The Historical Perspective of the Problem of Interpersonal Comparisons of Utility

The starting-point of the article is the inconsistency between the established practice of acceptance in many cases, of economic policy (i.e. progressive taxation, national insurance policies) and the theoretical rejection of interpersonal comparisons of utility who see it as an unscientific value judgement. The inconsistency is explained by identifying three groups of theorists: (1) those who thought of comparability as a value judgement and unacceptable for economic policy considerations (positivists), (2) those who agreed with the positivists, on the normative nature of comparability but accepted it as a basis for economic policy, and (3) those who thought of it as part of a scientific economics. The implication was that, despite the dominance of positivist methodology in other sub-fields, the historical experience points to the difficulty of applying positivist methodology to the issue of comparability. If the inconsistency is thus due to the inappropriateness of the positivist approach, the only possible solution is the explicit abandonment of this approach at least in matters related to the collective aspects of economics

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

A population-scale temporal case–control evaluation of COVID-19 disease phenotype and related outcome rates in patients with cancer in England (UKCCP)

Patients with cancer are at increased risk of hospitalisation and mortality following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, the SARS-CoV-2 phenotype evolution in patients with cancer since 2020 has not previously been described. We therefore evaluated SARS-CoV-2 on a UK populationscale from 01/11/2020-31/08/2022, assessing case-outcome rates of hospital assessment(s), intensive care admission and mortality. We observed that the SARS-CoV-2 disease phenotype has become less severe in patients with cancer and the non-cancer population. Case-hospitalisation rates for patients with cancer dropped from 30.58% in early 2021 to 7.45% in 2022 while case-mortality rates decreased from 20.53% to 3.25%. However, the risk of hospitalisation and mortality remains 2.10x and 2.54x higher in patients with cancer, respectively. Overall, the SARS-CoV-2 disease phenotype is less severe in 2022 compared to 2020 but patients with cancer remain at higher risk than the non-cancer population. Patients with cancer must therefore be empowered to live more normal lives, to see loved ones and families, while also being safeguarded with expanded measures to reduce the risk of transmission

Whole genome sequence analysis of platelet traits in the NHLBI Trans-Omics for Precision Medicine (TOPMed) initiative

Platelets play a key role in thrombosis and hemostasis. Platelet count (PLT) and mean platelet volume (MPV) are highly heritable quantitative traits, with hundreds of genetic signals previously identified, mostly in European ancestry populations. We here utilize whole genome sequencing (WGS) from NHLBI's Trans-Omics for Precision Medicine initiative (TOPMed) in a large multi-ethnic sample to further explore common and rare variation contributing to PLT (n = 61 200) and MPV (n = 23 485). We identified and replicated secondary signals at MPL (rs532784633) and PECAM1 (rs73345162), both more common in African ancestry populations. We also observed rare variation in Mendelian platelet-related disorder genes influencing variation in platelet traits in TOPMed cohorts (not enriched for blood disorders). For example, association of GP9 with lower PLT and higher MPV was partly driven by a pathogenic Bernard-Soulier syndrome variant (rs5030764, p.Asn61Ser), and the signals at TUBB1 and CD36 were partly driven by loss of function variants not annotated as pathogenic in ClinVar (rs199948010 and rs571975065). However, residual signal remained for these gene-based signals after adjusting for lead variants, suggesting that additional variants in Mendelian genes with impacts in general population cohorts remain to be identified. Gene-based signals were also identified at several genome-wide association study identified loci for genes not annotated for Mendelian platelet disorders (PTPRH, TET2, CHEK2), with somatic variation driving the result at TET2. These results highlight the value of WGS in populations of diverse genetic ancestry to identify novel regulatory and coding signals, even for well-studied traits like platelet traits

Remedial measures plan for a spill of solvent refined coal liquid at the SRC pilot plant, Ft. Lewis, Washington. Final Report

On December 19, 1979, a spill of SRC liquid occurred during transfer of the liquid from a storage tank to sample drums. Approximately 2,300 gallons of fluid flowed into the floor of the tank farm and infiltrated into the porous and permeable gravels at the site. Because of concern for the possible impact of the SRC fluid on the quality of ground water, surface water, and water supply sources at and near the site, GMRC commissioned Radian to evaluate the problem and recommend specific measures to mitigate any known or anticipated impacts. This report presents the results of Radian's investigations. Although ground-water contamination apparently has occurred as a result of the December 19 spill, the contamination plume is localized to the vicinity of the SRC plant and Lake Sequalitchew. A contamination plume apparently is presently moving toward Lake Sequalitchew, but the two pump wells included in the Remedial Measures Plan will arrest this movement. These wells will be pumped until phenol concentrations in the groundwater fall to acceptable levels. The source of contamination at the spill is being cut off by excavation of the contaminated soil and sealing of the floor of the tank farm. No public water supplies are appreciably endangered by the December 19 spill. A long-term ground-water monitoring plan is being implemented to ensure early discovery of any unanticipated impacts of the spill. If further water quality problems are disclosed, additional remedial measures will be undertaken as necessary

The new approach in the analysis of 2×2 tables

contingency tables, the null hypothesis of independence, cause and effect representativeness, the prior homogeneous population, the hypothesis of significant dependence,

Stochastic modeling of temporal variability of HIV-1 population

A multivariate stochastic model for describing the dynamics of complex non-numerical ensembles, such as observed in Human Immunodeficiency Virus (HIV) genome, is developed. This model is based on principle component analyses for numberized variables. The model coefficients are presented in the terms of deterministic trends with correlated lags. The results indicate that we may use this model in short-term forecast of HIV evolution, for evaluation of HIV drug resistance and for testing and validation of diagnostic expert rules. The model also reproduces the specific shape of the bi-modal distribution for the mutations numbe