The exact Darwin Lagrangian

Darwin (1920) noted that when radiation can be neglected it should be possible to eliminate the radiation degrees-of-freedom from the action of classical electrodynamics and keep the discrete particle degrees-of-freedom only. Darwin derived his well known Lagrangian by series expansion in $v/c$ keeping terms up to order $(v/c)^2$. Since radiation is due to acceleration the assumption of low speed should not be necessary. A Lagrangian is suggested that neglects radiation without assuming low speed. It cures deficiencies of the Darwin Lagrangian in the ultra-relativistic regime.Comment: 2.5 pages, no figure

Comparison of cardiovascular health profiles across population surveys from five high- to low-income countries

Aims With the greatest burden of cardiovascular disease morbidity and mortality increasingly observed in lower-income countries least prepared for this epidemic, focus is widening from risk factor management alone to primordial prevention to maintain high levels of cardiovascular health (CVH) across the life course. To facilitate this, the American Heart Association (AHA) developed CVH scoring guidelines to evaluate and track CVH. We aimed to compare the prevalence and trajectories of high CVH across the life course using nationally representative adult CVH data from five diverse high- to low-income countries. Methods Surveys with CVH variables (physical activity, cigarette smoking, body mass, blood pressure, blood glucose, and total cholesterol levels) were identified in Ethiopia, Bangladesh, Brazil, England, and the United States (US). Participants were included if they were 18-69y, not pregnant, and had data for these CVH metrics. Comparable data were harmonized and each of the CVH metrics was scored using AHA guidelines as high (2), moderate (1), or low (0) to create total CVH scores with higher scores representing better CVH. High CVH prevalence by age was compared creating country CVH trajectories. Results The analysis included 28,092 adults (Ethiopia n=7686, 55.2% male; Bangladesh n=6731, 48.4% male; Brazil n=7241, 47.9 % male; England n=2691, 49.5% male, and the US n=3743, 50.3% male). As country income level increased, prevalence of high CVH decreased (>90% in Ethiopia, >68% in Bangladesh and under 65% in the remaining countries). This pattern remained using either five or all six CVH metrics and following exclusion of underweight participants. While a decline in CVH with age was observed for all countries, higher income countries showed lower prevalence of high CVH already by age 18y. Excess body weight appeared the main driver of poor CVH in higher income countries, while current smoking was highest in Bangladesh. Conclusion Harmonization of nationally representative survey data on CVH trajectories with age in 5 highly diverse countries supports our hypothesis that CVH decline with age may be universal. Interventions to promote and preserve high CVH throughout the life course are needed in all populations, tailored to country-specific time courses of the decline. In countries where CVH remains relatively high, protection of whole societies from risk factor epidemics may still be feasible.This study was funded with support from the Institute for Global Health, Northwestern University [Catalyzer Award No. 1005]; from the DSI-NRF Centre of Excellence in Human Development hosted at the University of the Witwatersrand in South Africa, and the support of the University of the Witwatersrand research office

Plan de negocios para una empresa dedicada al servicio de intermediaci?n entre conductores y pasajeros de servicio de transporte p?blico individual (taxi) a trav?s de una plataforma tecnol?gica : aplicaci?n movil para smartphone

El presente plan de negocio consiste en la prestaci?n de servicio de intermediaci?n entre conductores y pasajeros de servicio de transporte p?blico individual (taxi) a trav?s de una plataforma tecnol?gica (aplicaci?n m?vil para smartphone), teniendo en consideraci?n adicionar a partir del segundo a?o el servicio de publicidad e investigaci?n de mercado, dirigido a las empresas anunciantes y a las que a?n no anuncian, utilizando como herramienta las unidades de transporte de servicio p?blico individual (taxis). Estas unidades ser?n adecuadas para el fin del modelo de negocio adicional. El modelo de negocio propone un portafolio de opciones como publicidad a trav?s de pantallas t?ctiles al interior del veh?culo, publicidad en la luna posterior del veh?culo mediante viniles removibles, aplicaci?n de encuestas y prueba de productos durante el trayecto de viaje del usuario y publicidad mediante folletos. El modelo de negocio adicional se basar? en alianzas estrat?gicas con agencias de publicidad, las cuales ofrecer?n dentro de su abanico de opciones los servicios mencionados a sus clientes. Por otro lado, el servicio de intermediaci?n se realizar? mediante una aplicaci?n m?vil que se descargar? f?cilmente en los dispositivos m?viles, las comisiones que se pagar?n a los conductores ser?n las m?s bajas del mercado permiti?ndoles obtener mayores ganancias por cada servicio, y cuyas tarifas ser?n atractivas para el mercado. El principal ingreso provendr? del servicio de intermediaci?n de taxi ya que representa el 90% de ingresos y el servicio de publicidad e investigaci?n solo el 10%

