CiteULike: Author Fraser

An Educational Intervention to Reduce Ventilator-Associated Pneumonia in an Integrated Health System: A Comparison of Effects

Hilary Babcock — 2008-08-18T18:17:28-00:00

Chest, Vol. 125, No. 6. (1 June 2004), pp. 2224-2231.

Study objectives: To determine whether an educational initiative could decrease rates of ventilator-associated pneumonia in a regional health-care system. Setting: Two teaching hospitals (one adult, one pediatric) and two community hospitals in an integrated health system. Design: Preintervention and postintervention observational study. Patients: Patients admitted to the four participating hospitals between January 1, 1999, and June 30, 2002, who acquired ventilator-associated pneumonia. Intervention: An educational program for respiratory care practitioners and ICU nurses emphasizing correct practices for the prevention of ventilator-associated pneumonia. The program included a self-study module on risk factors for, and strategies to prevent, ventilator-associated pneumonia and education-based in-services. Fact sheets and posters reinforcing the information were posted throughout the ICU and respiratory care departments. Measurements and results: Completion rates for the module were calculated by job title at each hospital. Rates of ventilator-associated pneumonia per 1,000 ventilator days were calculated for all hospitals combined and for each hospital separately. Overall 635 of 792 ICU nurses (80.1%) and 215 of 239 respiratory therapists (89.9%) completed the study module. There were 874 episodes of ventilator-associated pneumonia at the four hospitals during the 3.5-year study period out of 129,527 ventilator days. Ventilator-associated pneumonia rates for all four hospitals combined dropped by 46%, from 8.75/1,000 ventilator days in the year prior to the intervention to 4.74/1,000 ventilator days in the 18 months following the intervention (p < 0.001). Statistically significant decreased rates were observed at the pediatric hospital and at two of the three adult hospitals. No change in rates was seen at the community hospital with the lowest rate of study module completion among respiratory therapists (56%). Conclusions: Educational interventions can be associated with decreased rates of ventilator-associated pneumonia in the ICU setting. The involvement of respiratory therapy staff in addition to ICU nurses is important for the success of educational programs aimed at the prevention of ventilator-associated pneumonia. 10.1378/chest.125.6.2224

Beyond Definition: Organising Semantic Information in Bilingual Dictionaries

BL Fraser — 2008-08-14T17:12:18-00:00

Int J Lexicography, Vol. 21, No. 1. (1 March 2008), pp. 69-93.

This paper considers the process of organising semantic information in bilingual dictionaries with diachronic coverage, from selecting the textual source-material to designing the entries. The discussion centres on practical aspects of ancient Greek lexicography. First, the traditional semantic frameworks are described. Then, more recent approaches are noted, notably those of Adrados and of Chadwick, both of which aim to integrate contextual data within a semantic framework. Since the relevance of contextual information varies with lemma part of speech, different configurations are required for entries describing nouns, adjectives, and verbs. These are illustrated by three entries from a Greek-English dictionary currently being written at Cambridge. In order to organise data to this level of specificity, stylistic templates are indispensable, and digital software provides a means of providing them. However, systems designed for writing new dictionaries require different features from those designed for encoding pre-existing texts. A description is given of how the lexicographic requirements of the Cambridge dictionary were met by a user-designed system.1 10.1093/ijl/ecn002

Assessing the Determinants of Evolutionary Rates in the Presence of Noise.

Joshua B Plotkin — 2007-03-22T23:48:47-00:00

Mol Biol Evol (7 March 2007)

Although protein sequences are known to evolve at vastly different rates, little is known about what determines their rate of evolution. However, a recent study using principal component regression has concluded that evolutionary rates in yeast are primarily governed by a single determinant, related to translation frequency (Drummond et al. 2006). Here, we demonstrate that noise in biological data can confound principal component regressions, leading to spurious conclusions. When equalizing noise levels across seven predictor variables used in previous studies, we find no evidence that protein evolution is dominated by a single determinant. Our results indicate that a variety of factors - including expression level, gene dispensability, and protein-protein interactions - may independently affect evolutionary rates in yeast. More accurate measurements or more sophisticated statistical techniques will be required to determine which one, if any, of these factors dominates protein evolution.

Using protein complexes to predict phenotypic effects of gene mutation

Hunter Fraser — 2007-11-27T22:33:08-00:00

Genome Biology, Vol. 8 (27 November 2007), R252.

Comprehensive Treatment of Extensively Drug-Resistant Tuberculosis.

Carole D Mitnick — 2008-08-12T01:58:50-00:00

The New England journal of medicine, Vol. 359, No. 6. (7 August 2008), pp. 563-574.

BACKGROUND: Extensively drug-resistant tuberculosis has been reported in 45 countries, including countries with limited resources and a high burden of tuberculosis. We describe the management of extensively drug-resistant tuberculosis and treatment outcomes among patients who were referred for individualized outpatient therapy in Peru. METHODS: A total of 810 patients were referred for free individualized therapy, including drug treatment, resective surgery, adverse-event management, and nutritional and psychosocial support. We tested isolates from 651 patients for extensively drug-resistant tuberculosis and developed regimens that included five or more drugs to which the infecting isolate was not resistant. RESULTS: Of the 651 patients tested, 48 (7.4%) had extensively drug-resistant tuberculosis; the remaining 603 patients had multidrug-resistant tuberculosis. The patients with extensively drug-resistant tuberculosis had undergone more treatment than the other patients (mean [+/-SD] number of regimens, 4.2+/-1.9 vs. 3.2+/-1.6; P<0.001) and had isolates that were resistant to more drugs (number of drugs, 8.4+/-1.1 vs. 5.3+/-1.5; P<0.001). None of the patients with extensively drug-resistant tuberculosis were coinfected with the human immunodeficiency virus (HIV). Patients with extensively drug-resistant tuberculosis received daily, supervised therapy with an average of 5.3+/-1.3 drugs, including cycloserine, an injectable drug, and a fluoroquinolone. Twenty-nine of these patients (60.4%) completed treatment or were cured, as compared with 400 patients (66.3%) with multidrug-resistant tuberculosis (P=0.36). CONCLUSIONS: Extensively drug-resistant tuberculosis can be cured in HIV-negative patients through outpatient treatment, even in those who have received multiple prior courses of therapy for tuberculosis. Copyright 2008 Massachusetts Medical Society.

Fifty years of coiled-coils and alpha-helical bundles: A close relationship between sequence and structure.

David A D Parry — 2008-08-11T20:38:33-00:00

Journal of structural biology (8 February 2008)

alpha-Helical coiled coils are remarkable for the diversity of related conformations that they adopt in both fibrous and globular proteins, and for the range of functions that they exhibit. The coiled coils are based on a heptad (7-residue), hendecad (11-residue) or a related quasi-repeat of apolar residues in the sequences of the alpha-helical regions involved. Most of these, however, display one or more sequence discontinuities known as stutters or stammers. The resulting coiled coils vary in length, in the number of chains participating, in the relative polarity of the contributing alpha-helical regions (parallel or antiparallel), and in the pitch length and handedness of the supercoil (left- or right-handed). Functionally, the concept that a coiled coil can act only as a static rod is no longer valid, and the range of roles that these structures have now been shown to exhibit has expanded rapidly in recent years. An important development has been the recognition that the delightful simplicity that exists between sequence and structure, and between structure and function, allows coiled coils with specialized features to be designed de novo.

Detecting putative orthologs.

DP Wall — 2005-06-13T21:55:06-00:00

Bioinformatics, Vol. 19, No. 13. (1 September 2003), pp. 1710-1711.

We developed an algorithm that improves upon the common procedure of taking reciprocal best blast hits(rbh) in the identification of orthologs. The method-reciprocal smallest distance algorithm (rsd)-relies on global sequence alignment and maximum likelihood estimation of evolutionary distances to detect orthologs between two genomes. rsd finds many putative orthologs missed by rbh because it is less likely than rbh to be misled by the presence of a close paralog.

Risk Management in Primary Agricultural Production: Methods, Distribution, Rewards, and Structural Implications

Peter Barry — 2008-08-06T18:28:04-00:00

American Journal of Agricultural Economics, Vol. 58, No. 2. (1976), pp. 286-295.

Weight Loss with a Low-Carbohydrate, Mediterranean, or Low-Fat Diet

Iris Shai — 2008-07-17T16:07:15-00:00

N Engl J Med, Vol. 359, No. 3. (17 July 2008), pp. 229-241.

Background Trials comparing the effectiveness and safety of weight-loss diets are frequently limited by short follow-up times and high dropout rates. Methods In this 2-year trial, we randomly assigned 322 moderately obese subjects (mean age, 52 years; mean body-mass index [the weight in kilograms divided by the square of the height in meters], 31; male sex, 86%) to one of three diets: low-fat, restricted-calorie; Mediterranean, restricted-calorie; or low-carbohydrate, non-restricted-calorie. Results The rate of adherence to a study diet was 95.4% at 1 year and 84.6% at 2 years. The Mediterranean-diet group consumed the largest amounts of dietary fiber and had the highest ratio of monounsaturated to saturated fat (P<0.05 for all comparisons among treatment groups). The low-carbohydrate group consumed the smallest amount of carbohydrates and the largest amounts of fat, protein, and cholesterol and had the highest percentage of participants with detectable urinary ketones (P<0.05 for all comparisons among treatment groups). The mean weight loss was 2.9 kg for the low-fat group, 4.4 kg for the Mediterranean-diet group, and 4.7 kg for the low-carbohydrate group (P<0.001 for the interaction between diet group and time); among the 272 participants who completed the intervention, the mean weight losses were 3.3 kg, 4.6 kg, and 5.5 kg, respectively. The relative reduction in the ratio of total cholesterol to high-density lipoprotein cholesterol was 20% in the low-carbohydrate group and 12% in the low-fat group (P=0.01). Among the 36 subjects with diabetes, changes in fasting plasma glucose and insulin levels were more favorable among those assigned to the Mediterranean diet than among those assigned to the low-fat diet (P<0.001 for the interaction among diabetes and Mediterranean diet and time with respect to fasting glucose levels). Conclusions Mediterranean and low-carbohydrate diets may be effective alternatives to low-fat diets. The more favorable effects on lipids (with the low-carbohydrate diet) and on glycemic control (with the Mediterranean diet) suggest that personal preferences and metabolic considerations might inform individualized tailoring of dietary interventions. (ClinicalTrials.gov number, NCT00160108 .) 10.1056/NEJMoa0708681

Loss-of-function mutations in the Nav1.7 gene underlie congenital indifference to pain in multiple human populations

Goldberg — 2007-04-29T12:33:51-00:00

Clinical Genetics, Vol. 71, No. 4. (April 2007), pp. 311-319.

Large recurrent microdeletions associated with schizophrenia

Hreinn Stefansson — 2008-07-31T19:26:39-00:00

Nature (30 July 2008)

Replication and transcription: Shaping the landscape of the genome

Lyubomira Chakalova — 2005-09-01T17:01:42-00:00

Nature Reviews Genetics, Vol. 6, No. 9. (01 September 2005), pp. 669-677.

