Immunoprophylaxis against AIDS in macaques with a lentiviral DNA vaccine

AbstractWe earlier reported that immunization of macaques with a reverse transcriptase-deleted SHIVKU2 (ΔrtSHIVKU2) plasmid that contained HIV-1(HXB2) env and SIV gag–nef induced protection against AIDS caused by challenge virus SHIV89.6P with a heterologous env. We further deleted vif and integrase from ΔrtSHIVKU2 and substituted the 3′LTR with SV40 poly A sequences, creating Δ4SHIVKU2 (M) and a parallel construct containing gag–nef of HIV-1SF2, Δ4SHIVKU2 (H). Six macaques received two intramuscular injections of the (M) DNA, and another six received three injections of the (H) DNA. Three of the latter group received two post-challenge boosts with (M) DNA vaccine. Seven virus control macaques were inoculated with SHIV89.6P. All twelve immunized macaques were challenged with SHIV89.6P virus, and CMI responses were measured by ELISPOT assays.Virus control animals all developed progressive infection, whereas vaccinated macaques from both groups controlled virus replication, with plasma viral loads dropping to undetectable levels between weeks 6 and 126 p.i. This DNA vaccine was efficacious even though it encoded Env, Gag, and Nef that were genetically distinct from the proteins in the challenge virus. The DNA vaccine induced broad-based protection without using viral proteins to boost the immunity

Does the merger improve the operating performance of the company? Evidence from the beverage industry in India [version 2; peer review: 1 approved, 2 approved with reservations]

Background There is fierce market competition both locally and globally. Every organisation seeks to maintain itself and, more crucially, to develop quickly through inorganic means. The expansion of a company through mergers and acquisitions is an inorganic process. Organic growth takes a very long period and is time-bound, but inorganic growth through mergers may be achieved quickly. This research aimed to determine whether the operating results of Indian beverage firms have improved after the merger or not. Methods In order to assess merger-related advantages to the acquiring firms, this study used the operating performance technique, which contrasts the pre-merger and post-merger performance of corporations using accounting data. Secondary data were used to carry out this study. The operating performance was assessed on six operating parameters (ratios) i.e. Operating Profit Margin, Gross and Net Profit Margin, Debt-Equity, Return on Net Worth and Capital Employed. The comparison was done for three years pre and post-merger period of these operating ratios. Results The findings demonstrate that mergers do not seek to increase owner wealth. This finding shows that rather than just becoming larger and achieving covert goals, managers should pay more attention to post-merger integration challenges in order to produce merger-induced synergies. Conclusion This study shows that the M&As have not had a good effect on a company’s operating performance, especially for the chosen beverage companies in India. Since financial measures cannot fully account for the influence of mergers on business performance, future research may create other metrics for merger-related gains. Research that provides profound insights into the causes and trends of post-merger business performance through the different types of mergers and industries would also be beneficial

Mapping inequalities in exclusive breastfeeding in low- and middle-income countries, 2000–2018

Exclusive breastfeeding (EBF)—giving infants only breast-milk for the first 6 months of life—is a component of optimal breastfeeding practices effective in preventing child morbidity and mortality. EBF practices are known to vary by population and comparable subnational estimates of prevalence and progress across low- and middle-income countries (LMICs) are required for planning policy and interventions. Here we present a geospatial analysis of EBF prevalence estimates from 2000 to 2018 across 94 LMICs mapped to policy-relevant administrative units (for example, districts), quantify subnational inequalities and their changes over time, and estimate probabilities of meeting the World Health Organization’s Global Nutrition Target (WHO GNT) of ≥70% EBF prevalence by 2030. While six LMICs are projected to meet the WHO GNT of ≥70% EBF prevalence at a national scale, only three are predicted to meet the target in all their district-level units by 2030

Global, regional, and national progress towards Sustainable Development Goal 3.2 for neonatal and child health: all-cause and cause-specific mortality findings from the Global Burden of Disease Study 2019

Background Sustainable Development Goal 3.2 has targeted elimination of preventable child mortality, reduction of neonatal death to less than 12 per 1000 livebirths, and reduction of death of children younger than 5 years to less than 25 per 1000 livebirths, for each country by 2030. To understand current rates, recent trends, and potential trajectories of child mortality for the next decade, we present the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 findings for all-cause mortality and cause-specific mortality in children younger than 5 years of age, with multiple scenarios for child mortality in 2030 that include the consideration of potential effects of COVID-19, and a novel framework for quantifying optimal child survival. Methods We completed all-cause mortality and cause-specific mortality analyses from 204 countries and territories for detailed age groups separately, with aggregated mortality probabilities per 1000 livebirths computed for neonatal mortality rate (NMR) and under-5 mortality rate (USMR). Scenarios for 2030 represent different potential trajectories, notably including potential effects of the COVID-19 pandemic and the potential impact of improvements preferentially targeting neonatal survival. Optimal child survival metrics were developed by age, sex, and cause of death across all GBD location-years. The first metric is a global optimum and is based on the lowest observed mortality, and the second is a survival potential frontier that is based on stochastic frontier analysis of observed mortality and Healthcare Access and Quality Index. Findings Global U5MR decreased from 71.2 deaths per 1000 livebirths (95% uncertainty interval WI] 68.3-74-0) in 2000 to 37.1 (33.2-41.7) in 2019 while global NMR correspondingly declined more slowly from 28.0 deaths per 1000 live births (26.8-29-5) in 2000 to 17.9 (16.3-19-8) in 2019. In 2019,136 (67%) of 204 countries had a USMR at or below the SDG 3.2 threshold and 133 (65%) had an NMR at or below the SDG 3.2 threshold, and the reference scenario suggests that by 2030,154 (75%) of all countries could meet the U5MR targets, and 139 (68%) could meet the NMR targets. Deaths of children younger than 5 years totalled 9.65 million (95% UI 9.05-10.30) in 2000 and 5.05 million (4.27-6.02) in 2019, with the neonatal fraction of these deaths increasing from 39% (3.76 million 95% UI 3.53-4.021) in 2000 to 48% (2.42 million; 2.06-2.86) in 2019. NMR and U5MR were generally higher in males than in females, although there was no statistically significant difference at the global level. Neonatal disorders remained the leading cause of death in children younger than 5 years in 2019, followed by lower respiratory infections, diarrhoeal diseases, congenital birth defects, and malaria. The global optimum analysis suggests NMR could be reduced to as low as 0.80 (95% UI 0.71-0.86) deaths per 1000 livebirths and U5MR to 1.44 (95% UI 1-27-1.58) deaths per 1000 livebirths, and in 2019, there were as many as 1.87 million (95% UI 1-35-2.58; 37% 95% UI 32-43]) of 5.05 million more deaths of children younger than 5 years than the survival potential frontier. Interpretation Global child mortality declined by almost half between 2000 and 2019, but progress remains slower in neonates and 65 (32%) of 204 countries, mostly in sub-Saharan Africa and south Asia, are not on track to meet either SDG 3.2 target by 2030. Focused improvements in perinatal and newborn care, continued and expanded delivery of essential interventions such as vaccination and infection prevention, an enhanced focus on equity, continued focus on poverty reduction and education, and investment in strengthening health systems across the development spectrum have the potential to substantially improve USMR. Given the widespread effects of COVID-19, considerable effort will be required to maintain and accelerate progress. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd

Proper Assertion of the Deliberative Process Privilege: The Agency Head Requirement

Can any employee of an executive agency assert the deliberative process privilege in order to withhold information in response to a valid request? This Note examines the agency head requirement for assertion of the deliberative process privilege and concludes that only executive officials possessing policy-making authority may invoke the privilege. Such privilege determinations must come from a policy-making official in order to curb abuse and maintain the integrity of executive decisions. Recognition of such a policy-making distinction with regard to the agency head requirement will serve both the Executive’s and the public’s interest in ensuring effective governance

An Investigation into Household and Occupational Pesticide Exposures with Genetic Variants as Risk Factors for Parkinson's Disease

Epidemiologic studies suggest that pesticides are risk factors for Parkinson's Disease (PD) but predominantly assessed pesticide exposure as a broad category and often did not examine exposure modifying factors such as personal protective equipment (PPE) use and variants in genes that encode proteins involved in pesticide metabolism and distribution in the body. Only a handful have investigated household pesticide exposures alone. This dissertation research examined the relation between PD and exposures to pesticides from multiple exposure sources, including household use, occupational use, and ambient pesticide exposures from drift in addition to genetic variation in PON1 and ABCB1. We recruited 360 incident PD cases and 827 population controls between 2001 through 2011 from central California, collected data on demographics, covariates, residential and occupational address history, and exposures to chemicals by telephone, and participants provided either whole blood or saliva samples.Frequent use of any household pesticide increased PD risk by 47%; frequent use of products containing organophosphorus pesticides (OPs) increased risk more strongly by 71%, and frequent organothiophosphate use almost doubled the risk of PD. The largest odds ratios were estimated for frequent OP users who were carriers of the 192QQ paraoxonase genetic variant related to slower detoxification of OPs.Ever occupational pesticide use for > 10 years doubled the risk of PD compared to never occupational pesticide users. PD risk was also increased with occupational use of fungicides, herbicides, insecticides, carbamates, OPs, and organochlorine (OC) pesticides. Surprisingly, we found higher risks among those who reported using PPE, possibly because these workers felt compelled to use PPE when handling toxic pesticides. We replicated a prior finding of ABCB1 polymorphisms at both rs1045642 and rs2032582 modifying PD risk from occupational OC exposures. We also newly found that PD risk from occupational OP exposures is modified by these polymorphisms. However, we did not detect multiplicative interactions.Our results suggest that exposures to OPs, carbamates, and OCs increase PD risk, and the risk from commonly used pesticides, specifically OCs and OPs, may be increased more strongly in individuals who are genetically susceptible to neurotoxic effects of pesticides