Factors Associated With the Use of a Salt Substitute in Rural China.

Importance: Lowering sodium intake reduces blood pressure and may reduce the risk of cardiovascular diseases. The use of reduced-sodium salt (a salt substitute) may achieve sodium reduction, but its effectiveness may be associated with the context of its use. Objective: To identify factors associated with the use of salt substitutes in rural populations in China within the Salt Substitute and Stroke Study, a large-scale cluster randomized trial. Design, Setting, and Participants: This sequential mixed-methods qualitative evaluation, conducted from July 2 to August 28, 2018, in rural communities across 3 provinces in China, included a quantitative survey, collection of 24-hour urine samples, and face-to-face interviews. A random subsample of trial participants, selected from the 3 provinces, completed the quantitative survey (n = 1170) and provided urine samples (n = 1025). Interview respondents were purposively selected from the intervention group based on their different ranges of urinary sodium excretion levels. Statistical analysis was performed from September 18, 2018, to February 22, 2019. Exposures: The intervention group of the Salt Substitute and Stroke Study was provided with the free salt substitute while the control group continued to use regular salt. Main Outcomes and Measures: Knowledge, attitudes, and behaviors regarding the use of the salt substitute were measured using quantitative surveys, and urinary sodium levels were measured using 24-hour urine samples. Contextual factors were explored through semistructured interviews and integrated findings from surveys and interviews. Results: A total of 1170 individuals participated in the quantitative survey. Among the 1025 participants with successful urine samples, the mean (SD) age was 67.4 (7.5) years, and 502 (49.0%) were female. The estimated salt intake of participants who believed that high salt intake was good for health was higher; however, it was not significantly different (0.84 g/d [95% CI, -0.04 to 1.72 g/d]) from those who believed that high salt intake was bad for health. Thirty individuals participated in the qualitative interviews (18 women [60.0%]; mean [SD] age, 70.3 [6.0] years). Quantitative and qualitative data indicated high acceptability of and adherence to the salt substitute. Contextual factors negatively associated with the use of the salt substitute included a lack of knowledge about the benefits associated with salt reduction and consumption of high-sodium pickled foods. In addition, reduced antihypertensive medication was reported by a few participants using the salt substitute. Conclusions and Relevance: This study suggests that lack of comprehensive understanding of sodium reduction and salt substitutes and habitual consumption of high-sodium foods (such as pickled foods) were the main barriers to the use of salt substitutes to reduce sodium intake. These factors should be considered in future population-based, sodium-reduction interventions

Cost-Effectiveness of a Household Salt Substitution Intervention: Findings From 20 995 Participants of the Salt Substitute and Stroke Study

Background: SSaSS (Salt Substitute and Stroke Study), a 5-year cluster randomized controlled trial, demonstrated that replacing regular salt with a reduced-sodium, added-potassium salt substitute reduced the risks of stroke, major adverse cardiovascular events, and premature death among individuals with previous stroke or uncontrolled high blood pressure living in rural China. This study assessed the cost-effectiveness profile of the intervention. Methods: A within-trial economic evaluation of SSaSS was conducted from the perspective of the health care system and consumers. The primary health outcome assessed was stroke. We also quantified the effect on quality-adjusted life-years (QALYs). Health care costs were identified from participant health insurance records and the literature. All costs (in Chinese yuan [¥]) and QALYs were discounted at 5% per annum. Incremental costs, stroke events averted, and QALYs gained were estimated using bivariate multilevel models. Results: Mean follow-up of the 20 995 participants was 4.7 years. Over this period, replacing regular salt with salt substitute reduced the risk of stroke by 14% (rate ratio, 0.86 [95% CI, 0.77-0.96]; P=0.006), and the salt substitute group had on average 0.054 more QALYs per person. The average costs (¥1538 for the intervention group and ¥1649 for the control group) were lower in the salt substitute group (¥110 less). The intervention was dominant (better outcomes at lower cost) for prevention of stroke as well as for QALYs gained. Sensitivity analyses showed that these conclusions were robust, except when the price of salt substitute was increased to the median and highest market prices identified in China. The salt substitute intervention had a 95.0% probability of being cost-saving and a >99.9% probability of being cost-effective. Conclusions: Replacing regular salt with salt substitute was a cost-saving intervention for the prevention of stroke and improvement of quality of life among SSaSS participants

The effects of a community-based sodium reduction program in rural china - a cluster-randomized trial

Background Average sodium intake and stroke mortality in northern China are both among the highest in the world. An effective, low-cost strategy to reduce sodium intake in this population is urgently needed. Objective We sought to determine the effects of a community-based sodium reduction program on salt consumption in rural northern China. Design This study was a cluster-randomized trial done over 18 months in 120 townships (one village from each township) from five provinces. Sixty control villages were compared to 60 intervention villages that were given access to a reduced-sodium, added-potassium salt substitute in conjunction with a community-based health education program focusing on sodium reduction. The primary outcome was the difference in 24-hour urinary sodium excretion between randomized groups. Results Among 1,903 people with valid 24-hour urine collections, mean urinary sodium excretion in intervention compared with control villages was reduced by 5.5% (-14mmol/day, 95% confidence interval -26 to -1; p = 0.03), potassium excretion was increased by 16% (+7mmol/day, +4 to +10; p<0.001), and sodium to potassium ratio declined by 15% (-0.9, -1.2 to -0.5; p<0.001). Mean blood pressure differences were -1.1 mm Hg systolic (-3.3 to +1.1; p = 0.33) and -0.7 mm Hg diastolic (-2.2 to +0.8, p = 0.35) and the difference in the proportion with hypertension was -1.3% (-5.1 to 2.5, p = 0.56). Conclusion There were clear differences in population sodium and potassium intake between villages that were most likely a consequence of increased use of salt substitute. The absence of effects on blood pressure reflects the moderate changes in sodium and potassium intake achieved. Trial Registration Clinicaltrials.gov identifier: NCT01259700

Immune cell constitution in bone marrow microenvironment predicts outcome in adult ALL

As novel immunological treatments are gaining a foothold in the treatment of acute lymphoblastic leukemia (ALL), it is elemental to examine ALL immunobiology in more detail. We used multiplexed immunohistochemistry (mIHC) to study the immune contexture in adult precursor B cell ALL bone marrow (BM). In addition, we developed a multivariate risk prediction model that stratified a poor survival group based on clinical parameters and mIHC data. We analyzed BM biopsy samples of ALL patients (n = 52) and healthy controls (n = 14) using mIHC with 30 different immunophenotype markers and computerized image analysis. In ALL BM, the proportions of M1-like macrophages, granzyme B+CD57+CD8+ T cells, and CD27+ T cells were decreased, whereas the proportions of myeloid-derived suppressor cells and M2-like macrophages were increased. Also, the expression of checkpoint molecules PD1 and CTLA4 was elevated. In the multivariate model, age, platelet count, and the proportion of PD1+TIM3+ double-positive CD4+ T cells differentiated a poor survival group. These results were validated by flow cytometry in a separate cohort (n = 31). In conclusion, the immune cell contexture in ALL BM differs from healthy controls. CD4+PD1+TIM3+ T cells were independent predictors of poor outcome in our multivariate risk model, suggesting that PD1 might serve as an attractive immuno-oncological target in B-ALL.Peer reviewe