Biomedical subjects
Publications and source records attributed to E Levine.
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Zero-range processes, in which particles hop between sites on a lattice, are closely related to rewiring networks, in which rewiring of links between nodes takes place. Both systems exhibit a condensation transition for appropriate choices of the dynamical rules. The transition results in a macroscopically occupied site for zero-range processes and a macroscopically connected node for networks. Criticality, characterized by a scale-free distribution, is obtained only at the transition point. This is in contrast with the widespread scale-free complex networks. Here we propose a generalization of these models whereby criticality is obtained throughout an entire phase, and the scale-free distribution does not depend on any fine-tuned parameter.
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An interim goal of the NHS National Cancer Plan is that, by 2005, patients with cancer should be treated within one month of diagnosis and within two months from urgent general practitioner referral. Preoperative radiotherapy for rectal cancer reduces the risk of local recurrence and may translate into improved patient survival. We conducted a prospective audit of existing waiting times for preoperative radiotherapy experienced by 65 patients with rectal cancer referred to the Christie Cancer Centre, Manchester, UK, between May and November 2002. The median time between referral from the surgeon to the start of radiotherapy was 40 days (range 11-85). Only 4 patients (6%) received radiotherapy within 28 days of referral by the surgeon. 62 patients (95%) underwent surgery within 14 days of completing radiotherapy. Delays in the provision of preoperative radiotherapy were primarily due to shortages of radiography staff and equipment. Lack of such infrastructure will prove a major stumbling block to achieving the targets of the NHS Cancer Plan.
A class of models of two-species driven diffusive systems which is shown to exhibit phase separation in d=1 dimensions is introduced. Unlike previously studied models exhibiting similar phenomena, here the relative density of the two species is fluctuating within the macroscopic domain of the phase separtated state. The nature of the phase transition from the homogeneous to the phase-separated state is discussed in view of a recently introduced criterion for phase separation in one-dimensional driven systems.
Western corn rootworm, Diabrotica virgifera virgifera LeConte, has overcome crop rotation in several areas of the central United States. We expanded a simple model of adult behavior and population genetics to explain how rotation resistance may have developed and to study ways to manage the western corn rootworm in a landscape of corn, soybean, and winter wheat where evolution of resistance may occur. We modeled six alternative management strategies over a 15-yr time horizon, as well as a strategy involving a 2-yr rotation of corn and soybean in 85% of the landscape, to investigate their effectiveness from both a biological and economic perspective. Generally, resistance to crop rotation evolves in fewer than 15 yr, and the rate of evolution increases as the level of rotated landscape (selection pressure) increases. When resistance is recessive, all six alternative strategies were effective at preventing evolution of rotation resistance. The two most successful strategies were the use of transgenic rotated corn in a 2-yr rotation and a 3-yr rotation of corn, soybean, and wheat with unattractive wheat (for oviposition) preceding corn. Results were most sensitive to increases in the initial allele frequency and modifications of the density-dependent survival function. Economically, three alternative strategies were robust solutions to the problem, if technology fees were not too high. Repellant soybean, attractive rotated corn, and transgenic rotated corn, all in 2-yr rotations, were economically valuable approaches. However, even the currently common 2-yr rotation was economical when resistance was recessive and the actual costs of resistance would not be paid until far in the future.
PURPOSE: To investigate whether transforming growth factor beta-1 (TGFbeta1) single nucleotide polymorphisms were associated with the susceptibility of breast cancer patients to severe radiation-induced normal tissue damage. MATERIALS AND METHODS: PCR-RFLP assays were performed for TGFbeta1 gene polymorphisms on DNA obtained from 103 breast cancer patients who received radiotherapy. The G-800A, C-509T, T+869C and G+915C polymorphic sites were examined, and genotype and allele frequencies of two subgroups of patients were calculated and compared. RESULTS: The less prevalent -509T and +869C alleles were significantly associated with a subgroup of patients who developed severe radiation-induced normal tissue fibrosis (n=15) when compared with those who did not (n=88) (odds ratio=3.4, p=0.0036, and 2.37, p=0.035, respectively). Furthermore, patients with the -509TT or +869CC genotypes were between seven and 15 times more likely to develop severe fibrosis. CONCLUSIONS: These findings imply a role for the -509T and +869C alleles in the pathobiological mechanisms underlying susceptibility to radiation-induced fibrosis. Their predictive value would be limited to patients who are -509TT or +869CC, but if "fibrosis-associated" polymorphic sites in other genes could be identified, it may be possible to detect fibrosis prone individuals before radiotherapy with greater certainty.
A general criterion for the existence of phase separation in driven density-conserving one-dimensional systems is proposed. It is suggested that phase separation is related to the size dependence of the steady-state currents of domains in the system. A quantitative criterion for the existence of phase separation is conjectured using a correspondence made between driven diffusive models and zero-range processes. The criterion is verified in all cases where analytical results are available, and predictions for other models are provided.
The focused ion beam lift-out technique for scanning electron microscope (SEM) and transmission electron microscope (TEM) sample preparation was shown to be applicable to copper/low-k dielectric semiconductor technology. High resolution SEM, TEM, and scanning transmission electron microscope analyses were performed on metal contacts and resist vias with no evidence of the interface damage or metal smearing commonly observed with mechanical polishing. Ion milling of the sample ex situ to the substrate provided decoration and adjustment of the exposed plane of the section when necessary for SEM analysis.
The evolution of a two-dimensional driven lattice-gas model is studied on an LxxL(y) lattice. Scaling arguments and extensive numerical simulations are used to show that starting from random initial configuration the model evolves via two stages: (a) an early stage in which alternating stripes of particles and vacancies are formed along the direction y of the driving field, and (b) a stripe coarsening stage, in which the number of stripes is reduced and their average width increases. The number of stripes formed at the end of the first stage is shown to be a function of L(x)/L(straight phi)(y), with straight phi approximately 0.2. Thus, depending on this parameter, the resulting state could be either single or multistriped. In the second, stripe coarsening stage, the coarsening time is found to be proportional to L(y), becoming infinitely long in the thermodynamic limit. This implies that the multistriped state is thermodynamically stable. The results put previous studies of the model in a more general framework.
We introduce a method for validation of results obtained by clustering analysis of data. The method is based on resampling the available data. A figure of merit that measures the stability of clustering solutions against resampling is introduced. Clusters that are stable against resampling give rise to local maxima of this figure of merit. This is presented first for a one-dimensional data set, for which an analytic approximation for the figure of merit is derived and compared with numerical measurements. Next, the applicability of the method is demonstrated for higher-dimensional data, including gene microarray expression data.
The management of many chronic illnesses involves medications that must be injected on a frequent basis. With fewer support resources available, patients are increasingly being obliged to manage injectable medications themselves. Interferon beta-1a (IFNbeta-1a), recommended for the treatment of multiple sclerosis (MS), must be injected intramuscularly on a weekly basis. Patients are generally advised and taught to self-inject, if possible. This longitudinal study examined cognitive and affective contributions to the ability to self-inject and adherence to IFNbeta-1a over 6 months following initiation of medication. Participants were 101 patients with a relapsing form of MS. Injection self-efficacy expectations, injection anxiety, adherence expectations, method of injection administration, and 6-month adherence to IFNbeta-1a were fitted to a path analytic model. Pretreatment injection self-efficacy expectations were significantly related to 6-month adherence. This relation was mediated by the patient's ability to self-inject. Patients 'experienced level of injection anxiety was related to adherence but not to method of injection.
A simulation model of the population dynamics and genetics of the western corn rootworm, Diabrotica virgifera virgifera LeConte, was created for a landscape of corn, soybean, and other crops. Although the model was created to study a 2-locus problem for beetles having genes for resistance to both crop rotation and transgenic corn, during this first phase of the project, the model was simulated to evaluate only resistance management plans for transgenic corn. Allele expression in the rootworm and toxin dose in the corn plant were the two most important factors affecting resistance development. A dominant resistance allele allowed quick evolution of resistance to transgenic corn, whereas a recessive allele delayed resistance >99 yr. With high dosages of toxin and additive expression, the time required to reach 3% resistance allele frequency ranged from 13 to >99 yr. With additive expression, lower dosages permitted the resistant allele frequency to reach 3% in 2-9 yr with refuges occupying 5-30% of the land. The results were sensitive to delays in emergence by susceptible adults and configuration of the refuge (row strips versus blocks).
Two recently released, Mexican bean beetle, Epilachna varivestis, Mulsant, resistant soybean, Glycine max (L.) Merrill, germplasm lines, HC95-15MB and HC95-24MB, were examined for foliar and pod feeding resistance to adult bean leaf beetles, Cerotoma trifurcata (Forster), western corn rootworms, Diabrotica virgifera virgifera LeConte, and Japanese beetles, Popillia japonica Newman. Both lines were planted along with a susceptible control cultivar in 18 by 30-m plots and separate 0.8-ha size fields. Insects were sampled on a weekly basis with a sweep net. In late summer, defoliation ratings were recorded along with data on percentage pod feeding. Although a few significant differences in insect densities were obtained among the soybean lines on some sampling dates, no specific trends were observed in the ability of the resistant germplasm to reduce insect numbers. Insect population densities were similarly on all lines. However, both resistant lines were able to reduce defoliation during the growing season. Conversely, percentage pod feeding was similar among all the soybean lines, with no differences observed. The resistant germplasm lines appear able to lower levels of defoliation, and thus, offer a potential management tactic where leaf feeding, i.e., defoliation, is of concern. However, their ability to greatly reduce beetle population densities, and for the bean leaf beetle, to reduce pod feeding, appears limited.
Alopecia areata is considered to be a T-cell mediated autoimmune disease of the hair follicle. Current immunosuppressive approaches and immunomodulatory treatment with contact sensitizers such as diphenylcyclopropenone and squaric acid dibutylester are dealt with in this review article. The efficacy of the various modes of treatment is evaluated by a review of literature and their mode of action is discussed. In accordance with the mechanism of autoimmune pathogenesis of AA, improved future treatments may be immunosuppressive or immunomodulatory, or they should otherwise protect the hair follicle from the injurious effects of the inflammation. Such possible future therapeutic approaches include the use of liposomes as an improved vehicle, application of immunosuppressive cytokines like TGF-beta and IL-10, inhibition of apoptosis mediated by the Fas-FasL system, inhibition of the lymphocyte homing receptor CD44v10, induction of tolerance as well as principles of gene therapy.
This article presents the results of a survey distributed to military women within and outside the continental United States (CONUS and OCONUS) who had received prenatal care and delivered at one of six Army, Navy, or Air Force military facilities. This comparative descriptive study was undertaken to determine from the mothers' perspective (1) their needs, availability, accessibility, use, satisfaction, and preferences for prenatal care services, and (2) if prenatal care and birth outcomes were significantly different for CONUS versus OCONUS women. Both groups reported a high degree of satisfaction with services, clinics/offices, and health care staff. Significant group differences were reported in transportation, length of travel time, and cost of traveling, with the CONUS group reporting greater problems with each. For both groups, quality and consistency of health care were the two most important factors in their preference of provider. More than 20% of the mothers reported receiving no information on some of the common concerns of pregnancy. There were no significant group differences with regard to infant birth weight or length of hospital stay.
We present a coupled two-way clustering approach to gene microarray data analysis. The main idea is to identify subsets of the genes and samples, such that when one of these is used to cluster the other, stable and significant partitions emerge. The search for such subsets is a computationally complex task. We present an algorithm, based on iterative clustering, that performs such a search. This analysis is especially suitable for gene microarray data, where the contributions of a variety of biological mechanisms to the gene expression levels are entangled in a large body of experimental data. The method was applied to two gene microarray data sets, on colon cancer and leukemia. By identifying relevant subsets of the data and focusing on them we were able to discover partitions and correlations that were masked and hidden when the full dataset was used in the analysis. Some of these partitions have clear biological interpretation; others can serve to identify possible directions for future research.