Focussing Protons from a Kilojoule Laser for Intense Beam Heating using Proximal Target Structures.

Proton beams driven by chirped pulse amplified lasers have multi-picosecond duration and can isochorically and volumetrically heat material samples, potentially providing an approach for creating samples of warm dense matter with conditions not present on Earth. Envisioned on a larger scale, they could heat fusion fuel to achieve ignition. We have shown in an experiment that a kilojoule-class, multi-picosecond short pulse laser is particularly effective for heating materials. The proton beam can be focussed via target design to achieve exceptionally high flux, important for the applications mentioned. The laser irradiated spherically curved diamond-like-carbon targets with intensity 4 × 1018 W/cm2, producing proton beams with 3 MeV slope temperature. A Cu witness foil was positioned behind the curved target, and the gap between was either empty or spanned with a structure. With a structured target, the total emission of Cu Kα fluorescence was increased 18 fold and the emission profile was consistent with a tightly focussed beam. Transverse proton radiography probed the target with ps order temporal and 10 µm spatial resolution, revealing the fast-acting focussing electric field. Complementary particle-in-cell simulations show how the structures funnel protons to the tight focus. The beam of protons and neutralizing electrons induce the bright Kα emission observed and heat the Cu to 100 eV.

Measurement of charged-particle stopping in warm dense plasma.

We measured the stopping of energetic protons in an isochorically heated solid-density Be plasma with an electron temperature of ∼32 eV, corresponding to moderately coupled [(e^{2}/a)/(k_{B}T_{e}+E_{F})∼0.3] and moderately degenerate [k_{B}T_{e}/E_{F}∼2] "warm-dense matter" (WDM) conditions. We present the first high-accuracy measurements of charged-particle energy loss through dense plasma, which shows an increased loss relative to cold matter, consistent with a reduced mean ionization potential. The data agree with stopping models based on an ad hoc treatment of free and bound electrons, as well as the average-atom local-density approximation; this work is the first test of these theories in WDM plasma.

Older participants are frequently excluded from Parkinson's disease research.

BACKGROUND: The exclusion of older participants from clinical research is common and limits the generalisation of research findings. We aimed to assess the current potential for older patients to participate in Parkinson's disease (PD) research. METHOD: We performed a systematic analysis of data extracted from the World Health Organization Clinical Trials Registry Platform regarding 206 actively recruiting PD research studies. Data regarding study variables and exclusion on the grounds of an upper age limit was extracted from each registry entry and subsequently used for statistical analysis. RESULTS: Exclusion by arbitrary upper age limit is common, with 101 (49%) of studies excluding participants by age and with a mean upper age limit for exclusion of 79.3 years (range 64-95 years). Exclusion by age was significantly more common in studies with an estimated enrollment of fewer than 100 participants; OR 1.92 (95%CI 1.13-3.42) P = 0.018. Rates of exclusion by age were not significantly influenced by study subject, study location, source of funding, study duration or number of centres. CONCLUSION: Exclusion of participants from PD research on the basis of an upper age limit is common and particularly problematic in smaller studies. The exclusion of older participants seriously compromises the generalisation of findings from PD research to the large numbers of elderly PD patients seen in clinical practice.

The hyperdense internal carotid artery sign: prevalence and prognostic relevance in stroke thrombolysis.

Introduction. The hyperdense internal carotid artery sign (HICAS) has been suggested as a common marker of terminal internal carotid artery (ICA) thrombus associated with poor outcomes following thrombolysis. We aimed to investigate the prevalence and prognostic significance of the HICAS in an unselected cohort of patients receiving intravenous thrombolysis. Methods. Prethrombolysis NCCTs of 120 patients were examined for the presence of the HICAS and hyperdense middle cerebral artery sign (HMCAS). A poor outcome was defined as a discharge Barthel score <15 or inpatient death. Results. A HICAS was present in 3 patients (2.5%). Prethrombolysis neurological deficits were significantly more severe in patients with a HICAS (P = 0.019). HICAS was not significantly associated with a poor outcome (P = 0.323). HMCAS was significantly associated with severe prethrombolysis neurological deficits (P = 0.0025) and a poor outcome (P = 0.015). Conclusions. This study suggests that the prevalence of the HICAS may be lower than previously reported. The presence of a HICAS was associated with severe prethrombolysis neurological deficits in keeping with terminal ICA occlusion. The role of the HICAS as a prognostic marker in stroke thrombolysis remains unclear.

A readability assessment of online Parkinson's disease information.

BACKGROUND: Patients increasingly use the internet to access health information. Inadequate health literacy is common and frequently limits patient comprehension of healthcare literature. We aimed to assess the readability of online consumer-orientated Parkinson's disease (PD) information using two validated measures. METHOD: We identified the 100 highest ranked consumer-orientated PD webpages and determined webpage readability using the Flesch-Kincaid and Simple Measure Of Gobbledygook (SMOG) formulae. RESULTS: None of the webpages analysed complied with current readability guidelines. Commercial websites were significantly easier to read (p = 0.035). The Flesch-Kincaid formula significantly underestimated reading difficulty (p < 0.0001). Ease of reading correlated weakly with search engine ranking (r = 0.35, p = 0.0004). CONCLUSIONS: Only 1% of the top 100 PD information webpages are fully comprehensible to the average adult. Simple Measure Of Gobbledygook should be the preferred measure of webpage readability. Parkinson's disease information websites require major text revision to comply with readability guidelines and to be comprehensible to the average patient.

Neuropsychiatric features of Parkinson's disease.

Parkinson's disease is a chronic, progressive, neurodegenerative condition that damages central nervous system pathways. In addition to the well-recognised motor features of the disease, patients commonly experience non-motor symptoms including neuropsychiatric complications. These symptoms may precede motor symptoms and have a very significant impact on quality of life for patients and their carers.

Branchial elimination of superhydrophobic organic compounds by rainbow trout (Oncorhynchus mykiss).

The branchial elimination of pentachloroethane and four congeneric polychlorinated biphenyls by rainbow trout was measured using a fish respirometer-metabolism chamber and an adsorption resin column. Branchial elimination was characterized by calculating a set of apparent in vivo blood:water partition coefficients (P(BW)). Linear regression was performed on the logarithms of P(BW) estimates and the log K(OW) value for each compound to give the fitted equation: log P(BW)=0.76 x log K(OW)-1.0 (r(2)=0.98). The linear nature of this relationship provides support for existing models of chemical flux at fish gills and suggests that a near equilibrium condition was established between chemical in venous blood entering the gills, including dissolved and bound forms, and dissolved chemical in expired branchial water. In vivo P(BW) estimates were combined with P(BW) values determined in vitro for a set of lower log K(OW) compounds (Bertelson et al., Environ. Toxicol. Chem. 17 (1998) 1447-1455) to give the fitted relationship: log P(BW)=0.73 x log K(OW)-0.88 (r(2)=0.98). The slope of this equation is consistent with the suggestion that chemical binding to non-lipid organic material contributes substantially to blood:water chemical partitioning. An equation based on the composition of trout blood (water content and the total amount of organic material) was then derived to predict blood:water partitioning for compounds with log K(OW) values ranging from 0 to 8: log P(BW)=log[(10(0.73 log K(ow)) x 0.16)+0.84].

Holter monitor findings in asymptomatic male military aviators without structural heart disease.

PURPOSE: Our study was designed to determine the spectrum of Holter monitor findings in normal male military aviators to establish a reference for aircrew populations with cardiac related diagnoses. METHODS: We identified all individuals with normal cardiac catheterization in the United States Air Force Aeromedical Consultation Service cardiac catheterization database from January 1984 to December 1998. Cases with valvular disease, left or right bundle branch block, and referral diagnoses of ectopy or arrhythmia were then excluded. Results of Holter monitor studies performed on the remaining aviators prior to cardiac catheterization were then collected and tabulated. Frequency of isolated ectopy was classified as a percentage of the total beats on the Holter monitor: rare (< or =0.1%), occasional (>0.1 to 1.0%), frequent (>1.0 to 10%) and very frequent (>10%). RESULTS: From 1575 consecutive cardiac catheterizations reviewed, 303 aviators met the above inclusion criteria. Only 36 of 303 (11.9%) had no ectopy at all. Rare, occasional, frequent and very frequent isolated atrial ectopy occurred in 72.9%, 2.6%, 2.3% and 0.3%, respectively. The same categories of isolated ventricular ectopy occurred in 40.9%, 7.9%, 3.3% and 0.0%. Atrial and ventricular pairs occurred in 14.5% and 4.3%, respectively. Nonsustained supraventricular and ventricular tachycardia (duration 3 to 10 beats) occurred in 4.3% (13/303) and 0.7% (2/303), respectively. There were no sustained supraventricular or ventricular tachycardias. CONCLUSIONS: In this population, absence of ectopy is unusual while rare isolated ectopy is common. These findings may help define the aeromedical/clinical significance of Holter monitors performed on aircrew with underlying cardiac complaints or diagnoses.

Dietary supplementation with the anti-tumour promoter quercetin: its effects on matrix metalloproteinase gene regulation.

