Loss of function,missense, and intronic variants in NOTCH1 confer different risks for left ventricular outflow tract obstructive heart defects in two European cohorts

Loss of function variants in NOTCH1 cause left ventricular outflow tract obstructive defects (LVOTO). However, the risk conferred by rare and noncoding variants in NOTCH1 for LVOTO remains largely uncharacterized. In a cohort of 49 families affected by hypoplastic left heart syndrome, a severe form of LVOTO, we discovered predicted loss of function NOTCH1 variants in 6% of individuals. Rare or low-frequency missense variants were found in 16% of families. To make a quantitative estimate of the genetic risk posed by variants in NOTCH1 for LVOTO, we studied associations of 400 coding and noncoding variants in NOTCH1 in 1,085 cases and 332,788 controls from the UK Biobank. Two rare intronic variants in strong linkage disequilibrium displayed significant association with risk for LVOTO amongst European-ancestry individuals. This result was replicated in an independent analysis of 210 cases and 68,762 controls of non-European and mixed ancestry. In conclusion, carrying rare predicted loss of function variants in NOTCH1 confer significant risk for LVOTO. In addition, the two intronic variants seem to be associated with an increased risk for these defects. Our approach demonstrates the utility of population-based data sets in quantifying the specific risk of individual variants for disease-related phenotypes.     

计算机医嘱输入系统对用药错误的助长作用

背景：医院的计算机医嘱输入（computerized physician order entry，CPOE）系统被广泛认为能从技术上解决用药错误，后者是最常见的可以预防的医院诊疗错误的来源。已发表的研究表明，CPOE可减少高达81％的用药错误。然而，很少研究关注CPOE助长用药错误作用的范围或类型。     

Case series: Combined spinal epidural anesthesia for Cesarean delivery andex utero intrapartum treatment procedure

PURPOSE: To report the use of regional anesthesia and iv nitroglycerin to provide anesthesia and uterine relaxation for three Cesarean deliveries (CD) involving ex utero intrapartum treatment (EXIT) of potentially life-threatening airway obstruction in the newborn. CLINICAL FEATURES: Case 1--a 36-yr-old woman at 38 weeks' gestation was scheduled for an elective CD for fetal skeletal dysplasia and micrognathia. Case 2--a 34-yr-old woman at 35 weeks gestation had a fetal ultrasound revealing fixed neck flexion and micrognathia consistent with fetal arthrogryposis. Case 3--a 27-yr-old woman presented at 38 weeks gestation for CD for severe fetal micrognathia, with mandibular growth below the fifth percentile. For each case, a combined spinal epidural anesthetic was performed with 0.75% bupivacaine, fentanyl and morphine intrathecally followed by placement of a multiorifice epidural catheter. Prior to uterine incision patients received a loading dose followed by an iv infusion of nitroglycerin. Uterine relaxation was sufficient in all cases for delivery of the fetus, and allowed for evaluation by direct laryngoscopy and intubation while maintaining fetal-placental circulation. The surgical procedures were completed without incident. CONCLUSIONS: Anesthesia and uterine relaxation for CD and EXIT procedures can be safely provided with regional anesthesia and iv nitroglycerin.     

Classroom seating for children with attention deficit hyperactivity disorder: therapy balls versus chairs.

OBJECTIVE: The purpose of this study was to investigate the effects of therapy balls as seating on in-seat behavior and legible word productivity of students with attention deficit hyperactivity disorder (ADHD). Additionally, social validity was assessed to evaluate teacher and student opinions regarding the intervention. METHOD: A single subject, A-B-A-B interrupted time series design was employed across 3 students (2 males, 1 female) with ADHD. The study was conducted in a 4th grade inclusive classroom during daily language arts. During phases 1 and 3, the 3 participants and all other class members sat on chairs (in-seat on chair); during phases 2 and 4, everyone sat on therapy balls (in-seat on ball). Dependent variables were in-seat behavior and legible word productivity. Data were graphed and visually analyzed for differences between phases. RESULTS: Results demonstrated increases in in-seat behavior and legible word productivity for the students with ADHD when seated on therapy balls. Social validity findings indicated that generally the teacher and students preferred therapy balls. CONCLUSION: This study provides evidence that use of therapy balls for students with ADHD may facilitate in-seat behavior and legible word productivity.     

Risk of lung cancer among patients with head and neck cancer

A cohort of 5180 patients with head and neck cancer, who were part of the tumor registry of the Surveillance, Epidemiology, and End Results area of western Washington State, was followed up for as many as 15 years to determine the risk of lung cancer. A sample of 522 patients from this cohort was interviewed to determine smoking history. Lung cancer developed in 356 (6.9%) of the 5180 patients. The overall annual incidence of lung cancer remained relatively constant between approximately 1.0% and 2.0% during the 15 years of follow-up. Men had an increased risk of lung cancer compared with women (relative risk [RR] = 1.56; 95% confidence interval [CI] = 1.18 to 2.03). Compared with patients with oral cavity cancer (RR = 1.00), the relative risk of lung cancer developing by the site of the index tumor was 0.63 (95% CI = 0.40 to 0.98) for lip, 1.12 (95% CI = 0.81 to 1.56) for intrinsic larynx, 1.73 (95% CI = 1.21 to 2.47) for oropharynx, 1.84 (95% CI = 1.16 to 2.92) for hypopharynx, and 2.28 (95% CI = 1.60 to 3.24) for extrinsic larynx. Among the 522 patients who were interviewed, men smoked more than women ( p < 0.0001), and patients with laryngeal or pharyngeal cancer smoked more than patients with cancer of the lip or the oral cavity ( p < 0.05). Among patients with head and neck cancer, the risk of lung cancer is highest for men and for patients with cancer of the pharynx or extrinsic larynx. These findings may be explained by differences in smoking consumption. (Otolaryngol Head Neck Surg 1997;116:630-6.)     

Irregularly shaped small shadows on chest radiographs, dust exposure, and lung function in coalworkers' pneumoconiosis.

The predominant shapes of small opacities on the chest radiographs of 895 British coalminers have been studied. The aims were to determine whether irregular (as distinct from rounded) small opacities can be identified reproducibly, whether their occurrence is related to dust exposure, and whether they are associated with excess prevalence of respiratory symptoms or impairments of lung function. Six of the doctors responsible for regular radiological surveys of all British coalminers each classified all 895 radiographs twice and independently, using the International Labour Organisation's 1980 classification system. The majority view was that 39 films showed predominantly irregular small opacities, 131 showed predominantly small rounded opacities, and 587 showed no small opacities. Readers' opinions varied about the presence and shapes of shadows on the other 138 films. In general, consistency between readers (and within readers on repeated viewings) was satisfactory. The occurrence and profusion of irregular shadows were related significantly both to the men's ages and additionally to their cumulative exposure to respirable coalmine dust as determined from 15 years' dust monitoring close to where the miners had worked. For any given level of exposure, the average level of profusion of the small irregular opacities was less than the corresponding profusion of small rounded opacities. The prevalence rates of chronic cough and phlegm, and of breathlessness, were higher in those with small irregular opacities than in those with no small opacities (category 0/0), but the differences were not statistically significant after adjustment for other factors including smoking habits. The presence of irregular (but not rounded) small shadows was associated with an impairment in respiratory function averaging about 190 ml deficits in both FEV1 and FVC. These deficits were not explicable in terms of the men's ages, body sizes, and smoking habits and they were in addition to the lung function losses attributable to the miners' dust exposure as such. It is concluded that the presence and profusion of small irregular opacities should be taken into consideration when assessing the severity of coalworkers' simple pneumoconiosis.     

Morpheaform Basal Cell Carcinoma in African Americans

Background. Although it has been established that basal cell carcinoma is an uncommon diagnosis in black patients, the morpheaform subtype is very rare among these individuals.
Objective. The objective is to present two cases of morpheaform basal cell carcinoma in African-American patients.
Methods. This is a case series and a literature review using the Ovid Medline Database. Key words used in the search include "basal cell carcinoma,""African American,""black,""African,""negros,""morpheaform,""sclerosing,""fibrosing," and "scar-like basal cell carcinoma." The Ovid Medline Database was searched from 1966 to present and was restricted to the English language.
Results. A review of the Emory Dermatology clinic charts from 1989 to 2004 revealed two black patients with morpheaform basal cell carcinomas.
Conclusions. Although extremely rare, morpheaform pattern basal cell carcinoma must be considered in the differential diagnosis for black patients presenting with nonhealing lesions.