Cosmological implications of massive gravitons

The van Dam-Veltman-Zakharov (vDVZ) discontinuity requires that the mass $m$ of the graviton is exactly zero, otherwise measurements of the deflection of starlight by the Sun and the precession of Mercury's perihelion would conflict with their theoretical values. This theoretical discontinuity is open to question for numerous reasons. In this paper we show from a phenomenological viewpoint that the $m>0$ hypothesis is in accord with Supernova Ia and CMB observations, and that the large scale structure of the universe suggests that $m \sim 10^{-30}$eV$/c^2$.Comment: 13 pages, 1 figur

Expeditious synthesis of isolated Steroids-Fluorine prodrugs, their single crystal X-ray crystallography, DFT studies and mathematical modeling

In the present research article, we have synthesized novel steroidal-fluorine prodrugs using cholesterol (1), stigmasterol (4) and hydrocortisone acetate (7) isolated from the flowers of Allamanda violacea. These isolated compounds were converted into their fluorinated prodrugs Cholest-5-en-3β-yl-2-fluoro-benzoate (2), Cholest-5-en-3β-yl-4-fluoro-benzoate (3), 24α-ethylcholest-5, 22E-dien-3β-yl-2-fluoro benzoate (5), 24α-ethylcholest-5, 22E-dien-3β-yl-4-fluoro benzoate (6), 11, 17-dihydroxy-21-(2-fluoro benzoyloxy)-pregn-4-en-3, 20-dione (8) and 11, 17-dihydroxy-21-(4-fluoro benzoyloxy)-pregn-4-en-3, 20-dione (9). We also synthesized fluorinated prodrugs 25R-spirost-5-en-3β-yl-2-fluoro-benzoate (11) and 25R-spirost-5-en-3β-yl-4-fluoro-benzoate (12) from diosgenin (10) a steroidal sapogenin. The structure and stereochemistry of 25R-spirost-5-en-3β-yl-4-fluoro-benzoate (12) was confirmed with help of single crystal X-ray crystallography. The characterization of compounds have been carried out with the help of 1H, 13C NMR, FT-IR spectroscopy and mass spectrometry. Density functional theory (DFT) with 6-31G (d, p) basis set and B3LYP functional has been used for the Quantum chemical calculations. Global reactivity descriptors have also been calculated to find the electrophilicity and nucleophilicity of a molecule. Dipole moment, polarizability and first static hyperpolarizability have been calculated to get NLO properties of synthesized prodrugs. Lastly a nonlinear mathematical model has been proposed and analyzed to study the effect of catalysts on these reactions. Local and global stability analysis of the mathematical model along with the persistence of the system was checked using theory of nonlinear ordinary differential equations

Wnt antagonist secreted frizzled-related protein 4 upregulates adipogenic differentiation in human adipose tissue-derived mesenchymal stem cells

With more than 1.4 billion overweight or obese adults worldwide, obesity and progression of the metabolic syndrome are major health and economic challenges. To address mechanisms of obesity, adipose tissue-derived mesenchymal stem cells (ADSCs) are being studied to detail the molecular mechanisms involved in adipogenic differentiation. Activation of the Wnt signalling pathway has inhibited adipogenesis from precursor cells. In our study, we examined this anti-adipogenic effect in further detail stimulating Wnt with lithium chloride (LiCl) and 6-bromo indirubin 3'oxime (BIO). We also examined the effect of Wnt inhibition using secreted frizzled-related protein 4 (sFRP4), which we have previously shown to be pro-apoptotic, anti-angiogenic, and anti-tumorigenic. Wnt stimulation in LiCl and BIOtreated ADSCs resulted in a significant reduction (2.7-fold and 12-fold respectively) in lipid accumulation as measured by Oil red O staining while Wnt inhibition with sFRP4 induced a 1.5-fold increase in lipid accumulation. Furthermore, there was significant 1.2-fold increase in peroxisome proliferator-activated receptor gamma (PPAR ?) and CCAAT/enhancer binding protein alpha (C/EBPa), and 1.3-fold increase in acetyl CoA carboxylase protein levels. In contrast, the expression of adipogenic proteins (PPAR?, C/EBPa, and acetyl CoA carboxylase) were decreased significantly with LiCl (by 1.6, 2.6, and 1.9-fold respectively) and BIO (by 7, 17, and 5.6-fold respectively) treatments. These investigations demonstrate interplay between Wnt antagonism and Wnt activation during adipogenesis and indicate pathways for therapeutic intervention to control this process

High-Performance Computing for SKA Transient Search: Use of FPGA based Accelerators -- a brief review

This paper presents the High-Performance computing efforts with FPGA for the accelerated pulsar/transient search for the SKA. Case studies are presented from within SKA and pathfinder telescopes highlighting future opportunities. It reviews the scenario that has shifted from offline processing of the radio telescope data to digitizing several hundreds/thousands of antenna outputs over huge bandwidths, forming several 100s of beams, and processing the data in the SKA real-time pulsar search pipelines. A brief account of the different architectures of the accelerators, primarily the new generation Field Programmable Gate Array-based accelerators, showing their critical roles to achieve high-performance computing and in handling the enormous data volume problems of the SKA is presented here. It also presents the power-performance efficiency of this emerging technology and presents potential future scenarios.Comment: Accepted for JoAA, SKA Special issue on SKA (2022

The Formation of the First Massive Black Holes

Supermassive black holes (SMBHs) are common in local galactic nuclei, and SMBHs as massive as several billion solar masses already exist at redshift z=6. These earliest SMBHs may grow by the combination of radiation-pressure-limited accretion and mergers of stellar-mass seed BHs, left behind by the first generation of metal-free stars, or may be formed by more rapid direct collapse of gas in rare special environments where dense gas can accumulate without first fragmenting into stars. This chapter offers a review of these two competing scenarios, as well as some more exotic alternative ideas. It also briefly discusses how the different models may be distinguished in the future by observations with JWST, (e)LISA and other instruments.Comment: 47 pages with 306 references; this review is a chapter in "The First Galaxies - Theoretical Predictions and Observational Clues", Springer Astrophysics and Space Science Library, Eds. T. Wiklind, V. Bromm & B. Mobasher, in pres

Evaluating implementation of a fire-prevention injury prevention briefing in children's centres: cluster randomised controlled trial

Background: Many developed countries have high mortality rates for fire-related deaths in children aged 0–14 years with steep social gradients. Evidence-based interventions to promote fire safety practices exist, but the impact of implementing a range of these interventions in children’s services has not been assessed. We developed an Injury Prevention Briefing (IPB), which brought together evidence about effective fire safety interventions and good practice in delivering interventions; plus training and facilitation to support its use and evaluated its implementation. Methods: We conducted a cluster randomised controlled trial, with integrated qualitative and cost-effectiveness nested studies, across four study sites in England involving children’s centres in disadvantaged areas; participants were staff and families attending those centres. Centres were stratified by study site and randomised within strata to one of three arms: IPB plus facilitation (IPB+), IPB only, usual care. IPB+ centres received initial training and facilitation at months 1, 3, and 8. Baseline data from children’s centres were collected between August 2011 and January 2012 and follow-up data were collected between June 2012 and June 2013. Parent baseline data were collected between January 2012 and May 2012 and follow-up data between May 2013 and September 2013. Data comprised baseline and 12 month parent- and staff-completed questionnaires, facilitation contact data, activity logs and staff interviews. The primary outcome was whether families had a plan for escaping from a house fire. Treatment arms were compared using multilevel models to account for clustering by children’s centre. Results: 1112 parents at 36 children’s centres participated. There was no significant effect of the intervention on families’ possession of plans for escaping from a house fire (adjusted odds ratio (AOR) IPB only vs. usual care: 0.93, 95%CI 0.58, 1.49; AOR IPB+ vs. usual care 1.41, 95%CI 0.91, 2.20). However, significantly more families in the intervention arms reported more behaviours for escaping from house fires (AOR IPB only vs. usual care: 2.56, 95%CI 01.38, 4.76; AOR IPB+ vs. usual care 1.78, 95%CI 1.01, 3.15). Conclusion: Our study demonstrated that children’s centres can deliver an injury prevention intervention to families in disadvantaged communities and achieve changes in home safety behaviours

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Determination of the Configuration of a Zero-Pressure Balloon

The objective of this thesis is to develop mathematical models to determine the shape of a zero-pressure, cylinder balloon at float altitude

Systematic experiments in chemistry

xxix, 850 p. ; 24 cm