Biomedical subjects

K Davis

Publications and source records attributed to K Davis.

At least 19 recordsLinked to original sources

PubMed2006

IMBA Professional Plus: a flexible approach to internal dosimetry.

IMBA (Integrated Modules for Bioassay Analysis) is a suite of software modules that implement the current ICRP biokinetic and dosimetric models for estimation of intakes and doses. The IMBA modules have gone through extensive quality assurance, and are now used for routine formal dose assessment by Approved Dosimetry Services throughout the UK. HPA has continued to develop the IMBA modules. In addition, several projects, sponsored by organisations both in the USA and in Canada, have resulted in the development of customised user-friendly interfaces (IMBA Expert 'editions'). These enable users not only to use the standard ICRP models, but also to change many of the parameter values from ICRP defaults, and to apply sophisticated data handling techniques to internal dose calculations. These include: fitting measurement data with the maximum likelihood method; using multiple chronic and acute intakes; and dealing with different data types, such as urine, faces and whole body simultaneously. These interfaces were improved further as a result of user-feedback, and a general 'off-the-shelf' product, IMBA Professional, was developed and made available in January 2004. A new version, IMBA Professional Plus, was released in April 2005, which is both faster and more powerful than previous software. The aim of this paper is to describe the capabilities of IMBA Professional Plus, and the mathematical methods used.

Algorithms↗

PubMed2006

Simian varicella virus gene 61 encodes a viral transactivator but is non-essential for in vitro replication.

Simian varicella virus (SVV) is closely related to varicella-zoster virus (VZV), the causative agent of chickenpox and shingles. The SVV and VZV gene 61 polypeptides are homologs of the HSV-1 ICP0, a viral transactivator which appears to play a role in viral latency and reactivation. In this study, the molecular properties of the SVV 61 were characterized. The SVV open reading frame (ORF) 61 encodes a 54.1-kDa polypeptide with 37% amino acid identity to the VZV 61. Homology to the HSV-1 ICP-0 is limited to a conserved RING finger motif at the amino terminus of the protein. A nuclear localization sequence (nls) at the carboxy-terminus directs the SVV 61 to the cell nucleus, while a SVV 61nls(-) mutant is confined to the cell cytoplasm. The SVV 61 transactivates its own promoter as well as SVV immediate early (IE, ORF 62), early (ORFs 28 and 29), and late (ORF 68) gene promoters in transfected Vero cells. The RING finger and nls motifs are required for efficient SVV 61 transactivation. The SVV 61 has no effect on the ability of the major SVV transactivator (IE62) to induce SVV promoters. Generation and propagation of a SVV gene 61 deletion mutant demonstrated that the SVV 61 is non-essential for in vitro replication. SVV gene 61 is expressed in liver, lung, and neural ganglia of infected monkeys during acute simian varicella.

Amino Acid Sequence↗

PubMed2006

Randomised double-blind placebo-controlled trial of aloe vera for irritable bowel syndrome.

Aloe vera (AV) is suggested to be beneficial in treating irritable bowel syndrome (IBS) symptoms, but no scientific trials exist to confirm this. We aim to assess the efficacy of AV on IBS in refractory secondary care patients. Patients with IBS were randomised to receive AV or matching placebo for a month. Symptoms were assessed at baseline, 1 and 3 months. Fifty-eight patients randomised, 49 completed the protocol to 1 month and 41 to 3 months. Eleven of thirty-one (35%) AV patients, and 6 of 27 (22%) placebo patients responded at 1 month (p = 0.763). Diarrhoea predominant patients showed a trend towards a response to treatment at 1 month (10/23 V 2/14, p = 0.07). There was no evidence that AV benefits patients with IBS. However, we could not rule out the possibility that improvement occurred in patients with diarrhoea or alternating IBS whilst taking AV. Further investigations are warranted in patients with diarrhoea predominant IBS, in a less complex group of patients.

Adolescent↗

PubMed2006

Neo-epitopes are required for immunogenicity of the La/SS-B nuclear antigen in the context of late apoptotic cells.

Mechanisms responsible for the induction of anti-nuclear autoantibodies (ANA) following exposure of the immune system to an excess of apoptotic cells are incompletely understood. In this study, the immunogenicity of late apoptotic cells expressing heterologous or syngeneic forms of La/SS-B was investigated following subcutaneous administration to A/J mice, a non-autoimmune strain in which the La antigenic system is well understood. Immunization of A/J mice with late apoptotic thymocytes taken from mice transgenic (Tg) for the human La (hLa) nuclear antigen resulted in the production of IgG ANA specific for human and mouse forms of La in the absence of foreign adjuvants. Preparations of phenotypically healthy cells expressing heterologous hLa were also immunogenic. However, hLa Tg late apoptotic cells accelerated and enhanced the apparent heterologous healthy cell-induced anti-La humoral response, while non-Tg late apoptotic cells did not. Subcutaneous administration of late apoptotic cells was insufficient to break existing tolerance to the hLa antigen in hLa Tg mice or to the endogenous mouse La (mLa) antigen in A/J mice immunized with syngeneic thymocytes, indicating a requirement for the presence of heterologous epitopes for anti-La ANA production. Lymph node dendritic cells (DC) but not B cells isolated from non-Tg mice injected with hLa Tg late apoptotic cells presented immunodominant T helper cell epitopes of hLa. These studies support a model in which the generation of neo-T cell epitopes is required for loss of tolerance to nuclear proteins after exposure of the healthy immune system to an excess of cells in late stages of apoptosis.

Adjuvants, Immunologic↗

PubMed2005

Tobacco and alcohol use in lung transplant candidates and recipients.

Tobacco and alcohol use among lung transplant candidates and recipients is unknown. Our first goal was to describe tobacco and alcohol use before and after lung transplant in patients with cystic fibrosis (CF) and other pulmonary diseases (non-CF). Our second goal was to determine whether demographic variables, depression, anxiety and social support predicted tobacco and alcohol use. Self-report data from transplant candidates and recipients, and transplant nurse coordinator ratings of post-transplant smoking and drinking were utilized. Data from two samples were analyzed. Sample 1 comprised 219 patients being evaluated for lung transplant, and sample 2 comprised 45 transplant recipients who were 1-7 yrs post-transplant. The results from analyzing sample 1 indicated that 72% of non-CF patients and 16% of CF patients had a history of smoking cigarettes, and the majority of patients in both groups had consumed alcohol in the past. For CF patients, past smoking was related to higher depression scores, and past drinking was related to higher education and lower social support. For non-CF patients, a history of smoking was associated with being Caucasian and older. For CF patients, a history of drinking was associated with being older and less depressed, and for non-CF patients a history of drinking was associated with higher education and lower social support. Post-transplant 100% of recipients reported abstinence from tobacco, and over 60% reported abstinence from alcohol. Transplant coordinator ratings corroborated that no transplant recipients were using tobacco products or consuming alcohol in an excessive or problematic manner. For both groups, consuming alcohol after transplant was related to lower levels of social support. In conclusion, lung recipients remain abstinent from tobacco, and although over 30% of patients consume alcohol after transplant, it is not at problematic levels. Smoking and drinking behaviors were related to demographic variables, depression, and low social support.

Adult↗

PubMed2005

Clinical audit of the use of fresh-frozen plasma and platelets in a tertiary teaching hospital and the impact of a new transfusion request form.

AIM: To carry out an audit of the appropriateness of fresh-frozen plasma (FFP) and platelets (Plt) transfusion with reference to the Australian National Health and Medical Research Council/Australian Society of Blood Transfusion Clinical Practice Guidelines, and to assess the impact of a self-educating transfusion request form. METHODS: A prospective review of the clinical indications and laboratory data in all transfusion episodes of FFP and Plt occurring in a tertiary teaching hospital in South Australia in two 2-month periods of the years 2002 and 2003. RESULTS: Reversal of warfarin has emerged as the major indication to transfuse FFP (34%). More than 72% FFP and 88% Plt were prescribed in an appropriate manner, and the majority were monitored adequately. The transfusion request form further improved the appropriate uses and was met with a satisfactory compliance. Further grounds for improvement are in FFP usage by the haematology unit and in cardiac bypass surgery, and Plt by surgical units. CONCLUSION: Clinical transfusion audit helps to identify current pattern of usage and areas of improvement. A self-educating transfusion specific request form is also beneficial.

Blood Component Transfusion↗

PubMed2004

Localization and physical property experiments conducted by Opportunity at Meridiani Planum.

The location of the Opportunity landing site was determined to better than 10-m absolute accuracy from analyses of radio tracking data. We determined Rover locations during traverses with an error as small as several centimeters using engineering telemetry and overlapping images. Topographic profiles generated from rover data show that the plains are very smooth from meter- to centimeter-length scales, consistent with analyses of orbital observations. Solar cell output decreased because of the deposition of airborne dust on the panels. The lack of dust-covered surfaces on Meridiani Planum indicates that high velocity winds must remove this material on a continuing basis. The low mechanical strength of the evaporitic rocks as determined from grinding experiments, and the abundance of coarse-grained surface particles argue for differential erosion of Meridiani Planum.

Extraterrestrial Environment↗

PubMed2004

Ictal neocortical slowing in temporal lobe epilepsy.

BACKGROUND: Temporal lobe epilepsy (TLE) may affect brain regions outside the temporal lobe, causing impaired neocortical function during seizures. METHODS: The authors selected 11 consecutive patients with mesial TLE and hippocampal sclerosis who underwent intracranial EEG monitoring and had no seizures during a follow-up period of at least 1 year after temporal lobe resection. Secondarily generalized seizures were excluded, and up to three seizures were analyzed per patient (31 seizures total). Electrode contacts were assigned to one of nine cortical regions based on MRI surface reconstructions. EEG during seizures was analyzed for specific patterns including low-voltage fast (LVF), rhythmic polyspike, spike-wave, irregular slowing, and postictal suppression. RESULTS: Mesial and lateral temporal contacts on the side of seizure onset showed significant increases in ictal patterns such as LVF and polyspike activity, followed by postictal suppression. Bilateral frontal and ipsilateral parietal cortex exhibited large amplitude irregular slow waves during seizures. This frontoparietal slowing persisted into the postictal period. Perirolandic and occipital cortex were relatively spared. These EEG patterns were accompanied by bland staring, minor automatisms, and unresponsiveness or amnesia in the majority of patients studied. CONCLUSIONS: Prominent irregular slowing occurs in bilateral frontal and ipsilateral parietal association cortex during and after temporal lobe seizures. EEG slowing in the frontoparietal association cortex may signify physiologic impairment that contributes to widespread altered cerebral function during partial seizures.

Adolescent↗

PubMed2004

Localization and physical properties experiments conducted by Spirit at Gusev Crater.

The precise location and relative elevation of Spirit during its traverses from the Columbia Memorial station to Bonneville crater were determined with bundle-adjusted retrievals from rover wheel turns, suspension and tilt angles, and overlapping images. Physical properties experiments show a decrease of 0.2% per Mars solar day in solar cell output resulting from deposition of airborne dust, cohesive soil-like deposits in plains and hollows, bright and dark rock coatings, and relatively weak volcanic rocks of basaltic composition. Volcanic, impact, aeolian, and water-related processes produced the encountered landforms and materials.

Extraterrestrial Environment↗

PubMed2004

A case-based evaluation of SRD5A1, SRD5A2, AR, and ADRA1A as candidate genes for severity of BPH.

In men with a clinical diagnosis of benign prostatic hyperplasia (BPH), polytomous logistic regression analysis was conducted to evaluate associations between two silent polymorphisms in SRD5A1 (codon positions 30 and 116), two polymorphisms in SRD5A2 (Val89Leu substitution and C to T transition in intron 1), a trinucleotide (CAG)n repeat in androgen receptor (AR), and an Arg492Cys substitution in ADRA1A and clinical parameters that characterize severity of BPH. Candidate gene selection was based on two mechanistic pathways targeted by pharmacotherapy for BPH: (1) androgen metabolic loci contributing to prostate growth (static obstruction); and (2) factors affecting smooth muscle tone (dynamic obstruction). Polymorphisms in SRD5A2 were not associated with severity of BPH; however, SRD5A1 polymorphisms were associated with severity of BPH. The process(es) in which these silent single-nucleotide polymorphisms (SNPs) influence BPH phenotypes is unknown and additional studies will be needed to assess whether these SNPs have direct functional consequences. The characterization of additional molecular factors that contribute to static and dynamic obstruction may help predict response to pharmacotherapy and serve to identify novel drug targets for the clinical management of BPH.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

PubMed2004

Therapeutic efficacy of pooled buffy-coat platelet components prepared and stored with a platelet additive solution.

Despite the introduction of platelet additive solutions for the preparation of pooled platelet components, only a few studies of limited scope have evaluated the clinical efficacy of platelets stored in these solutions. The current report presents an analysis of data to evaluate the response to the transfusion of pooled buffy-coat components suspended in storage solution with reduced (35%) plasma content in comparison with 100% plasma products. During the euroSPRITE clinical trial of platelet components treated with a pathogen inactivation process, control treatment group platelet components were prepared in 100% allogeneic donor plasma (plasma control) or in platelet additive solution (T-Sol) mixed with plasma (T-Sol control). Control group thrombocytopenic patients received either plasma control or T-Sol control platelet components. One-hour and 24-h platelet count increments (CIs) and corrected count increments (CCIs) were analysed for these two types of preparation. In addition, haemostatic assessments were conducted for each transfusion. One-hour and 24-h mean platelet CIs and post-transfusion haemostatic scores were not significantly different for patients receiving platelet components suspended in 100% plasma and T-Sol plasma mixtures. Pooled buffy-coat platelet components prepared in reduced plasma content mixtures provided therapeutic platelet CIs with effective haemostasis.

Blood Component Transfusion↗

PubMed2004

Consistent cytotoxic-T-lymphocyte targeting of immunodominant regions in human immunodeficiency virus across multiple ethnicities.

Although there is increasing evidence that virus-specific cytotoxic-T-lymphocyte (CTL) responses play an important role in the control of human immunodeficiency virus (HIV) replication in vivo, only scarce CTL data are available for the ethnic populations currently most affected by the epidemic. In this study, we examined the CD8(+)-T-cell responses in African-American, Caucasian, Hispanic, and Caribbean populations in which clade B virus dominates and analyzed the potential factors influencing immune recognition. Total HIV-specific CD8(+)-T-cell responses were determined by enzyme-linked immunospot assays in 150 HIV-infected individuals by using a clade B consensus sequence peptide set spanning all HIV proteins. A total of 88% of the 410 tested peptides were recognized, and Nef- and Gag-specific responses dominated the total response for each ethnicity in terms of both breadth and magnitude. Three dominantly targeted regions within these proteins that were recognized by >90% of individuals in each ethnicity were identified. Overall, the total breadth and magnitude of CD8(+)-T-cell responses correlated with individuals' CD4 counts but not with viral loads. The frequency of recognition for each peptide was highly correlated with the relative conservation of the peptide sequence, the presence of predicted immunoproteasomal cleavage sites within the C-terminal half of the peptide, and a reduced frequency of amino acids that impair binding of optimal epitopes to the restricting class I molecules. The present study thus identifies factors that contribute to the immunogenicity of these highly targeted and relatively conserved sequences in HIV that may represent promising vaccine candidates for ethnically heterogeneous populations.

AIDS Vaccines↗

PubMed2003

Preliminary evaluation of an injectable anal sphincter bulking agent (Durasphere) in the management of faecal incontinence.

BACKGROUND: It has been previously shown that 'bulking' of internal anal sphincter defects may provide an effective method to treat patients with faecal incontinence, but the benefit wears off with time. AIM: To assess the efficacy of a larger molecule, bulking agent (Durasphere) over the short- and long-term in patients with an internal anal sphincter defect refractory to conservative management. PATIENTS: Eighteen patients (nine male, nine female) with a mean age of 60 years were recruited. All patients had persistent faecal leakage/soiling. METHODS: Durasphere was injected in the submucosal plane to restore anal canal symmetry. All patients had anorectal physiology, endoanal ultrasound, continence grading, patient satisfaction and quality of life scores assessed at 1, 3, 6 and 12 months. RESULTS: The mean follow-up is 28.5 months. Changes from baseline were not statistically significant up to 6 months. At 12 months there was significant improvement in the continence grading (P=0.003), patient satisfaction (P=0.053) and all quality of life subscales: lifestyle (P=0.004), coping (P=0.011), depression (P=0.024) and embarrassment (P=0.059). Anorectal physiological parameters apart from the maximum tolerable rectal volume at 12 months (P=0.036) showed no significant improvement. CONCLUSIONS: Anal sphincter bulking with Durasphere is safe and effective in the short term as well as the longer term. More importantly, there is no evidence of attenuation of effect over time.

Adult↗

PubMed2003

Symptoms and anal sphincter morphology following primary repair of third-degree tears.

BACKGROUND: Approximately 0.6-9 per cent of vaginal deliveries are complicated by third-degree tears. The precise impact of such injuries on future pelvic floor function remains unknown. The aim of this study was to define the extent of structural and physiological damage to the anal sphincter and to investigate anorectal function in women who sustained third-degree tears during vaginal delivery. METHODS: Fifty-six women who sustained a third-degree tear were investigated prospectively. All patients had a primary repair of the anal sphincter complex, and were assessed by anorectal physiology and endoanal ultrasonography at a mean of 3.6 months. Symptoms were assessed by direct personal interview and also by a self-completed questionnaire. RESULTS: Forty-four patients had a persistent anal sphincter defect on ultrasonography. The mean resting and squeeze anal canal pressures were significantly lower in patients with a combined defect than in those in whom the repair was intact (P = 0.036 and P = 0.005 respectively). At direct interview three patients volunteered current symptoms of faecal and/or urinary incontinence whereas 32 reported bothersome symptoms on the questionnaire (P < 0.001). CONCLUSION: The anatomical and physiological damage sustained during third-degree tears appears to be much greater than is generally appreciated. Primary repair does not provide lasting integrity. A self-administered questionnaire appears to be more accurate in defining the symptomatology.

Adolescent↗

PubMed2003

Translating the Short-Form Headache Impact Test (HIT-6) in 27 countries: methodological and conceptual issues.

The process of translating the Short-Form Headache Impact Test (HIT-6) in 27 countries and the comparability of the content of the translations is discussed. HIT-6 translations were developed using a standard forward-backward translation process, including a cognitive debriefing step and international harmonization of the translations. Prior to translating the HIT-6, modifications were made to the English-language source form, to improve translation equivalence. In general, the HIT-6 was not difficult to translate. The most difficult items included colloquial expressions such as 'fed up' and words whose intended meaning changed in translation such as 'school' or 'lie down.' Subjects generally found the HIT-6 translations to be clear and relevant. The translation process resulted in questionnaires that are both culturally appropriate and comparable in content.

Headache↗

PubMed2003

IMBA Expert: internal dosimetry made simple.

In 1997, a collaboration between British Nuclear Fuels plc (BNFL), Westlakes Research Institute and NRPB started, with the aim of producing IMBA (Integrated Modules for Bioassay Analysis), a suite of software modules that implement the new ICRP models for estimation of intakes and doses. This was partly in response to new UK regulations, and partly due to the requirement for a unified approach in estimating intakes and doses from bioassay measurements within the UK. Over the past 5 years, the IMBA modules have been developed further, have gone through extensive quality assurance, and are now used for routine dose assessment by approved dosimetry services throughout the UK. More recently, interest in the IMBA methodology has been shown by the United States Department of Energy (USDOE), and in 2001 an ambitious project to develop a software package (IMBA Expert USDOE Edition) which would meet the requirements of all of the major USDOE sites began. Interest in IMBA Expert is now being expressed in many other countries. The aim of this paper is to outline the origin and evolution of the IMBA modules (the past); to describe the full capabilities of the current IMBA Expert system (the present) and to indicate possible future directions in terms of capabilities and availability (the future).

Computer Simulation↗

PubMed2002

Search for R-parity violating supersymmetry in two-muon and four-jet topologies.

We present results of a search for R-parity-violating decay of the neutralino chi;01, taken as the lightest supersymmetric particle, to a muon and two jets. The decay proceeds through a lepton-number violating coupling lambda(')(2jk) (j=1,2; k=1,2,3), with R-parity conservation in all other production and decay processes. In the absence of candidate events from 77.5+/-3.9 pb(-1) of data collected by the D0 experiment at the Fermilab Tevatron in pp collisions at sqrt[s]=1.8 TeV, and with an expected background of 0.18+/-0.03+/-0.02 events, we set limits on squark and gluino masses within the framework of the minimal low-energy supergravity-supersymmetry model.

Journal Article↗

PubMed2002

Re-sequencing of multiple single nucleotide polymorphisms by liquid chromatography-electrospray ionization mass spectrometry.

Allelic discrimination of single nucleotide polymorphisms (SNPs) and, particularly, determination of the phase of multiple variations are of utmost importance in genetics. The physicochemical separation of alleles by completely denaturing ion-pair reversed-phase high-performance liquid chromatography and their on-line sequence determination by electrospray ionization mass spectrometry is demonstrated. Simultaneous genotyping of two and three simple sequence polymorphisms contained within 73-114 bp was accomplished with low femtomolar amounts of unpurified amplicons from polymerase chain reaction. Determination of allelic composition is enabled by the high accuracy (better than 0.019%) of intact mass measurements or by comparative sequencing using gas-phase fragmentation and tandem mass spectrometry in combination with fully automated, computer-aided data interpretation.

Chromatography, Liquid↗