81 research outputs found
Language policy and orthographic harmonization across linguistic, ethnic and national boundaries in Southern Africa
Drawing on online and daily newspapers, speakers' language and
writing practices, official government documents and prescribed spelling systems in
Southern Africa, the paper explores the challenges and possibilities of orthographic
reforms allowing for mobility across language clusters, ethnicity, regional and
national borders. I argue that this entails a different theorisation of language, and for
orthographies that account for the translocations and diasporic nature of late modern
African identities and lifestyles. I suggest an ideological shift from prescriptivism to
practice-orientated approaches to harmonisation in which orthographies are based
on descriptions of observable writing practices in the mobile linguistic universe.
The argument for orthographic reforms is counterbalanced with an expose on
current language policies which appear designed for an increasing rare monoglot
'standard' speaker, who speaks only a 'tribal' language. The implications of the
philosophical challenges this poses for linguists, language planners and policy
makers are thereafter discussed.IS
Discovery of High-Affinity Protein Binding Ligands – Backwards
BACKGROUND: There is a pressing need for high-affinity protein binding ligands for all proteins in the human and other proteomes. Numerous groups are working to develop protein binding ligands but most approaches develop ligands using the same strategy in which a large library of structured ligands is screened against a protein target to identify a high-affinity ligand for the target. While this methodology generates high-affinity ligands for the target, it is generally an iterative process that can be difficult to adapt for the generation of ligands for large numbers of proteins. METHODOLOGY/PRINCIPAL FINDINGS: We have developed a class of peptide-based protein ligands, called synbodies, which allow this process to be run backwards--i.e. make a synbody and then screen it against a library of proteins to discover the target. By screening a synbody against an array of 8,000 human proteins, we can identify which protein in the library binds the synbody with high affinity. We used this method to develop a high-affinity synbody that specifically binds AKT1 with a K(d)<5 nM. It was found that the peptides that compose the synbody bind AKT1 with low micromolar affinity, implying that the affinity and specificity is a product of the bivalent interaction of the synbody with AKT1. We developed a synbody for another protein, ABL1 using the same method. CONCLUSIONS/SIGNIFICANCE: This method delivered a high-affinity ligand for a target protein in a single discovery step. This is in contrast to other techniques that require subsequent rounds of mutational improvement to yield nanomolar ligands. As this technique is easily scalable, we believe that it could be possible to develop ligands to all the proteins in any proteome using this approach
Exploring the effect of implementation and context on a stepped-wedge randomised controlled trial of a vital sign triage device in routine maternity care in low-resource settings
© 2019 The Author(s). Background: Interventions aimed at reducing maternal mortality are increasingly complex. Understanding how complex interventions are delivered, to whom, and how they work is key in ensuring their rapid scale-up. We delivered a vital signs triage intervention into routine maternity care in eight low- and middle-income countries with the aim of reducing a composite outcome of morbidity and mortality. This was a pragmatic, hybrid effectiveness-implementation stepped-wedge randomised controlled trial. In this study, we present the results of the mixed-methods process evaluation. The aim was to describe implementation and local context and integrate results to determine whether differences in the effect of the intervention across sites could be explained. Methods: The duration and content of implementation, uptake of the intervention and its impact on clinical management were recorded. These were integrated with interviews (n = 36) and focus groups (n = 19) at 3 months and 6-9 months after implementation. In order to determine the effect of implementation on effectiveness, measures were ranked and averaged across implementation domains to create a composite implementation strength score and then correlated with the primary outcome. Results: Overall, 61.1% (n = 2747) of health care providers were trained in the intervention (range 16.5% to 89.2%) over a mean of 10.8 days. Uptake and acceptability of the intervention was good. All clusters demonstrated improved availability of vital signs equipment. There was an increase in the proportion of women having their blood pressure measured in pregnancy following the intervention (79.2% vs. 97.6%; OR 1.30 (1.29-1.31)) and no significant change in referral rates (3.7% vs. 4.4% OR 0.89; (0.39-2.05)). Availability of resources and acceptable, effective referral systems influenced health care provider interaction with the intervention. There was no correlation between process measures within or between domains, or between the composite score and the primary outcome. Conclusions: This process evaluation has successfully described the quantity and quality of implementation. Variation in implementation and context did not explain differences in the effectiveness of the intervention on maternal mortality and morbidity. We suggest future trials should prioritise in-depth evaluation of local context and clinical pathways. Trial registration: Trial registration: ISRCTN41244132. Registered on 2 Feb 2016
Safety and efficacy of a dapivirine vaginal ring for HIV prevention in women
BACKGROUND
The incidence of human immunodeficiency virus (HIV) infection remains high
among women in sub-Saharan Africa. We evaluated the safety and efficacy of extended
use of a vaginal ring containing dapivirine for the prevention of HIV infection
in 1959 healthy, sexually active women, 18 to 45 years of age, from seven communities
in South Africa and Uganda.
METHODS
In this randomized, double-blind, placebo-controlled, phase 3 trial, we randomly
assigned participants in a 2:1 ratio to receive vaginal rings containing either 25 mg
of dapivirine or placebo. Participants inserted the rings themselves every 4 weeks
for up to 24 months. The primary efficacy end point was the rate of HIV type 1
(HIV-1) seroconversion.
RESULTS
A total of 77 participants in the dapivirine group underwent HIV-1 seroconversion
during 1888 person-years of follow-up (4.1 seroconversions per 100 person-years),
as compared with 56 in the placebo group who underwent HIV-1 seroconversion
during 917 person-years of follow-up (6.1 seroconversions per 100 person-years).
The incidence of HIV-1 infection was 31% lower in the dapivirine group than in
the placebo group (hazard ratio, 0.69; 95% confidence interval [CI], 0.49 to 0.99; P = 0.04). There was no significant difference in efficacy of the dapivirine ring
among women older than 21 years of age (hazard ratio for infection, 0.63; 95% CI,
0.41 to 0.97) and those 21 years of age or younger (hazard ratio, 0.85; 95% CI, 0.45
to 1.60; P = 0.43 for treatment-by-age interaction). Among participants with HIV-1
infection, nonnucleoside reverse-transcriptase inhibitor resistance mutations were
detected in 14 of 77 participants in the dapivirine group (18.2%) and in 9 of 56
(16.1%) in the placebo group. Serious adverse events occurred more often in the
dapivirine group (in 38 participants [2.9%]) than in the placebo group (in 6 [0.9%]).
However, no clear pattern was identified.
CONCLUSIONS
Among women in sub-Saharan Africa, the dapivirine ring was not associated with
any safety concerns and was associated with a rate of acquisition of HIV-1 infection
that was lower than the rate with placebo.Supported by the International Partnership for Microbicides
(a not-for-profit product-development partnership), which receives
support from the Bill and Melinda Gates Foundation,
Irish Aid, the Ministry of Foreign Affairs of Denmark, the Ministry
of Foreign Affairs of the Netherlands, the Norwegian
Agency for Development Cooperation, the U.K. Department for
International Development, the American people through the
U.S. Agency for International Development, and the President’s
Emergency Plan for AIDS Relief.http://www.nejm.org2017-06-01am2017Family Medicin
APPLICATION OF FRACTIONAL CALCULUS IN GROUND HEAT FLUX ESTIMATION
Ground (soil) heat flux is important physical factor primarily because of its role i
PILOT PLANT FOR EXPLOITATION OF
are already be ing used for ther a peu tic pur poses. For the ex ploi ta tion of heat en ergy bor ing B-4 is very in ter est ing. It is a bor ing of a closed type, with the wa ter tem per a ture of about 75 °C and a flow rate of about 30 l/s. Wa ters with the flow rate of about 6 l/s are cur rently used for heat ing of the Gejzer ho tel, and wa ters of the flow rate of about 0,121 l/s for the pi lot dry ing plant. The pa per pres ents this pi lot plant. Key words: geothermal water, heat energy, drying, pilot plant
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