Is carbon dioxide pricing a driver in concrete mix design?

The global cement industry is responsible for 7% of anthropogenic carbon dioxide emissions and, as such, has a vital role to play in the transition to a low carbon dioxide economy. In recent years, this has been achieved by technological advances and increased use of supplementary cementitious materials, but the authors have recently shown that there are other means of achieving comparable carbon dioxide savings, for example, by reducing workability. However, price remains a considerable barrier to the widespread implementation of low carbon dioxide concrete. Using the same model for concrete mix design as was used to determine embodied carbon dioxide (ECD), variations in the cost of the components of concrete have now been considered. Considering 24 different mix designs, each spanning a range of characteristic strengths from 20 to 100 MPa, measures to reduce the carbon dioxide footprint were also found to reduce the material cost of the concrete. As such, it may be considered that the construction industry is already encouraged to reduce its ‘carbon footprint’. However, the concept of the carbon footprint was then considered in a more nuanced fashion, considering the ECD per unit strength. On such a basis, the cheapest mixes did not have the lowest ECD. Therefore, the impact of levying a charge on the carbon footprint was considered. To ensure low carbon dioxide concrete is also the cheapest, carbon dioxide emissions would have to be priced approximately one to two orders of magnitude higher than current market value. This would become the dominant factor in construction, with serious consequences for the industry. Furthermore, such charges may pose ethical problems, being viewed as a ‘licence to pollute’ and therefore undermining society's efforts to reduce the carbon dioxide emissions of the construction industry

The providing resources to enhance African American patients' readiness to make decisions about kidney disease (PREPARED) study: protocol of a randomized controlled trial.

BACKGROUND: Living related kidney transplantation (LRT) is underutilized, particularly among African Americans. The effectiveness of informational and financial interventions to enhance informed decision-making among African Americans with end stage renal disease (ESRD) and improve rates of LRT is unknown. METHODS/DESIGN: We report the protocol of the Providing Resources to Enhance African American Patients' Readiness to Make Decisions about Kidney Disease (PREPARED) Study, a two-phase study utilizing qualitative and quantitative research methods to design and test the effectiveness of informational (focused on shared decision-making) and financial interventions to overcome barriers to pursuit of LRT among African American patients and their families. Study Phase I involved the evidence-based development of informational materials as well as a financial intervention to enhance African American patients' and families' proficiency in shared decision-making regarding LRT. In Study Phase 2, we are currently conducting a randomized controlled trial in which patients with new-onset ESRD receive 1) usual dialysis care by their nephrologists, 2) the informational intervention (educational video and handbook), or 3) the informational intervention in addition to the option of participating in a live kidney donor financial assistance program. The primary outcome of the randomized controlled trial will include patients' self-reported rates of consideration of LRT (including family discussions of LRT, patient-physician discussions of LRT, and identification of a LRT donor). DISCUSSION: Results from the PREPARED study will provide needed evidence on ways to enhance the decision to pursue LRT among African American patients with ESRD

Heritable patterns of tooth decay in the permanent dentition: principal components and factor analyses

<p>Abstract</p> <p>Background</p> <p>Dental caries is the result of a complex interplay among environmental, behavioral, and genetic factors, with distinct patterns of decay likely due to specific etiologies. Therefore, global measures of decay, such as the DMFS index, may not be optimal for identifying risk factors that manifest as specific decay patterns, especially if the risk factors such as genetic susceptibility loci have small individual effects. We used two methods to extract patterns of decay from surface-level caries data in order to generate novel phenotypes with which to explore the genetic regulation of caries.</p> <p>Methods</p> <p>The 128 tooth surfaces of the permanent dentition were scored as carious or not by intra-oral examination for 1,068 participants aged 18 to 75 years from 664 biological families. Principal components analysis (PCA) and factor analysis (FA), two methods of identifying underlying patterns without <it>a priori </it>surface classifications, were applied to our data.</p> <p>Results</p> <p>The three strongest caries patterns identified by PCA recaptured variation represented by DMFS index (correlation, r = 0.97), pit and fissure surface caries (r = 0.95), and smooth surface caries (r = 0.89). However, together, these three patterns explained only 37% of the variability in the data, indicating that <it>a priori </it>caries measures are insufficient for fully quantifying caries variation. In comparison, the first pattern identified by FA was strongly correlated with pit and fissure surface caries (r = 0.81), but other identified patterns, including a second pattern representing caries of the maxillary incisors, were not representative of any previously defined caries indices. Some patterns identified by PCA and FA were heritable (h²= 30-65%, p = 0.043-0.006), whereas other patterns were not, indicating both genetic and non-genetic etiologies of individual decay patterns.</p> <p>Conclusions</p> <p>This study demonstrates the use of decay patterns as novel phenotypes to assist in understanding the multifactorial nature of dental caries.</p

