Characteristics Associated With Facebook Use and Interest in Digital Disease Support Among Older Adults With Atrial Fibrillation: Cross-Sectional Analysis of Baseline Data From the Systematic Assessment of Geriatric Elements in Atrial Fibrillation (SAGE-AF) Cohort

BACKGROUND: Online support groups for atrial fibrillation (AF) and apps to detect and manage AF exist, but the scientific literature does not describe which patients are interested in digital disease support. OBJECTIVE: The objective of this study was to describe characteristics associated with Facebook use and interest in digital disease support among older patients with AF who used the internet. METHODS: We used baseline data from the Systematic Assessment of Geriatric Elements in Atrial Fibrillation (SAGE-AF), a prospective cohort of older adults ( \u3e /=65 years) with AF at high stroke risk. Participants self-reported demographics, clinical characteristics, and Facebook and technology use. Online patients (internet use in the past 4 weeks) were asked whether they would be interested in participating in an online support AF community. Mobile users (owns smartphone and/or tablet) were asked about interest in communicating with their health care team about their AF-related health using a secure app. Logistic regression models identified crude and multivariable predictors of Facebook use and interest in digital disease support. RESULTS: Online patients (N=816) were aged 74.2 (SD 6.6) years, 47.8% (390/816) were female, and 91.1% (743/816) were non-Hispanic white. Roughly half (52.5%; 428/816) used Facebook. Facebook use was more common among women (adjusted odds ratio [aOR] 2.21, 95% CI 1.66-2.95) and patients with mild to severe depressive symptoms (aOR 1.50, 95% CI 1.08-2.10) and less common among patients aged \u3e /=85 years (aOR 0.27, 95% CI 0.15-0.48). Forty percent (40.4%; 330/816) reported interest in an online AF patient community. Interest in an online AF patient community was more common among online patients with some college/trade school or Bachelors/graduate school (aOR 1.70, 95% CI 1.10-2.61 and aOR 1.82, 95% CI 1.13-2.92, respectively), obesity (aOR 1.65, 95% CI 1.08-2.52), online health information seeking at most weekly or multiple times per week (aOR 1.84, 95% CI 1.32-2.56 and aOR 2.78, 95% CI 1.86-4.16, respectively), and daily Facebook use (aOR 1.76, 95% CI 1.26-2.46). Among mobile users, 51.8% (324/626) reported interest in communicating with their health care team via a mobile app. Interest in app-mediated communication was less likely among women (aOR 0.48, 95% CI 0.34-0.68) and more common among online patients who had completed trade school/some college versus high school/General Educational Development (aOR 1.95, 95% CI 1.17-3.22), sought online health information at most weekly or multiple times per week (aOR 1.86, 95% CI 1.27-2.74 and aOR 2.24, 95% CI 1.39-3.62, respectively), and had health-related apps (aOR 3.92, 95% CI 2.62-5.86). CONCLUSIONS: Among older adults with AF who use the internet, technology use and demographics are associated with interest in digital disease support. Clinics and health care providers may wish to encourage patients to join an existing online support community for AF and explore opportunities for app-mediated patient-provider communication

A multilevel neo-institutional analysis of infection prevention and control in English hospitals: coerced safety culture change?

Despite committed policy, regulative and professional efforts on healthcare safety, little is known about how such macro-interventions permeate organisations and shape culture over time. Informed by neo-institutional theory, we examined how inter-organisational influences shaped safety practices and inter-subjective meanings following efforts for coerced culture change. We traced macro-influences from 2000 to 2015 in infection prevention and control (IPC). Safety perceptions and meanings were inductively analysed from 130 in-depth qualitative interviews with senior- and middle-level managers from 30 English hospitals. A total of 869 institutional interventions were identified; 69% had a regulative component. In this context of forced implementation of safety practices, staff experienced inherent tensions concerning the scope of safety, their ability to be open and prioritisation of external mandates over local need. These tensions stemmed from conflicts among three co-existing institutional logics prevalent in the NHS. In response to requests for change, staff flexibly drew from a repertoire of cognitive, material and symbolic resources within and outside their organisations. They crafted 'strategies of action', guided by a situated assessment of first-hand practice experiences complementing collective evaluations of interventions such as 'pragmatic', 'sensible' and also 'legitimate'. Macro-institutional forces exerted influence either directly on individuals or indirectly by enriching the organisational cultural repertoire

Do-it-yourself digital: the production boundary, the productivity puzzle and economic welfare

Part of the debate about the ‘productivity puzzle’ concerns potential mismeasurement of GDP due to digital activities. This paper discusses some measurement issues arising from digitally-enabled substitutions in activity across the conventional production boundary. Production boundary issues are not new, as conventionally defined GDP statistics account for the monetary cost but not the time cost of consumption and production. This means changes in the way time is allocated between market and home production affect measured growth and productivity. Just as technological innovation in domestic appliances led to a substitution from home production into market consumption in the second half of the 20th century, today’s digital innovations are driving some reverse substitution out of the market into home production. Statistical agencies do not currently collect the data needed to measure the scale of the switch, but the available evidence suggests it may be enough to make a contribution to understanding the puzzling behaviour of measured productivityEconomics Statistics Centre of Excellenc

Bridged Analogues for p53-Dependent Cancer Therapy Obtained by S-Alkylation

A small library of anticancer, cell-permeating, stapled peptides based on potent dual-specific antagonist of p53–MDM2/MDMX interactions, PMI-N8A, was synthesized, characterized and screened for anticancer activity against human colorectal cancer cell line, HCT-116. Employed synthetic modifications included: S-alkylation-based stapling, point mutations increasing hydrophobicity in key residues as well as improvement of cell-permeability by introduction of polycationic sequence(s) that were woven into the sequence of parental peptide. Selected analogue, ArB14Co, was also tested in vivo and exhibited potent anticancer bioactivity at the low dose (3.0 mg/kg). Collectively, our findings suggest that application of stapling in combination with rational design of polycationic short analogues may be a suitable approach in the development of physiologically active p53–MDM2/MDMX peptide inhibitors

A Compensatory Mutation Provides Resistance to Disparate HIV Fusion Inhibitor Peptides and Enhances Membrane Fusion

Fusion inhibitors are a class of antiretroviral drugs used to prevent entry of HIV into host cells. Many of the fusion inhibitors being developed, including the drug enfuvirtide, are peptides designed to competitively inhibit the viral fusion protein gp41. With the emergence of drug resistance, there is an increased need for effective and unique alternatives within this class of antivirals. One such alternative is a class of cyclic, cationic, antimicrobial peptides known as θ-defensins, which are produced by many non-human primates and exhibit broad-spectrum antiviral and antibacterial activity. Currently, the θ-defensin analog RC-101 is being developed as a microbicide due to its specific antiviral activity, lack of toxicity to cells and tissues, and safety in animals. Understanding potential RC-101 resistance, and how resistance to other fusion inhibitors affects RC-101 susceptibility, is critical for future development. In previous studies, we identified a mutant, R5-tropic virus that had evolved partial resistance to RC-101 during in vitro selection. Here, we report that a secondary mutation in gp41 was found to restore replicative fitness, membrane fusion, and the rate of viral entry, which were compromised by an initial mutation providing partial RC-101 resistance. Interestingly, we show that RC-101 is effective against two enfuvirtide-resistant mutants, demonstrating the clinical importance of RC-101 as a unique fusion inhibitor. These findings both expand our understanding of HIV drug-resistance to diverse peptide fusion inhibitors and emphasize the significance of compensatory gp41 mutations. © 2013 Wood et al

Grifonin-1: A Small HIV-1 Entry Inhibitor Derived from the Algal Lectin, Griffithsin

Background: Griffithsin, a 121-residue protein isolated from a red algal Griffithsia sp., binds high mannose N-linked glycans of virus surface glycoproteins with extremely high affinity, a property that allows it to prevent the entry of primary isolates and laboratory strains of T- and M-tropic HIV-1. We used the sequence of a portion of griffithsin's sequence as a design template to create smaller peptides with antiviral and carbohydrate-binding properties. Methodology/Results: The new peptides derived from a trio of homologous β-sheet repeats that comprise the motifs responsible for its biological activity. Our most active antiviral peptide, grifonin-1 (GRFN-1), had an EC50 of 190.8±11.0 nM in in vitro TZM-bl assays and an EC50 of 546.6±66.1 nM in p24gag antigen release assays. GRFN-1 showed considerable structural plasticity, assuming different conformations in solvents that differed in polarity and hydrophobicity. Higher concentrations of GRFN-1 formed oligomers, based on intermolecular β-sheet interactions. Like its parent protein, GRFN-1 bound viral glycoproteins gp41 and gp120 via the N-linked glycans on their surface. Conclusion: Its substantial antiviral activity and low toxicity in vitro suggest that GRFN-1 and/or its derivatives may have therapeutic potential as topical and/or systemic agents directed against HIV-1

Documentation of in-hospital falls on incident reports: Qualitative investigation of an imperfect process

