CBETA: First Multipass Superconducting Linear Accelerator with Energy Recovery.

Energy recovery has been achieved in a multipass linear accelerator, demonstrating a technology for more compact particle accelerators operating at higher currents and reduced energy consumption. Energy delivered to the beam during the first four passes through the accelerating structure was recovered during four subsequent decelerating passes. High-energy efficiency was achieved by the use of superconducting accelerating cavities and permanent magnets. The fixed-field alternating-gradient optical system used for the return loop successfully transported electron bunches of 42, 78, 114, and 150 MeV in a common vacuum chamber. This new kind of accelerator, an eight-pass energy recovery linac, has the potential to accelerate much higher current than existing linear accelerators while maintaining small beam dimensions and consuming much less energy per electron.

Assessment of hydroxylated metabolites of polychlorinated biphenyls as potential xenoestrogens: a QSAR comparative analysis∗.

Alternative methods, including quantitative structure-activity relationships (QSAR), are being used increasingly when appropriate data for toxicity evaluation of chemicals are not available. Approximately 40 mono-hydroxylated polychlorinated biphenyls (OH-PCBs) have been identified in humans. They represent a health and environmental concern because some of them have been shown to have agonist or antagonist interactions with human hormone receptors. This could lead to modulation of steroid hormone receptor pathways and endocrine system disruption. We performed QSAR analyses using available estrogenic activity (human estrogen receptor ER alpha) data for 71 OH-PCBs. The modelling was performed using multiple molecular descriptors including electronic, molecular, constitutional, topological, and geometrical endpoints. Multiple linear regressions and recursive partitioning were used to best fit descriptors. The results show that the position of the hydroxyl substitution, polarizability, and meta adjacent un-substituted carbon pairs at the phenolic ring contribute towards greater estrogenic activity for these chemicals. These comparative QSAR models may be used for predictive toxicity, and identification of health consequences of PCB metabolites that lack empirical data. Such information will help prioritize such molecules for additional testing, guide future basic laboratory research studies, and help the health/risk assessment community understand the complex nature of chemical mixtures.

Once-daily, controlled-release tramadol and sustained-release diclofenac relieve chronic pain due to osteoarthritis: a randomized controlled trial.

OBJECTIVE: The present study was a randomized, parallel, double-blind comparison between controlled-release (CR) tramadol and sustained-release (SR) diclofenac in patients with chronic pain due to osteoarthritis of the hips and/or knees. METHODS: Patients with at least moderate pain intensity, and having received analgesics over the past three months, underwent a two- to seven-day washout of current analgesics before initiation of 200 mg CR tramadol or 75 mg SR diclofenac. During the eight-week study, patients returned to the clinic biweekly. CR tramadol doses were titrated to a maximum of 200 mg, 300 mg or 400 mg per day. SR diclofenac doses were titrated to 75 mg or 100 mg once daily, or 75 mg twice a day based on pain relief and the presence of side effects. For rescue analgesic, patients took acetaminophen as needed, up to 650 mg three times a day. RESULTS: Forty-five patients on CR tramadol and 52 patients on SR diclofenac were evaluable. Significant improvements from prestudy treatment were shown for visual analogue scale pain (P=0.0001), stiffness (P<0.0005) and physical function (P=0.0001) scores for both treatments. There were no significant differences between the two treatments in the Western Ontario and McMaster Universities subscales, overall pain, pain and sleep, or the clinical effectiveness evaluation. Overall incidence of adverse events was similar in both groups, with more opioid-related adverse events with CR tramadol, and two serious adverse events occurring with the use of SR diclofenac. CONCLUSIONS: CR tramadol is as effective as SR diclofenac in the treatment of pain due to knee or hip osteoarthritis, with the potential for fewer of the serious side effects that characterize nonsteroidal anti-inflammatory drug administration.

Socioeconomic influences on benzodiazepine consumption in an Irish Region.

Misuse of prescription sedatives is a significant problem for addiction treatment services. The aim of this study was to examine the prescribing of diazepam in disadvantaged Irish communities, and to identify factors which may predict diazepam consumption in that population. We examined prescribing trends for those aged 16-69 years in 2002 in a region of the state-funded General Medical Services Scheme. Material deprivation was based on the 2002 Small Area Health Research Unit (SAHRU) deprivation index. The average defined daily dose (DDD) was calculated and logistic regression analysis was used to predict diazepam use by age, gender and deprivation index. Results showed that patients living in the most-deprived areas were more likely to receive diazepam than patients living in the least-deprived areas (OR = 1.21, 95% CI 1.15-1.27). Female patients living in the most-deprived areas were also more likely to receive diazepam than those living in the least-deprived areas (OR = 1.36, 95% CI 1.18-1.57). It is concluded that there is a pattern of higher diazepam prescribing in areas of greatest deprivation, where prescription sedatives play a complex role within troubled families.

Understanding the needs of people using a cancer information service in Northern Ireland.

A retrospective analysis of first-time enquirers using a cancer information service in Belfast, Northern Ireland, is presented. Our results show that women are three times more likely to use the service than men, with relatives and friends more likely to seek information on behalf of cancer patients than patients themselves. Unlike patients with cancer at other sites, the number of enquiries from breast cancer patients [standard incidence rate (SIR) = 1.5] was greater than incidence figures for the general population would suggest. Individuals without a cancer diagnosis but with potentially cancer-related symptoms accounted for 30% of all enquiries. Breast changes accounted for 49% of calls, testicular abnormalities 19% and concerns about cervical smear test results 13%; prostate problems (12%) and changes in skin pigmentation were the other main sources of caller concern. Our results also demonstrate that cancer patients often have a poor understanding of commonly used medical terms. This analysis shows that individuals using a cancer information service are not representative of the population that develops the disease, highlights how media campaigns can encourage the awareness and reporting of new and pre-existing symptoms, and exposes some of the confusion and misconceptions about cancer that are experienced by sections of the Irish population.

Sunbathing intentions in Irish people travelling to Mediterranean summer holiday destinations.

As exposure to UV light is thought to be the most significant environmental and behavioural risk factor for avoiding skin cancer, we have analysed the sunbathing intentions and attitudes of Irish people travelling to Mediterranean and Iberian holiday destinations. Ninety per cent of respondents planned to get a suntan on their vacation with 44% likely to burn their skin in the process. Although all intended to apply sun cream on holiday only 40% would apply >SPF 15. Sixty-four per cent planned to sunbathe between 11.00 am and 3.00 pm, with 25% intending to spend <5 hours in the sun. One-third of those intending to sunbathe for >6 hours per day were aged between 16 and 24 years. Approximately eight out of 10 people thought suntans made them feel healthier or attractive. Fifty-six per cent regularly checked their moles but men were less likely to check their skin for pigment changes. The results provide baseline information on sunbathing attitudes of Irish people. They show that while most people feel they adopt a careful approach to sunbathing, the experiences and intentions, especially in younger people, are influenced by the desirability of a suntan, and reflect a behaviour that increases their risk of skin cancer.

Covalently linked gramicidin channels: effects of linker hydrophobicity and alkaline metals on different stereoisomers.

The direct role of the dioxolane group on the gating and single-channel conductance of different stereoisomers of the dioxolane-linked gramicidin A (gA) channels reconstituted in planar lipid bilayers was investigated. Four different covalently linked gA dimers were synthesized. In two of them, the linker was the conventional dioxolane described previously (SS and RR channels). Two gAs were covalently linked with a novel modified dioxolane group containing a retinal attachment (ret-SS and ret-RR gA dimers). These proteins also formed ion channels in lipid bilayers and were selective for monovalent cations. The presence of the bulky and hydrophobic retinal group immobilizes the dioxolane linker in the bilayer core preventing its rotation into the hydrophilic lumen of the pore. In 1 M HCl the gating kinetics of the SS or RR dimers were indistinguishable from their retinal counterparts; the dwell-time distributions of the open and closed states in the SS and ret-SS were basically the same. In particular, the inactivation of the RR was not prevented by the presence of the retinal group. It is concluded that neither the fast closing events in the SS or RR dimers nor the inactivation of the RR are likely to be a functional consequence of the flipping of the dioxolane inside the pore of the channel. On the other hand, the inactivation of the RR dimer was entirely eliminated when alkaline metals (Cs(+) or K(+)) were the permeating cations in the channel. In fact, the open state of the RR channel became extremely stable, and the gating characteristics of both the SS and RR channels were different from what was seen before with permeating protons. As in HCl, the presence of a retinal in the dioxolane linker did not affect the gating behavior of the SS and RR in Cs(+)- or K(+)-containing solutions. Alternative hypotheses concerning the gating of linked gA dimers are discussed.

Elimination of early rehospitalization in a randomized, controlled trial of multidisciplinary care in a high-risk, elderly heart failure population: the potential contributions of specialist care, clinical stability and optimal angiotensin-converting enzyme inhibitor dose at discharge.

BACKGROUND: Despite a growing body of data demonstrating the benefits of multidisciplinary care in heart failure, persistently high rates of readmission, especially within the first month of discharge, continue to be documented. AIMS: As part of an ongoing randomized study on the value of multidisciplinary care in a high risk (NYHA Class IV), elderly (mean age 69 years) heart failure population, we examined the effects of this intervention on previously high (20%) 1-month readmission rates. METHODS: Unlike previous studies of this approach, both multidisciplinary (MC) and routine care (RC) populations were cared for by the cardiology service, complied with adherence to clinical stability criteria prior to discharge (100% of patients) and received at least target dose angiotensin-converting enzyme (ACE) inhibition with perindopril prior to discharge (94% of indicated patients). We analysed death and unplanned readmission for heart failure at 1 month. RESULTS: This early report from the first 70 patients (67% male, 71% systolic dysfunction with a mean ejection fraction of 31.0+/-6.7%) enrolled in this study demonstrates elimination of 1-month hospital readmission in both RC and MC groups. This unexpected result represents a dramatic improvement both for this patient cohort (20% 30-day readmission rate prior to enrollment reduced to 0% following the index admission in both care groups) and in comparison with available data. CONCLUSIONS: Critical contributors to this improvement appear to be specialist cardiology care, adherence to clinical stability criteria prior to discharge and routine use of target or high-dose ACE inhibitor therapy prior to discharge. Widespread application of this approach may have a dramatic improvement in morbidity of CHF while limiting the escalating costs of this condition.

Synaptic differentiation between two phasic motoneurons to a crayfish fast muscle.

Synaptic differentiation among crustacean phasic motoneurons was investigated by characterizing the synaptic output and nerve terminal morphology of the two axons to the adductor exopodite muscle in the crayfish uropod. The muscle is of the fast type with short sarcomeres (2-3 micro m) and a low thin to thick filament number (6:1). On single muscle fibers, excitatory postsynaptic potentials generated by the large-diameter axon are significantly larger than those by the small-diameter axon suggesting a presynaptic origin for these differences. Nerve terminals arising from these two axons have typical phasic features, filiform shape and a low (6-8%) mitochondrial density. Synaptic contacts are similar in size between the two axons as is the length and number of active zone dense bars at these synapses. The large-diameter axon, however, exhibits a twofold larger area of nerve terminal than the small-diameter axon resulting in a higher density of synapses per muscle fiber. Hence, differences in synaptic density may in part account for differences in synaptic output between these paired phasic axons.

Preserving transfer independence among individuals with spinal cord injury.

STUDY DESIGN: Literature review. OBJECTIVES: Upper extremity (UE) joint degeneration, particularly at the shoulder, detrimentally influences functional independence, quality of life, cardiovascular disease risk, and life expectancy of individuals following spinal cord injury (SCI). This review (1) describes UE use for transfers among individuals with SCI; (2) describes contributing factors associated with UE joint degeneration and loss of transfer independence; (3) summarizes and identifies gaps in existing research; and (4) provides suggestions for future research. RESULTS: Investigations of wheelchair transfer related UE joint and function preservation among individuals with SCI should consider factors including age and length of time from SCI onset, interface between subject-wheelchair, pain, shoulder joint range of motion (ROM) and muscle strength deficiencies or imbalances, exercise capacity and tolerance for the physical strain of activities of daily living (ADL), body mass and composition, previous UE injury or disease history, and transfer techniques. Existing studies of transfers among individuals with SCI have relied on small groups of either asymptomatic or non-impaired subjects, with minimal integration of kinematic, kinetic and electromyographic data. Descriptions of UE joint ROM, forces, and moments produced during transfers are lacking. CONCLUSIONS: Biomechanical measurement and computer modeling have provided increasingly accurate tools for acquiring the data needed to guide intervention planning to prevent UE joint degeneration and preserve function among individuals with SCI. The identification of stressful sub-components during transfers will enable intervening clinicians and engineers who design and modify assistive and adaptive devices to better serve individuals with SCI.

The basics of heart failure management: are they being ignored?

BACKGROUND: Advances have been made in the medical management of congestive heart failure. However, there is concern that these changes may not be transmitted to the heart failure population in the community. Other impediments to improved prognosis, such as failure to apply non-pharmacological strategies and poor patient comprehension may also be prevalent in the community. AIMS: The purpose of this study was to assess physician practice and patient knowledge in a heart failure population admitted to a University Hospital in Ireland. METHODS: Patients admitted with a primary diagnosis of heart failure were studied. Estimation of ejection fraction was used to subdivide the population into heart failure with impaired and normal systolic function. Patients' course in hospital was noted with reference to management by cardiology or internal medicine, use of angiotensin-converting enzyme inhibition therapy and digoxin and application of dietary and rehabilitative services. Patient knowledge was assessed by questionnaire. RESULTS: Eighty patients were included in this study. Two-thirds of the population had impaired systolic function. The majority of patients were managed by internal medicine physicians, and this population was older and more likely to have normal systolic function. Prescription of converting enzyme inhibitor therapy was more frequently used in cardiology-managed patients (96 vs. 70%, P<0.05). Neither group applied dietary or rehabilitative advice to a significant level. Patient comprehension was poor, especially with regard to understanding of medicine and the value of weight measurement. CONCLUSION: The above data demonstrate a lack of use of rehabilitative and dietary services and poor patient knowledge. These deficiencies may play a role in determining outlook and may impede the expected improvement in prognosis that has been witnessed in large randomised studies.

The conduction of protons in different stereoisomers of dioxolane-linked gramicidin A channels.

Two different stereoisomers of the dioxolane-linked gramicidin A (gA) channels were individually synthesized (the SS and RR dimers;. Science. 244:813-817). The structural differences between these dimers arise from different chiralities within the dioxolane linker. The SS dimer mimics the helicity and the inter- and intramolecular hydrogen bonding of the monomer-monomer association of gA's. In contrast, there is a significant disruption of the helicity and hydrogen bonding pattern of the ion channel in the RR dimer. Single ion channels formed by the SS and RR dimers in planar lipid bilayers have different proton transport properties. The lipid environment in which the different dimers are reconstituted also has significant effects on single-channel proton conductance (g(H)). g(H) in the SS dimer is about 2-4 times as large as in the RR. In phospholipid bilayers with 1 M [H(+)](bulk), the current-voltage (I-V) relationship of the SS dimer is sublinear. Under identical experimental conditions, the I-V plot of the RR dimer is supralinear (S-shaped). In glycerylmonooleate bilayers with 1 M [H(+)](bulk), both the SS and RR dimers have a supralinear I-V plot. Consistent with results previously published (. Biophys. J. 73:2489-2502), the SS dimer is stable in lipid bilayers and has fast closures. In contrast, the open state of the RR channel has closed states that can last a few seconds, and the channel eventually inactivates into a closed state in either phospholipid or glycerylmonooleate bilayers. It is concluded that the water dynamics inside the pore as related to proton wire transfer is significantly different in the RR and SS dimers. Different physical mechanisms that could account for this hypothesis are discussed. The gating of the synthetic gA dimers seems to depend on the conformation of the dioxolane link between gA's. The experimental results provide an important framework for a detailed investigation at the atomic level of proton conduction in different and relatively simple ion channel structures.

Visible evidence for differences in synaptic effectiveness with activity-dependent vesicular uptake and release of FM1-43.

Activity-dependent uptake and release of the fluorescent probe FM1-43 were used to compare synaptic performance (rates of transmitter release and synaptic vesicle turnover) at different frequencies in phasic and tonic motor neurons innervating the crayfish leg extensor muscle and in the tonic motor neuron of the opener muscle. The phasic extensor motor neuron, which has a high quantal content of transmitter release, accumulated and released FM1-43 more rapidly than the tonic motor neuron, especially at low frequencies of stimulation. Individual bright spots appeared on the varicosities of the junctional terminals during stimulation in FM1-43; these spots corresponded to zones of immunostaining for the synaptic vesicle associated protein synaptotagmin, but they were larger and less numerous than synapses identified by electron microscopy and appear to represent one to several synapses with their associated clusters of synaptic vesicles. The number of bright spots observed on varicosities of the tonic terminal after stimulation at >/=20 Hz is generally similar to values for responding units (n) calculated from binomial distributions derived from quantal analysis. At frequencies of

Interdisciplinary pain assessment of spinal cord injury patients.

The purpose of "Interdisciplinary Pain Assessment of Spinal Cord Injury Patients," a model project funded by the American Association of Spinal Cord Injury Nurses, was to evaluate the McGill-Melzack Pain Questionnaire (MMPQ) for effectiveness in assessing pain in persons with spinal cord injury (SCI). Currently, the MMPQ is the instrument of choice for assessment of pain; however, normative psychometric data for use of the MMPQ for SCI related pain does not exist. Specifically, the research question addressed was "does the MMPQ adequately assess pain in patients with altered neurological pathways due to SCI?" To answer this question, an integrated literature search was conducted to identify pain characteristics of SCI-related pain types for comparison with the MMPQ pain characteristics in order to determine initial generlizability of the MMPQ to the seven defined SCI pain types. Secondly, 27 subjects with SCI (9 quadriplegic and 18 paraplegic subjects) were admitted voluntarily to the study over a five month interval. All subjects were asked to independently describe their pain, and locate their pain on a blank human body diagram, complete the MMPQ, and rate their pain severity by use of the pain visual graphic rating scale. Then MMPQ was determined to adequately present SCI pain adjectives. Overall, the MMPQ does provide a systematic framework for comprehensive assessment for the types of pain associated with SCI patients. Based on the findings of this study with a limited sample size, the MMPQ did differentiate pain experience by patients who are quadriplegic or paraplegic. The detailed procedure and results of this model project are presented in this article.