ResultsWe first compared transcriptomes between groups at individual timepoints and observed significant heterogeneity in differentially expressed genes (DEGs). Next, we utilized the likelihood ratio test to identify genes that exhibit different patterns of change over time between the 3 groups and identified 341 DEGs across time, including hemoglobin subunit alpha 2 (HBA1, HBA2), hemoglobin subunit beta (HBB), von Willebrand factor C and EGF domains (VWCE), and carbonic anhydrase 1 (CA1), which all demonstrated persistent upregulation in the COVID non-survivors compared to COVID survivors. Of the 341 DEGs, 314 demonstrated a similar pattern of persistent increased gene expression in COVID non-survivors compared to survivors, associated with canonical pathways of iron homeostasis signaling, erythrocyte interaction with oxygen and carbon dioxide, erythropoietin signaling, heme biosynthesis, metabolism of porphyrins, and iron uptake and transport.DiscussionThese findings describe significant differences in gene regulation during patient ICU course between survivors and non-survivors of COVID-19 ARDS. We identified multiple pathways that suggest heme and red blood cell metabolism contribute to disease outcomes. This approach is generalizable to larger cohorts and supports an approach of longitudinal sampling in ARDS molecular profiling studies, which may identify novel targetable pathways of injury and resolution.

BackgroundPeripheral arterial disease (PAD) is a prevalent vascular disorder characterized by atherosclerotic occlusion of peripheral arteries, resulting in reduced blood flow to the lower extremities and poor walking ability. Older patients with PAD are also at a markedly increased risk of cardiovascular events, including myocardial infarction. Recent evidence indicates that inorganic nitrate supplementation, which is abundant in certain vegetables, augments nitric oxide (NO) bioavailability and may have beneficial effects on walking, blood pressure, and vascular function in patients with PAD.ObjectiveWe sought to determine if short-term nitrate supplementation (via beetroot juice) improves peak treadmill time and coronary hyperemic responses to plantar flexion exercise relative to placebo (nitrate-depleted juice) in older patients with PAD. The primary endpoints were peak treadmill time and the peak coronary hyperemic response to plantar flexion exercise.MethodsEleven PAD patients (52–80 yr.; 9 men/2 women; Fontaine stage II) were randomized (double-blind) to either nitrate-rich (Beet-IT, 0.3 g inorganic nitrate twice/day; BRnitrate) or nitrate-depleted (Beet-IT, 0.04 g inorganic nitrate twice/day, BRplacebo) beetroot juice for 4 to 6 days, followed by a washout of 7 to 14 days before crossing over to the other treatment. Patients completed graded plantar flexion exercise with their most symptomatic leg to fatigue, followed by isometric handgrip until volitional fatigue at 40% of maximum on day 4 of supplementation, and a treadmill test to peak exertion 1–2 days later while continuing supplementation. Hemodynamics and exercise tolerance, and coronary blood flow velocity (CBV) responses were measured.ResultsAlthough peak walking time and claudication onset time during treadmill exercise did not differ significantly between BRplacebo and BRnitrate, the diastolic blood pressure response at the peak treadmill walking stage was significantly lower in the BRnitrate condition. Increases in CBV from baseline to peak plantar flexion exercise after BRplacebo and BRnitrate showed a trend for a greater increase in CBV at the peak workload of plantar flexion with BRnitrate (p = 0.06; Cohen’s d = 0.56).ConclusionOverall, these preliminary findings suggest that inorganic nitrate supplementation in PAD patients is safe, well-tolerated, and may improve the coronary hyperemic and blood pressure responses when their calf muscles are most predisposed to ischemia.Clinical trial registration:https://clinicaltrials.gov/, identifier NCT02553733.

Background Evaluation stress can impair inhibitory control, limiting the ability of children to perform cognitively. However, evidence on protective factors is lacking as stress-induced cognitive impairments are poorly understood. High physical activity has been related to better inhibitory control and has the potential to buffer the response to a stressor. We investigated the association of physical activity and stress-induced changes in inhibitory control as well as its underlying cognitive control processes (i.e., conflict monitoring and resolution). Method Participants (10 to 13 y) with either low ( N = 55) or high moderate-to-vigorous physical activity ( N = 55) completed the Trier Social Stress Test for Children (TSST-C) and a control task in a randomized order. During both conditions, salivary cortisol was collected. Additionally, a computerized Stroop task was administered before and after the experimental conditions. The N200 and positive slow wave (PSW) components of event-related potentials elicited by the Stroop task were recorded using electroencephalography. Results In comparison to the control task, the TSST-C elicited a pre-to post-test decrease of accuracy on incompatible trials. Path-analyses further revealed that this decrease was related to low physical activity and a reduced PSW amplitude. However, both the N200 and PSW amplitudes did not mediate the relation between physical activity groups and performance on the Stroop task. Conclusion In children, evaluation stress decreases inhibitory control partly due to a reduced effectiveness of conflict resolution processes. Only children with high physical activity maintain inhibitory control after facing the stressor. However, this protective effect cannot be attributed to changes in conflict monitoring and resolution.

Abstract Autonomic dysfunction is a common complication of type 2 diabetes mellitus (T2DM). However, the character of dysfunction varies in different reports. Differences in measurement methodology and complications might have influenced the inconsistent results. We sought to evaluate comprehensively the relationship between abnormal glucose metabolism and autonomic function at rest and the response to exercise in healthy individuals and T2DM patients. We hypothesized that both sympathetic and parasympathetic indices would decrease with the progression of abnormal glucose metabolism in individuals with few complications related to high sympathetic tone. Twenty healthy individuals and 11 T2DM patients without clinically evident cardiovascular disease other than controlled hypertension were examined. Resting muscle sympathetic nerve activity (MSNA), heart rate variability, spontaneous cardiovagal baroreflex sensitivity (CBRS), sympathetic baroreflex sensitivity and the MSNA response to handgrip exercise were measured. Resting MSNA was lower in patients with T2DM than in healthy control subjects (P = 0.011). Resting MSNA was negatively correlated with haemoglobin A1c in all subjects (R = −0.45, P = 0.024). The parasympathetic components of heart rate variability and CBRS were negatively correlated with glycaemic/insulin indices in all subjects and even in the control group only (all, P

Objective: To describe the creation of a scalable framework for a Remote Patient Monitoring (RPM) program tied to a large medical practice. Patients and Methods: In July 2020, at Mayo Clinic Rochester, we initiated the process to combine human-centered design, health systems engineering, and clinical expertise to develop and refine RPM programs and explore new medical conditions where RPM could be beneficial. We report on the creation of the overarching RPM program, the development of a hybrid nursing model, the technology used for each population, and the lessons learned throughout the process. Results: Four pilot programs for hospitalized patients with cirrhosis, acute kidney injury (AKI), post-pancreatectomy, and post-gastroenterology (GI) procedures were launched. The 4 programs enrolled a range from 0 patients (post-GI procedures) to 91 patients over 5 months (AKI) for RPM programs ranging from 30 days to 96.5 days in average duration. Three of the programs continue enrollment (cirrhosis, AKI, and post-pancreatectomy), and one program was discontinued. Conclusion: RPM can uniquely facilitate the transition from hospital to home, decrease hospital length of stay, and optimize hospital capacity and staffing resources in select scenarios. To achieve positive results at the health care system level, RPM interventions require a change in the model of care. However, not all care models or medical conditions lend themselves to RPM, which should be explored in pilot testing.

Computation competence (CC) in simple addition and subtraction using non-counting (NC) strategies is an important learning objective in Grade 1 mathematics but many children, especially low achievers in mathematics, struggle to acquire these skills. To provide these students with the support they need, it is important to have valid and reliable tools for assessing progress in CC and NC strategy use. Developing an assessment instrument for use in Grade 1, when some children start the year unable to solve any problems, is challenging, as is ensuring measurement invariance over a school year when children generally make large achievement gains. This paper presents a new assessment tool for CC and NC strategy use in Grade 1 that was tested in a longitudinal study with N = 1,017 children. Analyses using the Rasch model revealed acceptable mean square scores (MNSQ 0.83 – 1.20). Warm’s Weighted Likelihood Estimate (WLE) reliability scores were acceptable (pre-test .77; post-test .87). Measurement invariance over time was given. The instrument is promising for assessing CC and NC strategy use efficiently and accurately in Grade 1.

The EPICA (European Project for Ice Coring in Antarctica) Dome C (EDC) ice core drilling in East Antarctica reaches a depth of 3260 m. The reference EDC chronology, the AICC2012 (Antarctic Ice Core Chronology 2012), provides an age vs. depth relationship covering the last 800 kyr (thousands of years), with an absolute uncertainty rising up to 8000 years at the bottom of the ice core. The origins of this relatively large uncertainty are twofold: (1) the δ18Oatm, δO2/N2 and total air content (TAC) records are poorly resolved and show large gaps over the last 800 kyr, and (2) large uncertainties are associated with their orbital targets. Here, we present new highly resolved δ18Oatm, δO2/N2 and δ15N measurements for the EDC ice core covering the last five glacial–interglacial transitions; a new low-resolution TAC record over the period 440–800 ka BP (ka: 1000 years before 1950); and novel absolute 81Kr ages. We have compiled chronological and glaciological information including novel orbital age markers from new data on the EDC ice core as well as accurate firn modeling estimates in a Bayesian dating tool to construct the new AICC2023 chronology. For the first time, three orbital tools are used simultaneously. Hence, it is possible to observe that they are consistent with each other and with the other age markers over most of the last 800 kyr (70 %). This, in turn, gives us confidence in the new AICC2023 chronology. The average uncertainty in the ice chronology is reduced from 1700 to 900 years in AICC2023 over the last 800 kyr (1σ). The new timescale diverges from AICC2012 and suggests age shifts reaching 3800 years towards older ages over marine isotope stages (MISs) 5, 11 and 19. But the coherency between the new AICC2023 timescale and independent chronologies of other archives (Italian Lacustrine succession from Sulmona Basin, Dome Fuji ice core and northern Alpine speleothems) is improved by 1000 to 2000 years over these time intervals.

Abstract Background Low mobility during an acute hospitalization is frequent and associated with adverse effects, including persistent functional decline, institutionalization and death. However, we lack effective interventions to improve mobility that are scalable in everyday practice. The INTOMOB trial – INtervention to increase MOBility in older hospitalized medical patients – will test the effect of a multilevel intervention to improve mobility of older hospitalized patients on functional mobility. Methods The INTOMOB multicenter superiority parallel cluster randomized controlled trial will enroll in total 274 patients in Swiss hospitals. Community-dwelling adults aged ≥ 60 years, admitted to a general internal medicine ward with an anticipated length of hospital stay of ≥ 3 days, will be eligible for participation. Unit of randomization will be the wards. A multilevel mobility intervention will be compared to standard of care and target the patients (information and exercise booklets, mobility diary, iPad with exercise videos), healthcare professionals (e-learning, oral presentation, mobility checklist), and environment (posters and pictures on the wards). The primary outcome will be life-space level, measured by the University of Alabama at Birmingham Study of Aging Life-Space Assessment (LSA), at 30 days after enrollment. The LSA is a measure of functional mobility, i.e., how far participants move from bedroom to outside town. Secondary outcomes include, among others, LSA at 180 days, mobility and falls during hospitalization, muscle strength at discharge, and falls, emergency room visits, readmissions, and death within 180 days. Discussion This study has the potential to improve outcomes of older hospitalized patients through an intervention that should be scalable in clinical practice because it fosters patient empowerment and does not require additional resources. The tools provided to the patients can help them implement better mobility practices after discharge, which can contribute to better functional outcomes. The choice of a functional patient-reported outcome measure as primary outcome (rather than a “simple” objective mobility measure) reinforces the patient-centeredness of the study. Trial registration clinicaltrials.gov (NCT05639231, released on December 19 2022); Swiss National Clinical Trial Portal (SNCTP000005259, released on November 28 2022).

In this work, we present a revision of an open-split-based dual-inlet system for elemental and isotope ratio mass spectrometers (IRMSs), which was developed by the division of Climate and Environmental Physics of the University of Bern 2 decades ago. Besides discussing the corresponding improvements we show that with this inlet system (NIS-II, New Inlet System II) external precisions can be achieved that are high enough to perform measurements of multiply substituted isotopologues (clumped isotopes) on pure gases. For clumped-isotope ratios 35/32 and 36/32 of oxygen, we achieved standard deviations of 3.4×10-9 and 4.9×10-9, respectively, that we calculated from 60 interval means (20 s integration) of pure-oxygen gas measurements. Moreover, we report various performance tests and show that delta values of various air components can be measured with precisions of the order of tens of per meg and higher with the NIS-II. In addition, we demonstrate that our new open-split-based dual-inlet system allows us to measure some of these delta values with significantly higher precisions than an NIS-I (precursor of the NIS-II) and conventional changeover-valve-based dual-inlet systems (tests performed with two dual-inlet systems built by Elementar and Thermo Finnigan). Especially, our measurements point out that our inlet system provides reliable results at short idle times (20 s) and that the corresponding data do not need to be corrected for non-linearity. However, the sample consumption of our open-split-based dual-inlet system is several orders of magnitude higher than that of changeover-valve-based ones (0.33 sccm versus 0.005 sccm; standard cubic centimetres per minute). Due to the successful preliminary tests regarding measurements of clumped-isotope ratios, we will continue our work in this area to perform clumped-isotope studies according to common practices.

The southern coast of South Africa displays a highly dynamical climate as it is at the convergence of the Atlantic and Indian oceans, and it is located near the subtropical/temperate zone boundary with seasonal influence of easterlies and westerlies. The region hosts some key archeological sites with records of significant cognitive, technological and social developments. Reconstructions of the state and variability of past climate and environmental conditions around sites of archeological significance can provide crucial context for understanding the evolution of early humans. Here we present a short but high-resolution record of hydroclimate and temperature in South Africa. Our reconstructions are based on trace elements, calcite and fluid inclusion stable isotopes, as well as fluid inclusion microthermometry, from a speleothem collected in Bloukrantz cave, in the De Hoop Nature Reserve in the southern Cape region of South Africa. Our record covers the time period from 48.3 to 45.2 ka during marine isotope stage 3. Both δ18Oc and δ13Cc show strong variability and covary with Sr/Ca. This correlation suggests that the control on these proxies originates from internal cave processes such as prior carbonate precipitation, which we infer to be related to precipitation amount. The hydroclimate indicators furthermore suggest a shift towards overall drier conditions after 46 ka, coincident with cooling in Antarctica and drier conditions in the eastern part of South Africa corresponding to the summer rainfall zone (SRZ). Fluid inclusion-based temperature reconstructions show good agreement between the oxygen isotope and microthermometry methods, and results from the latter display little variation throughout the record, with reconstructed temperatures close to the present-day cave temperature of 17.5 ∘C. Overall, the BL3 speleothem record thus suggests relatively stable temperature from 48.3 to 45.2 ka, whereas precipitation was variable with marked drier episodes on sub-millennial timescales.

Marie Jeremy B San Pedro,1 James Paul S Gomez,1 Edgar U Leuenberger1– 3 1Asian Eye Institute, Makati, Philippines; 2Department of Ophthalmology, University of the East Ramon Magsaysay Memorial Medical Center Inc., Quezon City, Philippines; 3Department of Ophthalmology, Ospital ng Makati, Makati City, PhilippinesCorrespondence: Marie Jeremy B San Pedro, Email mariejeremy.sanpedro@gmail.comPurpose: This study aimed to compare the success and complication rates among patients implanted with Ahmed Glaucoma Valve (AGV) using the short and long tunnel technique through retrospective chart review.Patients and Methods: We reviewed 54 charts of adult patients who underwent AGV implantation using a Short-Needle Track (SNT) or Long-Needle Track (LNT) technique. Intraocular pressures (IOP), Best Corrected Visual Acuity (BCVA) and number of medications were recorded pre-operatively, and at Day 1, 3, 7, Month 1, 3, 6 post-operatively. Treatment success, occurrence of Hypertensive Phase (HP), complication and procedures done after AGV implantation were compared between the two groups using one-tailed Z-test of proportions.Results: A total of 20 (LNT) and 21 (SNT) charts were included in the study. There was no significant difference between the median postoperative IOP, BCVA, and number of anti-glaucoma medications between the two groups at each time interval. The comparison between the occurrence of HP (P = 0.435) and success rates (P = 0.476) between the two groups yielded no significant difference. Flat/shallow anterior chamber (AC) was seen exclusively in three eyes (14%) in the SNT group (P = 0.039). There was one occurrence of plate exposure in the LNT group (P = 0.149).Conclusion: The LNT technique of AGV Implantation may be used as an alternative to the traditional SNT (with autologous graft). The long needle track offers the advantage reducing the risk of complications arising from shallow anterior chamber post-operatively.Keywords: glaucoma drainage device, Ahmed glaucoma valve, long needle track technique, short needle track technique

