Galgo: a bi-objective evolutionary meta-heuristic identifies robust transcriptomic classifiers associated with patient outcome across multiple cancer types.

MOTIVATION: Statistical and machine-learning analyses of tumor transcriptomic profiles offer a powerful resource to gain deeper understanding of tumor subtypes and disease prognosis. Currently, prognostic gene-expression signatures do not exist for all cancer types, and most developed to date have been optimized for individual tumor types. In Galgo, we implement a bi-objective optimization approach that prioritizes gene signature cohesiveness and patient survival in parallel, which provides greater power to identify tumor transcriptomic phenotypes strongly associated with patient survival. RESULTS: To compare the predictive power of the signatures obtained by Galgo with previously studied subtyping methods, we used a meta-analytic approach testing a total of 35 large population-based transcriptomic biobanks of four different cancer types. Galgo-generated colorectal and lung adenocarcinoma signatures were stronger predictors of patient survival compared to published molecular classification schemes. One Galgo-generated breast cancer signature outperformed PAM50, AIMS, SCMGENE and IntClust subtyping predictors. In high-grade serous ovarian cancer, Galgo signatures obtained similar predictive power to a consensus classification method. In all cases, Galgo subtypes reflected enrichment of gene sets related to the hallmarks of the disease, which highlights the biological relevance of the partitions found. AVAILABILITY AND IMPLEMENTATION: The open-source R package is available on www.github.com/harpomaxx/galgo. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Commissioning for COPD care: a new, recordable metric that supports the patient interest.

BACKGROUND: Healthcare metrics have been used to drive improvement in outcome and delivery in UK hospital stroke and cardiac care. This model is attractive for chronic obstructive pulmonary disease (COPD) care because of disease frequency and the burden it places on primary, secondary and integrated care services. METHODS: Using 'hospital episode statistics' (UK 'coding'), we examined hospital 'bed days/1000 population' in 150 UK Primary Care Trusts (PCTs) during 2006-07 and 2007-08. Data were adjusted for COPD prevalence. We looked at year-on-year consistency and factors which influenced variation. RESULTS: There were 248 996 COPD admissions during 2006-08. 'Bed days/1000 PCT population' was consistent between years (r = 0.87; P < 0.001). There was a >2-fold difference in bed days between the best and worst performing PCTs which was primarily a consequence of variation in emergency admission rate (P < 0.001) and proportion of emergency admissions due to COPD (P < 0.001) and to only a lesser extent length of hospital stay (P < 0.001). CONCLUSIONS: Bed days/1000 population appears a useful annual metric of COPD care quality. Good COPD care keeps patients active and out of hospital and requires co-ordinated action from both hospital and community services, with an important role for integrated care. This metric demonstrates that current care is highly variable and offers a measurable target to commission against.

Lifestyle and health factors associated with progressing and remitting trajectories of untreated lower urinary tract symptoms among elderly men.

BACKGROUND: Knowledge of factors associated with the course of lower urinary tract symptoms (LUTS) before treatment is needed to inform preventive interventions. In a prospective study of elderly men untreated for LUTS, we identified factors associated with symptom progression and remission. METHODS: In community-dwelling US men aged ≥65 years, the American Urological Association Symptom Index (AUA-SI) was repeated four times, once at baseline (2000-2002) and then every 2 years thereafter. Analyses included 1740 men with all four AUA-SI assessments, who remained free from diagnosed prostate cancer, and who reported no treatment for LUTS or BPH during follow-up that averaged 6.9 (±0.4) years. LUTS change was determined with group-based trajectory modelingof the repeated AUA-SI measures. Multivariable logistic regression was then used to determine the baseline factors associated with progressing compared with stable trajectories, and with remitting compared with progressing trajectories. Lifestyle, body mass index (BMI) (kg/m(2)), mobility, mental health (Short-Form 12), medical history and prescription medications were considered for selection. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for variables in each model. RESULTS: We identified 10 AUA-SI trajectories: 4 stable (1277 men, 73%), three progressing (345 men, 20%), two remitting (98 men, 6%) and one mixed (20 men, 1%). Men in progressing compared with stable trajectories were more likely to have mobility limitations (OR=2.0, 95% CI: 1.0-3.8), poor mental health (OR=1.9, 95% CI: 1.1-3.4), BMI≥25.0 kg m(-2) (OR=1.7, 95% CI: 1.0-2.8), hypertension (OR=1.5, 95% CI: 1.0-2.4) and back pain (OR=1.5, 95% CI: 1.0-2.4). Men in remitting compared with progressing trajectories more often used central nervous system medications (OR=2.3, 95% CI: 1.1-4.9) and less often had a history of problem drinking (OR=0.4, 95% CI: 0.2-0.9). CONCLUSIONS: Several non-urological lifestyle and health factors were independently associated with risk of LUTS progression in older men.

