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Biomedical subjects

D West

Publications and source records attributed to D West.

At least 19 recordsLinked to original sources
PubMed2006

Isotope dependence of the lifetime of the vibration of oxygen in silicon.

By simply changing the isotopes of the Si atoms that neighbor an oxygen Oi atom in crystalline silicon, the measured decay rate tau of the asymmetric-stretch vibration (nu3=1136 cm-1) of oxygen (Oi) in silicon changes by a factor of approximately 2.5. These data establish that nu3 decays by creating one nu1 symmetric-stretch, local-vibrational mode of the Si-Oi-Si structure. If the residual energy (nu3-nu1) is less than the maximum frequency num of the host lattice, as for 28Si-16O-28Si in natural silicon, then it is emitted as one lattice mode, and tau depends on the density of one-phonon states at nu3-nu1. If (nu3-nu1)>num, as for 16O in single-isotope 30Si silicon, two lattice modes are created in addition to nu1, increasing tau. Prediction of tau for a particular defect clearly requires a detailed knowledge of that defect.

Journal Article↗
PubMed2006

First-principles calculations of vibrational lifetimes and decay channels: hydrogen-related modes in Si.

The vibrational lifetimes and decay channels of local vibrational modes are calculated from first principles at various temperatures. Our method can be used to predict the temperature dependence of the lifetime of any normal mode in any crystal. We focus here on the stretch modes of H2*, H+(BC), and VH x HV in Si. The frequencies are almost identical, but the lifetimes vary from 4 to 295 ps. The calculations correctly predict the lifetimes for T > 50 K and illustrate the critical importance of pseudolocal modes in the decay processes of high-frequency local vibrational modes.

Journal Article↗
PubMed2006

Population-based estimates of breast cancer risks associated with ATM gene variants c.7271T>G and c.1066-6T>G (IVS10-6T>G) from the Breast Cancer Family Registry.

The ATM gene variants segregating in ataxia-telangiectasia families are associated with increased breast cancer risk, but the contribution of specific variants has been difficult to estimate. Previous small studies suggested two functional variants, c.7271T>G and c.1066-6T>G (IVS10-6T>G), are associated with increased risk. Using population-based blood samples we found that 7 out of 3,743 breast cancer cases (0.2%) and 0 out of 1,268 controls were heterozygous for the c.7271T>G allele (P=0.1). In cases, this allele was more prevalent in women with an affected mother (odds ratio [OR]=5.5, 95% confidence interval [CI]=1.2-25.5; P=0.04) and delayed child-bearing (OR=5.1; 95% CI=1.0-25.6; P=0.05). The estimated cumulative breast cancer risk to age 70 years (penetrance) was 52% (95% CI=28-80%; hazard ratio [HR]=8.6; 95% CI=3.9-18.9; P<0.0001). In contrast, 13 of 3,757 breast cancer cases (0.3%) and 10 of 1,268 controls (0.8%) were heterozygous for the c.1066-6T>G allele (OR=0.4; 95% CI=0.2-1.0; P=0.05), and the penetrance was not increased (P=0.5). These findings suggest that although the more common c.1066-6T>G variant is not associated with breast cancer, the rare ATM c.7271T>G variant is associated with a substantially elevated risk. Since c.7271T>G is only one of many rare ATM variants predicted to have deleterious consequences on protein function, an effective means of identifying and grouping these variants is essential to assess the contribution of ATM variants to individual risk and to the incidence of breast cancer in the population.

Adolescent↗
PubMed2006

The human CD94 gene encodes multiple, expressible transcripts including a new partner of NKG2A/B.

CD94/NKG2A is an inhibitory receptor expressed by natural killer (NK) cells and a subset of CD8+ T cells. Ligation of CD94/NKG2A by its ligand HLA-E results in tyrosine phosphorylation of the NKG2A immunoreceptor tyrosine-based inhibitory motifs, and recruitment and activation of the SH2 domain-bearing tyrosine phosphatase-1, which in turn suppresses activation signals. The nkg2a gene encodes two isoforms, NKG2A and NKG2B, with the latter lacking the stem region. We identified three new alternative transcripts of the cd94 gene in addition to the originally described canonical CD94Full. One of the transcripts, termed CD94-T4, lacks the portion that encodes the stem region. CD94-T4 associates with both NKG2A and NKG2B, but preferentially associates with the latter. This is probably due to the absence of a stem region in both CD94-T4 and NKG2B. CD94-T4/NKG2B is capable of binding HLA-E and, when expressed in E6-1 Jurkat T cells, inhibits TCR mediated signals, demonstrating that this heterodimer is functional. Coevolution of stemless isoforms of CD94 and NKG2A that preferentially pair with each other to produce a functional heterodimer indicates that this may be more than a serendipitous event. CD94-T4/NKG2B may contribute to the plasticity of the NK immunological synapse by insuring an adequate inhibitory signal.

