Application of Magnetic Resonance to Assess Lyophilized Drug Product Reconstitution

Purpose Dynamic in-situ proton (1H) magnetic resonance imaging (MRI) and 1H T2-relaxometry experiments are described in an attempt to: (i) understand the physical processes, that occur during the reconstitution of lyophilized bovine serum albumen (BSA) and monoclonal antibody (mAb) proteins; and (ii) objectify the reconstitution time. Methods Rapid two-dimensional 1H MRI and diffusion weighted MRI were used to study the temporal changes in solids dissolution and characterise water mass transport characteristics. One-shot T2 relaxation time measurements were also acquired in an attempt to quantify the reconstitution time. Both MRI data and T2-relaxation data were compared to standard visual observations currently adopted by industry. The 1H images were further referenced to MRI calibration data to give quantitative values of protein concentration and, percentage of remaining undissolved solids. Results An algorithmic analysis the 1H T2-relaxation data shows it is possible to classify the reconstitution event into three regimes (undissolved, transitional and dissolved). Moreover, a combined analysis of the 2D 1H MRI and 1H T2-relaxation data gives a unique time point that characterises the onset of a reconstituted protein solution within well-defined error bars. These values compared favourably with those from visual observations. Diffusion weighted MRI showed that low concentration BSA and mAb samples showed distinct liquid-liquid phase separation attributed to two liquid layers with significant density gradients. Conclusions T2 relaxation time distributions (whose interpretation is validated from the 2D 1H MR images) provides a quick and effective framework to build objective, quantitative descriptors of the reconstitution process that facilitate the interpretation of subjective visual observations currently adopted as the standard practice industry.Medimmune PL

Vulnerability of low-arsenic aquifers to municipal pumping in Bangladesh

Sandy aquifers deposited >12,000 years ago, some as shallow as 30 m, have provided a reliable supply of low-arsenic (As) drinking water in rural Bangladesh. This study concerns the potential risk of contaminating these aquifers in areas surrounding the city of Dhaka where hydraulic heads in aquifers >150 m deep have dropped by 70 m in a few decades due to municipal pumping. Water levels measured continuously from 2012 to 2014 in 12 deep (>150 m), 3 intermediate (90-150 m) and 6 shallow (<90 m) community wells, 1 shallow private well, and 1 river piezometer show that the resulting drawdown cone extends 15-35 km east of Dhaka. Water levels in 4 low-As community wells within the 62-147 m depth range closest to Dhaka were inaccessible by suction for up to a third of the year. Lateral hydraulic gradients in the deep aquifer system ranged from 1.7 × 10-4 to 3.7 × 10-4 indicating flow towards Dhaka throughout 2012-2014. Vertical recharge on the edge of the drawdown cone was estimated at 0.21 ± 0.06 m/yr. The data suggest that continued municipal pumping in Dhaka could eventually contaminate some relatively shallow community wells

Application of Magnetic Resonance to Assess Lyophilized Drug Product Reconstitution

Dynamic in-situ proton (1H) magnetic resonance imaging (MRI) and 1H T2-relaxometry experiments are described in an attempt to: (i) understand the physical processes, that occur during the reconstitution of lyophilized bovine serum albumin (BSA) and monoclonal antibody (mAb) proteins; and (ii) objectify the reconstitution time

Constraints on the pMSSM from searches for squarks and gluinos by ATLAS

We study the impact of the jets and missing transverse momentum SUSY analyses of the ATLAS experiment on the phenomenological MSSM (pMSSM). We investigate sets of SUSY models with a flat and logarithmic prior in the SUSY mass scale and a mass range up to 1 and 3 TeV, respectively. These models were found previously in the study 'Supersymmetry without Prejudice'. Removing models with long-lived SUSY particles, we show that 99% of 20000 randomly generated pMSSM model points with a flat prior and 87% for a logarithmic prior are excluded by the ATLAS results. For models with squarks and gluinos below 600 GeV all models of the pMSSM grid are excluded. We identify SUSY spectra where the current ATLAS search strategy is less sensitive and propose extensions to the inclusive jets search channel

Where is SUSY?

The direct searches for Superymmetry at colliders can be complemented by direct searches for dark matter (DM) in underground experiments, if one assumes the Lightest Supersymmetric Particle (LSP) provides the dark matter of the universe. It will be shown that within the Constrained minimal Supersymmetric Model (CMSSM) the direct searches for DM are complementary to direct LHC searches for SUSY and Higgs particles using analytical formulae. A combined excluded region from LHC, WMAP and XENON100 will be provided, showing that within the CMSSM gluinos below 1 TeV and LSP masses below 160 GeV are excluded (m_{1/2} > 400 GeV) independent of the squark masses.Comment: 16 pages, 10 figure

Helicobacter pylori infection: approach of primary care physicians in a developing country

<p>Abstract</p> <p>Background</p> <p>The aim of the study was to assess the knowledge and practices of primary care physicians in diagnosis and management of <it>Helicobacter pylori (H. pylori) </it>infection in developing country.</p> <p>Methods</p> <p>This convenient sample based, cross sectional study was conducted in primary care physicians of Karachi, Pakistan from March 2008 to August 2008 through a pretested self-designed questionnaire, which contained 11 items pertaining to <it>H. pylori </it>route of transmission, diagnosis, indication for testing, treatment options, follow up and source of information.</p> <p>Results</p> <p>Out of 509 primary care physicians, 451 consented to participate with the response rate of 88.6%. Responses of 426 primary care physicians were analyzed after excluding 19 physicians. 78% of the physicians thought that contaminated water was the source of spread of infection, dyspepsia was the most frequent indication for investigating <it>H. pylori </it>infection (67% of the physicians), while 43% physicians were of the view that serology was the most appropriate test to diagnose active <it>H. pylori </it>infection. 77% of physicians thought that gastric ulcer was the most compelling indication for treatment, 61% physicians preferred Clarithromycin based triple therapy for 7–14 days. 57% of the physicians would confirm <it>H. pylori </it>eradication after treatment in selected patients and 47% physicians preferred serological testing for follow-up. In case of treatment failure, only 36% of the physicians were in favor of gastroenterologist referral.</p> <p>Conclusion</p> <p>The primary care physicians in this study lacked in knowledge regarding management of <it>H. pylori </it>infection. Internationally published guidelines and World gastroenterology organization (WGO) practice guideline on <it>H. pylori </it>for developing countries have little impact on current practices of primary care physicians. We recommend more teaching programs, continuous medical education activities regarding <it>H. pylori </it>infection.</p

Z boson production in Pb+Pb collisions at √Snn = 5.02 TeV measured by the ATLAS experiment

The production yield of Z bosons is measured in the electron and muon decay channels in Pb+Pb collisions at √S = 5.02 TeV with the ATLAS detector. Data from the 2015 LHC run corresponding to an integrated luminosity of 0.49 nb are used for the analysis. The Z boson yield, normalised by the total number of minimum-bias events and the mean nuclear thickness function, is measured as a function of dilepton rapidity and event centrality. The measurements in Pb+Pb collisions are compared with similar measurements made in proton-proton collisions at the same centre-of-mass energy. The nuclear modification factor is found to be consistent with unity for all centrality intervals. The results are compared with theoretical predictions obtained at next-to-leading order using nucleon and nuclear parton distribution functions. The normalised Z boson yields in Pb+Pb collisions lie 1-3σ above the predictions. The nuclear modification factor measured as a function of rapidity agrees with unity and is consistent with a next-to-leading-order QCD calculation including the isospin effect. nn -

Search for flavour-changing neutral currents in processes with one top quark and a photon using 81 fb−1 of pp collisions at s=13TeV with the ATLAS experiment

A search for flavour-changing neutral current (FCNC) events via the coupling of a top quark, a photon, and an up or charm quark is presented using 81 fb−1 of proton–proton collision data taken at a centre-of-mass energy of 13 TeV with the ATLAS detector at the LHC. Events with a photon, an electron or muon, a b-tagged jet, and missing transverse momentum are selected. A neural network based on kinematic variables differentiates between events from signal and background processes. The data are consistent with the background-only hypothesis, and limits are set on the strength of the tqγ coupling in an effective field theory. These are also interpreted as 95% CL upper limits on the cross section for FCNC tγ production via a left-handed (right-handed) tuγ coupling of 36 fb (78 fb) and on the branching ratio for t→γu of 2.8×10−5 (6.1×10−5). In addition, they are interpreted as 95% CL upper limits on the cross section for FCNC tγ production via a left-handed (right-handed) tcγ coupling of 40 fb (33 fb) and on the branching ratio for t→γc of 22×10−5 (18×10−5)