Use of mortality within 30 days of a COPD hospitalisation as a measure of COPD care in UK hospitals.

Mortality rate has been proposed as a metric of hospital chronic obstructive pulmonary disease (COPD) care in light of variation seen in national COPD audits. Using Hospital Episode Statistics (hospital 'coding') we examined 30-day mortality after COPD hospitalisation in 150 UK hospitals during 2006-2007 and 2007-2008. Mean and median 30-day mortalities were similar each year but the coefficient of variation was >20% and hospitals could change from a low or high quartile to the median by chance. We could not detect any reasons for hospitals being at the extremes. 30-day mortality after COPD hospitalisation is a complex variable and unlikely to be useful as a primary annual COPD metric.

Abdominal body composition measured by quantitative computed tomography and risk of non-spine fractures: the Osteoporotic Fractures in Men (MrOS) Study.

UNLABELLED: The effect of abdominal adiposity and muscle on fracture is unclear in older men; therefore, we examined the association among 749 men aged 65+. Among various adipose tissues and muscle groups, lower psoas muscle volume and higher fatty infiltration of abdominal muscle contribute to higher fracture risk independent of BMD. INTRODUCTION: The association of abdominal adiposity and muscle composition with incident fracture is unclear, especially in older men. Therefore, we examined the relationship of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), abdominal intermuscular adipose tissue (IMAT), and muscle volume with incident non-spine fractures among 749 men aged 65 and older. METHODS: A case-cohort study design was used with a total of 252 fracture cases and 497 non-cases. We measured volumes (in centimeters) of adipose and muscle tissues obtained from quantitative computed tomography scan at the L4-5 intervertebral space. Three groups of muscle and IMAT were evaluated: total abdominal, psoas, and paraspinal. Cox proportional hazards regression with a robust variance estimator was used to estimate the hazard ratio (HR) of non-spine fractures per standard deviation (SD) increase in the abdominal body composition measures. The mean age among men in the random subcohort was 74.2 ± 6.1 years, and the average follow-up time was 5.2 ± 1.1 years. RESULTS: After adjusting for age, race, clinic site, percent body fat, and femoral neck bone mineral density (BMD), no significant relationship was found between incident fractures and SAT or VAT. One SD increase in muscle volume at the psoas, but not paraspinal, was associated with 28 % lower fracture risk (95 % CI = 0.55-0.95). When IMAT models were further adjusted for corresponding muscle volumes, only abdominal IMAT was significantly associated with fracture risk (HR = 1.30 (95 % CI = 1.04-1.63)). CONCLUSION: Our findings suggest that lower total psoas muscle volume and higher IMAT of the total abdominal muscle contribute to higher fracture risk in older men independent of BMD.

A comparison of live and destructive sampling methods of determining the size of a parasitic tick populations.

The accuracy of a general and a specific method of collecting and counting ixodid ticks on live hosts was compared with that of a destructive technique which can only be applied to dead animals. Destructive sampling provided considerably more accurate results than either of the live sampling methods when applied to domestic goats (Capra hircus) and a duiker (Sylvicapra grimmia). The smaller the life stage and the tick species the less likely it is that it will be recovered by either of the live sampling techniques. Both live and destructive sampling yielded similar results for adult Amblyomma hebraeum, a large tick. A sub-sampling method, used to estimate larval numbers, was repeatable and an accurate predictor of population size for populations ranging from 50 to 1000 of unengorged A. hebraeum larvae.

Total contact povidone-iodine perfusion cast for the treatment of neuropathic ulcers.

The total contact povidone-iodine perfusion cast is an effective, conservative treatment for the neuropathic ulcer. This is accomplished by redistribution of forces exerted on the foot, as well as the antiseptic environment established by the povidone-iodine. The case study presented demonstrates a cost-effective treatment for the diabetic neuropathic ulcer.