Expression of Ki-67 and Bcl-2 in gastric epithelial cells: role of antralization in gastric carcinogenesis

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A qualitative evaluation of the impact of a Good Life Club on people living with dementia and care partners

Background: Research suggests there is a lack of post diagnostic support to enable people living with dementia to fulfil social and active lives throughout their dementia journey. Gardening has been found to have many benefits for people living with dementia. Although such research is important, most research frames people with dementia as passive recipients of stimulation. The impact of a community-based gardening group where people living with dementia are active in the development of an outdoor space is underdeveloped. Knowledge about the impact of participating in such groups is also sparse. The Good Life Club (GLC) was co-developed and evaluated to respond to these gaps. Objectives: The primary aim of this paper is to present the findings regarding the impact of attending the GLC on the self-reported wellbeing for people living with dementia and care partners. Methods: Qualitative data were collected via 22 semi-structured interviews. Fourteen interviews were conducted before the GLC and eight after the GLC. Thematic Analysis was used to analyse data. Dementia Care Mapping Data was collected to supplement the interview data. Findings: Four key themes were identified. The first was that participants considered having active participation in social life to be a key aspect of living a good life. The second was that the way the GLC was set up and delivered gave the participants ownership of the GLC and within this they felt able to contribute. The third was the importance of social connectedness and peer support to the wellbeing of both people living with dementia and care partners. Fourth, positive mood and wellbeing was directly experienced through gardening. Conclusions: The combination of long-term investment of time and energy to the GLC, on-going friendships and in-session autonomy, act as key ingredients in creating a group that is relaxed, full of humour and highly valued

Prevalence of chronic kidney disease among people living with HIV/AIDS in Burundi: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Since little is known about chronic kidney disease (CKD) among people living with HIV/AIDS (PLWHA) in Sub-Saharan Africa, the prevalence and nature of CKD were assessed in Burundi through a multicenter cross-sectional study.</p> <p>Methods</p> <p>Patients underwent assessments at baseline and 3 months later. Glomerular Filtration Rate (GFR) was estimated using abbreviated 4-variable Modification of Diet in Renal Diseases (MDRD) and Cockroft-Gault estimation methods. Patients were classified at month 3 into various CKD stages using the National Kidney Foundation (NKF) definition, which combines GFR and urinary abnormalities. Risk factors for presence of proteinuria (PRO) and aseptic leukocyturia (LEU) were further analyzed using multiple logistic regression.</p> <p>Results</p> <p>Median age of the patients in the study (N = 300) was 40 years, 70.3% were female and 71.7% were on highly active antiretroviral therapy. Using the MDRD method, CKD prevalence in patients was 45.7%, 30.2% of whom being classified as stage 1 according to the NKF classification, 13.5% as stage 2 and 2% as stage 3. No patient was classified as stage 4 or 5. Among CKD patients with urinary abnormality, PRO accounted for 6.1% and LEU for 18.4%. Significant associations were found between LEU and non-steroidal anti-inflammatory drug (NSAID) use, previous history of tuberculosis, low body mass index and female gender and between PRO and high viral load.</p> <p>Conclusion</p> <p>Our study, using a very sensitive definition for CKD evaluation, suggests a potentially high prevalence of CKD among PLWHA in Burundi. Patients should be regularly monitored and preventative measures implemented, such as monitoring NSAID use and adjustment of drug dosages according to body weight. Urine dipsticks could be used as a screening tool to detect patients at risk of renal impairment.</p

Structure-Based Stabilization of HIV-1 gp120 Enhances Humoral Immune Responses to the Induced Co-Receptor Binding Site

The human immunodeficiency virus type 1 (HIV-1) exterior envelope glycoprotein, gp120, possesses conserved binding sites for interaction with the primary virus receptor, CD4, and also for the co-receptor, generally CCR5. Although gp120 is a major target for virus-specific neutralizing antibodies, the gp120 variable elements and its malleable nature contribute to evasion of effective host-neutralizing antibodies. To understand the conformational character and immunogenicity of the gp120 receptor binding sites as potential vaccine targets, we introduced structure-based modifications to stabilize gp120 core proteins (deleted of the gp120 major variable regions) into the conformation recognized by both receptors. Thermodynamic analysis of the re-engineered core with selected ligands revealed significant stabilization of the receptor-binding regions. Stabilization of the co-receptor-binding region was associated with a marked increase in on-rate of ligand binding to this site as determined by surface plasmon resonance. Rabbit immunization studies showed that the conformational stabilization of core proteins, along with increased ligand affinity, was associated with strikingly enhanced humoral immune responses against the co-receptor-binding site. These results demonstrate that structure-based approaches can be exploited to stabilize a conformational site in a large functional protein to enhance immunogenic responses specific for that region

Alpha-2-Macroglobulin Is Acutely Sensitive to Freezing and Lyophilization: Implications for Structural and Functional Studies.