<p>Abstract</p> <p>Background</p> <p>Incident reporting is the prevailing approach to gathering data on accidental falls in hospitals for both research and quality assurance purposes, though is of questionable quality as staff time pressures, perception of blame and other factors are thought to contribute to under-reporting.</p> <p>Methods</p> <p>This research aimed to identify contextual factors influencing recording of in-hospital falls on incident reports. A qualitative multi-centre investigation using an open written response questionnaire was undertaken. Participants were asked to describe any factors that made them feel more or less likely to record a fall on an incident report. 212 hospital staff from 30 wards in 7 hospitals in Queensland, Australia provided a response. A framework approach was employed to identify and understand inter-relationships between emergent categories.</p> <p>Results</p> <p>Three main categories were developed. The first, determinants of reporting, describes a hierarchical structure of primary (principle of reporting), secondary (patient injury), and tertiary determinants that influenced the likelihood that an in-hospital fall would be recorded on an incident report. The tertiary determinants frequently had an inconsistent effect. The second and third main categories described environmental/cultural facilitators and barriers respectively which form a background upon which the determinants of reporting exists.</p> <p>Conclusion</p> <p>A distinctive framework with clear differences to recording of other types of adverse events on incident reports was apparent. Providing information to hospital staff regarding the purpose of incident reporting and the usefulness of incident reporting for preventing future falls may improve incident reporting practices.</p

Retrospective analysis of Schlafen11 (SLFN11) to predict the outcomes to therapies affecting the DNA damage response

BACKGROUND: The absence of the putative DNA/RNA helicase Schlafen11 (SLFN11) is thought to cause resistance to DNAdamaging agents (DDAs) and PARP inhibitors. METHODS: We developed and validated a clinically applicable SLFN11 immunohistochemistry assay and retrospectively correlated SLFN11 tumour levels to patient outcome to the standard of care therapies and olaparib maintenance. RESULTS: High SLFN11 associated with improved prognosis to the first-line treatment with DDAs platinum-plus-etoposide in SCLC patients, but was not strongly linked to paclitaxel–platinum response in ovarian cancer patients. Multivariate analysis of patients with relapsed platinum-sensitive ovarian cancer from the randomised, placebo-controlled Phase II olaparib maintenance Study19 showed SLFN11 tumour levels associated with sensitivity to olaparib. Study19 patients with high SLFN11 had a lower progression-free survival (PFS) hazard ratio compared to patients with low SLFN11, although both groups had the benefit of olaparib over placebo. Whilst caveated by small sample size, this trend was maintained for PFS, but not overall survival, when adjusting for BRCA status across the olaparib and placebo treatment groups, a key driver of PARP inhibitor sensitivity. CONCLUSION: We provide clinical evidence supporting the role of SLFN11 as a DDA therapy selection biomarker in SCLC and highlight the need for further clinical investigation into SLFN11 as a PARP inhibitor predictive biomarker

Of shepherds, sheep and sheepdogs?: governing the adherent self through complementary and competing ‘pastorates’

Foucault’s concept of ‘pastoral power’ describes an important technique for constituting obedient subjects. Derived from his analysis of the Christian pastorate, he saw pastoral power as a prelude to contemporary technologies of governing ‘beyond the State’, where ‘experts’ shepherd self-governing subjects. However, the specific practices of modern pastorate have been little developed. This papers examines the relational practices of pastoral power associated with the government of medicine use within the English healthcare system. The study shows how multiple pastors align their complimentary and variegated practices to conduct behaviours, but also how pastors compete for legitimacy, and face resistance through the mobilisation of alternate discourses and the strategic exploitation of pastoral competition. The paper offers a dynamic view of the modern pastorate within the contemporary assemblages of power

The impacts of increasing drought on forest dynamics, structure, and biodiversity in the United States

We synthesize insights from current understanding of drought impacts at stand‐to‐biogeographic scales, including management options, and we identify challenges to be addressed with new research. Large stand‐level shifts underway in western forests already are showing the importance of interactions involving drought, insects, and fire. Diebacks, changes in composition and structure, and shifting range limits are widely observed. In the eastern US, the effects of increasing drought are becoming better understood at the level of individual trees, but this knowledge cannot yet be confidently translated to predictions of changing structure and diversity of forest stands. While eastern forests have not experienced the types of changes seen in western forests in recent decades, they too are vulnerable to drought and could experience significant changes with increased severity, frequency, or duration in drought. Throughout the continental United States, the combination of projected large climate‐induced shifts in suitable habitat from modeling studies and limited potential for the rapid migration of tree populations suggests that changing tree and forest biogeography could substantially lag habitat shifts already underway. Forest management practices can partially ameliorate drought impacts through reductions in stand density, selection of drought‐tolerant species and genotypes, artificial regeneration, and the development of multistructured stands. However, silvicultural treatments also could exacerbate drought impacts unless implemented with careful attention to site and stand characteristics. Gaps in our understanding should motivate new research on the effects of interactions involving climate and other species at the stand scale and how interactions and multiple responses are represented in models. This assessment indicates that, without a stronger empirical basis for drought impacts at the stand scale, more complex models may provide limited guidance.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134257/1/gcb13160_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134257/2/gcb13160.pd