Are we there yet? on a journey towards more contextually relevant resources in speech-language therapy and audiology

Audiologists and speech-language therapists working in developing contexts like South Africa have the opportunity to address a range of needs through their research. One of these needs is the development of assessments and therapy materials that are appropriate for their clients’particular language needs and cultural background. This editorial paper aims to introduce original research in speech-language therapy and audiology, which has been carried out in South Africa and other developing contexts and is presented in this volume of the journal. In addition we suggest that while the focus of much research is on the destination or end product that is developed, there is a need to share the methodologies that are used to reach that goal so that more research can be carried out by a wider pool of students, researchers and clinicians. We describe some of the methods that we have used in our research – often in small scale projects with budgetary constraints, which would be feasible for clinicians in their routine clinical contexts. Our hope is that others can build on these approaches, critique and share their own strategies for the ultimate advancement of the professions in southern Africa

Are we there yet? On a journey towards more contextually relevant resources in speech-language therapy and audiology

Audiologists and speech-language therapists working in developing contexts like South Africa have the opportunity to address a range of needs through their research. One of these needs is the development of assessments and therapy materials that are appropriate for their clients’particular language needs and cultural background. This editorial paper aims to introduce original research in speech-language therapy and audiology, which has been carried out in South Africa and other developing contexts and is presented in this volume of the journal. In addition we suggest that while the focus of much research is on the destination or end product that is developed, there is a need to share the methodologies that are used to reach that goal so that more research can be carried out by a wider pool of students, researchers and clinicians. We describe some of the methods that we have used in our research – often in small scale projects with budgetary constraints, which would be feasible for clinicians in their routine clinical contexts. Our hope is that others can build on these approaches, critique and share their own strategies for the ultimate advancement of the professions in southern Africa

Creating and Capturing Value at Work : Who Benefits? Part 1: Thematic Literature Review

How organisations create value and for whom are questions that in the fairly recent past have become much harder to answer clearly. The Great Recession, the growth of digital-age business models, and declining trust in corporations mean that the question of ‘who gains from work’ is now one which requires deep political, social, philosophical and academic debate. For the CIPD, this debate is central to our purpose of championing better work and working lives, and as such is an important one for the HR profession to take the lead in. This report examines how work generates value, and the capacity for organisations and individuals to benefit from work. In doing so, it highlights some real challenges and opportunities the HR profession faces when considering workplaces today. Creating value for financial stakeholders, employees and the community requires a balance which in many complex organisations is hard to reach. With this research we hope to highlight the challenge in understanding this balance, the business models and stakeholders involved, and the kinds of measures we can create to map the outcomes of work

Creating and Capturing Value at Work : Who Benefits? Part 2: Measurements Report

In Creating and Capturing Value at Work: Who benefits? Part 1, we made four key arguments 1. Value has to be considered as an integrated process, combining creation and capture. 2. The relationship between valuecreation and capture can be complex and varied, and cannot be ‘read off’ easily, located as it is in specific institutional, legal, governance and organisational contexts. 3. Notwithstanding the dominance of the maximising shareholder value (MSV) model, there is scope for strategic choices that mediate the relationship between value-creation and capture. 4. Disciplinary perspectives act as different lenses or prisms with which to view value and that reframing value from a multidisciplinary perspective has significant potential to improve our understanding of the value process and the scope for – and challenges in – exercising strategic choice to deliver value outcomes. In this follow-up report some of these key arguments are applied more concretely to measures or indicators of value. Measures of value can be narrow or broad. Value can also be measured at different levels. And measures of value can also appear to be – and be – inconsistent with each other. The idiom of ‘what gets measured gets managed’ is at one level true and yet can obscure costly, perverse and unintended consequences. Measures or indicators of value in businesses range from a relatively small number that are required by financial regulation and the vast array of measures collected in organisations at organisational, sub-unit and individual levels. Measures of value and costs of that value (that is, externalities) also exist at an extra-organisational level, for example at the level of the national or regional economy

Bright spots as climate‐smart marine spatial planning tools for conservation and blue growth

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Seismic structure across the rift valley of the Mid-Atlantic Ridge at 23°20′ (MARK area): Implications for crustal accretion processes at slow spreading ridges

International audienc

Early clinical development of artemether-lumefantrine dispersible tablet: palatability of three flavours and bioavailability in healthy subjects

BACKGROUND\ud \ud Efforts to ease administration and enhance acceptability of the oral anti-malarial artemether-lumefantrine (A-L) crushed tablet to infants and children triggered the development of a novel dispersible tablet of A-L. During early development of this new formulation, two studies were performed in healthy subjects, one to evaluate the palatability of three flavours of A-L, and a second one to compare the bioavailability of active principles between the dispersible tablet and the tablet (administered crushed and intact).\ud \ud METHODS\ud \ud Study 1 was performed in 48 healthy schoolchildren in Tanzania. Within 1 day, all subjects tasted a strawberry-, orange- and cherry-flavoured oral A-L suspension for 10 seconds (without swallowing) in a randomized, single-blind, crossover fashion. The palatability of each formulation was rated using a visual analogue scale (VAS). Study 2 was an open, randomized crossover trial in 48 healthy adults given single doses of A-L (80 mg artemether + 480 mg lumefantrine) with food. The objectives were to compare the bioavailability of artemether, dihydroartemisinin (DHA) and lumefantrine between the dispersible tablet and the tablet administered crushed (primary objective) and intact (secondary objective).\ud \ud RESULTS\ud \ud Study 1 showed no statistically significant difference in VAS scores between the three flavours but cherry had the highest score in several ratings (particularly for overall liking). Study 2 demonstrated that the dispersible and crushed tablets delivered bioequivalent artemether, DHA and lumefantrine systemic exposure (area under the curve [AUC]); mean ± SD AUC0-tlast were 208 ± 113 vs 195 ± 93 h.ng/ml for artemether, 206 ± 81 vs 199 ± 84 h.ng/ml for DHA and 262 ± 107 vs 291 ± 106 h x μg/ml for lumefantrine. Bioequivalence was also shown for peak plasma concentrations (Cmax) of DHA and lumefantrine. Compared with the intact tablet, the dispersible tablet resulted in bioequivalent lumefantrine exposure, but AUC and Cmax values of artemether and DHA were 20-35% lower.\ud \ud CONCLUSIONS\ud \ud Considering that cherry was the preferred flavour, and that the novel A-L dispersible tablet demonstrated similar pharmacokinetic performances to the tablet administered crushed, a cherry-flavoured A-L dispersible tablet formulation was selected for further development and testing in a large efficacy and safety study in African children with malaria

Genome-Wide Association Identifies Nine Common Variants Associated With Fasting Proinsulin Levels and Provides New Insights Into the Pathophysiology of Type 2 Diabetes

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10−8). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10−4), improved β-cell function (P = 1.1 × 10−5), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10−6). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk

To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10−8), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio