INTRODUCTION: The development of new therapeutics is often characterised by promising animal research that fails to translate into clinical efficacy; this holds for the development of gene therapy in ...glioma. We set out to test the hypothesis that this is because of limitations in the internal and external validity of studies reporting the use of gene therapy in rodent models of glioma. METHOD: We systematically identified studies testing gene therapy in rodent glioma models by searching three online databases. The number of animals treated and median survival were extracted and studies graded using a 9-point quality checklist. We calculated median survival ratios and used random effects meta-analysis to provide estimates of efficacy. We explored the effects of study design and quality and searched for evidence of publication bias. RESULTS: We found 194 publications using gene therapy in experimental glioma, describing 427 experiments involving 6366 animals. Overall, genetherapy improved median survival by 1.60 fold (95%CI 1.53-1.67). Study quality was low and the type of gene therapy did not account for observed differences in outcome. Study design characteristics accounted for a significant proportion of between-study heterogeneity and we observedsimilar findings in a subset of data limited to the most common genetherapy. CONCLUSION: As the dysregulation of key molecular pathways is characteristic of gliomas, gene therapy remains a promising treatment forglioma. Nevertheless, we have identified areas for improvement in conduct and reporting of such studies. Further work should focus on genes of interest in paradigms that recapitulate human disease. This may improve the translation of such therapies into the clinic.
We have studied the growth behavior of citric acid, tartaric acid, adipic acid and ammonium bisulfate particles in ethanol vapor with an organic tandem differential mobility analyzer technique ...(OTDMA). Time dependence of the change in the particle size due to interaction with ethanol vapor was determined. The results show that adipic acid particles have normal deliquescence-hysteresis type of growth behavior, whereas the growth of the other particle types is strongly time dependent due to chemical reactions with timescales on the order of seconds. Citric acid and tartaric acid obviously undergo auto-protonation catalyzed esterification due to their favorable molecular structure, whereas adipic acid has unfavorable structure for intramolecular catalysis. As a rather strong acid, ammonium bisulfate can transfer a proton to ethanol and hence a sulfate esterification reaction takes place. We suggest that time dependent growth behavior can be used for detection of acidic species in atmospheric aerosols.
We present a measurement of the W boson production charge asymmetry in p$\bar{p}$→W+X→eν+X events at a center of mass energy of 1.96 TeV, using 9.7 fb-1 of integrated luminosity collected with the D0 ...detector at the Fermilab Tevatron Collider. The neutrino longitudinal momentum is determined by using a neutrino weighting method, and the asymmetry is measured as a function of the W boson rapidity. The measurement extends over wider electron pseudorapidity region than previous results and is the most precise to date, allowing for precise determination of proton parton distribution functions in global fits.
We study the production of the exotic charged charmoniumlike state Z(c)(+/-)(3900) in p (p) over bar collisions through the sequential process psi(4260) -> Z(c)(+/-)(3900)(pi)(-/+), ...Z(c)(+/-)(3900) -> J/psi pi(+/-). Using the subsample of candidates originating from semi-inclusive weak decays of b-flavored hadrons, we measure the invariant mass and natural width to be M = 3902.6(-5.0)(+5.2)(stat)(-1.4)(+3.3)(syst) MeV and Gamma = 32(-21)(+28)(stat)(-7)(+26)(syst) MeV, respectively. We search for prompt production of the Z(c)(+/-)(3900) through the same sequential process. No significant signal is observed, and we set an upper limit of 0.70 at the 95% credibility level on the ratio of prompt production to the production via b-hadron decays. The study is based on 10.4 fb(-1) of p (p) over bar collision data collected by the D0 experiment at the Fermilab Tevatron collider.
We present a study of the normalized transverse momentum distribution of W bosons produced in $p\bar{p}$ collisions, using data corresponding to an integrated luminosity of 4.35 fb-1 collected with ...the D0 detector at the Fermilab Tevatron collider at $\sqrt{s}$ = 1.96 TeV. The measurement focuses on the transverse momentum region below 15 GeV, which is of special interest for electroweak precision measurements; it relies on the same detector calibration methods which were used for the precision measurement of the W boson mass. The measured distribution is compared to different QCD predictions and a procedure is given to allow the comparison of any further theoretical models to the D0 data.
We have investigated re‐epithelialization following induction of suction blisters in humans in intact blisters, open wounds, i.e. blister roofs removed immediately after blister induction, and ...calcipotriol‐pretreated open wounds. Intact blisters simulate blister healing in bullous disease, while open wounds simulate re‐epithelialization during wound healing. Re‐epithelialization was clearly faster in open wounds than in intact blisters, and was not affected by calcipotriol pretreatment. Bullous pemphigoid antigen 2 (BP180), bullous pemphigoid antigen 1 (BP230), plectin/hemidesmosomal 1 protein (HD1), laminin 5, laminin α5, laminin β1, type VII collagen, tenascin‐C, β4, αvβ5, α5 and α9 integrins were studied in intact blisters and open wounds by immunohistochemistry. Hemidesmosomal plaque proteins BP230 and plectin/HD1, which connect the keratin cytoskeleton to the hemidesmosome, appeared earlier at the leading edge in intact blisters than in open wounds. Band‐like immunostaining in the basement membrane for laminin 5, α5 and β1 chains was continuous in blister bases, but partially discontinuous in open wound bases. The other antigens studied showed similar expression in intact blisters and open wounds. BP180, BP230, plectin/HD1, β4 integrin, laminin 5 and tenascin‐C expression were further studied in calcipotriol‐pretreated open wounds. Calcipotriol did not affect the expression of these antigens. The immunohistochemical results suggest that the keratin cytoskeleton is linked to the basal plasma membrane of migrating basal cells via BP230 and plectin/HD1 earlier in the more slowly re‐epithelializing blisters than in open wounds. An intact laminin sheath may inhibit keratinocyte migration in intact blisters.
We measure the mass of the top quark in lepton + jets final states using the full sample of p (p) over bar collision data collected by the D0 experiment in Run II of the Fermilab Tevatron Collider at ...root s = 1.96 TeV, corresponding to 9.7 fb(-1) of integrated luminosity. We use a matrix element technique that calculates the probabilities for each event to result from t (t) over bar production or background. The overall jet energy scale is constrained in situ by the mass of theW boson. We measure m(t) = 174.98 +/- 0.76 GeV. This constitutes the most precise single measurement of the top-quark mass.
Translating experimental findings into clinically effective therapies is one of the major bottlenecks of modern medicine. As this has been particularly true for cerebrovascular research, attention ...has turned to the quality and validity of experimental cerebrovascular studies. We set out to assess the study design, statistical analyses, and reporting of cerebrovascular research. We assessed all original articles published in the Journal of Cerebral Blood Flow and Metabolism during the year 2008 against a checklist designed to capture the key attributes relating to study design, statistical analyses, and reporting. A total of 156 original publications were included (animal, in vitro, human). Few studies reported a primary research hypothesis, statement of purpose, or measures to safeguard internal validity (such as randomization, blinding, exclusion or inclusion criteria). Many studies lacked sufficient information regarding methods and results to form a reasonable judgment about their validity. In nearly 20% of studies, statistical tests were either not appropriate or information to allow assessment of appropriateness was lacking. This study identifies a number of factors that should be addressed if the quality of research in basic and translational biomedicine is to be improved. We support the widespread implementation of the ARRIVE (Animal Research Reporting In Vivo Experiments) statement for the reporting of experimental studies in biomedicine, for improving training in proper study design and analysis, and that reviewers and editors adopt a more constructively critical approach in the assessment of manuscripts for publication.
The Large Hadron Collider beauty (LHCb) experiment at CERN is undergoing an upgrade in preparation for the Run 3 data collection period at the Large Hadron Collider (LHC). As part of this upgrade, ...the trigger is moving to a full software implementation operating at the LHC bunch crossing rate. We present an evaluation of a CPU-based and a GPU-based implementation of the first stage of the high-level trigger. After a detailed comparison, both options are found to be viable. This document summarizes the performance and implementation details of these options, the outcome of which has led to the choice of the GPU-based implementation as the baseline.
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