Micro-additive manufacturing techniques have the potential to meet the demand for miniaturised functional components for minimally invasive surgical instruments. These techniques create monolithic, compliant mechanisms with micro-sized free-form structures that can be tailored to patient-specific surgical procedures. The automated design synthesis of the mechanisms using building blocks results in structures that are shape-programmable. This is achieved through an algorithmic-based computational workflow, which automatically converts user-specified 2D and 3D curves into discrete curve segments. The actuated motion of the mechanisms can be designed to move in a specific way, both forwardly and inversely. The mechanisms are manufactured using micro-laser powder bed fusion and hardenable stainless steel 17-4 PH. By carefully selecting the process parameters, it is possible to 3D-print micro-sized features such as a compliant beam thickness of 80 μm and an actuation hole of 100 μm. Both 2D planar curved mechanisms and 3D spatial curved mechanisms have been implemented and experimentally validated.

Abstract: Background: Children with Attention Deficit Hyperactivity Disorder (ADHD) often face problems in the engagement and adherence of health-promoting behaviors, such as physical activity and sports. Stimulant treatment is effective for managing core symptoms, but it remains unclear if this type of treatment also normalizes the engagement in health-promoting behavior. In this case-control study, we aim to compare physical activity and sports participation between children with ADHD and healthy peers. Motor skills and aerobic fitness are investigated as potential mediators of differences between groups. Methods: Children with ADHD were matched to healthy peers based on sex, age, and socioeconomic status. Participants (N=120; age: 10.8±1.4) reported their physical activity and sports participation using a 7-day recall protocol. Their engagement in activities at moderate and vigorous intensity as well as participation in individual and team sports was derived from the protocol. Participants further completed the Movement Assessment Battery for Children-2 (MABC-2) and a submaximal test on a cycling ergometer (PWC170). Results: Children with ADHD showed lower vigorous physical activity and participation in individual sports than healthy peers. They also achieved lower scores on the MABC-2 and the PWC170. Based on path-analyses, low PWC170 partially mediated the ADHD-related fewer engagement in vigorous physical activity and individual sports. Conclusion: Children with ADHD undergoing stimulant treatment show less participation in vigorous physical activity and individual sports than healthy peers. Poor aerobic fitness partly contributes to the relation between ADHD and low physical activity.

Abstract Background The distribution of airway responsiveness in a general population of non-smokers without respiratory symptoms has not been established, limiting its use in clinical and epidemiological practice. We derived reference equations depending on individual characteristics (i.e., sex, age, baseline lung function) for relevant percentiles of the methacholine two-point dose-response slope. Methods In a reference sample of 1567 adults of the SAPALDIA cross-sectional survey (1991), defined by excluding subjects with respiratory conditions, responsiveness during methacholine challenge was quantified by calculating the two-point dose-response slope (O'Connor). Weighted L1-regression was used to estimate reference equations for the 95th , 90th , 75th and 50th percentiles of the two-point slope. Results Reference equations for the 95th , 90th , 75th and 50th percentiles of the two-point slope were estimated using a model of the form a + b* Age + c* FEV1 + d* (FEV1)2 , where FEV1 corresponds to the pre-test (or baseline) level of FEV1. For the central half of the FEV1 distribution, we used a quadratic model to describe the dependence of methacholine slope on baseline FEV1. For the first and last quartiles of FEV1, a linear relation with FEV1 was assumed (i.e., d was set to 0). Sex was not a predictor term in this model. A negative linear association with slope was found for age. We provide an Excel file allowing calculation of the percentile of methacholine slope of a subject after introducing age – pre-test FEV1 – and results of methacholine challenge of the subject. Conclusion The present study provides equations for four relevant percentiles of methacholine two-point slope depending on age and baseline FEV1 as basic predictors in an adult reference population of non-obstructive and non-atopic persons. These equations may help clinicians and epidemiologists to better characterize individual or population airway responsiveness.

Abstract Background The aim was to determine if effects from smoking on lung function measured over 11 years differ between men and women. Methods In a prospective population based cohort study (Swiss Study on Air Pollution and Lung Diseases in Adults) current smokers in 1991 (18 – 60 yrs) were reassessed in 2002 (n = 1792). Multiple linear regression was used to estimate effects from pack-years of cigarettes smoked to 1991 and mean packs of cigarettes smoked per day between 1991 and 2002 on change in lung volume and flows over the 11 years. Results In both sexes, packs smoked between assessments were related to lung function decline but pack-years smoked before 1991 were not. Mean annual decline in FEV1 was -10.4 mL(95%CI -15.3, -5.5) per pack per day between assessments in men and -13.8 mL(95%CI-19.5,-8.1) in women. Decline per pack per day between 1991 and 2002 was lower in women who smoked in 1991 but quit before 2002 compared to persistent smokers (-6.4 vs -11.6 mL, p = 0.05) but this was not seen in men (-14.3 vs -8.8 mL p = 0.49). Smoking related decline was accelerated in men and women with airway obstruction, particularly in women where decline in FEV1 was three fold higher in participants with FEV1/FVC Conclusion There are differences in effects from smoking on lung function between men and women. Lung function recovers faster in women quitters than in men. Women current smokers with airway obstruction experience a greater smoking related decline in lung function than men.

IntroductionTimber harvests influence coarse woody debris (CWD) dynamics both initially and long-term—contributing a significant amount of CWD as slash immediately after harvest, but also removing some or all of the mature trees necessary to produce CWD over time. Whereas shelterwood and other similar timber harvest systems retain varying amounts of the overstory, preserving CWD production after harvest, commercial clearcutting essentially eliminates sources of fresh CWD until regenerating trees are large enough to contribute CWD through fallen limbs or trunks, often decades after harvest. Forestry best management practices (BMPs) are critical for reducing the water quality impacts of timber harvest, but their effects on riparian and stream CWD are not well understood.MethodsThe current project explores CWD dynamics (surveyed in 2001, 2004, 2009, and 2020) in three eastern Kentucky watersheds receiving differing timber harvest treatments in 1983: unharvested control, BMPs (clearcut with a protected streamside management zone), and no BMPs (clearcut).ResultsAnalysis of hydrology data over the period of record demonstrated significant flooding in 2004 that likely “reset” CWD in the study watersheds. Coarse woody debris volume was higher in control (3.33 m3/ha) than no BMP (1.03 m3/ha) in 2020, with CWD accumulation rates ranging from 0.039 m3/ha in the no BMP watershed to 0.19 m3/ha in the control.DiscussionWhile not significantly different, CWD volume was nominally higher in the BMP watershed than the No BMP watershed, suggesting that, in addition to their many other benefits, streamside management zones help facilitate CWD provisioning during stand initiation after a commercial clearcut harvest. Furthermore, this study suggests that provisioning of CWD may not recover after clearcut harvesting for 100 years or more.

Background: To reduce adverse outcomes of low hospital mobility, we need interventions that are scalable in everyday practice. This study assessed the feasibility and acceptability of the INTOMOB multilevel intervention addressing barriers to hospital mobility without requiring unavailable resources. Methods: The INTOMOB intervention, targeting older patients, healthcare professionals (HCPs) and the hospital environment, was implemented on acute general internal medicine wards of three hospitals (12/2022–03/2023). Feasibility and acceptability of the intervention were assessed and two types of accelerometers compared in a mixed methods study (patient and HCP surveys and interviews). Quantitative data were analyzed descriptively and qualitative data using a deductive approach. Results were integrated through meta-inferences. Results: Of 20 patients (mean age 74.1 years), 90% found the intervention helpful and 82% said the environment intervention (posters) stimulated mobility. The majority of 44 HCPs described the intervention as clear and helpful. There was no major implementation or technical issue. About 60% of patients and HCPs preferred a wrist-worn over an ankle-worn accelerometer. Conclusions: The INTOMOB intervention is feasible and well accepted. Patients’ and HCPs’ feedback allowed to further improve the intervention that will be tested in a cluster randomized trial and provides useful information for future mobility-fostering interventions.

Ammonia (NH3) in the atmosphere affects both the environment and human health. It is therefore increasingly recognised by policy makers as an important air pollutant that needs to be mitigated, though it still remains unregulated in many countries. In order to understand the effectiveness of abatement strategies, routine NH3 monitoring is required. Current reference protocols, first developed in the 1990s, use daily samplers with offline analysis; however, there have been a number of technologies developed since, which may be applicable for high time resolution routine monitoring of NH3 at ambient concentrations. The following study is a comprehensive field intercomparison held over an intensively managed grassland in southeastern Scotland using currently available methods that are reported to be suitable for routine monitoring of ambient NH3. In total, 13 instruments took part in the field study, including commercially available technologies, research prototype instruments, and legacy instruments. Assessments of the instruments' precision at low concentrations (< 10 ppb) and at elevated concentrations (maximum reported concentration of 282 ppb) were undertaken. At elevated concentrations, all instruments performed well and with precision (r2 > 0.75). At concentrations below 10 ppb, however, precision decreased, and instruments fell into two distinct groups, with duplicate instruments split across the two groups. It was found that duplicate instruments performed differently as a result of differences in instrument setup, inlet design, and operation of the instrument. New metrological standards were used to evaluate the accuracy in determining absolute concentrations in the field. A calibration-free CRDS optical gas standard (OGS, PTB, DE) served as an instrumental reference standard, and instrument operation was assessed against metrological calibration gases from (i) a permeation system (ReGaS1, METAS, CH) and (ii) primary standard gas mixtures (PSMs) prepared by gravimetry (NPL, UK). This study suggests that, although the OGS gives good performance with respect to sensitivity and linearity against the reference gas standards, this in itself is not enough for the OGS to be a field reference standard, because in field applications, a closed path spectrometer has limitations due to losses to surfaces in sampling NH3, which are not currently taken into account by the OGS. Overall, the instruments compared with the metrological standards performed well, but not every instrument could be compared to the reference gas standards due to incompatible inlet designs and limitations in the gas flow rates of the standards. This work provides evidence that, although NH3 instrumentation have greatly progressed in measurement precision, there is still further work required to quantify the accuracy of these systems under field conditions. It is the recommendation of this study that the use of instruments for routine monitoring of NH3 needs to be set out in standard operating protocols for inlet setup, calibration, and routine maintenance in order for datasets to be comparable.

