OPTIMAL, an occupational therapy led self-management support programme for people with multimorbidity in primary care: a randomized controlled trial.

BACKGROUND: We investigated the effectiveness of an occupational therapy led self-management support programme, OPTIMAL, designed to address the challenges of living with multiple chronic conditions or multimorbidity in a primary care setting. METHODS: Pragmatic feasibility randomised controlled trial including fifty participants with multimorbidity recruited from family practice and primary care settings. OPTIMAL is a six-week community-based programme, led by occupational therapy facilitators and focuses on problems associated with managing multimorbidity. The primary outcome was frequency of activity participation. Secondary outcomes included self-perception of, satisfaction with and ability to perform daily activities, independence in activities of daily living, anxiety and depression, self-efficacy, health-related quality of life, self-management support, healthcare utilisation and individualised goal attainment. Outcomes were collected within two weeks of intervention completion. RESULTS: There was a significant improvement in frequency of activity participation, measured using the Frenchay Activities Index, for the intervention group compared to the control group (Adjusted Mean Difference at follow up 4.22. 95% Confidence Interval 1.59-6.85). There were also significant improvements in perceptions of activity performance and satisfaction, self-efficacy, independence in daily activities and quality of life. Additionally, the intervention group demonstrated significantly higher levels of goal achievement, following the intervention. No significant differences were found between the two groups in anxiety, depression, self-management scores or healthcare utilisation. CONCLUSIONS: OPTIMAL significantly improved frequency of activity participation, self-efficacy and quality of life for patients with multimorbidity. Further work is required to test the sustainability of these effects over time but this study indicates that it is a promising intervention that can be delivered in primary care and community settings. TRIAL NUMBER: ISRCTN67235963

Chandra Detection of a TypeII Quasar at z=3.288

We report on observations of a TypeII quasar at redshift z=3.288, identified as a hard X-ray source in a 185 ks observation with the Chandra X-ray Observatory and as a high-redshift photometric candidate from deep, multiband optical imaging. CXOJ084837.9+445352 (hereinafter CXO52) shows an unusually hard X-ray spectrum from which we infer an absorbing column density N(H) = (4.8+/-2.1)e23 / cm2 (90% confidence) and an implied unabsorbed 2-10 keV rest-frame luminosity of L(2-10) = 3.3e44 ergs/s, well within the quasar regime. Hubble Space Telescope imaging shows CXO52 to be elongated with slight morphological differences between the WFPC2 F814W and NICMOS F160W bands. Optical and near-infrared spectroscopy of CXO52 show high-ionization emission lines with velocity widths ~1000 km/s and flux ratios similar to a Seyfert2 galaxy or radio galaxy. The latter are the only class of high-redshift TypeII luminous AGN which have been extensively studied to date. Unlike radio galaxies, however, CXO52 is radio quiet, remaining undetected at radio wavelengths to fairly deep limits, f(4.8GHz) < 40 microJy. High-redshift TypeII quasars, expected from unification models of active galaxies and long-thought necessary to explain the X-ray background, are poorly constrained observationally with few such systems known. We discuss recent observations of similar TypeII quasars and detail search techniques for such systems: namely (1) X-ray selection, (2) radio selection, (3) multi-color imaging selection, and (4) narrow-band imaging selection. Such studies are likely to begin identifying luminous, high-redshift TypeII systems in large numbers. We discuss the prospects for these studies and their implications to our understanding of the X-ray background.Comment: 28 pages, 5 figures; to appear in The Astrophysical Journa

Cosmological parameters from SDSS and WMAP

We measure cosmological parameters using the three-dimensional power spectrum P(k) from over 200,000 galaxies in the Sloan Digital Sky Survey (SDSS) in combination with WMAP and other data. Our results are consistent with a ``vanilla'' flat adiabatic Lambda-CDM model without tilt (n=1), running tilt, tensor modes or massive neutrinos. Adding SDSS information more than halves the WMAP-only error bars on some parameters, tightening 1 sigma constraints on the Hubble parameter from h~0.74+0.18-0.07 to h~0.70+0.04-0.03, on the matter density from Omega_m~0.25+/-0.10 to Omega_m~0.30+/-0.04 (1 sigma) and on neutrino masses from <11 eV to <0.6 eV (95%). SDSS helps even more when dropping prior assumptions about curvature, neutrinos, tensor modes and the equation of state. Our results are in substantial agreement with the joint analysis of WMAP and the 2dF Galaxy Redshift Survey, which is an impressive consistency check with independent redshift survey data and analysis techniques. In this paper, we place particular emphasis on clarifying the physical origin of the constraints, i.e., what we do and do not know when using different data sets and prior assumptions. For instance, dropping the assumption that space is perfectly flat, the WMAP-only constraint on the measured age of the Universe tightens from t0~16.3+2.3-1.8 Gyr to t0~14.1+1.0-0.9 Gyr by adding SDSS and SN Ia data. Including tensors, running tilt, neutrino mass and equation of state in the list of free parameters, many constraints are still quite weak, but future cosmological measurements from SDSS and other sources should allow these to be substantially tightened.Comment: Minor revisions to match accepted PRD version. SDSS data and ppt figures available at http://www.hep.upenn.edu/~max/sdsspars.htm

Avicin D, a Plant Triterpenoid, Induces Cell Apoptosis by Recruitment of Fas and Downstream Signaling Molecules into Lipid Rafts

Avicins, a family of triterpene electrophiles originally identified as potent inhibitors of tumor cell growth, have been shown to be pleiotropic compounds that also possess antioxidant, anti-mutagenic, and anti-inflammatory activities. We previously showed that Jurkat cells, which express a high level of Fas, are very sensitive to treatment with avicins. Thus, we hypothesized that avicins may induce cell apoptosis by activation of the Fas pathway. By using a series of cell lines deficient in cell death receptors, we demonstrated that upon avicin D treatment, Fas translocates to the cholesterol- and sphingolipid-enriched membrane microdomains known as lipid rafts. In the lipid rafts, Fas interacts with Fas-associated death domain (FADD) and Caspase-8 to form death-inducing signaling complex (DISC) and thus mediates cell apoptosis. Interfering with lipid raft organization by using a cholesterol-depleting compound, methyl-β-cyclodextrin, not only prevents the clustering of Fas and its DISC complex but also reduces the sensitivity of the cells to avicin D. Avicin D activates Fas pathways independent of the association between extracellular Fas ligands and Fas receptors. A deficiency in Fas and its downstream signaling molecules leads to the resistance of the cells to avicin D treatment. Taken together, our results demonstrate that avicin D triggers the redistribution of Fas in the membrane lipid rafts, where Fas activates receptor-mediated cell death

Factors associated with self-efficacy for managing recovery in the trauma intensive care population: A prospective cohort study

Objective: The aim of this paper was to identify factors associated with self-efficacy for managing recovery in the trauma intensive care population. Introduction: Injury accounts for 6.5% of disease burden in Australia, with similar levels being reported in other developed countries. While some studies regarding self-efficacy have identified a relationship to patient recovery post acute injury, others have been inconclusive. This study will identify factors associated with self-efficacy for managing recovery in the trauma intensive care population. Methods: A prospective cohort study of patients aged ≥18 years, admitted to a metropolitan tertiary hospital in South East Queensland between June 2008 and August 2010 for the acute treatment of injury. Demographic, injury, acute care and psychosocial factors were considered. The primary outcome was self-efficacy measured by the 6-item self-efficacy scale (SES) 1 and 6 months post hospital discharge. All factors significant (p < 0.10) on univariate analysis were included in multivariable modelling where p < 0.05 was considered significant. Results: A total of 88 patients were included. The mean self-efficacy score at 1 and 6 months was similar (6.8 vs 6.9 respectively). Self-efficacy at 1 month, psychological distress (K-10) Score and illness perception (K10) Score accounted for 68.4% (adjusted R2) of the variance in 6 month self-efficacy (F3,75) = 57.17, p < 0.001. Illness perception was the strongest contributor to 6 month self-efficacy (beta = −0.516), followed by psychological distress (beta = −0.243) and self-efficacy at 1 month (beta = 0.205). Conclusion: Significant factors associated with self-efficacy for managing recovery at 6 months included 1 month self-efficacy, illness perception and psychological distress. To promote patient recovery, screening patients at 1 month in order to commence relevant interventions could be beneficial

The microsporidian parasites Nosema ceranae and Nosema apis are widespread in honeybee (Apis mellifera) colonies across Scotland

Nosema ceranae is spreading into areas where Nosema apis already exists. N. ceranae has been reported to cause an asymptomatic infection that may lead, ultimately, to colony collapse. It is thought that there may be a temperature barrier to its infiltration into countries in colder climates. In this study, 71 colonies from Scottish Beekeeper’s Association members have been screened for the presence of N. apis and N. ceranae across Scotland. We find that only 11 of the 71 colonies tested positive for spores by microscopy. However, 70.4 % of colonies screened by PCR revealed the presence of both N. ceranae and N. apis, with only 4.2 or 7 % having either strain alone and 18.3 % being Nosema free. A range of geographically separated colonies testing positive for N. ceranae were sequenced to confirm their identity. All nine sequences confirmed the presence of N. ceranae and indicated the presence of a single new variant. Furthermore, two of the spore-containing colonies had only N. ceranae present, and these exhibited the presence of smaller spores that could be distinguished from N. apis by the analysis of average spore size. Differential quantification of the PCR product revealed N. ceranae to be the dominant species in all seven samples tested. In conclusion, N. ceranae is widespread in Scotland where it exists in combination with the endemic N. apis. A single variant, identical to that found in France (DQ374655) except for the addition of a single nucleotide polymorphism, is present in Scotland

Gender differences in the clinical management of patients with angina pectoris: a cross-sectional survey in primary care

Non peer reviewedPublisher PD

Avicin D: A Protein Reactive Plant Isoprenoid Dephosphorylates Stat 3 by Regulating Both Kinase and Phosphatase Activities

Avicins, a class of electrophilic triterpenoids with pro-apoptotic, anti-inflammatory and antioxidant properties, have been shown to induce redox-dependant post-translational modification of cysteine residues to regulate protein function. Based on (a) the cross-talk that occurs between redox and phosphorylation processes, and (b) the role of Stat3 in the process of apoptosis and carcinogenesis, we chose to study the effects of avicins on the processes of phosphorylation/dephosphorylation in Stat3. Avicins dephosphorylate Stat3 in a variety of human tumor cell lines, leading to a decrease in the transcriptional activity of Stat3. The expression of Stat3-regulated proteins such as c-myc, cyclin D1, Bcl2, survivin and VEGF were reduced in response to avicin treatment. Underlying avicin-induced dephosphorylation of Stat3 was dephosphorylation of JAKs, as well as activation of protein phosphatase-1. Downregulation of both Stat3 activity and expression of Stat 3-controlled pro-survival proteins, contributes to the induction of apoptosis in avicin treated tumor cells. Based on the role of Stat3 in inflammation and wounding, and the in vivo inhibition of VEGF by avicins in a mouse skin carcinogenesis model, it is likely that avicin-induced inhibition of Stat3 activity results in the suppression of the pro-inflammatory and pro-oxidant stromal environment of tumors. Activation of PP-1, which also acts as a cellular economizer, combined with the redox regulation by avicins, can aid in redirecting metabolism from growth promoting anabolic to energy sparing pathways

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice