Identification of a mutation associated with fatal Foal Immunodeficiency Syndrome in the Fell and Dales pony.

The Fell and Dales are rare native UK pony breeds at risk due to falling numbers, in-breeding, and inherited disease. Specifically, the lethal Mendelian recessive disease Foal Immunodeficiency Syndrome (FIS), which manifests as B-lymphocyte immunodeficiency and progressive anemia, is a substantial threat. A significant percentage (∼10%) of the Fell ponies born each year dies from FIS, compromising the long-term survival of this breed. Moreover, the likely spread of FIS into other breeds is of major concern. Indeed, FIS was identified in the Dales pony, a related breed, during the course of this work. Using a stepwise approach comprising linkage and homozygosity mapping followed by haplotype analysis, we mapped the mutation using 14 FIS-affected, 17 obligate carriers, and 10 adults of unknown carrier status to a ∼1 Mb region (29.8 - 30.8 Mb) on chromosome (ECA) 26. A subsequent genome-wide association study identified two SNPs on ECA26 that showed genome-wide significance after Bonferroni correction for multiple testing: BIEC2-692674 at 29.804 Mb and BIEC2-693138 at 32.19 Mb. The associated region spanned 2.6 Mb from ∼29.6 Mb to 32.2 Mb on ECA26. Re-sequencing of this region identified a mutation in the sodium/myo-inositol cotransporter gene (SLC5A3); this causes a P446L substitution in the protein. This gene plays a crucial role in the regulatory response to osmotic stress that is essential in many tissues including lymphoid tissues and during early embryonic development. We propose that the amino acid substitution we identify here alters the function of SLC5A3, leading to erythropoiesis failure and compromise of the immune system. FIS is of significant biological interest as it is unique and is caused by a gene not previously associated with a mammalian disease. Having identified the associated gene, we are now able to eradicate FIS from equine populations by informed selective breeding.

Hospital transfer of patients with acute myocardial infarction: the effects of age, race, and insurance type.

BACKGROUND: Many factors precipitate the transfer of patients hospitalized for acute myocardial infarction, including clinical status and the need for diagnostic testing and therapeutic interventions not available at the admitting hospital. The objectives of this study were to assess the frequency of transfer to another hospital and to determine whether nonmedical factors, such as age, sex, race, and insurance status, are associated with transfer. METHODS: We conducted a prospective study of patients with acute myocardial infarction who were enrolled in the National Registry of Myocardial Infarction 2 from June 1994 through March 1998. The Registry involves 1674 hospitals in the United States. All patients survived to the time of hospital discharge or until transfer. Multivariable logistic regression models, with transfer as the outcome variable, were developed for the entire sample, as well as for subgroups determined by the interventional capabilities of the admitting hospital. RESULTS: Of 537,283 patients with acute myocardial infarction, 152,310 (28%) were transferred to another hospital after admission. After adjustment for differences in clinical and hospital characteristics, factors that were most associated with a reduced odds of transfer included older age (odds ratio [OR] = 0.43; 95% confidence interval [CI]: 0.42 to 0.44 for those aged >75 vs. <65 years), African-American race (OR = 0.69; 95% CI: 0.67 to 0.71 for African Americans vs. whites), and Medicaid/self-pay insurance status (OR = 0.68; 95% CI: 0.66 to 0.70 for Medicaid/self-pay vs. commercial insurance). These effects were most apparent for patients admitted to hospitals without full invasive diagnostic and therapeutic capabilities, but persisted to some extent among those admitted to hospitals with full invasive services. CONCLUSION: Our findings suggest that nonmedical factors, including age, race, and insurance type, affect decisions regarding the transfer of patients hospitalized with acute myocardial infarction. As only a minority of the nation's hospitals offers a full range of cardiovascular diagnostic and therapeutic procedures, these findings reinforce ongoing concerns about disparities in access to health care services for some patients.

The XMaS beamline at ESRF: instrumental developments and high-resolution diffraction studies.

The beamline, which is situated on a bending magnet at ESRF, comprises a unique combination of instrumentation for high-resolution and magnetic single-crystal diffraction. White-beam operation is possible, as well as focused and unfocused monochromatic modes. In addition to an eleven-axis Huber diffractometer, which facilitates simple operation in both vertical and horizontal scattering geometries, there is an in-vacuum polarization analyser and slit system, mirrors for harmonic rejection, sub 4.2 K and 1 Tesla magnetic field sample environment, plus a diamond phase plate for polarization conditioning. The instrumentation developed specifically for this beamline is described, and its use illustrated by recent scientific results.

Magnetism in nickel and synchrotron beam polarization studied by X-ray diffraction.

The ratio of the magnetic to the charge form factors of nickel has been determined by white-beam X-ray diffraction. The measurements were made on the new UK magnetic scattering beamline (XMaS) on a dipole source at the ESRF. The data comprise the three (h,h,0) reflections (4,4,0), (6,6,0) and (8,8,0) and the seven high-order (h,0,0) reflections (6,0,0) to (18,0,0), which doubles the range of wavevectors compared to previous studies. The data have been analysed using Hartree-Fock free-ion wave functions and core electron polarization effects were included. The results support the interpretation of neutron data obtained at lower momentum transfer for the e(g) and t(2g) orbital occupancies. The polarization of the dipole source is deduced to vary from 99.88 to 99.83% between 5 and 15 keV, respectively. This high value makes it an extremely suitable source for studies of ferromagnetism.

Computerized tomography in orthopedic surgery.

Computerized tomography has been demonstrated to be highly effective and accurate in delineating soft tissue and bony cross-sectional anatomy. The technique is very helpful in: (A) delineating the 3-dimensional extents of destructive lesions; (B) defining the nature of lesions by revealing their tissue densities and invasive characteristics; and (C) delineating the cross-sectional anatomy of complex geometric lesions; for example, fractures of the pelvis and spine. These features enable the orthopedic surgeon to better diagnose pathological lesions, plan surgical procedures, screen patients for metastases, and facilitate percutaneous biopsy or aspiration of difficult anatomic sites. While these applications are becoming well established, additional uses are under investigation in the areas of trauma, and in clinical research of metabolic bone disease.