Alternative Splicing↗
PubMed2006

Practical experiences of moving molecular diagnostics into routine use at the Veterinary Laboratories Agency.

The practical bench application of molecular tests (here defined as nucleic acid-based tests) in a routine testing situation is not without its challenges. This paper outlines the approaches we take at the Veterinary Laboratories Agency (VLA) and highlights some of the practical issues which we have found to be important for the successful introduction and use of molecular tests in a routine testing environment. The potential advantages of molecular tests, and factors which dictate which tests are adopted for routine testing, are discussed before giving some examples of molecular tests in routine use at the VLA. The instrumentation, reagents and assays we use are outlined, followed by sections of how we approach validation and how we manage and resource the transfer of molecular tests into routine use.

Laboratories↗
PubMed2005

Patient valuation of pharmacist services for self care with OTC medications.

BACKGROUND AND OBJECTIVES: The objectives of this study were to determine whether patients would be willing to pay for pharmacist self-care services on proper use of over-the-counter medications. In addition, we examined whether patients' willingness to pay was associated with community pharmacy setting and patients' socio-economic factors. METHODS: A self-administered questionnaire was handed out to patrons of community pharmacies in Arkansas, USA. The questionnaire contained question items related to patients' willingness to pay, community pharmacy setting, prescription drug insurance and socio-economic information. Patients' willingness to pay was measured using the checklist method. RESULTS AND DISCUSSION: A total of 262 questionnaires were completed. More than twice as many patients (51%) are now willing to pay for pharmacist services for patient self care than a decade ago. They were willing to pay about US5 dollars for a 5-min consultation. Willingness to pay was significantly associated with community pharmacy setting (chi-square, P = 0.030). Grocery/chain pharmacy patrons were more willing to pay than independent pharmacy patrons. CONCLUSION: This increased patient willingness to pay, along with growing self-care markets, provides pharmacists with opportunities to develop self-care clinics or services.

Adult↗
PubMed2003

First-principles calculations of pseudolocal vibrational modes: the case of Cu and Cu pairs in Si.

Pseudolocal vibrational modes (pLVMs) are defect-related vibrational modes which are localized despite being below the phonon maximum. Such modes are sometimes seen as phonon replicas in photoluminescence spectra. The pLVMs associated with two copper-related defects are calculated from first-principles density-functional theory in periodic supercells. The localization of the pLVMs is quantified using the magnitude of the eigenvectors of the dynamical matrix.

Journal Article↗
PubMed2001

Prospective study of fungaemia in a single cancer institution over a 10-y period: aetiology, risk factors, consumption of antifungals and outcome in 140 patients.

Over a 10-y period (1989-99) we prospectively evaluated all patients with fungaemia among 16,555 admissions (21,004 blood cultures) at a national cancer referral institution in the Slovak Republic. A prospective protocol was completed on 140 patients with fungaemia, which was then analysed in terms of aetiology, clinical characteristics, potential risk factors and outcome. The most frequently isolated organism was C. albicans, in 75 patients (52.9%), followed by non-albicans Candida spp. in 45 patients (32.1%). Non-Candida spp. yeasts represented 16 episodes in 16 patients (11.4%). Moulds caused 4 episodes in 4 patients (3.6% of all fungaemias) and all were caused by Fusarium spp. Mucositis (p = 0.025), > or = 3 positive blood cultures (p = 0.02), acute leukaemia (p = 0.00001), neutropenia (p = 0.0015), quinolone prophylaxis (p < 0.000005) and breakthrough fungaemia (p = 0.004) during prophylaxis with fluconazole (p = 0.03) and itraconazole (p = 0.005) were significantly more associated with non-Candida than C. albicans spp. Furthermore, attributable mortality was higher in the subgroup of non-Candida than C. albicans spp. (50.0 vs. 18.7%, p < 0.02). The only independent risk factor for inferior outcome was antifungal therapy of < 10 d duration (odds ratio 2.1, 95% confidence interval, p < 0.001). Aetiology, neutropenia and mucositis were not independent risk factors for higher mortality in multivariate analysis; however, they were risk factors for inferior outcome in univariate analysis (p < 0.05-0.005).

