Nonparametric estimation of ROC curves in the absence of a gold standard

In the evaluation of diagnostic accuracy of tests, a gold standard on the disease status is required. However, in many complex diseases, it is impossible or unethical to obtain such a gold standard. If an imperfect standard is used, the estimated accuracy of the tests would be biased. This type of bias is called imperfect gold standard bias. In this article we develop a nonparametric maximum likelihood method for estimating ROC curves and their areas of ordinal-scale tests in the absence of a gold standard. Our simulation study shows that the proposed estimators for the ROC curve areas have good finite-sample properties in terms of bias and mean squared error. Further simulation studies show that our nonparametric approach is comparable to the binormal parametric method, and is easier to implement. Finally, we illustrate the application of the proposed method in a real clinical study on assessing the accuracy of seven specific pathologists in detecting carcinoma in situ of the uterine cervix.     

Sorting nexins--unifying trends and new perspectives

The sorting nexins (SNXs) are a family of PX domain-containing proteins found in yeast and mammalian cells that have been proposed to regulate intracellular trafficking. Mammalian SNXs have been suggested to function variously in pro-degradative sorting, internalization, endosomal recycling, or simply in endosomal sorting. In yeast, the defining function for these proteins is a regulation of cargo retrieval. Here we examine recent data on the SNX family of proteins and attempt to draw out unifying themes between the work performed in yeast and mammalian systems.     

Structure of the bundle-forming pilus from enteropathogenic Escherichia coli

Bundle-forming pili (BFP) are essential for the full virulence of enteropathogenic Escherichia coli (EPEC) because they are required for localized adherence to epithelial cells and auto-aggregation. We report the high resolution structure of bundlin, the monomer of BFP, solved by NMR. The structure reveals a new variation in the topology of type IVb pilins with significant differences in the composition and relative orientation of elements of secondary structure. In addition, the structural parameters of native BFP filaments were determined by electron microscopy after negative staining. The solution structure of bundlin was assembled according to these helical parameters to provide a plausible atomic resolution model for the BFP filament. We show that EPEC and Vibriocholerae type IVb pili display distinct differences in their monomer subunits consistent with data showing that bundlin and TcpA cannot complement each other, but assemble into filaments with similar helical organization.     

Compensating bends in a 16-base-pair DNA oligomer containing a T(3)A(3) segment: A NMR study of global DNA curvature

In-phase ligated DNA containing T(n)A(n) segments fail to exhibit the retarded polyacrylamide gel electrophoresis (PAGE) migration observed for in-phase ligated A(n)T(n) segments, a behavior thought to be correlated with macroscopic DNA curvature. The lack of macroscopic curvature in ligated T(n)A(n) segments is thought to be due to cancellation of bending in regions flanking the TpA steps. To address this issue, solution-state NMR, including residual dipolar coupling (RDC) restraints, was used to determine a high-resolution structure of [d(CGAGGTTTAAACCTCG)2], a DNA oligomer containing a T3A3 tract. The overall magnitude and direction of bending, including the regions flanking the central TpA step, was measured using a radius of curvature, Rc, analysis. The Rc for the overall molecule indicated a small magnitude of global bending (Rc = 138 +/- 23 nm) towards the major groove, whereas the Rc for the two halves (72 +/- 33 nm and 69 +/- 14 nm) indicated greater localized bending into the minor groove. The direction of bending in the regions flanking the TpA step is in partial opposition (109 degrees), contributing to cancellation of bending. The cancellation of bending did not correlate with a pattern of roll values at the TpA step, or at the 5' and 3' junctions, of the T3A3 segment, suggesting a simple junction/roll model is insufficient to predict cancellation of DNA bending in all T(n)A(n) junction sequence contexts. Importantly, Rc analysis of structures refined without RDC restraints lacked the precision and accuracy needed to reliably measure bending.     

Fine-mapping and candidate gene analysis of bovine spinal muscular atrophy

Bovine spinal muscular atrophy (SMA), an autosomal recessive neurodegenerative disease, has been mapped at moderate resolution to the distal part of Chromosome 24. In this article we confirm this location and fine-map the SMA locus to an interval of approximately 0.8 cM at the very distal end of BTA24. Despite remarkable similarity to human SMA, the causative gene SMN can be excluded in bovine SMA. However, the interval where the disease now has been mapped contains BCL2, like SMN an antiapoptotic factor, and shown to bind to SMN. Moreover, knockout mice lacking the BCL2 gene show rapid motor neuron degeneration with early postnatal onset, as observed in bovine SMA. A comparative cattle/human map of the distal end of BTA24, based on the emerging bovine genome sequencing data, shows conserved synteny to HSA18 with hints of a segmental duplication and pericentic inversion just after the last available bovine marker DIK4971. This synteny lets us conclude that SMA is in immediate vicinity of the telomere. Candidate gene analysis of BCL2, however, excludes most of this gene, except its promoter region, and draws attention to the neighboring gene VPS4B, part of the endosomal protein-sorting machinery ESCRT-III which is involved in several neurodegenerative diseases. Stefan Krebs and Ivica Medugorac contributed equally to this work and agreed to be considered as first authors.     

Ferruginous pygmy-owl (Glaucidium brasilianum) and eastern screech-owl (Megascopes asio): new hosts for Philornis mimicola (Diptera: Muscidae) and Ornithodoros concanensis (Acari: Argasidae)

While banding ferruginous pygmy-owls (Glaucidium brasilianum) and Eastern screech-owls (Megascops asio) in south Texas during 2004, we recorded Philornis mimicola (Diptera: Muscidae) and Ornithodoros concanensis (Acari: Argasidae) parasitizing nestlings. Inspection of nestlings revealed 54 P. mimicola and one O. concanensis. Inspection of nest material revealed 111 P. mimicola, including 57 puparia. The effect (e.g., blood loss, anemia) of these hematophagous parasites might have contributed to the demise of at least one Eastern screech-owl nestling. This is the first record of P. mimicola and O. concanensis parasitizing ferruginous pygmy-owls and Eastern screech-owls.     

Body mass index of married Bangladeshi women: trends and association with socio-demographic factors

Body mass index (BMI) is a good indicator of nutritional status in a population. In underdeveloped countries like Bangladesh, this indicator provides a method that can assist intervention to help eradicate many preventable diseases. This study aimed to report on changes in the BMI of married Bangladeshi women who were born in the past three decades and its association with socio-demographic factors. Data for 10,115 married and currently non-pregnant Bangladeshi women were extracted from the 2007 Bangladesh Demographic and Health Survey (BDHS). The age range of the sample was 15-49 years. The mean BMI was 20.85 ± 3.66 kg/m(2), and a decreasing tendency in BMI was found among birth year cohorts from 1972 to 1992. It was found that the proportion of underweight females has been increasing in those born during the last 20 years of the study period (1972 to 1992). Body mass index increased with increasing age, education level of the woman and her husband, wealth index, age at first marriage and age at first delivery, and decreased with increasing number of ever-born children. Lower BMI was especially pronounced among women who were living in rural areas, non-Muslims, employed women, women not living with their husbands (separated) or those who had delivered at home or non-Caesarean delivery.