Accuracy of WHO CD4 cell count criteria for virological failure of antiretroviral therapy

OBJECTIVES: To examine the accuracy of the World Health Organization immunological criteria for virological failure of antiretroviral treatment. METHODS: Analysis of 10 treatment programmes in Africa and South America that monitor both CD4 cell counts and HIV-1 viral load. Adult patients with at least two CD4 counts and viral load measurements between month 6 and 18 after starting a non-nucleoside reverse transcriptase inhibitor-based regimen were included. WHO immunological criteria include CD4 counts persistently <100 cells/microl, a fall below the baseline CD4 count, or a fall of >50% from the peak value. Virological failure was defined as two measurements > or =10 0000 copies/ml (higher threshold) or > or =500 copies/ml (lower threshold). Measures of accuracy with exact binomial 95% confidence intervals (CI) were calculated. RESULTS: A total of 2009 patients were included. During 1856 person-years of follow up 63 patients met the immunological criteria and 35 patients (higher threshold) and 95 patients (lower threshold) met the virological criteria. Sensitivity [95% confidence interval (CI)] was 17.1% (6.6-33.6%) for the higher and 12.6% (6.7-21.0%) for the lower threshold. Corresponding results for specificity were 97.1% (96.3-97.8%) and 97.3% (96.5-98.0%), for positive predictive value 9.5% (3.6-19.6%) and 19.0% (10.2-30.9%) and for negative predictive value 98.5% (97.9-99.0%) and 95.7% (94.7-96.6%). CONCLUSIONS: The positive predictive value of the WHO immunological criteria for virological failure of antiretroviral treatment in resource-limited settings is poor, but the negative predictive value is high. Immunological criteria are more appropriate for ruling out than for ruling in virological failure in resource-limited settings.

On the Limits of Greenwich Mean Time, or The Failure of a Modernist Revolution

On the Limits of Greenwich Mean Time, or The Failure of a Modernist Revolution From the introduction of World Standard Time in 1884 to Einstein’s theory of relativity, the nature and regulation of time was a highly contested issue in modernism, with profound political, social and epistemological consequences. Modernist aesthetic sensibilities widely revolted against the increasingly strict rule of the clock, which, as Georg Simmel observed in “The Metropolis and Mental Life,” was established as the necessary basis of a capitalist, urban life. This paper will focus on the contending conceptions of time arising in key modernist texts by authors like Joyce, Woolf and Conrad. I will argue that the uniformity and regularity of time necessary to a rising capitalist society came under attack in a similar way by both modernist literary aesthetics and new scientific discoveries. However, while Einstein’s theory of relativity may have led to a subsequent change of paradigm in scientific thought, it has failed to significantly alter social and popular conceptions of time. Although alternative ways of thinking and living with time are proposed by modernist authors, they remain isolated aesthetic experiments, ineffectual against the regulatory pressure of economic and social structures. In this struggle about the nature of time, so I suggest, science and literature join force against a society that is increasingly governed by economic reason. The fact that they lost this struggle can serve as a striking illustration of an increasing shift of social influence from science and art towards economy.

Correlation between serum total globulins and gamma globulins and their use to diagnose failure of passive transfer in foals.

Various assays have been used as an aid to diagnose failure of passive transfer (FPT) of immunoglobulins in neonatal foals, but often lack sensitivity as screening tests, or are time consuming to perform and impractical as confirmatory tests. The aim of the present study was to evaluate whether measurement of serum total globulins (TG; i.e. total protein minus albumin) can be used to estimate the electrophoretic gamma globulin (EGG) fraction in hospitalised neonatal foals with suspected FPT. Sample data from 56 foals were evaluated retrospectively. The coefficient of rank correlation was 0.84. The area under the curve of ROC analysis was 0.887, 0.922 and 0.930 for EGG concentrations <2 g/L, < 4 g/L and <8 g/L, respectively. Cut-offs for TG achieved ≥90% sensitivity for detecting EGG <2 g/L, < 4 g/L and <8 g/L, with negative predictive values of >97% and >94%, using prevalence of 15% and 30%, respectively. These results suggest that measurement of TG can be used as a guide to predicting EGG, provided that appropriate cut-off values are selected, and this technique could be a useful initial screening test for FPT in foals.

Pitfalls and premature failure of the Freedom SOLO stentless valve.

OBJECTIVES This study reports a series of pitfalls, premature failures and explantations of the third-generation Freedom SOLO (FS) bovine pericardial stentless valve. METHODS A total of 149 patients underwent aortic valve replacement using the FS. Follow-up was 100% complete with an average observation time of 5.5 ± 2.3 years (maximum 8.7 years) and a total of 825 patient-years. Following intraoperative documentation, all explanted valve prostheses underwent histological examination. RESULTS Freedom from structural valve deterioration (SVD) at 5, 6, 7, 8 and 9 years was 92, 88, 80, 70 and 62%, respectively. Fourteen prostheses required explantation due to valve-independent dysfunction (n = 5; i.e. thrombus formation, oversizing, aortic dilatation, endocarditis and suture dehiscence) or valve-dependent failure (acute leaflet tears, n = 4 and severe stenosis, n = 5). Thus, freedom from explantation at 5, 6, 7, 8 and 9 years was 95, 94, 91, 81 and 72%, respectively. An acute vertical tear along the non-coronary/right coronary commissure to the base occurred at a mean of 6.0 years (range 4.3-7.3 years) and affected size 25 and 27 prostheses exclusively. Four FS required explantation after a mean of 7.5 years (range 7.0-8.3 years) due to severe functional stenosis and gross calcification that included the entire aortic root. CONCLUSIONS The FS stentless valve is safe to implant and shows satisfying mid-term results in our single institution experience. Freedom from SVD and explantation decreased markedly after only 6-7 years, so that patients with FS require close observation and follow-up. Exact sizing, symmetric positioning and observing patient limitations are crucial for optimal outcome.

Pitfalls and premature failure of the Freedom SOLO stentless valve

Gebiet: Chirurgie Abstract: Objectives This study reports a series of pitfalls, premature failures and explantations of the third generation Freedom SOLO bovine pericardial stentless valve. – – Methods 149 patients underwent aortic valve replacement (AVR) using the FS. Follow-up was 100% complete with an average observation time of 5.5±2.3 years (max. 8.7 years) and a total of 825 patient years. Following intraoperative documentation, all explanted valve prostheses underwent histological examination. – – Results Freedom from structural valve deterioration (SVD) at 5, 6, 7, 8 and 9 years was 92%, 88%, 80% and 70% and 62%, respectively. 14 prostheses required explantation due to valve-independent dysfunction (n=5, i.e. thrombus formation, oversizing, aortic dilatation, endocarditis and suture dehiscence) or valve-dependent failure (acute leaflet tears, n=4, severe stenosis, n=5). Thus freedom from explantation at 5, 6, 7, 8 and 9 years was 95%, 94%, 91% and 81% and 72%, respectively. An acute vertical tear along the non-coronary/right-coronary commissure to the base occurred at a mean of 6.0 years [range 4.3?7.3 years] and affected size 25 and 27 prostheses exclusively. Four FS required explantation after a mean of 7.5 years [range 7.0?8.3 years] due to severe functional stenosis and gross calcification that included the entire aortic root. – – Conclusions The Freedom SOLO stentless valve is safe to implant and shows satisfying mid-term results in our single institution experience. Freedom from SVD and explantation decreased markedly after only 6 ? 7 years, so that patients with FS require close observation and follow-up. Exact sizing, symmetric positioning and observing patient limitations are crucial for optimal outcome.

Failure of fixed orthodontic retainers: A systematic review

OBJECTIVE To evaluate the risk of failure of fixed orthodontic retention protocols. DATA Screening for inclusion eligibility, quality assessment of studies and data extraction was performed independently by two authors. SOURCES The electronic databases MEDLINE, EMBASE and CENTRAL were searched with no restrictions on publication date or language using detailed strategies. The main outcome assessed was bond failure. STUDY SELECTION Twenty-seven studies satisfied the inclusion criteria. Randomised controlled trials and prospective studies were evaluated according to the Cochrane risk of bias tool. Retrospective studies were graded employing the predetermined criteria of Bondemark. RESULTS Nine randomised controlled trials, four of which were of low quality, were identified. Six studies had a prospective design and all were of low quality. Twelve studies were retrospective. The quality of trial reporting was poor in general. Four studies assessing glass-fibre retainers, three RCTs and one prospective, reported bond failures from 11 to 71%, whereas twenty studies evaluating multistranded retainers – nine RCTs, two prospective and nine retrospective – reported failures ranging from 12 to 50%. One comparison was performed, multistranded wires vs. polyehtylene woven ribbon (RR: 1.74; 95% CI: 0.45, 6.73; p=0.42). CONCLUSION The quality of the available evidence is low. No conclusive evidence was found in order to guide orthodontists in the selection of the best protocol. CLINICAL SIGNIFICANCE Although fixed orthodontic retainers have been used for years in clinical practice, the selection of the best treatment protocol still remains a subjective issue. The available studies, and their synthesis, cannot provide reliable evidence in this field.

Influence of Abutment Design on Stiffness, Strength, and Failure of Implant-Supported Monolithic Resin Nano Ceramic (RNC) Crowns

BACKGROUND Recent technical development allows the digital manufacturing of monolithic reconstructions with high-performance materials. For implant-supported crowns, the fixation requires an abutment design onto which the reconstruction can be bonded. PURPOSE The aim of this laboratory investigation was to analyze stiffness, strength, and failure modes of implant-supported, computer-assisted design and computer-aided manufacturing (CAD/CAM)-generated resin nano ceramic (RNC) crowns bonded to three different titanium abutments. MATERIALS AND METHODS Eighteen monolithic RNC crowns were produced and loaded in a universal testing machine under quasi-static condition according to DIN ISO 14801. With regard to the type of titanium abutment, three groups were defined: (1) prefabricated cementable standard; (2) CAD/CAM-constructed individualized; and (3) novel prefabricated bonding base. Stiffness and strength were measured and analyzed statistically with Wilcoxon rank sum test. Sections of the specimens were examined microscopically. RESULTS Stiffness demonstrated high stability for all specimens loaded in the physiological loading range with means and standard deviations of 1,579 ± 120 N/mm (group A), 1,733 ± 89 N/mm (group B), and 1,704 ± 162 N/mm (group C). Mean strength of the novel prefabricated bonding base (group C) was 17% lower than of the two other groups. Plastic deformations were detectable for all implant-abutment crown connections. CONCLUSIONS Monolithic implant crowns made of RNC seem to represent a feasible and stable prosthetic construction under laboratory testing conditions with strength higher than the average occlusal force, independent of the different abutment designs used in this investigation.

