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Biomedical subjects

R Stephens

Publications and source records attributed to R Stephens.

At least 19 recordsLinked to original sources
PubMed2006

Palliative chemotherapy beyond three courses conveys no survival or consistent quality-of-life benefits in advanced non-small-cell lung cancer.

This randomised multicentre trial was conducted to establish the optimal duration of palliative chemotherapy in advanced non-small-cell lung cancer (NSCLC). We compared a policy of three vs six courses of new-generation platinum-based combination chemotherapy with regard to effects on quality of life (QoL) and survival. Patients with stage IIIB or IV NSCLC and WHO performance status (PS) 0-2 were randomised to receive three (C3) or six (C6) courses of carboplatin (area under the curve (AUC) 4, Chatelut's formula, equivalent to Calvert's AUC 5) on day 1 and vinorelbine 25 mg m(-2) on days 1 and 8 of a 3-week cycle. Key end points were QoL at 18 weeks, measured with EORTC Quality of Life Questionnaire (QLQ)-C30 and QLQ-LC13, and overall survival. Secondary end points were progression-free survival and need of palliative radiotherapy. Two hundred and ninety-seven patients were randomised (C3 150, C6 147). Their median age was 65 years, 30% had PS 2 and 76% stage IV disease. Seventy-eight and 54% of C3 and C6 patients, respectively, completed all scheduled chemotherapy courses. Compliance with QoL questionnaires was 88%. There were no significant group differences in global QoL, pain or fatigue up to 26 weeks. The dyspnoea palliation rate was lower in the C3 arm at 18 and 26 weeks (P<0.05), but this finding was inconsistent across different methods of analysis. Median survival in the C3 group was 28 vs 32 weeks in the C6 group (P=0.75, HR 1.04, 95% CI 0.82-1.31). One- and 2-year survival rates were 25 and 9% vs 25 and 5% in the C3 and C6 arm, respectively. Median progression-free survival was 16 and 21 weeks in the C3 and C6 groups, respectively (P=0.21, HR 0.86, 95% CI 0.68-1.08). In conclusion, palliative chemotherapy with carboplatin and vinorelbine beyond three courses conveys no survival or consistent QoL benefits in advanced NSCLC.

Adult↗
PubMed2006

Fast-electron transport and heating of solid targets in high-intensity laser interactions measured by K alpha fluorescence.

We present experimental results on fast-electron energy deposition into solid targets in ultrahigh intensity laser-matter interaction. X-ray K alpha emission spectroscopy with absolute photon counting served to diagnose fast-electron propagation in multilayered targets. Target heating was measured from ionization-shifted K alpha emission. Data show a 200 microm fast-electron range in solid Al. The relative intensities of spectrally shifted Al K alpha lines imply a mean temperature of a few tens of eV up to a 100 microm depth. Experimental results suggest refluxing of the electron beam at target rear side. They were compared with the predictions of both a collisional Monte Carlo and a collisional-electromagnetic, particle-fluid transport code. The validity of the code modeling of heating in such highly transient conditions is discussed.

Journal Article↗
PubMed2006

Transcriptomic response to differentiation induction.

BACKGROUND: Microarrays used for gene expression studies yield large amounts of data. The processing of such data typically leads to lists of differentially-regulated genes. A common terminal data analysis step is to map pathways of potentially interrelated genes. METHODS: We applied a transcriptomics analysis tool to elucidate the underlying pathways of leukocyte maturation at the genomic level in an established cellular model of leukemia by examining time-course data in two subclones of U-937 cells. Leukemias such as Acute Promyelocytic Leukemia (APL) are characterized by a block in the hematopoietic stem cell maturation program at a point when expansion of clones which should be destined to mature into terminally-differentiated effector cells get locked into endless proliferation with few cells reaching maturation. Treatment with retinoic acid, depending on the precise genomic abnormality, often releases the responsible promyelocytes from this blockade but clinically can yield adverse sequellae in terms of potentially lethal side effects, referred to as retinoic acid syndrome. RESULTS: Briefly, the list of genes for temporal patterns of expression was pasted into the ABCC GRID Promoter TFSite Comparison Page website tool and the outputs for each pattern were examined for possible coordinated regulation by shared regelems (regulatory elements). We found it informative to use this novel web tool for identifying, on a genomic scale, genes regulated by drug treatment. CONCLUSION: Improvement is needed in understanding the nature of the mutations responsible for controlling the maturation process and how these genes regulate downstream effects if there is to be better targeting of chemical interventions. Expanded implementation of the techniques and results reported here may better direct future efforts to improve treatment for diseases not restricted to APL.

Cell Differentiation↗
PubMed2006

Patient and physician reporting of symptoms and health-related quality of life in trials of treatment for early prostate cancer: considerations for future studies.

AIMS: Clinical trials in early prostate cancer (EPC) have used a variety of outcome measures, including patient-reported outcomes (PROs) and physician-reported data. We review published studies and suggest a set of outcome measures and a portfolio of more detailed questionnaire options to produce a more homologous data set for future clinical trials. MATERIALS AND METHODS: A literature search combining the terms 'quality of life' or 'symptoms' and 'prostate cancer' or 'prostate adenocarcinoma' was carried out. Relevant papers were reviewed to assess key areas of toxicity and quality of life (QoL). These were discussed by a panel with a special interest in the assessment of QoL measures and PROs. RESULTS: Twenty-one validated candidate questionnaires were identified. The Short Form 12 was recommended due to its combination of brevity and assessment of pain, general and mental health, physical, social and emotional function. Specific questionnaires should assess localised symptoms after treatment, including sexual function, erectile dysfunction, bowel function and lower urinary tract symptoms (LUTS). The modular use of separate symptom indices was recommended. For sexual function, the International Index of Erectile Function and the International Continence Society questionnaire were considered the best available. The International Continence Society Male Short Form questionnaire best addressed LUTS. Incontinence of stool (solid, liquid or gas) and its effect on function should be assessed. The Vaizey questionnaire is recommended. The Radiation Therapy Oncology Group scale, which is physician administered, remains helpful in studies including radiotherapy, as it places current trials within appropriate historical context. Rates of procedures to treat complications and pharmaceutical interventions for treatment-related symptoms should be recorded at the time of each questionnaire follow-up. CONCLUSION: Although novel therapies may produce different toxicities, the current recommendations should help to produce trial protocols that will allow comparable data to be generated within clinical trials comparing outcome from surgery, radiotherapy and other targeted ablative therapies for EPC.

Brachytherapy↗
PubMed2005

Age-related decline in Digit-Symbol performance: eye-movement and video analysis.

Examines age-related decline in Digit-Symbol performance using variables obtained from a slow-motion analysis of a first person perspective video filmed during test completion, including superimposed cross-hairs indicating eye movements. Standard WAIS-3 DSCT scores and the video-derived variables were compared across two age groups (mean age 20 years vs. mean age 59 years). The older group performed more poorly overall, t(16)=-2.359, p=.031. The correlation between writing time per item and overall performance was (negatively) larger in the older group compared with the younger group, z=-2.180, p=.014. There was no difference between the groups' correlation coefficients with respect to key search latency and overall performance, z=-0.064, p=.525. Overall these results suggest that characterisation of the age-related slowing on Digit-Symbol tests as a psychomotor deficit is appropriate.

Adolescent↗
PubMed2005

Ultraintense laser-produced fast-electron propagation in gas jets.

We study the propagation of fast electrons in a gas at different densities. A large relativistic electron current is produced by focusing a short-pulse ultrahigh-intensity laser on a metallic target. It then propagates in a gas jet placed behind the foil. Shadowgraphy in the gas shows an electron cloud moving at sub-relativistic average velocities. The experiment shows (i) the essential role of the density of background material for allowing propagation of fast electrons, (ii) the importance of the ionization phase which produces free electrons available for the return current, and (iii) the effect of electrostatic fields on fast-electron propagation.

Journal Article↗
PubMed2005

Comparison of laser ion acceleration from the front and rear surfaces of thin foils.

The comparative efficiency and beam characteristics of high-energy ions generated by high-intensity short-pulse lasers (approximately 1-6 x 10(19) W/cm2) from both the front and rear surfaces of thin metal foils have been measured under identical conditions. Using direct beam measurements and nuclear activation techniques, we find that rear-surface acceleration produces higher energy particles with smaller divergence and a higher efficiency than front-surface acceleration. Our observations are well reproduced by realistic particle-in-cell simulations, and we predict optimal criteria for future applications.

Journal Article↗
PubMed2005

Longevity of the immune response and memory to blood-stage malaria infection.

Immunity to malaria develops slowly with protection against the parasite lagging behind protection against disease symptoms. The data on the longevity of protective immune responses are sparse. However, studies of antibody responses associated with protection reveal that they consist of a short- and a long-lived component. Compared with the antibody levels observed in other infection and immunization systems, the levels of the short-lived antibody compartment drop below the detectable threshold with unusual rapidity. The prevalence of long-lived antibodies is comparable to that seen after bacterial and protozoan infections. There is even less available data concerning T cell longevity in malaria infection, but what there is seems to indicate that T cell memory is short in the absence of persistent antigen. In general, the degree and duration of parasite persistence represent a major factor determining how immune response longevity and protection correlate. The predilection for short-lived immune responses in malaria infection could be caused by a number of mechanisms resulting from the interplay of normal regulatory mechanisms of the immune system and immune evasion by the parasite. In conclusion, it appears that the parasite-host relationship has developed to favor some short-lived responses, which allow the host to survive while allowing the parasite to persist. Anti-malarial immune responses present a complex picture, and many aspects of regulation and longevity of the response require further research.

Animals↗
PubMed2005

Neuropsychological impairment as a consequence of football (soccer) play and football heading: preliminary analyses and report on university footballers.

Previous research has claimed neuropsychological impairment occurs as a result of professional and amateur football play, and, specifically, football heading. However, much of this research exhibits substantial methodological problems. By investigating less committed amateur level footballers, the current study sought to gain some insight into the developmental history of any neuropsychological consequences of football play. University football, rugby and noncontact sports players were compared on a range of biographical and neuropsychological test variables. While playing their chosen sports, rugby players sustained many more head injuries than footballers and noncontact sportsmen, but footballers did not sustain significantly more head injuries than noncontact sportsmen. The number of head injuries sustained predicted Trails B and TAP Divided Attention latencies in a positive fashion. After controlling for the number of head injuries sustained, sport group effects were detected with TAP Divided Attention accuracy scores, with footballers exhibiting poorest performance. After controlling for the number of head injuries sustained, the total amount of heading done by footballers predicted the number of Wisconsin Card Sorting category shifts in a negative fashion. Nevertheless, over interpretation of all of these results should be resisted because of the exploratory nature of the analyses and the possibility that the sport groups may differ in ways other than just the nature of their sports activities.

Adult↗
PubMed2005

Managing waiting time for radiotherapy: a single machine unit experience.

Waiting time (WT) for radiotherapy (RT) is a significant clinical problem. This paper examines various strategies for managing WT for patients treated with radical and palliative intent in the new setting of a rural single machine unit in Australia. Cohorts of patients undergoing both radical and palliative RT in Bendigo had their WT prospectively recorded. Matched cohorts from the hub centre (Peter MacCallum Cancer Centre, Melbourne) treated with palliative intent were also collated. Strategies implemented included a devoted priority meeting, palliative points system, and reallocation of appointment times. The audit was to continue until best practice guidelines were bettered. Three cohorts of patients were compared. There is a significant trend for increasing numbers of patients treated per month since the centre opened (P < 0.0001). The ratio of palliative to radical intent patients remained stable between 46 and 52%. Mean WT for palliative RT reduced from 25 days in the first cohort to 7 days in the final cohort (P < 0.0005). Waiting time for palliative RT was initially longer at Bendigo than the hub centre (P < 0.0005), but by the final cohort there was a non-significant difference favouring the Bendigo cohort (P = 0.26). Waiting time for radical treatment also improved throughout the three cohorts in Bendigo (P < 0.0005). A number of new strategies have successfully resulted in the abolition of lengthy WT for RT in Bendigo despite the increasing demand for the RT service.

Analysis of Variance↗
PubMed2005

Estimation of the additional costs of chemotherapy for patients with advanced non-small cell lung cancer.