We present a novel high-resolution inverse modelling system (“FLEXVAR”) based on FLEXPART-COSMO back trajectories driven by COSMO meteorological fields at 7 km×7 km resolution over the European COSMO-7 domain and the four-dimensional variational (4DVAR) data assimilation technique. FLEXVAR is coupled offline with the global inverse modelling system TM5-4DVAR to provide background mole fractions (“baselines”) consistent with the global observations assimilated in TM5-4DVAR. We have applied the FLEXVAR system for the inverse modelling of European CH4 emissions in 2018 using 24 stations with in situ measurements, complemented with data from five stations with discrete air sampling (and additional stations outside the European COSMO-7 domain used for the global TM5-4DVAR inversions). The sensitivity of the FLEXVAR inversions to different approaches to calculate the baselines, different parameterizations of the model representation error, different settings of the prior error covariance parameters, different prior inventories, and different observation data sets are investigated in detail. Furthermore, the FLEXVAR inversions are compared to inversions with the FLEXPART extended Kalman filter (“FLExKF”) system and with TM5-4DVAR inversions at 1∘×1∘ resolution over Europe. The three inverse modelling systems show overall good consistency of the major spatial patterns of the derived inversion increments and in general only relatively small differences in the derived annual total emissions of larger country regions. At the same time, the FLEXVAR inversions at 7 km×7 km resolution allow the observations to be better reproduced than the TM5-4DVAR simulations at 1∘×1∘. The three inverse models derive higher annual total CH4 emissions in 2018 for Germany, France, and BENELUX compared to the sum of anthropogenic emissions reported to UNFCCC and natural emissions estimated from the Global Carbon Project CH4 inventory, but the uncertainty ranges of top-down and bottom-up total emission estimates overlap for all three country regions. In contrast, the top-down estimates for the sum of emissions from the UK and Ireland agree relatively well with the total of anthropogenic and natural bottom-up inventories.

Lee Jerome Briones,1 James Paul Gomez,2 Edgar Felipe Leuenberger1– 3 1Department of Ophthalmology, University of the East Ramon Magsaysay Memorial Medical Center Inc, Quezon City, Philippines; 2Department of Ophthalmology, Asian Eye Institute, Makati City, Philippines; 3Department of Ophthalmology, Ospital ng Makati, Makati City, PhilippinesCorrespondence: Lee Jerome Briones, Department of Ophthalmology, University of the East Ramon Magsaysay Memorial Medical Center Inc, 64 Aurora Boulevard, Quezon City, 1113, Philippines, Tel +639178271894, Email jerome.briones@gmail.comPurpose: This study aimed to determine if near visual acuity measurements using a Philippine peso bill are comparable to a standard Jaeger chart.Study Design: This is a cross-sectional study comparing the near visual acuity measurements of a Philippine peso bill and a Jaeger chart among sixty subjects.Methods: LogMAR scores from the two methods were analyzed using Wilcoxon Mann–Whitney test. The relationship of the logMAR scores between these methods was determined using Spearman rank order correlation. The Bland-Altman plot was used to determine the comparability between quantitative measurements for near visual acuity using the standard Jaeger chart (reference) and the Philippine peso bill.Results: There were no significant differences in the proportion of Jaeger scores and mean logMAR equivalents between the two methods (p > 0.05). The scatter plot diagram shows a positive upward trend with a very strong and significant correlation between logMAR scores of Jaeger chart and Philippine peso bill methods (r = 0.9258, p < 0.0001). With a concordance correlation coefficient of 0.9505, there is a high agreement between these two measures. The Philippine peso bill overestimates the Jaeger chart visual acuity by 0.04 logMAR units. We suspect that the contrast between the background color and the serial numbers of the peso bill may have brought about this outcome.Conclusion: The Philippine peso bill may be used as an alternative measuring tool for near visual acuity. However, there is a tendency to overestimate the scores obtained using the Philippine peso bill. Future studies are recommended to validate the results in a tele-ophthalmology setting.Keywords: Jaeger chart, near vision, near visual acuity testing, telemedicine, tele-ophthalmology

Acute kidney injury (AKI) survivors have a dynamic posthospital course which warrants close monitoring. Remote patient monitoring (RPM) could be used to improve quality and efficiency of AKI survivor care. Objective: The objective of this report was to describe the development and preliminary feasibility of an AKI RPM program launched in October 2021. Setting: Academic medical center. Patients: Patients enrolled in the AKI RPM program were those who experienced AKI during a hospitalization and underwent nephrology consultation. Measurements/Methods: At enrollment, patients were provided with home monitoring technology and underwent weekly laboratory assessments. Nurses evaluated the data daily and adhered to prespecified protocols for management and escalation of care if needed. Results: Twenty patients were enrolled in AKI RPM in the first 5 months. Median duration of program participation was 36 (31, 40) days. Eight patients (40%) experienced an unplanned readmission, or an emergency department visit, half (N = 4) of which were attributed to AKI and related circumstances. Of the 9 postgraduation survey respondents, all were satisfied with the RPM program and 89% would recommend RPM to other patients with similar health conditions. Limitations: Acute kidney injury RPM was made possible by the existing infrastructure in our integrated health system and the robust resources available in the Mayo Clinic Center for Digital Health. Such infrastructure may not be universally available which could limit scale and generalizability of such a program. Conclusions: Remote patient monitoring can offer a unique opportunity to bridge the care transition from hospital to home and increase access to quality care for the AKI survivors.