Splicing of NOD2 (CARD15) RNA transcripts

Euphemia Leung — 2008-08-01T17:29:06-00:00

Molecular Immunology, Vol. 44, No. 4. (January 2007), pp. 284-294.

Mutated variants of NOD2, a cytosolic Toll-like receptor (TLR) that recognizes bacterial peptidoglycan, are responsible for increased susceptibility to Crohn's disease (CD). TLRs and their related plant counterparts, the disease-resistance R proteins, undergo alternative splicing as a means of controlling activity. Here we report that regions of NOD2 RNA transcripts that encode the N-terminal and leucine-rich repeat (LRR) domains are alternatively spliced, potentially creating at least eight putative NOD2 variants. The most common variant is a short truncated isoform designated NOD2-short which terminates at residue position 820 leaving three LRR domains. An N-terminally spliced variant designated NOD2-190 contains only CARD1 and a partial CARD2 domain. The expression of transcripts encoding full-length and alternatively spliced forms of NOD2 was altered in blood mononuclear cells and monocytic cell lines stimulated by bacterial products. NOD2-short and NOD2-190 were inactive and unresponsive to muramyl dipeptide (MDP), but did not antagonize the activity of wild-type NOD2. Alternative splicing of NOD2 transcripts represents a potential mechanism by which the intracellular bacterial sensing activity of NOD2 is altered or down-regulated.

Codon Usage and Selection on Proteins

Joshua Plotkin — 2006-12-15T23:16:00-00:00

Journal of Molecular Evolution, Vol. V63, No. 5. (14 November 2006), pp. 635-653.

A multivariate method for measurement error correction using pairs of concentration biomarkers.

GE Fraser — 2008-07-27T05:04:43-00:00

Annals of epidemiology, Vol. 17, No. 1. (January 2007), pp. 64-73.

PURPOSE: Measurement error is a pervasive problem in behavioral epidemiology, and available methods of correction all have generally untenable assumptions. We propose a multivariate method with more realistic assumptions. METHODS: The method uses two concentration biomarkers for each nutritional variable of interest and structural equation modeling. This produces corrected estimates of the effects on an outcome variable of changing the true exposure variables by one standard deviation, a standardized regression calibration. However, hypothesis testing in original units is preserved. The main assumptions are that certain error correlations between dietary estimates and biomarkers or between biomarkers be close to zero. RESULTS: Two illustrative models used simulated data with the covariance structure of a real data set. The corrections produced often were very substantial. A sensitivity analysis allowed error correlations to depart from zero over a modest range. Root mean square biases show the advantage of the corrected approach. Relatively large calibration studies are needed for adequate precision. CONCLUSIONS: As long as concentration biomarkers are selected carefully, error-corrected multivariate hypothesis testing and standardized effect estimation is possible. With the deviations from assumptions that were tested, the corrected method usually produces much less biased results than an uncorrected analysis.

Transcriptional regulatory networks in bacteria: from input signals to output responses.

AS Seshasayee — 2006-10-18T10:41:20-00:00

Curr Opin Microbiol, Vol. 9, No. 5. (October 2006), pp. 511-519.

Transcriptional regulatory systems play a central role in coordinating bacterial responses to diverse stimuli. These systems can be studied in progressive stages: from input signals to the final output. At the input stage, transcription factors (TFs) can be classified by their activation from endogenous or exogenous stimuli; in Escherichia coli, up to three-quarters of regulators are estimated to respond directly to extracellular signals through phosphorylation and small-molecule binding. At the processing stage, the signals feed into a densely connected network. The endogenous regulators form most of the connections between TFs and, by dynamically rewiring interactions, they coordinate and distribute the appropriate responses for distinct cellular conditions. At the output stage, network motifs (which are specific patterns of interconnections within a small group of TFs and target genes) determine the precise temporal programme of gene expression changes. Eventually, these components of the regulatory system could be assembled to describe complex bacterial behaviour at the level of whole organisms.

Contaminated heparin associated with adverse clinical events and activation of the contact system.

TK Kishimoto — 2008-07-19T20:25:07-00:00

The New England journal of medicine, Vol. 358, No. 23. (5 June 2008), pp. 2457-2467.

BACKGROUND: There is an urgent need to determine whether oversulfated chondroitin sulfate (OSCS), a compound contaminating heparin supplies worldwide, is the cause of the severe anaphylactoid reactions that have occurred after intravenous heparin administration in the United States and Germany. METHODS: Heparin procured from the Food and Drug Administration, consisting of suspect lots of heparin associated with the clinical events as well as control lots of heparin, were screened in a blinded fashion both for the presence of OSCS and for any biologic activity that could potentially link the contaminant to the observed clinical adverse events. In vitro assays for the activation of the contact system and the complement cascade were performed. In addition, the ability of OSCS to recapitulate key clinical manifestations in vivo was tested in swine. RESULTS: The OSCS found in contaminated lots of unfractionated heparin, as well as a synthetically generated OSCS reference standard, directly activated the kinin-kallikrein pathway in human plasma, which can lead to the generation of bradykinin, a potent vasoactive mediator. In addition, OSCS induced generation of C3a and C5a, potent anaphylatoxins derived from complement proteins. Activation of these two pathways was unexpectedly linked and dependent on fluid-phase activation of factor XII. Screening of plasma samples from various species indicated that swine and humans are sensitive to the effects of OSCS in a similar manner. OSCS-containing heparin and synthetically derived OSCS induced hypotension associated with kallikrein activation when administered by intravenous infusion in swine. CONCLUSIONS: Our results provide a scientific rationale for a potential biologic link between the presence of OSCS in suspect lots of heparin and the observed clinical adverse events. An assay to assess the amidolytic activity of kallikrein can supplement analytic tests to protect the heparin supply chain by screening for OSCS and other highly sulfated polysaccharide contaminants of heparin that can activate the contact system.

Interchromosomal Huddle Kickstarts Antiviral Defense

Stefan Schoenfelder — 2008-07-19T05:53:23-00:00

Cell, Vol. 134, No. 1. (11 July 2008), pp. 14-16.

Long-distance chromosomal interactions are emerging as a potential mechanism of gene expression control. In this issue, Apostolou and Thanos (2008) describe how viral infection elicits interchromosomal associations between the interferon-[beta] (IFN-[beta]) gene enhancer and DNA binding sites of the transcription factor NF-[kappa]B, resulting in the initiation of transcription and an antiviral response.

Measuring trust in wi-fi hotspots

Tim Kindberg — 2008-07-18T22:47:50-00:00

(2008), pp. 173-182.

Xen and the art of virtualization

Paul Barham — 2005-04-24T03:21:56-00:00

(2003), pp. 164-177.

Numerous systems have been designed which use virtualization to subdivide the ample resources of a modern computer. Some require specialized hardware, or cannot support commodity operating systems. Some target 100% binary compatibility at the expense of performance. Others sacrifice security or functionality for speed. Few offer resource isolation or performance guarantees; most provide only best-effort provisioning, risking denial of service.This paper presents Xen, an x86 virtual machine monitor which allows multiple commodity operating systems to share conventional hardware in a safe and resource managed fashion, but without sacrificing either performance or functionality. This is achieved by providing an idealized virtual machine abstraction to which operating systems such as Linux, BSD and Windows XP, can be ported with minimal effort.Our design is targeted at hosting up to 100 virtual machine instances simultaneously on a modern server. The virtualization approach taken by Xen is extremely efficient: we allow operating systems such as Linux and Windows XP to be hosted simultaneously for a negligible performance overhead --- at most a few percent compared with the unvirtualized case. We considerably outperform competing commercial and freely available solutions in a range of microbenchmarks and system-wide tests.

The efficacy of azathioprine for the treatment of inflammatory bowel disease: a 30 year review.

AG Fraser — 2008-07-18T03:13:54-00:00

Gut, Vol. 50, No. 4. (April 2002), pp. 485-489.

BACKGROUND: There are limited data on factors predicting response to azathioprine and uncertainty regarding the optimal duration of treatment. PATIENTS AND METHODS: The notes of patients attending the Oxford IBD clinic from 1968 to 1999 were reviewed. Remission was defined as no need for oral steroids for at least three months and relapse was defined as active disease requiring steroids. RESULTS: A total of 622 of 2205 patients were treated with azathioprine (272 Crohn's disease, 346 ulcerative colitis, and four indeterminate colitis). Mean duration of the initial course of treatment was 634 days. The overall remission rates were 45% for Crohn's disease and 58% for ulcerative colitis. For the 424 patients who received more than six months of treatment, remission rates were 64% and 87%, respectively. Factors favouring remission were ulcerative colitis (p=0.0001), lower white blood cell (WBC) or neutrophil count (p=0.0001), higher mean cell volume (p=0.0001), and older age (p=0.05). For Crohn's disease, colonic disease favoured remission (p=0.03). Factors that were not significant were age, sex, lymphocyte count, and dose (mg/kg). The proportion of patients remaining in remission at one, three, and five years was 0.95, 0.69, and 0.55, respectively. The chance of remaining in remission was higher if WBC was less than 5 x 10(9) (p=0.03) and in male patients (p=0.01; Crohn's disease only). There was no difference in relapse rates between Crohn's disease and ulcerative colitis. After stopping azathioprine, the proportion of patients remaining in remission at one, three, and five years was 0.63, 0.44, and 0.35 (222 patients). Duration of azathioprine treatment did not affect the relapse rate after stopping treatment (p=0.68). CONCLUSIONS: Azathioprine is effective treatment for ulcerative colitis and Crohn's disease. The efficacy of azathioprine is reasonably well sustained over five years.

Identifying and preventing pain in animals

Daniel Weary — 2008-07-14T22:37:54-00:00

Applied Animal Behaviour Science, Vol. 100, No. 1-2. (October 2006), pp. 64-76.

Animals are routinely subjected to painful procedures, such as tail docking for puppies, castration for piglets, dehorning for dairy calves, and surgery for laboratory rats. Disease and injury, such as tumours in mice and sole ulcers on the feet of dairy cows, may also cause pain. In this paper we describe some of the ways in which the pain that animals experience can be recognized and quantified. We also describe ways in which pain can be avoided or reduced, by reconsidering how procedures are performed and whether they are actually required. Ultimately, reducing the pain that animals experience will require scientific innovation paired with changed cultural values, and willingness to address regulatory, technological and economic constraints.

Cosmic Anger: Abdus Salam - The First Muslim Nobel Scientist [Chapter 1]

Gordon Fraser — 2008-07-12T15:22:25-00:00

(24 April 2008)

This book presents a biography of Abdus Salam, the first Muslim to win a Nobel Prize for Science (Physics 1979), who was nevertheless excommunicated and branded as a heretic in his own country. His achievements are often overlooked, even besmirched. Realizing that the whole world had to be his stage, he pioneered the International Centre for Theoretical Physics in Trieste, a vital focus of Third World science which remains as his monument. A staunch Muslim, he was ashamed of the decline of science in the heritage of Islam, and struggled doggedly to restore it to its former glory. Undermined by his excommunication, these valiant efforts were doomed.

The alliance for cellular signaling plasmid collection: a flexible resource for protein localization studies and signaling pathway analysis.

JR Zavzavadjian — 2007-06-27T02:46:42-00:00

Mol Cell Proteomics, Vol. 6, No. 3. (March 2007), pp. 413-424.

Cellular responses to inputs that vary both temporally and spatially are determined by complex relationships between the components of cell signaling networks. Analysis of these relationships requires access to a wide range of experimental reagents and techniques, including the ability to express the protein components of the model cells in a variety of contexts. As part of the Alliance for Cellular Signaling, we developed a robust method for cloning large numbers of signaling ORFs into Gateway entry vectors, and we created a wide range of compatible expression platforms for proteomics applications. To date, we have generated over 3000 plasmids that are available to the scientific community via the American Type Culture Collection. We have established a website at www.signaling-gateway.org/data/plasmid/ that allows users to browse, search, and blast Alliance for Cellular Signaling plasmids. The collection primarily contains murine signaling ORFs with an emphasis on kinases and G protein signaling genes. Here we describe the cloning, databasing, and application of this proteomics resource for large scale subcellular localization screens in mammalian cell lines.

Kcnq1ot1/Lit1 noncoding RNA mediates transcriptional silencing by targeting to the perinucleolar region.

F Mohammad — 2008-07-11T18:37:02-00:00

Molecular and cellular biology, Vol. 28, No. 11. (June 2008), pp. 3713-3728.

The Kcnq1ot1 antisense noncoding RNA has been implicated in long-range bidirectional silencing, but the underlying mechanisms remain enigmatic. Here we characterize a domain at the 5' end of the Kcnq1ot1 RNA that carries out transcriptional silencing of linked genes using an episomal vector system. The bidirectional silencing property of Kcnq1ot1 maps to a highly conserved repeat motif within the silencing domain, which directs transcriptional silencing by interaction with chromatin, resulting in histone H3 lysine 9 trimethylation. Intriguingly, the silencing domain is also required to target the episomal vector to the perinucleolar compartment during mid-S phase. Collectively, our data unfold a novel mechanism by which an antisense RNA mediates transcriptional gene silencing of chromosomal domains by targeting them to distinct nuclear compartments known to be rich in heterochromatic machinery.

Gene regulation through nuclear organization

Tom Sexton — 2007-11-06T06:48:24-00:00

Nature Structural & Molecular Biology, Vol. 14, No. 11. (05 November 2007), pp. 1049-1055.

FATKit: A framework for the extraction and analysis of digital forensic data from volatile system memory

Jr Petroni — 2008-07-10T16:10:39-00:00

Digital Investigation, Vol. 3, No. 4. (December 2006), pp. 197-210.

We present the Forensic Analysis ToolKit (FATKit) - a modular, extensible framework that increases the practical applicability of volatile memory forensic analysis by freeing human analysts from the prohibitively-tedious aspects of low-level data extraction. FATKit allows analysts to focus on higher-level tasks by providing novel methods for automatically deriving digital object definitions from C source code, extracting those objects from memory images, and visualizing the underlying data in various ways. FATKit presently includes modules for general virtual address space reconstruction and visualization, as well as Linux- and Windows-specific kernel analysis.

SmartGov: A Knowledge-Based Platform for Transactional Electronic Services

P Georgiadis — 2008-07-09T14:52:41-00:00

Electronic Government (2002), pp. 3-7.

Public transaction services (such as e-forms) although perceived the future of e-government have not yet realised their full potential. E-forms have a significant role in e-government, as they are the basis for implementing most of the twenty public services that all member states have to provide to their citizens and businesses. The aim of the SmartGov project is to specify, develop, deploy and evaluate a knowledge-based platform to assist public sector employees to generate online transaction services by simplifying their development, maintenance and integration with already installed IT systems. This platform will be evaluated in two European countries (in one Ministry and one Local Authority). This paper outlines key issues in the development of the SmartGov system platform.

The Transit Light Curve Project. IV. Five Transits of the Exoplanet OGLE-TR-10b

Matthew Holman — 2008-07-08T17:06:26-00:00

(30 Oct 2006)

We present I and B photometry of five distinct transits of the exoplanet OGLE-TR-10b. By modeling the light curves, we find the planetary radius to be R_P = 1.06 +/- 0.08 R_Jup and the stellar radius to be R_S = 1.10 +/- 0.07 R_sun. The uncertainties are dominated by statistical errors in the photometry. Our estimate of the planetary radius is smaller than previous estimates that were based on lower-precision photometry, and hence the planet is not as anomalously large as was previously thought. We provide updated determinations of all the system parameters, including the transit ephemerides.

The role of polymer deposited in differential dielectric etch

S Fang — 2008-07-08T05:54:05-00:00

The 42nd national symposium of the American Vacuum Society, Vol. 14, No. 3. (1996), pp. 1092-1095.

Dielectric etch capabilities of a high density plasma etcher have been investigated for the Damascene etch. Here, the patterning of vias, pads, and interconnects by the selective etch stop film approach was evaluated. In particular, the role of fluorocarbon polymer film was studied in etch lag effects and differential dielectric etch (oxide versus nitride). The result shows that the highly selective etch relies on the selective deposition and fluorine scavenging. This article provides the physical insights for the success of the differential dielectric etch. While the investigation is under the Damascene etch, the fundamental understanding can be applied to any highly selective etching of oxide versus nitride. ©1996 American Vacuum Society

A first-draft human protein-interaction map.

B Lehner — 2005-11-17T00:51:39-00:00

Genome Biol, Vol. 5, No. 9. (2004)

BACKGROUND: Protein-interaction maps are powerful tools for suggesting the cellular functions of genes. Although large-scale protein-interaction maps have been generated for several invertebrate species, projects of a similar scale have not yet been described for any mammal. Because many physical interactions are conserved between species, it should be possible to infer information about human protein interactions (and hence protein function) using model organism protein-interaction datasets. RESULTS: Here we describe a network of over 70,000 predicted physical interactions between around 6,200 human proteins generated using the data from lower eukaryotic protein-interaction maps. The physiological relevance of this network is supported by its ability to preferentially connect human proteins that share the same functional annotations, and we show how the network can be used to successfully predict the functions of human proteins. We find that combining interaction datasets from a single organism (but generated using independent assays) and combining interaction datasets from two organisms (but generated using the same assay) are both very effective ways of further improving the accuracy of protein-interaction maps. CONCLUSIONS: The complete network predicts interactions for a third of human genes, including 448 human disease genes and 1,482 genes of unknown function, and so provides a rich framework for biomedical research.

The influence of inadequate antimicrobial treatment of bloodstream infections on patient outcomes in the ICU setting.

EH Ibrahim — 2008-07-03T05:08:29-00:00

Chest, Vol. 118, No. 1. (July 2000), pp. 146-155.

STUDY OBJECTIVE: To evaluate the relationship between the adequacy of antimicrobial treatment for bloodstream infections and clinical outcomes among patients requiring ICU admission. DESIGN: Prospective cohort study. SETTING: A medical ICU (19 beds) and a surgical ICU (18 beds) from a university-affiliated urban teaching hospital. PATIENTS: Between July 1997 and July 1999, 492 patients were prospectively evaluated. INTERVENTION: Prospective patient surveillance and data collection. RESULTS: One hundred forty-seven patients (29.9%) received inadequate antimicrobial treatment for their bloodstream infections. The hospital mortality rate of patients with a bloodstream infection receiving inadequate antimicrobial treatment (61.9%) was statistically greater than the hospital mortality rate of patients with a bloodstream infection who received adequate antimicrobial treatment (28.4%; relative risk, 2. 18; 95% confidence interval [CI], 1.77 to 2.69; p < 0.001). Multiple logistic regression analysis identified the administration of inadequate antimicrobial treatment as an independent determinant of hospital mortality (adjusted odds ratio [AOR], 6.86; 95% CI, 5.09 to 9.24; p < 0.001). The most commonly identified bloodstream pathogens and their associated rates of inadequate antimicrobial treatment included vancomycin-resistant enterococci (n = 17; 100%), Candida species (n = 41; 95.1%), oxacillin-resistant Staphylococcus aureus (n = 46; 32.6%), coagulase-negative staphylococci (n = 96; 21.9%), and Pseudomonas aeruginosa (n = 22; 10.0%). A statistically significant relationship was found between the rates of inadequate antimicrobial treatment for individual microorganisms and their associated rates of hospital mortality (Spearman correlation coefficient = 0.8287; p = 0.006). Multiple logistic regression analysis also demonstrated that a bloodstream infection attributed to Candida species (AOR, 51.86; 95% CI, 24.57 to 109.49; p < 0.001), prior administration of antibiotics during the same hospitalization (AOR, 2.08; 95% CI, 1.58 to 2.74; p = 0.008), decreasing serum albumin concentrations (1-g/dL decrements) (AOR, 1.37; 95% CI, 1.21 to 1.56; p = 0.014), and increasing central catheter duration (1-day increments) (AOR, 1.03; 95% CI, 1.02 to 1.04; p = 0.008) were independently associated with the administration of inadequate antimicrobial treatment. CONCLUSIONS: The administration of inadequate antimicrobial treatment to critically ill patients with bloodstream infections is associated with a greater hospital mortality compared with adequate antimicrobial treatment of bloodstream infections. These data suggest that clinical efforts should be aimed at reducing the administration of inadequate antimicrobial treatment to hospitalized patients with bloodstream infections, especially individuals infected with antibiotic-resistant bacteria and Candida species.

A map of the interactome network of the metazoan C. elegans.

S Li — 2005-08-30T17:59:47-00:00

Science, Vol. 303, No. 5657. (23 January 2004), pp. 540-543.

To initiate studies on how protein-protein interaction (or "interactome") networks relate to multicellular functions, we have mapped a large fraction of the Caenorhabditis elegans interactome network. Starting with a subset of metazoan-specific proteins, more than 4000 interactions were identified from high-throughput, yeast two-hybrid (HT=Y2H) screens. Independent coaffinity purification assays experimentally validated the overall quality of this Y2H data set. Together with already described Y2H interactions and interologs predicted in silico, the current version of the Worm Interactome (WI5) map contains approximately 5500 interactions. Topological and biological features of this interactome network, as well as its integration with phenome and transcriptome data sets, lead to numerous biological hypotheses.

Evolutionary plasticity of genetic interaction networks

Julia Tischler — 2008-03-27T15:08:54-00:00

Nat Genet, Vol. 40, No. 4. (April 2008), pp. 390-391.

Confirmation of Organized Modularity in the Yeast Interactome

Nicolas Bertin — 2007-11-22T18:25:23-00:00

PLoS Biology, Vol. 5, No. 6. (1 June 2007), e153.

Coevolution of gene expression among interacting proteins.

HB Fraser — 2005-09-01T17:48:34-00:00

Proc Natl Acad Sci U S A, Vol. 101, No. 24. (15 June 2004), pp. 9033-9038.

Physically interacting proteins or parts of proteins are expected to evolve in a coordinated manner that preserves proper interactions. Such coevolution at the amino acid-sequence level is well documented and has been used to predict interacting proteins, domains, and amino acids. Interacting proteins are also often precisely coexpressed with one another, presumably to maintain proper stoichiometry among interacting components. Here, we show that the expression levels of physically interacting proteins coevolve. We estimate average expression levels of genes from four closely related fungi of the genus Saccharomyces using the codon adaptation index and show that expression levels of interacting proteins exhibit coordinated changes in these different species. We find that this coevolution of expression is a more powerful predictor of physical interaction than is coevolution of amino acid sequence. These results demonstrate that gene expression levels can coevolve, adding another dimension to the study of the coevolution of interacting proteins and underscoring the importance of maintaining coexpression of interacting proteins over evolutionary time. Our results also suggest that expression coevolution can be used for computational prediction of protein-protein interactions.

The genome sequence of the malaria mosquito Anopheles gambiae.

RA Holt — 2005-05-09T17:13:03-00:00

Science, Vol. 298, No. 5591. (4 October 2002), pp. 129-149.

Anopheles gambiae is the principal vector of malaria, a disease that afflicts more than 500 million people and causes more than 1 million deaths each year. Tenfold shotgun sequence coverage was obtained from the PEST strain of A. gambiae and assembled into scaffolds that span 278 million base pairs. A total of 91% of the genome was organized in 303 scaffolds; the largest scaffold was 23.1 million base pairs. There was substantial genetic variation within this strain, and the apparent existence of two haplotypes of approximately equal frequency ("dual haplotypes") in a substantial fraction of the genome likely reflects the outbred nature of the PEST strain. The sequence produced a conservative inference of more than 400,000 single-nucleotide polymorphisms that showed a markedly bimodal density distribution. Analysis of the genome sequence revealed strong evidence for about 14,000 protein-encoding transcripts. Prominent expansions in specific families of proteins likely involved in cell adhesion and immunity were noted. An expressed sequence tag analysis of genes regulated by blood feeding provided insights into the physiological adaptations of a hematophagous insect.

MobGeoSen: facilitating personal geosensor data collection and visualization using mobile phones

Eiman Kanjo — 2008-06-30T13:00:17-00:00

Personal and Ubiquitous Computing

Abstract Mobile sensing and mapping applications are becoming more prevalent because sensing hardware is becoming more portable and more affordable. However, most of the hardware uses small numbers of fixed sensors that report and share multiple sets of environmental data which raises privacy concerns. Instead, these systems can be decentralized and managed by individuals in their public and private spaces. This paper describes a robust system called MobGeoSens which enables individuals to monitor their local environment (e.g. pollution and temperature) and their private spaces (e.g. activities and health) by using mobile phones in their day to day life. The MobGeoSen is a combination of software components that facilitates the phone’s internal sensing devices (e.g. microphone and camera) and external wireless sensors (e.g. data loggers and GPS receivers) for data collection. It also adds a new dimension of spatial localization to the data collection process and provides the user with both textual and spatial cartographic displays. While collecting the data, individuals can interactively add annotations and photos which are automatically added and integrated in the visualization file/log. This makes it easy to visualize the data, photos and annotations on a spatial and temporal visualization tool. In addition, the paper will present ways in which mobile phones can be used as noise sensors using an on-device microphone. Finally, we present our experiences with school children using the above mentioned system to measure their exposure to environmental pollution.

Independent coordinates for strange attractors from mutual information

Andrew Fraser — 2006-09-06T13:32:21-00:00

Physical Review A, Vol. 33, No. 2. (February 1986), 1134.

The mutual information I is examined for a model dynamical system and for chaotic data from an experiment on the Belousov-Zhabotinskii reaction. An N log N algorithm for calculating I is presented. As proposed by Shaw; a minimum in I is found to be a good criterion for the choice of time delay in phase-portrait reconstruction from time-series data. This criterion is shown to be far superior to choosing a zero of the autocorrelation function.

Evidence-based clinical guidelines: a new system to better determine true strength of recommendation

Roddy — 2006-05-22T03:27:33-00:00

Journal of Evaluation in Clinical Practice, Vol. 12, No. 3. (June 2006), pp. 347-352.

Stress reduction through consolation in chimpanzees

Orlaith Fraser — 2008-06-26T19:42:04-00:00

Proceedings of the National Academy of Sciences, Vol. 105, No. 25. (24 June 2008), pp. 8557-8562.

Consolation, i.e., postconflict affiliative interaction directed from a third party to the recipient of aggression, is assumed to have a stress-alleviating function. This function, however, has never been demonstrated. This study shows that consolation in chimpanzees reduces behavioral measures of stress in recipients of aggression. Furthermore, consolation was more likely to occur in the absence of reconciliation, i.e., postconflict affiliative interaction between former opponents. Consolation therefore may act as an alternative to reconciliation when the latter does not occur. In the debate about empathy in great apes, evidence for the stress-alleviating function of consolation in chimpanzees provides support for the argument that consolation could be critical behavior. Consistent with the argument that relationship quality affects their empathic responses, we found that consolation was more likely between individuals with more valuable relationships. Chimpanzees may thus respond to distressed valuable partners by consoling them, thereby reducing their stress levels, especially in the absence of reconciliation. 10.1073/pnas.0804141105

Regression Calibration in Studies with Correlated Variables Measured with Error

Gary Fraser — 2008-06-25T15:45:28-00:00

Am. J. Epidemiol., Vol. 154, No. 9. (1 November 2001), pp. 836-844.

Regression calibration is a technique that corrects biases in regression results in situations where exposure variables are measured with error. The existence of a calibration substudy, where accurate and crude measurement methods are related by a second regression analysis, is assumed. The cost of measurement error in multivariate analyses is loss of statistical power. In this paper, calibration data from California Seventh-day Adventists are used to simulate study populations and new calibration studies. Applying regression calibration logistic analyses, the authors estimate power for pairs of nutritional variables. The results demonstrate substantial loss of power if variables measured with error are strongly correlated. Biases in estimated effects in cases where regression calibration is not performed can be large and are corrected by regression calibration. When the true coefficient has zero value, the corresponding coefficient in a crude analysis will usually have a nonzero expected value. Then type I error probabilities are not nominal, and the erroneous appearance of statistical significance can readily occur, particularly in large studies. Major determinants of power with use of regression calibration are collinearity between the variables measured with error and the size of correlations between crude and corresponding true variables. Where there is important collinearity, useful gains in power accrue with calibration study size up to 1,000 subjects. 10.1093/aje/154.9.836

Global Transposon Mutagenesis and a Minimal Mycoplasma Genome

Clyde Hutchison — 2007-11-14T13:32:22-00:00

Science, Vol. 286, No. 5447. (10 December 1999), pp. 2165-2169.

10.1126/science.286.5447.2165

High-efficiency transformation of Plasmodium falciparum by the lepidopteran transposable element piggyBac.

B Balu — 2008-06-22T04:12:57-00:00

Proceedings of the National Academy of Sciences of the United States of America, Vol. 102, No. 45. (8 November 2005), pp. 16391-16396.

Functional analysis of the Plasmodium falciparum genome is restricted because of the limited ability to genetically manipulate this important human pathogen. We have developed an efficient transposon-mediated insertional mutagenesis method much needed for high-throughput functional genomics of malaria parasites. A drug-selectable marker, human dihydrofolate reductase, added to the lepidopteran transposon piggyBac, transformed parasites by integration into the P. falciparum genome in the presence of a transposase-expressing helper plasmid. Multiple integrations occurred at the expected TTAA target sites throughout the genome of the parasite. We were able to transform P. falciparum with this piggyBac element at high frequencies, in the range of 10(-3), and obtain stable clones of insertional mutants in a few weeks instead of 6-12 months. Our results show that the piggyBac transposition system can be used as an efficient, random integration tool needed for large-scale, whole-genome mutagenesis of malaria parasites. The availability of such an adaptable genetic tool opens the way for much needed forward genetic approaches to study this lethal human parasite.

Quantum interference control of free-carrier density in GaAs

JM Fraser — 2006-12-17T19:52:56-00:00

Physical Review B (Condensed Matter and Materials Physics), Vol. 68, No. 8. (2003)

We have carried out theoretical and experimental investigations of optical phase controlled-free carrier injection in semiconductors via quantum interference between different absorption pathways connecting the same initial and final states in the valence and conduction bands. The interference schemes are theoretically modeled within a Fermi Golden rule approximation which also allows for a description in terms of the susceptibility formalism of nonlinear optics. Two different types of schemes involving interference between n and m multiphoton absorption events are considered depending on whether n + m is even or odd. If n + m is odd, phase control of carrier density can be observed only in a noncentrosymmetric crystal; if n + m is even, interference can be observed in both centrosymmetric and noncentrosymmetric materials. The interference contribution to the density control is related to the imaginary part of the nonlinear electric susceptibility n + m–1. Experimentally we have investigated carrier density control effects in GaAs at room temperature using nominally 150 fs optical pulses and considered an example for each of the two schemes: one-photon vs two-photon absorption with 0.775 and 1.55 µm pulses and one-photon vs three-photon absorption with 0.675 and 2.03 µm pulses. The main experimental features, including degree of phase control, are in good agreement with theory. We extract the relative magnitude of the imaginary and real components of 2 and 3 for GaAs at 1.55 µm and 2.03 µm, respectively.

Coma with diffuse white matter hemorrhages in juvenile diabetic ketoacidosis.

FH Mahmud — 2008-06-17T05:53:48-00:00

Pediatrics, Vol. 120, No. 6. (December 2007)

Cerebral edema is the most common neurologic complication of diabetic ketoacidosis in children. A minority of young patients with intracerebral crises in diabetic ketoacidosis present with cerebrovascular accidents. We report 2 adolescent patients with diabetic ketoacidosis who presented with coma and diffuse white matter hemorrhages in the absence of either cerebral edema or cerebrovascular accidents. These 2 cases illustrate a novel clinical and neuropathologic description of diffuse white matter hemorrhages, possibly related to a cytotoxic process as the underlying mechanism. These case descriptions emphasize that pediatric patients with diabetic ketoacidosis and coma can present with pathology not related to either cerebral edema or cerebrovascular accidents.

Uncover Genetic Interactions in Caenorhabditis elegans by RNA Interference

Fortunato — 2005-11-30T18:47:46-00:00

Bioscience Reports, Vol. 25, No. 5-6. (October 2005), pp. 299-307.

Supporting awareness and interaction through collaborative virtual interfaces

Mike Fraser — 2008-06-16T02:40:44-00:00

(1999), pp. 27-36.

Revealing delay in collaborative environments

Carl Gutwin — 2007-12-29T14:18:35-00:00

(2004), pp. 503-510.

Designing the spectator experience

Stuart Reeves — 2005-06-28T17:50:44-00:00

(2005), pp. 741-750.