Linkage disequilibrium (association) analysis was used to evaluate a candidate region near the CTLA4/CD28 genes using a multi-ethnic collection of families with one or more children affected by IDDM. In the data set unique to this study (Spanish, French, Mexican-American, Chinese and Korean), the transmission/disequilibrium test (TDT) revealed a highly significant deviation for transmission of alleles at the (AT)n microsatellite marker in the 3' untranslated region (P = 0.002) and the A/G polymorphism in the first exon (P = 0.00002) of the CTLA4 gene. The overall evidence for transmission deviation of the CTLA4 A/G alleles is also highly significant (P = 0.00005) in the combined data set (669 multiplex and 357 simplex families) from this study and a previous report on families from USA, Italy, UK, Spain and Sardinia. Significant heterogeneity was observed in these data sets. The British, Sardinian and Chinese data sets did not show any deviation for the A/G polymorphism, while the Caucasian-American data set showed a weak transmission deviation. Strong deviation for transmission was seen in the three Mediterranean-European populations (Italian, Spanish and French) (P = 10(-5)), the Mexican-American population (P = 0.002) and the Korean population (P = 0.03). These results suggest that a true IDDM susceptibility locus (designated IDDM12) is located near CTLA4.
JSTOR is a not-for-profit service that helps scholars, researchers, and students discover, use, and build upon a wide range of content in a trusted digital archive. We use information technology and tools to increase productivity and facilitate new forms of scholarship. For more information about JSTOR, please contact support@jstor.org.. Biometrika Trust is collaborating with JSTOR to digitize, preserve and extend access to Biometrika. SUMMARY A theoretical optimal stopping rule based on the minimization of the testing cost and expected penalty due to the unremoved bugs is derived without the equal failure rate assumption under Nayak's (1988) recapture debugging procedure. Two adaptive stopping rules suitable for practical use are constructed and tested by simulation. The estimation of the number of undetected bugs is also considered via remaining failure rate estimation.
OBJECTIVE -Children who develop cerebral edema (CE) during diabetic ketoacidosis (DKA) exhibit definable signs and symptoms of neurological collapse early enough to allow intervention to prevent brain damage. Our objective was to develop a model for early detection of CE in children with DKA. RESEARCH DESIGN AND METHODS-A training sample of 26 occurrences of DKA complicated by severe CE and 69 episodes of uncomplicated DKA was reviewed. Signs of neurological disease were incorporated into a bedside evaluation protocol that was applied to an independent test sample of 17 patients previously reported to have developed symptomatic CE during treatment for DKA. Head computed tomograms and their reports were reviewed.RESULTS -The protocol allowed 92% sensitivity and 96% specificity for the recognition of CE sufficiently early for intervention. The diagnostic criteria were fulfilled in two temporal patterns, defining early-and late-onset CE. Although initial computed tomograms were often normal, the findings also included diffuse CE and focal brain injury, the latter only in patients with an early onset of abnormal neurological signs.CONCLUSIONS -CE may occur in the absence of acute changes on head computed tomograms. Early detection of CE at the bedside using an evidence-based protocol permits intervention in time to prevent permanent brain damage. Diabetes Care 27:1541-1546, 2004M ost children with diabetic ketoacidosis (DKA) exhibit abnormal neurological function. Therefore, evidence-based guidance for discerning the patients who require lifesaving intervention is needed. Cerebral dysfunction in DKA is usually a manifestation of metabolic derangement, but cerebral edema (CE) arises in ϳ1% of episodes and is a complication that frequently causes irreversible brain damage and death (1-7). Neurological collapse from CE is typically described as having sudden onset and progressing rapidly, with recovery depending on prompt reduction of intracranial pressure (4,8 -10). The object of this study was to delineate the signs and symptoms of neurological compromise that predict progression to severe CE in children with DKA.CE occurs rarely in patients older than age 20 years (8,11,12), despite the presence of asymptomatic CE in most adults and children with DKA (13-16). This age dependence may point to developmental changes in cerebral metabolism as critical elements in the pathogenesis of CE. For example, children's brains are reported to have higher fuel and oxygen requirements than those of adults (17,18). Hypoxia is further implicated because the brains of patients with DKA may extract blood oxygen less efficiently than healthy individuals (16) and the reported association of symptomatic CE with low partial pressures of carbon dioxide in arterial blood may reflect harmful cerebral vasoconstriction (5,6). Exuberant rehydration with hypotonic fluid and bicarbonate administration may aggravate the CE (5,6,9,11,12,19 -22); however, the evidence that CE is primarily iatrogenic is not compelling (6,8,(23)(24)(25)(26)(27)(28)(29)...
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