Effects of intervention with the SAFE strategy on trachoma across Ethiopia.

BACKGROUND/AIMS: The impact of the SAFE strategy (surgery, antibiotics, face washing, environmental hygiene), recommended to eliminate blinding trachoma, is not well explored. We determined the operational effectiveness of the whole SAFE intervention package. METHODS: Analytical cross-sectional trachoma surveys were conducted in four program areas across Ethiopia before and after 3 years of intervention with the SAFE strategy. A total of 8358 children 1-9 years, 4684 people above 14 and 3572 households were assessed in the follow-up evaluations using methodologies recommended by the WHO. Effects were measured by comparing follow-up proportions with baseline estimates of four key indicators. RESULTS: Coverage was 36% for trichiasis surgery, 59% for antibiotic and 57% for health-promotion services. Prevalence of trachoma trichiasis (TT) decreased from 4.6% (95% CI: 3.6% to 5.8%) down to 2.9% (CI: 2.1% to 3.9%). Prevalence of trachoma inflammation-follicular (TF) dropped from 36.7% (33.9% to 39.6%) to 18.4% (CI: 15.4% to 21.8%). The proportion of unclean faces and households not using latrines fell from 72.8% (68.9% to 76.4%) and 74.5% (69.9% to 78.7%) down to 47.0% (CI: 43% to 51%) and 51.7% (47.2% to 56.2%), respectively. All the reductions related with antibiotic (TF), face washing (clean face) and environmental (latrine) components were statistically significant except for Surgery (TT). CONCLUSIONS: Considerable decline in the magnitude of trachoma and its risk factors was observed in areas where the SAFE strategy was implemented. The coverage of services should be maintained or improved in order to eliminate blinding trachoma by the year 2020

Patient-Reported Satisfaction and Study Drug Discontinuation: Post-Hoc Analysis of Findings from ROCKET AF.

IntroductionPatient-reported outcomes (PROs) and satisfaction endpoints are increasingly important in clinical trials and may be associated with treatment adherence. In this post hoc substudy from ROCKET AF, we examined whether patient-reported satisfaction was associated with study drug discontinuation.MethodsROCKET AF (n = 14,264) compared rivaroxaban with warfarin for prevention of stroke and systemic embolism in patients with atrial fibrillation. We analyzed treatment satisfaction scores: the Anti-Clot Treatment Scale (ACTS) and Treatment Satisfaction Questionnaire for Medication version II (TSQM II). We compared satisfaction with study drug between the two treatment arms, and examined the association between satisfaction and patient-driven study drug discontinuation (stopping study drug due to withdrawal of consent, noncompliance, or loss to follow-up).ResultsA total of 1577 (11%) patients participated in the Patient Satisfaction substudy; 1181 (8.3%) completed both the ACTS and TSQM II 4 weeks after starting study drug. Patients receiving rivaroxaban did not experience significant differences in satisfaction compared with those receiving warfarin. During a median follow-up of 1.6 years, 448 premature study drug discontinuations occurred (213 rivaroxaban group; 235 warfarin group), of which 116 (26%) were patient-driven (52 [24%] rivaroxaban group; 64 [27%] warfarin group). No significant differences were observed between satisfaction level and rates of patient-driven study drug discontinuation.ConclusionsStudy drug satisfaction did not predict rate of study drug discontinuation. No significant difference was observed between satisfaction with warfarin and rivaroxaban, as expected given the double-blind trial design. Although these results are negative, the importance of PRO data will only increase, and these analyses may inform future studies that explore the relationship between drug-satisfaction PROs, adherence, and clinical outcomes. CLINICALTRIALS.GOV: NCT00403767.FundingThe ROCKET AF trial was funded by Johnson & Johnson and Bayer

The endoplasmic reticulum remains functionally connected by vesicular transport after its fragmentation in cells expressing Z-alpha(1)-antitrypsin

α1-Antitrypsin is a serine protease inhibitor produced in the liver that is responsible for the regulation of pulmonary inflammation. The commonest pathogenic gene mutation yields Z-α1-antitrypsin, which has a propensity to self-associate forming polymers that become trapped in inclusions of endoplasmic reticulum (ER). It is unclear whether these inclusions are connected to the main ER network in Z-α1-antitrypsin-expressing cells. Using live cell imaging, we found that despite inclusions containing an immobile matrix of polymeric α1-antitrypsin, small ER resident proteins can diffuse freely within them. Inclusions have many features to suggest they represent fragmented ER, and some are physically separated from the tubular ER network, yet we observed cargo to be transported between them in a cytosol-dependent fashion that is sensitive to N-ethylmaleimide and dependent on Sar1 and sec22B. We conclude that protein recycling occurs between ER inclusions despite their physical separation.—Dickens, J. A., Ordóñez, A., Chambers, J. E., Beckett, A. J., Patel, V., Malzer, E., Dominicus, C. S., Bradley, J., Peden, A. A., Prior, I. A., Lomas, D. A., Marciniak, S. J. The endoplasmic reticulum remains functionally connected by vesicular transport after its fragmentation in cells expressing Z-α1-antitrypsin

National Mesothelioma Virtual Bank: A standard based biospecimen and clinical data resource to enhance translational research

Background: Advances in translational research have led to the need for well characterized biospecimens for research. The National Mesothelioma Virtual Bank is an initiative which collects annotated datasets relevant to human mesothelioma to develop an enterprising biospecimen resource to fulfill researchers' need. Methods: The National Mesothelioma Virtual Bank architecture is based on three major components: (a) common data elements (based on College of American Pathologists protocol and National North American Association of Central Cancer Registries standards), (b) clinical and epidemiologic data annotation, and (c) data query tools. These tools work interoperably to standardize the entire process of annotation. The National Mesothelioma Virtual Bank tool is based upon the caTISSUE Clinical Annotation Engine, developed by the University of Pittsburgh in cooperation with the Cancer Biomedical Informatics Grid™ (caBIG™, see http://cabig.nci.nih.gov). This application provides a web-based system for annotating, importing and searching mesothelioma cases. The underlying information model is constructed utilizing Unified Modeling Language class diagrams, hierarchical relationships and Enterprise Architect software. Result: The database provides researchers real-time access to richly annotated specimens and integral information related to mesothelioma. The data disclosed is tightly regulated depending upon users' authorization and depending on the participating institute that is amenable to the local Institutional Review Board and regulation committee reviews. Conclusion: The National Mesothelioma Virtual Bank currently has over 600 annotated cases available for researchers that include paraffin embedded tissues, tissue microarrays, serum and genomic DNA. The National Mesothelioma Virtual Bank is a virtual biospecimen registry with robust translational biomedical informatics support to facilitate basic science, clinical, and translational research. Furthermore, it protects patient privacy by disclosing only de-identified datasets to assure that biospecimens can be made accessible to researchers. © 2008 Amin et al; licensee BioMed Central Ltd

Abrasive water jet drilling of advanced sustainable bio-fibre-reinforced polymer/hybrid composites : a comprehensive analysis of machining-induced damage responses

This paper aims at investigating the effects of variable traverse speeds on machining-induced damage of fibre-reinforced composites, using the abrasive water jet (AWJ) drilling. Three different types of epoxy-based composites laminates fabricated by vacuum bagging technique containing unidirectional (UD) flax, hybrid carbon-flax and carbon fibre-reinforced composite were used. The drilling parameters used were traverse speeds of 20, 40, 60 and 80 mm/min, constant water jet pressure of 300 MPa and a hole diameter of 10 mm. The results obtained depict that the traverse speed had a significant effect with respect to both surface roughness and delamination drilling-induced damage responses. Evidently, an increase in water jet traverse speed caused an increase in both damage responses of the three samples. Significantly, the CFRP composite sample recorded the lowest surface roughness damage response, followed by C-FFRP, while FFRP exhibited the highest. However, samples of FFRP and hybrid C-FFRP recorded lowest and highest delamination damage responses, respectively. The discrepancy in both damage responses, as further validated with micrographs of colour video microscopy (CVM), scanning electron microscopy (SEM) and X-ray micro-computed tomography (X-ray μCT), is attributed to the different mechanical properties of the reinforced fibres, fibre orientation/ply stacking and hybridisation of the samples.Peer reviewe

Circulating Progenitor Cells Identify Peripheral Arterial Disease in Patients With Coronary Artery Disease

RATIONALE: Peripheral arterial disease (PAD) is a clinical manifestation of extracoronary atherosclerosis. Despite sharing the same risk factors, only 20% to 30% of patients with coronary artery disease (CAD) develop PAD. Decline in the number of bone marrow–derived circulating progenitor cells (PCs) is thought to contribute to the pathogenesis of atherosclerosis. Whether specific changes in PCs differentiate patients with both PAD and CAD from those with CAD alone is unknown. OBJECTIVE: Determine whether differences exist in PCs counts of CAD patients with and without known PAD. METHODS AND RESULTS: 1497 patients (mean age: 65 years; 62% men) with known CAD were identified in the Emory Cardiovascular Biobank. Presence of PAD (n=308) was determined by history, review of medical records, or imaging and was classified as carotid (53%), lower extremity (41%), upper extremity (3%), and aortic disease (33%). Circulating PCs were enumerated by flow cytometry. Patients with CAD and PAD had significantly lower PC counts compared with those with only CAD. In multivariable analysis, a 50% decrease in cluster of differentiation 34 (CD34+) or CD34+/vascular endothelial growth factor receptor-2 (VEGFR2+) counts was associated with a 31% (P=0.032) and 183% (P=0.002) increase in the odds of having PAD, respectively. CD34+ and CD34+/VEGFR2+ counts significantly improved risk prediction metrics for prevalent PAD. Low CD34+/VEGFR2+ counts were associated with a 1.40-fold (95% confidence interval, 1.03–1.91) and a 1.64-fold (95% confidence interval, 1.07–2.50) increases in the risk of mortality and PAD-related events, respectively. CONCLUSIONS: PAD is associated with low CD34+ and CD34+/VEGFR2+ PC counts. Whether low PC counts are useful in screening for PAD needs to be investigated

Performance deficits of NK1 receptor knockout mice in the 5 choice serial reaction time task: effects of d Amphetamine, stress and time of day.

Background The neurochemical status and hyperactivity of mice lacking functional substance P-preferring NK1 receptors (NK1R-/-) resemble abnormalities in Attention Deficit Hyperactivity Disorder (ADHD). Here we tested whether NK1R-/- mice express other core features of ADHD (impulsivity and inattentiveness) and, if so, whether they are diminished by d-amphetamine, as in ADHD. Prompted by evidence that circadian rhythms are disrupted in ADHD, we also compared the performance of mice that were trained and tested in the morning or afternoon. Methods and Results The 5-Choice Serial Reaction-Time Task (5-CSRTT) was used to evaluate the cognitive performance of NK1R-/- mice and their wildtypes. After training, animals were tested using a long (LITI) and a variable (VITI) inter-trial interval: these tests were carried out with, and without, d-amphetamine pretreatment (0.3 or 1 mg/kg i.p.). NK1R-/- mice expressed greater omissions (inattentiveness), perseveration and premature responses (impulsivity) in the 5-CSRTT. In NK1R-/- mice, perseveration in the LITI was increased by injection-stress but reduced by d-amphetamine. Omissions by NK1R-/- mice in the VITI were unaffected by d-amphetamine, but premature responses were exacerbated by this psychostimulant. Omissions in the VITI were higher, overall, in the morning than the afternoon but, in the LITI, premature responses of NK1R-/- mice were higher in the afternoon than the morning. Conclusion In addition to locomotor hyperactivity, NK1R-/- mice express inattentiveness, perseveration and impulsivity in the 5-CSRTT, thereby matching core criteria for a model of ADHD. Because d-amphetamine reduced perseveration in NK1R-/- mice, this action does not require functional NK1R. However, the lack of any improvement of omissions and premature responses in NK1R-/- mice given d-amphetamine suggests that beneficial effects of this psychostimulant in other rodent models, and ADHD patients, need functional NK1R. Finally, our results reveal experimental variables (stimulus parameters, stress and time of day) that could influence translational studies

Determination of an optimal response cut-off able to predict progression-free survival in patients with well-differentiated advanced pancreatic neuroendocrine tumours treated with sunitinib: an alternative to the current RECIST-defined response.

BACKGROUND: Sunitinib prolongs progression-free survival (PFS) in patients with advanced pancreatic neuroendocrine tumours (pNET). Response Evaluation Criteria in Solid Tumors (RECIST)-defined partial responses (PR; classically defined as ⩾30% size decrease from baseline) are infrequent. METHODS: Individual data of pNET patients from the phase II [NCT00056693] and pivotal phase III [NCT00428597] trials of sunitinib were analysed in this investigator-initiated, post hoc study. The primary objective was to determine the optimal RECIST (v.1.0) response cut-off value to identify patients who were progression-free at 11 months (median PFS in phase III trial); and the most informative time-point (highest area under the curve (AUC) by receiver operating characteristic (ROC) analysis and logistic regression) for prediction of benefit (PFS) from sunitinib. RESULTS: Data for 237 patients (85 placebo; 152 sunitinib (n=66.50 mg \u274-weeks on/2-weeks off\u27 schedule; n=86 \u2737.5 mg continuous daily dosing (CDD)\u27)) and 788 scans were analysed. The median PFS for sunitinib and placebo were 9.3 months (95% CI 7.6-12.2) and 5.4 months (95% CI 3.5-6.01), respectively (hazard ratio (HR) 0.43 (95% CI 0.29-0.62); P CONCLUSIONS: A 10% reduction within marker lesions identifies pNET patients benefiting from sunitinib treatment with implications for maintenance of dose intensity and future trial design