I was on the college web page and saw this year’s Alumni Awards recipients. Who is the earliest alum to be honored?

Abbot Pennings answers a question about the alumni awards, archived from the SNC website

Two-stage study designs for analyzing disease-associated covariates: linkage thresholds and case-selection strategies

The incorporation of disease-associated covariates into studies aiming to identify susceptibility genes for complex human traits is a challenging problem. Accounting for such covariates in genetic linkage and association analyses may help reduce the genetic heterogeneity inherent in these complex phenotypes. For Genetic Analysis Workshop 15 (GAW15) Problem 3 simulated data, our goal was to compare the power of several two-stage study designs to identify rheumatoid arthritis-related genes on chromosome 9 (disease severity), 11 (IgM), and 18 (anti-cyclic citrinullated protein), with knowledge of the answers. Five study designs incorporating an initial linkage step, followed by a case-selection scheme and case-control association analysis by logistic regression, were considered. The linkage step was either qualitative-trait linkage analysis as implemented in MERLIN-nonparametric linkage (NPL), or quantitative-trait locus analysis as implemented in MERLIN-REGRESS. A set of cases representing either one case from each available family, one case per linked family (NPL ≥ 0), or one case from each family identified by ordered-subset analysis was chosen for comparison with the full set of 2000 simulated controls. As expected, the performance of these study designs depended on the disease model used to generate the data, especially the simulated allele frequency difference between cases and controls. The quantitative trait loci analysis performed well in identifying these loci, and the power to identify disease-associated alleles was increased by using ordered-subset analysis as a case selection tool

Astro2010: State of the Profession Position Paper: The Value of Observatory-Class Missions

The dramatic success of NASA’s astrophysics science program over the past 20 years has resulted from a series of assets in space ranging from Small Explorers to Observatory-Class missions. NASA’s Observatory-Class missions, such as the Chandra X-ray Observatory (CXO), the Hubble Space Telescope (HST), and the Spitzer Space Telescope (SST), form the cornerstone of this program by providing all researchers, regardless of institutional affiliation, a spectrum of science opportunities across programs large and small. These observatories stand out in their breadth of capabilities and consequent diversity of high impact science, their reach within the scientific community, and their proven ability to inspire the nation. Each mission was designed to address specific scientific imperatives recognized by past Decadal Survey Committees, whether it was to refine the extragalactic distance scale, examine galaxies as they were in the distant past, determine the relationship between black holes and quasars, observe the ultimate fate of stars in their death throes, or reveal heavily obscured regions of star-formation. These were ambitious goals, as are those envisioned for future Observatory-Class missions, such as the James Webb Space Telescope (JWST)

Simple method for sub-diffraction resolution imaging of cellular structures on standard confocal microscopes by three-photon absorption of quantum dots

This study describes a simple technique that improves a recently developed 3D sub-diffraction imaging method based on three-photon absorption of commercially available quantum dots. The method combines imaging of biological samples via tri-exciton generation in quantum dots with deconvolution and spectral multiplexing, resulting in a novel approach for multi-color imaging of even thick biological samples at a 1.4 to 1.9-fold better spatial resolution. This approach is realized on a conventional confocal microscope equipped with standard continuous-wave lasers. We demonstrate the potential of multi-color tri-exciton imaging of quantum dots combined with deconvolution on viral vesicles in lentivirally transduced cells as well as intermediate filaments in three-dimensional clusters of mouse-derived neural stem cells (neurospheres) and dense microtubuli arrays in myotubes formed by stacks of differentiated C2C12 myoblasts

Meeting Report: Measuring Endocrine-Sensitive Endpoints within the First Years of Life

An international workshop titled “Assessing Endocrine-Related Endpoints within the First Years of Life” was held 30 April–1 May 2007, in Ottawa, Ontario, Canada. Representatives from a number of pregnancy cohort studies in North America and Europe presented options for measuring various endocrine-sensitive endpoints in early life and discussed issues related to performing and using those measures. The workshop focused on measuring reproductive tract developmental endpoints [e.g., anogenital distance (AGD)], endocrine status, and infant anthropometry. To the extent possible, workshop participants strove to develop or recommend standardized measurements that would allow comparisons and pooling of data across studies. The recommended outcomes include thigh fat fold, breast size, vaginal cytology, AGD, location of the testis, testicular size, and growth of the penis, with most of the discussion focusing on the genital exam. Although a number of outcome measures recommended during the genital exam have been associated with exposure to endocrine-disrupting chemicals, little is known about how predictive these effects are of later reproductive health or other chronic health conditions

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

Neurologic Factors in Female Sexual Function and Dysfunction

Sexual dysfunction affects both men and women, involving organic disorders, psychological problems, or both. Overall, the state of our knowledge is less advanced regarding female sexual physiology in comparison with male sexual function. Female sexual dysfunction has received little clinical and basic research attention and remains a largely untapped field in medicine. The epidemiology of female sexual dysfunction is poorly understood because relatively few studies have been done in community settings. In the United States, female sexual dysfunction has been estimated to affect 40% of women in the general population. Among the elderly, however, it has been reported that up to 87% of women complain of sexual dissatisfaction. Several studies have shown that the prevalence of female sexual arousal disorders correlates significantly with increasing age. These studies have shown that sexual arousal and frequency of coitus in the female decreases with increasing age. The pathophysiology of female sexual dysfunction appears more complex than that of males, involving multidimensional hormonal, neurological, vascular, psychological, and interpersonal aspects. Organic female sexual disorders may include a wide variety of vascular, neural, or neurovascular factors that lead to problems with libido, lubrication, and orgasm. However, the precise etiology and mechanistic pathways of age-related female sexual arousal disorders are yet to be determined. In the past two decades, some advances have been made in exploring the basic hemodynamics and neuroregulation of female sexual function and dysfunction in both animal models and in human studies. In this review, we summarize neural regulation of sexual function and neurological causes of sexual dysfunction in women

The Space Infrared Interferometric Telescope (SPIRIT): High-resolution imaging and spectroscopy in the far-infrared

We report results of a recently-completed pre-Formulation Phase study of SPIRIT, a candidate NASA Origins Probe mission. SPIRIT is a spatial and spectral interferometer with an operating wavelength range 25 - 400 microns. SPIRIT will provide sub-arcsecond resolution images and spectra with resolution R = 3000 in a 1 arcmin field of view to accomplish three primary scientific objectives: (1) Learn how planetary systems form from protostellar disks, and how they acquire their inhomogeneous composition; (2) characterize the family of extrasolar planetary systems by imaging the structure in debris disks to understand how and where planets of different types form; and (3) learn how high-redshift galaxies formed and merged to form the present-day population of galaxies. Observations with SPIRIT will be complementary to those of the James Webb Space Telescope and the ground-based Atacama Large Millimeter Array. All three observatories could be operational contemporaneously.Comment: 20 pages, 12 figures, accepted for publication in J. Adv. Space Res. on 26 May 200

Power estimation for non-standardized multisite studies

AbstractA concern for researchers planning multisite studies is that scanner and T1-weighted sequence-related biases on regional volumes could overshadow true effects, especially for studies with a heterogeneous set of scanners and sequences. Current approaches attempt to harmonize data by standardizing hardware, pulse sequences, and protocols, or by calibrating across sites using phantom-based corrections to ensure the same raw image intensities. We propose to avoid harmonization and phantom-based correction entirely. We hypothesized that the bias of estimated regional volumes is scaled between sites due to the contrast and gradient distortion differences between scanners and sequences. Given this assumption, we provide a new statistical framework and derive a power equation to define inclusion criteria for a set of sites based on the variability of their scaling factors. We estimated the scaling factors of 20 scanners with heterogeneous hardware and sequence parameters by scanning a single set of 12 subjects at sites across the United States and Europe. Regional volumes and their scaling factors were estimated for each site using Freesurfer's segmentation algorithm and ordinary least squares, respectively. The scaling factors were validated by comparing the theoretical and simulated power curves, performing a leave-one-out calibration of regional volumes, and evaluating the absolute agreement of all regional volumes between sites before and after calibration. Using our derived power equation, we were able to define the conditions under which harmonization is not necessary to achieve 80% power. This approach can inform choice of processing pipelines and outcome metrics for multisite studies based on scaling factor variability across sites, enabling collaboration between clinical and research institutions

X-Ray Phase-Contrast Tomography of Renal Ischemia-Reperfusion Damage

Purpose: The aim of the study was to investigate microstructural changes occurring in unilateral renal ischemia-reperfusion injury in a murine animal model using synchrotron radiation. Material and Methods: The effects of renal ischemia-reperfusion were investigated in a murine animal model of unilateral ischemia. Kidney samples were harvested on day 18. Grating-Based Phase-Contrast Imaging (GB-PCI) of the paraffin-embedded kidney samples was performed at a Synchrotron Radiation Facility (beam energy of 19 keV). To obtain phase information, a two-grating Talbot interferometer was used applying the phase stepping technique. The imaging system provided an effective pixel size of 7.5 mu m. The resulting attenuation and differential phase projections were tomographically reconstructed using filtered back-projection. Semi-automated segmentation and volumetry and correlation to histopathology were performed. Results: GB-PCI provided good discrimination of the cortex, outer and inner medulla in non-ischemic control kidneys. Post-ischemic kidneys showed a reduced compartmental differentiation, particularly of the outer stripe of the outer medulla, which could not be differentiated from the inner stripe. Compared to the contralateral kidney, after ischemia a volume loss was detected, while the inner medulla mainly retained its volume (ratio 0.94). Post-ischemic kidneys exhibited severe tissue damage as evidenced by tubular atrophy and dilatation, moderate inflammatory infiltration, loss of brush borders and tubular protein cylinders. Conclusion: In conclusion GB-PCI with synchrotron radiation allows for non-destructive microstructural assessment of parenchymal kidney disease and vessel architecture. If translation to lab-based approaches generates sufficient density resolution, and with a time-optimized image analysis protocol, GB-PCI may ultimately serve as a non-invasive, non-enhanced alternative for imaging of pathological changes of the kidney