Cognitive–behavioural therapy compared with standardised medical care for adults with dissociative non-epileptic seizures: the CODES RCT

BACKGROUND: Dissociative (non-epileptic) seizures are potentially treatable by psychotherapeutic interventions; however, the evidence for this is limited. OBJECTIVES: To evaluate the clinical effectiveness and cost-effectiveness of dissociative seizure-specific cognitive-behavioural therapy for adults with dissociative seizures. DESIGN: This was a pragmatic, multicentre, parallel-arm, mixed-methods randomised controlled trial. SETTING: This took place in 27 UK-based neurology/epilepsy services, 17 liaison psychiatry/neuropsychiatry services and 18 cognitive-behavioural therapy services. PARTICIPANTS: Adults with dissociative seizures in the previous 8 weeks and no epileptic seizures in the previous year and meeting other eligibility criteria were recruited to a screening phase from neurology/epilepsy services between October 2014 and February 2017. After psychiatric assessment around 3 months later, eligible and interested participants were randomised between January 2015 and May 2017. INTERVENTIONS: Standardised medical care consisted of input from neurologists and psychiatrists who were given guidance regarding diagnosis delivery and management; they provided patients with information booklets. The intervention consisted of 12 dissociative seizure-specific cognitive-behavioural therapy 1-hour sessions (plus one booster session) that were delivered by trained therapists, in addition to standardised medical care. MAIN OUTCOME MEASURES: The primary outcome was monthly seizure frequency at 12 months post randomisation. The secondary outcomes were aspects of seizure occurrence, quality of life, mood, anxiety, distress, symptoms, psychosocial functioning, clinical global change, satisfaction with treatment, quality-adjusted life-years, costs and cost-effectiveness. RESULTS: In total, 698 patients were screened and 368 were randomised (standardised medical care alone, n = 182; and cognitive-behavioural therapy plus standardised medical care, n = 186). Primary outcome data were obtained for 85% of participants. An intention-to-treat analysis with multivariate imputation by chained equations revealed no significant between-group difference in dissociative seizure frequency at 12 months [standardised medical care: median of seven dissociative seizures (interquartile range 1-35 dissociative seizures); cognitive-behavioural therapy and standardised medical care: median of four dissociative seizures (interquartile range 0-20 dissociative seizures); incidence rate ratio 0.78, 95% confidence interval 0.56 to 1.09; p = 0.144]. Of the 16 secondary outcomes analysed, nine were significantly better in the arm receiving cognitive-behavioural therapy at a p-value < 0.05, including the following at a p-value ≤ 0.001: the longest dissociative seizure-free period in months 7-12 inclusive post randomisation (incidence rate ratio 1.64, 95% confidence interval 1.22 to 2.20; p = 0.001); better psychosocial functioning (Work and Social Adjustment Scale, standardised treatment effect -0.39, 95% confidence interval -0.61 to -0.18; p < 0.001); greater self-rated and clinician-rated clinical improvement (self-rated: standardised treatment effect 0.39, 95% confidence interval 0.16 to 0.62; p = 0.001; clinician rated: standardised treatment effect 0.37, 95% confidence interval 0.17 to 0.57; p < 0.001); and satisfaction with treatment (standardised treatment effect 0.50, 95% confidence interval 0.27 to 0.73; p < 0.001). Rates of adverse events were similar across arms. Cognitive-behavioural therapy plus standardised medical care produced 0.0152 more quality-adjusted life-years (95% confidence interval -0.0106 to 0.0392 quality-adjusted life-years) than standardised medical care alone. The incremental cost-effectiveness ratio (cost per quality-adjusted life-year) for cognitive-behavioural therapy plus standardised medical care versus standardised medical care alone based on the EuroQol-5 Dimensions, five-level version, and imputed data was £120,658. In sensitivity analyses, incremental cost-effectiveness ratios ranged between £85,724 and £206,067. Qualitative and quantitative process evaluations highlighted useful study components, the importance of clinical experience in treating patients with dissociative seizures and potential benefits of our multidisciplinary care pathway. LIMITATIONS: Unlike outcome assessors, participants and clinicians were not blinded to the interventions. CONCLUSIONS: There was no significant additional benefit of dissociative seizure-specific cognitive-behavioural therapy in reducing dissociative seizure frequency, and cost-effectiveness over standardised medical care was low. However, this large, adequately powered, multicentre randomised controlled trial highlights benefits of adjunctive dissociative seizure-specific cognitive-behavioural therapy for several clinical outcomes, with no evidence of greater harm from dissociative seizure-specific cognitive-behavioural therapy. FUTURE WORK: Examination of moderators and mediators of outcome. TRIAL REGISTRATION: Current Controlled Trials ISRCTN05681227 and ClinicalTrials.gov NCT02325544. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 43. See the NIHR Journals Library website for further project information

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Patients’ Perspectives of Oral and Injectable Type 2 Diabetes Medicines, Their Body Weight and Medicine-Taking Behavior in the UK: A Systematic Review and Meta-Ethnography

From Springer Nature via Jisc Publications Router.Publication status: PublishedHistory: received 2018-06-21, epub 2018-08-17, ppub 2018-10AbstractThe aim of this review is to identify peoples’ perspectives of their glucose-lowering and anti-obesity drugs in relation to diabetes and weight control and to explore how these views affect medication adherence. Theoretical perspectives associated with medicine-taking behavior are also explored. The systematic review was based on a meta-ethnography of qualitative studies identified through a search of 12 medical and social science databases and subsequent citation searches. The quality of all studies was assessed. Sixteen studies were included with data from 360 UK individuals. No relevant studies were identified which focused on anti-obesity and non-insulin injectable drugs. The review revealed that the patients’ perspectives and emotional state were influenced by starting and/or changing to a new glucose-lowering medicine. These were also influenced by prior medication experience, disease perceptions and interactions with clinicians. Despite reports of positive experiences with and positive perceptions of medicines, and of participation in strategies to regain life control, medication non-adherence was common. Accepting glucose-lowering medicines impacted on the individual’s perception of lifestyle changes, and it was notable that weight loss was not perceived as a strategy to support diabetes management. Synthesis revealed that more than one theory is required to explain medicine-taking behavior. New insights into the underlying factors of poor adherence and the specific practical issues identified in this review can help in the development of patient-centered interventions.Funding: Diabetes UK

A mutation in Nischarin causes otitis media via LIMK1 and NF-κB pathways

Otitis media (OM), inflammation of the middle ear (ME), is a common cause of conductive hearing impairment. Despite the importance of the disease, the aetiology of chronic and recurrent forms of middle ear inflammatory disease remains poorly understood. Studies of the human population suggest that there is a significant genetic component predisposing to the development of chronic OM, although the underlying genes are largely unknown. Using N-ethyl-N-nitrosourea mutagenesis we identified a recessive mouse mutant, edison, that spontaneously develops a conductive hearing loss due to chronic OM. The causal mutation was identified as a missense change, L972P, in the Nischarin (NISCH) gene. edison mice develop a serous or granulocytic effusion, increasingly macrophage and neutrophil rich with age, along with a thickened, inflamed mucoperiosteum. We also identified a second hypomorphic allele, V33A, with only modest increases in auditory thresholds and reduced incidence of OM. NISCH interacts with several proteins, including ITGA5 that is thought to have a role in modulating VEGF-induced angiogenesis and vascularization. We identified a significant genetic interaction between Nisch and Itga5; mice heterozygous for Itga5-null and homozygous for edison mutations display a significantly increased penetrance and severity of chronic OM. In order to understand the pathological mechanisms underlying the OM phenotype, we studied interacting partners to NISCH along with downstream signalling molecules in the middle ear epithelia of edison mouse. Our analysis implicates PAK1 and RAC1, and downstream signalling in LIMK1 and NF-κB pathways in the development of chronic OM