A Human Minor Histocompatibility Antigen Specific for B Cell Acute Lymphoblastic Leukemia

Human minor histocompatibility antigens (mHags) play an important role in the induction of cytotoxic T lymphocyte (CTL) reactivity against leukemia after human histocompatibility leukocyte antigen (HLA)-identical allogeneic bone marrow transplantation (BMT). As most mHags are not leukemia specific but are also expressed by normal tissues, antileukemia reactivity is often associated with life-threatening graft-versus-host disease (GVHD). Here, we describe a novel mHag, HB-1, that elicits donor-derived CTL reactivity in a B cell acute lymphoblastic leukemia (B-ALL) patient treated by HLA-matched BMT. We identified the gene encoding the antigenic peptide recognized by HB-1–specific CTLs. Interestingly, expression of the HB-1 gene was only observed in B-ALL cells and Epstein-Barr virus–transformed B cells. The HB-1 gene–encoded peptide EEKRGSLHVW is recognized by the CTL in association with HLA-B44. Further analysis reveals that a polymorphism in the HB-1 gene generates a single amino acid exchange from His to Tyr at position 8 within this peptide. This amino acid substitution is critical for recognition by HB-1–specific CTLs. The restricted expression of the polymorphic HB-1 Ag by B-ALL cells and the ability to generate HB-1–specific CTLs in vitro using peptide-loaded dendritic cells offer novel opportunities to specifically target the immune system against B-ALL without the risk of evoking GVHD

Organizational culture, team climate and diabetes care in small office-based practices

Contains fulltext : 71456.pdf ( ) (Open Access)BACKGROUND: Redesigning care has been proposed as a lever for improving chronic illness care. Within primary care, diabetes care is the most widespread example of restructured integrated care. Our goal was to assess to what extent important aspects of restructured care such as multidisciplinary teamwork and different types of organizational culture are associated with high quality diabetes care in small office-based general practices. METHODS: We conducted cross-sectional analyses of data from 83 health care professionals involved in diabetes care from 30 primary care practices in the Netherlands, with a total of 752 diabetes mellitus type II patients participating in an improvement study. We used self-reported measures of team climate (Team Climate Inventory) and organizational culture (Competing Values Framework), and measures of quality of diabetes care and clinical patient characteristics from medical records and self-report. We conducted multivariate analyses of the relationship between culture, climate and HbA1c, total cholesterol, systolic blood pressure and a sum score on process indicators for the quality of diabetes care, adjusting for potential patient- and practice level confounders and practice-level clustering. RESULTS: A strong group culture was negatively associated to the quality of diabetes care provided to patients (beta = -0.04; p = 0.04), whereas a more 'balanced culture' was positively associated to diabetes care quality (beta = 5.97; p = 0.03). No associations were found between organizational culture, team climate and clinical patient outcomes. CONCLUSION: Although some significant associations were found between high quality diabetes care in general practice and different organizational cultures, relations were rather marginal. Variation in clinical patient outcomes could not be attributed to organizational culture or teamwork. This study therefore contributes to the discussion about the legitimacy of the widespread idea that aspects of redesigning care such as teamwork and culture can contribute to higher quality of care. Future research should preferably combine quantitative and qualitative methods, focus on possible mediating or moderating factors and explore the use of instruments more sensitive to measure such complex constructs in small office-based practices

Money talks: moral economies of earning a living in neoliberal East Africa

Neoliberal restructuring has targeted not just the economy, but also polity, society and culture, in the name of creating capitalist market societies. The societal repercussions of neoliberal policy and reform in terms of moral economy remain understudied. This article seeks to address this gap by analysing moral economy characteristics and dynamics in neoliberalised communities, as perceived by traders in Uganda and sex workers in Kenya. The interview data reveal perceived drivers that contributed to a significant moral dominance of money, self-interest, short-termism, opportunism and pragmatism. Equally notable are a perceived (i) close interaction between political–economic and moral–economic dynamics, and (ii) significant impact of the political–economic structure on moral agency. Respondents primarily referred to material factors usually closely linked to neoliberal reform, as key drivers of local moral economies. We thus speak of a neoliberalisation of moral economies, itself part of the wider process of embedding and locking-in market society structures in the two countries. An improved political economy of moral economy can help keep track of this phenomenon

Physiological modeling, tight glycemic control, and the ICU clinician: what are models and how can they affect practice?

Critically ill patients are highly variable in their response to care and treatment. This variability and the search for improved outcomes have led to a significant increase in the use of protocolized care to reduce variability in care. However, protocolized care does not address the variability of outcome due to inter- and intra-patient variability, both in physiological state, and the response to disease and treatment. This lack of patient-specificity defines the opportunity for patient-specific approaches to diagnosis, care, and patient management, which are complementary to, and fit within, protocolized approaches

Search for the Standard Model Higgs boson produced in association with top quarks and decaying into bb¯ in pp collisions at √s=8 TeV with the ATLAS detector

A search for the Standard Model Higgs boson produced in association with a top-quark pair, tt¯H, is presented. The analysis uses 20.3 fb−1 of pp collision data at √s=8TeV, collected with the ATLAS detector at the Large Hadron Collider during 2012. The search is designed for the H→bb¯ decay mode and uses events containing one or two electrons or muons. In order to improve the sensitivity of the search, events are categorised according to their jet and b-tagged jet multiplicities. A neural network is used to discriminate between signal and background events, the latter being dominated by tt¯+jets production. In the single-lepton channel, variables calculated using a matrix element method are included as inputs to the neural network to improve discrimination of the irreducible tt¯+bb¯ background. No significant excess of events above the background expectation is found and an observed (expected) limit of 3.4 (2.2) times the Standard Model cross section is obtained at 95% confidence level. The ratio of the measured tt¯H signal cross section to the Standard Model expectation is found to be μ=1.5±1.1 assuming a Higgs boson mass of 125GeV

Measurement of distributions sensitive to the underlying event in inclusive Z-boson production in pp collisions at √s = 7 TeV with the ATLAS detector

A measurement of charged-particle distributions sensitive to the properties of the underlying event is presented for an inclusive sample of events containing a Z-boson, decaying to an electron or muon pair. The measurement is based on data collected using the ATLAS detector at the LHC in proton–proton collisions at a centre-of-mass energy of 7 TeV with an integrated luminosity of 4.6 fb −¹. Distributions of the charged particle multiplicity and of the charged particle transverse momentum are measured in regions of azimuthal angle defined with respect to the Z-boson direction. The measured distributions are compared to similar distributions measured in jet events, and to the predictions of various Monte Carlo generators implementing different underlying event models

A measurement of the ratio of the production cross sections for W and Z bosons in association with jets with the ATLAS detector

The ratio of the production cross sections for W and Z bosons in association with jets has been measured in proton–proton collisions at √s=7TeV with the ATLAS experiment at the Large Hadron Collider. The measurement is based on the entire 2011 dataset, corresponding to an integrated luminosity of 4.6fb−1. Inclusive and differential cross-section ratios for massive vector bosons decaying to electrons and muons are measured in association with jets with transverse momentum pT>30GeV and jet rapidity |y|<4.4. The measurements are compared to next-to-leading-order perturbative QCD calculations and to predictions from different Monte Carlo generators implementing leading-order matrix elements supplemented by parton showers