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Articles by D. C Bauer
Total Records ( 4 ) for D. C Bauer
  E. M Simonsick , A. B Newman , L Ferrucci , S Satterfield , T. B Harris , N Rodondi , D. C Bauer and for the Health ABC Study
 

Background  Health risks associated with subclinical hypothyroidism in older adults are unclear. Our objective was to compare the functional mobility of people aged 70 to 79 years by thyroid function categorized by thyrotropin (TSH) level as euthyroid (≥0.4 to <4.5 mIU/L), mild subclinical hypothyroid (≥4.5 to <7.0 mIU/L), or moderate subclinical hypothyroid (≥7.0 to ≤20.0 mIU/L with a normal free thyroxine level) cross-sectionally and over 2 years.

Methods  A total of 2290 community-dwelling residents participating in the year 2 clinic visit (July 1998–June 1999) of the Health, Aging, and Body Composition (Health ABC) Study, who had measured TSH level, had the capacity to walk 20 m unaided, and were not taking thyroid medication or had TSH levels consistent with hyperthyroidism or hypothyroidism. Main outcome measures included self-reported and performance-based measures of mobility (usual and rapid gait speed and endurance walking ability) assessed at study baseline (year 2) and 2 years later.

Results  In age- and sex-adjusted analyses, the mild subclinical hypothyroid group (vs the euthyroid group) demonstrated better mobility (faster mean usual and rapid gait speed [1.20 vs 1.15 m/s and 1.65 vs 1.56 m/s, respectively; P < .001] and had a higher percentage of those with good cardiorespiratory fitness and reported walking ease [39.2% vs 28.0% and 44.7% vs 36.5%, respectively; P < .001]). After 2 years, persons with mild subclinical hypothyroidism experienced a similar decline as the euthyroid group but maintained their mobility advantage. Persons with moderate subclinical hypothyroidism had similar mobility and mobility decline as the euthyroid group.

Conclusion  Generally, well-functioning 70- to 79-year-old individuals with subclinical hypothyroidism do not demonstrate increased risk of mobility problems, and those with mild elevations in TSH level show a slight functional advantage.

  J. S Lee , P Buzkova , H. A Fink , J Vu , L Carbone , Z Chen , J Cauley , D. C Bauer , A. R Cappola and J. Robbins
 

Background  Subclinical thyroid dysfunction is common in older adults and affects bone metabolism, but its effects on fracture risk have not been reported. We sought to determine prospectively whether older men and women with subclinical hyperthyroidism or hypothyroidism have an increased risk of hip fracture.

Methods  Prospective cohort of 3567 US community-dwelling adults, 65 years or older, with biochemically defined subclinical thyroid dysfunction or euthyroidism was enrolled from June 10, 1989, through May 30, 1990, and followed up through 2004. Main outcome measures included incidence and hazard ratios (HRs), with 95% confidence intervals (CIs), of confirmed incident hip fractures for groups with subclinical hypothyroidism, subclinical hyperthyroidism, and euthyroidism as defined at baseline.

Results  During 39 952 person-years (median follow-up, 13 years), hip fracture incidence (per 1000 men-years) was 13.65 in men with subclinical hyperthyroidism (n = 29) and 10.27 in men with subclinical hypothyroidism (n = 184), both greater than 5.0 in men with euthyroidism (n = 1159). Men with subclinical hypothyroidism had a multivariable-adjusted HR of 2.31 (95% CI, 1.25-4.27); those with subclinical hyperthyroidism, 3.27 (0.99-11.30). After excluding those with baseline use of thyroid-altering medications, men with endogenous subclinical hyperthyroidism had a higher HR of 4.91 (95% CI, 1.13-21.27), as did men with endogenous subclinical hypothyroidism (2.45, 1.27-4.73). Hip fracture incidence (per 1000 women-years) was 8.93 in women with subclinical hypothyroidism (n = 359) and 10.90 in women with subclinical hyperthyroidism (n = 142) compared with 10.18 in women with euthyroidism (n = 1694). No clear association between subclinical dysfunction and fracture was observed in women.

Conclusions  Older men with subclinical hyperthyroidism or hypothyroidism are at increased risk for hip fracture. Whether treatment of the subclinical syndrome reduces this risk is unknown.

  D. C Bauer and T. L. Bailey
 

Motivation: Modeling transcriptional regulation using thermo-dynamic modeling approaches has become increasingly relevant as a way to gain a detailed understanding of transcriptional regulation. Thermodynamic models are able to model the interactions between transcription factors (TFs) and DNA that lead to a specific transcriptional output of the target gene. Such models can be ‘trained’ by fitting their free parameters to data on the transcription rate of a gene and the concentrations of its regulating factors. However, the parameter fitting process is computationally very expensive and this limits the number of alternative types of model that can be explored.

Results: In this study, we evaluate the ‘optimization landscape’ of a class of static, quantitative models of regulation and explore the efficiency of a range of optimization methods. We evaluate eight optimization methods: two variants of simulated annealing (SA), four variants of gradient descent (GD), a hybrid SA/GD algorithm and a genetic algorithm. We show that the optimization landscape has numerous local optima, resulting in poor performance for the GD methods. SA with a simple geometric cooling schedule performs best among all tested methods. In particular, we see no advantage to using the more sophisticated ‘LAM’ cooling schedule. Overall, a good approximate solution is achievable in minutes using SA with a simple cooling schedule.

Contact: [email protected]; [email protected]

Supplementary information: Supplementary data are available at Bioinformatics online.

 
 
 
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