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David V Glidden

Publications and source records attributed to David V Glidden.

26 records · Page 2Linked to original sources
PubMed2003

Multipoint affected sibpair linkage methods for localizing susceptibility genes of complex diseases.

Recently, Liang et al. ([2001] Hum. Hered. 51:64-78) proposed a general multipoint linkage method for estimating the chromosomal position of a putative susceptibility locus. Their technique is computationally simple and does not require specification of penetrance or a mode of inheritance. In complex genetic diseases, covariate data may be available which reflect etiologic or locus heterogeneity. We developed approaches to incorporating covariates into the method of Liang et al. ([2001] Hum. Hered. 51:64-78) with particular attention to exploiting age-at-onset information. The results of simulation studies, and a worked data example using a family data set ascertained through probands with schizophrenia, suggest that utilizing covariate information can yield substantial efficiency gains in localizing susceptibility genes.

Age of Onset↗
PubMed2002

Anti-beta2-glycoprotein I antibodies in pediatric systemic lupus erythematosus and antiphospholipid syndrome.

OBJECTIVE: To determine whether serum beta2-glycoprotein I antibody (anti-beta2GPI) detection improves identification of pediatric subjects at risk for antiphospholipid syndrome (APS). METHODS: Serum antiphospholipid antibodies (aPL) were identified by anticardiolipin enzyme-linked immunosorbent assay (ELISA), lupus anticoagulant assays, and syphilis screening in children with primary APS, systemic lupus erythematosus (SLE), or SLE plus APS. Anti-beta2GPI level and isotype were determined by beta2GPI ELISA and correlated with clinical manifestations and other aPL assays. RESULTS: One hundred-ten subjects under 22 years of age and of mixed ethnicity were evaluated. Fifty-seven had SLE (including 14 with APS), 25 had primary APS, 16 had SLE-like APS, 6 were healthy children with aPL detected incidentally, 4 had other rheumatic diseases and 2 had other conditions. Anti-beta2GPI were detected in 48% of SLE subjects and did not improve aPL detection over standard tests. Anti-beta2GPI were associated with stroke (P = 0.014), but not with other APS manifestations, and were rarely detected in primary APS. Among subjects with APS manifesting as chronic thrombocytopenia, anti-beta(2)GPI distinguished subjects with SLE from those with primary APS. CONCLUSIONS: With the exception of stroke, anti-beta2GPI detection does not improve identification of pediatric APS over that of traditional aPL assays. Anti-beta2GPI are rare in pediatric primary APS, but may predict evolution of chronic thrombocytopenia to SLE.

Adolescent↗
PubMed2002

Ascertainment adjustment in complex diseases.

Genetic studies of complex diseases must confront two statistically difficult issues simultaneously. First, in many settings, to minimize the number of individuals to be genotyped, families enriched for disease must be oversampled. Also, statistical models in family studies should allow for residual association. This association will represent unmeasured genetic and environmental factors influencing disease risk. Dealing with these features simultaneously is both compelling and challenging. Burton et al. [2000] (Am. J. Hum. Gen. 69: 1505-14) recently discussed this issue and suggested that ascertainment corrections may lead to problematic parameter estimation. We revisit the issues and examples of Burton et al. [2000] (Am. J. Hum. Genet. 69: 1505-14) and present a more optimistic assessment. Estimation in this context is conceptually straightforward, but may be more problematic in practice. Specifically, we find that even slight misspecification of the random effects distribution in ascertainment-adjusted likelihood can yield severely biased parameter estimates. This result should make scientists wary when interpreting results from ascertainment-adjusted variance-component models. .

Bias↗
PubMed2002

Increased incidence in post-transplant diabetes mellitus in children: a case-control analysis.

There is limited information regarding the incidence and features of post-transplant diabetes mellitus (PTDM) in pediatric renal transplant recipients. We noted a recent increased frequency of PTDM and reviewed charts of children who underwent renal transplantation from 1 September 1986 to 31 August 1999 to characterize the risk factors and natural history of PTDM. Sixteen children were identified with PTDM, and were each matched with two transplanted controls who did not develop PTDM. Clinical presentation varied from asymptomatic hyperglycemia to hyperosmolar dehydration or diabetic ketoacidosis. The mean time from transplantation to PTDM presentation was 1.2 years (range 1 day to 6.2 years). Significant risk factors for PTDM included: first degree family history of type 2 DM [odds ratio (OR) 23.9]; second degree family history of type 2 DM (OR 5.8); tacrolimus use (OR 9.1 versus cyclosporin); and hyperglycemia in the 2 weeks immediately after transplantation (OR 4.7). Seven of eight children with persistent PTDM continue to receive insulin. Patients with persistent PTDM had later onset disease (mean 1.9 years) compared to those with transient PTDM (0.3 years), suggesting different pathophysiologic processes. We suggest that all children undergoing renal transplantation be screened routinely for PTDM after transplantation, and that such patients may benefit from the avoidance of tacrolimus, as it may cause permanent beta-cell injury.

Adolescent↗
PubMed2002

Research publications in vascular and interventional radiology: research topics, study designs, and statistical methods.

PURPOSE: Statistical analysis is the universal language of medical research and is a vital tool for communicating the results of vascular and interventional radiology (VIR) procedures. Major articles in two radiology journals were surveyed to characterize the research topics, study designs, and statistical methods seen in recent VIR research publications. MATERIALS AND METHODS: The authors retrospectively reviewed 130 major clinical VIR articles published from July 2000 to June 2001: 72 articles (55%) from JVIR and 58 articles (45%) from RADIOLOGY: Articles were categorized by research topic and study design. Data were collected on the statistical methodology of each article. RESULTS: Research topics included vascular intervention in 65 of 130 articles (50%), nonvascular intervention in 26 (20%), vascular imaging in 23 (18%), biopsy in nine (7%), and other topics in seven (5%). Study design was descriptive in 87 studies (67%), comparative in 39 studies (30%), and involved secondary data analysis in four studies (3%). Of 126 primary clinical studies, outcome was cross-sectional (assessed at a single time point) in 40 studies (32%) and longitudinal (measured over time) in 86 studies (68%). Median sample size was 61. Basic tests of association (t-test, chi(2) test, etc.) were used in 71 articles (56%) and advanced tests of association (regression analysis) were presented in 25 (20%). Survival analysis was applied in 34 articles (27%). Decision statistics such as sensitivity/specificity were not used commonly (12%). Confidence intervals and power calculations were reported infrequently (15% and 7%, respectively). CONCLUSIONS: VIR publications focus on time-dependent outcomes after therapeutic interventions. Readers should understand basic tests of association and survival analysis--these include only 20 named statistical tests.

Periodicals as Topic↗
PubMed2002

Robust inference for event probabilities with non-Markov event data.

Multistate event data, in which a single subject is at risk for multiple events, is common in biomedical applications. This article considers nonparametric estimation of the vector of probabilities of state membership at time t. Estimators, derived under the Markov assumption, have been shown (Datta and Satten, 2001, Statistics and Probability Letters 55, 403-411) to be consistent for data that is non-Markov. Inference, however, must take into account possibly non-Markov transitions when constructing confidence bands for event curves. We develop robust confidence bands for these curves, evaluate them via simulation, and illustrate the method on two datasets.

AIDS-Related Opportunistic Infections↗
PubMed2002

Predictors of 30-month outcome after perinatal depression: role of proton MRS and socioeconomic factors.

The objective was to determine in infants with perinatal depression whether the relative concentrations of N-acetylaspartate and lactate in the neonatal period are associated with (1) neurodevelopmental outcome at 30 mo of age or (2) deterioration in outcome from age 12 to 30 mo; and to determine whether socioeconomic factors are associated with deterioration in outcome. Thirty-seven term neonates were prospectively studied with single-voxel proton magnetic resonance spectroscopy of the basal nuclei and intervascular boundary zones. Thirty-month outcomes were classified as normal [if Mental Development Index of the Bayley Scales of Infant Development (MDI) >85 and neuromotor scores (NMS) <3; n = 15], abnormal [if MDI or=3 at 12 and 30 mo; n = 11], or deteriorated [if normal at 12 mo and abnormal at 30 mo (MDI or=3); n = 11]. Thirty percent (11/37) of our cohort deteriorated between 12 and 30 mo. N-acetylaspartate/choline decreased across the groups ordered as normal, deteriorated, and abnormal [in basal nuclei (p <or= 0.001) and intervascular boundary zones (p = 0.04)], but was not different between the normal and deteriorated groups (p = 0.08). Lactate/choline similarly increased across the groups [in basal nuclei (p = 0.01) and intervascular boundary zones (p = 0.05)]. The odds of deterioration, if normal at 12 mo, increased by a factor of 5.1 (95% confidence interval: 1.3-19.8) with each decrease in one of four household income strata. Infants with perinatal depression are at high risk of developmental deterioration between 12 and 30 mo of age, particularly if in a lower income home or with intermediate values of cerebral metabolites on neonatal proton magnetic resonance spectroscopy.

Apgar Score↗