The voltage-gated sodium channel gene SCN2A and idiopathic generalized epilepsy.

We tested the hypothesis that genetic variation in the human sodium channel gene SCN2A confers liability to idiopathic generalized epilepsy (IGE). We performed a systematic search for mutations in 46 familial IGE cases and detected three novel polymorphisms, however, allele frequencies did not differ significantly between patients and controls. A rare mutation (R1918H) was identified in one patient but was absent in one further affected family member. Thus, our results do not suggest a major role of SCN2A in the etiology of IGE.     

Forecasting Daily Patient Volumes in the Emergency Department

Background: Shifts in the supply of and demand for emergency department (ED) resources make the efficient allocation of ED resources increasingly important. Forecasting is a vital activity that guides decision‐making in many areas of economic, industrial, and scientific planning, but has gained little traction in the health care industry. There are few studies that explore the use of forecasting methods to predict patient volumes in the ED. Objectives: The goals of this study are to explore and evaluate the use of several statistical forecasting methods to predict daily ED patient volumes at three diverse hospital EDs and to compare the accuracy of these methods to the accuracy of a previously proposed forecasting method. Methods: Daily patient arrivals at three hospital EDs were collected for the period January 1, 2005, through March 31, 2007. The authors evaluated the use of seasonal autoregressive integrated moving average, time series regression, exponential smoothing, and artificial neural network models to forecast daily patient volumes at each facility. Forecasts were made for horizons ranging from 1 to 30 days in advance. The forecast accuracy achieved by the various forecasting methods was compared to the forecast accuracy achieved when using a benchmark forecasting method already available in the emergency medicine literature. Results: All time series methods considered in this analysis provided improved in‐sample model goodness of fit. However, postsample analysis revealed that time series regression models that augment linear regression models by accounting for serial autocorrelation offered only small improvements in terms of postsample forecast accuracy, relative to multiple linear regression models, while seasonal autoregressive integrated moving average, exponential smoothing, and artificial neural network forecasting models did not provide consistently accurate forecasts of daily ED volumes. Conclusions: This study confirms the widely held belief that daily demand for ED services is characterized by seasonal and weekly patterns. The authors compared several time series forecasting methods to a benchmark multiple linear regression model. The results suggest that the existing methodology proposed in the literature, multiple linear regression based on calendar variables, is a reasonable approach to forecasting daily patient volumes in the ED. However, the authors conclude that regression‐based models that incorporate calendar variables, account for site‐specific special‐day effects, and allow for residual autocorrelation provide a more appropriate, informative, and consistently accurate approach to forecasting daily ED patient volumes.     

Thromboxane synthetase inhibitors and antihypertensive agents. 2. N-[(1H-imidazol-1-yl)alkyl]-1H-isoindole-1,3(2H)-diones and N-[(1H-1,2,4-triazol-1-yl)alkyl]-1H-isoindole-1,3(2H)-diones as unique antihypertensive agents

A series of N-[(1H-heteroaryl)alkyl]-1H-isoindole-1,3(2H)-diones were prepared as part of a continuing investigation into the biological properties of compounds that were both thromboxane synthetase inhibitors and potential antihypertensive agents. The most active thromboxane synthetase inhibition was found for the title imidazole derivatives wherein a hexyl or octyl chain separated the heterocyclic ends of the molecule (5,6) or with substitution on the isoindole portion of the molecule (18, 19, 21, 22, 25, 26). Compounds with shorter alkyl chain separations had good antihypertensive effects (1-5, 8-10, 19-22, 27-30). Butyl derivative 3 was chosen for further evaluation as a potential antihypertensive agent with thromboxane synthetase inhibitory properties.     

Eumelanin is a Major Determinant for2‐Amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP) Incorporation into Hair of Mice

Mice with different hair pigmentation were studied to evaluate the role of melanin in the incorporation of 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP) into hair. Mice C57BL/6J‐c2j/+ (white), C57BL/6J‐Ay (yellow), C57L/J (grey), C57BR/cdJ (brown) and C57BL/6J (black) were dosed with PhIP: 7–9 days old (total amount: 0.006 or 0.58 mg/kg b.wt., for 4 days) and adults (total amount 50 mg/kg b.wt. during 8 weeks). Hair was collected either 30 days after the last PhIP administration (new‐born mice) or 8 weeks after the first administration (adult mice). PhIP was incorporated into black hair to a greater extent than into brown, grey, yellow and non‐pigmented hair. The concentration of PhIP in the hair of new‐born mice exposed to 0.58 mg PhIP/kg b.wt. were (mean±S.D.): 328±135 (black), 134±41 (brown), 9.1±1.2 (yellow) and 5.2±1.4 (white) ng/g hair. The PhIP concentrations in the hair of adult mice exposed to 50 mg/kg b.wt. were: 4750±1449 (black), 810±235 (brown), 541±119 (grey), 35.5±4.6 (yellow) and 21.6±8.8 (white) ng/g, and the eumelanin hair concentration in the same animals decreased in a similar pattern. A linear relationship (r²=1.00, P<0.0001) between the relative PhIP incorporation and the eumelanin concentration in hair was found.