BACKGROUND: A large multicentre randomised trial, the Big Lung Trial, which in part compared supportive care with or without cisplatin-based chemotherapy in patients with advanced non-small cell lung cancer, provided an opportunity to evaluate the impact on the UK National Health Service of the costs incurred with the use of chemotherapy. METHODS: This costing study was based on the retrospective collection of resource use data from hospital records. Case notes from 194 patients (98 chemotherapy + supportive care (C), 96 supportive care alone (NoC)) were inspected in eight centres recruiting the largest numbers of patients into the Big Lung Trial. Quantities were multiplied by fixed unit costs to calculate a total cost for each patient. The main outcome measure was the total cost incurred by the use of secondary care resources (including investigations, chemotherapy, radiotherapy, surgical procedures, inpatient days, outpatient attendances, and hospice inpatient care) in the two groups. RESULTS: Patients randomised to receive cisplatin-based chemotherapy had an average of 3.4 more inpatient bed days than the mean of 11.9 days for patients randomised to supportive care alone, and more outpatient attendances. NoC patients were more likely to have received palliative radiotherapy. The mean total cost for C patients was 5355 sterling pound compared with 3595 sterling pound for the NoC group, difference 760 sterling pound (95% CI 781 sterling pound to 2742 sterling pound ). When split, the cost in the C group associated with the administration of chemotherapy was 1233 sterling pound and non-chemotherapy costs were 4122 sterling pound . CONCLUSION: The additional cost of chemotherapy was not offset by a reduction in subsequent costs (as the non-chemotherapy costs were similar), so the survival benefit of about 10 weeks observed in the C group was achieved with the cost of chemotherapy administration.

Adult↗
PubMed2004

Ultralow emittance, multi-MeV proton beams from a laser virtual-cathode plasma accelerator.

The laminarity of high-current multi-MeV proton beams produced by irradiating thin metallic foils with ultraintense lasers has been measured. For proton energies >10 MeV, the transverse and longitudinal emittance are, respectively, <0.004 mm mrad and <10(-4) eV s, i.e., at least 100-fold and may be as much as 10(4)-fold better than conventional accelerator beams. The fast acceleration being electrostatic from an initially cold surface, only collisions with the accelerating fast electrons appear to limit the beam laminarity. The ion beam source size is measured to be <15 microm (FWHM) for proton energies >10 MeV.

Journal Article↗
PubMed2004

A descriptive study of the variation in baseline levels of antiendotoxin core antibodies between US and UK populations.

Low levels of naturally occurring antibodies to the core section of endotoxin (EndoCAb) have been shown to be predictors of poor outcome following major surgery. We performed a retrospective study comparing pre-operative levels in US surgical patients, UK surgical patients and healthy volunteers. Both IgM and IgG EndoCAb levels were higher in the US surgical patients when compared with the other groups (approximately twice as high in the case of IgG EndoCAb). This may reflect genetic or environmental variability between the patient groups, differences in the disease processes, the disparity in the delivery of health care between the two countries or degradation of the samples in transfer.

Antibodies, Bacterial↗
PubMed2003

Spatial uniformity of laser-accelerated ultrahigh-current MeV electron propagation in metals and insulators.

The evolution of laser-generated MeV, MA electron beams propagating through conductors and insulators has been studied by comparing measurement and modeling of the distribution of MeV protons that are sheath accelerated by the propagated electrons. We find that electron flow through metals is uniform and can be laser imprinted, whereas propagation through insulators induces spatial disruption of the fast electrons. Agreement is found with material dependent modeling.

Journal Article↗
PubMed2003

Isochoric heating of solid-density matter with an ultrafast proton beam.

A new technique is described for the isochoric heating (i.e., heating at constant volume) of matter to high energy-density plasma states (>10(5) J/g) on a picosecond time scale (10(-12)sec). An intense, collimated, ultrashort-pulse beam of protons--generated by a high-intensity laser pulse--is used to isochorically heat a solid density material to a temperature of several eV. The duration of heating is shorter than the time scale for significant hydrodynamic expansion to occur; hence the material is heated to a solid density warm dense plasma state. Using spherically shaped laser targets, a focused proton beam is produced and used to heat a smaller volume to over 20 eV. The technique described of ultrafast proton heating provides a unique method for creating isochorically heated high-energy density plasma states.

Journal Article↗