Occupational Exposure to Trichloroethylene and Cancer Risk for Workers at the Paducah Gaseous Diffusion Plant

Objective: The Paducah Gaseous Diffusion Plant (PGDP) became operational in 1952; it is located in the western part of Kentucky. We conducted a mortality study for adverse health effects that workers may have suffered while working at the plant, including exposures to chemicals. Materials and Methods: We studied a cohort of 6820 workers at the PGDP for the period 1953 to 2003; there were a total of 1672 deaths to cohort members. Trichloroethylene (TCE) is a specific concern for this workforce; exposure to TCE occurred primarily in departments that clean the process equipment. The Life Table Analysis System (LTAS) program developed by NIOSH was used to calculate the standardized mortality ratios for the worker cohort and standardized rate ratio relative to exposure to TCE (the U.S. population is the referent for age-adjustment). LTAS calculated a significantly low overall SMR for these workers of 0.76 (95% CI: 0.72-0.79). A further review of three major cancers of interest to Kentucky produced significantly low SMR for trachea, bronchus, lung cancer (0.75, 95% CI: 0.72-0.79) and high SMR for Non-Hodgkin\u27s lymphoma (NHL) (1.49, 95% CI: 1.02-2.10). Results: No significant SMR was observed for leukemia and no significant SRRs were observed for any disease. Both the leukemia and lung cancer results were examined and determined to refect regional mortality patterns. However, the Non-Hodgkin\u27s Lymphoma finding suggests a curious amplification when living cases are included with the mortality experience. Conclusions: Further examination is recommended of this recurrent finding from all three U.S. Gaseous Diffusion plants

Acoustics and oceanographic observations collected during the QPE Experiment by Research Vessels OR1, OR2 and OR3 in the East China Sea in the Summer of 2009

This document describes data, sensors, and other useful information pertaining to the ONR sponsored QPE field program to quantify, predict and exploit uncertainty in observations and prediction of sound propagation. This experiment was a joint operation between Taiwanese and U.S. researchers to measure and assess uncertainty of predictions of acoustic transmission loss and ambient noise, and to observe the physical oceanography and geology that are necessary to improve their predictability. This work was performed over the continental shelf and slope northeast of Taiwan at two sites: one that was a relatively flat, homogeneous shelf region and a more complex geological site just shoreward of the shelfbreak that was influenced by the proximity of the Kuroshio Current. Environmental moorings and ADCP moorings were deployed and a shipboard SeaSoar vehicle was used to measure environmental spatial structure. In addition, multiple bottom moored receivers and a horizontal hydrophone array were deployed to sample transmission loss from a mobile source and ambient noise. The acoustic sensors, environmental sensors, shipboard resources, and experiment design, and their data, are presented and described in this technical report.Funding was provided by the Office of Naval Research under Contract No. N00014-08-1-076

Genotype-Phenotype Correlation in the Long-QT Syndrome

Background —The congenital long-QT syndrome (LQTS) is caused by mutations on several genes, all of which encode cardiac ion channels. The progressive understanding of the electrophysiological consequences of these mutations opens unforeseen possibilities for genotype-phenotype correlation studies. Preliminary observations suggested that the conditions ("triggers") associated with cardiac events may in large part be gene specific. Methods and Results —We identified 670 LQTS patients of known genotype (LQT1, n=371; LQT2, n=234; LQT3, n=65) who had symptoms (syncope, cardiac arrest, sudden death) and examined whether 3 specific triggers (exercise, emotion, and sleep/rest without arousal) differed according to genotype. LQT1 patients experienced the majority of their events (62%) during exercise, and only 3% occurred during rest/sleep. These percentages were almost reversed among LQT2 and LQT3 patients, who were less likely to have events during exercise (13%) and more likely to have events during rest/sleep (29% and 39%). Lethal and nonlethal events followed the same pattern. Corrected QT interval did not differ among LQT1, LQT2, and LQT3 patients (498, 497, and 506 ms, respectively). The percent of patients who were free of recurrence with β-blocker therapy was higher and the death rate was lower among LQT1 patients (81% and 4%, respectively) than among LQT2 (59% and 4%, respectively) and LQT3 (50% and 17%, respectively) patients. Conclusions —Life-threatening arrhythmias in LQTS patients tend to occur under specific circumstances in a gene-specific manner. These data allow new insights into the mechanisms that relate the electrophysiological consequences of mutations on specific genes to clinical manifestations and offer the possibility of complementing traditional therapy with gene-specific approaches

Discovering Sequence Motifs with Arbitrary Insertions and Deletions

Biology is encoded in molecular sequences: deciphering this encoding remains a grand scientific challenge. Functional regions of DNA, RNA, and protein sequences often exhibit characteristic but subtle motifs; thus, computational discovery of motifs in sequences is a fundamental and much-studied problem. However, most current algorithms do not allow for insertions or deletions (indels) within motifs, and the few that do have other limitations. We present a method, GLAM2 (Gapped Local Alignment of Motifs), for discovering motifs allowing indels in a fully general manner, and a companion method GLAM2SCAN for searching sequence databases using such motifs. glam2 is a generalization of the gapless Gibbs sampling algorithm. It re-discovers variable-width protein motifs from the PROSITE database significantly more accurately than the alternative methods PRATT and SAM-T2K. Furthermore, it usefully refines protein motifs from the ELM database: in some cases, the refined motifs make orders of magnitude fewer overpredictions than the original ELM regular expressions. GLAM2 performs respectably on the BAliBASE multiple alignment benchmark, and may be superior to leading multiple alignment methods for “motif-like” alignments with N- and C-terminal extensions. Finally, we demonstrate the use of GLAM2 to discover protein kinase substrate motifs and a gapped DNA motif for the LIM-only transcriptional regulatory complex: using GLAM2SCAN, we identify promising targets for the latter. GLAM2 is especially promising for short protein motifs, and it should improve our ability to identify the protein cleavage sites, interaction sites, post-translational modification attachment sites, etc., that underlie much of biology. It may be equally useful for arbitrarily gapped motifs in DNA and RNA, although fewer examples of such motifs are known at present. GLAM2 is public domain software, available for download at http://bioinformatics.org.au/glam2

Combined duodenal and jejunal atresia forming a bile filled cyst, presenting as an abdominal mass: A case report and review of the literature

The simultaneous occurrence of duodenal and jejunoileal atresia in the newborn is very rare. This is not surprising considering the unrelated embryogenesis behind the development of the two congenital anomalies. We present a case of duodenal atresia associated with an apple peel jejunoileal atresia in a newborn presenting with a prenatal diagnosis of an abdominal cystic mass and a palpable abdominal mass at birth. Exploration revealed a type 3 duodenal atresia followed by a type 3b proximal jejunal atresia (apple peel configuration), with a dilated short segment of bowel between the two. This segment of bowel was the cystic structure detected prenatally and preoperatively on exam. Double foregut atresias should be considered in the differential diagnosis of right upper quadrant cystic masses in the newborn period