Pharmacokinetics of Ganciclovir after Oral Valganciclovir versus Intravenous Ganciclovir in Allogeneic Stem Cell Transplant Patients with Graft-versus-Host Disease of the Gastrointestinal Tract

AbstractThe pharmacokinetics of ganciclovir after oral valganciclovir versus intravenous ganciclovir were compared in allogeneic stem cell transplant recipients with stable graft-versus-host disease of the gastrointestinal tract. Twenty-two evaluable adult patients were randomized to receive a single dose of open-label study drug (900 mg of oral valganciclovir or 5 mg/kg of intravenous ganciclovir). After a washout period of 2 to 7 days, patients were crossed over to receive the alternate study drug. Ganciclovir and valganciclovir concentrations in plasma were measured over 24 hours after dosing. Noninferiority of 900 mg of valganciclovir relative to intravenous ganciclovir was concluded if the lower limit of the 1-sided 95% confidence interval of the ratio of least-square means of the ganciclovir area under the curve (AUC) for the 2 study drugs was >80%. Valganciclovir was found to be rapidly absorbed and converted into ganciclovir. The ganciclovir exposure after 900 mg of valganciclovir noninferior to that of intravenous ganciclovir (AUC0-∞, 52.1 and 53.8 μg·h/mL, respectively; 95% confidence interval of the ratio of least square means of AUC0-∞, 82.48%-118.02%). Oral valganciclovir could be a useful alternative to intravenous ganciclovir in certain stable stem cell transplant patients who require prophylaxis or preemptive therapy for cytomegalovirus infection

Wanted dead or alive : high diversity of macroinvertebrates associated with living and ’dead’ Posidonia oceanica matte

The Mediterranean endemic seagrass Posidonia oceanica forms beds characterised by a dense leaf canopy and a thick root-rhizome ‘matte’. Death of P. oceanica shoots leads to exposure of the underlying matte, which can persist for many years, and is termed ‘dead’ matte. Traditionally, dead matte has been regarded as a degraded habitat. To test whether this assumption was true, the motile macroinvertebrates of adjacent living (with shoots) and dead (without shoots) matte of P. oceanica were sampled in four different plots located at the same depth (5–6 m) in Mellieha Bay, Malta (central Mediterranean). The total number of species and abundance were significantly higher (ANOVA; P<0.05 and P<0.01, respectively) in the dead matte than in living P. oceanica matte, despite the presence of the foliar canopy in the latter. Multivariate analysis (MDS) clearly showed two main groups of assemblages, corresponding to the two matte types. The amphipods Leptocheirus guttatus and Maera grossimana, and the polychaete Nereis rava contributed most to the dissimilarity between the two different matte types. Several unique properties of the dead matte contributing to the unexpected higher number of species and abundance of motile macroinvertebrates associated with this habitat are discussed. The findings have important implications for the conservation of bare P. oceanica matte, which has been generally viewed as a habitat of low ecological value.peer-reviewe

Learning to look : evaluating the student experience of an interactive image appraisal activity

Introduction: Student radiographers have expressed difficulty in performing image appraisal tasks. The purpose of this study was to investigate the value of a workshop delivered to level 4 undergraduate students. All students completed an image appraisal activity, inputting their appraisal into software that displayed their response alongside an expert opinion. They were asked to identify and discuss any discrepancy. Methods: All Level 4 students participated in an image appraisal workshop and were subsequently invited to take part in a focus group immediately after the activity. Twenty-three students took part in three focus groups (n = 7; n = 8; n = 8). A thematic analysis of transcripts was performed alongside validation from observations during the image appraisal activity. Results: Findings demonstrate that despite teaching and resources being available, students had focused on learning a generic checklist for image appraisal, had not appreciated the application of projection specific criteria and felt underprepared. The use of specific criteria and repetition within the task was considered useful. They identified learning needs and misconceptions through peer discussion and via the expert opinion, highlighting the value of feedback. Students enjoyed the workshop and made suggestions for implementation into the curriculum. Conclusion: Educators must not assume that the provision of resources will result in students developing deep knowledge. Teaching and learning strategies that are task specific are recommended to avoid a surface approach to learning. Time, repetition and appropriate feedback are essential to enable learners to develop competence and confidence for complex visual tasks, such as image appraisal

Design, Performance, and Calibration of CMS Hadron-Barrel Calorimeter Wedges

Extensive measurements have been made with pions, electrons and muons on four production wedges of the Compact Muon Solenoid (CMS) hadron barrel (HB) calorimeter in the H2 beam line at CERN with particle momenta varying from 20 to 300 GeV/c. Data were taken both with and without a prototype electromagnetic lead tungstate crystal calorimeter (EB) in front of the hadron calorimeter. The time structure of the events was measured with the full chain of preproduction front-end electronics running at 34 MHz. Moving-wire radioactive source data were also collected for all scintillator layers in the HB. These measurements set the absolute calibration of the HB prior to first pp collisions to approximately 4%

Energy Response and Longitudinal Shower Profiles Measured in CMS HCAL and Comparison With Geant4

The response of the CMS combined electromagnetic and hadron calorimeter to beams of pions with momenta in the range 5-300 GeV/c has been measured in the H2 test beam at CERN. The raw response with the electromagnetic compartment calibrated to electrons and the hadron compartment calibrated to 300 GeV pions may be represented by sigma = (1.2) sqrt{E} oplus (0.095) E. The fraction of energy visible in the calorimeter ranges from 0.72 at 5 GeV to 0.95 at 300 GeV, indicating a substantial nonlinearity. The intrinsic electron to hadron ratios are fit as a function of energy and found to be in the range 1.3-2.7 for the electromagnetic compartment and 1.4-1.8 for the hadronic compartment. The fits are used to correct the non-linearity of the e pi response to 5% over the entire measured range resulting in a substantially improved resolution at low energy. Longitudinal shower profile have been measured in detail and compared to Geant4 models, LHEP-3.7 and QGSP-2.8. At energies below 30 GeV, the data, LHEP and QGSP are in agreement. Above 30 GeV, LHEP gives a more accurate simulation of the longitudinal shower profile

Synchronization and Timing in CMS HCAL

The synchronization and timing of the hadron calorimeter (HCAL) for the Compact Muon Solenoid has been extensively studied with test beams at CERN during the period 2003-4, including runs with 40 MHz structured beam. The relative phases of the signals from different calorimeter segments are timed to 1 ns accuracy using a laser and equalized using programmable delay settings in the front-end electronics. The beam was used to verify the timing and to map out the entire range of pulse shapes over the 25 ns interval between beam crossings. These data were used to make detailed measurements of energy-dependent time slewing effects and to tune the electronics for optimal performance

Design, Performance and Calibration of the CMS Forward Calorimeter Wedges

We report on the test beam results and calibration methods using charged particles of the CMS Forward Calorimeter (HF). The HF calorimeter covers a large pseudorapidity region (3\l |\eta| \le 5), and is essential for large number of physics channels with missing transverse energy. It is also expected to play a prominent role in the measurement of forward tagging jets in weak boson fusion channels. The HF calorimeter is based on steel absorber with embedded fused-silica-core optical fibers where Cherenkov radiation forms the basis of signal generation. Thus, the detector is essentially sensitive only to the electromagnetic shower core and is highly non-compensating (e/h \approx 5). This feature is also manifest in narrow and relatively short showers compared to similar calorimeters based on ionization. The choice of fused-silica optical fibers as active material is dictated by its exceptional radiation hardness. The electromagnetic energy resolution is dominated by photoelectron statistics and can be expressed in the customary form as a/\sqrt{E} + b. The stochastic term a is 198% and the constant term b is 9%. The hadronic energy resolution is largely determined by the fluctuations in the neutral pion production in showers, and when it is expressed as in the electromagnetic case, a = 280% and b = 11%

Design, Performance, and Calibration of CMS Hadron Endcap Calorimeters

Detailed measurements have been made with the CMS hadron calorimeter endcaps (HE) in response to beams of muons, electrons, and pions. Readout of HE with custom electronics and hybrid photodiodes (HPDs) shows no change of performance compared to readout with commercial electronics and photomultipliers. When combined with lead-tungstenate crystals, an energy resolution of 8\% is achieved with 300 GeV/c pions. A laser calibration system is used to set the timing and monitor operation of the complete electronics chain. Data taken with radioactive sources in comparison with test beam pions provides an absolute initial calibration of HE to approximately 4\% to 5\%

Design, Performance, and Calibration of the CMS Hadron-Outer Calorimeter

The CMS hadron calorimeter is a sampling calorimeter with brass absorber and plastic scintillator tiles with wavelength shifting fibres for carrying the light to the readout device. The barrel hadron calorimeter is complemented with an outer calorimeter to ensure high energy shower containment in the calorimeter. Fabrication, testing and calibration of the outer hadron calorimeter are carried out keeping in mind its importance in the energy measurement of jets in view of linearity and resolution. It will provide a net improvement in missing \et measurements at LHC energies. The outer hadron calorimeter will also be used for the muon trigger in coincidence with other muon chambers in CMS

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio