PubMed Health⌕ Search

Biomedical subjects

David Craft

Publications and source records attributed to David Craft.

10 recordsLinked to original sources
PubMed2006

Dose-volume objectives in multi-criteria optimization.

Unlike conventional optimization with dose-volume (DV) constraints, multi-criteria optimization (MCO) with DV objectives provides tradeoff information which we believe is necessary for choosing better treatment plans. We show that the MCO formulation with DV objectives is better suited to convex approximation than conventional formulations with DV constraints. We provide a relaxation of the integer programming formulation which reduces the computation time for a single plan from over 5 h to about 2 min, without significantly compromising the results. We also derive a heuristic to improve on the relaxed solutions, adding only a few additional minutes of computation time. We apply these techniques to a skull based tumour case and a paraspinal tumour case. Based on a careful examination of the driving terms in the relaxed formulation and the heuristic, we argue that our techniques should apply more generally for DV objectives in multi-objective IMRT treatment planning.

Algorithms↗
PubMed2006

Comparison of Acinetobacter baumannii isolates from the United Kingdom and the United States that were associated with repatriated casualties of the Iraq conflict.

Acinetobacter isolates associated with casualties from the Iraq conflict from the United States were compared with those from the United Kingdom by pulsed-field gel electrophoresis and integron analysis. Representatives of the main outbreak strain associated with casualties from both countries were indistinguishable in DNA profile. Two further outbreak strains were common to both sets of isolates.

Acinetobacter Infections↗
PubMed2006

Identification of Acinetobacter species and genotyping of Acinetobacter baumannii by multilocus PCR and mass spectrometry.

Members of the genus Acinetobacter are ubiquitous in soil and water and are an important cause of nosocomial infections. A rapid method is needed to genotype Acinetobacter isolates to determine epidemiology and clonality during infectious outbreaks. Multilocus PCR followed by electrospray ionization mass spectrometry (PCR/ESI-MS) is a method that uses the amplicon base compositions to genotype bacterial species. In order to identify regions of the Acinetobacter genome useful for this method, we sequenced regions of six housekeeping genes (trpE, adk, efp, mutY, fumC, and ppa) from 267 isolates of Acinetobacter. Isolates were collected from infected and colonized soldiers and civilians involved in an outbreak in the military health care system associated with the conflict in Iraq, from previously characterized outbreaks in European hospitals, and from culture collections. Most of the isolates from the Iraqi conflict were Acinetobacter baumannii (189 of 216 isolates). Among these, 111 isolates had genotypes identical or very similar to those associated with well-characterized A. baumannii isolates from European hospitals. Twenty-seven isolates from the conflict were found to have genotypes representing different Acinetobacter species, including 8 representatives of Acinetobacter genomospecies 13TU and 13 representatives of Acinetobacter genomospecies 3. Analysis by the PCR/ESI-MS method using nine primer pairs targeting the most information-rich regions of the trpE, adk, mutY, fumC, and ppa genes distinguished 47 of the 48 A. baumannii genotypes identified by sequencing and identified at the species level at least 18 Acinetobacter species. Results obtained with our genotyping method were essentially in agreement with those obtained by pulse-field gel electrophoresis analysis. The PCR/ESI-MS genotyping method required 4 h of analysis time to first answer with additional samples subsequently analyzed every 10 min. This rapid analysis allows tracking of transmission for the implementation of appropriate infection control measures on a time scale previously not achievable.

Acinetobacter↗
PubMed2005

Exploration of tradeoffs in intensity-modulated radiotherapy.

The purpose of this study is to calculate Pareto surfaces in multi-criteria radiation treatment planning and to analyse the dependency of the Pareto surfaces on the objective functions used for the volumes of interest. We develop a linear approach that allows us to calculate truly Pareto optimal treatment plans, and we apply it to explore the tradeoff between tumour dose homogeneity and critical structure sparing. We show that for two phantom and two clinical cases, a smooth (as opposed to kinked) Pareto tradeoff curve exists. We find that in the paraspinal cases the Pareto surface is invariant to the response function used on the spinal cord: whether the mean cord dose or the maximum cord dose is used, the Pareto plan database is similar. This is not true for the lung studies, where the choice of objective function on the healthy lung tissue influences the resulting Pareto surface greatly. We conclude that in the special case when the tumour wraps around the organ at risk, e.g. prostate cases and paraspinal cases, the Pareto surface will be largely invariant to the objective function used to model the organ at risk.

Humans↗
PubMed2005

Integrated sample processing system involving on-column protein adsorption, sample washing, and enzyme digestion for protein identification by LC-ESI MS/MS.

An automated system has been developed for protein identification using mass spectrometry that incorporates sample cleanup, preconcentration, and protein digestion in a single stage. The procedure involves the adsorption of a protein or a protein mixture from solution onto a hydrophobic medium that is contained within a microcolumn. The protein is digested while still bound to the hydrophobic support. The peptides are then eluted from surface digestion to an electrospray ionization mass spectrometer for detection and sequencing. The entire system is fully automated wherein the mass spectrometer is collecting data continuously. We demonstrate that this system is capable of identifying standard protein samples at concentrations down to 100 nM. Further development of this technique may offer a potential solution for proteomics applications that require unattended operation, such as on-line monitoring and identification of microorganisms on the basis of the detection of their protein biomarkers.

Adsorption↗
PubMed2005

Increasing clindamycin resistance among methicillin-resistant Staphylococcus aureus in 57 northeast United States military treatment facilities.

BACKGROUND: Increasing community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) has led many to use clindamycin for CA-MRSA disease, whereas others suggest caution because of inducible clindamycin resistance and rely on drugs such as trimethoprim-sulfamethoxazole (TMP-SMX). AIM: To analyze the change in antibiotic susceptibility pattern of S. aureus isolates from 2001 to 2004 in a closed health care system, a period during which clindamycin and TMP-SMX use increased 99 and 62%, respectively. METHODS: S. aureus cultures from 57 military hospitals and clinics from 2001-2002 and 2003-2004 were compared for body site and antibiotic sensitivity, particularly the potentially inducible clindamycin-susceptible erythromycin-resistant pattern. A portion was evaluated by a double disk diffusion test (D test). RESULTS: Numbers of S. aureus-positive cultures obtained from "wound" sites rose significantly in both pediatric (138 to 215, P < 0.001) and adult (715 to 972, P < 0.001) isolates, with a rise in MRSA in children (6 of 138 to 60 of 215, P < 0.001) and in adults (161 of 715 to 324 of 972, P < 0.001). Clindamycin resistance increased among pediatric S. aureus isolates (1 of 207 to 13 of 327, P < 0.05), whereas >96% remained TMP-SMX-susceptible. Five methicillin-susceptible S. aureus (MSSA), 2 MRSA of 41 pediatric and 36 MSSA, 43 MRSA of 437 adult S. aureus specimens were D test-positive. CONCLUSIONS: In late 2004, most S. aureus from our region are still beta-lactam-susceptible. Most of the MRSA are still susceptible to clindamycin and do not appear to have inducible resistance. We must closely monitor the rates of constitutive and inducible clindamycin resistance as well as consider treatment alternatives that may slow the rate of clindamycin resistance.

Adolescent↗
PubMed2003

Mass spectrometric study of the effects of hydrophobic surface chemistry and morphology on the digestion of surface-bound proteins.

Our previous work has demonstrated that reversed-phase chromatographic micro-beads can be used to capture proteins from complex biological matrices and the surface-bound proteins can be enzymatically digested for protein identification by mass spectrometry (MS). Here we examine the peptides generated from digestion of proteins bound to various types of micro-bead surfaces in order to determine the effects of surface chemistry and surface morphology on the digestion process. Detailed examinations of site cleavages and sequence coverage are carried out for a tryptic digestion of cytochrome c adsorbed on reversed-phase polystyrene divinylbenzene (Poros R2 beads) versus C(18) bonded-phase silica beads. It is shown that although the surface does not completely hinder the digestion of cleavage sites of the protein, the digestion products are clearly different than those obtained from a solution digest. Specifically, a partial digestion results from surface digestion, resulting in a greater number of missed cleavages than a comparable solution digest. Subsequent comparisons of peptide mass maps generated from the digestion of various proteins on surfaces with altering chemistry (C(4), C(8), C(18), and R2 beads), or with different surface morphology, were performed. The results reveal that surface chemistry plays only a minor role in affecting the peptide mass maps, and surface morphology had no noticeable effects on the resulting peptide mass maps. It is also shown that the mass spectrometric detection method used to analyze the digested peptides can significantly influence the information content on cleavage sites and the extent of sequence coverage. The use of a combination of MALDI, LC/off-line MALDI, and LC/ESI MS is demonstrated to be crucial in revealing subtle changes in the peptide mass maps.

Chromatography, High Pressure Liquid↗
PubMedDate not supplied

Microcolumn capture and digestion of proteins combined with mass spectrometry for protein identification.

A procedure has been developed for protein identification using mass spectrometry (MS) that incorporates sample cleanup, preconcentration, and protein digestion in a single-stage system. The procedure involves the adsorption of a protein, or protein mixture, from solution onto a hydrophobic resin that is contained within a microcolumn. Sample loading is accomplished by flowing the protein solution through the microcolumn, where the protein adsorbs to the hydrophobic surface. The protein is digested while still bound to the hydrophobic surface by flowing a buffered trypsin solution through the column bed. The peptide fragments are subsequently eluted for detection by MALDI or ESI-MS. The procedure is demonstrated using dilute protein samples containing high concentrations of salt, urea, and modest amount of sodium dodecyl sulfate relative to protein. Peptide fragments are also detected by MS from a 500 nM bacteriorhodopsin solution digested in a microcolumn. In this case, a combined cyanogen bromide/trypsin digestion was performed in-column. The procedure is applied to the MALDI-MS/MS identification of proteins present in an individual fraction collected by ion exchange HPLC separation of E. coli total cell extract. An additional application is illustrated in the analysis of a human plasma fraction. A total of 14 proteins, which were present in the sample at sub-micromolar concentrations, were identified from ESI-MS/MS. The microcolumn digestion procedure represents the next step toward a system for fully automated protein analysis through capture and digestion of the adsorbed protein on hydrophobic surfaces.

Chromatography, Ion Exchange↗