Assessing health and well-being among older people in rural South Africa

Background: The population in developing countries is ageing, which is likely to increase the burden of noncommunicable diseases and disability. Objective: To describe factors associated with self-reported health, disability and quality of life (QoL) of older people in the rural northeast of South Africa. Design: Cross-sectional survey of 6,206 individuals aged 50 and over. We used multivariate analysis to examine relationships between demographic variables and measures of self-reported health (Health Status), functional ability (WHODASi) and quality of life (WHOQoL). Results: About 4,085 of 6,206 people eligible (65.8%) completed the interview. Women (Odds Ratio (OR) 1.30, 95% CI 1.09, 1.55), older age (OR2.59, 95% CI 1.97, 3.40), lower education (OR1.62, 95% CI 1.31,2.00), single status (OR1.18, 95% CI 1.01, 1.37) and not working at present (OR1.29, 95% CI 1.06, 1.59) were associated with a low health status. Women were also more likely to report a higher level of disability (OR1.38, 95% CI 1.14, 1.66), as were older people (OR2.92, 95% CI 2.25, 3.78), those with no education (OR1.57, 95% CI 1.26, 1.97), with single status (OR1.25, 95% CI 1.06, 1.46) and not working at present (OR1.33, 95% CI 1.06, 1.66). Older age (OR1.35, 95% CI 1.06, 1.74), no education (OR1.39, 95% CI 1.11, 1.73), single status (OR1.28, 95% CI 1.10, 1.49), a low household asset score (OR1.52, 95% CI 1.19, 1.94) and not working at present (OR1.32; 95% CI 1.07, 1.64) were all associated with lower quality of life. Conclusions: This study presents the first population-based data from South Africa on health status, functional ability and quality of life among older people. Health and social services will need to be restructured to provide effective care for older people living in rural South Africa with impaired functionality and other health problems

Interventions for behaviour change and self-management in stroke secondary prevention: protocol for an overview of reviews

Abstract Background Stroke secondary prevention guidelines recommend medication prescription and adherence, active education and behavioural counselling regarding lifestyle risk factors. To impact on recurrent vascular events, positive behaviour/s must be adopted and sustained as a lifestyle choice, requiring theoretically informed behaviour change and self-management interventions. A growing number of systematic reviews have addressed complex interventions in stroke secondary prevention. Differing terminology, inclusion criteria and overlap of studies between reviews makes the mechanism/s that affect positive change difficult to identify or replicate clinically. Adopting a two-phase approach, this overview will firstly comprehensively summarise systematic reviews in this area and secondly identify and synthesise primary studies in these reviews which provide person-centred, theoretically informed interventions for stroke secondary prevention. Methods An overview of reviews will be conducted using a systematic search strategy across the Cochrane Database of Systematic Reviews, PubMed and Epistomonikas. Inclusion criteria: systematic reviews where the population comprises individuals post-stroke or TIA and where data relating to person-centred risk reduction are synthesised for evidence of efficacy when compared to standard care or no intervention. Primary outcomes of interest include mortality, recurrent stroke and other cardiovascular events. In phase 1, two reviewers will independently (1) assess the eligibility of identified reviews for inclusion; (2) rate the quality of included reviews using the ROBIS tool; (3) identify unique primary studies and overlap between reviews; (4) summarise the published evidence supporting person-centred behavioural change and self-management interventions in stroke secondary prevention and (5) identify evidence gaps in this field. In phase 2, two independent reviewers will (1) examine person-centred, primary studies in each review using the Template for Intervention Description and Replication (TIDieR checklist), itemising, where present, theoretical frameworks underpinning interventions; (2) group studies employing theoretically informed interventions by the intervention delivered and by the outcomes reported (3) apply GRADE quality of evidence for each intervention by outcome/s identified from theoretically informed primary studies. Disagreement between reviewers at each process stage will be discussed and a third reviewer consulted. Discussion This overview will comprehensively bring together the best available evidence supporting person-centred, stroke secondary prevention strategies in an accessible format, identifying current knowledge gaps

Theory of Star Formation

We review current understanding of star formation, outlining an overall theoretical framework and the observations that motivate it. A conception of star formation has emerged in which turbulence plays a dual role, both creating overdensities to initiate gravitational contraction or collapse, and countering the effects of gravity in these overdense regions. The key dynamical processes involved in star formation -- turbulence, magnetic fields, and self-gravity -- are highly nonlinear and multidimensional. Physical arguments are used to identify and explain the features and scalings involved in star formation, and results from numerical simulations are used to quantify these effects. We divide star formation into large-scale and small-scale regimes and review each in turn. Large scales range from galaxies to giant molecular clouds (GMCs) and their substructures. Important problems include how GMCs form and evolve, what determines the star formation rate (SFR), and what determines the initial mass function (IMF). Small scales range from dense cores to the protostellar systems they beget. We discuss formation of both low- and high-mass stars, including ongoing accretion. The development of winds and outflows is increasingly well understood, as are the mechanisms governing angular momentum transport in disks. Although outstanding questions remain, the framework is now in place to build a comprehensive theory of star formation that will be tested by the next generation of telescopes.Comment: 120 pages, to appear in ARAA. No changes from v1 text; permission statement adde

Rapid intraoperative insulin assay: a novel method to differentiate insulinoma from nesidioblastosis in the pediatric patient

Introduction: Hyperinsulinism is the most common cause of recurrent and persistent hypoglycemia in infancy and childhood. Causes can include nesidioblastosis, pancreatic islet cell tumors such as insulinoma, and associations with multiple endocrine neoplasia syndromes. Although new, improved imaging techniques have allowed for more precise preoperative localization of insulinomas, the differentiation of nesidioblastosis and insulinoma, particularly in children, can be challenging. To improve intraoperative localization and confirmation of successful resection of insulinoma, a novel hormonal assay, the rapid intraoperative insulin assay, is reported for the first time in a pediatric patient. This intraoperative radioimmunoassay for insulin yields results within several minutes and confirms complete resection of insulinoma. Case description: We present a case of pancreatic insulinoma in a child with symptoms of severe hypoglycemia, causing seizures. The insulinoma was enucleated laparoscopically, and rapid intra-operative insulin assay used to determine the success of the procedure. Discussion and evaluation: This rapid intra-operative test provides a valuable adjunct for determining complete excision in complicated cases of recurrent or questionable insulinoma. Although not a common problem, for pediatric patients in whom the diagnosis is not clear, this test may provide a novel approach to confirming disease. Conclusion: We propose the use of this assay in facilitating intra-operative resection and confirmation of complete excision in pediatric patients. This population may especially benefit from this novel assay to confirm complete resection and to differentiate multiple etiologies of hyperinsulinism

Nitric Oxide Facilitates Delivery and Mediates Improved Outcome of Autologous Bone Marrow Mononuclear Cells in a Rodent Stroke Model

Bone marrow mononuclear cells (MNC) represent an investigational treatment for stroke. The objective of this study was to determine the relevance of vasoactive mediators, generated in response to MNC injection, as factors regulating cerebral perfusion (CP), the biodistribution of MNC, and outcome in stroke.Long Evans rats underwent transient middle cerebral artery occlusion. MNC were extracted from the bone marrow at 22 hrs and injected via the internal carotid artery or the femoral vein 2 hours later. CP was measured with MRI or continuous laser Doppler flowmetry. Serum samples were collected to measure vasoactive mediators. Animals were treated with the Nitric Oxide (NO) inhibitor, L-NAME, to establish the relevance of NO-signaling to the effect of MNC. Lesion size, MNC biodistribution, and neurological deficits were assessed.CP transiently increased in the peri-infarct region within 30 min after injecting MNC compared to saline or fibroblast control. This CP increase corresponded temporarily to serum NO elevation and was abolished by L-NAME. Pre-treatment with L-NAME reduced brain penetration of MNC and prevented MNC from reducing infarct lesion size and neurological deficits.NO generation in response to MNC may represent a mechanism underlying how MNC enter the brain, reduce lesion size, and improve outcome in ischemic stroke

Synergistic effects of oncolytic reovirus and docetaxel chemotherapy in prostate cancer

Reovirus type 3 Dearing (T3D) has demonstrated oncolytic activity in vitro, in in vivo murine models and in early clinical trials. However the true potential of oncolytic viruses may only be realized fully in combination with other modalities such as chemotherapy, targeted therapy and radiotherapy. In this study, we examine the oncolytic activity of reovirus T3D and chemotherapeutic agents against human prostate cancer cell lines, with particular focus on the highly metastatic cell line PC3 and the chemotherapeutic agent docetaxel. Docetaxel is the standard of care for metastatic prostate cancer and acts by disrupting the normal process of microtubule assembly and disassembly. Reoviruses have been shown to associate with microtubules and may require this association for efficient viral replication

Reovirus exerts potent oncolytic effects in head and neck cancer cell lines that are independent of signalling in the EGFR pathway

Background: reovirus exploits aberrant signalling downstream of Ras to mediate tumor-specific oncolysis. Since ~90% squamous cell carcinomas of the head and neck (SCCHN) over-express EGFR and SCCHN cell lines are sensitive to oncolytic reovirus, we conducted a detailed analysis of the effects of reovirus in 15 head and neck cancer cell lines. Both pre- and post-entry events were studied in an attempt to define biomarkers predictive of sensitivity/resistance to reovirus. In particular, we analysed the role of EGFR/Ras signalling in determining virus-mediated cytotoxicity in SCCHN. Methods: to test whether EGFR pathway activity was predictive of increased sensitivity to reovirus, correlative analyses between reoviral IC50 by MTT assay and EGFR levels by western blot and FACS were conducted. Inhibition or stimulation of EGFR signalling were analysed for their effect on reoviral oncolysis by MTT assay, and viral growth by TCID50 assay. We next analysed the effects of inhibiting signalling downstream of Ras, by specific inhibitors of p38MAPK, PI3-K or MEK, on reoviral killing examined by MTT assay. The role of PKR in reoviral killing was also determined by blockade of PKR using 2-aminopurine and assaying for cell survival by MTT assay. The apoptotic response of SCCHN to reovirus was examined by western blot analysis of caspase 3 cleavage. Results: correlative analyses between reoviral sensitivity and EGFR levels revealed no association. Intermediate sub-viral and core particles showed the same infectivity/cytotoxicity as intact reovirus. Therefore, sensitivity was not determined by cell entry. In 4 cell lines, oncolysis and viral growth were both unaffected by inhibition or stimulation of EGFR signalling. Inhibition of signalling downstream of Ras did not abrogate reoviral oncolysis and, in addition, modulation of PKR using 2-aminopurine did not alter reovirus sensitivity in resistant cell lines. Caspase 3 cleavage was not detected in infected cells and oncolysis was observed in pan-caspase inhibited cells. Conclusions: in summary, reovirus is potently oncolytic in a broad panel of SCCHN cell lines. Attempts to define sensitivity/resistance by analysis of the EGFR/Ras/MAPK pathway have failed to provide a clear predictive biomarker of response. Further analysis of material from in vitro and clinical studies is ongoing in an attempt to shed further light on this issue

Mutations in the Catalytic Loop HRD Motif Alter the Activity and Function of Drosophila Src64

The catalytic loop HRD motif is found in most protein kinases and these amino acids are predicted to perform functions in catalysis, transition to, and stabilization of the active conformation of the kinase domain. We have identified mutations in a Drosophila src gene, src64, that alter the three HRD amino acids. We have analyzed the mutants for both biochemical activity and biological function during development. Mutation of the aspartate to asparagine eliminates biological function in cytoskeletal processes and severely reduces fertility, supporting the amino acid's critical role in enzymatic activity. The arginine to cysteine mutation has little to no effect on kinase activity or cytoskeletal reorganization, suggesting that the HRD arginine may not be critical for coordinating phosphotyrosine in the active conformation. The histidine to leucine mutant retains some kinase activity and biological function, suggesting that this amino acid may have a biochemical function in the active kinase that is independent of its side chain hydrogen bonding interactions in the active site. We also describe the phenotypic effects of other mutations in the SH2 and tyrosine kinase domains of src64, and we compare them to the phenotypic effects of the src64 null allele

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration