Thermophysical optimization of specialized concrete pavement materials for collection of surface heat energy and applications for shallow heat storage

There is great potential to use pavement structures to collect and/or store solar energy for the heating and cooling of adjacent buildings, e.g. airport terminals, shopping malls, etc. Therefore, pavement materials comprising both conventional and unconventional concrete mixtures with a wide range of densities, thermal conductivities, specific heat capacities, and thermal diffusivities were investigated. Their thermo-physical properties were then used as inputs to a one dimensional transient heat transport model in order to evaluate the temperature changes at the various depths at which heat might be abstracted or stored. The results indicated that a high diffusivity pavement, e.g. incorporating high conductive aggregates and/or metallic fibres, can significantly enhance heat transfer as well as reduction of thermal stresses across the concrete slab. On the other hand a low diffusivity concrete can induce a more stable temperature at shallower depth enabling easier heat storage in the pavement as well as helping to reduce the risk of damage due to freeze-thaw cycling in cold regions

A brave new world: the new normal for general practice after the COVID-19 pandemic

General practice in the UK transformed almost overnight in March 2020 in response to the COVID-19 pandemic. Practices largely shut their doors, face-to-face consultations almost exclusively became remote consultations, research evidence was implemented within days of being published, and much routine work postponed and labelled ‘non-essential’. As we settle into this (temporary) new way of working, we have a unique opportunity to reflect on our old and new working practices and decide what we should continue, change, and stop doing. Specifically, we consider what this ‘new normal’ could be in terms of remote consulting, practice re-organisation, use and implementation of evidence, advanced care planning, patient behaviour and chronic disease management, and implications for future practice, research, and policy

Acetate as a model for aspartate-based CXCR4 chemokine receptor binding of cobalt and nickel complexes of cross-bridged tetraazamacrocycles

A number of disease states including WHIM syndrome, HIV infection and cancer have been linked to the chemokine receptor CXCR4. High-affinity CXCR4 antagonist transition metal complexes of configurationally restricted bis-tetraazamacrocyclic ligands have been identified in previous studies. Recently synthesised and structurally characterised Co2+/Co3+ and Ni2+ acetate complexes of mono-macrocycle cross-bridged ligands have been used to mimic their known coordination interaction with the aspartate side chains on binding to CXCR4. Here, X-ray crystal structures for three Co2+/Co3+ acetate complexes and five Ni2+ acetate complexes are presented and demonstrate flexibility in the mode of binding to the acetate ligand concomitantly with the requisite cis-V-configured cross-bridged tetraazamacrocyle. Complexes of the smaller Co3+ metal ion exclusively bind acetate by chelating both oxygens of acetate. Larger Co2+ and Ni2+ metal ions in cross-bridged tetraazamacrocycles show a clear tendency to coordinate acetate in a monodentate fashion with a coordinated water molecule completing the octahedral coordination sphere. However, in unbridged tetraazamacrocycle acetate structures reported in the literature, the coordination preference is to chelate both acetate oxygens. We conclude that the short ethylene cross-bridge restricts the equatorial bulk of the macrocycle, prompting the metal ion to fill the equator with the larger monodentate acetate plus water ligand set. In unbridged ligand examples, the flexible macrocycle expands equatorially and generally only allows chelation of the sterically smaller acetate alone. These results provide insight for generation of optimised bis-macrocyclic CXCR4 antagonists utilising cobalt and nickel ions

Does a local financial incentive scheme reduce inequalities in the delivery of clinical care in a socially deprived community? A longitudinal data analysis.

BACKGROUND: Socioeconomic deprivation is associated with inequalities in health care and outcomes. Despite concerns that the Quality and Outcomes Framework pay-for-performance scheme in the UK would exacerbate inequalities in primary care delivery, gaps closed over time. Local schemes were promoted as a means of improving clinical engagement by addressing local health priorities. We evaluated equity in achievement of target indicators and practice income for one local scheme. METHODS: We undertook a longitudinal survey over four years of routinely recorded clinical data for all 83 primary care practices. Sixteen indicators were developed that covered five local clinical and public health priorities: weight management; alcohol consumption; learning disabilities; osteoporosis; and chlamydia screening. Clinical indicators were logit transformed from a percentage achievement scale and modelled allowing for clustering of repeated measures within practices. This enabled our study of target achievements over time with respect to deprivation. Practice income was also explored. RESULTS: Higher practice deprivation was associated with poorer performance for five indicators: alcohol use registration (OR 0.97; 95 % confidence interval 0.96,0.99); recorded chlamydia test result (OR 0.97; 0.94,0.99); osteoporosis registration (OR 0.98; 0.97,0.99); registration of repeat prednisolone prescription (OR 0.98; 0.96,0.99); and prednisolone registration with record of dual energy X-ray absorptiometry (DEXA) scan/referral (OR 0.92; 0.86,0.97); practices in deprived areas performed better for one indicator (registration of osteoporotic fragility fracture (OR 1.26; 1.04,1.51). The deprivation-achievement gap widened for one indicator (registered females aged 65-74 with a fracture referred for a DEXA scan; OR 0.97; 0.95,0.99). Two other indicators indicated a similar trend over two years before being withdrawn (registration of fragility fracture and over-75 s with a fragility fracture assessed and treated for osteoporosis risk). For one indicator the deprivation-achievement gap reduced over time (repeat prednisolone prescription (OR 1.01; 1.01,1.01). Larger practices and those serving more affluent areas earned more income per patient than smaller practices and those serving more deprived areas (t = -3.99; p =0.0001). CONCLUSIONS: Any gaps in achievement between practices were modest but mostly sustained or widened over the duration of the scheme. Given that financial rewards may not reflect the amount of work undertaken by practices serving more deprived patients, future pay-for-performance schemes also need to address fairness of rewards in relation to workload

The association of cold weather and all-cause and cause-specific mortality in the island of Ireland between 1984 and 2007

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.This article has been made available through the Brunel Open Access Publishing Fund.Background This study aimed to assess the relationship between cold temperature and daily mortality in the Republic of Ireland (ROI) and Northern Ireland (NI), and to explore any differences in the population responses between the two jurisdictions. Methods A time-stratified case-crossover approach was used to examine this relationship in two adult national populations, between 1984 and 2007. Daily mortality risk was examined in association with exposure to daily maximum temperatures on the same day and up to 6 weeks preceding death, during the winter (December-February) and cold period (October-March), using distributed lag models. Model stratification by age and gender assessed for modification of the cold weather-mortality relationship. Results In the ROI, the impact of cold weather in winter persisted up to 35 days, with a cumulative mortality increase for all-causes of 6.4% (95%CI=4.8%-7.9%) in relation to every 1oC drop in daily maximum temperature, similar increases for cardiovascular disease (CVD) and stroke, and twice as much for respiratory causes. In NI, these associations were less pronounced for CVD causes, and overall extended up to 28 days. Effects of cold weather on mortality increased with age in both jurisdictions, and some suggestive gender differences were observed. Conclusions The study findings indicated strong cold weather-mortality associations in the island of Ireland; these effects were less persistent, and for CVD mortality, smaller in NI than in the ROI. Together with suggestive differences in associations by age and gender between the two Irish jurisdictions, the findings suggest potential contribution of underlying societal differences, and require further exploration. The evidence provided here will hope to contribute to the current efforts to modify fuel policy and reduce winter mortality in Ireland

A brave new world: the new normal for general practice after the COVID-19 pandemic

