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Background Heart failure with preserved ejection fraction (HFpEF) is a complex syndrome increasing in prevalence and affecting millions worldwide but with limited evidence‐based therapies. Results from explanatory clinical trials suggest that spironolactone may help to improve outcomes in patients with HFpEF. We sought to investigate the effectiveness of spironolactone in reducing death and hospitalization outcomes for patients with HFpEF in a real‐world setting. Methods and Results We used electronic health records from the US Veterans Affairs (VA) health care system between 2002 and 2012 to identify patients with HFpEF who were followed longitudinally through 2014 using a validated algorithm. Among our HFpEF cohort that is 96% men, 85% White individuals, and aged 74±11 years, 3690 spironolactone users and 49 191 nonusers were identified and followed for a median of 2.9 (interquartile range [IQR], 1.5–2.4) and 3.3 (IQR, 1.6–5.9) years, respectively. We evaluated the effect of spironolactone use on all‐cause death and number of days hospitalized per year for heart failure or for any cause by fitting generalized estimating equation–based Poisson and negative binomial models. Crude rates of 10.3 versus 13.5 deaths and 394.0 versus 485.9 days hospitalized were observed per 100 person‐years for spironolactone users versus nonusers, respectively. After multivariable adjustment, there was a 21% reduction (95% CI, 13–29; P

Background Heart failure (HF) is a serious condition with increasing prevalence, high morbidity, and increased mortality. Obesity is an established risk factor for HF. Fluctuation in body mass index (BMI) has shown a higher risk of cardiovascular outcomes. We investigated the association between BMI variability and incident HF. Methods and Results In the UK Biobank, we established a prospective cohort after excluding participants with prevalent HF or cancer at enrollment. A total of 99 368 White participants with ≥3 BMI measures during >2 years preceding enrollment were included, with a median follow‐up of 12.5 years. The within‐participant variability of BMI was evaluated using standardized SD and coefficient of variation. The association of BMI variability with incident HF was assessed using Fine and Gray's competing risk model, adjusting for confounding factors and participant‐specific rate of BMI change. Higher BMI variability measured in both SD and coefficient of variation was significantly associated with higher risk in HF incidence (SD: hazard ratio [HR], 1.05 [95% CI, 1.03–1.08], P

Abstract We conduct a large-scale meta-analysis of heart failure genome-wide association studies (GWAS) consisting of over 90,000 heart failure cases and more than 1 million control individuals of European ancestry to uncover novel genetic determinants for heart failure. Using the GWAS results and blood protein quantitative loci, we perform Mendelian randomization and colocalization analyses on human proteins to provide putative causal evidence for the role of druggable proteins in the genesis of heart failure. We identify 39 genome-wide significant heart failure risk variants, of which 18 are previously unreported. Using a combination of Mendelian randomization proteomics and genetic cis-only colocalization analyses, we identify 10 additional putatively causal genes for heart failure. Findings from GWAS and Mendelian randomization-proteomics identify seven (CAMK2D, PRKD1, PRKD3, MAPK3, TNFSF12, APOC3 and NAE1) proteins as potential targets for interventions to be used in primary prevention of heart failure.

Abstract In patients with heart failure with preserved ejection fraction (HFpEF), sudden cardiac death (SCD) accounts for approximately 25–30% of all‐cause mortality and 40% of cardiovascular mortality in properly adjudicated large clinical trials. The mechanism of SCD in HFpEF remains unknown but thought to be driven by arrhythmic events. Apart from atrial fibrillation, which is prevalent in approximately 45% of HFpEF patients, the true burden of other cardiac arrhythmias in HFpEF remains undetermined. The incidence and risk of clinically significant advanced cardiac conduction disease with bradyarrhythmias and ventricular arrhythmias remain less known. Recommendations have been made for long‐term cardiac rhythm monitoring to determine the incidence of arrhythmias and clarify mechanisms and mode of death in HFpEF patients. In animal studies, spontaneous ventricular arrhythmias and SCD are significantly elevated in HFpEF animals compared with controls without heart failure. In humans, these studies are scant, with a few published small‐size studies suggesting an increased incidence of ventricular arrhythmias in HFpEF. Higher rates of clinically significant conduction disease and cardiac pacing are seen in HFpEF compared with the general population. Excepting atrial fibrillation, the predictive effect of other arrhythmias on heart failure hospitalization, all‐cause mortality, and precisely SCD remains unknown. Given the high occurrence of SCD in the HFpEF population, it could potentially become a target for therapeutic interventions if driven by arrhythmias. Studies to address these knowledge gaps are urgently warranted. In this review, we have summarized data on arrhythmias and SCD in HFpEF while highlighting avenues for future research in this area.

OBJECTIVES/GOALS: The correction of spinopelvic parameters is associated with better outcomes in patients with adult spinal deformity (ASD). This study presents a novel artificial intelligence (AI) tool that automatically predicts spinopelvic parameters from spine x-rays with high accuracy and without need for any manual entry. METHODS/STUDY POPULATION: The AI model was trained/validated on 761 sagittal whole-spine x-rays to predict the following parameters: Sagittal Vertical Axis (SVA), Pelvic Tilt (PT), Pelvic Incidence (PI), Sacral Slope (SS), Lumbar Lordosis (LL), T1-Pelvic Angle (T1PA), and L1-Pelvic Angle (L1PA). A separate test set of 40 x-rays was labeled by 4 reviewers including fellowship-trained spine surgeons and a neuroradiologist. Median errors relative to the most senior reviewer were calculated to determine model accuracy on test and cropped-test (i.e. lumbosacral) images. Intraclass correlation coefficients (ICC) were used to assess inter-rater reliability RESULTS/ANTICIPATED RESULTS: The AI model exhibited the following median (IQR) parameter errors: SVA[2.1mm (8.5mm), p=0.97], PT [1.5° (1.4°), p=0.52], PI[2.3° (2.4°), p=0.27], SS[1.7° (2.2°), p=0.64], LL [2.6° (4.0°), p=0.89], T1PA [1.3° (1.1°), p=0.41], and L1PA [1.3° (1.2°), p=0.51]. The parameter errors on cropped lumbosacral images were: LL[2.9° (2.6°), p=0.80] and SS[1.9° (2.2°), p=0.78]. The AI model exhibited excellent reliability at all parameters in both whole-spine (ICC: 0.92-1.0) and lumbosacral x-rays: (ICC: 0.92-0.93). DISCUSSION/SIGNIFICANCE: Our AI model accurately predicts spinopelvic parameters with excellent reliability comparable to fellowship-trained spine surgeons and neuroradiologists. Utilization of predictive AI tools in spine-imaging can substantially aid in patient selection and surgical planning.

While the genetic basis of heart failure has been explored by genetic studies, the differences between subtypes are not well understood. Here, the authors performed genetic analyses on the two major subtypes of heart failure in a large biobank with genetic and health record data, finding unique genetic architecture for each subtype.

This study investigates a low-temperature three-circuit cooling system for a 55 kW industrial electric motor. The cooling system provides an increase of the power-to-dimension ratio by 63%, together with an improvement in motor performance. The three-circuit cooling system includes water cooling of the housing and stator and air-cooling of the motor’s interior. The test results show that the motor efficiency was maintained in the range between 92.5 and 94.5%, with respect to the motor’s power. With power increases up to 90 kW, a winding temperature of 67 °C was observed during three hours of operation. This advancement is particularly valuable for vehicles, ships, and aircraft applications, where maximizing power within limited space is crucial. An analysis of the experimental data showed that the cooling system operates at an average efficiency of 79.2%, indicating that roughly 20% of heat was accumulated in the rotor. This leads to a gradual temperature rise, particularly in the rotor, posing a risk of overheating and failure during motor overloads above 90 kW. Enhancing the cooling efficiency within the motor’s interior can be achieved by incorporating extra heat exchangers, implementing evaporative heat transfer, and employing water-cooling circuits at lower temperatures. This, in turn, can boost the electric motor’s power-to-dimension ratio.

Heart failure is a major cause of cardiovascular morbidity and mortality. Here, the authors report results of a genome-wide association study meta-analysis, characterizing the role of common genetic variants in heart failure, finding overlap with common cardiovascular risk factors and imaging measures of cardiac structure/function.

Abstract Remdesivir is the first US Food and Drug Administration (FDA)‐approved drug for the treatment of coronavirus disease 2019 (COVID‐19). We conducted a retrospective pharmacogenetic study to examine remdesivir‐associated liver enzyme elevation among Million Veteran Program participants hospitalized with COVID‐19 between March 15, 2020, and June 30, 2021. Pharmacogene phenotypes were assigned using Stargazer. Linear regression was performed on peak log‐transformed enzyme values, stratified by population, adjusted for age, sex, baseline liver enzymes, comorbidities, and 10 population‐specific principal components. Patients on remdesivir had higher peak alanine aminotransferase (ALT) values following treatment initiation compared with patients not receiving remdesivir. Remdesivir administration was associated with a 33% and 24% higher peak ALT in non‐Hispanic White (NHW) and non‐Hispanic Black (NHB) participants (p

Abstract Background Improving contractility in heart failure with reduced ejection fraction (HFrEF) has resurfaced as a potential treatment goal. Inotropic therapy is now better understood through its underlying mechanism as opposed to the observed effect of increasing contractility. Calcitropes are a subgroup of inotropes that largely depend on the stimulation of adenylyl cyclase to transform ATP into cyclic adenosine monophosphate (cAMP). At least two clinically relevant calcitropes—istaroxime and probenecid—improve contractility through an increase in systolic intracellular calcium without activating cAMP production. Probenecid, which has been safely used clinically for decades in non-cardiac conditions, has recently been identified as an agonist of the transient receptor potential vanilloid 2 channel. Translational studies have shown that it improves calcium cycling and contractility without activating noxious pathways associated with cAMP-dependent calcitropes and can improve cardiac function in patients with HFrEF. Methods The Re-Prosper-HF study (Repurposing Probenecid for the Treatment of Heart Failure with Reduced Ejection Fraction) is a three-site double-blinded randomized-controlled trial that will test the hypothesis that probenecid can improve cardiac function in patients with HFrEF. Up to 120 patients will be randomized in this double-blind, placebo-controlled study that will assess whether oral probenecid administered at 1 g orally twice per day for 180 days in patients with NYHA II-III HFrEF improves systolic function (aim 1), functional status (aim 2), and self-reported health status (aim 3). Discussion Findings from this study will provide data informing its use for improving symptomatology in patients with HFrEF as well as exploratory data for outcomes such as hospital admission rates. Trial tegistration The Re-Prosper HF Study (Re-Prosper HF) is registered on ClinicalTrials.gov with the identifier as NCT04551222. Registered on 9 September 2020.

Abstract Aims This study aims to develop the first race‐specific and sex‐specific risk prediction models for heart failure with preserved (HFpEF) and reduced ejection fraction (HFrEF). Methods and results We created a cohort of 1.8 million individuals who had an outpatient clinic visit between 2002 and 2007 within the Veterans Affairs (VA) Healthcare System and obtained information on HFpEF, HFrEF, and several risk factors from electronic health records (EHR). Variables were selected for the risk prediction models in a ‘derivation cohort’ that consisted of individuals with baseline date in 2002, 2003, or 2004 using a forward stepwise selection based on a change in C‐index threshold. Discrimination and calibration were assessed in the remaining participants (internal ‘validation cohort’). A total of 66 831 individuals developed HFpEF, and 92 233 developed HFrEF (52 679 and 71 463 in the derivation cohort) over a median of 11.1 years of follow‐up. The HFpEF risk prediction model included age, diabetes, BMI, COPD, previous MI, antihypertensive treatment, SBP, smoking status, atrial fibrillation, and estimated glomerular filtration rate (eGFR), while the HFrEF model additionally included previous CAD. For the HFpEF model, C‐indices were 0.74 (SE = 0.002) for white men, 0.76 (0.005) for black men, 0.79 (0.015) for white women, and 0.77 (0.026) for black women, compared with 0.72 (0.002), 0.72 (0.004), 0.77 (0.017), and 0.75 (0.028), respectively, for the HFrEF model. These risk prediction models were generally well calibrated in each race‐specific and sex‐specific stratum of the validation cohort. Conclusions Our race‐specific and sex‐specific risk prediction models, which used easily obtainable clinical variables, can be a useful tool to implement preventive strategies or subtype‐specific prevention trials in the nine million users of the VA healthcare system and the general population after external validation.

Abstract Hereditary transthyretin-mediated (hATTR) amyloidosis is an underdiagnosed, progressively debilitating disease caused by mutations in the transthyretin (TTR) gene. V122I, a common pathogenic TTR mutation, is found in 3–4% of individuals of African ancestry in the United States and has been associated with cardiomyopathy and heart failure. To better understand the phenotypic consequences of carrying V122I, we conducted a phenome-wide association study scanning 427 ICD diagnosis codes in UK Biobank participants of African ancestry (n = 6062). Significant associations were tested for replication in the Penn Medicine Biobank (n = 5737) and the Million Veteran Program (n = 82,382). V122I was significantly associated with polyneuropathy in the UK Biobank (odds ratio [OR] = 6.4, 95% confidence interval [CI] 2.6–15.6, p = 4.2 × 10−5), which was replicated in the Penn Medicine Biobank (OR = 1.6, 95% CI 1.2–2.4, p = 6.0 × 10–3) and Million Veteran Program (OR = 1.5, 95% CI 1.2–1.8, p = 1.8 × 10−4). Polyneuropathy prevalence among V122I carriers was 2.1%, 9.0%, and 4.8% in the UK Biobank, Penn Medicine Biobank, and Million Veteran Program, respectively. The cumulative incidence of common hATTR amyloidosis manifestations (carpal tunnel syndrome, polyneuropathy, cardiomyopathy, heart failure) was significantly enriched in V122I carriers compared with non-carriers (HR = 2.8, 95% CI 1.7–4.5, p = 2.6 × 10−5) in the UK Biobank, with 37.4% of V122I carriers having at least one of these manifestations by age 75. Our findings show that V122I carriers are at increased risk of polyneuropathy. These results also emphasize the underdiagnosis of disease in V122I carriers with a significant proportion of subjects showing phenotypic changes consistent with hATTR amyloidosis. Greater understanding of the manifestations associated with V122I is critical for earlier diagnosis and treatment.

Understanding and mitigating the degradation of batteries is important for financial as well as environmental reasons. Many studies look at cell degradation in terms of capacity losses and the mechanisms causing them. However, in this study, we take a closer look at how degradation affects heat sources in batteries, thereby requiring dynamic cooling strategies for battery systems throughout the battery life. In this work, we have studied and compared reversible (entropy-related) and non-reversible heat sources in a commercial LCO-graphite lithium-ion battery (LIB) alongside measuring the surface temperature as a function of the State of Health (SoH). In addition, we studied the effect of different thermal management strategies on both degradation and cooling efficiency. We found that entropic heating plays a major role in overall heat generation. This causes large variations in heat generation and battery temperature over both State of Charge (SoC) and charge versus discharge. The maximum battery temperature increases when the cell degrades as irreversible heat generation increases. Temperature variations over the cell thickness are substantial and increase drastically when the cell degrades. In addition, significant increases in thickness were observed as a result of cell degradation. Furthermore, cycling at elevated temperatures resulted in a larger thickness increase with significant gas production.

Abstract Along with its heavy toll of morbidity and mortality, the coronavirus disease 2019 (COVID-19) pandemic exposed several limitations of the current global research response. The slow and inefficient process of carrying out traditional randomized clinical trials led regulatory authorities to hastily approve treatments and tests without sufficient evidence of safety and efficacy. We here outline issues with the current research platform, summarize shortcomings of traditional randomized clinical trials particularly apparent at the time of pandemics, and highlight the advantages of pragmatic clinical trials as an alternative to rapidly generate the needed clinical evidence. We further discuss barriers and challenges to pragmatic clinical trials implementation and explore opportunities for research institutions and regulatory authorities to facilitate widespread adoption of this vital research tool. As a subsequent wave of COVID-19, and/or another epidemic, are all but inevitable in our lifetime, we must ensure that our research infrastructure is conducive to carrying out pragmatic clinical trials to expeditiously generate the needed evidence and blunt the epidemic’s toll on human lives and livelihoods.

The evaporation of N-Methyl-2-Pyrrolidone (NMP) solvent during the large-scale production of LiNixMn1−x−yCoyO2 (NMC) cathodes usually occurs in convection ovens. This paper aims to close the gap between the industrial convection drying method and the conventional vacuum oven typically used at the laboratory scale. Multiple studies focus on modeling convection dryers to reduce energy consumption, but few have studied their impact on the cathode quality experimentally and compared them to vacuum-dried cathodes. A convection oven designed for LIB electrode drying was developed to investigate the influence of drying kinetics on the formation of small electrode surface cracks (2) and binder migration. The drying kinetics were revealed through thermogravimetric analysis (TGA) at drying temperatures of 50 and 100 °C and hot air velocities of 0.5 and 1 m/s. Even at these relatively low drying rates, structural differences were detected when comparing the two drying methods, illustrating the importance of implementing drying conditions that represent the industry process in laboratories. Surface cracking increased with drying rates, and cathodes with multiple cracks after calendering obtained a higher discharge capacity at discharge currents >C/2. An alternative surface analysis with less sample preparation was sufficient for determining the relative change in binder migration.

SARS-CoV-2 has caused symptomatic COVID-19 and widespread death across the globe. We sought to determine genetic variants contributing to COVID-19 susceptibility and hospitalization in a large biobank linked to a national United States health system. We identified 19,168 (3.7%) lab-confirmed COVID-19 cases among Million Veteran Program participants between March 1, 2020, and February 2, 2021, including 11,778 Whites, 4,893 Blacks, and 2,497 Hispanics. A multi-population genome-wide association study (GWAS) for COVID-19 outcomes identified four independent genetic variants (rs8176719, rs73062389, rs60870724, and rs73910904) contributing to COVID-19 positivity, including one novel locus found exclusively among Hispanics. We replicated eight of nine previously reported genetic associations at an alpha of 0.05 in at least one population-specific or the multi-population meta-analysis for one of the four MVP COVID-19 outcomes. We used rs8176719 and three additional variants to accurately infer ABO blood types. We found that A, AB, and B blood types were associated with testing positive for COVID-19 compared with O blood type with the highest risk for the A blood group. We did not observe any genome-wide significant associations for COVID-19 severity outcomes among those testing positive. Our study replicates prior GWAS findings associated with testing positive for COVID-19 among mostly White samples and extends findings at three loci to Black and Hispanic individuals. We also report a new locus among Hispanics requiring further investigation. These findings may aid in the identification of novel therapeutic agents to decrease the morbidity and mortality of COVID-19 across all major ancestral populations.

The temperature of the lithium-ion battery is a crucial measurement during usage for better operation, safety and health of the battery. In-situ monitoring of the internal temperature of the cells is an important input for temperature control of battery management systems and various other related measurements of the battery, such as state-of-charge and state-of-health. Currently, most commercial battery management systems rely on the surface temperature measurements of the cell. However, the internal temperature is comparatively higher than the surface temperature due to heat generation within the cell and lower heat rejection compared to the surface; therefore, accurate internal temperature monitoring methods are essential to improve our knowledge of battery safety and health. This paper reviews the most recent studies of various online internal temperature monitoring techniques under two main themes of hard sensors and soft sensors. The hard sensors include sensors that need to be inserted into the cell and other methods that use contact-less measuring techniques to infer the internal temperature. The soft sensors include estimators/observers that use surface measurements and various models to estimate the internal temperature. More focus is given to the soft sensors due to the lack of an existing, in-depth review of these. These methods are analyzed in detail with their accuracy, implementation, measurement frequency, and the common challenges and benefits are discussed. Further, possible future trends in internal temperature sensing are also discussed.

Introduction Coronary artery disease (CAD), the leading cause of mortality worldwide, is characterised by an earlier onset and more severe disease in South Asians as compared to Western populations. Methods This is an observational study on 928 individuals who attended three tertiary care centres in Kerala, India from 2014-to 2017. The demographic, anthropometric, behavioural factors and the lipoprotein (Lp(a)) and cholesterol values were compared between the two groups and across disease severity. The Chi-square test was used to compare the categorical variables and independent sample t-test for the continuous variables. Multivariable logistic regression was performed to investigate the association of demographic, clinical and behavioural factors with the disease. Odds ratios are presented with a 95% confidence interval. In individuals below 50 years, two logistic regression models were compared to investigate the improvement in modelling the association of the independent factors and Lp(a) with the occurrence of the disease. Results We included 682 patients in the diseased group and 246 patients treated for non-coronary conditions in the control group. Those in the control group were significantly younger than in the diseased group(pConclusion Age, diabetes, hypertension and tobacco use appear to be associated more with the occurrence of coronary artery disease in adults of all ages. Lipoprotein(a), cholesterol and BMI categories do not seem to be related to disease status in all ages. However, in individuals below 50 years, diabetes, tobacco use and lipoprotein (a) are significantly associated with the occurrence of the disease.

Background: This study aimed to determine the toileting ability (TA) of patients undergoing primary reverse total shoulder arthroplasty (RTSA) and identify factors associated with TA postoperatively. Methods: A questionnaire regarding toileting was administered to 119 patients who underwent primary RTSA with a minimum 1-year follow-up. Patients were separated into 2 groups based on whether the arm that underwent RTSA was the one used for toileting (study group, n = 74) or not (control group, n = 45). Patient-reported TA was calculated both before and after RTSA. Multivariate analysis was performed to identify factors associated with TA postoperatively. Results: Impairment in TA before RTSA was higher in the study group and affected almost three-quarters of the patients (72%). In the study group, primary RTSA resulted in a statistically significant improvement in TA (P < .001), and no difference in TA was found between groups after RTSA (P = .076). Postoperatively, 92% of the patients in the study group were able to manage toileting with the involved extremity (54% without difficulty and 38% with some degree of difficulty). Only 1 patient (1.3%) was totally unable to manage toileting with either arm postoperatively. The patients at risk of toileting difficulties postoperatively were those who had preoperative toileting difficulties and lower postoperative internal rotation range of motion. Conclusions: Over 90% of patients can manage toileting after primary RTSA, and total toileting inability is rare after the procedure (1.3%). Patients should be counseled that after primary RTSA, they have a high probability of being able to manage toileting with independence even if it is with some difficulty.

Background: Reverse total shoulder arthroplasty (RTSA) can lead to limited postoperative internal rotation (IR). We assessed how IR is measured and reported in the RTSA literature and examined the relationships between these measures and patient-reported ability to perform activities of daily living. Methods: We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials for articles published in English from January 2000 through September 2018 that reported clinical outcomes after RTSA (minimum 12-month follow-up). We included studies reporting IR range of motion (ROM) and/or patient-reported functional outcomes related to IR. We identified 255 studies, 35% of which were excluded because they reported no IR outcome measures, leaving 165 studies for analysis. Results: Studies reported 3 methods of measuring IR ROM: (1) vertebral level (VL) method (ie, the most proximal VL reached by the extended thumb with the arm behind the back), (2) degrees of IR with the arm abducted to 90°, and (3) degrees of IR with the arm in a neutral position. The VL measurement was reported in 89% of studies, but the methods of reporting this measure varied. Only 9% of studies reported functional outcomes related to IR. No study correlated clinical measurements of IR ROM with functional outcomes. Conclusions: Measures and reporting of shoulder IR after RTSA varied widely. This variability makes it difficult to assess associations between postoperativce IR limitation and functional abilities. Standardization of IR measures and reporting is needed to allow meta-analysis of data related to this important outcome.

Abstract Background In a real-world setting, the effect of pulse rate measured at the time of diagnosis and serially during follow-up and management, on outcomes in heart failure with reduced ejection fraction (HFrEF), has not been well-studied. Furthermore, how beta-blockade use in a real-world situation modifies this relation between pulse rate and outcomes in HFrEF is not well-known. Hence, we identified a large, national, real-world cohort of HFrEF to examine the association of pulse rate and outcomes. Methods Using Veterans Affairs (VA) national electronic health records we identified incident HFrEF cases between 2006 and 2012. We examined the associations of both baseline and serially measured pulse rates, with mortality and days hospitalized per year for heart failure and for any cause, using crude and multivariable Cox proportional hazards and Poisson or negative binomial models, respectively. The exposure was examined as continuous, dichotomous, and categorical. Post-hoc analyses addressed the interaction of pulse rate and beta-blocker target dose. Results We identified 51,194 incident HFrEF cases (67 ± 12 years, 98% male, 77% white. A significant positive, near linear relationship was observed for both baseline and serially measured pulse rates with all-cause mortality, all-cause hospitalization and heart failure hospitalization after adjusting for covariates including beta-blocker use. Patients who had a pulse rate ≥ 70 bpm in the past 6 months had 36% (95% CI: 31–42%), 25% (95% CI: 19–32%), and 51% (95% CI: 33–72%) increased rates of mortality, all-cause hospitalization, and heart failure hospitalization, respectively, compared to patients with pulse rates

Functional appliances are widely used for regulating and directing growth in which commonly used are Frankel regulator and twinblock. Frankel regulator expands the orofacial arena for allowing growth by passive expansion, whereas twin block aids sagittal correction in retrusive mandible. Heres, an attempt to bring about both the changes in a single appliance where sagittal correction as well as keeping away constricted musculature is desired. In this appliance, passive and active expansion has been used simultaneously for better results. In the hindsight of the results, we could get in this case using Twinkle R 3D appliance, we hope that this appliance will be helpful in many more similar cases and act as adundum in clinician's armamentarium.

PurposeThe aims of this study were to (1) quantify the multidimensional attributes of male and female basketball athletes under 16 years of age (U16) and under 18 years of age (U18), and (2) identify attributes that distinguish selection into a talent pathway according to sex and age group.Methods67 male and 71 female athletes competing in U16 and U18 selection trials for a state based Australian basketball talent pathway completed a multidimensional testing battery. The test battery consisted of anthropometric, physical (20- linear sprint, countermovement jump height, Yo-Yo Intermittent Recovery Test Level 2), technical (Basketball Jump Shooting Accuracy Test), tactical (video decision making), and psychological (Sports Orientation Questionnaire, Psychological Performance Inventory-Alternative) assessments. Mean differences and independent t-tests were used to assess comparative differences between selected and non-selected athletes within each age and sex cohort. Stepwise discriminant analyses were used to identify attributes that were the strongest discriminators of selection in each group (male U16, male U18, female U16, and female U18).ResultsThe discrimminant models showed for male U16 athletes smaller height (ES = -0.18) and greater shooting accuracy (ES = 0.52) was most discriminant of selection. Results were largely homogenous for male U18 athletes with lower visualisation score (ES = -0.62) most discriminant of selection. In female cohorts, faster 20-m sprint time (ES = -0.66) and taller height (ES = 0.58) was most discriminant of selection in U16 athletes while greater shooting accuracy (ES = 0.67), countermovement jump height (ES = 1.04), and height (ES = 0.65) was most discriminant of selection in U18 athletes.ConclusionsThese results emphasise the differing selection priorities within adolescent basketball cohorts according to sex and age group. The testing of anthropometric, physical and technical attributes may hold particular utility in adolescent female basketball given their identified importance to selection across U16 and U18 cohorts.

The present study examines the fluency effect and factors which may influence its prevalence. The fluency effect is a phenomenon first reported by Keysar (2010) that purports that people attribute less believability to those with accented speech as opposed to those with native accents, despite the content of speech being identical. The fluency effect is thought to be due to language processing efficiency alone, rather than to any influence outside of the language processing system. This claim, however, is untested. The present study first replicates the experiment conducted by Keysar (2010) where participants were asked to listen to trivia facts and indicate whether they are true or false. Participants were then asked to complete measures for additional potential influencing factors. The additional factors of interest for this project are the prejudicial views and biases of the participants as measured by the Feeling Thermometer and the Implicit Association Test respectively. In contrast to earlier work, this study showed no evidence of a fluency effect. The study also showed no evidence that prejudices and biases affected the participants’ responses to statements by different speakers.

The Reverse electrodialysis heat engine (REDHE) combines a reverse electrodialysis stack for power generation with a thermal regeneration unit to restore the concentration difference of the salt solutions. Current approaches for converting low-temperature waste heat to electricity with REDHE have not yielded conversion efficiencies and profits that would allow for the industrialization of the technology. This review explores the concept of Heat-to-Hydrogen with REDHEs and maps crucial developments toward industrialization. We discuss current advances in membrane development that are vital for the breakthrough of the RED Heat Engine. In addition, the choice of salt is a crucial factor that has not received enough attention in the field. Based on ion properties relevant for both the transport through IEMs and the feasibility for regeneration, we pinpoint the most promising salts for use in REDHE, which we find to be KNO3, LiNO3, LiBr and LiCl. To further validate these results and compare the system performance with different salts, there is a demand for a comprehensive thermodynamic model of the REDHE that considers all its units. Guided by such a model, experimental studies can be designed to utilize the most favorable process conditions (e.g., salt solutions).

Abstract Background Heart failure (HF) with preserved ejection fraction (HFpEF) comprises nearly half of prevalent HF, yet is challenging to curate in a large database of electronic medical records (EMR) since it requires both accurate HF diagnosis and left ventricular ejection fraction (EF) values to be consistently ≥50%. Methods We used the national Veterans Affairs EMR to curate a cohort of HFpEF patients from 2002 to 2014. EF values were extracted from clinical documents utilizing natural language processing and an iterative approach was used to refine the algorithm for verification of clinical HFpEF. The final algorithm utilized the following inclusion criteria: any International Classification of Diseases-9 (ICD-9) code of HF (428.xx); all recorded EF ≥50%; and either B-type natriuretic peptide (BNP) or aminoterminal pro-BNP (NT-proBNP) values recorded OR diuretic use within one month of diagnosis of HF. Validation of the algorithm was performed by 3 independent reviewers doing manual chart review of 100 HFpEF cases and 100 controls. Results We established a HFpEF cohort of 80,248 patients (out of a total 1,155,376 patients with the ICD-9 diagnosis of HF). Mean age was 72 years; 96% were males and 12% were African-Americans. Validation analysis of the HFpEF algorithm had a sensitivity of 88%, specificity of 96%, positive predictive value of 96%, and a negative predictive value of 87% to identify HFpEF cases. Conclusion We developed a sensitive, highly specific algorithm for detecting HFpEF in a large national database. This approach may be applicable to other large EMR databases to identify HFpEF patients.

Selenium (Se) is a trace nutrient that promotes human health through its incorporation into selenoproteins in the form of the redox-active amino acid selenocysteine (Sec). There are 25 selenoproteins in humans, and many of them play essential roles in the protection against oxidative stress. Selenoproteins, such as glutathione peroxidase and thioredoxin reductase, play an important role in the reduction of hydrogen and lipid hydroperoxides, and regulate the redox status of Cys in proteins. Emerging evidence suggests a role for endoplasmic reticulum selenoproteins, such as selenoproteins K, S, and T, in mediating redox homeostasis, protein modifications, and endoplasmic reticulum stress. Selenoprotein P, which functions as a carrier of Se to tissues, also participates in regulating cellular reactive oxygen species. Cellular reactive oxygen species are essential for regulating cell growth and proliferation, protein folding, and normal mitochondrial function, but their excess causes cell damage and mitochondrial dysfunction, and promotes inflammatory responses. Experimental evidence indicates a role for individual selenoproteins in cardiovascular diseases, primarily by modulating the damaging effects of reactive oxygen species. This review examines the roles that selenoproteins play in regulating vascular and cardiac function in health and disease, highlighting their antioxidant and redox actions in these processes.

Sodium is an essential mineral and nutrient used in dietary practices across the world and is important to maintain proper blood volume and blood pressure. A high sodium diet is associated with increased expression of β—myosin heavy chain, decreased expression of α/β—myosin heavy chain, increased myocyte enhancer factor 2/nuclear factor of activated T cell transcriptional activity, and increased salt-inducible kinase 1 expression, which leads to alteration in myocardial mechanical performance. A high sodium diet is also associated with alterations in various proteins responsible for calcium homeostasis and myocardial contractility. Excessive sodium intake is associated with the development of a variety of comorbidities including hypertension, chronic kidney disease, stroke, and cardiovascular diseases. While the American College of Cardiology/American Heart Association/Heart Failure Society of America guidelines recommend limiting sodium intake to both prevent and manage heart failure, the evidence behind such recommendations is unclear. Our review article highlights evidence and underlying mechanisms favoring and contradicting limiting sodium intake in heart failure.

Background The purpose of this study was to evaluate the relationship between serum sodium at the time of diagnosis and long term clinical outcomes in a large national cohort of patients with heart failure with preserved ejection fraction. Methods and Results We studied 25 440 patients with heart failure with preserved ejection fraction treated at Veterans Affairs medical centers across the United States between 2002 and 2012. Serum sodium at the time of heart failure diagnosis was analyzed as a continuous variable and in categories as follows: low (115.00–134.99 mmol/L), low‐normal (135.00–137.99 mmol/L), referent group (138.00–140.99 mmol/L), high normal (141.00–143.99 mmol/L), and high (144.00–160.00 mmol/L). Multivariable Cox regression and negative binomial regression were performed to estimate hazard ratios (95% confidence interval [CI]) and incidence density ratios (95% CI) for the associations of serum sodium with mortality and hospitalizations (heart failure and all‐cause), respectively. The average age of patients was 70.8 years, 96.2% were male, and 14% were black. Compared with the referent group, low, low‐normal, and high sodium values were associated with 36% (95% CI, 28%–44%), 6% (95% CI, 1%–12%), and 9% (95% CI, 1%–17%) higher risk of all‐cause mortality, respectively. Low and low‐normal serum sodium were associated with 48% (95% CI, 10%–100%) and 38% (95% CI, 8%–77%) higher risk of number of days of heart failure hospitalizations per year, and with 44% (95% CI, 32%–56%) and 18% (95% CI, 10%–27%) higher risk of number of days of all‐cause hospitalizations per year, respectively. Conclusions Both elevated and reduced serum sodium, including values currently considered within normal range, are associated with adverse outcomes in patients with heart failure with preserved ejection fraction.

Over the last four decades, abnormalities in the methionine-homocysteine cycle and associated folate metabolism have garnered great interest due to the reported link between hyperhomocysteinemia and human pathology, especially atherothrombotic cardiovascular disease. However, clinical trials of B-vitamin supplementation including high doses of folic acid have not demonstrated any benefit in preventing or treating cardiovascular disease. In addition to the fact that these clinical trials may have been shorter in duration than appropriate for modulating chronic disease states, it is likely that reduction of the blood homocysteine level may be an oversimplified approach to a complex biologic perturbation. The methionine-homocysteine cycle and folate metabolism regulate redox and methylation reactions and are, in turn, regulated by redox and methylation status. Under normal conditions, a normal redox-methylation balance, or “methoxistasis”, exists, coordinated by the methionine-homocysteine cycle. An abnormal homocysteine level seen in pathologic states may reflect a disturbance of methoxistasis. We propose that future research should be targeted at estimating the deviation from methoxistasis and how best to restore it. This approach could lead to significant advances in preventing and treating cardiovascular diseases, including heart failure.

Although selenium metabolism is intricately linked to cardiovascular biology and function, and deficiency of selenium is associated with cardiac pathology, utilization of selenium in the prevention and treatment of cardiovascular disease remains an elusive goal. From a reductionist standpoint, the major function of selenium in vivo is antioxidant defense via its incorporation as selenocysteine into enzyme families such as glutathione peroxidases and thioredoxin reductases. In addition, selenium compounds are heterogeneous and have complex metabolic fates resulting in effects that are not entirely dependent on selenoprotein expression. This complex biology of selenium in vivo may underlie the fact that beneficial effects of selenium supplementation demonstrated in preclinical studies using models of oxidant stress-induced cardiovascular dysfunction, such as ischemia-reperfusion injury and myocardial infarction, have not been consistently observed in clinical trials. In fact, recent studies have yielded data that suggest that unselective supplementation of selenium may, indeed, be harmful. Interesting biologic actions of selenium are its simultaneous effects on redox balance and methylation status, a combination that may influence gene expression. These combined actions may explain some of the biphasic effects seen with low and high doses of selenium, the potentially harmful effects seen in normal individuals, and the beneficial effects noted in preclinical studies of disease. Given the complexity of selenium biology, systems biology approaches may be necessary to reach the goal of optimization of selenium status to promote health and prevent disease.

Los resultados de este estudio (N = 198) sugieren que la inteligencia emocional es un predictor significativo de la eticidad individual, la percepción de la condición ética de los demás y la percepción de que el comportamiento no ético facilita el éxito. Especialmente, la inteligencia emocional muestra varianza añadida en la percepción de la condición ética de los demás, sobre la explicada por la eticidad individual. La relación entre la inteligencia emocional y la percepción de que el comportamiento no ético facilita el éxito está totalmente mediada por la autoestima. Los resultados sugieren que los trabajadores emocionalmente inteligentes, frente a los bajos en inteligencia emocional, son más expertos en la interpretación de la eticidad de las acciones de los demás y potencialmente menos propensos a participar en las acciones poco éticas. Se discuten las implicaciones para la investigación y la práctica.