Dietary modification, especially the consumption of larger amounts of fruits and vegetables can act to decrease the risk of a variety of human cancers. Quercetin, a bioflavonoid widely distributed in fruits and vegetables has been shown to have a chemoprotective role in cancer, through complex effects on signal transduction involved in cell proliferation and angiogenesis. In this study we examined the effects of dietary supplementation of quercetin (30 mg per day) incorporated into a black currant drink. Healthy male subjects aged between 33 and 64 years (mean=47.1 years) received either quercetin or placebo for 14 days. Blood samples were taken at baseline and upon completion of the study and analysed for full blood count, matrix metalloproteinase-2 (MMP-2), tissue inhibitor of matrix metalloproteinse-1 and -2 (TIMP-1 and -2) plasma levels using ELISA techniques. RNA was extracted from the peripheral blood lymphocytes and reverse transcriptase-polymerase chain reaction (RT-PCR) carried out for MMP-2 and TIMP-1, TIMP-2 gene expression determination. Supplementation of the diet with quercetin did not alter the MMP-2 or TIMP-2 gene transcription or plasma protein levels of the healthy subjects in this study. The TIMP-1 gene transcription and plasma protein levels (311+/-70 ng/ml at baseline to 183+/-35 ng/ml post-supplementation, P<0.05) of the subjects in this study were, however, significantly decreased following quercetin supplementation. This is an interesting result, as there is some controversy over the functions of TIMP-1 in tumour progression. In certain model systems, artificially increased TIMP-1 levels prevent or decrease tumour growth. However, in other studies high levels of TIMP-1 have been correlated with aggressive disease and poor prognosis in patients with certain malignancies. This study has outlined a potential role for the anti-tumour promoter quercetin as a dietary mediator of the carcinogenic cascade.

The natural history of Wolff-Parkinson-White syndrome in 228 military aviators: a long-term follow-up of 22 years.

BACKGROUND: Wolff-Parkinson-White (WPW) syndrome poses a risk for tachyarrhythmias and sudden cardiac death. Most WPW studies have relatively limited numbers of subjects and brief follow-up periods. METHODS: We reviewed records of 238 consecutive military aviators with WPW syndrome evaluated from 1955 to 1999. Follow-up was by questionnaires, telephone interviews, or death certificates. Events included sudden cardiac death and supraventricular tachycardia (SVT) (by electrocardiographic [ECG] documentation or suggestive symptoms). RESULTS: The mean age was 34.3 years (range 17-56 years). Forty-two (42/238, 17.6%) had SVT (WPW syndrome) and 196 of 238 (82.4%) had the WPW ECG pattern only. The mean follow-up of 21.8 years (range 2-41 years) was obtained on 228 of 238 (96%) for a total of 4906 patient-years. Sudden cardiac death occurred in 1 of 228, an incidence of 0.0002 per patient-year (95% confidence interval 0.0-0.001). SVT occurred in 47 of 228 (20.6%) or 0.01 per patient-year. One hundred eighty-seven (187/228, 82%) initially had the WPW ECG pattern only; 28 of 187 (15.0%) reported SVT during follow-up. Forty-one (41/228, 18%) initially had WPW syndrome; 19 of 41(46.3%) reported additional SVT during follow-up. CONCLUSION: Sudden cardiac death risk was low (0.02%/patient-year) in this WPW population. The SVT incidence was 1% per patient-year. Referral bias and some characteristics of the unique military aviator population may partly account for these low event rates. However, these results may be more applicable to unselected populations than are tertiary referral-based studies.

Dietary uptake kinetics of 2,2',5,5'-tetrachlorobiphenyl in rainbow trout.

The disposition of [UL-(14)C]2,2',5,5'-tetrachlorobiphenyl (TCB) in rainbow trout (Oncorhynchus mykiss) was studied in acute dietary exposures using TCB-contaminated fathead minnows (Pimephales promelas). Trout were sampled at several postfeeding time points and TCB-derived radioactivity was measured in gut contents and selected tissues. Gastric evacuation was exponential with time and was 95% complete within 36 h of feeding. The ratio of activity in upper intestinal tissue to that in blood declined between 6 and 48 h, as did the lumenal contents/tissue ratio. Stomach content lipid declined between 0 and 24 h, while the lipid content of chyme remained relatively constant. These observations are consistent with liquid phase emptying of lipid and TCB to the upper intestine followed by rapid coassimilation. Tissue/blood activity ratios for the stomach, lower intestine, muscle, liver, and kidney were constant and probably represented near equilibrium conditions. The fat/blood activity ratio increased through 96 h, indicating that TCB was redistributing to fat. The lower intestinal tissue/feces activity ratio increased between 6 and 24 h and then declined rapidly. Fecal lipid content also increased between 6 and 24 h, but the amount of this increase was insufficient to explain observed changes in the distribution of TCB-derived activity. A small amount of 3-hydroxy TCB was detected in feces. Generally, however, metabolism had little or no impact on the uptake, distribution or elimination of TCB. Measured assimilation efficiencies exceeded 90% and are the highest ever reported in fish feeding studies with TCB.

Medicine and management: a conflict facing general practice?

Partners and practice managers are beginning to understand implications of management issues raised by recent reforms. Practices involved in this study agree the need for improvement, but partners and managers were often unable to define improvements needed. Demonstrates that effective management structure is vital to future success for general practice. To achieve this involves understanding new managerial challenges practices must meet and different organizational competences required. To change requires a radical restructure of many practice roles and several options are considered. Regardless of the chosen option the question of training remains. There is a need to involve consultants, managers, and doctors already advancing the boundaries of practice development, in a dialogue with institutions providing management training, to design suitable programmes. Academic institutions too often produce management programmes geared towards the old environment, whereas managerial skills which changes in the NHS demand from future practice managers are now required.

Crossing boundaries: communication between professional groups.

The NHS reforms increased emphasis on a managerial culture. In primary care this raised questions about responsibility and philosophical approaches. Greater integration between agencies brings benefits, but creates tensions. Failure to bridge the gap may result in dysfunctional teams and compromised quality of patient care. The different orientations may manifest themselves in several ways but lead to frictions that can breed hostility and prevent effective teamwork. Explores issues involving social service and community nurse teams in Dorset to identify a new framework for working, by recognizing and respecting differences and by creating a climate of dialogue. The process involves three stages. First, mutual awareness by use of meta planning which revealed several important themes, different priorities, political dynamics and organizational constraints. Second, behavioural contracting facilitated by role reversal and third, the development of consensus working protocols as a bridge for professional gaps.

Toxicokinetics and metabolism of aniline and 4-chloroaniline in medaka (Oryzias latipes).

The in vivo toxicokinetics and in vitro hepatic microsomal metabolism of [14C]aniline and [14C]4-chloroaniline in medaka (Oryzias latipes) were investigated to provide a basis upon which to interpret the toxicological responses of small aquarium fish to aniline derivatives. During static aqueous exposures of up to 320 min, parent equivalents failed to reach steady state and results from depuration studies clearly demonstrated biphasic elimination. Due to low elimination rates, 40 to 20% of absorbed aniline and 4-chloroaniline doses, respectively, remained within the fish through 330 min postexposure. Based on an analysis of excreted metabolites, N-acetylation was the dominant route of in vivo metabolism for 4-chloroaniline, with no indication of ring hydroxylation, while the evidence suggested that polar conjugates were the dominant in vivo aniline metabolites. The toxicokinetics and in vivo metabolism of both aniline and 4-chloroaniline were best described by a two-compartment model that was consistent with the assumption that metabolites of the parent amines were accumulating in the fish. In partial support of the hypothesis that these amines are being metabolically activated in medaka, N-hydroxylation of aniline and 4-chloraniline to phenylhydroxylamine and 4-chlorophenylhydroxylamine were quantified in hepatic microsomal preparations.

Aspects of psychology in sports medicine.

Psychology's impact as an ergogenic aid across sports and competitive levels has been well documented. In addition, exercise can play a major role in disease prevention and health enhancement while also enhancing psychological well-being. In addition to its preventive value, exercise is being recognized as a valuable therapeutic tool. Like most therapeutic modalities, however, exercise also has some potentially negative qualities.

Does self-efficacy predict performance in experienced weightlifters?

Previous studies that have examined self-efficacy-performance relationships have used novice performers. It is unclear if these findings would generalize to "experienced" performers. Based on Bandura's self-efficacy theory, this study was designed to investigate (a) the effects of false information feedback on self-efficacy beliefs and subsequent weightlifting performance, and (b) whether self-efficacy or past performance is most related to subsequent weightlifting performance. Experienced weightlifters engaged in six performance sessions, each consisting of a one-repetition-maximum bench press. Male subjects (N = 36) were randomly assigned to one of three treatment groups: accurate performance information, false information that they lifted more than their actual lift, or false information that they lifted less than their actual lift. Before each session, subjects indicated the amount of weight they were 100%, 75%, and 50% confident they could lift. Results replicated existing research findings regarding deception and performance; false positive feedback increased future bench press performance. In addition, results indicated that past weightlifting performance accounted for nearly all of the variance in subsequent performance. This finding is discussed in light of the difficulty in extending the predictions of self-efficacy theory to sport settings where athletes have gained experience by undergoing repeated training trials.