Supporting surveillance capacity for antimicrobial resistance: Laboratory capacity strengthening for drug resistant infections in low and middle income countries.

Development of antimicrobial resistance (AMR) threatens our ability to treat common and life threatening infections. Identifying the emergence of AMR requires strengthening of surveillance for AMR, particularly in low and middle-income countries (LMICs) where the burden of infection is highest and health systems are least able to respond. This work aimed, through a combination of desk-based investigation, discussion with colleagues worldwide, and visits to three contrasting countries (Ethiopia, Malawi and Vietnam), to map and compare existing models and surveillance systems for AMR, to examine what worked and what did not work. Current capacity for AMR surveillance varies in LMICs, but and systems in development are focussed on laboratory surveillance. This approach limits understanding of AMR and the extent to which laboratory results can inform local, national and international public health policy. An integrated model, combining clinical, laboratory and demographic surveillance in sentinel sites is more informative and costs for clinical and demographic surveillance are proportionally much lower. The speed and extent to which AMR surveillance can be strengthened depends on the functioning of the health system, and the resources available. Where there is existing laboratory capacity, it may be possible to develop 5-20 sentinel sites with a long term view of establishing comprehensive surveillance; but where health systems are weaker and laboratory infrastructure less developed, available expertise and resources may limit this to 1-2 sentinel sites. Prioritising core functions, such as automated blood cultures, reduces investment at each site. Expertise to support AMR surveillance in LMICs may come from a variety of international, or national, institutions. It is important that these organisations collaborate to support the health systems on which AMR surveillance is built, as well as improving technical capacity specifically relating to AMR surveillance. Strong collaborations, and leadership, drive successful AMR surveillance systems across countries and contexts

Increased Oxidative Burden Associated with Traffic Component of Ambient Particulate Matter at Roadside and Urban Background Schools Sites in London

As the incidence of respiratory and allergic symptoms has been reported to be increased in children attending schools in close proximity to busy roads, it was hypothesised that PM from roadside schools would display enhanced oxidative potential (OP). Two consecutive one-week air quality monitoring campaigns were conducted at seven school sampling sites, reflecting roadside and urban background in London. Chemical characteristics of size fractionated particulate matter (PM) samples were related to the capacity to drive biological oxidation reactions in a synthetic respiratory tract lining fluid. Contrary to hypothesised contrasts in particulate OP between school site types, no robust size-fractionated differences in OP were identified due high temporal variability in concentrations of PM components over the one-week sampling campaigns. For OP assessed both by ascorbate (OPAA m−3) and glutathione (OPGSH m−3) depletion, the highest OP per cubic metre of air was in the largest size fraction, PM1.9–10.2. However, when expressed per unit mass of particles OPAA µg−1 showed no significant dependence upon particle size, while OPGSH µg−1 had a tendency to increase with increasing particle size, paralleling increased concentrations of Fe, Ba and Cu. The two OP metrics were not significantly correlated with one another, suggesting that the glutathione and ascorbate depletion assays respond to different components of the particles. Ascorbate depletion per unit mass did not show the same dependence as for GSH and it is possible that other trace metals (Zn, Ni, V) or organic components which are enriched in the finer particle fractions, or the greater surface area of smaller particles, counter-balance the redox activity of Fe, Ba and Cu in the coarse particles. Further work with longer-term sampling and a larger suite of analytes is advised in order to better elucidate the determinants of oxidative potential, and to fuller explore the contrasts between site types.\ud \u

Insights into udder health and intramammary antibiotic usage on Irish dairy farms during 2003-2010

By international standards, Ireland is a relatively small dairy producer. However, the industry plays a critical role to the national economy, accounting for approximately 3% of national gross domestic product. This paper presents insights into udder health and intramammary antibiotic usage on Irish dairy farms during 2003-2010, based on data from several sources. Three data sources were used, including data on milk recording data, intramammary antibiotic sales and animal health assessment. The milk recording data included a single unadjusted herd-level somatic cell count (SCC) value for each herd at each milk recording, being the arithmetic mean of cow-level SCC of each cow at that recording, weighted by cow-level yield. These data were used to calculate the percentage of herds each month where the unadjusted herd SCC exceeded 200,000 and 400,000 cells/mL. Two logistic generalised estimating-equations (GEE) models were developed, the outcome variable being either the probability that the monthly SCC of a herd was greater than 400,000 cells/mL or less than or equal to 200,000 cells/mL. Spring herds had a lower probability of a high SCC (> 400,000 cells/mL) during February to October compared to non-Spring herds but a higher probability between November to January. The odds of a high SCC were greater in 2005, 2006, 2009 and 2010 but less in 2007 and 2008 compared to 2004. Smaller herds had higher odds of having a high SCC compared to larger herds. We present the number of intramammary tubes and the quantity of active substance (kg) sold annually in Ireland during 2003-2010. We infer an incidence of clinical mastitis of 54.0 cases per 100 cow-years at risk, assuming 4 tubes per treatment regime, one affected quarter per cow, tubes restricted to clinical cases only and 100% of treated cases considered new cases, based on data collected on sales of in-lactation intra-mammary antibiotics. With differing assumptions, this estimate varied between 25.8 and 77.0 cases per 100 cow-years at risk. Using data on sales of dry cow therapy intra-mammary antibiotics, we also infer that most Irish dairy farmers use blanket dry cow therapy. It is important that Ireland has an objective understanding of current levels of udder health, to facilitate benchmarking and improvement into the future. Udder health is a concern on a number of Irish dairy farms. High SCC results were present throughout the year, but more marked towards the start and end of each milking season. Animal Health Ireland recently commenced a major national programme, CellCheck, in collaboration with a broad range of stakeholders, to support national SCC improvement. In this paper, relevant European and national legislation is also reviewed

Gastric and intestinal barrier impairment in tropical enteropathy and HIV: limited impact of micronutrient supplementation during a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Although micronutrient supplementation can reduce morbidity and mortality due to diarrhoea, nutritional influences on intestinal host defence are poorly understood. We tested the hypothesis that micronutrient supplementation can enhance barrier function of the gut.</p> <p>Methods</p> <p>We carried out two sub-studies nested within a randomised, double-blind placebo-controlled trial of daily micronutrient supplementation in an urban community in Lusaka, Zambia. In the first sub-study, gastric pH was measured in 203 participants. In the second sub-study, mucosal permeability, lipopolysaccharide (LPS) and anti-LPS antibodies, and serum soluble tumour necrosis factor receptor p55 (sTNFR55) concentrations were measured in 87 participants. Up to three stool samples were also analysed microbiologically for detection of asymptomatic intestinal infection. Gastric histology was subsequently analysed in a third subset (n = 37) to assist in interpretation of the pH data. Informed consent was obtained from all participants after a three-stage information and consent process.</p> <p>Results</p> <p>Hypochlorhydria (fasting gastric pH > 4.0) was present in 75 (37%) of participants. In multivariate analysis, HIV infection (OR 4.1; 95%CI 2.2-7.8; <it>P </it>< 0.001) was associated with hypochlorhydria, but taking anti-retroviral treatment (OR 0.16; 0.04-0.67; <it>P </it>= 0.01) and allocation to micronutrient supplementation (OR 0.53; 0.28-0.99; <it>P </it>< 0.05) were protective. Hypochlorhydria was associated with increased risk of salmonellosis. Mild (grade 1) gastric atrophy was found in 5 participants, irrespective of <it>Helicobacter pylori </it>or HIV status. Intestinal permeability, LPS concentrations in serum, anti-LPS IgG, and sTNFR55 concentrations did not differ significantly between micronutrient and placebo groups. Anti-LPS IgM was reduced in the micronutrient recipients (<it>P <</it>0.05).</p> <p>Conclusions</p> <p>We found evidence of a specific effect of HIV on gastric pH which was readily reversed by anti-retroviral therapy and not mediated by gastric atrophy. Micronutrients had a modest impact on gastric pH and one marker of bacterial translocation.</p> <p>Trial Registration</p> <p>Current Controlled Trials ISRCTN31173864</p

A proposal for a coordinated effort for the determination of brainwide neuroanatomical connectivity in model organisms at a mesoscopic scale

In this era of complete genomes, our knowledge of neuroanatomical circuitry remains surprisingly sparse. Such knowledge is however critical both for basic and clinical research into brain function. Here we advocate for a concerted effort to fill this gap, through systematic, experimental mapping of neural circuits at a mesoscopic scale of resolution suitable for comprehensive, brain-wide coverage, using injections of tracers or viral vectors. We detail the scientific and medical rationale and briefly review existing knowledge and experimental techniques. We define a set of desiderata, including brain-wide coverage; validated and extensible experimental techniques suitable for standardization and automation; centralized, open access data repository; compatibility with existing resources, and tractability with current informatics technology. We discuss a hypothetical but tractable plan for mouse, additional efforts for the macaque, and technique development for human. We estimate that the mouse connectivity project could be completed within five years with a comparatively modest budget.Comment: 41 page

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

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal