Complement-Mediated Opsonic Activity in Normal and Infected Human Cerebrospinal Fluid: Early Response During Bacterial Meningitis

A local defense mechanism in bacterial meningitis was evaluated in humans by measuring complement-mediated opsonic activity (CMOA) in normal and infected cerebrospinal fluid (CSF) with a complement-dependent phagocytic bactericidal assay. CMOA was absent in normal untreated CSF and remained undetectable in 20 samples of CSF from patients with viral meningitis and five samples from patients with acute meningococcemia. In contrast, 15 of 27 samples of CSF from patients with acute bacterial meningitis had a measurable CMOA, which was correlated with protein concentrations (P < 0.01) and C4 hemolytic activity (P < 0.001) in the CSF. A favorable outcome of bacterial meningitis was associated with the presence of CMOA in CSF (P < 0.005). Recovery was also correlated with higher levels of C4 (P < 0.01) and C3 (P < 0.05) in CSF and with lower concentrations of microorganisms in the sample of CSF collected at the time of admission (P < 0.01). Thus, CMOA, although absent in normal CSF, can appear in CSF during acute bacterial meningitis, particularly in patients who recover completel

1993 Progress Reports

The 1993 Progress Reports which contain Blueberry Tax Supported Weed Management and Pruning Project Reports, and CSRS Supported Weed Management and Pruning Project Reports, pertain to and report on research conducted in 1992. They were prepared for the Maine Wild Blueberry Commission and the University of Maine Wild Blueberry Advisory Committee by researchers at the University of Maine, Orono. Projects in this report include: Progress Reports 1. Effects of Irrigation on Low bush Blueberry Yield and Quality 2. Economics of Investing in Irrigation for Lowbush Blueberries 3. Diammonium Phosphate Study 4. Phosphorus Dose/Response Curve 5. Winter Injury Protection by Potassium 6. Multiple Cropping of Wild Stands 7. Effect of Boron on Lowbush Blueberry Fruit Set and Yield 8.Determination of Pesticide Residue Levels in Freshly Harvested and Processed Lowbush Blueberries 9. Effects of Calcium Salts and Citric Acids on the Quality of Canned Lowbush Blueberries- missing 10. Investigation of PreProcess Changes- missing 11. The Effect of Fertilization and Irrigation on Blueberry Fruit Control - missing 12. Pollination Ecology of Lowbush Blueberry in Maine 13. Control of Secondary Blueberry Pests 14. Control of Blueberry Maggot 15. Biology and Action Thresholds of Secondary Blueberry Pests 16. Cold-Hardiness of Native Lowbush Blueberries 17. Design, Fabrication, and Testing of an Experimental Sterilizer for Blueberry Fields 18. Canned Product Quality - Heat Resistant Molds 19. Sanitation for Disease Control Blueberry Tax Supported Weed Management and Pruning Project Reports 20. Evaluation of Postemergence Applications of Tribenuron Methyl for Bunchberry Control 21. Comparison of Poast and Select for Suppression of Bunchgrass 22. Effect of Time of Fall Pruning on Growth and Productivity of Blueberries. and Evaluation of Infrared Burner to Prune Blueberries 23. Evaluation of Velpar impregnated DAP for weed control 24. Thresholds of Dogbane and Bracken Fern for Mechanical and Chemical Control in Lowbush Blueberry Fields 25. Effect of Time and Rate of Application of Clopyralid for Control of Vetch in Lowbush Blueberries 26. Hexazinone Ground Water Survey 27. Composting Blueberry Processing Waste 28. Hexazinone Movement in a Blueberry Soil in Maine CSRS Supported Weed Management and Pruning Project Reports 29. Evaluation of the Suitability of Remote Sensing to Evaluate Plant Cover in Lowbush Blueberry Fields 30. Obstruction Removal in Lowbush Blueberry Fields 31. Evaluation of Pressurized Rope Wick Wick Master Wiper for Treating Weeds Growing Above Lowbush Blueberries 32. Evaluation of Infrared Burner for Weed Control 33. Blueberry Extension Education Program Base Miscellaneous 34. Comparison of N, NP, and NPK Fertilizers to Correct Nitrogen and Phosphorus Deficienc

1993-94 Progress Report

The 1993 edition of the Progress Reports was prepared for the Maine Wild Blueberry Commission and the University of Maine Wild Blueberry Advisory Committee by researchers at the University of Maine, Orono. Projects in this report include: 1. Effects of irrigation on lowbush blueberry yield and quality 2. The Economics of investigating irrigation for lowbush blueberries 3. Phosphorus dose/response curve 4. Winter injury protection by potassium 5. Multiple cropping of wild stands 6. Effect of Boron and Calcium on lowbush blueberry fruit set and yield 7. Comparison of N, NP, and NPK fertilizers to correct nitrogen and phosphorus deficiency 8. Determination of pesticide residue levels in freshly harvested and processed lowbush blueberries 9. Effects of calcium salts and citric acid on the quality of canned lowbush blueberries 10. Investigation of preprocess changes (chemical, microbiological, and/or physical) that can lead to the development of a simple and inexpensive method to measure preprocess berry spoilage 11. The effect of fertilization and irrigation in blueberry fruit quality 12. Pollination Ecology of lowbush blueberry in Maine 13. Current importance of insects in lowbush blueberry fields 14. Application of heat as a method of controlling secondary pest insects on lowbush blueberry: a feasibility study 15. Control of blueberry maggot 16. Control of secondary blueberry pest insects 17. Biology and action thresholds of secondary blueberry pest insects 18. Cold-hardiness of native lowbush blueberry 19. Design, fabrication, and testing of an experimental sterilizer for blueberry fields 20. Canned Product Quality--Heat-resistant molds 21. Sanitation for disease control 22. Evaluation of Velpar® impregnated DAP and Pronone® for weed control 23. Evaluation of postemergence applications of tribenuron methyl for bunchberry control 24. Evaluation of postemergence applications of a tank mix of tribenuron methyl and hexazinone for bunchberry control 25. Thresholds of dogbane and bracken fem by mechanical and chemical control in lowbush blueberry fields 26. Effect of time of application of clopyralid for control of vetch and effect on flowering in lowbush blueberries 27. Effect of time of fall pruning on growth and productivity of blueberries and evaluation of infrared burner to prune blueberries 28. Evaluation of infrared burner for selective seedling weed control 29. Evaluation of pressurized rope wick Wick Master wiper for treating weeds growing above lowbush blueberries 30. Blueberry Extension Education Program Base 31. Blueberry ICM program for Hancock County 32. Composting blueberry processing waste 33. Hexazinone ground water survey 34. Investigations of Lowbush Blueberry Fruit bud Cold-hardiness 35. Design, Fabrication, and Testing of an Experimental Sterilizer for Blueberry Field

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Target Cell Cyclophilins Facilitate Human Papillomavirus Type 16 Infection

Following attachment to primary receptor heparan sulfate proteoglycans (HSPG), human papillomavirus type 16 (HPV16) particles undergo conformational changes affecting the major and minor capsid proteins, L1 and L2, respectively. This results in exposure of the L2 N-terminus, transfer to uptake receptors, and infectious internalization. Here, we report that target cell cyclophilins, peptidyl-prolyl cis/trans isomerases, are required for efficient HPV16 infection. Cell surface cyclophilin B (CyPB) facilitates conformational changes in capsid proteins, resulting in exposure of the L2 N-terminus. Inhibition of CyPB blocked HPV16 infection by inducing noninfectious internalization. Mutation of a putative CyP binding site present in HPV16 L2 yielded exposed L2 N-terminus in the absence of active CyP and bypassed the need for cell surface CyPB. However, this mutant was still sensitive to CyP inhibition and required CyP for completion of infection, probably after internalization. Taken together, these data suggest that CyP is required during two distinct steps of HPV16 infection. Identification of cell surface CyPB will facilitate the study of the complex events preceding internalization and adds a putative drug target for prevention of HPV–induced diseases

Sporadic hemangioblastomas are characterized by cryptic VHL inactivation

Hemangioblastomas consist of 10-20% neoplastic “stromal” cells within a vascular tumor cell mass of reactive pericytes, endothelium and lymphocytes. Familial cases of central nervous system hemangioblastoma uniformly result from mutations in the Von Hippel-Lindau (VHL) gene. In contrast, inactivation of VHL has been previously observed in only a minority of sporadic hemangioblastomas, suggesting an alternative genetic etiology. We performed deep-coverage DNA sequencing on 32 sporadic hemangioblastomas (whole exome discovery cohort n = 10, validation n = 22), followed by analysis of clonality, copy number alteration, and somatic mutation. We identified somatic mutation, loss of heterozygosity and/or deletion of VHL in 8 of 10 discovery cohort tumors. VHL inactivating events were ultimately detected in 78% (25/32) of cases. No other gene was significantly mutated. Overall, deep-coverage sequence analysis techniques uncovered VHL alterations within the neoplastic fraction of these tumors at higher frequencies than previously reported. Our findings support the central role of VHL inactivation in the molecular pathogenesis of both familial and sporadic hemangioblastomas

The Role of Information and Financial Reporting in Corporate Governance and Debt Contracting

We review recent literature on the role of financial reporting transparency in reducing governance-related agency conflicts among managers, directors, and shareholders, as well as in reducing agency conflicts between shareholders and creditors, and offer researchers some suggested avenues for future research. Key themes include the endogenous nature of debt contracts and governance mechanisms with respect to information asymmetry between contracting parties, the heterogeneous nature of the informational demands of contracting parties, and the heterogeneous nature of the resulting governance and debt contracts. We also emphasize the role of a commitment to financial reporting transparency in facilitating informal multiperiod contracts among managers, directors, shareholders, and creditors

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

Clinical Utility of Random Anti–Tumor Necrosis Factor Drug–Level Testing and Measurement of Antidrug Antibodies on the Long-Term Treatment Response in Rheumatoid Arthritis

Objective: To investigate whether antidrug antibodies and/or drug non-trough levels predict the long-term treatment response in a large cohort of patients with rheumatoid arthritis (RA) treated with adalimumab or etanercept and to identify factors influencing antidrug antibody and drug levels to optimize future treatment decisions.  Methods: A total of 331 patients from an observational prospective cohort were selected (160 patients treated with adalimumab and 171 treated with etanercept). Antidrug antibody levels were measured by radioimmunoassay, and drug levels were measured by enzyme-linked immunosorbent assay in 835 serial serum samples obtained 3, 6, and 12 months after initiation of therapy. The association between antidrug antibodies and drug non-trough levels and the treatment response (change in the Disease Activity Score in 28 joints) was evaluated.  Results: Among patients who completed 12 months of followup, antidrug antibodies were detected in 24.8% of those receiving adalimumab (31 of 125) and in none of those receiving etanercept. At 3 months, antidrug antibody formation and low adalimumab levels were significant predictors of no response according to the European League Against Rheumatism (EULAR) criteria at 12 months (area under the receiver operating characteristic curve 0.71 [95% confidence interval (95% CI) 0.57, 0.85]). Antidrug antibody–positive patients received lower median dosages of methotrexate compared with antidrug antibody–negative patients (15 mg/week versus 20 mg/week; P = 0.01) and had a longer disease duration (14.0 versus 7.7 years; P = 0.03). The adalimumab level was the best predictor of change in the DAS28 at 12 months, after adjustment for confounders (regression coefficient 0.060 [95% CI 0.015, 0.10], P = 0.009). Etanercept levels were associated with the EULAR response at 12 months (regression coefficient 0.088 [95% CI 0.019, 0.16], P = 0.012); however, this difference was not significant after adjustment. A body mass index of ≥30 kg/m2 and poor adherence were associated with lower drug levels.  Conclusion: Pharmacologic testing in anti–tumor necrosis factor–treated patients is clinically useful even in the absence of trough levels. At 3 months, antidrug antibodies and low adalimumab levels are significant predictors of no response according to the EULAR criteria at 12 months

Non-Standard Errors

In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty: Non-standard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for better reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants