599 research outputs found
Vitamin A Status of Women and Children in Yaoundé and Douala, Cameroon, is Unchanged One Year after Initiation of a National Vitamin A Oil Fortification Program.
Vitamin A (VA) fortification of cooking oil is considered a cost-effective strategy for increasing VA status, but few large-scale programs have been evaluated. We conducted representative surveys in Yaoundé and Douala, Cameroon, 2 years before and 1 year after the introduction of a mandatory national program to fortify cooking oil with VA. In each survey, 10 different households were selected within each of the same 30 clusters (n = ~300). Malaria infection and plasma indicators of inflammation and VA (retinol-binding protein, pRBP) status were assessed among women aged 15-49 years and children aged 12-59 months, and casual breast milk samples were collected for VA and fat measurements. Refined oil intake was measured by a food frequency questionnaire, and VA was measured in household oil samples post-fortification. Pre-fortification, low inflammation-adjusted pRBP was common among children (33% <0.83 ”mol/L), but not women (2% <0.78 ”mol/L). Refined cooking oil was consumed by >80% of participants in the past week. Post-fortification, only 44% of oil samples were fortified, but fortified samples contained VA concentrations close to the target values. Controlling for age, inflammation, and other covariates, there was no difference in the mean pRBP, mean breast milk VA, prevalence of low pRBP, or prevalence of low milk VA between the pre- and post-fortification surveys. The frequency of refined oil intake was not associated with VA status indicators post-fortification. In sum, after a year of cooking oil fortification with VA, we did not detect evidence of increased plasma RBP or milk VA among urban women and preschool children, possibly because less than half of the refined oil was fortified. The enforcement of norms should be strengthened, and the program should be evaluated in other regions where the prevalence of VA deficiency was greater pre-fortification
Federated learning in medicine: Facilitating multiâinstitutional collaborations without sharing patient data
Class switching and meiotic defects in mice lacking the E3 ubiquitin ligase RNF8
53BP1 is a well-known mediator of the cellular response to DNA damage. Two alternative mechanisms have been proposed to explain 53BP1âs interaction with DNA double-strand breaks (DSBs), one by binding to methylated histones and the other via an RNF8 E3 ligaseâdependent ubiquitylation pathway. The formation of RNF8 and 53BP1 irradiation-induced foci are both dependent on histone H2AX. To evaluate the contribution of the RNF8-dependent pathway to 53BP1 function, we generated RNF8 knockout mice. We report that RNF8 deficiency results in defective class switch recombination (CSR) and accumulation of unresolved immunoglobulin heavy chainâassociated DSBs. The CSR DSB repair defect is milder than that observed in the absence of 53BP1 but similar to that found in H2AXâ/â mice. Moreover, similar to H2AX but different from 53BP1 deficiency, RNF8â/â males are sterile, and this is associated with defective ubiquitylation of the XY chromatin. Combined loss of H2AX and RNF8 does not cause further impairment in CSR, demonstrating that the two genes function epistatically. Importantly, although 53BP1 foci formation is RNF8 dependent, its binding to chromatin is preserved in the absence of RNF8. This suggests a two-step mechanism for 53BP1 association with chromatin in which constitutive loading is dependent on interactions with methylated histones, whereas DNA damageâinducible RNF8-dependent ubiquitylation allows its accumulation at damaged chromatin
Specific Roles of XRCC4 Paralogs PAXX and XLF during V(D)J Recombination.
Paralog of XRCC4 and XLF (PAXX) is a member of the XRCC4 superfamily and plays a role in nonhomologous end-joining (NHEJ), a DNA repair pathway critical for lymphocyte antigen receptor gene assembly. Here, we find that the functions of PAXX and XLF in V(D)J recombination are masked by redundant joining activities. Thus, combined PAXX and XLF deficiency leads to an inability to join RAG-cleaved DNA ends. Additionally, we demonstrate that PAXX function in V(D)J recombination depends on its interaction with Ku. Importantly, we show that, unlike XLF, the role of PAXX during the repair of DNA breaks does not overlap with ATM and the RAG complex. Our findings illuminate the role of PAXX in V(D)J recombination and support a model in which PAXX and XLF function during NHEJ repair of DNA breaks, whereas XLF, the RAG complex, and the ATM-dependent DNA damage response promote end joining by stabilizing DNA ends.Cancer Research UK (Grant IDs: C6/A18796, C6946/A14492, C6/A18796), European Research Council (Grant ID: 310917), Wellcome Trust (Grant ID: WT092096), University of Cambridge, Institut PasteurThis is the final version of the article. It first appeared from Elsevier (Cell Press) via http://dx.doi.org/10.1016/j.celrep.2016.08.06
Cost-effectiveness of a Community-based Hypertension Improvement Project (ComHIP) in Ghana: results from a modelling study.
Objective
To undertake a cost-effectiveness analysis of a Community-based Hypertension Improvement Project (ComHIP) compared with standard hypertension care in Ghana.
Design
Cost-effectiveness analysis using a Markov model.SettingLower Manya Krobo, Eastern Region, Ghana.InterventionWe evaluated ComHIP, an intervention with multiple components, including: community-based education on cardiovascular disease (CVD) risk factors and healthy lifestyles; community-based screening and monitoring of blood pressure by licensed chemical sellers and CVD nurses; community-based diagnosis, treatment, counselling, follow-up and referral of hypertension patients by CVD nurses; telemedicine consultation by CVD nurses and referral of patients with severe hypertension and/or organ damage to a physician; information and communication technologies messages for healthy lifestyles, treatment adherence support and treatment refill reminders for hypertension patients; Commcare, a cloud-based health records system linked to short-message service (SMS)/voice messaging for treatment adherence, reminders and health messaging. ComHIP was evaluated under two scale-up scenarios: (1) ComHIP as currently implemented with support from international partners and (2) ComHIP under full local implementation.
Main outcome measures
Incremental cost per disability-adjusted life-year (DALY) averted from a societal perspective over a time horizon of 10 years.
Results
ComHIP is unlikely to be a cost-effective intervention, with current ComHIP implementation and ComHIP under full local implementation costing on average US6530 per DALY averted, respectively. Results were robust to uncertainty analyses around model parameters.
Conclusions
High overhead costs and high patient costs in ComHIP suggest that the societal costs of ensuring appropriate hypertension care are high and may not produce sufficient impact to achieve cost-effective implementation. However, these results are limited by the evidence quality of the effectiveness estimates, which comes from observational data rather than from randomised controlled study design
THE TOOLS AND MONTE CARLO WORKING GROUP Summary Report from the Les Houches 2009 Workshop on TeV Colliders
This is the summary and introduction to the proceedings contributions for the
Les Houches 2009 "Tools and Monte Carlo" working group.Comment: 144 Pages. Workshop site
http://wwwlapp.in2p3.fr/conferences/LesHouches/Houches2009/ . Conveners were
Butterworth, Maltoni, Moortgat, Richardson, Schumann and Skand
Large-Scale Conformational Changes of Trypanosoma cruzi Proline Racemase Predicted by Accelerated Molecular Dynamics Simulation
Chagas' disease, caused by the protozoan parasite Trypanosoma cruzi (T. cruzi), is a life-threatening illness affecting 11â18 million people. Currently available treatments are limited, with unacceptable efficacy and safety profiles. Recent studies have revealed an essential T. cruzi proline racemase enzyme (TcPR) as an attractive candidate for improved chemotherapeutic intervention. Conformational changes associated with substrate binding to TcPR are believed to expose critical residues that elicit a host mitogenic B-cell response, a process contributing to parasite persistence and immune system evasion. Characterization of the conformational states of TcPR requires access to long-time-scale motions that are currently inaccessible by standard molecular dynamics simulations. Here we describe advanced accelerated molecular dynamics that extend the effective simulation time and capture large-scale motions of functional relevance. Conservation and fragment mapping analyses identified potential conformational epitopes located in the vicinity of newly identified transient binding pockets. The newly identified open TcPR conformations revealed by this study along with knowledge of the closed to open interconversion mechanism advances our understanding of TcPR function. The results and the strategy adopted in this work constitute an important step toward the rationalization of the molecular basis behind the mitogenic B-cell response of TcPR and provide new insights for future structure-based drug discovery
Effective Lagrangian for and Vertices in the mSUGRA model
Complete expressions of the and vertices are
derived in the framework of supersymmetry with minimal flavor violation. With
the minimal supergravity (mSUGRA) model, a numerical analysis of the
supersymmetric contributions to the Wilson Coefficients at the weak scale is
presented.Comment: 12 pages + 7 ps figures, Late
Predictions for Higgs production at the Tevatron and the associated uncertainties
We update the theoretical predictions for the production cross sections of
the Standard Model Higgs boson at the Fermilab Tevatron collider, focusing on
the two main search channels, the gluon-gluon fusion mechanism and
the Higgs-strahlung processes with , including all
relevant higher order QCD and electroweak corrections in perturbation theory.
We then estimate the various uncertainties affecting these predictions: the
scale uncertainties which are viewed as a measure of the unknown higher order
effects, the uncertainties from the parton distribution functions and the
related errors on the strong coupling constant, as well as the uncertainties
due to the use of an effective theory approach in the determination of the
radiative corrections in the process at next-to-next-to-leading
order. We find that while the cross sections are well under control in the
Higgs--strahlung processes, the theoretical uncertainties are rather large in
the case of the gluon-gluon fusion channel, possibly shifting the central
values of the next-to-next-to-leading order cross sections by more than
. These uncertainties are thus significantly larger than the
error assumed by the CDF and D0 experiments in their recent
analysis that has excluded the Higgs mass range 162-166 GeV at the 95%
confidence level. These exclusion limits should be, therefore, reconsidered in
the light of these large theoretical uncertainties.Comment: 40 pages, 12 figures. A few typos are corrected and some updated
numbers are provide
- âŠ