Alpha-2-macroglobulin is an abundant secreted protein that is of particular interest because of its diverse ligand binding profile and multifunctional nature, which includes roles as a protease inhibitor and as a molecular chaperone. The activities of alpha-2-macroglobulin are typically dependent on whether its conformation is native or transformed (i.e. adopts a more compact conformation after interactions with proteases or small nucleophiles), and are also influenced by dissociation of the native alpha-2-macroglobulin tetramer into stable dimers. Alpha-2-macroglobulin is predominately present as the native tetramer in vivo; once purified from human blood plasma, however, alpha-2-macroglobulin can undergo a number of conformational changes during storage, including transformation, aggregation or dissociation. We demonstrate that, particularly in the presence of sodium chloride or amine containing compounds, freezing and/or lyophilization of alpha-2-macroglobulin induces conformational changes with functional consequences. These conformational changes in alpha-2-macroglobulin are not always detected by standard native polyacrylamide gel electrophoresis, but can be measured using bisANS fluorescence assays. Increased surface hydrophobicity of alpha-2-macroglobulin, as assessed by bisANS fluorescence measurements, is accompanied by (i) reduced trypsin binding activity, (ii) increased chaperone activity, and (iii) increased binding to the surfaces of SH-SY5Y neurons, in part, via lipoprotein receptors. We show that sucrose (but not glycine) effectively protects native alpha-2-macroglobulin from denaturation during freezing and/or lyophilization, thereby providing a reproducible method for the handling and long-term storage of this protein.Early Career Fellowship from the National Health and Medical Research Council GNT1012521(A.R.W.); Wellcome Trust Programme Grant (J.R.K., C.M.D.) 094425/Z/10/Z; Samsung GRO Grant (M.R.W.)This is the final version of the article. It first appeared from PLoS via http://dx.doi.org/10.1371/journal.pone.013003

Deep-Inelastic Inclusive ep Scattering at Low x and a Determination of alpha_s

A precise measurement of the inclusive deep-inelastic e^+p scattering cross section is reported in the kinematic range 1.5<= Q^2 <=150 GeV^2 and 3*10^(-5)<= x <=0.2. The data were recorded with the H1 detector at HERA in 1996 and 1997, and correspond to an integrated luminosity of 20 pb^(-1). The double differential cross section, from which the proton structure function F_2(x,Q^2) and the longitudinal structure function F_L(x,Q^2) are extracted, is measured with typically 1% statistical and 3% systematic uncertainties. The measured partial derivative (dF_2(x,Q^2)/dln Q^2)_x is observed to rise continuously towards small x for fixed Q^2. The cross section data are combined with published H1 measurements at high Q^2 for a next-to-leading order DGLAP QCD analysis.The H1 data determine the gluon momentum distribution in the range 3*10^(-4)<= x <=0.1 to within an experimental accuracy of about 3% for Q^2 =20 GeV^2. A fit of the H1 measurements and the mu p data of the BCDMS collaboration allows the strong coupling constant alpha_s and the gluon distribution to be simultaneously determined. A value of alpha _s(M_Z^2)=0.1150+-0.0017 (exp) +0.0009-0.0005 (model) is obtained in NLO, with an additional theoretical uncertainty of about +-0.005, mainly due to the uncertainty of the renormalisation scale.Comment: 68 pages, 24 figures and 18 table

Measurement of the top quark mass using the matrix element technique in dilepton final states

We present a measurement of the top quark mass in pp¯ collisions at a center-of-mass energy of 1.96 TeV at the Fermilab Tevatron collider. The data were collected by the D0 experiment corresponding to an integrated luminosity of 9.7  fb−1. The matrix element technique is applied to tt¯ events in the final state containing leptons (electrons or muons) with high transverse momenta and at least two jets. The calibration of the jet energy scale determined in the lepton+jets final state of tt¯ decays is applied to jet energies. This correction provides a substantial reduction in systematic uncertainties. We obtain a top quark mass of mt=173.93±1.84  GeV

Capacity management of nursing staff as a vehicle for organizational improvement

<p>Abstract</p> <p>Background</p> <p>Capacity management systems create insight into required resources like staff and equipment. For inpatient hospital care, capacity management requires information on beds and nursing staff capacity, on a daily as well as annual basis. This paper presents a comprehensive capacity model that gives insight into required nursing staff capacity and opportunities to improve capacity utilization on a ward level.</p> <p>Methods</p> <p>A capacity model was developed to calculate required nursing staff capacity. The model used historical bed utilization, nurse-patient ratios, and parameters concerning contract hours to calculate beds and nursing staff needed per shift and the number of nurses needed on an annual basis in a ward. The model was applied to three different capacity management problems on three separate groups of hospital wards. The problems entailed operational, tactical, and strategic management issues: optimizing working processes on pediatric wards, predicting the consequences of reducing length of stay on nursing staff required on a cardiology ward, and calculating the nursing staff consequences of merging two internal medicine wards.</p> <p>Results</p> <p>It was possible to build a model based on easily available data that calculate the nursing staff capacity needed daily and annually and that accommodate organizational improvements. Organizational improvement processes were initiated in three different groups of wards. For two pediatric wards, the most important improvements were found to be improving working processes so that the agreed nurse-patient ratios could be attained. In the second case, for a cardiology ward, what-if analyses with the model showed that workload could be substantially lowered by reducing length of stay. The third case demonstrated the possible savings in capacity that could be achieved by merging two small internal medicine wards.</p> <p>Conclusion</p> <p>A comprehensive capacity model was developed and successfully applied to support capacity decisions on operational, tactical, and strategic levels. It appeared to be a useful tool for supporting discussions between wards and hospital management by giving objective and quantitative insight into staff and bed requirements. Moreover, the model was applied to initiate organizational improvements, which resulted in more efficient capacity utilization.</p

Chemotherapy effectiveness in trial-underrepresented groups with early breast cancer:A retrospective cohort study

BACKGROUND: Adjuvant chemotherapy in early stage breast cancer has been shown to reduce mortality in a large meta-analysis of over 100 randomised trials. However, these trials largely excluded patients aged 70 years and over or with higher levels of comorbidity. There is therefore uncertainty about whether the effectiveness of adjuvant chemotherapy generalises to these groups, hindering patient and clinician decision-making. This study utilises administrative healthcare data-real world data (RWD)-and econometric methods for causal analysis to estimate treatment effectiveness in these trial-underrepresented groups. METHODS AND FINDINGS: Women with early breast cancer aged 70 years and over and those under 70 years with a high level of comorbidity were identified and their records extracted from Scottish Cancer Registry (2001-2015) data linked to other routine health records. A high level of comorbidity was defined as scoring 1 or more on the Charlson comorbidity index, being in the top decile of inpatient stays, and/or having 5 or more visits to specific outpatient clinics, all within the 5 years preceding breast cancer diagnosis. Propensity score matching (PSM) and instrumental variable (IV) analysis, previously identified as feasible and valid in this setting, were used in conjunction with Cox regression to estimate hazard ratios for death from breast cancer and death from all causes. The analysis adjusts for age, clinical prognostic factors, and socioeconomic deprivation; the IV method may also adjust for unmeasured confounding factors. Cohorts of 9,653 and 7,965 were identified for women aged 70 years and over and those with high comorbidity, respectively. In the ≥70/high comorbidity cohorts, median follow-up was 5.17/6.53 years and there were 1,935/740 deaths from breast cancer. For women aged 70 years and over, the PSM-estimated HR was 0.73 (95% CI 0.64-0.95), while for women with high comorbidity it was 0.67 (95% CI 0.51-0.86). This translates to a mean predicted benefit in terms of overall survival at 10 years of approximately3% (percentage points) and 4%, respectively. A limitation of this analysis is that use of observational data means uncertainty remains both from sampling uncertainty and from potential bias from residual confounding. CONCLUSIONS: The results of this study, as RWD, should be interpreted with caution and in the context of existing and emerging randomised data. The relative effectiveness of adjuvant chemotherapy in reducing mortality in patients with early stage breast cancer appears to be generalisable to the selected trial-underrepresented groups.</p

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente