Institutional isomorphism, negativity bias and performance information use by politicians : a survey experiment

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Identification of a novel retroviral gene unique to human immunodeficiency virus type 2 and simian immunodeficiency virus SIVMAC

Human and simian immunodeficiency-associated retroviruses are extraordinarily complex, containing at least five genes, tat, art, sor, R, and 3' orf, in addition to the structural genes gag, pol, and env. Recently, nucleotide sequence analysis of human immunodeficiency virus type 2 (HIV-2) and simian immunodeficiency virus SIVMAC revealed the existence of still another open reading frame, termed X, which is highly conserved between these two viruses but absent from HIV-1. In this report, we demonstrate for the first time that the X open reading frame represents a functional retroviral gene in both HIV-2 and SIVMAC and that it encodes a virion-associated protein of 14 and 12 kilodaltons, respectively. We also describe the production of recombinant TrpE/X fusion proteins in Escherichia coli and show that sera from some HIV-2-infected individuals specifically recognize these proteins

Highly active cationic cobalt(II) hydroformylation catalysts

© 2020 American Association for the Advancement of Science. All rights reserved. The cobalt complexes HCo(CO)4 and HCo(CO)3(PR3) were the original industrial catalysts used for the hydroformylation of alkenes through reaction with hydrogen and carbon monoxide to produce aldehydes. More recent and expensive rhodium-phosphine catalysts are hundreds of times more active and operate under considerably lower pressures. Cationic cobalt(II) bisphosphine hydrido-carbonyl catalysts that are far more active than traditional neutral cobalt(I) catalysts and approach rhodium catalysts in activity are reported here. These catalysts have low linear-to-branched (L:B) regioselectivity for simple linear alkenes. However, owing to their high alkene isomerization activity and increased steric effects due to the bisphosphine ligand, they have high L:B selectivities for internal alkenes with alkyl branches. These catalysts exhibit long lifetimes and substantial resistance to degradation reactions

Association Between Medication Adherence and the Outcomes of Heart Failure

Background Previous studies of heart failure patients have demonstrated an association between cardiovascular medication adherence and hospitalizations or a composite end point of hospitalization and death. Few studies have assessed the impact of treatment adherence within large general medical populations that distinguish the health outcomes of emergency department visits, hospitalization, and death. Objective To determine the association of incremental cardiovascular medication adherence on emergency department visits, hospitalization, and death in adult heart failure patients in Indiana. Design Retrospective cohort study conducted using electronic health record data from the statewide Indiana Network for Patient Care (INPC) between 2004 and 2009. Methods Patients were at least 18 years of age with a diagnosis of heart failure and prescribed at least one cardiovascular medication for heart failure. Adherence was measured as the proportion of days covered (PDC) using pharmacy transaction data. Clinical end points included emergency department visits, hospital admissions, length of hospital stay, and mortality. Generalized linear models were used to determine the effect of a 10% increase in PDC on clinical end points adjusting for age, sex, race, Charlson comorbidity index, and medications. Results Electronic health records were available for 55,312 patients (mean age ± standard deviation [SD] 68 ± 16 years; 54% women; 65% white). Mean PDC for all heart failure medications was 63% ± 23%. For every 10% increase in PDC, emergency department visits decreased 11% (rate ratio [RR] 0.89; 95% confidence interval [CI] 0.89‐0.89), hospital admissions decreased 6% (RR 0.94; 95% CI 0.94‐0.94), total length of hospital stay decreased 1% (RR 0.99; 95% CI 0.99‐1.00), and all‐cause mortality decreased 9% (odds ratio 0.91; 95% CI 0.90‐0.92). Conclusion Incremental medication adherence was associated with reductions in emergency department visits, hospital admissions, length of hospital stay, and all‐cause mortality

Are Mandates the Answer? Improving Palliative Care and Pain Management in Vermont

Background: The Vermont legislature (bill H.435, Sec. 19) has tasked the Vermont Board of Medical Practice (VBMP) with making a formal recommendation on improving Vermont health professionals’ knowledge and practice of Palliative Care and Pain Management (PC/PM). In collaboration with the VBMP, our group set out to answer the following questions: • How confident/competent are VT physicians in the practice of PC/PM? • What are the barriers to achieving optimal patient care in PC/PM? • Do VT physicians believe mandatory CME would improve the overall quality of care in PC/PM? • What are the best methods of providing Continuing Medical Education (CME)?https://scholarworks.uvm.edu/comphp_gallery/1040/thumbnail.jp

Individualism and the extended-self: cross-cultural differences in the valuation of authentic objects

The current studies examine how valuation of authentic items varies as a function of culture. We find that U.S. respondents value authentic items associated with individual persons (a sweater or an artwork) more than Indian respondents, but that both cultures value authentic objects not associated with persons (a dinosaur bone or a moon rock) equally. These differences cannot be attributed to more general cultural differences in the value assigned to authenticity. Rather, the results support the hypothesis that individualistic cultures place a greater value on objects associated with unique persons and in so doing, offer the first evidence for how valuation of certain authentic items may vary cross-culturally

High resolution time-course mapping of early transcriptomic, molecular and cellular phenotypes in Huntington\u27s disease CAG knock-in mice across multiple genetic backgrounds.

Huntington\u27s disease is a dominantly inherited neurodegenerative disease caused by the expansion of a CAG repeat in the HTT gene. In addition to the length of the CAG expansion, factors such as genetic background have been shown to contribute to the age at onset of neurological symptoms. A central challenge in understanding the disease progression that leads from the HD mutation to massive cell death in the striatum is the ability to characterize the subtle and early functional consequences of the CAG expansion longitudinally. We used dense time course sampling between 4 and 20 postnatal weeks to characterize early transcriptomic, molecular and cellular phenotypes in the striatum of six distinct knock-in mouse models of the HD mutation. We studied the effects of the HttQ111 allele on the C57BL/6J, CD-1, FVB/NCr1, and 129S2/SvPasCrl genetic backgrounds, and of two additional alleles, HttQ92 and HttQ50, on the C57BL/6J background. We describe the emergence of a transcriptomic signature in HttQ111/+  mice involving hundreds of differentially expressed genes and changes in diverse molecular pathways. We also show that this time course spanned the onset of mutant huntingtin nuclear localization phenotypes and somatic CAG-length instability in the striatum. Genetic background strongly influenced the magnitude and age at onset of these effects. This work provides a foundation for understanding the earliest transcriptional and molecular changes contributing to HD pathogenesis

Clinical efficacy and safety of a light mask for prevention of dark adaptation in treating and preventing progression of early diabetic macular oedema at 24 months (CLEOPATRA): a multicentre, phase 3, randomised controlled trial

Background: We aimed to assess 24-month outcomes of wearing an organic light-emitting sleep mask as an intervention to treat and prevent progression of non-central diabetic macular oedema. Methods: CLEOPATRA was a phase 3, single-blind, parallel-group, randomised controlled trial undertaken at 15 ophthalmic centres in the UK. Adults with non-centre-involving diabetic macular oedema were randomly assigned (1:1) to wearing either a light mask during sleep (Noctura 400 Sleep Mask, PolyPhotonix Medical, Sedgefield, UK) or a sham (non-light) mask, for 24 months. Randomisation was by minimisation generated by a central web-based computer system. Outcome assessors were masked technicians and optometrists. The primary outcome was the change in maximum retinal thickness on optical coherence tomography (OCT) at 24 months, analysed using a linear mixed-effects model incorporating 4-monthly measurements and baseline adjustment. Analysis was done using the intention-to-treat principle in all randomised patients with OCT data. Safety was assessed in all patients. This trial is registered with Controlled-Trials.com, number ISRCTN85596558. Findings: Between April 10, 2014, and June 15, 2015, 308 patients were randomly assigned to wearing the light mask (n=155) or a sham mask (n=153). 277 patients (144 assigned the light mask and 133 the sham mask) contributed to the mixed-effects model over time, including 246 patients with OCT data at 24 months. The change in maximum retinal thickness at 24 months did not differ between treatment groups (mean change −9·2 μm [SE 2·5] for the light mask vs −12·9 μm [SE 2·9] for the sham mask; adjusted mean difference −0·65 μm, 95% CI −6·90 to 5·59; p=0·84). Median compliance with wearing the light mask at 24 months was 19·5% (IQR 1·9–51·6). No serious adverse events were related to either mask. The most frequent adverse events related to the assigned treatment were discomfort on the eyes (14 with the light mask vs seven with the sham mask), painful, sticky, or watery eyes (14 vs six), and sleep disturbance (seven vs one). Interpretation: The light mask as used in this study did not confer long-term therapeutic benefit on non-centre-involving diabetic macular oedema and the study does not support its use for this indication. Funding: The Efficacy and Mechanism Evaluation Programme, a Medical Research Council and National Institute for Health Research partnership

A systems approach to prion disease

Prions cause transmissible neurodegenerative diseases and replicate by conformational conversion of normal benign forms of prion protein (PrPC) to disease-causing PrPSc isoforms. A systems approach to disease postulates that disease arises from perturbation of biological networks in the relevant organ. We tracked global gene expression in the brains of eight distinct mouse strain–prion strain combinations throughout the progression of the disease to capture the effects of prion strain, host genetics, and PrP concentration on disease incubation time. Subtractive analyses exploiting various aspects of prion biology and infection identified a core of 333 differentially expressed genes (DEGs) that appeared central to prion disease. DEGs were mapped into functional pathways and networks reflecting defined neuropathological events and PrPSc replication and accumulation, enabling the identification of novel modules and modules that may be involved in genetic effects on incubation time and in prion strain specificity. Our systems analysis provides a comprehensive basis for developing models for prion replication and disease, and suggests some possible therapeutic approaches

Altered Expression of Mitoferrin and Frataxin, Larger Labile Iron Pool and Greater Mitochondrial DNA Damage in the Skeletal Muscle of Older Adults

Mitochondrial dysfunction and iron (Fe) dyshomeostasis are invoked among the mechanisms contributing to muscle aging, possibly via a detrimental mitochondrial-iron feed-forward loop. We quantified the labile Fe pool, Fe isotopes, and the expression of mitochondrial Fe handling proteins in muscle biopsies obtained from young and older adults. The expression of key proteins of mitochondrial quality control (MQC) and the abundance of the mitochondrial DNA common deletion (mtDNA4977) were also assessed. An inverse association was found between total Fe and the heavier Fe isotope (56Fe), indicating an increase in labile Fe abundance in cells with greater Fe content. The highest levels of labile Fe were detected in old participants with a Short Physical Performance Battery (SPPB) score 64 7 (low-functioning, LF). Protein levels of mitoferrin and frataxin were, respectively, higher and lower in the LF group relative to young participants and older adults with SPPB scores 65 11 (high-functioning, HF). The mtDNA4977 relative abundance was greater in old than in young participants, regardless of SPPB category. Higher protein levels of Pink1 were detected in LF participants compared with young and HF groups. Finally, the ratio between lipidated and non-lipidated microtubule-associated protein 1A/1B-light chain 3 (i.e., LC3B II/I), as well as p62 protein expression was lower in old participants regardless of SPPB scores. Our findings indicate that cellular and mitochondrial Fe homeostasis is perturbed in the aged muscle (especially in LF older adults), as reflected by altered levels of mitoferrin and frataxin, which, together with MQC derangements, might contribute to loss of mtDNA stability