Introducción y objetivos: Zephyranthes bifida (Amaryllidaceae) fue incluida recientemente como única especie polimórfica del subgénero Neorhodophiala. Su historia taxonómica no ha sido reseñada, pudiendo tratarse de un aporte valioso para dilucidar el posible complejo de especies que sugiere la gran variación morfológica observada en su amplio rango de distribución. El presente trabajo tiene como objetivo presentar la historia taxonómica de Z. bifida con la lista completa de sinónimos, junto con algunas observaciones morfológicas. M&M: Se consultaron publicaciones originales, floras y bases de datos digitales. Se elaboró una tabla con la lista completa de sinónimos en la que se incluyó para cada uno, el nombre científico, año y referencia de la publicación, tipo de evento taxonómico y sus sinónimos. En el marco de estudios morfométricos realizados con individuos adultos de ocho poblaciones de la provincia de Buenos Aires, se encontraron ciertas medidas de caracteres que resultaron novedosas al compararlas con las descripciones de Z. bifida. Resultados y conclusiones: Se registraron 49 eventos taxonómicos. A partir del estudio realizado, se propone incluir dos sinónimos nuevos para Z. bifida y reconocer un nombre como ilegítimo, de modo que actualmente se asocia con 43 sinónimos legítimos, tres nombres ilegítimos y dos isónimos sin estatus nomenclatural. El seguimiento de ejemplares cultivados permitió observar que un mismo bulbo puede generar inflorescencias con los dos tipos de espata, descartándose la hipótesis de que esta variable morfológica podría corresponder a taxones diferentes.

BackgroundRemote patient monitoring (RPM) is an option for continuously managing the care of patients in the comfort of their homes or locations outside hospitals and clinics. Patient engagement with RPM programs is essential for achieving successful outcomes and high quality of care. When relying on technology to facilitate monitoring and shifting disease management to the home environment, it is important to understand the patients’ experiences to enable quality improvement. ObjectiveThis study aimed to describe patients’ experiences and overall satisfaction with an RPM program for acute and chronic conditions in a multisite, multiregional health care system. MethodsBetween January 1, 2021, and August 31, 2022, a patient experience survey was delivered via email to all patients enrolled in the RPM program. The survey encompassed 19 questions across 4 categories regarding comfort, equipment, communication, and overall experience, as well as 2 open-ended questions. Descriptive analysis of the survey response data was performed using frequency distribution and percentages. ResultsSurveys were sent to 8535 patients. The survey response rate was 37.16% (3172/8535) and the completion rate was 95.23% (3172/3331). Survey results indicated that 88.97% (2783/3128) of participants agreed or strongly agreed that the program helped them feel comfortable managing their health from home. Furthermore, 93.58% (2873/3070) were satisfied with the RPM program and ready to graduate when meeting the program goals. In addition, patient confidence in this model of care was confirmed by 92.76% (2846/3068) of the participants who would recommend RPM to people with similar conditions. There were no differences in ease of technology use according to age. Those with high school or less education were more likely to agree that the equipment and educational materials helped them feel more informed about their care plans than those with higher education levels. ConclusionsThis multisite, multiregional RPM program has become a reliable health care delivery model for the management of acute and chronic conditions outside hospitals and clinics. Program participants reported an excellent overall experience and a high level of satisfaction in managing their health from the comfort of their home environment.

TAE Technologies’ fifth-generation fusion device, C-2W (also called ‘Norman’), is the world’s largest compact-toroid device and has made significant progress in field-reversed configuration (FRC) plasma performance. C-2W produces record breaking, macroscopically stable, high-temperature advanced beam-driven FRC plasmas, dominated by injected fast particles and sustained in steady state, which is primarily limited by neutral-beam (NB) pulse duration. The NB power supply system has recently been upgraded to extend the pulse length from 30 ms to 40 ms, which allows for a longer plasma lifetime and thus better characterization and further enhancement of FRC performance. An active plasma control system is routinely used in C-2W to produce consistent FRC performance as well as for reliable machine operations using magnet coils, edge-biasing electrodes, gas injection and tunable-energy NBs. Google’s machine learning framework for experimental optimization has also been routinely used to enhance plasma performance. Dedicated plasma optimization experimental campaigns, particularly focused on the external magnetic field profile and NB injection (NBI) optimizations, have produced a superior FRC plasma performance; for instance, achieving a total plasma energy of ∼13 kJ, a trapped poloidal magnetic flux of ∼16 mWb (based on the rigid-rotor model) and plasma sustainment in steady state up to ∼40 ms. Furthermore, under some operating conditions, the electron temperature of FRC plasmas at a quiescent phase has successfully reached up to ∼1 keV at the peak inside the FRC separatrix for the first time. The overall FRC performance is well correlated with the NB and edge-biasing systems, where higher total plasma energy is obtained with higher NBI power and applied voltage on biasing electrodes. C-2W operations have now reached a mature level where the machine can produce hot, stable, long-lived, and repeatable plasmas in a well-controlled manner.

Wall et al. describe the selective activation of an adenosine A1 receptor-mediated intracellular pathway that provides potent analgesia in the absence of sedation or cardiorespiratory depression, paving the way for novel medicines based on the far-reaching concept of selective Gα agonism.

