Blame, Symbolic Stigma and HIV Misconceptions are Associated with Support for Coercive Measures in Urban India

This study was designed to examine the prevalence of stigma and its underlying factors in two large Indian cities. Cross-sectional interview data were collected from 1,076 non-HIV patients in multiple healthcare settings in Mumbai and Bengaluru, India. The vast majority of participants supported mandatory testing for marginalized groups and coercive family policies for PLHA, stating that they “deserved” their infections and “didn’t care” about infecting others. Most participants did not want to be treated at the same clinic or use the same utensils as PLHA and transmission misconceptions were common. Multiple linear regression showed that blame, transmission misconceptions, symbolic stigma and negative feelings toward PLHA were significantly associated with both stigma and discrimination. The results indicate an urgent need for continued stigma reduction efforts to reduce the suffering of PLHA and barriers to prevention and treatment. Given the high levels of blame and endorsement of coercive policies, it is crucial that such programs are shaped within a human rights framework

Clinical Use and Therapeutic Potential of IVIG/SCIG, Plasma-Derived IgA or IgM, and Other Alternative Immunoglobulin Preparations

Intravenous and subcutaneous immunoglobulin preparations, consisting of IgG class antibodies, are increasingly used to treat a broad range of pathological conditions, including humoral immune deficiencies, as well as acute and chronic inflammatory or autoimmune disorders. A plethora of Fab- or Fc-mediated immune regulatory mechanisms has been described that might act separately or in concert, depending on pathogenesis or stage of clinical condition. Attempts have been undertaken to improve the efficacy of polyclonal IgG preparations, including the identification of relevant subfractions, mild chemical modification of molecules, or modification of carbohydrate side chains. Furthermore, plasma-derived IgA or IgM preparations may exhibit characteristics that might be exploited therapeutically. The need for improved treatment strategies without increase in plasma demand is a goal and might be achieved by more optimal use of plasma-derived proteins, including the IgA and the IgM fractions. This article provides an overview on the current knowledge and future strategies to improve the efficacy of regular IgG preparations and discusses the potential of human plasma-derived IgA, IgM, and preparations composed of mixtures of IgG, IgA, and IgM

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Influence of Foundation Soil on the Seismic Factor of Safety of Geosynthetic-Lined Solid-Waste Landfills: Equivalent Linear Approach

This paper is focused on the influence of foundation soil on the seismic factor of the safety of a typical side-hill type solid-waste landfill. New analytical expressions are derived and presented to calculate the displacement, shear strain, and seismic accelerations within the landfill body and in the foundation soil. A new equivalent-linear-based approach is proposed to compute the seismic factor of the safety (FSavg) of municipal solid waste (MSW) landfills considering the effect of the foundation type. In the present study, four different foundation types are considered: shallow sand deposit (foundation type I), deep sand deposit (foundation type II), shallow clay deposit (foundation type III), and deep clay deposit (foundation type IV). Moreover, the proposed method considered the strain-dependent equivalent-linear material parameters (secant shear modulus and damping ratio) rather than a small-strain shear modulus and a fixed damping ratio. The acceleration ratios (ratio of surface to bedrock accelerations) obtained from the proposed method are in good agreement with the DEEPSOIL version 6.1 equivalent-linear results. The maximum shear strain within the landfill body significantly decreases with an increase in the input excitation frequency from 0.2 to 3 Hz. In addition, the landfill enters higher vibration modes. At higher vibration modes, a portion of the seismic acceleration acts in one direction, and the remaining portion acts in the opposite direction. This phenomenon reduces the net amount of acceleration acting on the landfill body that, in turn, results in a higher safety factor. The seismic factor of the safety values computed from the present equivalent-linear analysis is compared with the results of the present linear and pseudodynamic analyses. The parametric study revealed that the critical and safe foundation type for the seismic stability of MSW landfills also changes with a change in the input motion frequency. For an input frequency of 3.0 Hz, foundation type I is identified as the most critical one with the lowest FSavg, and foundation type IV is the safest one with the highest FSavg. Similarly, for an input frequency of 1.75 Hz, foundation type II is identified as the most critical foundation with the lowest FSavg, and foundation type III is on the safest side with the highest FSavg

Seismic active thrust on rigid retaining wall using strain dependent dynamic properties

© 2018 American Society of Civil Engineers. An analytical model is proposed for the evaluation of seismic active thrust on retaining wall resting on sandy soil. Foundation and backfill soil is idealized as Kelvin-Voigt solid. The governing differential equation of vertically propagating shear wave is solved by maintaining the displacement continuity and stress compatibility at the interface between backfill and foundation soil. Nonlinear distribution of accelerations induced in the backfill soil is then used to compute the seismic inertia force. Total seismic active thrust is obtained by solving the force equilibrium equation of the triangular failure wedge. The present method computes the strain-dependent shear-wave velocity and damping ratio of sand from its modulus reduction and damping ratio curves using an iterative scheme. Amplification and deamplification of the input excitations in the foundation soil and backfill soil are compared with results of dynamic centrifuge tests reported in the literature. An increase in the magnitude of seismic active thrust is observed when the retaining wall is situated on sandy soil in place of the rigid stratum, and the percentage increase is 18% in comparison to the latest method available in the literature. The seismic active thrust values for long period input excitations are nearly 13 to 17% higher compared to short-period input excitations. The parametric study reveals that depth of backfill and foundation soil, impedance ratio, amplitude, and frequency of input motion dominate the response of the backfill soil under seismic condition