Characterization of the exradin W1 plastic scintillation detector for small field applications in proton therapy.

Accurate dosimetry in small field proton therapy is challenging, particularly for applications such as ocular therapy, and suitable detectors for this purpose are sought. The Exradin W1 plastic scintillating fibre detector is known to out-perform most other detectors for determining relative dose factors for small megavoltage photon beams used in radiotherapy but its potential in small proton beams has been relatively unexplored in the literature. The 1 mm diameter cylindrical geometry and near water equivalence of the W1 makes it an attractive alternative to other detectors. This study examines the dosimetric performance of the W1 in a 74 MeV proton therapy beam with particular focus on detector response characteristics relevant to relative dose measurement in small fields suitable for ocular therapy. Quenching of the scintillation signal is characterized and demonstrated not to impede relative dose measurements at a fixed depth. The background cable-only (Cerenkov and radio-fluorescence) signal is 4 orders of magnitude less than the scintillation signal, greatly simplifying relative dose measurements. Comparison with other detectors and Monte Carlo simulations indicate that the W1 is useful for measuring relative dose factors for field sizes down to 5 mm diameter and shallow spread out Bragg peaks down to 6 mm in depth.

Are multiple-trial experiments appropriate for eyewitness identification studies? Accuracy, choosing, and confidence across trials.

Eyewitness identification experiments typically involve a single trial: A participant views an event and subsequently makes a lineup decision. As compared to this single-trial paradigm, multiple-trial designs are more efficient, but significantly reduce ecological validity and may affect the strategies that participants use to make lineup decisions. We examined the effects of a number of forensically relevant variables (i.e., memory strength, type of disguise, degree of disguise, and lineup type) on eyewitness accuracy, choosing, and confidence across 12 target-present and 12 target-absent lineup trials (N = 349; 8,376 lineup decisions). The rates of correct rejections and choosing (across both target-present and target-absent lineups) did not vary across the 24 trials, as reflected by main effects or interactions with trial number. Trial number had a significant but trivial quadratic effect on correct identifications (OR = 0.99) and interacted significantly, but again trivially, with disguise type (OR = 1.00). Trial number did not significantly influence participants' confidence in correct identifications, confidence in correct rejections, or confidence in target-absent selections. Thus, multiple-trial designs appear to have minimal effects on eyewitness accuracy, choosing, and confidence. Researchers should thus consider using multiple-trial designs for conducting eyewitness identification experiments.

High resolution genotyping of Bacillus anthracis outbreak strains using four highly mutable single nucleotide repeat markers.

AIMS: Bacillus anthracis is a genetically monomorphic bacterium with little diversity to be expected during an outbreak. This study used more rapidly evolving genetic markers on outbreak samples to ascertain genetic diversity. METHODS AND RESULTS: Forty-seven isolates from a B. anthracis outbreak during the summer of 2005 in South Dakota were analysed using single nucleotide polymorphisms (SNP) and multi-locus VNTR analysis (MLVA). Results indicated that all of the outbreak strains belonged to a single clonal lineage. However, analysis of four single nucleotide repeat (SNR) markers resolved these isolates into six distinct genotypes providing insights into disease transmission. CONCLUSIONS: Strain determination of unknown B. anthracis samples can be ascertained by SNP and MLVA markers. However, comparison of many samples obtained during an outbreak will require markers with higher rates of mutation to ascertain genetic diversity. SIGNIFICANCE AND IMPACT OF THE STUDY: SNR4 analysis allowed discrimination of closely related B. anthracis isolates and epidemiological tracking of the outbreak. When used in conjunction with other genotyping schemes that allow broad genetic relationships to be determined, SNR markers are powerful tools for detailed tracking of natural B. anthracis outbreaks and could also prove useful in forensic investigations.

A high resolution four-locus multiplex single nucleotide repeat (SNR) genotyping system in Bacillus anthracis.

The allelic identities of Single Nucleotide Repeat (SNR) markers in Bacillus anthracis are typically ascertained by DNA sequencing through the direct repeat. Here we describe a reproducible method for genotyping closely related isolates by using four SNR loci in a multiplex-PCR capillary electrophoresis system amenable to high-throughput analysis.

Bipolar membrane electroacidification of demineralized skim milk.

The aim of this study was to evaluate the effect of decreasing the mineral content of skim milk by electrodialysis (ED) prior to electroacidification with bipolar membrane (BMEA) on the performance of the process, the chemical composition, and the physicochemical and functional properties of the isolates produced. ED used to demineralize the skim milk solution was very efficient. However, the electroacidification parameters were influenced by the demineralization level of the skim milk solution: the energy efficiency was decreased with an increase in demineralization, but it was still possible to perform BMEA at a very low conductivity level. Moreover, the isolates produced by BMEA after electrodialysis demineralization at different rates showed similar chemical composition, except on potassium and lactose contents for 75% demineralized isolate. These isolates, except on protein load for 75% demineralization rate, showed similar physicochemical and functional properties, whatever the demineralization rate.

A novel class of apical sodium co-dependent bile acid transporter inhibitors: the 2,3-disubstituted-4-phenylquinolines.

A series of 2,3-disubstituted-4-phenylquinolines were prepared and were found to inhibit the apical sodium co-dependent bile acid transporter (ASBT). Alkyl and ester substitution at the 3-position showed comparable activities while substitution at the 2-position was much more sensitive to the nature of the substituent. The synthesis and in vitro potency data are presented for this novel class of compounds.

Home care: moving forward with continuous quality improvement.

The utility of examining the effectiveness of home care is illustrated by selected examples and applications. The growth rate of home care over the past decade, questions regarding the possibly substantial differences between the quality of home care in rural and urban America, and empirical evidence that suggests inferior quality of home care for health maintenance organization patients support the need for measuring and monitoring outcomes of home care. The conclusions of a research program targeted at developing a system of outcome measures for home care, and the resulting national demonstration program to implement and refine that system, are summarized.

Attitudes towards co-workers affected by occupational hearing loss. I: Questionnaire development and inquiry.

Previous studies have shown that attitudes of workers towards their hearing impaired colleagues strongly contribute to the psychosocial disadvantages associated with occupational hearing loss (OHL). A questionnaire has been designed to characterize such attitudes. In phase I, a preliminary version consisting of 45 items was divided equally into scales of knowledge, attitudes and reported behaviour towards co-workers affected by OHL. Answers from 176 workers from a metal products plant enabled us to identify discriminative items that belonged to an appropriate factorial structure. In phase II, the response of 125 miners to a second version of the questionnaire, comprising 32 items, permitted further refinement. The final version was tested with 250 workers from three plants. Answers on the scale measuring knowledge showed that noise-exposed workers were not aware of the major consequences of OHL. Attitudes towards hearing impaired co-workers were generally favourable, but this finding appeared to reflect a strong social desirability bias. Reported behaviour indicated that a majority of workers are not inclined to adopt types of conduct that favour communication with people having OHL. Those workers who perceive themselves to be moderately to severely hearing impaired had a more negative image of hearing impaired workers, while reporting more facilitating and helping types of behaviour towards them, they also reported much more frequent contact with them. The findings provide strong indications that hearing impairment in noisy industrial settings frequently goes unnoticed and that many workers who are at risk of developing OHL are often unaware that some of their co-workers are already affected. These findings offer useful leads for the development of an awareness programme on the consequences of OHL.

Humanism in medical education: a study of educational needs perceived by trainees of three Canadian schools.

The authors examined how medical trainees and recent graduates of three Quebec medical schools value 16 dimensions of medical competence classified in four broad categories: clinical, technological, humanistic, and social and preventive. To assess perceived educational needs, the trainees' perceptions of the importance that medical faculties attribute to these same dimensions in the education of physicians were also examined. The survey was conducted in 1986-87 via a questionnaire mailed to 2,030 individuals, including freshmen, juniors, interns, residents, and newly practicing generalists; 80.3% responded. Compared with the views attributed to the faculty, the medical trainees gave more importance to basic diagnostic and therapeutic skills such as the medical history, the physical examination, and the treatment of common diseases. They also valued to a greater extent non-biological dimensions of clinical competence, such as communication with patients, patient education, the social context of disease, and the multidisciplinary nature of patient care, while they ascribed less importance to medical technology and rare diseases. The study raises the question of the relevance of medical education to medical practice by suggesting that those who are preparing themselves to become doctors may not be receiving the training they wish to receive.

Reflected pressure waves in the ascending aorta: effect of glyceryl trinitrate.

Reflected pressure waves returning to the ascending aorta are an important contribution to aortic systolic pressure and thus the load on the left ventricle. The effect of glyceryl trinitrate on pressure wave reflections in the ascending aorta was studied using the transmission of arterial pressure between two high fidelity pressure transducers. Glyceryl trinitrate 0.3 mg sublingually reduced systolic arterial pressure by 11 mmHg owing to a reduction of the late systolic pressure peak. Mean arterial pressure fell 2 mmHg, but heart rate and aortic flow did not change. The aortic input impedance was reduced at the first harmonic (control 18.4(4.1); glyceryl trinitrate 10.8(2.4) kPa.s.litre-1; p less than 0.005) but characteristic impedance was not changed (control 12.7(3.8); glyceryl trinitrate 14.2(3.3) kPa.s.litre-1). The first two harmonics of apparent phase velocity were reduced by glyceryl trinitrate (1.05 Hz: control 3314(798); glyceryl trinitrate 1772(495) cm.s-1; p less than 0.01; 2.1 Hz: control 1246(269); glyceryl trinitrate 754(127) cm.s-1; p less than 0.05), yet the foot to foot wave velocity was unchanged (control 688(112); glyceryl trinitrate 726(112) cm.s-1). There was a significant reduction in the amplitude of the global reflection coefficient at 1.05 Hz (control 0.70(0.09); glyceryl trinitrate 0.48(0.08); p less than 0.001) and at 2.1 Hz (control 0.48(0.07); glyceryl trinitrate 0.23(0.06); p less than 0.005) with no significant change in phase. Glyceryl trinitrate reduces cardiac pulsatile load by diminishing the amplitude of wave reflections arriving back in the aorta during systole yet has no effect on aortic compliance or arteriolar resistance. This study demonstrates a method of evaluating the effect of vasoactive drugs on cardiac pulsatile load.

Plasma kinetics of oral retinol in cancer patients.

Concurrent with a phase I trial of retinol in patients with advanced cancer, we studied the plasma kinetics of both retinol and its major metabolites, retinyl palmitate and retinyl stearate. Retinol was administered to 12 patients in daily oral doses of 60,000, 100,000, 150,000, or 200,000 units/m2. Patients remained on treatment until the development of dose-limiting toxic effects or disease progression. Retinoid plasma kinetics were studied on the first day of treatment, at Weeks 2 and 4, and every 2-3 months thereafter as long as the patient remained on therapy. A high-performance liquid chromatography assay was used to quantitate the plasma concentration of both retinol and its fatty acid esters. There was no significant change in the plasma retinol concentration up to 24 hours after a single oral dose of retinol (P greater than 0.05). However, the plasma concentration of retinyl palmitate and retinyl stearate markedly increased with a mean time to peak plasma concentration of 4.3 +/- 0.7 hours. Retinyl palmitate rapidly disappeared from the plasma with an initial phase half-life of 2.2 +/- 0.9 hours. The terminal phase half-life appeared prolonged and could not be accurately determined. Retinyl stearate was detected in the plasma of all patients with plasma concentrations paralleling and ranging from 20% to 40% those of retinyl palmitate. With prolonged retinol administration, peak plasma retinyl palmitate concentrations increased with both increasing retinol dose (P less than 0.001) and increasing duration of treatment (P = 0.001). In three patients with low pretreatment plasma retinol concentrations, daily retinol administration was associated with a rise in plasma retinol concentration. Because only one patient developed serious toxic effects and all patients had markedly increased plasma concentrations of retinyl esters, no conclusion could be made about the relationship between plasma retinyl ester concentration and retinol toxicity.

Correlative electrocardiographic studies in myocardial infarction.

The electrocardiogram remains our first and most widely available tool to study myocardial infarction. We have attempted to suggest that we must be both more circumspect and adventurous in its use. The traditional electrocardiographic labels imply a level of precision that is unwarranted and so obscure real, often clinically important differences that exist among patients. We believe the electrocardiogram becomes more powerful when it is used with other noninvasive tests, and all such tests are best interpreted within rather than removed from the clinical context. We suggest as well that frequently after infarction, zones of viable muscle exist that are still vulnerable to ischemia. These zones may lie within or be remote from the actual infarct region, and noninvasive tests should be milked for clues that these regions are present, for while there is little to be done for necrotic tissue after infarction, there is considerable therapy available, both medical and surgical, to rescue tissue at risk of ischemia after infarction.

Cytotoxicity of mitomycin C on clonogenic human carcinoma cells is not enhanced by hypoxia.

The bioreductive alkylating agent mitomycin C (mitomycin) has been shown to have greater activity under hypoxic than oxic conditions on murine cell lines such as the EMT-6 fibrosarcoma cell line. Solid tumors are known to contain hypoxic cells and are relatively resistant to ionizing radiation and some chemotherapeutic agents. We tested the cytotoxicity of mitomycin against fresh biopsies of human carcinomas under both hypoxic and oxic conditions in the human tumor clonogenic assay (HTCA). Additionally, we examined the metabolism of mitomycin by sonicates of the murine EMT-6 cells and the human WiDR colon carcinoma cells. We confirmed that under our clonogenic assay conditions the EMT-6 cell line was more sensitive to mitomycin under hypoxic than oxic conditions. Additionally, we established that EMT-6 cells also metabolize mitomycin at a more rapid rate under hypoxic than oxic conditions. However, these effects of hypoxia on mitomycin activity were not demonstrable for the human WiDR colon cancer cell line. In addition to these findings, the cytotoxicity of mitomycin was either unchanged or reduced under hypoxic conditions for ten fresh human tumors tested for mitomycin sensitivity in HTCA. Based on these observations, we conclude that the potentiating effect of hypoxia on mitomycin metabolism and biological activity may be peculiar to the murine EMT-6 and S-180 cell lines and that mitomycin C is not likely to have differential efficacy against hypoxic human carcinoma cells.

Early recognition of the patient at late high risk: incomplete infarction and vulnerable myocardium.

The process of identifying patients with myocardial infarction (MI) at high risk after hospital discharge should begin at admission. By using basic clinical and laboratory information, enhanced by a wide variety of noninvasive tests, not only can individual patients at risk be recognized, but also the processes that determine risk can, at least in part, be appreciated. Outcome is affected by the extent of damaged tissue and, apparently, by the amount of potentially ischemic muscle. MI may change the coronary circulation such that a new and fragile balance between supply and demand results, both within and outside the infarct zone; that is, the infarct may be incomplete and the viable muscle within it may then be vulnerable to later ischemia. Muscle outside the infarct zone may be left in much the same precarious state. Also, coronary spasm may not be infrequent in the weeks after MI. These factors together may underlie recurrent post-MI myocardial ischemia.

Myocardial metabolic alterations after contrast angiography.

Contrast media used during angiography are known to produce transient alterations in cardiovascular physiology. However, little information is available concerning what alterations, if any, occur in myocardial metabolism after contrast angiography. Sixteen patients with symptoms of ischemic heart disease undergoing elective left ventriculography were studied. Coronary sinus and arterial blood samples were obtained for free fatty acids, glucose and lactate before and after performing left ventriculography with Renografin-76. Coronary blood flow was determined by the thermodilution technique. Five minutes after ventriculography, the arterial level of free fatty acids had decreased by 18.0 +/- 4.9 percent (mean +/- standard deviation) from the baseline (before angiography) samples (probability [p] less than 0.001). Associated with this decrease in arterial free fatty acids was an increase in the myocardial uptake of this substrate. At 5 minutes after left ventriculography, the free fatty acid uptake had increased 48.5 +/- 33.0 percent compared with the baseline value (p less than 0.001). After the injection of contrast medium, there was no significant change in the arterial levels of glucose or lactate. However, significant decreases in the myocardial uptake of glucose and lactate were demonstrated (-72.5 +/- 44.5 percent [p less than 0.001] and -43.2 +/- 22.9 percent [p less than 0.001], respectively) at 5 minutes. The changes in arterial free fatty acids and in the myocardial uptake of the various substrates persisted throughout the sampling period of 20 minutes after ventriculography. These results demonstrate that contrast medium significantly alters myocardial metabolism. These metabolic alterations persist longer than the hemodynamic changes induced by contrast angiography.

Voluntary heart rate lowering following a cardiovascular arousing task.

The purpose of the research was to evaluate the effect of feedback-assisted voluntary control to lower heart rate (HR), following a non-somatic mediated task designed to induce cardiovascular activation. Twenty-seven male subjects participated in this study and were randomly divided into three groups. All subjects were submitted to an arousing mental arithmetic task for a 1 min period, followed either by a feedback-assisted HR lowering task (FG), by an unassisted HR lowering task (ICG), or by a relaxation period (RCG). During this period (2 min duration), ICG and RCG subjects were required, as a help for HR deceleration or relaxation, to track visually a sweeping line similar in form to the continuous analogue feedback of the FG subjects. This sequence, interspaced by a 1 min rest period, was repeated 10 times. Results showed that the mental arithmetic task was effective in producing consistent and repetitive HR acceleration. All three groups showed significative HR lowering during the following voluntary HR control or relaxation period. However, there was no difference in the speed or depth of HR lowering. It appeared that continuous-analogue feedback was not more effective than instructions to relax to assist HR return to lower levels.