Biomedical subjects

David L Craft

Publications and source records attributed to David L Craft.

9 recordsLinked to original sources

PubMed2006

Maximizing operating room and recovery room capacity in an era of constrained resources.

HYPOTHESIS: Three parallel processing operating rooms (ORs) (concurrent induction and turnover) with a dedicated 3-bed mini-recovery room (mini-postanesthesia care unit [PACU]) will optimize patient throughput and main PACU workload when compared with 4 traditional ORs or 4 parallel processing ORs. DESIGN: Statistical and mathematical models projected the impact of parallel processing on case throughput and PACU use. SETTING: Academic medical center with 48 traditional ORs using serial induction and turnover and 1 experimental OR, the operating room of the future, with parallel processing. PARTICIPANTS: All surgical cases from October 2002 through March 2004 (N = 49 887). INTERVENTIONS: A statistical model projected the duration of induction, surgery, turnover, and PACU stay for cases performed in a traditional OR (n = 48 667) based on the operating room of the future (n = 1220) experience. A fluid queuing model compared each combination using specific probability density functions. MAIN OUTCOME MEASURES: Each OR configuration was evaluated for case throughput and minutes of work sent to the PACU. RESULTS: Although all cases save OR time with parallel processing, only select surgeon-case combinations translate time saved into additional cases per day (26%). Without additional PACU slots, output from 4 parallel processing ORs further stresses the PACU. Three parallel processing ORs and a mini-PACU balances incremental volume by offsetting PACU utilization in 84% of cases. CONCLUSION: In a PACU-constrained environment, 3 parallel processing ORs with a mini-PACU configuration offers increased throughput and decreased PACU workload.

Academic Medical Centers↗

PubMed2006

Approximating convex pareto surfaces in multiobjective radiotherapy planning.

Radiotherapy planning involves inherent tradeoffs: the primary mission, to treat the tumor with a high, uniform dose, is in conflict with normal tissue sparing. We seek to understand these tradeoffs on a case-to-case basis, by computing for each patient a database of Pareto optimal plans. A treatment plan is Pareto optimal if there does not exist another plan which is better in every measurable dimension. The set of all such plans is called the Pareto optimal surface. This article presents an algorithm for computing well distributed points on the (convex) Pareto optimal surface of a multiobjective programming problem. The algorithm is applied to intensity-modulated radiation therapy inverse planning problems, and results of a prostate case and a skull base case are presented, in three and four dimensions, investigating tradeoffs between tumor coverage and critical organ sparing.

Algorithms↗

PubMed2005

Evaluation of public health interventions for Anthrax: a report to the secretary's council on Public Health Preparedness.

To aid in understanding how best to respond to a bioterror anthrax attack, we analyze a system of differential equations that includes a disease progression model, a set of spatially distributed queues for distributing antibiotics, and vaccination (pre-event and/or post-event). We derive approximate expressions for the number of casualties as a function of key parameters and management levers, including the time at which the attack is detected, the number of days to distribute antibiotics, the adherence to prophylactic antibiotics, and the fraction of the population that is preimmunized. We compare a variety of public health intervention policies in the event of a hypothetical anthrax attack in a large metropolitan area. Modeling assumptions were decided by the Anthrax Modeling Working Group of the Secretary's Council on Public Health Preparedness. Our results highlight the primary importance of rapid antibiotic distribution and lead us to argue for ensuring post-attack surge capacity to rapidly produce enough anthrax vaccine for an additional 100 million people.

Anthrax↗

PubMed2004

Cloning and characterization of three fatty alcohol oxidase genes from Candida tropicalis strain ATCC 20336.

Candida tropicalis (ATCC 20336) converts fatty acids to long-chain dicarboxylic acids via a pathway that includes among other reactions the oxidation of omega-hydroxy fatty acids to omega-aldehydes by a fatty alcohol oxidase (FAO). Three FAO genes (one gene designated FAO1 and two putative allelic genes designated FAO2a and FAO2b), have been cloned and sequenced from this strain. A comparison of the DNA sequence homology and derived amino acid sequence homology between these three genes and previously published Candida FAO genes indicates that FAO1 and FAO2 are distinct genes. Both genes were individually cloned and expressed in Escherichia coli. The substrate specificity and K(m) values for the recombinant FAO1 and FAO2 were significantly different. Particularly striking is the fact that FAO1 oxidizes omega-hydroxy fatty acids but not 2-alkanols, whereas FAO2 oxidizes 2-alkanols but not omega-hydroxy fatty acids. Analysis of extracts of strain H5343 during growth on fatty acids indicated that only FAO1 was highly induced under these conditions. FAO2 contains one CTG codon, which codes for serine (amino acid 177) in C. tropicalis but codes for leucine in E. coli. An FAO2a construct, with a TCG codon (codes for serine in E. coli) substituted for the CTG codon, was prepared and expressed in E. coli. Neither the substrate specificity nor the K(m) values for the FAO2a variant with a serine at position 177 were radically different from those of the variant with a leucine at that position.

Alcohol Oxidoreductases↗

PubMed2003

Emergency response to an anthrax attack.

We developed a mathematical model to compare various emergency responses in the event of an airborne anthrax attack. The system consists of an atmospheric dispersion model, an age-dependent dose-response model, a disease progression model, and a set of spatially distributed two-stage queueing systems consisting of antibiotic distribution and hospital care. Our results underscore the need for the extremely aggressive and timely use of oral antibiotics by all asymptomatics in the exposure region, distributed either preattack or by nonprofessionals postattack, and the creation of surge capacity for supportive hospital care via expanded training of nonemergency care workers at the local level and the use of federal and military resources and nationwide medical volunteers. The use of prioritization (based on disease stage andor age) at both queues, and the development and deployment of modestly rapid and sensitive biosensors, while helpful, produce only second-order improvements.

Anthrax↗

PubMed2003

Analyzing bioterror response logistics: the case of smallpox.

To evaluate existing and alternative proposals for emergency response to a deliberate smallpox attack, we embed the key operational features of such interventions into a smallpox disease transmission model. We use probabilistic reasoning within an otherwise deterministic epidemic framework to model the 'race to trace', i.e., attempting to trace (via the infector) and vaccinate an infected person while (s)he is still vaccine-sensitive. Our model explicitly incorporates a tracing/vaccination queue, and hence can be used as a capacity planning tool. An approximate analysis of this large (16 ODE) system yields closed-form estimates for the total number of deaths and the maximum queue length. The former estimate delineates the efficacy (i.e., accuracy) and efficiency (i.e., speed) of contact tracing, while the latter estimate reveals how congestion makes the race to trace more difficult to win, thereby causing more deaths. A probabilistic analysis is also used to find an approximate closed-form expression for the total number of deaths under mass vaccination, in terms of both the basic reproductive ratio and the vaccination capacity. We also derive approximate thresholds for initially controlling the epidemic for more general interventions that include imperfect vaccination and quarantine.

Bioterrorism↗

PubMed2003

Identification and characterization of the CYP52 family of Candida tropicalis ATCC 20336, important for the conversion of fatty acids and alkanes to alpha,omega-dicarboxylic acids.

Candida tropicalis ATCC 20336 excretes alpha,omega-dicarboxylic acids as a by-product when cultured on n-alkanes or fatty acids as the carbon source. Previously, a beta-oxidation-blocked derivative of ATCC 20336 was constructed which showed a dramatic increase in the production of dicarboxylic acids. This paper describes the next steps in strain improvement, which were directed toward the isolation and characterization of genes encoding the omega-hydroxylase enzymes catalyzing the first step in the omega-oxidation pathway. Cytochrome P450 monooxygenase (CYP) and the accompanying NADPH cytochrome P450 reductase (NCP) constitute the hydroxylase complex responsible for the first and rate-limiting step of omega-oxidation of n-alkanes and fatty acids. 10 members of the alkane-inducible P450 gene family (CYP52) of C. tropicalis ATCC20336 as well as the accompanying NCP were cloned and sequenced. The 10 CYP genes represent four unique genes with their putative alleles and two unique genes for which no allelic variant was identified. Of the 10 genes, CYP52A13 and CYP52A14 showed the highest levels of mRNA induction, as determined by quantitative competitive reverse transcription-PCR during fermentation with pure oleic fatty acid (27-fold increase), pure octadecane (32-fold increase), and a mixed fatty acid feed, Emersol 267 (54-fold increase). The allelic pair CYP52A17 and CYP52A18 was also induced under all three conditions but to a lesser extent. Moderate induction of CYP52A12 was observed. These results identify the CYP52 and NCP genes as being involved in alpha,omega-dicarboxylic acid production by C. tropicalis and provide the foundation for biocatalyst improvement.

Alkanes↗

PubMed2002

Emergency response to a smallpox attack: the case for mass vaccination.

In the event of a smallpox bioterrorist attack in a large U.S. city, the interim response policy is to isolate symptomatic cases, trace and vaccinate their contacts, quarantine febrile contacts, but vaccinate more broadly if the outbreak cannot be contained by these measures. We embed this traced vaccination policy in a smallpox disease transmission model to estimate the number of cases and deaths that would result from an attack in a large urban area. Comparing the results to mass vaccination from the moment an attack is recognized, we find that mass vaccination results in both far fewer deaths and much faster epidemic eradication over a wide range of disease and intervention policy parameters, including those believed most likely, and that mass vaccination similarly outperforms the existing policy of starting with traced vaccination and switching to mass vaccination only if required.

Centers for Disease Control and Prevention, U.S.↗

PubMed2002

A mathematical model of the impact of novel treatments on the A beta burden in the Alzheimer's brain, CSF and plasma.

With the advent of novel therapies for Alzheimer's disease, there is pressing need for biomarkers that are easy to monitor, such as the amyloid-beta (A beta) levels in the cerebrospinal fluid (CSF) and plasma. To gain a better understanding of the explanatory power of these biomarkers, we formulate and analyze a compartmental mathematical model for the A beta accumulation in the brain, CSF and plasma, throughout the course of Alzheimer's treatment. Our analysis reveals that the total A beta burden in the brain is dictated by a unitless quantity called the polymerization ratio, which is the product of the production and elongation rates divided by the product of the fragmentation and loss rates. In this ratio, the production rate and loss rate include a source and sink term, respectively, related to the intercompartmental transport. Our results suggest that production inhibitors are likely to reduce the A beta levels in all three compartments. In contrast, agents that ingest monomers off of polymers, or that increase fragmentation or block elongation, may also reduce A beta burden in the brain, but may produce little change in--or even transiently increase--CSF and plasma A beta levels. Hence, great care must be taken when interpreting these biomarkers.

Alzheimer Disease↗