Are we advancing universal health coverage through cataract services? Protocol for a scoping review.

INTRODUCTION: Universal health coverage (UHC) includes the dimensions of equity in access, quality services that improve health and protection against financial hardship. Cataract continues to be the leading cause of blindness globally, despite cataract surgery being an efficacious intervention. The aim of this scoping review is to map the nature, extent and global distribution of data on cataract services for UHC in terms of equity, access, quality and financial protection. METHODS AND ANALYSIS: The search will be constructed by an Information Specialist and undertaken in MEDLINE, Embase and Global Health databases. We will include all published non-interventional primary research studies and systematic reviews that report a quantitative assessment of access, equity, quality or financial protection of cataract surgical services for adults at the subnational, national, regional or global level from population-based surveys or routinely collected health service data since 1 January 2000 and published through to February 2020.Screening and data charting will be undertaken using Covidence systematic review software. Titles and abstracts of identified studies will be screened by two authors independently. Full-text articles of potentially relevant studies will be obtained and reviewed independently by two authors against the inclusion criteria. Any discrepancies between the authors will be resolved by discussion, and with a third author as necessary. A data charting form will be developed and piloted on three studies by three authors and amendments made as necessary. Data will be extracted by two reviewers independently and summarised narratively and using maps. ETHICS AND DISSEMINATION: Ethical approval was not sought as the scoping review will only use published and publicly accessible data. The review will be published in an open access peer-reviewed journal. A summary of the results will be developed for website posting, stakeholder meetings and inclusion in the ongoing Lancet Global Health Commission on Global Eye Health

Analytic philosophy for biomedical research: the imperative of applying yesterday's timeless messages to today's impasses

The mantra that "the best way to predict the future is to invent it" (attributed to the computer scientist Alan Kay) exemplifies some of the expectations from the technical and innovative sides of biomedical research at present. However, for technical advancements to make real impacts both on patient health and genuine scientific understanding, quite a number of lingering challenges facing the entire spectrum from protein biology all the way to randomized controlled trials should start to be overcome. The proposal in this chapter is that philosophy is essential in this process. By reviewing select examples from the history of science and philosophy, disciplines which were indistinguishable until the mid-nineteenth century, I argue that progress toward the many impasses in biomedicine can be achieved by emphasizing theoretical work (in the true sense of the word 'theory') as a vital foundation for experimental biology. Furthermore, a philosophical biology program that could provide a framework for theoretical investigations is outlined

T Cell-Dependence of Lassa Fever Pathogenesis

Lassa virus (LASV), the causative agent of Lassa fever (LF), is endemic in West Africa, accounting for substantial morbidity and mortality. In spite of ongoing research efforts, LF pathogenesis and mechanisms of LASV immune control remain poorly understood. While normal laboratory mice are resistant to LASV, we report that mice expressing humanized instead of murine MHC class I (MHC-I) failed to control LASV infection and develop severe LF. Infection of MHC-I knockout mice confirmed a key role for MHC-I-restricted T cell responses in controlling LASV. Intriguingly we found that T cell depletion in LASV-infected HHD mice prevented disease, irrespective of high-level viremia. Widespread activation of monocyte/macrophage lineage cells, manifest through inducible NO synthase expression, and elevated IL-12p40 serum levels indicated a systemic inflammatory condition. The absence of extensive monocyte/macrophage activation in T cell-depleted mice suggested that T cell responses contribute to deleterious innate inflammatory reactions and LF pathogenesis. Our observations in mice indicate a dual role for T cells, not only protecting from LASV, but also enhancing LF pathogenesis. The possibility of T cell-driven enhancement and immunopathogenesis should be given consideration in future LF vaccine development

Expected Performance of the ATLAS Experiment - Detector, Trigger and Physics

A detailed study is presented of the expected performance of the ATLAS detector. The reconstruction of tracks, leptons, photons, missing energy and jets is investigated, together with the performance of b-tagging and the trigger. The physics potential for a variety of interesting physics processes, within the Standard Model and beyond, is examined. The study comprises a series of notes based on simulations of the detector and physics processes, with particular emphasis given to the data expected from the first years of operation of the LHC at CERN

Evidentialism and Moral Encroachment

Moral encroachment holds that the epistemic justification of a belief can be affected by moral factors. If the belief might wrong a person or group more evidence is required to justify the belief. Moral encroachment thereby opposes evidentialism, and kindred views, which holds that epistemic justification is determined solely by factors pertaining to evidence and truth. In this essay I explain how beliefs such as ‘that woman is probably an administrative assistant’—based on the evidence that most women employees at the firm are administrative assistants—motivate moral encroachment. I then describe weaknesses of moral encroachment. Finally I explain how we can countenance the moral properties of such beliefs without endorsing moral encroachment, and I argue that the moral status of such beliefs cannot be evaluated independently from the understanding in which they are embedded

Subtype-associated differences in HIV-1 reverse transcription affect the viral replication

Background: The impact of the products of the pol gene, specifically, reverse transcriptase (RT) on HIV-1 replication, evolution, and acquisition of drug resistance has been thoroughly characterized for subtype B. For subtype C, which accounts of almost 60% of HIV cases worldwide, much less is known. It has been reported that subtype C HIV-1 isolates have a lower replication capacity than B; however, the basis of these differences remains unclear. Results: We analyzed the impact of the pol gene products from HIV-1 B and C subtypes on the maturation of HIV virions, accumulation of reverse transcription products, integration of viral DNA, frequency of point mutations in provirus and overall viral replication. Recombinant HIV-1 viruses of B and C subtypes comprising the pol fragments encoding protease, integrase and either the whole RT or a chimeric RT from different isolates of the C and B subtypes, were used for infection of cells expressing CXCR4 or CCR5 co-receptors. The viruses carrying different fragments of pol from the isolates of B and C subtypes did not reveal differences in Gag and GagPol processing and viral RNA incorporation into the virions. However, the presence of the whole RT from subtype C, or the chimeric RT containing either the polymerase or the connection and RNase H domains from C isolates, caused significantly slower viral replication regardless of B or C viral backbone. Subtype C RT carrying viruses displayed lower levels of accumulation of strong-stop cDNA in permeabilized virions during endogenous reverse transcription, and decreased accumulation of both strong-stop and positive strand reverse transcription products in infected cells and in isolated reverse transcription complexes. This decreased accumulation correlated with lower levels of viral DNA integration in cells infected with viruses carrying the whole RT or RT domains from subtype C isolates. The single viral genome assay analysis did not reveal significant differences in the frequency of point mutations between the RT from B or C subtypes. Conclusions: These data suggest that the whole RT as well as distinct polymerase and connection-RNase H domains from subtype C HIV-1 confer a lower level of accumulation of reverse transcripts in the virions and reverse transcription complexes as compared to subtype B, resulting in a lower overall level of virus replication

Superhumps in Cataclysmic Binaries. XXIV. Twenty More Dwarf Novae

We report precise measures of the orbital and superhump period in twenty more dwarf novae. For ten stars, we report new and confirmed spectroscopic periods - signifying the orbital period P_o - as well as the superhump period P_sh. These are GX Cas, HO Del, HS Vir, BC UMa, RZ Leo, KV Dra, KS UMa, TU Crt, QW Ser, and RZ Sge. For the remaining ten, we report a medley of P_o and P_sh measurements from photometry; most are new, with some confirmations of previous values. These are KV And, LL And, WX Cet, MM Hya, AO Oct, V2051 Oph, NY Ser, KK Tel, HV Vir, and RX J1155.4-5641. Periods, as usual, can be measured to high accuracy, and these are of special interest since they carry dynamical information about the binary. We still have not quite learned how to read the music, but a few things are clear. The fractional superhump excess epsilon [=(P_sh-P_o)/P_o] varies smoothly with P_o. The scatter of the points about that smooth curve is quite low, and can be used to limit the intrinsic scatter in M_1, the white dwarf mass, and the mass-radius relation of the secondary. The dispersion in M_1 does not exceed 24%, and the secondary-star radii scatter by no more than 11% from a fixed mass-radius relation. For the well-behaved part of epsilon(P_o) space, we estimate from superhump theory that the secondaries are 18+-6% larger than theoretical ZAMS stars. This affects some other testable predictions about the secondaries: at a fixed P_o, it suggests that the secondaries are (compared with ZAMS predictions) 40+-14% less massive, 12+-4% smaller, 19+-6% cooler, and less luminous by a factor 2.5(7). The presence of a well-defined mass-radius relation, reflected in a well-defined epsilon(P_o) relation, strongly limits effects of nuclear evolution in the secondaries.Comment: PDF, 62 pages, 7 tables, 21 figures; accepted, in press, to appear November 2003, PASP; more info at http://cba.phys.columbia.edu

Gene Expression Signature Analysis Identifies Vorinostat as a Candidate Therapy for Gastric Cancer

Gastric cancer continues to be one of the deadliest cancers in the world and therefore identification of new drugs targeting this type of cancer is thus of significant importance. The purpose of this study was to identify and validate a therapeutic agent which might improve the outcomes for gastric cancer patients in the future. manifested a reversed pattern.We showed that analysis of gene expression signature may represent an emerging approach to discover therapeutic agents for gastric cancer, such as vorinostat. The observation of altered gene expression after vorinostat treatment may provide the clue to identify the molecular mechanism of vorinostat and those patients likely to benefit from vorinostat treatment

Differences in Muscle Protein Synthesis and Anabolic Signaling in the Postabsorptive State and in Response to Food in 65–80 Year Old Men and Women

Women have less muscle than men but lose it more slowly during aging. To discover potential underlying mechanism(s) for this we evaluated the muscle protein synthesis process in postabsorptive conditions and during feeding in twenty-nine 65–80 year old men (n = 13) and women (n = 16). We discovered that the basal concentration of phosphorylated eEF2Thr56 was ∼40% less (P<0.05) and the basal rate of MPS was ∼30% greater (P = 0.02) in women than in men; the basal concentrations of muscle phosphorylated AktThr308, p70s6kThr389, eIF4ESer209, and eIF4E-BP1Thr37/46 were not different between the sexes. Feeding increased (P<0.05) AktThr308 and p70s6kThr389 phosphorylation to the same extent in men and women but increased (P<0.05) the phosphorylation of eIF4ESer209 and eIF4E-BP1Thr37/46 in men only. Accordingly, feeding increased MPS in men (P<0.01) but not in women. The postabsorptive muscle mRNA concentrations for myoD and myostatin were not different between sexes; feeding doubled myoD mRNA (P<0.05) and halved that of myostatin (P<0.05) in both sexes. Thus, there is sexual dimorphism in MPS and its control in older adults; a greater basal rate of MPS, operating over most of the day may partially explain the slower loss of muscle in older women