Guidance on stakeholder engagement practices to inform the development of areawide vector control methods

This is the final version. Available from the publisher via the DOI in this record.British Academ

Randomized trial of neoadjuvant chemotherapy in oropharyngeal carcinoma

The objective of the study was to evaluate the effect of neoadjuvant chemotherapy on the survival of patients with oropharyngeal cancer. Patients with a squamous cell carcinoma of the oropharynx for whom curative radiotherapy or surgery was considered feasible were entered in a multicentric randomized trial comparing neoadjuvant chemotherapy followed by loco-regional treatment to the same loco-regional treatment without chemotherapy. The loco-regional treatment consisted either of surgery plus radiotherapy or of radiotherapy alone. Three cycles of chemotherapy consisting of Cisplatin (100 mg/m2) on day 1 followed by a 24-hour i.v. infusion of fluorouracil (1000 mg/m2/day) for 5 days were delivered every 21 days. 2–3 weeks after the end of chemotherapy, local treatment was performed. The trial was conducted by the Groupe d'Etude des Tumeurs de la Tête Et du Cou (GETTEC). A total of 318 patients were enrolled in the study between 1986 and 1992. Overall survival was significantly better (P = 0.03) in the neoadjuvant chemotherapy group than in the control group, with a median survival of 5.1 years versus 3.3 years in the no chemotherapy group. The effect of neoadjuvant chemotherapy on event-free survival was smaller and of borderline significance (P = 0.11). Stratification of the results on the type of local treatment, surgery plus radiotherapy or radiotherapy alone, did not reveal any heterogeneity in the effect of chemotherapy. © 2000 Cancer Research Campaign http://www.bjcancer.co

Cytokines and growth factors cross-link heparan sulfate

The glycosaminoglycan heparan sulfate (HS), present at the surface of most cells and ubiquitous in extracellular matrix, binds many soluble extracellular signalling molecules such as chemokines and growth factors, and regulates their transport and effector functions. It is, however, unknown whether upon binding HS these proteins can affect the long-range structure of HS. To test this idea, we interrogated a supramolecular model system, in which HS chains grafted to streptavidin-functionalized oligoethylene glycol monolayers or supported lipid bilayers mimic the HS-rich pericellular or extracellular matrix, with the biophysical techniques quartz crystal microbalance (QCM-D) and fluorescence recovery after photobleaching (FRAP). We were able to control and characterize the supramolecular presentation of HS chains—their local density, orientation, conformation and lateral mobility—and their interaction with proteins. The chemokine CXCL12α (or SDF-1α) rigidified the HS film, and this effect was due to protein-mediated cross-linking of HS chains. Complementary measurements with CXCL12α mutants and the CXCL12γ isoform provided insight into the molecular mechanism underlying cross-linking. Fibroblast growth factor 2 (FGF-2), which has three HS binding sites, was also found to cross-link HS, but FGF-9, which has just one binding site, did not. Based on these data, we propose that the ability to cross-link HS is a generic feature of many cytokines and growth factors, which depends on the architecture of their HS binding sites. The ability to change matrix organization and physico-chemical properties (e.g. permeability and rigidification) implies that the functions of cytokines and growth factors may not simply be confined to the activation of cognate cellular receptors

Computer-assisted detection of pulmonary embolism: evaluation of pulmonary CT angiograms performed in an on-call setting

Item does not contain fulltextPURPOSE: The purpose of the study was to assess the stand-alone performance of computer-assisted detection (CAD) for evaluation of pulmonary CT angiograms (CTPA) performed in an on-call setting. METHODS: In this institutional review board-approved study, we retrospectively included 292 consecutive CTPA performed during night shifts and weekends over a period of 16 months. Original reports were compared with a dedicated CAD system for pulmonary emboli (PE). A reference standard for the presence of PE was established using independent evaluation by two readers and consultation of a third experienced radiologist in discordant cases. RESULTS: Original reports had described 225 negative studies and 67 positive studies for PE. CAD found PE in seven patients originally reported as negative but identified by independent evaluation: emboli were located in segmental (n = 2) and subsegmental arteries (n = 5). The negative predictive value (NPV) of the CAD algorithm was 92% (44/48). On average there were 4.7 false positives (FP) per examination (median 2, range 0-42). In 72% of studies or=10 FP. CONCLUSION: CAD identified small emboli originally missed under clinical conditions and found 93% of the isolated subsegmental emboli. On average there were 4.7 FP per examination.1 april 201

Optimization of the Magnetic Field Topology in the Hall Effect Rocket with Magnetic Shielding

NASA's Hall Effect Rocket with Magnetic Shielding (HERMeS) 12.5kW Technology Demonstration Unit-1 (TDU-1) has been the subject of extensive technology maturation in preparation for flight system development. The TDU-1 thruster implements a magnetically shielded field topology and has demonstrated the elimination of the discharge channel erosion. Extensive wear testing the TDU Hall thrusters has identified the thruster front pole covers as the next life limiting component. This effort aims to explore and investigate alternate magnetic field topologies to assess whether reductions in the front pole cover erosion can be attained while still maintaining very low erosion rates on the discharge channel walls. NASA GRC and JPL have begun a magnetic field topology characterization and optimization study by designing four candidate magnetic field topologies that reduce the effectiveness of the shielding along the discharge channel walls with the intent to also reduce the erosion rates along the pole covers. Three of the four candidate magnetic field topologies have been manufactured subjected to an extensive test campaign that includes performance, plume, and stability characterization. In Phase I of the testing campaign, the thruster's oscillation magnitude and Laser Induced fluorescence (LIF) measurements of the plasma plume were performed for the three candidate topologies. In Phase I, the thruster's oscillation magnitude and LIF measurements were performed for the three candidate topologies. Phase I test results found that the B1 configuration attained lower oscillation levels than B0. Additionally, LIF measurements along the discharge chamber centerline found that upstream retraction of the thruster's peak magnetic field does result in an upstream shift of the acceleration zone but the magnitude of the shift does not correspond one-to-one to the shift in the location of the peak radial magnetic field magnitude. Phase II test segment will include performing performance, stability, plume, and erosion measurements for the various candidate magnetic field topologies

Cardiothoracic CT: one-stop-shop procedure? Impact on the management of acute pulmonary embolism

In the treatment of pulmonary embolism (PE) two groups of patients are traditionally identified, namely the hemodynamically stable and instable groups. However, in the large group of normotensive patients with PE, there seems to be a subgroup of patients with an increased risk of an adverse outcome, which might benefit from more aggressive therapy than the current standard therapy with anticoagulants. Risk stratification is a commonly used method to define subgroups of patients with either a high or low risk of an adverse outcome. In this review the clinical parameters and biomarkers of myocardial injury and right ventricular dysfunction (RVD) that have been suggested to play an important role in the risk stratification of PE are described first. Secondly, the use of more direct imaging techniques like echocardiography and CT in the assessment of RVD are discussed, followed by a brief outline of new imaging techniques. Finally, two risk stratification models are proposed, combining the markers of RVD with cardiac biomarkers of ischemia to define whether patients should be admitted to the intensive care unit (ICU) and/or be given thrombolysis, admitted to the medical ward, or be safely treated at home with anticoagulant therapy

Progression of coronary artery calcification and thoracic aorta calcification in kidney transplant recipients

BACKGROUND: Vascular calcification independently predicts cardiovascular disease, the major cause of death in kidney transplant recipients (KTRs). Longitudinal studies of vascular calcification in KTRs are few and small and have short follow-up. We assessed the evolution of coronary artery (CAC) and thoracic aorta calcification and their determinants in a cohort of prevalent KTRs. STUDY DESIGN: Longitudinal. SETTING & PARTICIPANTS: The Agatston score of coronary arteries and thoracic aorta was measured by 16-slice spiral computed tomography in 281 KTRs. PREDICTORS: Demographic, clinical, and biochemical parameters were recorded simultaneously. OUTCOMES & MEASUREMENTS: The Agatston score was measured again 3.5 or more years later. RESULTS: Repeated analyzable computed tomographic scans were available for 197 (70%) KTRs after 4.40 ± 0.28 years; they were not available for the rest of patients because of death (n = 40), atrial fibrillation (n = 1), other arrhythmias (n = 4), refusal (n = 35), or technical problems precluding confident calcium scoring (n = 4). CAC and aorta calcification scores increased significantly (by a median of 11% and 4% per year, respectively) during follow-up. By multivariable linear regression, higher baseline CAC score, history of cardiovascular event, use of a statin, and lower 25-hydroxyvitamin D(3) level were independent determinants of CAC progression. Independent determinants of aorta calcification progression were higher baseline aorta calcification score, higher pulse pressure, use of a statin, older age, higher serum phosphate level, use of aspirin, and male sex. Significant regression of CAC or aorta calcification was not observed in this cohort. LIMITATIONS: Cohort of prevalent KTRs with potential survival bias; few patients with diabetes and nonwhites, limiting the generalizability of results. CONCLUSION: In contrast to previous small short-term studies, we show that vascular calcification progression is substantial within 4 years in prevalent KTRs and is associated with several traditional and nontraditional cardiovascular risk factors, some of which are modifiable