Table builder problem - confidentiality for linked tables

The aim of this project is to investigate solutions to the problem of improving access to detailed survey data, while ensuring no person or organisation is likely to be identified, or otherwise put at risk of having their data disclosed, and to link general findings back to the ABS Table Builder problem. We focussed on making contributions in two main areas, namely: 1. Identification of sensitive cells in a table, 2. Maximizing data utility and minimising information loss - ensuring the table provides useful information

A. R. P. Walker Lecture - Food and the gut

No Abstract

Targeted therapy of short-bowel syndrome with teduglutide: the new kid on the block.

Extensive intestinal resection impairs the absorptive capacity and results in short-bowel syndrome-associated intestinal failure (SBS-IF), when fluid, electrolyte, acid-base, micro-, and macronutrient homeostasis cannot be maintained on a conventional oral diet. Several factors, including the length and site of the resected intestine, anatomical conformation of the remnant bowel, and the degree of postresection intestinal adaptation determine the disease severity. While mild SBS patients achieve nutritional autonomy with dietary modification (eg, hyperphagia, small frequent meals, and oral rehydration fluids), those with moderate-to-severe disease may develop SBS-IF and become dependent on parenteral support (PS) in the form of intravenous fluids and/or nutrition for sustenance of life. SBS-IF is a chronic debilitating disease associated with a poor quality of life, and carries significant morbidity and health care costs. Medical management of SBS-IF is primarily focused on individually tailored symptomatic treatment strategies, such as antisecretory and antidiarrheal agents to mitigate fluid losses, and PS. However, PS administration is associated with potentially life-threatening complications, such as central venous thromboses, bloodstream infections, and liver disease. In pursuit of a targeted therapy to augment intestinal adaptation, research over the past 2 decades has identified glucagon-like peptide, an intestinotrophic gut peptide that has been shown to enhance intestinal absorptive capacity by causing an increase in the villus length, crypt depth, and mesenteric blood flow and by decreasing gastrointestinal motility and secretions. Teduglutide, a recombinant analog of glucagon-like peptide-2, is the first targeted therapeutic agent to gain approval for use in adult SBS-IF. Teduglutide was shown to result in significant (20%-100%) reduction in PS-volume requirement and have a satisfactory safety profile in three randomized control trials. Further research is warranted to see if reduction in PS dependency translates to improved quality of life and reduced PS-associated complications

IRVE-II Post-Flight Trajectory Reconstruction

NASA s Inflatable Re-entry Vehicle Experiment (IRVE) II successfully demonstrated an inflatable aerodynamic decelerator after being launched aboard a sounding rocket from Wallops Flight Facility (WFF). Preliminary day of flight data compared well with pre-flight Monte Carlo analysis, and a more complete trajectory reconstruction performed with an Extended Kalman Filter (EKF) approach followed. The reconstructed trajectory and comparisons to an attitude solution provided by NASA Sounding Rocket Operations Contract (NSROC) personnel at WFF are presented. Additional comparisons are made between the reconstructed trajectory and pre and post-flight Monte Carlo trajectory predictions. Alternative observations of the trajectory are summarized which leverage flight accelerometer measurements, the pre-flight aerodynamic database, and on-board flight video. Finally, analysis of the payload separation and aeroshell deployment events are presented. The flight trajectory is reconstructed to fidelity sufficient to assess overall project objectives related to flight dynamics and overall, IRVE-II flight dynamics are in line with expectation

Microbial Induction of Immunity, Inflammation, and Cancer

The human microbiota presents a highly active metabolic that influences the state of health of our gastrointestinal tracts as well as our susceptibility to disease. Although much of our initial microbiota is adopted from our mothers, its final composition and diversity is determined by environmental factors. Westernization has significantly altered our microbial function. Extensive experimental and clinical evidence indicates that the westernized diet, rich in animal products and low in complex carbohydrates, plus the overuse of antibiotics and underuse of breastfeeding, leads to a heightened inflammatory potential of the microbiota. Chronic inflammation leads to the expression of certain diseases in genetically predisposed individuals. Antibiotics and a “clean” environment, termed the “hygiene hypothesis,” has been linked to the rise in allergy and inflammatory bowel disease, due to impaired beneficial bacterial exposure and education of the gut immune system, which comprises the largest immune organ within the body. The elevated risk of colon cancer is associated with the suppression of microbial fermentation and butyrate production, as butyrate provides fuel for the mucosa and is anti-inflammatory and anti-proliferative. This article will summarize the work to date highlighting the complicated and dynamic relationship between the gut microbiota and immunity, inflammation and carcinogenesis

Design of Launch Abort System Thrust Profile and Concept of Operations

This paper describes how the Abort Motor thrust profile has been tailored and how optimizing the Concept of Operations on the Launch Abort System (LAS) of the Orion Crew Exploration Vehicle (CEV) aides in getting the crew safely away from a failed Crew Launch Vehicle (CLV). Unlike the passive nature of the Apollo system, the Orion Launch Abort Vehicle will be actively controlled, giving the program a more robust abort system with a higher probability of crew survival for an abort at all points throughout the CLV trajectory. By optimizing the concept of operations and thrust profile the Orion program will be able to take full advantage of the active Orion LAS. Discussion will involve an overview of the development of the abort motor thrust profile and the current abort concept of operations as well as their effects on the performance of LAS aborts. Pad Abort (for performance) and Maximum Drag (for separation from the Launch Vehicle) are the two points that dictate the required thrust and shape of the thrust profile. The results in this paper show that 95% success of all performance requirements is not currently met for Pad Abort. Future improvements to the current parachute sequence and other potential changes will mitigate the current problems, and meet abort performance requirements

Gliotoxin effects on fungal growth: Mechanisms and exploitation

Although initially investigated for its antifungal properties, little is actually known about the effect of gliotoxin on Aspergillus fumigatus and other fungi. We have observed that exposure of A. fumigatus to exogenous gliotoxin (14 lg/ml), under gliotoxin-limited growth conditions, results in significant alteration of the expression of 27 proteins (up- and down-regulated >1.9-fold; p < 0.05) including de novo expression of Cu, Zn superoxide dismutase, up-regulated allergen Asp f3 expression and down-regulated catalase and a peroxiredoxin levels. Significantly elevated glutathione GSH levels (p < 0.05), along with concomitant resistance to diamide, were evident in A. fumigatus ∆gliT, lacking gliotoxin oxidoreductase, a gliotoxin self-protection gene. Saccharomyces cerevisiae deletents (∆sod1 and ∆yap1) were hypersensitive to exogenous gliotoxin, while ∆gsh1 was resistant. Significant gliotoxin-mediated (5 µg/ml) growth inhibition (p < 0.001) of Aspergillus nidulans, Aspergillus terreus, Aspergillus niger, Cochliobolus heterostrophus and Neurospora crassa was also observed. Growth of Aspergillus flavus, Fusarium graminearum and Aspergillus oryzae was significantly inhibited (p < 0.001) at gliotoxin (10 lg/ml), indicating differential gliotoxin sensitivity amongst fungi. Re-introduction of gliT into A. fumigatus DgliT, at a different locus (ctsD; AFUA_4G07040, an aspartic protease), with selection on gliotoxin, facilitated deletion of ctsD without use of additional antibiotic selection markers. Absence of ctsD expression was accompanied by restoration of gliT expression, and resistance to gliotoxin. Thus, we propose gliT/gliotoxin as a useful selection marker system for fungal transformation. Finally, we suggest incorporation of gliotoxin sensitivity assays into all future fungal functional genomic studies

Regulation of Nonribosomal Peptide Synthesis: bis-Thiomethylation Attenuates Gliotoxin Biosynthesis in Aspergillus fumigatus

Gliotoxin is a redox-active nonribosomal peptide produced by Aspergillus fumigatus. Like many other disulfide-containing epipolythiodioxopiperazines, a bis-thiomethylated form is also produced. In the case of gliotoxin, bisdethiobis(methylthio)gliotoxin (BmGT) is formed for unknown reasons by a cryptic enzyme. Here, we identify the S-adenosylmethionine- dependent gliotoxin bis-thiomethyltransferase (GtmA), which converts dithiogliotoxin to BmGT. This activity, which is induced by exogenous gliotoxin, is only detectable in protein lysates of A. fumigatus deficient in the gliotoxin oxidoreductase, gliT. Thus, GtmA is capable of substrate bis-thiomethylation. Deletion of gtmA completely abrogates BmGT formation and we now propose that the purpose of BmGT formation is primarily to attenuate gliotoxin biosynthesis. Phylogenetic analysis reveals 124 GtmA homologs within the Ascomycota phylum. GtmA is encoded outside the gliotoxin biosynthetic cluster and primarily serves to negatively regulate gliotoxin biosynthesis. This mechanism of postbiosynthetic regulation of nonribosomal peptide synthesis appears to be quite unusual