Cultural Legacies and Political Preferences: The Failure of Separatism in the Swiss Jura

The study of secession generally stresses the causal influence of cultural identities, political preferences, or ecological factors. Whereas these different views are often considered to be mutually exclusive, this paper proposes a two-stage model in which they are complementary. We posit that cultural identities matter for explaining secessionism, but not because of primordial attachments. Rather, religious and linguistic groups matter because their members are imbued with cultural legacies that lead to distinct political preferences – in this case preferences over welfare statism. Further, ecological constraints such as geography and topography affect social interaction with like-minded individuals. On the basis of both these political preferences and ecological constraints, individuals then make rational choices about the desirability of secession. Instrumental considerations are therefore crucial in explaining the decision to secede, but not in a conventional pocketbook manner. To examine this theory, we analyze the 2013 referendum on the secession of the Jura Bernois region from the Canton of Berne in Switzerland, using municipal level census and referendum data. The results lend support to the theory and suggest one way in which the politics of identity, based on factors like language and religion, can be fused with the politics of interest (preferences for more or less state intervention into the polity and economy) to better understand group behavior.

Obesity, age, sex, diagnosis, and fixation mode differently affect early cup failure in total hip arthroplasty: a matched case-control study of 4420 patients

Studies about the influence of patient characteristics on mechanical failure of cups in total hip replacement have applied different methodologies and revealed inconclusive results. The fixation mode has rarely been investigated. Therefore, we conducted a detailed analysis of the influence of patient characteristics and fixation mode on cup failure risks.

A Preliminary Impact Assessment of Doha Round Results on Agricultural Policies in Turkey

Turkish agriculture has been experiencing a period of unique policy experiment over the last couple years. A World Bank-initiated project, called the Agricultural Reform Implementation Project (ARIP), has been at the forefront of policy change. It was initially promoted by the Bank as an exemplary reform package which could also be adopted by other developing countries. It was introduced in 2001 as part of a major International Monetary Fund (IMF)/World Bank-imposed program of “structural adjustment” after the country had been hit by a major financial crisis. The project has finally come to an end in 2009, and there is now an urgent need for a retrospective assessment of its overall impact on the agricultural sector. Has it fulfilled its ambitious objective of reforming and restructuring Turkish agriculture? Or should it be recorded as a failure of the neo-liberal doctrine? This book aims at finding answers to these questions by investigating the legacy of ARIP from a multi-disciplinary perspective.

Mechanical restoration and failure analyses of a hydrogel and scaffold composite strategy for annulus fibrosus repair

Unrepaired defects in the annulus fibrosus of intervertebral disks are associated with degeneration and persistent back pain. A clinical need exists for a disk repair strategy that can seal annular defects, be easily delivered during surgical procedures, and restore biomechanics with low risk of herniation. Multiple annulus repair strategies were developed using poly(trimethylene carbonate) scaffolds optimized for cell delivery, polyurethane membranes designed to prevent herniation, and fibrin-genipin adhesive tuned to annulus fibrosus shear properties. This three-part study evaluated repair strategies for biomechanical restoration, herniation risk and failure mode in torsion, bending and compression at physiological and hyper-physiological loads using a bovine injury model. Fibrin-genipin hydrogel restored some torsional stiffness, bending ROM and disk height loss, with negligible herniation risk and failure was observed histologically at the fibrin-genipin mid-substance following rigorous loading. Scaffold-based repairs partially restored biomechanics, but had high herniation risk even when stabilized with sutured membranes and failure was observed histologically at the interface between scaffold and fibrin-genipin adhesive. Fibrin-genipin was the simplest annulus fibrosus repair solution evaluated that involved an easily deliverable adhesive that filled irregularly-shaped annular defects and partially restored disk biomechanics with low herniation risk, suggesting further evaluation for disk repair may be warranted. Statement of significance Lower back pain is the leading cause of global disability and commonly caused by defects and failure of intervertebral disk tissues resulting in herniation and compression of adjacent nerves. Annulus fibrosus repair materials and techniques have not been successful due to the challenging mechanical and chemical microenvironment and the needs to restore biomechanical behaviors and promote healing with negligible herniation risk while being delivered during surgical procedures. This work addressed this challenging biomaterial and clinical problem using novel materials including an adhesive hydrogel, a scaffold capable of cell delivery, and a membrane to prevent herniation. Composite repair strategies were evaluated and optimized in quantitative three-part study that rigorously evaluated disk repair and provided a framework for evaluating alternate repair techniques.