On the segmentation and classification of hand radiographs

This research is part of a wider project to build predictive models of bone age using hand radiograph images. We examine ways of finding the outline of a hand from an X-ray as the first stage in segmenting the image into constituent bones. We assess a variety of algorithms including contouring, which has not previously been used in this context. We introduce a novel ensemble algorithm for combining outlines using two voting schemes, a likelihood ratio test and dynamic time warping (DTW). Our goal is to minimize the human intervention required, hence we investigate alternative ways of training a classifier to determine whether an outline is in fact correct or not. We evaluate outlining and classification on a set of 1370 images. We conclude that ensembling with DTW improves performance of all outlining algorithms, that the contouring algorithm used with the DTW ensemble performs the best of those assessed, and that the most effective classifier of hand outlines assessed is a random forest applied to outlines transformed into principal components

Wide-Field InfraRed Survey Telescope (WFIRST) Final Report

In December 2010, NASA created a Science Definition Team (SDT) for WFIRST, the Wide Field Infra-Red Survey Telescope, recommended by the Astro 2010 Decadal Survey as the highest priority for a large space mission. The SDT was chartered to work with the WFIRST Project Office at GSFC and the Program Office at JPL to produce a Design Reference Mission (DRM) for WFIRST. Part of the original charge was to produce an interim design reference mission by mid-2011. That document was delivered to NASA and widely circulated within the astronomical community. In late 2011 the Astrophysics Division augmented its original charge, asking for two design reference missions. The first of these, DRM1, was to be a finalized version of the interim DRM, reducing overall mission costs where possible. The second of these, DRM2, was to identify and eliminate capabilities that overlapped with those of NASA's James Webb Space Telescope (henceforth JWST), ESA's Euclid mission, and the NSF's ground-based Large Synoptic Survey Telescope (henceforth LSST), and again to reduce overall mission cost, while staying faithful to NWNH. This report presents both DRM1 and DRM2.Comment: 102 pages, 57 figures, 17 table

Exoplanet Characterization and the Search for Life

Over 300 extrasolar planets (exoplanets) have been detected orbiting nearby stars. We now hope to conduct a census of all planets around nearby stars and to characterize their atmospheres and surfaces with spectroscopy. Rocky planets within their star's habitable zones have the highest priority, as these have the potential to harbor life. Our science goal is to find and characterize all nearby exoplanets; this requires that we measure the mass, orbit, and spectroscopic signature of each one at visible and infrared wavelengths. The techniques for doing this are at hand today. Within the decade we could answer long-standing questions about the evolution and nature of other planetary systems, and we could search for clues as to whether life exists elsewhere in our galactic neighborhood.Comment: 7 pages, 2 figures, submitted to Astro2010 Decadal Revie

Calibration of myocardial T2 and T1 against iron concentration.

BACKGROUND: The assessment of myocardial iron using T2* cardiovascular magnetic resonance (CMR) has been validated and calibrated, and is in clinical use. However, there is very limited data assessing the relaxation parameters T1 and T2 for measurement of human myocardial iron. METHODS: Twelve hearts were examined from transfusion-dependent patients: 11 with end-stage heart failure, either following death (n=7) or cardiac transplantation (n=4), and 1 heart from a patient who died from a stroke with no cardiac iron loading. Ex-vivo R1 and R2 measurements (R1=1/T1 and R2=1/T2) at 1.5 Tesla were compared with myocardial iron concentration measured using inductively coupled plasma atomic emission spectroscopy. RESULTS: From a single myocardial slice in formalin which was repeatedly examined, a modest decrease in T2 was observed with time, from mean (± SD) 23.7 ± 0.93 ms at baseline (13 days after death and formalin fixation) to 18.5 ± 1.41 ms at day 566 (p<0.001). Raw T2 values were therefore adjusted to correct for this fall over time. Myocardial R2 was correlated with iron concentration [Fe] (R2 0.566, p<0.001), but the correlation was stronger between LnR2 and Ln[Fe] (R2 0.790, p<0.001). The relation was [Fe] = 5081•(T2)-2.22 between T2 (ms) and myocardial iron (mg/g dry weight). Analysis of T1 proved challenging with a dichotomous distribution of T1, with very short T1 (mean 72.3 ± 25.8 ms) that was independent of iron concentration in all hearts stored in formalin for greater than 12 months. In the remaining hearts stored for <10 weeks prior to scanning, LnR1 and iron concentration were correlated but with marked scatter (R2 0.517, p<0.001). A linear relationship was present between T1 and T2 in the hearts stored for a short period (R2 0.657, p<0.001). CONCLUSION: Myocardial T2 correlates well with myocardial iron concentration, which raises the possibility that T2 may provide additive information to T2* for patients with myocardial siderosis. However, ex-vivo T1 measurements are less reliable due to the severe chemical effects of formalin on T1 shortening, and therefore T1 calibration may only be practical from in-vivo human studies

Analytic philosophy for biomedical research: the imperative of applying yesterday's timeless messages to today's impasses

The mantra that "the best way to predict the future is to invent it" (attributed to the computer scientist Alan Kay) exemplifies some of the expectations from the technical and innovative sides of biomedical research at present. However, for technical advancements to make real impacts both on patient health and genuine scientific understanding, quite a number of lingering challenges facing the entire spectrum from protein biology all the way to randomized controlled trials should start to be overcome. The proposal in this chapter is that philosophy is essential in this process. By reviewing select examples from the history of science and philosophy, disciplines which were indistinguishable until the mid-nineteenth century, I argue that progress toward the many impasses in biomedicine can be achieved by emphasizing theoretical work (in the true sense of the word 'theory') as a vital foundation for experimental biology. Furthermore, a philosophical biology program that could provide a framework for theoretical investigations is outlined

Ex vivo mycobacterial growth inhibition assay (MGIA) for tuberculosis vaccine testing - a protocol for mouse splenocytes

The testing of vaccines for tuberculosis is costly and time-consuming, and dependent on preclinical animal challenge models and clinical trials. We have recently developed a mycobacterial growth inhibition assay (MGIA) to test vaccine efficacy ex vivo. This assay measures the summative effect of the host immune response and may serve as a novel tool to facilitate vaccine testing. It has generated much interest recently, and to facilitate technology transfer and reproducibility between laboratories, we here describe a detailed protocol for an ex vivo MGIA in mouse splenocytes.</jats:p

The association between levels of alcohol consumption and mental health problems and academic performance among young university students

Purpose: Mental health problems and harmful alcohol consumption have been found to be high among young university students compared to the general population in Australia. This research aimed to investigate the association between levels of drinking and mental health problems and academic performance among university students aged 18 to 24 years. Methods: This study used a quantitative cross-sectional design using data that were collected in 2014 as part of the Youth Alcohol Project (YAP). Participants were randomly drawn from a cross sectional sample of 6000 undergraduate students. Included in the study were only students who were within the age of 18-24, undergraduate, and internally enrolled at the main campus. A total of 2518 undergraduate students aged 18 to 24 years who were enrolled internally at Curtin University Bentley campus were randomly recruited. Data were collected through an online survey. Students were invited to participate in the study through their student email address. The email invitations coincided with the release of semester results to increase the likelihood of students accessing their emails. A further 628 students were randomly recruited through face to face intercept survey during the campus market days. Data were collected by trained research assistants. Validated instruments were used to collected data on levels of alcohol consumption, mental health, and academic performance. Results: A considerable proportion of participants (44%) reported consuming alcohol at hazardous or harmful levels. Multiple logistic regression analysis showed that students who were consuming alcohol at hazardous levels were 1.2 times more likely to report psychological distress than those with lower levels of alcohol consumption (aOR 1.2, 95% CI: 1.1-1.5). In addition, being late for class (aOR 1.7, 95% CI:1.1-2.4), missing classes (aOR = 2.6, 95% CI: 1.9-2.6), inability to concentrate in class (aOR = 2.6, 95% CI: 1.9-3.4), and inability to complete assignments (aOR = 3.5, 95% CI 2.0-6.0) independently predicted for moderate or hazardous alcohol consumption. Conclusion: The study shows that a considerable proportion of undergraduate students at university consume alcohol at hazardous or harmful levels. In addition, high levels of alcohol consumption are associated with poor academic performance and mental health outcomes among students. The results of the study warrant multi-strategy interventions that focus on policy, organisational, educational, environmental and economic strategies that will help to reduce alcohol related harms among university students

Pharmacogenetic Associations of MMP9 and MMP12 Variants with Cardiovascular Disease in Patients with Hypertension

MMP-9 and -12 function in tissue remodeling and may play roles in cardiovascular disease (CVD). We assessed associations of four MMP polymorphisms and three antihypertensive drugs with cardiovascular outcomes.Hypertensives (n = 42,418) from a double-blind, randomized, clinical trial were randomized to chlorthalidone, amlodipine, lisinopril, or doxazosin treatment (mean follow up, 4.9 years). The primary outcome was coronary heart disease (CHD). Secondary outcomes included combined CHD, all CVD outcomes combined, stroke, heart failure (HF), and mortality. Genotype-treatment interactions were tested. = 0.015). for CHD and composite CVD. The data suggest that these genes may provide useful clinical information with respect to treatment decisions

Investigating Bacterial Sources of Toxicity as an Environmental Contributor to Dopaminergic Neurodegeneration

Parkinson disease (PD) involves progressive neurodegeneration, including loss of dopamine (DA) neurons from the substantia nigra. Select genes associated with rare familial forms of PD function in cellular pathways, such as the ubiquitin-proteasome system (UPS), involved in protein degradation. The misfolding and accumulation of proteins, such as α-synuclein, into inclusions termed Lewy Bodies represents a clinical hallmark of PD. Given the predominance of sporadic PD among patient populations, environmental toxins may induce the disease, although their nature is largely unknown. Thus, an unmet challenge surrounds the discovery of causal or contributory neurotoxic factors that could account for the prevalence of sporadic PD. Bacteria within the order Actinomycetales are renowned for their robust production of secondary metabolites and might represent unidentified sources of environmental exposures. Among these, the aerobic genera, Streptomyces, produce natural proteasome inhibitors that block protein degradation and may potentially damage DA neurons. Here we demonstrate that a metabolite produced by a common soil bacterium, S. venezuelae, caused DA neurodegeneration in the nematode, Caenorhabditis elegans, which increased as animals aged. This metabolite, which disrupts UPS function, caused gradual degeneration of all neuronal classes examined, however DA neurons were particularly vulnerable to exposure. The presence of DA exacerbated toxicity because neurodegeneration was attenuated in mutant nematodes depleted for tyrosine hydroxylase (TH), the rate-limiting enzyme in DA production. Strikingly, this factor caused dose-dependent death of human SH-SY5Y neuroblastoma cells, a dopaminergic line. Efforts to purify the toxic activity revealed that it is a highly stable, lipophilic, and chemically unique small molecule. Evidence of a robust neurotoxic factor that selectively impacts neuronal survival in a progressive yet moderate manner is consistent with the etiology of age-associated neurodegenerative diseases. Collectively, these data suggest the potential for exposures to the metabolites of specific common soil bacteria to possibly represent a contributory environmental component to PD