The effect of age and demographics on rib shape

Elderly populations have a higher risk of rib fractures and other associated thoracic injuries than younger adults, and the changes in body morphology that occur with age are a potential cause of this increased risk. Rib centroidal path geometry for 20 627 ribs was extracted from computed tomography (CT) scans of 1042 live adult subjects, then fitted to a six‐parameter mathematical model that accurately characterizes rib size and shape, and a three‐parameter model of rib orientation within the body. Multivariable regression characterized the independent effect of age, height, weight, and sex on the rib shape and orientation across the adult population, and statistically significant effects were seen from all demographic factors (P < 0.0001). This study reports a novel aging effect whereby both the rib end‐to‐end separation and rib aspect ratio are seen to increase with age, producing elongated and flatter overall rib shapes in elderly populations, with age alone explaining up to 20% of population variability in the aspect ratio of mid‐level ribs. Age was not strongly associated with overall rib arc length, indicating that age effects were related to shape change rather than overall bone length. The rib shape effect was found to be more strongly and directly associated with age than previously documented age‐related changes in rib angulation. Other demographic results showed height and sex being most strongly associated with rib size, and weight most strongly associated with rib pump‐handle angle. Results from the study provide a statistical model for building rib shapes typical of any given demographic by age, height, weight, and sex, and can be used to help build population‐specific computational models of the thoracic rib cage. Furthermore, results also quantify normal population ranges for rib shape parameters which can be used to improve the assessment and treatment of rib skeletal deformity and disease.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137729/1/joa12632_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137729/2/joa12632.pd

A Pragmatic Test for Detecting Association between a Dichotomous Trait and the Genotypes of Affected Families, Controls and Independent Cases

The efficient analysis of hybrid designs [e.g., affected families, controls, and (optionally) independent cases] is attractive because it should have increased power to detect associations between genetic variants and disease. However, the computational complexity of such an analysis is not trivial, especially when the data contain pedigrees of arbitrary size and structure. To address this concern, we developed a pragmatic test of association that summarizes all of the available evidence in certain hybrid designs, irrespective of pedigree size or structure. Under the null hypothesis of no association, our proposed test statistic (POPFAM+) is the quadratic form of two correlated tests: a population-based test (e.g., wQLS), and a family-based test (e.g., PDT). We use the parametric bootstrap in conjunction with an estimate of the correlation to compute p-values, and we illustrate the potential for increased power when (1) the heritability of the trait is high; and, (2) the marker-specific association is driven by the over-representation of risk alleles in cases, and by the preferential transmission of risk alleles from heterozygous parents to their affected offspring. Based on simulation, we show that type I error is controlled, and that POPFAM+ is more powerful than wQLS or PDT alone. In a real data application, we used POPFAM+ to analyze 43 genes of a hybrid epilepsy study containing 85 affected families, 80 independent cases, 234 controls, and 118 reference samples from the International HapMap Project. The results of our analysis identified a promising epilepsy candidate gene for follow-up sequencing: malic enzyme 2 (ME2; min p &lt; 0.0084)

Comparison of Body Size, Morphomics, and Kidney Function as Covariates of High‐Dose Methotrexate Clearance in Obese Adults with Primary Central Nervous System Lymphoma

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154919/1/phar2379.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154919/2/phar2379_am.pd

Even perturbations of self-similar Vaidya space-time

We study even parity metric and matter perturbations of all angular modes in self-similar Vaidya space-time. We focus on the case where the background contains a naked singularity. Initial conditions are imposed describing a finite perturbation emerging from the portion of flat space-time preceding the matter-filled region of space-time. The most general perturbation satisfying the initial conditions is allowed impinge upon the Cauchy horizon (CH), whereat the perturbation remains finite: there is no ``blue-sheet'' instability. However when the perturbation evolves through the CH and onto the second future similarity horizon of the naked singularity, divergence necessarily occurs: this surface is found to be unstable. The analysis is based on the study of individual modes following a Mellin transform of the perturbation. We present an argument that the full perturbation remains finite after resummation of the (possibly infinite number of) modes.Comment: Accepted for publication in Physical Review D, 27 page

Development of the preterm gut microbiome in twins at risk of necrotising enterocolitis and sepsis

The preterm gut microbiome is a complex dynamic community influenced by genetic and environmental factors and is implicated in the pathogenesis of necrotising enterocolitis (NEC) and sepsis. We aimed to explore the longitudinal development of the gut microbiome in preterm twins to determine how shared environmental and genetic factors may influence temporal changes and compared this to the expressed breast milk (EBM) microbiome. Stool samples (n = 173) from 27 infants (12 twin pairs and 1 triplet set) and EBM (n = 18) from 4 mothers were collected longitudinally. All samples underwent PCR-DGGE (denaturing gradient gel electrophoresis) analysis and a selected subset underwent 454 pyrosequencing. Stool and EBM shared a core microbiome dominated by Enterobacteriaceae, Enterococcaceae, and Staphylococcaceae. The gut microbiome showed greater similarity between siblings compared to unrelated individuals. Pyrosequencing revealed a reduction in diversity and increasing dominance of Escherichia sp. preceding NEC that was not observed in the healthy twin. Antibiotic treatment had a substantial effect on the gut microbiome, reducing Escherichia sp. and increasing other Enterobacteriaceae. This study demonstrates related preterm twins share similar gut microbiome development, even within the complex environment of neonatal intensive care. This is likely a result of shared genetic and immunomodulatory factors as well as exposure to the same maternal microbiome during birth, skin contact and exposure to EBM. Environmental factors including antibiotic exposure and feeding are additional significant determinants of community structure, regardless of host genetics

Regional maps of rib cortical bone thickness and cross-sectional geometry

Here we present detailed regional bone thickness and cross-sectional measurements from full adult ribs using high resolution CT scans processed with a cortical bone mapping technique. Sixth ribs from 33 subjects ranging from 24 to 99 years of age were used to produce average cortical bone thickness maps and to provide average ± 1SD corridors for expected cross-section properties (cross-sectional areas and inertial moments) as a function of rib length. Results obtained from CT data were validated at specific rib locations using direct measurements from cut sections. Individual thickness measurements from CT had an accuracy (mean error) and precision (SD error) of -0.013 ± 0.167 mm (R2 coefficient of determination of 0.84). CT-based measurement errors for rib cross-sectional geometry were -0.1 ± 13.1% (cortical bone cross-sectional area) and 4.7 ± 1.8% (total cross-sectional area). Rib cortical bone thickness maps show the expected regional variation across a typical rib’s surface. The local mid-rib maxima in cortical thickness along the pleural rib aspect ranged from range 0.9 to 2.6 mm across the study population with an average map maximum of 1.4 mm. Along the cutaneous aspect, rib cortical bone thickness ranged from 0.7 to 1.9 mm with an average map thickness of 0.9 mm. Average cross-sectional properties show a steady reduction in total cortical bone area from 10% along the rib’s length through to the sternal end, whereas overall cross-sectional area remains relatively constant along the majority of the rib’s length before rising steeply towards the sternal end. On average, male ribs contained more cortical bone within a given cross-section than was seen for female ribs. Importantly, however, this difference was driven by male ribs having larger overall cross-sectional areas, rather than by sex differences in the bone thickness observed at specific local cortex sites. The cortical bone thickness results here can be used directly to improve the accuracy of current human body and rib models. Furthermore, the measurement corridors obtained from adult subjects across a wide age range can be used to validate future measurements from more widely available image sources such as clinical CT where gold standard reference measures (e.g. such as direct measurements obtained from cut sections) are otherwise unobtainable.Cortical Bone Mapping (CBM) of whole-rib CT scans was performed and maps of average adult cortical bone thickness and rib cross-sectional geometry were produced. Results were validated against cross-sectional rib histology images, whereby bone thickness accuracy was measured at under 0.02 mm and precision was measured at under 0.17 mm. Subsequent errors in bone cross-sectional area were under 5%. Results can drive advancements in the fidelity of current human body computational models.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152009/1/joa13045.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152009/2/joa13045_am.pd

A community based intervention program to enhance neighborhood cohesion: The Learning Families Project in Hong Kong

published_or_final_versio

Col-OSSOS: Colors of the Interstellar Planetesimal 1I/`Oumuamua

The recent discovery by Pan-STARRS1 of 1I/2017 U1 (`Oumuamua), on an unbound and hyperbolic orbit, offers a rare opportunity to explore the planetary formation processes of other stars, and the effect of the interstellar environment on a planetesimal surface. 1I/`Oumuamua's close encounter with the inner Solar System in 2017 October was a unique chance to make observations matching those used to characterize the small-body populations of our own Solar System. We present near-simultaneous g$^\prime$, r$^\prime$, and J photometry and colors of 1I/`Oumuamua from the 8.1-m Frederick C. Gillett Gemini North Telescope, and $gri$ photometry from the 4.2 m William Herschel Telescope. Our g$^\prime$r$^\prime$J observations are directly comparable to those from the high-precision Colours of the Outer Solar System Origins Survey (Col-OSSOS), which offer unique diagnostic information for distinguishing between outer Solar System surfaces. The J-band data also provide the highest signal-to-noise measurements made of 1I/`Oumuamua in the near-infrared. Substantial, correlated near-infrared and optical variability is present, with the same trend in both near-infrared and optical. Our observations are consistent with 1I/`Oumuamua rotating with a double-peaked period of $8.10 \pm 0.42$ hours and being a highly elongated body with an axial ratio of at least 5.3:1, implying that it has significant internal cohesion. The color of the first interstellar planetesimal is at the neutral end of the range of Solar System $g-r$ and $r-J$ solar-reflectance colors: it is like that of some dynamically excited objects in the Kuiper belt and the less-red Jupiter Trojans.Comment: Accepted to ApJ