Background While children with Autism Spectrum Disorder show heterogeneous cognitive profiles, they share common deficits in social-cognitive abilities and executive function. Moderate endurance exercise is known to elicit changes in the psychophysiological state, which can translate into immediate, but transient benefits for both cognitive domains. However, the cognitive response of children with Autism Spectrum Disorder to acute exercise remains unclear. We addressed this research deficit by investigating the effects of a single endurance exercise session on face recognition abilities and affective response inhibition. Methods We recruited 30 children with Autism Spectrum Disorder aged 7 to 12 years from local clinicals in Basel, Switzerland and via social media. Using a randomized cross-over design, participants completed a moderately-intense, 20-min exercise session on a cycling ergometer and control condition, which involved sitting on the ergometer. We collected heart rate and ratings of perceived exertion during these sessions. Before and after the experimental conditions, participants completed two computerized cognitive tasks. During the Mooney Face Recognition task, they had to categorize stimuli into faces and objects. In the affective Go/NoGo task, participants were instructed to inhibit their response to either sad or happy faces and press a button to all other faces. Results The experimental manipulation was successful as a main effect of condition indicated a higher heart rate and rating of perceived exertion in the exercise compared to the control condition. With regard to cognitive performance, the repeated measures ANOVA revealed an interaction of time and condition for the Mooney Face Recognition task, indicating an increase in reaction time in the exercise compared to the control condition. In contrast, no interaction of time and condition was found for accuracy on this task as well as accuracy and reaction time on the affective Go/NoGo task. Conclusion In children with Autism Spectrum Disorder, a single exercise does not seem to benefit social-cognitive abilities and executive function temporarily. A short cycling bout rather impairs the ability to recognize faces, suggesting that the maintenance of supervised exercise demands a set of joint resources. As these results are in conflict with the well-documented benefit of acute exercise in healthy populations, the atypical cognitive response in children with Autism Spectrum Disorder indicates a moderating role of this neurodevelopmental condition.

A growing body of work clearly documents the gendered inequalities in health. The COVID-19 pandemic further exposed these deep inequities: men appear to be more vulnerable to poorer outcomes, but most of the global health workforce is female who are at increased risk of exposure to hospital infection. However, researchers often fail to adequately embed gender as part of the public health research. This paper reports findings from a synthesis exercise that identified some of the challenges of integrating gender in the design and processes of research studies in four projects conducted in six low- and middle-income countries. Through a collective retrospective meta-synthesis process with researchers from each project, we identified two main themes; (i) we deep dive on two of the structural pillars of conducting public health research (design and process) and (ii) we describe some of the underlying opportunities and resistances to the integration of a gender perspective in these research projects. In conclusion, we suggest that public health funding bodies require researchers to integrate gender in public health research from early on as part of the design and to conduct gendered analysis, as part of the overall drive towards more equitable health systems delivery.

BackgroundBuruli ulcer, caused by Mycobacterium ulcerans, is a neglected tropical skin disease that is primarily endemic in West and Central Africa, including Côte d'Ivoire. Studies indicate that M. ulcerans infections are caused by contact with an environmental reservoir of the bacteria, governed by specific human biological conditions. Yet, the nature of this reservoir and the exact mode of transmission remain unknown.MethodologyTo identify ecologic risk factors of Buruli ulcer in south-central Côte d'Ivoire, we pursued a qualitative study matched with geo-referencing inquiry. Embedded in a broader integrated wound management research project, we (i) mapped households and water sources of laboratory confirmed Buruli ulcer cases and (ii) interviewed 12 patients and four health care workers to assess exposure to surface water and to deepen the understanding of perceived transmission pathways.Principal findingsWater availability, accessibility, and affordability were reported as key determinants for choosing water resources. Furthermore, perceived risks were related to environmental, structural, and individual factors. Despite the presence of improved water sources (e.g., drilled wells), communities heavily relied on unprotected surface water for a multitude of activities. The nearby Bandama River and seasonal waterbodies were frequently used for washing, bathing, and collection of water for drinking and cooking. Many residents also reported to cross the river on a daily basis for agricultural chores, and hence, are exposed to stagnant water during farming activities.Conclusions/significanceOur study in two Buruli ulcer endemic villages in south-central Côte d'Ivoire revealed a wide range of water-related domestic activities that might expose people to an increased risk of contracting the disease. Environmental, biological, social, and cultural risk factors are closely interlinked and should be considered in future investigations of Buruli ulcer transmission. Active participation of the communities is key to better understand their circumstances to advance research and fight against Buruli ulcer and other neglected tropical diseases.

Objectives: To analyze the treatment success rate (TSR = sum of cured or treatment completed) in the tuberculosis (TB) program for drug-susceptible TB (DS-TB) at the “Centre Hospitalier Régional Spécialisé” in Macenta, Forest Region, Republic of Guinea. Methods: This cohort study included patients who started treatment for DS-TB between 2010 and 2017. Data collection was part of the documentation for the national TB program. Descriptive analysis was applied to determine the TSR in various patient groups. Further, logistic regression was performed to determine factors influencing the TSR in new and relapsed cases versus all other previously treated cases. A subgroup analysis for only microbiologically confirmed pulmonary TB was added. Results: The study included 3969 patients. The TSR increased from 68.3% in 2010 to 80.8% in 2017 (p < 0.001). Mortality (11.2%) mainly occurred in early treatment months, while loss to follow-up (5.9%) increased towards later treatment months. Risk factors for low TSR were advanced age, positive HIV status, long travel distances (>100 km) to the clinic, and late treatment refill. Conclusion: The TSR in the Forest Region of Guinea remained below the WHO goal of 90%. Reaching this target remains a challenge in rural areas with high early mortality and increased risk of loss to follow-up.