592 research outputs found
Simulation of Heavily Irradiated Silicon Pixel Sensors and Comparison with Test Beam Measurements
Charge collection measurements performed on heavily irradiated p-spray DOFZ
pixel sensors with a grazing angle hadron beam provide a sensitive
determination of the electric field within the detectors. The data are compared
with a complete charge transport simulation of the sensor which includes signal
trapping and charge induction effects. A linearly varying electric field based
upon the standard picture of a constant type-inverted effective doping density
is inconsistent with the data. A two-trap double junction model implemented in
the ISE TCAD software can be tuned to produce a doubly-peaked electric field
which describes the data reasonably well. The modeled field differs somewhat
from previous determinations based upon the transient current technique. The
model can also account for the level of charge trapping observed in the data.Comment: 8 pages, 11 figures. Talk presented at the 2004 IEEE Nuclear Science
Symposium, October 18-21, Rome, Italy. Submitted to IEEE Transactions on
Nuclear Scienc
IgE is associated with exacerbations and lung function decline in COPD
Background: Both allergen-specifc IgE and total IgE in serum play a major role in asthma. However, the role of IgE
in chronic obstructive pulmonary disease (COPD) is poorly understood. It was the aim of this study to systematically
analyze the relationship between serum IgE levels and disease characteristics in large COPD cohorts.
Methods: COSYCONET is a comprehensively characterized cohort of patients with COPD: total IgE and IgE specifc to
common aeroallergens were measured in serum of 2280 patients, and related to clinical characteristics of the patients.
WISDOM is another large COPD population (2477 patients): this database contains the information whether total IgE
in serum was elevated (âĽ100 IU/l) or normal in patients with COPD.
Results: Both in COSYCONET and WISDOM, total IgE was elevated (âĽ100 IU/l) in>30% of the patients, higher in men
than in women, and higher in currently than in not currently smoking men. In COSYCONET, total IgE was elevated in
patients with a history of asthma and/or allergies. Men with at least one exacerbation in the last 12 months (50.6%
of all men in COSYCONET) had higher median total IgE (71.3 IU/l) than men without exacerbations (48.3 IU/l): this
diference was also observed in the subgroups of not currently smoking men and of men without a history of asthma.
Surprisingly, a history of exacerbations did not impact on total IgE in women with COPD. Patients in the highest ter tiles of total IgE (>91.5 IU/ml, adjusted OR: 1.62, 95% CI 1.12â2.34) or allergen-specifc IgE (>0.19 IU/ml, adjusted OR:
2.15, 95% CI 1.32â3.51) were at risk of lung function decline (adjusted by: age, gender, body mass index, initial lung
function, smoking status, history of asthma, history of allergy).
Conclusion: These data suggest that IgE may play a role in specifc COPD subgroups. Clinical trials using antibodies
targeting the IgE pathway (such as omalizumab), especially in men with recurrent exacerbations and elevated serum
IgE, could elucidate potential therapeutic implications of our observations
A first-in-human clinical study of a new SP-B and SP-C enriched synthetic surfactant (CHF5633) in preterm babies with respiratory distress syndrome
Objective CHF5633 (Chiesi Farmaceutici S.p.A., Parma, Italy) is the first fully synthetic surfactant enriched by peptide analogues of two human surfactant proteins. We planned to assess safety and tolerability of CHF5633 and explore preliminary efficacy. Design Multicentre cohort study. Patients Forty infants from 27+0 to 33+6 weeks gestation with respiratory distress syndrome requiring fraction of inspired oxygen (FiO2) âĽ0.35 were treated with a single dose of CHF5633 within 48âhours after birth. The first 20 received 100 mg/kg and the second 20 received 200âmg/kg. Outcome measures Adverse events (AEs) and adverse drug reactions (ADRs) were monitored with complications of prematurity considered AEs if occurring after dosing. Systemic absorption and immunogenicity were assessed. Efficacy was assessed by change in FiO2 after dosing and need for poractant-alfa rescue. Results Rapid and sustained improvements in FiO2 were observed in 39 (98%) infants. One responded neither to CHF5633 nor two poractant-alfa doses. A total of 79 AEs were experienced by 19 infants in the 100âmg/kg cohort and 53 AEs by 20 infants in the 200âmg/kg cohort. Most AEs were expected complications of prematurity. Two unrelated serious AEs occurred in the second cohort. One infant died of necrotising enterocolitis and another developed viral bronchiolitis after discharge. The single ADR was an episode of transient endotracheal tube obstruction following a 200âmg/kg dose. Neither systemic absorption, nor antibody development to either peptide was detected. Conclusions Both CHF5633 doses were well tolerated and showed promising clinical efficacy profile. These encouraging data provide a basis for ongoing randomised controlled trials
From abstract to impact in cardiovascular research: factors predicting publication and citation
Aims Through a 4-year follow-up of the abstracts submitted to the European Society of Cardiology Congress in 2006, we aimed at identifying factors predicting high-quality research, appraising the quality of the peer review and editorial processes, and thereby revealing potential ways to improve future research, peer review, and editorial work. Methods and results All abstracts submitted in 2006 were assessed for acceptance, presentation format, and average reviewer rating. Accepted and rejected studies were followed for 4 years. Multivariate regression analyses of a representative selection of 10% of all abstracts (n= 1002) were performed to identify factors predicting acceptance, subsequent publication, and citation. A total of 10 020 abstracts were submitted, 3104 (31%) were accepted for poster, and 701 (7%) for oral presentation. At Congress level, basic research, a patient number ⼠100, and prospective study design were identified as independent predictors of acceptance. These factors differed from those predicting full-text publication, which included academic affiliation. The single parameter predicting frequent citation was study design with randomized controlled trials reaching the highest citation rates. The publication rate of accepted studies was 38%, whereas only 24% of rejected studies were published. Among published studies, those accepted at the Congress received higher citation rates than rejected ones. Conclusions Research of high quality was determined by study design and largely identified at Congress level through blinded peer review. The scientometric follow-up revealed a marked disparity between predictors of full-text publication and those predicting citation or acceptance at the Congres
Association between exercise frequency with renal and cardiovascular outcomes in diabetic and non-diabetic individuals at high cardiovascular risk
Background: Guidelines recommend physical activity to reduce cardiovascular (CV) events. The association between
physical activity and progression of chronic kidney disease (CKD) with and without diabetes is unknown. We assessed
the association of self-reported physical activity with renal and CV outcomes in high-risk patients agedâĽ55 years over
a median follow-up of 56 months in post-hoc analysis of a previously randomized trial program.
Methods: Analyses were done with Cox regression analysis, mixed models for repeated measures, ANOVA and Ď2
-
test. 31,312 patients, among them 19,664 with and 11,648 without diabetes were analyzed.
Results: Physical activity was inversely associated with renal outcomes (doubling of creatinine, end-stage kidney
disease (ESRD)) and CV outcomes (CV death, myocardial infarction, stroke, heart failure hospitalization). Moderate
activity (at least 2 times/week to every day) was associated with lower risk of renal outcomes and lower incidence of
new albuminuria (p<0.0001 for both) compared to lower exercise levels. Similar results were observed for those with
and without diabetes without interaction for renal outcomes (p=0.097â0.27). Physical activity was associated with
reduced eGFR decline with a moderate association between activity and diabetes status (p=0.05).
Conclusions: Moderate physical activity was associated with improved kidney outcomes with a threshold at two
sessions per week. The association of physical activity with renal outcomes did not meaningfully difer with or without
diabetes but absolute beneft of activity was even greater in people with diabetes. Thus, risks were similar between
those with diabetes undertaking high physical activity and those without diabetes but low physical activity.
Clinical trial registration: http://clinicaltrials.gov.uniqueidentifer:NCT00153101
Relations between lipoprotein(a) concentrations, LPA genetic variants, and the risk of mortality in patients with established coronary heart disease: a molecular and genetic association study
Background:
Lipoprotein(a) concentrations in plasma are associated with cardiovascular risk in the general population. Whether lipoprotein(a) concentrations or LPA genetic variants predict long-term mortality in patients with established coronary heart disease remains less clear.
Methods:
We obtained data from 3313 patients with established coronary heart disease in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. We tested associations of tertiles of lipoprotein(a) concentration in plasma and two LPA single-nucleotide polymorphisms ([SNPs] rs10455872 and rs3798220) with all-cause mortality and cardiovascular mortality by Cox regression analysis and with severity of disease by generalised linear modelling, with and without adjustment for age, sex, diabetes diagnosis, systolic blood pressure, BMI, smoking status, estimated glomerular filtration rate, LDL-cholesterol concentration, and use of lipid-lowering therapy. Results for plasma lipoprotein(a) concentrations were validated in five independent studies involving 10â195 patients with established coronary heart disease. Results for genetic associations were replicated through large-scale collaborative analysis in the GENIUS-CHD consortium, comprising 106â353 patients with established coronary heart disease and 19â332 deaths in 22 studies or cohorts.
Findings:
The median follow-up was 9¡9 years. Increased severity of coronary heart disease was associated with lipoprotein(a) concentrations in plasma in the highest tertile (adjusted hazard radio [HR] 1¡44, 95% CI 1¡14â1¡83) and the presence of either LPA SNP (1¡88, 1¡40â2¡53). No associations were found in LURIC with all-cause mortality (highest tertile of lipoprotein(a) concentration in plasma 0¡95, 0¡81â1¡11 and either LPA SNP 1¡10, 0¡92â1¡31) or cardiovascular mortality (0¡99, 0¡81â1¡2 and 1¡13, 0¡90â1¡40, respectively) or in the validation studies.
Interpretation:
In patients with prevalent coronary heart disease, lipoprotein(a) concentrations and genetic variants showed no associations with mortality. We conclude that these variables are not useful risk factors to measure to predict progression to death after coronary heart disease is established.
Funding:
Seventh Framework Programme for Research and Technical Development (AtheroRemo and RiskyCAD), INTERREG IV Oberrhein Programme, Deutsche Nierenstiftung, Else-Kroener Fresenius Foundation, Deutsche Stiftung fĂźr Herzforschung, Deutsche Forschungsgemeinschaft, Saarland University, German Federal Ministry of Education and Research, Willy Robert Pitzer Foundation, and Waldburg-Zeil Clinics Isny
Performance of the CMS Cathode Strip Chambers with Cosmic Rays
The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device
in the CMS endcaps. Their performance has been evaluated using data taken
during a cosmic ray run in fall 2008. Measured noise levels are low, with the
number of noisy channels well below 1%. Coordinate resolution was measured for
all types of chambers, and fall in the range 47 microns to 243 microns. The
efficiencies for local charged track triggers, for hit and for segments
reconstruction were measured, and are above 99%. The timing resolution per
layer is approximately 5 ns
Performance and Operation of the CMS Electromagnetic Calorimeter
The operation and general performance of the CMS electromagnetic calorimeter
using cosmic-ray muons are described. These muons were recorded after the
closure of the CMS detector in late 2008. The calorimeter is made of lead
tungstate crystals and the overall status of the 75848 channels corresponding
to the barrel and endcap detectors is reported. The stability of crucial
operational parameters, such as high voltage, temperature and electronic noise,
is summarised and the performance of the light monitoring system is presented
Association between exercise frequency with renal and cardiovascular outcomes in diabetic and non-diabetic individuals at high cardiovascular risk
Background: Guidelines recommend physical activity to reduce cardiovascular (CV) events. The association between physical activity and progression of chronic kidney disease (CKD) with and without diabetes is unknown. We assessed the association of self-reported physical activity with renal and CV outcomes in high-risk patients agedââĽâ55 years over a median follow-up of 56 months in post-hoc analysis of a previously randomized trial program.
Methods
Analyses were done with Cox regression analysis, mixed models for repeated measures, ANOVA and Ď2-test. 31,312 patients, among them 19,664 with and 11,648 without diabetes were analyzed.
Results
Physical activity was inversely associated with renal outcomes (doubling of creatinine, end-stage kidney disease (ESRD)) and CV outcomes (CV death, myocardial infarction, stroke, heart failure hospitalization). Moderate activity (at least 2 times/week to every day) was associated with lower risk of renal outcomes and lower incidence of new albuminuria (pâ<â0.0001 for both) compared to lower exercise levels. Similar results were observed for those with and without diabetes without interaction for renal outcomes (pâ=â0.097â0.27). Physical activity was associated with reduced eGFR decline with a moderate association between activity and diabetes status (pâ=â0.05).
Conclusions
Moderate physical activity was associated with improved kidney outcomes with a threshold at two sessions per week. The association of physical activity with renal outcomes did not meaningfully differ with or without diabetes but absolute benefit of activity was even greater in people with diabetes. Thus, risks were similar between those with diabetes undertaking high physical activity and those without diabetes but low physical activity.
Clinical trial registration:
http://clinicaltrials.gov.uniqueidentifier
:NCT00153101
Ablation of the androgen receptor from vascular smooth muscle cells demonstrates a role for testosterone in vascular calcification
Vascular calcification powerfully predicts mortality and morbidity from cardiovascular disease. Men have a greater risk of cardiovascular disease, compared to women of a similar age. These gender disparities suggest an influence of sex hormones. Testosterone is the primary and most well-recognised androgen in men. Therefore, we addressed the hypothesis that exogenous androgen treatment induces vascular calcification. Immunohistochemical analysis revealed expression of androgen receptor (AR) in the calcified media of human femoral artery tissue and calcified human valves. Furthermore, in vitro studies revealed increased phosphate (Pi)-induced mouse vascular smooth muscle cell (VSMC) calcification following either testosterone or dihydrotestosterone (DHT) treatment for 9 days. Testosterone and DHT treatment increased tissue non-specific alkaline phosphatase (Alpl) mRNA expression. Testosterone-induced calcification was blunted in VSMC-specific AR-ablated (SM-ARKO) VSMCs compared to WT. Consistent with these data, SM-ARKO VSMCs showed a reduction in Osterix mRNA expression. However, intriguingly, a counter-intuitive increase in Alpl was observed. These novel data demonstrate that androgens play a role in inducing vascular calcification through the AR. Androgen signalling may represent a novel potential therapeutic target for clinical intervention
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