10,511 research outputs found

    Collaborative study to evaluate a candidate World Health Organization international standard for chikungunya virus for nucleic acid amplification technique (NAT)-based assays

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    Collaborative Study Group - Portugal:Maria João Alves, Líbia Zé-Zé (National Institute of Health Dr. Ricardo Jorge, Center for Vectors and Infectious Diseases Research)This report describes the World Health Organization (WHO) project to develop an international standard (IS) for Chikungunya virus (CHIKV) RNA for use with nucleic acid amplification technique (NAT)-based assays. An international collaborative study was conducted to determine the potency of the candidate standard using a range of NAT-based assays for CHIKV, and to evaluate the suitability of the candidate for the calibration of secondary reference materials and the standardization of CHIKV viral load measurements. The candidate standard consisted of a heat inactivated CHIKV strain of the East/South/Central African genotype (ESCA), also known as the Indian Ocean Lineage, isolated from a patient returning from India to the United States in 20061 , diluted in human negative plasma. The lyophilized candidate preparation (Sample 1), the corresponding liquid-frozen bulk material (Sample 2) and three different clinical samples (Sample 3, Sample 4 and Sample 5) were included in the collaborative study. Twenty-five laboratories representing 14 countries participated in the study to evaluate the material using their routine CHIKV NAT assays. Twenty-four laboratories returned 31 data sets from 17 commercial assays and 14 in-house methods. Of these 31 methods, 11 were quantitative and 20 were qualitative. The results of the study indicate the suitability of the candidate material of the CHIKV strain of ESCA genotype (Sample 1) as the proposed 1st WHO IS for CHIKV. It is therefore proposed that the candidate material (PEI code 11785/16) is established as the 1st WHO IS for CHIKV RNA for NAT-based assays with an assigned potency of 2,500,000 International Units (IU)/mL when reconstituted in 0.5 mL of nuclease-free water. On-going studies for real-time and accelerated stability of the proposed IS indicate that the preparation is stable and suitable for long-term use under the proposed storage conditions.info:eu-repo/semantics/publishedVersio

    Virological outcomes of second-line protease inhibitor-based treatment for human immunodeficiency virus type 1 in a high-prevalence rural South African setting: a competing-risks prospective cohort analysis

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    Background. Second-line antiretroviral therapy (ART) based on ritonavir-boosted protease inhibitors (bPIs) represents the only available option after first-line failure for the majority of individuals living with human immunodeficiency virus (HIV) worldwide. Maximizing their effectiveness is imperative. Methods. This cohort study was nested within the French National Agency for AIDS and Viral Hepatitis Research (ANRS) 12249 Treatment as Prevention (TasP) cluster-randomized trial in rural KwaZulu-Natal, South Africa. We prospectively investigated risk factors for virological failure (VF) of bPI-based ART in the combined study arms. VF was defined by a plasma viral load >1000 copies/mL ≥6 months after initiating bPI-based ART. Cumulative incidence of VF was estimated and competing risk regression was used to derive the subdistribution hazard ratio (SHR) of the associations between VF and patient clinical and demographic factors, taking into account death and loss to follow-up. Results. One hundred one participants contributed 178.7 person-years of follow-up. Sixty-five percent were female; the median age was 37.4 years. Second-line ART regimens were based on ritonavir-boosted lopinavir, combined with zidovudine or tenofovir plus lamivudine or emtricitabine. The incidence of VF on second-line ART was 12.9 per 100 person-years (n = 23), and prevalence of VF at censoring was 17.8%. Thirteen of these 23 (56.5%) virologic failures resuppressed after a median of 8.0 months (interquartile range, 2.8-16.8 months) in this setting where viral load monitoring was available. Tuberculosis treatment was associated with VF (SHR, 11.50 [95% confidence interval, 3.92-33.74]; P < .001). Conclusions. Second-line VF was frequent in this setting. Resuppression occurred in more than half of failures, highlighting the value of viral load monitoring of second-line ART. Tuberculosis was associated with VF; therefore, novel approaches to optimize the effectiveness of PI-based ART in high-tuberculosis-burden settings are needed

    Managing the environmental impact of research

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    The environmental impact of research increasingly needs to be taken into account in design and execution. This makes good financial sense. However, it is especially in the research world as one of the key reasons for doing health research is to improve our knowledge to improve health. Specifically, doing research in a more sustainable way allows us to generate more knowledge with the same resource. Research not only needs to be done increasingly sustainably, but the content of the research needs to direct how we promote health and deliver healthcare in more sustainable ways

    Non-universal gauge boson ZZ' and the spin correlation of top quark pair production at ee+e^{-}e^{+} colliders

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    In the off-diagonal basis, we discuss the contributions of the non-universal gauge boson ZZ' predicted by the topcolor-assisted technicolor (TC2TC2) model to the spin configurations and the spin correlation observable of the top quark pair production via the process ee+ttˉe^{-}e^{+}\to t\bar{t}. Our numerical results show that the production cross sections for the like-spin states, which vanish in the standard model, can be significantly large as MZSM_{Z'}\approx \sqrt{S}. With reasonable values of the ZZ' mass MZM_{Z'} and the coupling parameter k1k_{1}, ZZ' exchange can generate large corrections to the spin correlation observable.Comment: 16 pages, 5 figure

    Physics Beyond the Standard Model and Cosmological Connections: A Summary from LCWS 06

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    The International Linear Collider (ILC) is likely to provide us important insights into the sector of physics that may supersede our current paradigm viz., the Standard Model. In anticipation of the possibility that the ILC may come up in the middle of the next decade, several groups are vigourously investigating its potential to explore this new sector of physics. The Linear Collider Workshop in Bangalore (LCWS06) had several presentations of such studies which looked at supersymmetry, extra dimensions and other exotic possibilities which the ILC may help us discover or understand. Some papers also looked at the understanding of cosmology that may emerge from studies at the ILC. This paper summarises these presentations.Comment: 8 pages (including cover page) LaTeX, Summary talk presented at the International Linear Collider Workshop in Bangalore, India in March 200

    Impact of question order on prioritisation of outcomes in the development of a core outcome set: a randomised controlled trial

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    BACKGROUND: Core outcome set (COS) developers increasingly employ Delphi surveys to elicit stakeholders' opinions of which outcomes to measure and report in trials of a particular condition or intervention. Research outside of Delphi surveys and COS development demonstrates that question order can affect response rates and lead to 'context effects', where prior questions determine an item's meaning and influence responses. This study examined the impact of question order within a Delphi survey for a COS for oesophageal cancer surgery. METHODS: A randomised controlled trial was nested within the Delphi survey. Patients and health professionals were randomised to receive a survey including clinical and patient-reported outcomes (PROs), where the PRO section appeared first or last. Participants rated (1-9) the importance of 68 items for inclusion in a COS (ratings 7-9 considered 'essential'). Analyses considered the impact of question order on: (1) survey response rates; (2) participants' responses; and (3) items retained at end of the survey. RESULTS: In total, 116 patients and 71 professionals returned completed surveys. Question order did not affect response rates among patients, but fewer professionals responded when clinical items appeared first (difference = 31.3%, 95% confidence interval [CI] = 13.6-48.9%, P = 0.001). Question order led to different context effects within patients and professionals. While patients rated clinical items highly, irrespective of question order, more PROs were rated essential when appearing last rather than first (difference = 23.7%, 95% CI = 10.5-40.8%). Among professionals, the greatest impact was on clinical items; a higher percentage rated essential when appearing last (difference = 11.6%, 95% CI = 0.0-23.3%). An interaction between question order and the percentage of PRO/clinical items rated essential was observed for patients (P = 0.025) but not professionals (P = 0.357). Items retained for further consideration at the end of the survey were dependent on question order, with discordant items (retained by one question order group only) observed in patients (18/68 [26%]) and professionals (20/68 [29%]). CONCLUSIONS: In the development of a COS, participants' ratings of potential outcomes within a Delphi survey depend on the context (order) in which the outcomes are asked, consequently impacting on the final COS. Initial piloting is recommended with consideration of the randomisation of items in the survey to reduce potential bias. TRIAL REGISTRATION: The randomised controlled trial reported within this paper was nested within the development of a core outcome set to investigate processes in core outcome set development. Outcomes were not health-related and trial registration was not therefore applicable
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