Whole Exome Sequencing and Large-Scale Targeted Sequencing to Identify Novel Candidate Genes in Idiopathic Short Stature

Short stature is a common problem in pediatric endocrinology. With the exception of chronic disease and overt hormonal deficiencies, patients with short stature often go without a definitive diagnosis, and are therefore classified as having idiopathic short stature. Treatment with growth hormone therapy is of limited effect in many of these individuals, highlighting the multiple pathways involved in human growth. Height has been shown to be more than 90% heritable, and a large portion of the genetic variation in height can be explained by the additive effects of many common variants; however, there is a substantial contribution of rare variants with larger effect size, particularly at the extremes of height. The chapters of this thesis describe the use of both whole exome sequencing as well as large-scale targeted sequencing in patients with extreme short stature as strategies to discover novel or rare pathogenic variants that lead to short stature phenotypes. A number of pathogenic variants were identified including novel mutations in the insulin-like growth factor 1 receptor (IGF1R) and natriuretic peptide receptor-B (NPR2). These studies also highlight the potential for the detection of a large number of candidate genes, complicating interpretation of results in both the research and clinical settings

The money bail system places undue burden on the incarcerated poor- but risk informed release can change that

The money bail system widely used throughout the American criminal justice system requires a defendant to pay a specified sum of money or await their trail from a jail cell, placing undue burden on the poor. New research by Dottie Carmichael, Heather Caspers, Nicholas Davis, Trey Marchbanks, George Naufal and Steve Wood focuses on the use of validated risk assessment ..

A Self-Assembled, Low-Cost, Microstructured Layer for Extremely Stretchable Gold Films

We demonstrate a simple, low-cost, and green approach to deposit a microstructured coating on the silicone elastomer polydimethylsiloxane (PDMS) that can be coated with gold to produce highly stretchable and conductive films. The microstructured coating is fabricated using an aqueous emulsion of poly(vinyl acetate) (PVAc): common, commercially available white glue. The aqueous glue emulsion self-assembles on the PDMS surface to generate clustered PVAc globules, which can be conformally coated with gold. The microstructured surface provides numerous defect sites that localize strain when the structure is stretched, resulting in the initiation of numerous microcracks. As the structure is further elongated, the microcracks interact with one another, preventing long-range crack propagation and thus preserving the conduction pathway. The resistance of PDMS/glue/gold structures remains remarkably low (23x the initial resistance) up to 65% elongation, making these structure useful as stretchable interconnects. Decreasing the concentration of the PVAc aqueous emulsion reduces the density of defect sites of the microstructure, which increases the change in resistance of the gold films with stretching. In this way, we can tune the resistance changes of the PDMS/glue/gold structures and increase their sensitivity to strain. We demonstrate the use of these structures as wearable, soft strain sensors

Towards a National Housing Strategy for Homeless Youth

This policy brief, "Towards a National Housing Strategy for Homeless Youth", is part of a series developed by the Hollywood Homeless Youth Partnership (HHYP) to advance policy and practice recommendations focused on preventing and ending youth homelessness. This brief emerges from "No Way Home: Understanding the Needs and Experiences of Homeless Youth in Hollywood", a report released by the HHYP in November 2010 presenting findings from a multi-method needs assessment conducted with 389 homeless youth ages 12 to 25 in the Hollywood community.The purpose of this brief is to address the inadequacies of prioritizing permanent housing as the only solution for homeless youth, identify the major limitations of our existing housing programs, and advocate for developing a national housing strategy and funding a full housing continuum for homeless young people that is responsive to their unique needs and circumstances. This brief is being released at a time of unprecedented interest in the issue of youth homelessness -- we hope it will inform federal and local planning and decision-making and help advance our national agenda of preventing and ending youth homelessness

Joint and individual analysis of breast cancer histologic images and genomic covariates

A key challenge in modern data analysis is understanding connections between complex and differing modalities of data. For example, two of the main approaches to the study of breast cancer are histopathology (analyzing visual characteristics of tumors) and genetics. While histopathology is the gold standard for diagnostics and there have been many recent breakthroughs in genetics, there is little overlap between these two fields. We aim to bridge this gap by developing methods based on Angle-based Joint and Individual Variation Explained (AJIVE) to directly explore similarities and differences between these two modalities. Our approach exploits Convolutional Neural Networks (CNNs) as a powerful, automatic method for image feature extraction to address some of the challenges presented by statistical analysis of histopathology image data. CNNs raise issues of interpretability that we address by developing novel methods to explore visual modes of variation captured by statistical algorithms (e.g. PCA or AJIVE) applied to CNN features. Our results provide many interpretable connections and contrasts between histopathology and genetics

Hydrological and associated biogeochemical consequences of rapid global warming during the Paleocene-Eocene Thermal Maximum

The Paleocene-Eocene Thermal Maximum (PETM) hyperthermal, ~ 56 million years ago (Ma), is the most dramatic example of abrupt Cenozoic global warming. During the PETM surface temperatures increased between 5 and 9 °C and the onset likely took < 20 kyr. The PETM provides a case study of the impacts of rapid global warming on the Earth system, including both hydrological and associated biogeochemical feedbacks, and proxy data from the PETM can provide constraints on changes in warm climate hydrology simulated by general circulation models (GCMs). In this paper, we provide a critical review of biological and geochemical signatures interpreted as direct or indirect indicators of hydrological change at the PETM, explore the importance of adopting multi-proxy approaches, and present a preliminary model-data comparison. Hydrological records complement those of temperature and indicate that the climatic response at the PETM was complex, with significant regional and temporal variability. This is further illustrated by the biogeochemical consequences of inferred changes in hydrology and, in fact, changes in precipitation and the biogeochemical consequences are often conflated in geochemical signatures. There is also strong evidence in many regions for changes in the episodic and/or intra-annual distribution of precipitation that has not widely been considered when comparing proxy data to GCM output. Crucially, GCM simulations indicate that the response of the hydrological cycle to the PETM was heterogeneous – some regions are associated with increased precipitation – evaporation (P – E), whilst others are characterised by a decrease. Interestingly, the majority of proxy data come from the regions where GCMs predict an increase in PETM precipitation. We propose that comparison of hydrological proxies to GCM output can be an important test of model skill, but this will be enhanced by further data from regions of model-simulated aridity and simulation of extreme precipitation events

Maternal Drinking During Pregnancy: Attention and Short-Term Memory in 14-Year-Old Offspring—A Longitudinal Prospective Study

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66151/1/j.1530-0277.1994.tb00904.x.pd

Assimilation of Oil-Derived Elements by Oysters Due to the Deepwater Horizon Oil Spill

During and after the Deepwater Horizon Oil Spill (DWHOS), oysters (Crassostrea virginica) were exposed to oil and susceptible to incidental consumption of surface and subsurface oil materials. We determined the contribution of oil materials from the DWHOS to diet of oysters by comparing carbon (C) and nitrogen (N) stable isotope ratios in oyster shell to ratios in suspended particulate matter (SPM) and in fresh and weathered oil. Average δ13C and δ15N values in oyster shell (−21 ± 1‰ and 9−11‰, respectively) were consistent with consumption of naturally available SPM as opposed to values in oil (−27 ± 0.2‰, 1.6 ± 0.4‰). Stable isotope ratios in oyster adductor muscle were similar to shell for δ15N but not δ13C, suggesting either a recent shift in diet composition or differential assimilation of C between tissue types. We found no evidence of assimilation of oil-derived C and N and, therefore, no evidence of an oyster-based conduit to higher trophic levels. Trace elements in shell were inconclusive to corroborate oil exposure. These findings are not an indication that oysters were not exposed to oil; rather they imply oysters either did not consume oil-derived materials or consumed too little to be detectable compared to natural diet