Development and external validation study of a melanoma risk prediction model incorporating clinically assessed naevi and solar lentigines

Background: Melanoma risk prediction models could be useful for matching preventive interventions to patients’ risk. Objectives: To develop and validate a model for incident first‐primary cutaneous melanoma using clinically assessed risk factors. Methods: We used unconditional logistic regression with backward selection from the Australian Melanoma Family Study (461 cases and 329 controls) in which age, sex and city of recruitment were kept in each step, and we externally validated it using the Leeds Melanoma Case–Control Study (960 cases and 513 controls). Candidate predictors included clinically assessed whole‐body naevi and solar lentigines, and self‐assessed pigmentation phenotype, sun exposure, family history and history of keratinocyte cancer. We evaluated the predictive strength and discrimination of the model risk factors using odds per age‐ and sex‐adjusted SD (OPERA) and the area under curve (AUC), and calibration using the Hosmer–Lemeshow test. Results: The final model included the number of naevi ≥ 2 mm in diameter on the whole body, solar lentigines on the upper back (a six‐level scale), hair colour at age 18 years and personal history of keratinocyte cancer. Naevi was the strongest risk factor; the OPERA was 3·51 [95% confidence interval (CI) 2·71–4·54] in the Australian study and 2·56 (95% CI 2·23–2·95) in the Leeds study. The AUC was 0·79 (95% CI 0·76–0·83) in the Australian study and 0·73 (95% CI 0·70–0·75) in the Leeds study. The Hosmer–Lemeshow test P‐value was 0·30 in the Australian study and < 0·001 in the Leeds study. Conclusions: This model had good discrimination and could be used by clinicians to stratify patients by melanoma risk for the targeting of preventive interventions. What's already known about this topic? Melanoma risk prediction models may be useful in prevention by tailoring interventions to personalized risk levels. For reasons of feasibility, time and cost many melanoma prediction models use self‐assessed risk factors. However, individuals tend to underestimate their naevus numbers. What does this study add? We present a melanoma risk prediction model, which includes clinically‐assessed whole‐body naevi and solar lentigines, and self‐assessed risk factors including pigmentation phenotype and history of keratinocyte cancer. This model performs well on discrimination, the model's ability to distinguish between individuals with and without melanoma, and may assist clinicians to stratify patients by melanoma risk for targeted preventive interventions

Initial Results from the Royal College of Radiologists' UK National Audit of Anal Cancer Radiotherapy 2015

Aims: UK guidance was recently developed for the treatment of anal cancer using intensity-modulated radiotherapy (IMRT). We audited the current use of radiotherapy in UK cancer centres for the treatment of anal cancer against such guidance. We describe the acute toxicity of IMRT in comparison with patient population in the audit treated with two-phase conformal radiotherapy and the previous published data from two-phase conformal radiotherapy, in the UK ACT2 trial. Materials and methods: A Royal College of Radiologists' prospective national audit of patients treated with radiotherapy in UK cancer centres was carried out over a 6 month period between February and July 2015. Results: Two hundred and forty-two cases were received from 40/56 cancer centres (71%). In total, 231 (95%) underwent full dose radiotherapy with prophylactic nodal irradiation. Of these, 180 (78%) received IMRT or equivalent, 52 (22%) two-phase conformal (ACT2) technique. The number of interruptions in radiotherapy treatment in the ACT2 trial was 15%. Interruptions were noted in 7% (95% confidence interval 0–14%) of courses receiving two-phase conformal and 4% (95% confidence interval 1–7%) of those receiving IMRT. The percentage of patients completing the planned radiotherapy dose, irrelevant of gaps, was 90% (95% confidence interval 82–98%) and 96% (95% confidence interval 93–99%), in two-phase conformal and IMRT respectively. The toxicity reported in the ACT2 trial, in patients receiving two-phase conformal in the audit and in patients receiving IMRT in the audit was: any toxic effect 71%, 54%, 48%, non-haematological 62%, 49%, 40% and haematological 26%, 13%, 18%, respectively. Conclusions: IMRT implementation for anal cancer is well underway in the UK with most patients receiving IMRT delivery, although its usage is not yet universal. This audit confirms that IMRT results in reduced acute toxicity and minimised treatment interruptions in comparison with previous two-phase conformal techniques

Impact of Chlamydia trachomatis in the reproductive setting: British Fertility Society Guidelines for practice

Chlamydia trachomatis infection of the genital tract is the most common sexually transmitted infection and has a world-wide distribution. The consequences of infection have an adverse effect on the reproductive health of women and are a common cause of infertility. Recent evidence also suggests an adverse effect on male reproduction. There is a need to standardise the approach in managing the impact of C. trachomatis infection on reproductive health. We have surveyed current UK practice towards screening and management of Chlamydia infections in the fertility setting. We found that at least 90% of clinicians surveyed offered screening. The literature on this topic was examined and revealed a paucity of solid evidence for estimating the risks of long-term reproductive sequelae following lower genital tract infection with C. trachomatis. The mechanism for the damage that occurs after Chlamydial infections is uncertain. However, instrumentation of the uterus in women with C. trachomatis infection is associated with a high risk of pelvic inflammatory disease, which can be prevented by appropriate antibiotic treatment and may prevent infected women from being at increased risk of the adverse sequelae, such as ectopic pregnancy and tubal factor infertility. Recommendations for practice have been proposed and the need for further studies is identified

Integrating sequence and array data to create an improved 1000 Genomes Project haplotype reference panel

A major use of the 1000 Genomes Project (1000GP) data is genotype imputation in genome-wide association studies (GWAS). Here we develop a method to estimate haplotypes from low-coverage sequencing data that can take advantage of single-nucleotide polymorphism (SNP) microarray genotypes on the same samples. First the SNP array data are phased to build a backbone (or 'scaffold') of haplotypes across each chromosome. We then phase the sequence data 'onto' this haplotype scaffold. This approach can take advantage of relatedness between sequenced and non-sequenced samples to improve accuracy. We use this method to create a new 1000GP haplotype reference set for use by the human genetic community. Using a set of validation genotypes at SNP and bi-allelic indels we show that these haplotypes have lower genotype discordance and improved imputation performance into downstream GWAS samples, especially at low-frequency variants. © 2014 Macmillan Publishers Limited. All rights reserved

A calibration procedure for a coherent scattering matrix radar

Cover title reads 'A calibration procedure for a coherent polarimetric radar'SIGLEAvailable from British Library Document Supply Centre- DSC:5644.91(RSRE-M--3889) / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Preliminary experience with high response pressure measurements in a multistage, high speed compressor

Paper presented to 9. Int. Symp. on Measuring Techniques for Transonic and Supersonic Flows in Cascades and Turbomachines, Oxford (GB) Mar 1988SIGLEAvailable from British Library Document Supply Centre- DSC:8670.19(RAE-TM-P--1141) / BLDSC - British Library Document Supply CentreGBUnited Kingdo

The effect of dry period duration and dietary energy density on milk production, bioenergetic status and postpartum ovarian function in Holstein-Friesian dairy cows

Peer-reviewed.This is the author’s version of a work that was accepted for publication in Journal of Dairy Science. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Journal of Dairy Science, 92(12), Dec 2009. DOI: 10.3168/jds.2009-2374Following parturition, it is typical for dairy cows to enter a period of negative energy balance (NEB) and body condition loss to support mammary milk synthesis, and this is associated with compromised reproductive performance. Alternative management strategies during the prepartum (dry) and early post partum periods may ameliorate this. Forty mature Holstein-Friesian cows were assigned to one of two dry period treatments (standard 8 week dry period (SDP) or no planned dry period (NDP)) and one of two dietary energy density treatments (standard TMR (STMR) or high quality TMR (HTMR)). Milk yield during weeks 1 to 12 postpartum was reduced (P = 0.01) in cows assigned to the NDP treatment. Energy balance (P < 0.001) and body condition score (P = 0.07) during weeks 1 to 4 postpartum were increased in cows assigned to the NDP treatment compared to the cows assigned to the SDP, and BCS increased (P<0.001) from weeks 5 to 12 postpartum in the NDP cows compared to the SDP cows. During the first 12 weeks postpartum, cows assigned to the HTMR had greater (P = 0.02) milk yields and reduced (P < 0.001) milk fat concentration compared to the cows assigned the STMR diet. BCS was greater (P = 0.01) from weeks 5 to 12 postpartum in HTMR cows compared to STMR cows. During the period from weeks -3 to +3 relative to parturition, circulating concentrations of insulin (P = 0.001), glucose (P < 0.001) and IGF-I (P = 0.004) were greater in cows on the NDP treatment compared to cows on the SDP treatment. Cows assigned to the HTMR had greater circulating insulin (P = 0.04) and glucose (P = 0.001) concentrations compared to the STMR cows from weeks -3 to +3 relative to parturition. The first postpartum ovulation occurred earlier for cows on the NDP treatment compared to cows on the SDP treatment (16.9 vs. 24.8 days postpartum; P = 0.02). Cows assigned to the STMR tended to have a higher conception rate to first service (P = 0.07) compared to cows assigned to the HTMR. Energy balance and metabolic status can be improved by either eliminating the dry period or by feeding a higher energy diet, but effects on the reproductive axis appear to be different