Adolescent↗
PubMed2001

Circulatory responses to maternal hyperoxaemia and hypoxaemia assessed non-invasively in fetal sheep at 0.3-0.5 gestation in acute experiments.

OBJECTIVES: To determine fetal haemodynamic responses to hyperoxaemia and hypoxaemia in early pregnancy. DESIGN: Repeated measurements in acute experiments. SETTING: Experimental physiology laboratory. METHODS: Non-invasive Doppler ultrasound of the umbilical vein, ductus venosus, umbilical and common carotid arteries of 12 fetal lambs (0.27-0.56 gestation) during maternal hyperoxaemia and hypoxaemia under ketamine anaesthesia. The effect of gestational age, hyperoxaemia, and hypoxaemia were assessed based on analysis of variance for dependent measurements and P < or = 0.05 was considered significant. Differences between groups were considered significant if the 95% confidence interval did not include zero. RESULTS: Gestational age had a significant effect on the blood velocity in the umbilical vein and ductus venosus. There were no circulatory changes during hyperoxaemia, but a simultaneous increase of pCO2 was an important confounder. However, hypoxaemia caused significantly reduced heart rate, reduced maximum and weighted mean blood velocity, and augmented pulsation in the umbilical vein. Hypoxaemia also caused reduced velocities in the ductus venosus (peak velocity during systole and minimum during diastole, and time-averaged velocity) and augmented pulsation of the flow velocity. Additionally, the pulsatility of blood flow increased in the umbilical artery and was reduced in the common carotid artery. CONCLUSIONS: Maternal hypoxaemia in early pregnancy causes similar fetal circulatory responses to those in late pregnancy: bradycardia, reduced venous flow velocities, augmented pulsatility in veins and a redistributional flow velocity pattern of the umbilical and common carotid arteries.

Animals↗
PubMed2001

Recombinant Neisseria meningitidis transferrin binding protein A protects against experimental meningococcal infection.

To better characterize the vaccine potential of Neisseria meningitidis transferrin binding proteins (Tbps), we have overexpressed TbpA and TbpB from Neisseria meningitidis isolate K454 in Escherichia coli. The ability to bind human transferrin was retained by both recombinant proteins, enabling purification by affinity chromotography. The recombinant Tbps were evaluated individually and in combination in a mouse intraperitoneal-infection model to determine their ability to protect against meningococcal infection and to induce cross-reactive and bactericidal antibodies. For the first time, TbpA was found to afford protection against meningococcal challenge when administered as the sole immunogen. In contrast to the protection conferred by TbpB, this protection extended to a serogroup C isolate and strain B16B6, a serogroup B isolate with a lower-molecular-weight TbpB than that from strain K454. However, serum from a TbpB-immunized rabbit was found to be significantly more bactericidal than that from a TbpA-immunized animal. Our evidence demonstrates that TbpA used as a vaccine antigen may provide protection against a wider range of meningococcal strains than does TbpB alone. This protection appears not to be due to complement-mediated lysis and indicates that serum bactericidal activity may not always be the most appropriate predictor of efficacy for protein-based meningococcal vaccines.

Animals↗
PubMed2001

Seven human immunodeficiency virus (HIV) antigen-antibody combination assays: evaluation of HIV seroconversion sensitivity and subtype detection.

In this study, we evaluated the performance of two prototype human immunodeficiency virus (HIV) antigen-antibody (Ag-Ab) combination assays, one from Abbott Laboratories (AxSYM HIV Ag-Ab) and the other from bioMerieux (VIDAS HIV Duo Ultra), versus five combination assays commercially available in Europe. The assays were Enzygnost HIV Integral, Genscreen Plus HIV Ag-Ab, Murex HIV Ag-Ab Combination, VIDAS HIV Duo, and Vironostika HIV Uniform II Ag-Ab. All assays were evaluated for the ability to detect p24 antigen from HIV-1 groups M and O, antibody-positive plasma samples from HIV-1 groups M and O, HIV-2, and 19 HIV seroconversion panels. Results indicate that although all combination assays can detect antibodies to HIV-1, group M, subtypes A to G, circulating recombinant form (CRF) A/E, and HIV-1 group O, their sensitivity varied considerably when tested using diluted HIV-1 group O and HIV-2 antibody-positive samples. Among combination assays, the AxSYM, Murex, and VIDAS HIV Duo Ultra assays exhibited the best antigen sensitivity (at approximately 25 pg of HIV Ag/ml) for detection of HIV-1 group M, subtypes A to G and CRF A/E, and HIV-1 group O isolates. However, the VIDAS HIV Duo Ultra assay had a lower sensitivity for HIV-1 group M and subtype C, and was unable to detect subtype C antigen even at 125 pg of HIV Ag/ml. The HIV antigen sensitivity of the VIDAS HIV Duo and Genscreen Plus combination assays was approximately 125 pg of HIV Ag/ml for detection of all HIV-1 group M isolates except HIV-1 group O while the sensitivity of Vironostika HIV Uniform II Ag-Ab and Enzygnost HIV Integral Ag-Ab assays for all the group M subtypes was >125 pg of HIV Ag/ml. Among the combination assays, the AxSYM assay had the best performance for detection of early seroconversion samples, followed by the Murex and VIDAS HIV Duo Ultra assays.

