How to improve Drenchrite

Understanding the strengths and weaknesses of DrenchRite and how it relates to faecal egg count reduction tests (FECRT) will lead to clearer interpretation of DrenchRite results and a better perspective on both tests. In previous studies efficacy was estimated for worms resistant to BZ, LEV and BZILEV combinations by FECRT, DrenchRite and post mortem worm counts. Correlations of in vivo efficacy with FECRT determined by them were: Trichostrongylus colubriformis 88%, Ostertagia circumcincta 56% and Haemonchus contortus 69%. The low correlation for O. circumcincta was associated with the variability in estimating species composition when O. circumcincta was present at low levels. Correlations of DrenchRite with in vivo efficacy were: O. circumcincta 87%, T. colubriformis 82% and H. contortus 80%. The correlation between resistance determined by Larval Development Assay (LDA) and FECRT was not high at 61% (averaged over drugs and species). Similar data for Macrocyclic Lactones (ML) resistant worms are not yet available. Previous studies have shown for some LDA systems that eggs are more likely to be inhibited in development to L3s early (2-3 weeks post infection (PI)) and late (beyond 10 weeks PI) after infection and are most resilient to the effect of drugs at about 7 weeks PI. No systematic changes in DrenchRite results were observed over age of worm infection when tested weekly for 2 to 14 week old worms. Large bowel worms of sheep have not generally been examined under LDA conditions so a study was undertaken to determine the LD50s of susceptible Oesophagostomum columbianum (nodule worm) and Chabertia ovina (large mouthed bowel worm) on DrenchRite plates. LD50s for BZ and LEV were approximately 0.04 and 0.8 uM respectively for both worms. For the ML O. columbianum had a much higher LD50 (45 nM) than C. ovina (8 nM). In relation to the other common sheep worms, development characteristics of C. ovina in LDA is like H. contortus while O. columbianum is more like O. circumcincta. Both large bowel worms were very sensitive to BZILEV combinations, with LD50s 4 to 8 fold lower than those observed for H. contortus and O. circumcincta

Long-term effects of intensive glycemic and blood pressure control and fenofibrate use on kidney outcomes

Background and objectives In people with type 2 diabetes, aggressive control of glycemia, BP, and lipids have resulted in conflicting short-term (<5 years) kidney outcomes. We aimed to determine the long-term kidney effects of these interventions. Design, setting, participants, & measurements The Action to Control Cardiovascular Risk in Diabetes (ACCORD) was a multifactorial intervention study in people with type 2 diabetes at high risk for cardiovascular disease (n=10,251), to examine the effects of intensive glycemic control (hemoglobin A1c <6.0% versus 7%-7.9%), BP control (systolic BP <120 mm Hg versus <140 mm Hg) or fenofibrate versus placebo added to simvastatin on cardiovascular events and death. The glycemia trial lasted 3.7 years and participants were followed for another 6.5 years in ACCORDION, the ACCORD Follow-On Study. The post hoc primary composite kidney outcome was defined as incident macroalbuminuria, creatinine doubling, need for dialysis, or death by any cause. Cox proportional hazards regression estimated the effect of each intervention on the composite outcome and individual components. In secondary outcome analyses, competing risk regression was used to account for the risk of death in incident kidney outcomes. Analyses were adjusted for sociodemographics, randomization groups, and clinical factors. Results There were 988 cases of incident macroalbuminuria, 954 with doubling of creatinine, 351 requiring dialysis, and 1905 deaths. Hazard ratios (HRs) for the composite outcome with intensive glycemic, BP control, and fenofibrate use compared with standard therapy were 0.92 (95% confidence interval [95% CI], 0.86 to 0.98), 1.16 (95% CI, 1.05 to 1.28), and 1.16 (95% CI, 1.06 to 1.27). Multivariable, secondary outcome analyses showed that in the glycemia trial, only macroalbuminuria was significantly decreased (HR, 0.68; 95% CI, 0.59 to 0.77). In the BP and lipid trials, only creatinine doubling was affected (HR, 1.64; 95% CI, 1.30 to 2.06 and HR, 2.00; 95% CI, 1.61 to 2.49, respectively). Conclusions In people with type 2 diabetes at high risk for cardiovascular disease, intensive glycemic control may result in a long-term reduction in macroalbuminuria; however, intensive BP control and fenofibrates may increase the risk for adverse kidney events

RETurn to work After stroKE (RETAKE) Trial: protocol for a mixed-methods process evaluation using normalisation process theory

Objectives: This mixed-method process evaluation underpinned by normalisation process theory aims to measure fidelity to the intervention, understand the social and structural context in which the intervention is delivered and identify barriers and facilitators to intervention implementation. Setting: RETurn to work After stroKE (RETAKE) is a multicentre individual patient randomised controlled trial to determine whether Early Stroke Specialist Vocational Rehabilitation (ESSVR) plus usual care is a clinically and cost-effective therapy to facilitate return to work after stroke, compared with usual care alone. This protocol paper describes the embedded process evaluation. Participants and outcome measures: Intervention training for therapists will be observed and use of remote mentor support reviewed through documentary analysis. Fidelity will be assessed through participant questionnaires and analysis of therapy records, examining frequency, duration and content of ESSVR sessions. To understand the influence of social and structural contexts, the process evaluation will explore therapists' attitudes towards evidence-based practice, competency to deliver the intervention and evaluate potential sources of contamination. Longitudinal case studies incorporating non-participant observations will be conducted with a proportion of intervention and usual care participants. Semistructured interviews with stroke survivors, carers, occupational therapists, mentors, service managers and employers will explore their experiences as RETAKE participants. Analysis of qualitative data will draw on thematic and framework approaches. Quantitative data analysis will include regression models and descriptive statistics. Qualitative and quantitative data will be independently analysed by process evaluation and Clinical Trials Research Unit teams, respectively. Linked data, for example, fidelity and describing usual care will be synthesised by comparing and integrating quantitative descriptive data with the qualitative findings. Ethics and dissemination: Approval obtained through the East Midlands - Nottingham 2 Research Ethics Committee (Ref: 18/EM/0019) and the National Health ServiceResearch Authority. Dissemination via journal publications, stroke conferences, social media and meetings with national Stroke clinical leads. Trial registration number: ISRCTN12464275

TRY plant trait database – enhanced coverage and open access

Plant traits—the morphological, anatomical, physiological, biochemical and phenological characteristics of plants—determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits—almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Plant functional and taxonomic diversity in European grasslands along climatic gradients

Aim: European grassland communities are highly diverse, but patterns and drivers of their continental-scale diversity remain elusive. This study analyses taxonomic and functional richness in European grasslands along continental-scale temperature and precipitation gradients. Location: Europe. Methods: We quantified functional and taxonomic richness of 55,748 vegetation plots. Six plant traits, related to resource acquisition and conservation, were analysed to describe plant community functional composition. Using a null-model approach we derived functional richness effect sizes that indicate higher or lower diversity than expected given the taxonomic richness. We assessed the variation in absolute functional and taxonomic richness and in functional richness effect sizes along gradients of minimum temperature, temperature range, annual precipitation, and precipitation seasonality using a multiple general additive modelling approach. Results: Functional and taxonomic richness was high at intermediate minimum temperatures and wide temperature ranges. Functional and taxonomic richness was low in correspondence with low minimum temperatures or narrow temperature ranges. Functional richness increased and taxonomic richness decreased at higher minimum temperatures and wide annual temperature ranges. Both functional and taxonomic richness decreased with increasing precipitation seasonality and showed a small increase at intermediate annual precipitation. Overall, effect sizes of functional richness were small. However, effect sizes indicated trait divergence at extremely low minimum temperatures and at low annual precipitation with extreme precipitation seasonality. Conclusions: Functional and taxonomic richness of European grassland communities vary considerably over temperature and precipitation gradients. Overall, they follow similar patterns over the climate gradients, except at high minimum temperatures and wide temperature ranges, where functional richness increases and taxonomic richness decreases. This contrasting pattern may trigger new ideas for studies that target specific hypotheses focused on community assembly processes. And though effect sizes were small, they indicate that it may be important to consider climate seasonality in plant diversity studies

How to improve Drenchrite

Understanding the strengths and weaknesses of DrenchRite and how it relates to faecal egg count reduction tests (FECRT) will lead to clearer interpretation of DrenchRite results and a better perspective on both tests. In previous studies efficacy was estimated for worms resistant to BZ, LEV and BZILEV combinations by FECRT, DrenchRite and post mortem worm counts. Correlations of in vivo efficacy with FECRT determined by them were: Trichostrongylus colubriformis 88%, Ostertagia circumcincta 56% and Haemonchus contortus 69%. The low correlation for O. circumcincta was associated with the variability in estimating species composition when O. circumcincta was present at low levels. Correlations of DrenchRite with in vivo efficacy were: O. circumcincta 87%, T. colubriformis 82% and H. contortus 80%. The correlation between resistance determined by Larval Development Assay (LDA) and FECRT was not high at 61% (averaged over drugs and species). Similar data for Macrocyclic Lactones (ML) resistant worms are not yet available. Previous studies have shown for some LDA systems that eggs are more likely to be inhibited in development to L3s early (2-3 weeks post infection (PI)) and late (beyond 10 weeks PI) after infection and are most resilient to the effect of drugs at about 7 weeks PI. No systematic changes in DrenchRite results were observed over age of worm infection when tested weekly for 2 to 14 week old worms. Large bowel worms of sheep have not generally been examined under LDA conditions so a study was undertaken to determine the LD50s of susceptible Oesophagostomum columbianum (nodule worm) and Chabertia ovina (large mouthed bowel worm) on DrenchRite plates. LD50s for BZ and LEV were approximately 0.04 and 0.8 uM respectively for both worms. For the ML O. columbianum had a much higher LD50 (45 nM) than C. ovina (8 nM). In relation to the other common sheep worms, development characteristics of C. ovina in LDA is like H. contortus while O. columbianum is more like O. circumcincta. Both large bowel worms were very sensitive to BZILEV combinations, with LD50s 4 to 8 fold lower than those observed for H. contortus and O. circumcincta

Breast cancer cell line proliferation blocked by the Src-related Rak tyrosine kinase

10.1002/ijc.10925International Journal of Cancer1042139-146IJCN