HBM4EU from the Coordinator's perspective : lessons learnt from managing a large-scale EU project

Artikelnummer: 114072We discuss some important management issues of the Human Biomonitoring Initiative (HBM4EU) from the perspective of the Coordinator that may be valuable for the design and management of similar projects. As a large-scale international collaborative project, HBM4EU comprised 118 institutions from 30 countries and the European Environment Agency and had a budget of about €74 million. It has set up an innovative cooperative network of national and EU authorities and scientific institutions at the science-policy interface. A project of this scale raises major management challenges and requires transparent, efficient, and well-organized administrative and scientific steering structures. We present four major points: First, prior to the beginning of the project, the Consortium Agreement needs to be well elaborated to prevent conflicts during the project lifetime. Second, a strong role for national and EU policy-making authorities in the administrative governance structure enhances the interest of recipients of project results. Third, large-scale international collaborative projects need an elaborate and well-financed scientific governance structure. Fourth, a differentiation of funding rates among project activities threatens to create conflicts. HBM4EU provides a prototype for EU funded large-scale projects targeting future policies for realizing the Green Deal and Zero Pollution Ambition in the field of chemicals, health, and environment

Operating capability and current status of the reactivated NASA Lewis Research Center Hypersonic Tunnel Facility

The NASA Lewis Research Center's Hypersonic Tunnel Facility (HTF) is a free-jet, blowdown propulsion test facility that can simulate up to Mach-7 flight conditions with true air composition. Mach-5, -6, and -7 nozzles, each with a 42 inch exit diameter, are available. Previously obtained calibration data indicate that the test flow uniformity of the HTF is good. The facility, without modifications, can accommodate models approximately 10 feet long. The test gas is heated using a graphite core induction heater that generates a nonvitiated flow. The combination of clean-air, large-scale, and Mach-7 capabilities is unique to the HTF and enables an accurate propulsion performance determination. The reactivation of the HTF, in progress since 1990, includes refurbishing the graphite heater, the steam generation plant, the gaseous oxygen system, and all control systems. All systems were checked out and recertified, and environmental systems were upgraded to meet current standards. The data systems were also upgraded to current standards and a communication link with NASA-wide computers was added. In May 1994, the reactivation was complete, and an integrated systems test was conducted to verify facility operability. This paper describes the reactivation, the facility status, the operating capabilities, and specific applications of the HTF

Characterization of Fibroblast Growth Factor Receptor 1 in Small-Cell Lung Cancer

Introduction:There remains a significant therapeutic need for small-cell lung cancer (SCLC). We and others have reported high frequency of copy number gains in cytogenetic bands encoding fibroblast growth factor receptor 1 (FGFR1) in SCLC tumors and cell lines.Methods:Thirteen SCLC cell lines and 68 SCLC patient tumor samples were studied for FGFR1 amplification. Growth inhibition assays were performed using PD173074, a pan-FGFR inhibitor to determine the correlation between FGFR1 expression and drug sensitivity.Results:We did not detect FGFR1 mutations in SCLC cell lines. Focal amplification of FGFR1 gene was found in five tumor samples (7%), with high-level focal amplification in only one tumor sample (1%). Amplification owing to polysomy of chromosome 8, where FGFR1 locates, was observed in 22 tumor samples (32%). There was no correlation between FGFR1 gene copy number and messenger RNA expression or protein expression in SCLC cells. FGFR inhibitor sensitivity correlated with FGFR1 copy number determined by real-time polymerase chain reaction assay (r= −0.79; p = 0.01).Conclusion:FGFR1 gene mutations and focal amplification are rare in SCLC, but polysomy of chromosome 8 is relatively common. FGFR1 copy number gain predicts sensitivity to FGFR inhibition, and FGFR expression correlates inversely with chemosensitivity

Agreement in the scoring of respiratory events and sleep among international sleep centers.

To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.Abstract STUDY OBJECTIVES: The American Academy of Sleep Medicine (AASM) guidelines for polysomnography (PSG) scoring are increasingly being adopted worldwide, but the agreement among international centers in scoring respiratory events and sleep stages using these guidelines is unknown. We sought to determine the interrater agreement of PSG scoring among international sleep centers. DESIGN: Prospective study of interrater agreement of PSG scoring. SETTING: Nine center-members of the Sleep Apnea Genetics International Consortium (SAGIC). MEASUREMENTS AND RESULTS: Fifteen previously recorded deidentified PSGs, in European Data Format, were scored by an experienced technologist at each site after they were imported into the locally used analysis software. Each 30-sec epoch was manually scored for sleep stage, arousals, apneas, and hypopneas using the AASM recommended criteria. The computer-derived oxygen desaturation index (ODI) was also recorded. The primary outcome for analysis was the intraclass correlation coefficient (ICC) of the apnea-hypopnea index (AHI). The ICCs of the respiratory variables were: AHI = 0.95 (95% confidence interval: 0.91-0.98), total apneas = 0.77 (0.56-0.87), total hypopneas = 0.80 (0.66-0.91), and ODI = 0.97 (0.93-0.99). The kappa statistics for sleep stages were: wake = 0.78 (0.77-0.79), nonrapid eye movement = 0.77 (0.76-0.78), N1 = 0.31 (0.30-0.32), N2 = 0.60 (0.59-0.61), N3 = 0.67 (0.65-0.69), and rapid eye movement = 0.78 (0.77-0.79). The ICC of the arousal index was 0.68 (0.50-0.85). CONCLUSION: There is strong agreement in the scoring of respiratory events among the SAGIC centers. There is also substantial epoch-by-epoch agreement in scoring sleep variables. Our results suggest that centralized scoring of PSGs may not be necessary in future research collaboration among international sites where experienced, well-trained scorers are involved.NHLBI P01 HL094307 HL093463 Tzagournis Medical Research Endowment Funds of The Ohio State Universit

PCA-induced respiratory depression simulating stroke following endoluminal repair of abdominal aortic aneurysm: a case report

<p>Abstract</p> <p>Aim</p> <p>To report a case of severe respiratory depression with PCA fentanyl use simulating stroke in a patient who underwent routine elective endoluminal graft repair for abdominal aortic aneurysm (AAA)</p> <p>Case presentation</p> <p>A 78-year-old obese lady underwent routine endoluminal graft repair for AAA that was progressively increasing in size. Following an uneventful operation postoperative analgesia was managed with a patient-controlled analgesia (PCA) device with fentanyl. On the morning following operation the patient was found to be unusually drowsy and unresponsive to stimuli. Her GCS level was 11 with plantars upgoing bilaterally. A provisional diagnosis of stroke was made. Urgent transfer to a high-dependency unit (HDU) was arranged and she was given ventilatory support with a BiPap device. CT was performed and found to be normal. Arterial blood gas (ABG) analysis showed respiratory acidosis with PaCO₂81 mmHg, PaO₂140 mmHg, pH 7.17 and base excess -2 mmol/l. A total dose of 600 mcg of fentanyl was self-administered in the 16 hours following emergence from general anaesthesia. Naloxone was given with good effect. There was an increase in the creatinine level from 90 μmol/L preoperatively to 167 μmol/L on the first postoperative day. The patient remained on BiPap for two days that resulted in marked improvement in gas exchange. Recovery was complete.</p

CPAP, weight loss, or both for obstructive sleep apnea

BACKGROUNd: Obesity and obstructive sleep apnea tend to coexist and are associated with inflammation, insulin resistance, dyslipidemia, and high blood pressure, but their causal relation to these abnormalities is unclear. METHODS: We randomly assigned 181 patients with obesity, moderate-to-severe obstructive sleep apnea, and serum levels of C-reactive protein (CRP) greater than 1.0 mg per liter to receive treatment with continuous positive airway pressure (CPAP), a weight-loss intervention, or CPAP plus a weight-loss intervention for 24 weeks. We assessed the incremental effect of the combined interventions over each one alone on the CRP level (the primary end point), insulin sensitivity, lipid levels, and blood pressure. RESULTS: Among the 146 participants for whom there were follow-up data, those assigned to weight loss only and those assigned to the combined interventions had reductions in CRP levels, insulin resistance, and serum triglyceride levels. None of these changes were observed in the group receiving CPAP alone. Blood pressure was reduced in all three groups. No significant incremental effect on CRP levels was found for the combined interventions as compared with either weight loss or CPAP alone. Reductions in insulin resistance and serum triglyceride levels were greater in the combined-intervention group than in the group receiving CPAP only, but there were no significant differences in these values between the combined-intervention group and the weight-loss group. In per-protocol analyses, which included 90 participants who met prespecified criteria for adherence, the combined interventions resulted in a larger reduction in systolic blood pressure and mean arterial pressure than did either CPAP or weight loss alone. CONCLUSIONS: In adults with obesity and obstructive sleep apnea, CPAP combined with a weight-loss intervention did not reduce CRP levels more than either intervention alone. In secondary analyses, weight loss provided an incremental reduction in insulin resistance and serum triglyceride levels when combined with CPAP. In addition, adherence to a regimen of weight loss and CPAP may result in incremental reductions in blood pressure as compared with either intervention alone. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT0371293 .)

1950: Abilene Christian College Bible Lectures - Full Text

Introduction We offer with interest and pleasure another volume of a great series of discourses delivered at Abilene Christian College. The following were given in February, 1950. The first of these Lectureships was held in the year 1919, and was published by the Firm Foundation Publishing House in book form. With little exception they have appeared each year since that time. The printing was done by others a few times. Those who are fortunate enough to have a complete set of these fine gospel sermons are possessed of a treasure in religious literature. Only a few of the later years can now be supplied. The rest are numbered among the “rare books” and we frequently have calls for them, but of course cannot supply them. Any reader having a copy for sale is requested to write the office of the Firm Foundation at Austin, Texas. The “Lectureship” of Abilene Christian College has become a great annual affair to the churches of Christ; thousands are in attendance, many of them coming from Canada and other countries besides all over the United States. This annual “mass meeting” must not be understood to be a “Convention” of the churches of Christ. We have no such conventions and do not endorse them. The Lectureship is simply a feature in the work of Abilene Christian College, a series of gospel sermons to which friends and patrons of the school and others are invited. It is our hope that the contents of this book may enrich the life, and strengthen the faith of the reader. G. H. F. SHOWALTER Austin, Texas August 20, 195

Tissue-Specific Gene Delivery via Nanoparticle Coating

Author Manuscript: 2010 August 1.The use of biomaterials for gene delivery can potentially avoid many of the safety concerns with viral gene delivery. However, the efficacy of polymeric gene delivery methods is low, particularly in vivo. One significant concern is that the interior and exterior composition of polymeric gene delivery nanoparticles are often coupled, with a single polymer backbone governing all functions from biophysical properties of the polymer/DNA particle to DNA condensation and release. In this work we develop electrostatically adsorbed poly(glutamic acid)-based peptide coatings to alter the exterior composition of a core gene delivery particle and thereby affect tissue-specificity of gene delivery function in vivo. We find that with all coating formulations tested, the coatings reduce potential toxicity associated with uncoated cationic gene delivery nanoparticles following systemic injection. Particles coated with a low 2.5:1 peptide:DNA weight ratio (w/w) form large 2 μ sized particles in the presence of serum that can facilitate specific gene delivery to the liver. The same particles coated at a higher 20:1 w/w form small 200 nm particles in the presence of serum that can facilitate specific gene delivery to the spleen and bone marrow. Thus, variations in nanoparticle peptide coating density can alter the tissue-specificity of gene delivery in vivo.National Institutes of Health (U.S.) (BRP: 1R01CA124427-01)National Institutes of Health (U.S.) (EB 000244)National Institutes of Health (U.S.) (U54 CA119349-01)David & Lucile Packard Foundation (Fellowship 1999-1453A