This is the final version. Available on open access from the Royal College of General Practitioners via the DOI in this recordGeneral practice in the UK transformed almost overnight in March 2020 in response to the COVID-19 pandemic. Practices largely shut their doors, face-to-face consultations almost exclusively became remote consultations, research evidence was implemented within days of being published, and much routine work postponed and labelled ‘non-essential’. As we settle into this (temporary) new way of working, we have a unique opportunity to reflect on our old and new working practices and decide what we should continue, change, and stop doing. Specifically, we consider what this ‘new normal’ could be in terms of remote consulting, practice re-organisation, use and implementation of evidence, advanced care planning, patient behaviour and chronic disease management, and implications for future practice, research, and policy

Increased sensitivity of p53-deficient cells to anticancer agents due to loss of Pms2

A large fraction of human tumours carries mutations in the p53 gene. p53 plays a central role in controlling cell cycle checkpoint regulation, DNA repair, transcription, and apoptosis upon genotoxic stress. Lack of p53 function impairs these cellular processes, and this may be the basis of resistance to chemotherapeutic regimens. By virtue of the involvement of DNA mismatch repair in modulating cytotoxic pathways in response to DNA damaging agents, we investigated the effects of loss of Pms2 on the sensitivity to a panel of widely used anticancer agents in E1A/Ha-Ras-transformed p53-null mouse fibroblasts either proficient or deficient in Pms2. We report that lack of the Pms2 gene is associated with an increased sensitivity, ranging from 2–6-fold, to some types of anticancer agents including the topoisomerase II poisons doxorubicin, etoposide and mitoxantrone, the platinum compounds cisplatin and oxaliplatin, the taxanes docetaxel and paclitaxel, and the antimetabolite gemcitabine. In contrast, no change in sensitivity was found after treatment with 5-fluorouracil. Cell cycle analysis revealed that both, Pms2-deficient and -proficient cells, retain the ability to arrest at the G2/M upon cisplatin treatment. The data indicate that the concomitant loss of Pms2 function chemosensitises p53-deficient cells to some types of anticancer agents, that Pms2 positively modulates cell survival by mechanisms independent of p53, and that increased cytotoxicity is paralleled by increased apoptosis. Tumour-targeted functional inhibition of Pms2 may be a valuable strategy for increasing the efficacy of anticancer agents in the treatment of p53-mutant cancers

Variations in achievement of evidence-based, high-impact quality indicators in general practice : An observational study

BACKGROUND: There are widely recognised variations in the delivery and outcomes of healthcare but an incomplete understanding of their causes. There is a growing interest in using routinely collected 'big data' in the evaluation of healthcare. We developed a set of evidence-based 'high impact' quality indicators (QIs) for primary care and examined variations in achievement of these indicators using routinely collected data in the United Kingdom (UK). METHODS: Cross-sectional analysis of routinely collected, electronic primary care data from a sample of general practices in West Yorkshire, UK (n = 89). The QIs covered aspects of care (including processes and intermediate clinical outcomes) in relation to diabetes, hypertension, atrial fibrillation, myocardial infarction, chronic kidney disease (CKD) and 'risky' prescribing combinations. Regression models explored the impact of practice and patient characteristics. Clustering within practice was accounted for by including a random intercept for practice. RESULTS: Median practice achievement of the QIs ranged from 43.2% (diabetes control) to 72.2% (blood pressure control in CKD). Considerable between-practice variation existed for all indicators: the difference between the highest and lowest performing practices was 26.3 percentage points for risky prescribing and 100 percentage points for anticoagulation in atrial fibrillation. Odds ratios associated with the random effects for practices emphasised this; there was a greater than ten-fold difference in the likelihood of achieving the hypertension indicator between the lowest and highest performing practices. Patient characteristics, in particular age, gender and comorbidity, were consistently but modestly associated with indicator achievement. Statistically significant practice characteristics were identified less frequently in adjusted models. CONCLUSIONS: Despite various policy and improvement initiatives, there are enduring inappropriate variations in the delivery of evidence-based care. Much of this variation is not explained by routinely collected patient or practice variables, and is likely to be attributable to differences in clinical and organisational behaviour