Birth seasonality studies in a large Prader-Willi syndrome cohort.

Prader-Willi syndrome (PWS) is generally due to sporadic paternal deletions of the chromosome 15q11-q13 region followed by maternal disomy 15. Advanced maternal age is more commonly seen in those with maternal disomy 15. Environmental factors (e.g., drug use, occupational chemical exposure, infectious agents, and irradiation) could account for chromosome changes. Previous evidence of differences in male and female gametogenesis could suggest an environmental role in the causation of the paternal 15q11-q13 deletion seen in PWS. Certain occupations such as hydrocarbon-exposing occupations (e.g., landscaping, farming, and painting) and viral exposure (e.g., human coronavirus 229E causing upper respiratory infections in adults with an incorporation site in the human genome at chromosome 15q11) can be seasonal in nature and contribute to chromosome damage. To assess, we reviewed birth seasonality data in a large cohort of individuals with PWS recruited nationally (N = 355) but no significant differences were seen by month between those with the 15q11-q13 deletion compared with maternal disomy 15 when analyzing quarterly seasonal patterns. Although early evidence supported birth seasonality differences in PWS, a larger number of individuals in our recent study using advanced genetic testing methods did not find this observation

A Bayesian analysis of small n sequential multiple assignment randomized trials (snSMARTs)

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146269/1/sim7900.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146269/2/sim7900_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146269/3/A_Bayesian_Analysis_of_snSMART_Revision_Supplimentary.pd

Early Diagnosis in Prader-Willi Syndrome Reduces Obesity and Associated Co-Morbidities.

Prader-Willi syndrome (PWS) is an imprinting genetic disorder characterized by lack of expression of genes on the paternal chromosome 15q11-q13 region. Growth hormone (GH) replacement positively influences stature and body composition in PWS. Our hypothesis was that early diagnosis delays onset of obesity in PWS. We studied 352 subjects with PWS, recruited from the NIH Rare Disease Clinical Research Network, to determine if age at diagnosis, ethnicity, gender, and PWS molecular class influenced the age they first become heavy, as determined by their primary care providers, and the age they first developed an increased appetite and began seeking food. The median ages that children with PWS became heavy were 10 years, 6 years and 4 years for age at diagnosis < 1 year, between 1 and 3 years, and greater than 3 years of age, respectively. The age of diagnosis and ethnicity were significant factors influencing when PWS children first became heavy (p < 0.01), however gender and the PWS molecular class had no influence. Early diagnosis delayed the onset of becoming heavy in individuals with PWS, permitting early GH and other treatment, thus reducing the risk of obesity-associated co-morbidities. Non-white individuals had an earlier onset of becoming heavy

Micro-cutting of single-crystal metal: Finite-element analysis of deformation and material removal

This paper presents analysis of mechanics in a micro-cutting process of a single-crystal metal – mechanisms of deformation and material removal related to an anisotropic crystallographic structure of a work-piece. A crystal-plasticity theory was implemented in a finite-element (FE) modelling scheme to consider inherently anisotropic deformation of a single-crystal metal at micro-scale. A new shear-strain-based criterion and several conventional strain-based criteria were employed to simulate the material removal process, and their effect on the anisotropy of cutting forces was studied. Subsequently, the micro-cutting process of single-crystal copper was predicted using FE modelling by combining the crystal-plasticity theory and the proposed criterion of material removal. The validity of the present FE modelling methodology was corroborated through a comprehensive comparison between FE simulations and experimental data in terms of cutting forces, chip morphology, deformation field, pile-up patterns and misorientation angle in the work-piece

Exciton Optical Absorption in Self-Similar Aperiodic Lattices

Exciton optical absorption in self-similar aperiodic one-dimensional systems is considered, focusing our attention on Thue-Morse and Fibonacci lattices as canonical examples. The absorption line shape is evaluated by solving the microscopic equations of motion of the Frenkel-exciton problem on the lattice, in which on-site energies take on two values, according to the Thue-Morse or Fibonacci sequences. Results are compared to those obtained in random lattices with the same stechiometry and size. We find that aperiodic order causes the occurrence of well-defined characteristic features in the absorption spectra which clearly differ from the case of random systems, indicating a most peculiar exciton dynamics. We successfully explain the obtained spectra in terms of the two-center problem. This allows us to establish the origin of all the absorption lines by considering the self-similar aperiodic lattices as composed of two-center blocks, within the same spirit of the renormalization group ideas.Comment: 16 pages in REVTeX 3.0. 2 figures on request to F. D-A ([email protected]

Multicentre study of maternal and neonatal outcomes in individuals with Prader-Willi syndrome.

INTRODUCTION:Prader-Willi syndrome (PWS) is a complex genetic disorder associated with three different genetic subtypes: deletion of the paternal copy of 15q11-q13, maternal UPD for chromosome 15 and imprinting defect. Patients are typically diagnosed because of neonatal hypotonia, dysmorphism and feeding difficulties; however, data on the prenatal features of PWS are limited. OBJECTIVE:The aim of the study was to identify and compare frequencies of prenatal and neonatal clinical features of PWS among the three genetic subtypes. METHODS:Data from 355 patients with PWS from the Rare Diseases Clinical Research Network PWS registry were used to analyse multiple maternal and neonatal factors collected during an 8-year multisite study. RESULTS:Among our cohort of 355 patients with PWS (61% deletion, 36% UPD and 3% imprinting defect) 54% were born by caesarean section, 26% were born prematurely and 34% with a low birth weight (frequencies 32%, 9.6% and 8.1%, respectively, in the general population). Fetal movements were reported as decreased in 72%. All babies were hypotonic, and 99% had feeding difficulties. Low Apgar scores (<7) were noted in 17.7% and 5.6% of patients, respectively, compared with 1% and 1.4%, respectively, in the general population. Maternal age and pre-pregnancy weight were significantly higher in the UPD group (p=0.01 and <0.001, respectively). CONCLUSION:We found a higher rate of perinatal complications in PWS syndrome compared with the general population. No significant differences in the genetic subtypes were noted except for a higher maternal age and pre-pregnancy weight in the UPD subgroup