A life cycle assessment of recycled polypropylene fibre in concrete footpaths

This study assesses the environmental impact of four alternatives for reinforcing 100 m² of concrete footpath (Functional Unit, FU) by using cradle to gate life cycle assessment (LCA), based on the Australian context. Specifically, the four options considered are a) producing steel reinforcing mesh (SRM), b)producing virgin polypropylene (PP) fibre, c) recycling industrial PP waste and d) recycling domestic PP waste. The FU yields 364 kg of SRM (in a) and 40 kg of PP fibres (in b, c and d), necessary to achieve the same degree of reinforcing in concrete. All the activities required to produce these materials are considered in the study, namely manufacturing and transportation, and also recycling and reprocessing in the case of industrial and domestic recycled PP waste fibres. These processes are individually analysed and quantified in terms of material consumption, water use, and emissions into the environment. This allows for the impacts from producing recycled fibres to be compared with those from producing virgin PP fibre and SRM, which are traditionally used. The LCA results show that industrial recycled PP fibre offers important environmental benefits over virgin PP fibre. Specifically, the industrial recycled PP fibrecan save 50% of CO₂ equivalent, 65% of PO₄ equivalent, 29% of water and 78% of oil equivalent, compared to the virgin PP fibre. When compared to the SRM, the industrial recycled PP fibre can save 93% of CO₂ equivalent, 97% of PO₄ equivalent, 99% of water and 91% of oil equivalent. The domestic recycled PP fibre also generates reduced environmental impacts compared to virgin PP fibre, except for higher consumption of water associated with the washing processes

Shifting gears versus sudden stops: qualitative study of consultations about driving in patients with cognitive impairment

Objective General practitioners (GPs) report finding consultations on fitness to drive (FtD) in people with cognitive impairment difficult and potentially damaging to the physician–patient relationship. We aimed to explore GP and patient experiences to understand how the negative impacts associated with FtD consultations may be mitigated. Methods Individual qualitative interviews were conducted with GPs (n=12) and patients/carers (n=6) in Ireland. We recruited a maximum variation sample of GPs using criteria of length of time qualified, practice location and practice size. Patients with cognitive impairment were recruited via driving assessment services and participating general practices. Interviews were audio-recorded, transcribed and analysed thematically by the multidisciplinary research team using an approach informed by the framework method. Results The issue of FtD arose in consultations in two ways: introduced by GPs to proactively prepare patients for future driving cessation or by patients who urgently needed a medical report for an expiring driving license. The former strategy, implementable by GPs who had strong relational continuity with their patients, helped prevent crisis consultations from arising. The latter scenario became acrimonious if cognition had not been openly discussed with patients previously and was now potentially impacting on their right to drive. Patients called for greater clarity and empathy for the threat of driving cessation from their GPs. Conclusion GPs used their longitudinal relationship with cognitively impaired patients to reduce the potential for conflict in consultations on FtD. These efforts could be augmented by explicit discussion of cognitive impairment at an earlier stage for all affected patients. Patients would benefit from greater input into planning driving cessation and acknowledgement from their GPs of the impact this may have on their quality of life.Road Safety Authority of Irelan

Developing trauma-informed teacher education in England

Trauma-informed practice in education is an area of growing interest in England and internationally. Embracing trauma-informed practice in schools requires trauma and related content to be included in teacher education. Over a period of eight years, a short course was developed and incorporated into the teacher preparation programmes at a large university in England. Through methods of teacher educator self-study and autoethnography, we examine the process of the course’s development and identify mechanisms, enablers and barriers to change in the current policy context of teacher education in England. Important factors that supported change were the gradual development, external collaboration, positive outcomes as a warrant and source of motivation, the development of champions and enthusiasts for trauma-informed practice, and departmental leadership support. Barriers to the development were the constraints of prescribed content on initial teacher education courses, prevailing practices in some schools and settings, challenges in adapting material suitably for all education phases, and some beginning teachers’ responses to personally relevant course content. The successful introduction of the short course demonstrates that inclusion of trauma-informed content in initial teacher education is possible even in an unfavourable policy environment

Cost-effectiveness of donepezil and memantine in moderate to severe Alzheimer's disease (the DOMINO-AD trial).

OBJECTIVE: Most investigations of pharmacotherapy for treating Alzheimer's disease focus on patients with mild-to-moderate symptoms, with little evidence to guide clinical decisions when symptoms become severe. We examined whether continuing donepezil, or commencing memantine, is cost-effective for community-dwelling, moderate-to-severe Alzheimer's disease patients. METHODS: Cost-effectiveness analysis was based on a 52-week, multicentre, double-blind, placebo-controlled, factorial clinical trial. A total of 295 community-dwelling patients with moderate/severe Alzheimer's disease, already treated with donepezil, were randomised to: (i) continue donepezil; (ii) discontinue donepezil; (iii) discontinue donepezil and start memantine; or (iv) continue donepezil and start memantine. RESULTS: Continuing donepezil for 52 weeks was more cost-effective than discontinuation, considering cognition, activities of daily living and health-related quality of life. Starting memantine was more cost-effective than donepezil discontinuation. Donepezil-memantine combined is not more cost-effective than donepezil alone. CONCLUSIONS: Robust evidence is now available to inform clinical decisions and commissioning strategies so as to improve patients' lives whilst making efficient use of available resources. Clinical guidelines for treating moderate/severe Alzheimer's disease, such as those issued by NICE in England and Wales, should be revisited. © 2016 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd

Prognostic value of the 6-gene OncoMasTR test in hormone receptor–positive HER2-negative early-stage breast cancer: Comparative analysis with standard clinicopathological factors

Aim: The aim of the study was to assess the prognostic performance of a 6-gene molecular score (OncoMasTR Molecular Score [OMm]) and a composite risk score (OncoMasTR Risk Score [OM]) and to conduct a within-patient comparison against four routinely used molecular and clinicopathological risk assessment tools: Oncotype DX Recurrence Score, Ki67, Nottingham Prognostic Index and Clinical Risk Category, based on the modified Adjuvant! Online definition and three risk factors: patient age, tumour size and grade. Methods: Biospecimens and clinicopathological information for 404 Irish women also previously enrolled in the Trial Assigning Individualized Options for Treatment [Rx] were provided by 11 participating hospitals, as the primary objective of an independent translational study. Gene expression measured via RT-qPCR was used to calculate OMm and OM. The prognostic value for distant recurrence-free survival (DRFS) and invasive disease-free survival (IDFS) was assessed using Cox proportional hazards models and Kaplan-Meier analysis. All statistical tests were two-sided ones. Results: OMm and OM (both with likelihood ratio statistic [LRS] P Discussion: Both OncoMasTR scores were significantly prognostic for DRFS and IDFS and provided additional prognostic information to the molecular and clinicopathological risk factors/tools assessed. OM was also the most accurate risk classification tool for identifying DR. A concise 6-gene signature with superior risk stratification was shown to increase prognosis reliability, which may help clinicians optimise treatment decisions. Trial registration: ClinicalTrials.gov NCT02050750 NCT00310180.</p

Making knowledge visible: Using expert yellow pages to map capabilities in professional services firms

Accepted versio

Diversity oriented biosynthesis via accelerated evolution of modular gene clusters.

Erythromycin, avermectin and rapamycin are clinically useful polyketide natural products produced on modular polyketide synthase multienzymes by an assembly-line process in which each module of enzymes in turn specifies attachment of a particular chemical unit. Although polyketide synthase encoding genes have been successfully engineered to produce novel analogues, the process can be relatively slow, inefficient, and frequently low-yielding. We now describe a method for rapidly recombining polyketide synthase gene clusters to replace, add or remove modules that, with high frequency, generates diverse and highly productive assembly lines. The method is exemplified in the rapamycin biosynthetic gene cluster where, in a single experiment, multiple strains were isolated producing new members of a rapamycin-related family of polyketides. The process mimics, but significantly accelerates, a plausible mechanism of natural evolution for modular polyketide synthases. Detailed sequence analysis of the recombinant genes provides unique insight into the design principles for constructing useful synthetic assembly-line multienzymes

DOMINO-AD protocol: donepezil and memantine in moderate to severe Alzheimer's disease - a multicentre RCT.

BACKGROUND: Alzheimer's disease (AD) is the commonest cause of dementia. Cholinesterase inhibitors, such as donepezil, are the drug class with the best evidence of efficacy, licensed for mild to moderate AD, while the glutamate antagonist memantine has been widely prescribed, often in the later stages of AD. Memantine is licensed for moderate to severe dementia in AD but is not recommended by the England and Wales National Institute for Health and Clinical Excellence. However, there is little evidence to guide clinicians as to what to prescribe as AD advances; in particular, what to do as the condition progresses from moderate to severe. Options include continuing cholinesterase inhibitors irrespective of decline, adding memantine to cholinesterase inhibitors, or prescribing memantine instead of cholinesterase inhibitors. The aim of this trial is to establish the most effective drug option for people with AD who are progressing from moderate to severe dementia despite treatment with donepezil. METHOD: DOMINO-AD is a pragmatic, 15 centre, double-blind, randomized, placebo controlled trial. Patients with AD, currently living at home, receiving donepezil 10 mg daily, and with Standardized Mini-Mental State Examination (SMMSE) scores between 5 and 13 are being recruited. Each is randomized to one of four treatment options: continuation of donepezil with memantine placebo added; switch to memantine with donepezil placebo added; donepezil and memantine together; or donepezil placebo with memantine placebo. 800 participants are being recruited and treatment continues for one year. Primary outcome measures are cognition (SMMSE) and activities of daily living (Bristol Activities of Daily Living Scale). Secondary outcomes are non-cognitive dementia symptoms (Neuropsychiatric Inventory), health related quality of life (EQ-5D and DEMQOL-proxy), carer burden (General Health Questionnaire-12), cost effectiveness (using Client Service Receipt Inventory) and institutionalization. These outcomes are assessed at baseline, 6, 18, 30 and 52 weeks. All participants will be subsequently followed for 3 years by telephone interview to record institutionalization. DISCUSSION: There is considerable debate about the clinical and cost effectiveness of anti-dementia drugs. DOMINO-AD seeks to provide clear evidence on the best treatment strategies for those managing patients at a particularly important clinical transition point. TRIAL REGISTRATION: Current controlled trials ISRCTN49545035.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

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

The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb29