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Biomedical subjects

L Evans

Publications and source records attributed to L Evans.

At least 37 records · Page 2Linked to original sources

Constitutive expression of recombinant proteins in the methylotrophic yeast Hansenula polymorpha using the PMA1 promoter.

The methylotrophic yeast H. polymorpha is a popular system for the expression of recombinant proteins using the strong and regulatable methanol oxidase (MOX) promoter. Here we show that the constitutive PMA1 promoter can programme the expression of two heterologous proteins, glucose oxidase and human serum albumin. A constitutive promoter provides a useful additional facility to the H. polymorpha expression system because it allows a simplified fermentation regime, avoids the use of methanol, which is both toxic and an explosive hazard, and allows more flexibility for ectopic gene expression during the course of academic studies. A fragment previously isolated in a promoter screen, using glucose oxidase (GOD) as a reporter gene, was shown to consist of the promoter region and the first 659 bp of the H. polymorpha PMA1 gene, encoding the plasma membrane H(+)-ATPase. When the PMA1 promoter was optimally aligned with the GOD coding region, it produced 185 mg/l glucose oxidase in high cell density fed batch fermentations, whereas in previous experiments using the MOX promoter, a yield of 500 mg/l was recovered. The PMA1 promoter was also used to express recombinant human serum albumin (rHA) in H. polymorpha. In high cell density fermentations the PMA1 promoter produced 460 mg/l rHA, whereas 280 mg/l rHA was obtained using the MOX promoter. Taken together, these experiments show that the HpPMA1 programmes the constitutive expression of recombinant proteins and provides a yield comparable to that from the MOX promoter.

Alcohol Oxidoreductases↗

Measurement of fidelity in psychiatric rehabilitation.

Until recently, most psychiatric rehabilitation models have been poorly defined and few have had systematic methods for measuring their implementation. We review the historical roots for the development of fidelity measures and describe recent applications in both research and practice.

Humans↗

Examination of the validity of the Social Support Survey using confirmatory factor analysis.

The Social Support Survey (SSS), validated by Richman, Rosenfeld, and Hardy (1993), is a multidimensional self-report measure of social support tested with student athletes. The SSS contains eight dimensions of support. For each dimension of support the same four questions are posed. The SSS could, therefore, be scored in two ways: (a) to derive a score for the support dimensions; (b) to derive a score for the questions posed across all eight support dimensions. Confirmatory factor analyses of the SSS on 416 university athletes revealed poor fits to models for both the eight support dimensions and the four questions across all eight dimensions. This problem was clarified by using a multitrait-multimethod model, which led to improved model fit but revealed that most of the SSS items were two-dimensional. Caution should, therefore, be exercised in using the SSS as a measure of multidimensional social support.

Adult↗

Risks older drivers face themselves and threats they pose to other road users.

BACKGROUND: Although there is an ever increasing literature on older drivers, there is no comprehensive up-to-date presentation of how older drivers are impacted by traffic safety, and how they impact the road safety of others. METHODS: This paper uses 1994-1996 US data to determine how many rates related to traffic safety depend on the age and sex of road users (fatalities, fatalities per licensed driver, etc.) Threats drivers pose to other road users are estimated by driver involvement in pedestrian fatality crashes. RESULTS: It is found that renewing the licence of a 70-year-old male driver for another year poses, on average, 40% less threat to other road users than renewing the license of a 40-year-old male driver. The fatality risks drivers themselves face generally increase as they age, with the increased risk of death in the same severity crash being a major contributor. If this factor is removed, crash risks for 70-year-old male drivers are not materially higher than for 40-year-old male drivers; for female drivers they are. CONCLUSIONS: Most driver rates increase substantially by age 80, in many cases to values higher than those for 20-year-olds. Given that a death occurs, the probability that it is a traffic fatality declines steeply with age, from well over 20% for late teens through mid twenties, to under one per cent at age 65, and under half a per cent at age 80.

Accidents, Traffic↗

Detection of biomolecules in the near-infrared spectral region via a fiber-optic immunosensor.

The design, development, and application of a fluorescent fiber-optic immunosensor (FFOI) procedure for the detection of antibody/antigen binding within the near-infrared (NIR) spectral region is reported. The technique was developed through the combined use of fiber-optics, semiconductor laser excitation, fluorescence detection, NIR dye, and immunochemical techniques. The antibody is immobilized on the FFOI's sensing tip and utilized as a recognition component for trace amounts of specific antigen. The FFOI is constructed to utilize antibody sandwich technique. Three individual immunoassays are reported. The first two assays utilize the FFOI and NN382, a commercial NIR dye, for the detection of human immunoglobulin G (IgG). In these assays, goat anti-human IgG antibody (GAHG) is immobilized on the sensitive terminal of the FFOI followed by the exposure of the antibody-coated terminal to human IgG. The probe is then introduced to GAHG labeled with NN382, generating a signal. The third assay utilizes the FFOI for the detection of trace amounts of Legionella pneumophila serogroup 1 (LPS1). In this assay, rabbit anti-LPS1 antibody is immobilized on the sensitive terminal of the FFOI followed by exposure to LPS1. The antigen-coated probe is then treated with monoclonal anti-LPS1 antibody followed by incubation with GAHG labeled with NN382. The assays are optimized to detect the corresponding antigen via the NIR-FFOI. Typical measurements are performed in 10-15 min. A 780-nm semiconductor laser provides the excitation of the immune complex and the resulting emission is detected by a 820-nm silicon photodiode detector. The intensity of the resulting fluorescence is directly proportional to the concentration of the antigen. Solutions of IgG and LPS1 with concentrations as low as 10(-11) M and 0.5 ng/ml, respectively, have been detected with a minimum interference.

Animals↗

Chicken food calls are functionally referential.

Male chickens, Gallus gallus domesticus, usually produce characteristic 'food' calls upon discovering edible objects, and are more likely to do so in the presence of a hen. Food calling is thus dependent upon food and modulated by social context, which is consistent with the idea that hens respond because they anticipate a feeding opportunity. An alternative model suggests that female behaviour is not mediated by the predicted presence of food but rather by social information, such as a low probability of male aggression. We conducted two playback experiments to explore the type of information encoded in food-associated vocal signals. Isolated hens were played recorded food calls and we compared their responses with those evoked by ground alarm calls (which have similar acoustic characteristics) and by contact calls (which are produced under similar social circumstances). Hens responded to food call playbacks by fixating downwards with the frontal binocular field. This anticipatory feeding movement was specific to food calls and did not occur in either of the control conditions. Food calls also affected looking downwards selectively. There were no differences between the call types in their effects on social behaviour, such as approach and contact calling, nor were there differences in the nonspecific effects of sound playback, such as orienting towards the loudspeaker or increased locomotor activity. Chicken food calls appear to provide conspecifics with information about the presence of food. This property has not hitherto been demonstrated in any natural system of animal acoustic signals. Copyright 1999 The Association for the Study of Animal Behaviour.

Journal Article↗

A pharmacokinetic model for tenidap in normal volunteers and rheumatoid arthritis patients.

PURPOSE: To develop a pharmacokinetic model for tenidap and to identify important relationships between the pharmacokinetic parameters and available covariates. METHODS: Plasma concentration data from several phase I and phase II studies were used to develop a pharmacokinetic model for tenidap, a novel anti-rheumatic drug. An appropriate pharmacokinetic model was selected on the basis of individual nonlinear regression analyses and an EM algorithm was used to perform a nonlinear mixed-effects analysis. Scatter plots of posterior individual pharmacokinetic parameters were used to identify possible covariate effects. RESULTS: Predicted responses were in good agreement with the observed data. A bi-exponential model with zero order absorption was subsequently used to develop the mixed-effects model. Covariate relationships selected on the basis of differences in the objective function, although statistically significant, were not particularly strong. CONCLUSIONS: The pharmacokinetics of tenidap can be described by a bi-exponential model with zero order absorption. Based on differences in the log-likelihood, significant covariate-parameter relationships were identified between smoking and CL, and between gender and Vss and CLd. Simulated sparse data analyses indicated that the model would be robust for the analysis of sparse data generated in observational studies.

Adult↗

Using clinical indicators in emergency medicine: documenting performance improvements to justify increased resource allocation.

OBJECTIVES: To demonstrate how emergency department triage scale and thrombolysis indicator data can be used to document the impact of a substantial increase in resource allocation. METHODS: Descriptive study in an emergency department of an adult tertiary hospital in Perth, Australia during similar periods of the year both before and after a substantial increase in emergency department staff, equipment, and system resources. The study group comprised a total of 11,048 emergency department attendances and all cases of emergency department initiated thrombolysis or acute angioplasty. Outcome was measured using numbers seen and percentage seen within indicator threshold time together with admission rates in each of the five triage categories as well as by using time from presentation to initiation of reperfusion treatment in acute myocardial infarction. RESULTS: The proportion of patients seen within the prescribed indicator time increased by 16.4% (95% confidence interval 14.4% to 18.2%). The increase was most pronounced in triage category 2 (32.7%). Median time to thrombolysis fell by 30 minutes to 37 minutes (p = 0.0002). CONCLUSIONS: Use of the Australasian national triage scale and time to thrombolysis clinical indicator data allows a quantitative assessment of the impact of increased emergency department resource allocation.

Adult↗

Individualized interventions to prevent bed-related falls and reduce siderail use.

Five categories of problems that often result in siderail use: memory disorder, impaired mobility, injury risk, nocturia/incontinence, and sleep disturbance. As nursing homes work toward meeting the Health Care Financing Administration's mandate to examine siderail use, administrators and staff need to implement interventions that support safety and individualize care for residents. While no one intervention represents a singular solution to siderail use, a range of interventions, tailored to individual needs, exist. This article describes the process of selecting individualized interventions to reduce bed-related falls.

Accidental Falls↗

Bone densitometry should be included in the evaluation of candidates for lung transplantation.

Bone loss and fractures are common complications of heart and liver transplantation, and are likely related to high-dose immunosuppressive therapy. We have previously demonstrated that many patients with end-stage lung disease already have osteoporosis and may be at even greater risk for fracture after lung transplantation. The purpose of this study is to determine the incidence of fracture in lung transplant recipients on osteoporosis prevention regimens, the relationship of fracture to pretransplant bone mineral density, and the impact of fracture on quality of life after lung transplantation. Twenty-one lung transplant candidates were prospectively evaluated with spine radiographs and bone mineral densitometry. Bone density was expressed as T scores, the number of standard deviations from the mean bone density of a young normal population of the same gender. Of 21 patients, 8 (38%) fractured during the first year. The mean pretransplant lumbar spine T score was significantly lower in the fracture patients (P = .03). Four of the 7 surviving fracture patients and 1 of the 10 patients who survived without fracture believed that chronic pain diminished their quality of life (X2 = 4.408; P = .04). These findings suggest that bone mineral density should be routinely included in the evaluation of lung transplant candidates. Patients with extremely low bone density or osteoporotic fracture should be counseled about the increased risk of fracture after transplantation.

Absorptiometry, Photon↗

A comparison of the ability of experts and non-experts to differentiate between adult and child human bite marks using receiver operating characteristic (ROC) analysis.

Fifty colour prints of human bite marks were sent to 109 observers who were asked to decide using a six point rating scale, whether the marks had been produced by the teeth of an adult or a child. The observers consisted of accredited senior forensic dentists, accredited junior forensic dentists, general dental practitioners, final year dental students, police officers and social workers. The results were compared against a "gold standard" which was the actual verdict from the case. Comparison of the results between the groups of observers and the standard was made using Receiver Operating Characteristics (ROC) methodology. The best decisions were made by senior/junior experts or final year dental students. General dental practitioners and police officers were least able to differentiate correctly between adult and child bite marks. The effect of training is important and its effects need to be assessed in more detail in future studies.

Adult↗

Primary nursing--an alternative approach for midwives.

In task allocation and team nursing systems the least complex task is given to the least trained staff member and the most complex task is given to a more skilled worker, registered nurses often do no more than checking up on others. Primary nursing is a way of thinking and working with patients that challenges outdated and traditional nursing hierarchies and supports the way forward for professional nurses. Primary nursing allows nurses to provide consistent individualised care and encourages the nurse to practice with greater professional autonomy. Task allocation, team nursing and even patient allocation methods of nursing are not wholly supportive of individualised and humanistic care. In contrast, primary nursing presents a structure in which the care planner and principle care giver are the same person. With the focus on helping the client to make her own decisions and greater professional autonomy for nurses, primary nursing is an ideal method of patient care delivery for the specialty of post-natal nursing. The way nursing activities are organised reflects the attitude towards holistic care of the patient and primary nursing is an unconditional patient-centred method of nursing care delivery and the way forward for the professionalism and autonomy of nurses.

Humans↗

Perceptions of women on the impact of menorrhagia on their health using multi-attribute utility assessment.

OBJECTIVE: To assess patient preferences regarding the treatment of menorrhagia using the multi-attribute utility methodologies, to produce a clinically applicable scale, and to assess health outcomes following treatment of menorrhagia. METHODS: Women referred to the gynaecology department for the treatment of menorrhagia were interviewed regarding the effects of menorrhagia on different aspects of their life. Their concerns were categorised into main components of health (domains). The relative importance of each domain was rated by the women using importance points which were distributed to represent the perceived importance of each domain. A series of statements (intra-domain statements) was developed for each domain, which described various possible conditions of that component of health. These were also rated using a one metre visual analogue scale with numerical anchor points at zero (worst) and 100 (best). RESULTS: The components of health considered most important were, in order of impact, family life, followed by physical health, work life, psychological health, practical difficulties and social life. The scores for the intra-domain statements were combined into a scale to allow the calculation of a final health state utility for a particular outcome based upon the statements the patient chooses within each domain. DISCUSSION: In planning treatment for menorrhagia clinicians can assess a woman's current perception of their health, using a simple to administer clinical scale.

Adult↗

Does concurrent drug intake affect the long-term outcome of group cognitive behaviour therapy in panic disorder with or without agoraphobia?

The present study investigated the impact of pre-existing pharmacotherapy regimes on the long-term outcome of brief intensive group cognitive-behavioural therapy (BIGCBT) in the treatment of panic disorder with or without agoraphobia in 106 patients (74 females). Forty patients were allocated to BIGCBT without medication, 40 to BIGCBT plus anti-anxiety medication, 10 to BIGCBT plus anti-depressant medication and 16 to BIGCBT plus combined anti-anxiety and anti-depressant medications. The mean follow-up period was 3.2 yr and ranged from 1.1 to 6.2 yr. The results demonstrated that patients who received BIGCBT concurrent with pre-existing medication regimes did not differ significantly (P > 0.001) from each other or from patients who underwent BIGCBT without medication on any of the dependent measures either at pre-treatment assessment or long-term follow-up. However, BIGCBT (with or without pharmacotherapy) was associated with significant (P < 0.001) long-term improvements in frequency of panic attacks, avoidance behaviour and questionnaire measures of anxiety, depression and agoraphobia. Furthermore, the large majority (80%) of patients in the BIGCBT without medication group remained medication-free at long-term follow-up. Of those patients who underwent BIGCBT concurrent with pre-existing pharmacotherapy, a large percentage (44%) reported no longer taking medication for their condition at long-term follow-up. Overall, it is concluded that pre-existing medication regimes (anti-anxiety, anti-depressant or combinations of these) do not significantly enhance or detract from the long-term outcome of a BIGCBT program used in the treatment of panic disorder and agoraphobia.

Adolescent↗

A prospective study of the effect of limb-threatening ischaemia and its surgical treatment on the quality of life.

OBJECTIVE: To assess the quality of life after treatment for limb-threatening ischaemia. DESIGN: An open, prospective, observational study in a Vascular Unit of a University Hospital. MATERIALS: One hundred and fifty consecutive patients presenting with actual or threatened tissue loss of the leg. METHODS: A single, experienced observer assessed the patients for pain, mobility, anxiety, depression, self-care and lifestyle at presentation, 6 and 12 months later. RESULTS: Six different treatment outcomes were recognised: successful angioplasty, successful thrombolysis/thrombectomy, successful surgical bypass, amputation after failed revascularisation, primary unilateral amputation and primary bilateral amputation. Pain was significantly improved in all groups (p < 0.05) except for patients after failed revascularization (p = 0.08). Mobility improved in patients who underwent angioplasty (p = 0.05) or a successful surgical bypass (p = 0.001). Anxiety and depression both improved significantly only after surgical reconstruction (p < 0.02). Self-care ability improved significantly after angioplasty (p < 0.05), surgical reconstruction (p < 0.005) and unilateral primary amputation (p < 0.05), but was unaltered in the other groups. Lifestyle significantly deteriorated following thrombolysis/thrombectomy and failed surgical reconstruction (p < 0.05), but was maintained in all other groups. CONCLUSIONS: The treatment of limb-threatening ischaemia should aim to maintain pre-morbid lifestyle, an aim which is best achieved by limb-salvage. The patient's own expectations and needs have a major bearing on the choice of therapy.

Activities of Daily Living↗

A CD2/CD28 chimeric receptor triggers the CD28 signaling pathway in CTLL.2 cells.

We are evaluating strategies to enhance the in vivo proliferation and function of adoptively transferred antigen-specific T cells. Although the CD28 costimulatory pathway is important for T cell activation and proliferation, the expression of the ligands for CD28 is highly restricted. We have generated a chimeric receptor composed of the signaling domains of CD28 and the extracellular domain of CD2 which binds the widely expressed ligand CD58. The CD2/CD28 chimeric receptor was introduced into CTLL.2 cells via retrovirus infection and was shown to be expressed on the cell surface. By monitoring early and late components of the CD28 signaling pathway, the chimeric receptor was demonstrated to trigger the CD28 pathway in response to CD2 cross-linking. The possible utility of the CD2/CD28 chimeric receptor for adoptive immunotherapy is discussed.

Animals↗