AIDS Serodiagnosis↗
PubMed2000

Apoptosis and proliferation in nongenotoxic carcinogenesis: species differences and role of PPARalpha.

Peroxisome proliferators (PPs) are nongenotoxic rodent hepatocarcinogens that cause liver enlargement and hepatocarcinogenesis associated with peroxisome proliferation, induction of hepatocyte DNA synthesis and suppression of apoptosis. Acyl CoA oxidase (ACO) is a key enzyme of peroxisomal beta-oxidation and its transcriptional activation by PPs is often used as marker for the rodent response. PPs activate the peroxisome proliferator activated receptor-alpha, PPARalpha. Recent data suggest a role for tumour necrosis factor alpha (TNFalpha). This cytokine appears to be permissive for a PPARalpha-dependent growth response to PPs. Humans and guinea pigs appear to be nonresponsive to the adverse effects of PPs noted in rodents. These species differences can be attributed to reduced quantity of full length functional PPARalpha in human liver and evidence supports the presence of a truncated form of PPARalpha, hPPARalpha8/14 in human liver. In addition, species differences could be attributed to qualitative differences in the PPARalpha-mediated response because the promoter for human ACO differs in sequence and activity from the rat equivalent. These data contribute to our understanding of how chemicals may cause tumours in rodents and how this response may differ in humans.

Animals↗
PubMed2000

Model selection for a medical diagnostic decision support system: a breast cancer detection case.

There are a number of different quantitative models that can be used in a medical diagnostic decision support system (MDSS) including parametric methods (linear discriminant analysis or logistic regression), non-parametric models (K nearest neighbor, or kernel density) and several neural network models. The complexity of the diagnostic task is thought to be one of the prime determinants of model selection. Unfortunately, there is no theory available to guide model selection. Practitioners are left to either choose a favorite model or to test a small subset using cross validation methods. This paper illustrates the use of a self-organizing map (SOM) to guide model selection for a breast cancer MDSS. The topological ordering properties of the SOM are used to define targets for an ideal accuracy level similar to a Bayes optimal level. These targets can then be used in model selection, variable reduction, parameter determination, and to assess the adequacy of the clinical measurement system. These ideas are applied to a successful model selection for a real-world breast cancer database. Diagnostic accuracy results are reported for individual models, for ensembles of neural networks, and for stacked predictors.

Algorithms↗
PubMed2000

Improving diagnostic accuracy using a hierarchical neural network to model decision subtasks.

A number of quantitative models including linear discriminant analysis, logistic regression, k nearest neighbor, kernel density, recursive partitioning, and neural networks are being used in medical diagnostic support systems to assist human decision-makers in disease diagnosis. This research investigates the decision accuracy of neural network models for the differential diagnosis of six erythematous-squamous diseases. Conditions where a hierarchical neural network model can increase diagnostic accuracy by partitioning the decision domain into subtasks that are easier to learn are specifically addressed. Self-organizing maps (SOM) are used to portray the 34 feature variables in a two dimensional plot that maintains topological ordering. The SOM identifies five inconsistent cases that are likely sources of error for the quantitative decision models; the lower bound for the diagnostic decision error based on five errors is 0.0140. The traditional application of the quantitative models cited above results in diagnostic error levels substantially greater than this target level. A two-stage hierarchical neural network is designed by combining a multilayer perceptron first stage and a mixture-of-experts second stage. The second stage mixture-of-experts neural network learns a subtask of the diagnostic decision, the discrimination between seborrheic dermatitis and pityriasis rosea. The diagnostic accuracy of the two stage neural network approaches the target performance established from the SOM with an error rate of 0.0159.

Chronic Disease↗