ASCORE: an up-to-date cardiovascular risk score for hypertensive patients reflecting contemporary clinical practice developed using the (ASCOT-BPLA) trial data.

A number of risk scores already exist to predict cardiovascular (CV) events. However, scores developed with data collected some time ago might not accurately predict the CV risk of contemporary hypertensive patients that benefit from more modern treatments and management. Using data from the randomised clinical trial Anglo-Scandinavian Cardiac Outcomes Trial-BPLA, with 15 955 hypertensive patients without previous CV disease receiving contemporary preventive CV management, we developed a new risk score predicting the 5-year risk of a first CV event (CV death, myocardial infarction or stroke). Cox proportional hazard models were used to develop a risk equation from baseline predictors. The final risk model (ASCORE) included age, sex, smoking, diabetes, previous blood pressure (BP) treatment, systolic BP, total cholesterol, high-density lipoprotein-cholesterol, fasting glucose and creatinine baseline variables. A simplified model (ASCORE-S) excluding laboratory variables was also derived. Both models showed very good internal validity. User-friendly integer score tables are reported for both models. Applying the latest Framingham risk score to our data significantly overpredicted the observed 5-year risk of the composite CV outcome. We conclude that risk scores derived using older databases (such as Framingham) may overestimate the CV risk of patients receiving current BP treatments; therefore, 'updated' risk scores are needed for current patients

Comparing the Effect of Concept Mapping and Conventional Methods on Nursing Students' Practical Skill Score

Background: Development of practical skills in the field of nursing education has remained a serious and considerable challenge in nursing education. Moreover, newly graduated nurses may have weak practical skills, which can be a threat to patients’ safety. Objectives: The present study was conducted to compare the effect of concept mapping and conventional methods on nursing students’ practical skills. Patients and Methods: This quasi-experimental study was conducted on 70 nursing students randomly assigned into two groups of 35 people. The intervention group was taught through concept mapping method, while the control group was taught using conventional method. A two-part instrument was used including a demographic information form and a checklist for direct observation of procedural skills. Descriptive statistics, chi-square, independent samples t-tests and paired t-test were used to analyze data. Results: Before education, no significant differences were observed between the two groups in the three skills of cleaning (P = 0.251), injection (P = 0.185) and sterilizing (P = 0.568). The students mean scores were significantly increased after the education and the difference between pre and post intervention of students mean scores were significant in the both groups (P < 0.001). However, after education, in all three skills the mean scores of the intervention group were significantly higher than the control group (P < 0.001). Conclusions: Concept mapping was superior to conventional skill teaching methods. It is suggested to use concept mapping in teaching practical courses such as fundamentals of nursing

Mortality Risk Prediction by an Insurance Company and Long-Term Follow-Up of 62,000 Men

Background: Insurance companies use medical information to classify the mortality risk of applicants. Adding genetic tests to this assessment is currently being debated. This debate would be more meaningful, if results of present-day risk prediction were known. Therefore, we compared the predicted with the observed mortality of men who applied for life insurance, and determined the prognostic value of the risk assessment. Methods: Long-term follow-up was available for 62,334 male applicants whose mortality risk was predicted with medical evaluation and they were assigned to five groups with increasing risk from 1 to 5. We calculated all cause standardized mortality ratios relative to the Dutch population and compared groups with Cox's regression. We compared the discriminative ability of risk assessments as indicated by a concordance index (c). Results: In 844,815 person years we observed 3,433 deaths. The standardized mortality relative to the Dutch male population was 0.76 (95 percent confidence interval, 0.73 to 0.78). The standardized mortality ratios ranged from 0.54 in risk group 1 to 2.37 in group 5. A large number of risk factors and diseases were significantly associated with increased mortality. The algorithm of prediction was significantly, but only slightly better than summation of the number of disorders and risk factors (c-index, 0.64 versus 0.60, P,0.001). Conclusions: Men applying for insurance clearly had better survival relative to the general population. Readily available medical evaluation enabled accurate prediction of the mortality risk of large groups, but the deceased men could not have been identified with the applied prediction method

A recurrent mosaic mutation of SMO, encoding the hedgehog signal transducer smoothened, is the major cause of Curry-Jones syndrome

Curry-Jones syndrome (CJS) is a multisystem disorder characterized by patchy skin lesions, polysyndactyly, diverse cerebral malformations, unicoronal craniosynostosis, iris colobomas, microphthalmia, and intestinal malrotation with myofibromas or hamartomas. Cerebellar medulloblastoma has been described in a single affected individual; in another, biopsy of skin lesions showed features of trichoblastoma. The combination of asymmetric clinical features, patchy skin manifestations, and neoplastic association previously led to the suggestion that this could be a mosaic condition, possibly involving hedgehog (Hh) signaling. Here, we show that CJS is caused by recurrent somatic mosaicism for a nonsynonymous variant in SMO (c.1234C&gt;T [p.Leu412Phe]), encoding smoothened (SMO), a G-protein-coupled receptor that transduces Hh signaling. We identified eight mutation-positive individuals (two of whom had not been reported previously) with highly similar phenotypes and demonstrated varying amounts of the mutant allele in different tissues. We present detailed findings from brain MRI in three mutation-positive individuals. Somatic SMO mutations that result in constitutive activation have been described in several tumors, including medulloblastoma, ameloblastoma, and basal cell carcinoma. Strikingly, the most common of these mutations is the identical nonsynonymous variant encoding p.Leu412Phe. Furthermore, this substitution has been shown to activate SMO in the absence of Hh signaling, providing an explanation for tumor development in CJS. This raises therapeutic possibilities for using recently generated Hh-pathway inhibitors. In summary, our work uncovers the major genetic cause of CJS and illustrates strategies for gene discovery in the context of low-level tissue-specific somatic mosaicism

Parental smoking and childhood cancer: results from the United Kingdom Childhood Cancer Study

There are strong a priori reasons for considering parental smoking behaviour as a risk factor for childhood cancer but case – control studies have found relative risks of mostly only just above one. To investigate this further, self-reported smoking habits in parents of 3838 children with cancer and 7629 control children included in the United Kingdom Childhood Cancer Study (UKCCS) were analysed. Separate analyses were performed for four major groups (leukaemia, lymphoma, central nervous system tumours and other solid tumours) and more detailed diagnostic subgroups by logistic regression. In the four major groups, after adjustment for parental age and deprivation there were nonsignificant trends of increasing risk with number of cigarettes smoked for paternal preconception smoking and nonsignificant trends of decreasing risk for maternal preconception smoking (all P-values for trend >0.05). Among the diagnostic subgroups, a statistically significant increased risk of developing hepatoblastoma was found in children whose mothers smoked preconceptionally (OR=2.68, P=0.02) and strongest (relative to neither parent smoking) for both parents smoking (OR=4.74, P=0.003). This could be a chance result arising from multiple subgroup analysis. Statistically significant negative trends were found for maternal smoking during pregnancy for all diagnoses together (P<0.001) and for most individual groups, but there was evidence of under-reporting of smoking by case mothers. In conclusion, the UKCCS does not provide significant evidence that parental smoking is a risk factor for any of the major groups of childhood cancers

Basal cytokeratins and their relationship to the cellular origin and functional classification of breast cancer

Recent publications have classified breast cancers on the basis of expression of cytokeratin-5 and -17 at the RNA and protein levels, and demonstrated the importance of these markers in defining sporadic tumours with bad prognosis and an association with BRCA1-related breast cancers. These important observations using different technology platforms produce a new functional classification of breast carcinoma. However, it is important in developing hypotheses about the pathogenesis of this tumour type to review the nomenclature that is being used to emphasize potential confusion between terminology that defines clinical subgroups and markers of cell lineage. This article reviews the lineages in the normal breast in relation to what have become known as the 'basal-like' carcinomas

Hyperspectral phasor analysis enables multiplexed 5D in vivo imaging

Time-lapse imaging of multiple labels is challenging for biological imaging as noise, photobleaching and phototoxicity compromise signal quality, while throughput can be limited by processing time. Here, we report software called Hyper-Spectral Phasors (HySP) for denoising and unmixing multiple spectrally overlapping fluorophores in a low signal-to-noise regime with fast analysis. We show that HySP enables unmixing of seven signals in time-lapse imaging of living zebrafish embryos

Pattern and determinants of hospitalization during heat waves: an ecologic study

<p>Abstract</p> <p>Background</p> <p>Numerous studies have investigated mortality during a heatwave, while few have quantified heat associated morbidity. Our aim was to investigate the relationship between hospital admissions and intensity, duration and timing of heatwave across the summer months.</p> <p>Methods</p> <p>The study area (Veneto Region, Italy) holds 4577408 inhabitants (on January 1^st, 2003), and is subdivided in seven provinces with 60 hospitals and about 20000 beds for acute care. Five consecutive heatwaves (three or more consecutive days with Humidex above 40°C) occurred during summer 2002 and 2003 in the region. From the regional computerized archive of hospital discharge records, we extracted the daily count of hospital admissions for people aged ≥75, from June 1 through August 31 in 2002 and 2003. Among people aged over 74 years, daily hospital admissions for disorders of fluid and electrolyte balance, acute renal failure, and heat stroke (grouped in a single nosologic entity, heat diseases, HD), respiratory diseases (RD), circulatory diseases (CD), and a reference category chosen a priori (fractures of the femur, FF) were independently analyzed by Generalized Estimating Equations.</p> <p>Results</p> <p>Heatwave duration, not intensity, increased the risk of hospital admissions for HD and RD by, respectively, 16% (p < .0001) and 5% (p < .0001) with each additional day of heatwave duration. At least four consecutive hot humid days were required to observe a major increase in hospital admissions, the excesses being more than twofold for HD (p < .0001) and about 50% for RD (p < .0001). Hospital admissions for HD peaked equally at the first heatwave (early June) and last heatwave (August) in 2004 as did RD. No correlation was found for FF or CD admissions.</p> <p>Conclusion</p> <p>The first four days of an heatwave had only minor effects, thus supporting heat health systems where alerts are based on duration of hot humid days. Although the finding is based on a single late summer heatwave, adaptations to extreme temperature in late summer seem to be unlikely.</p