Host phenotype characteristics and MC1R in relation to early-onset basal cell carcinoma.

Basal cell carcinoma (BCC) incidence is increasing, particularly among adults under the age of 40 years. Pigment-related characteristics are associated with BCC in older populations, but epidemiologic studies among younger individuals and analyses of phenotype-genotype interactions are limited. We examined self-reported phenotypes and melanocortin 1 receptor gene (MC1R) variants in relation to early-onset BCC. BCC cases (n=377) and controls with benign skin conditions (n=390) under the age of 40 years were identified through Yale's Dermatopathology database. Factors most strongly associated with early-onset BCC were skin reaction to first summer sun for 1 hour (severe sunburn vs. tan odds ratio (OR)=12.27, 95% confidence interval (CI)=4.08-36.94) and skin color (very fair vs. olive OR=11.06, 95% CI=5.90-20.74). Individuals with two or more MC1R non-synonymous variants were 3.59 times (95% CI=2.37-5.43) more likely to have BCC than those without non-synonymous variants. All host characteristics and MC1R were more strongly associated with multiple BCC case status (37% of cases) than a single BCC case status. MC1R, number of moles, skin reaction to first summer sun for 1 hour, and hair and skin color were independently associated with BCC. BCC risk conferred by MC1R tended to be stronger among those with darker pigment phenotypes, traditionally considered to be at low risk of skin cancer

Which strategies support the effective use of clinical practice guidelines and clinical quality registry data to inform health service delivery? A systematic review

Background Empirical evidence suggests data and insights from the clinical practice guidelines and clinical quality registries are not being fully utilised, leaving health service managers, clinicians and providers without clear guidance on how best to improve healthcare delivery. This lack of uptake of existing research knowledge represents low value to the healthcare system and needs to change. Methods Five electronic databases (MEDLINE, Embase, CINAHL, Cochrane Central and Cochrane Database of Systematic Reviews) were systematically searched. Included studies were published between 2000 and 2020 reporting on the attributes, evidence usage and impact of clinical practice guidelines and clinical quality registries on health service delivery. Results Twenty-six articles including one randomised controlled trial, eight before-and-after studies, eight case studies/reviews, five surveys and four interview studies, covering a wide range of medical conditions and conducted in the USA, Australia and Europe, were identified. Five complementary strategies were derived to maximise the likelihood of best practice health service delivery: (1) feedback and transparency, (2) intervention sustainability, (3) clinical practice guideline adherence, (4) productive partnerships and (5) whole-of-team approach. Conclusion These five strategies, used in context-relevant combinations, are most likely to support the application of existing high-quality data, adding value to health service delivery. The review highlighted the limitations of study design in opportunistic registry studies that do not produce clear, usable evidence to guide changes to health service implementation practices. Recommendations include exploration of innovative methodologies, improved coordination of national registries and the use of incentives to encourage guideline adherence and wider dissemination of strategies used by successful registries

Gravitational waves, black holes and cosmic strings in cylindrical symmetry

Gravitational waves in cylindrically symmetric Einstein gravity are described by an effective energy tensor with the same form as that of a massless Klein- Gordon field, in terms of a gravitational potential generalizing the Newtonian potential. Energy-momentum vectors for the gravitational waves and matter are defined with respect to a canonical flow of time. The combined energy-momentum is covariantly conserved, the corresponding charge being the modified Thorne energy. Energy conservation is formulated as the first law expressing the gradient of the energy as work and energy-supply terms, including the energy flux of the gravitational waves. Projecting this equation along a trapping horizon yields a first law of black-hole dynamics containing the expected term involving area and surface gravity, where the dynamic surface gravity is defined with respect to the canonical flow of time. A first law for dynamic cosmic strings also follows. The Einstein equation is written as three wave equations plus the first law, each with sources determined by the combined energy tensor of the matter and gravitational waves.Comment: 10 pages, revtex. Published version with further detail

Second primary cancer risk - the impact of applying different definitions of multiple primaries: results from a retrospective population-based cancer registry study

Background: There is evidence that cancer survivors are at increased risk of second primary cancers. Changes in the prevalence of risk factors and diagnostic techniques may have affected more recent risks.<p></p> Methods: We examined the incidence of second primary cancer among adults in the West of Scotland, UK, diagnosed with cancer between 2000 and 2004 (n = 57,393). We used National Cancer Institute Surveillance Epidemiology and End Results and International Agency for Research on Cancer definitions of multiple primary cancers and estimated indirectly standardised incidence ratios (SIR) with 95% confidence intervals (CI).<p></p> Results: There was a high incidence of cancer during the first 60 days following diagnosis (SIR = 2.36, 95% CI = 2.12 to 2.63). When this period was excluded the risk was not raised, but it was high for some patient groups; in particular women aged <50 years with breast cancer (SIR = 2.13, 95% CI = 1.58 to 2.78), patients with bladder (SIR = 1.41, 95% CI = 1.19 to 1.67) and head & neck (SIR = 1.93, 95% CI = 1.67 to 2.21) cancer. Head & neck cancer patients had increased risks of lung cancer (SIR = 3.75, 95% CI = 3.01 to 4.62), oesophageal (SIR = 4.62, 95% CI = 2.73 to 7.29) and other head & neck tumours (SIR = 6.10, 95% CI = 4.17 to 8.61). Patients with bladder cancer had raised risks of lung (SIR = 2.18, 95% CI = 1.62 to 2.88) and prostate (SIR = 2.41, 95% CI = 1.72 to 3.30) cancer.<p></p> Conclusions: Relative risks of second primary cancers may be smaller than previously reported. Premenopausal women with breast cancer and patients with malignant melanomas, bladder and head & neck cancers may benefit from increased surveillance and advice to avoid known risk factors

Annulated Dialkoxybenzenes as Catholyte Materials for Non‐aqueous Redox Flow Batteries: Achieving High Chemical Stability through Bicyclic Substitution

1,4‐Dimethoxybenzene derivatives are materials of choice for use as catholytes in non‐aqueous redox flow batteries, as they exhibit high open‐circuit potentials and excellent electrochemical reversibility. However, chemical stability of these materials in their oxidized form needs to be improved. Disubstitution in the arene ring is used to suppress parasitic reactions of their radical cations, but this does not fully prevent ring‐addition reactions. By incorporating bicyclic substitutions and ether chains into the dialkoxybenzenes, a novel catholyte molecule, 9,10‐bis(2‐methoxyethoxy)‐1,2,3,4,5,6,7,8‐octahydro‐1,4:5,8‐dimethanenoanthracene (BODMA), is obtained and exhibits greater solubility and superior chemical stability in the charged state. A hybrid flow cell containing BODMA is operated for 150 charge–discharge cycles with a minimal loss of capacity.A novel bicyclical substituted dialkoxy‐benzene molecule, 9,10‐bis(2‐methoxy‐ethoxy)‐1,2,3,4,5,6,7,8‐octahydro‐1,4:5,8‐dimethanenoanthracene (BODMA), is developed for use as catholyte materials in non‐aqueous redox flow batteries with greater solubility (in their neutral state) and improved chemical stability (in their charged state). A hybrid flow cell using BODMA demonstrates stable efficiencies and capacity over 150 cycles. The molecular design approach of BODMA can be inspirational for future development of redox active molecules.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139992/1/aenm201701272.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139992/2/aenm201701272-sup-0001-S1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139992/3/aenm201701272_am.pd

The role of collaboration in the UK green supply chains: an exploratory study of the perspectives of suppliers, logistics and retailers

Many companies around the world have started to realise that working alone will not be sufficient in their move towards a greener supply chain (SC). More specifically, recent UK government regulations on implementing strict CO2 reduction encourage SC operators to work collaboratively, in production and logistics or other operations, to achieve their green objectives. In this research, we look at some underlying factors of SC collaboration, focussing on suppliers, logistics and retailers, for the purpose of improving the environmental sustainability of companies’ SCs. To facilitate our study, we conduct case studies in two overseas supplier companies with the aim of providing a better understanding of how green issues imposed by European and UK customers influence the companies’ actions to meet agreed environmental goals. Based on the initial analysis of the case studies, we develop a conceptual framework which indicates that SC collaboration plays an important role in ensuring companies achieve environmental sustainability of their SCs. Subsequently, staff in middle-management and related roles in sixteen companies operating in the UK are interviewed. This allows us to understand their business practices in terms of SC collaboration with their suppliers and buyers to achieve the goal of CO2 reduction. Finally, drawing upon the information from company reports and websites, a number of UK leading retailers’ actions to reduce CO2 emissions are investigated. We develop a conceptual framework of SC collaboration for environmental sustainability to help companies improve their level of collaboration between suppliers and buyers in terms of meeting their environmental objectives. The proposed framework will serve as a base model for the companies using or considering SC collaboration to achieve their environmental agendas, in line with governmental green regulatory requirements

The effects of benzofury (5-APB) on the dopamine transporter and 5-HT2-dependent vasoconstriction in the rat

5-APB, commonly marketed as ‘benzofury’ is a new psychoactive substance and erstwhile ‘legal high’ which has been implicated in 10 recent drug-related deaths in the UK. This drug was available on the internet and in ‘head shops’ and was one of the most commonly sold legal highs up until its recent UK temporary ban (UK Home Office). Despite its prominence, very little is known about its pharmacology. This study was undertaken to examine the pharmacology of 5-APB in vitro. We hypothesized that 5-APB would activate the dopamine and 5-HT systems which may underlie its putative stimulant and hallucinogenic effects. Autoradiographic studies showed that 5-APB displaced both [125I]RTI-121 and [3H]ketanserin from rat brain tissue suggesting affinity at the dopamine transporter and 5-HT2 receptor sites respectively. Voltammetric studies in rat accumbens brain slices revealed that 5-APB slowed dopamine reuptake, and at high concentrations caused reverse transport of dopamine. 5-APB also caused vasoconstriction of rat aorta, an effect antagonized by the 5-HT2A receptor antagonist ketanserin, and caused contraction of rat stomach fundus, which was reversed by the 5-HT2B receptor antagonist RS-127445. These data show that 5-APB interacts with the dopamine transporter and is an agonist at the 5-HT2A and 5-HT2B receptors in the rat. Thus 5-APB’s pharmacology is consistent with it having both stimulant and hallucinogenic properties. In addition, 5-APB’s activity at the 5-HT2B receptor may cause cardiotoxicity

Cord blood calcium, phosphate, magnesium, and alkaline phosphatase gestational age-specific reference intervals for preterm infants

<p>Abstract</p> <p>Background</p> <p>The objective was to determine the influence of gestational age, maternal, and neonatal variables on reference intervals for cord blood bone minerals (calcium, phosphate, magnesium) and related laboratory tests (alkaline phosphatase, and albumin-adjusted calcium), and to develop gestational age specific reference intervals based on infants without influential pathological conditions.</p> <p>Methods</p> <p>Cross-sectional study. 702 babies were identified as candidates for this study in a regional referral neonatal unit. After exclusions (for anomalies, asphyxia, maternal magnesium sulfate administration, and death), relationships were examined between cord blood serum laboratory analytes (calcium, phosphate, magnesium, alkaline phosphatase, and albumin-adjusted calcium) with gestation age and also with maternal and neonatal variables using multiple linear regression. Infants with influential pathological conditions were omitted from the development of gestational age specific reference intervals for the following categories: 23-27, 28-31, 32-34, 35-36 and > 36 weeks.</p> <p>Results</p> <p>Among the 506 preterm and 54 terms infants included in the sample. Phosphate, magnesium, and alkaline phosphatase in cord blood serum decreased with gestational age, calcium increased with gestational age. Those who were triplets, small for gestational age, and those whose mother had pregnancy-induced hypertension were influential for most of the analytes. The reference ranges for the preterm infants ≥ 36 weeks were: phosphate 1.5 to 2.6 mmol/L (4.5 to 8.0 mg/dL), calcium: 2.1 to 3.1 mmol/L (8.3 to 12.4 mg/dL); albumin-adjusted calcium: 2.3 to 3.2 mmol/L (9.1 to 12.9 mg/dL); magnesium 0.6 to 1.0 mmol/L (1.4 to 2.3 mg/dL), and alkaline phosphatase 60 to 301 units/L.</p> <p>Conclusions</p> <p>These data suggest that gestational age, as well as potentially pathogenic maternal and neonatal variables should be considered in the development of reference intervals for preterm infants.</p