Design and implementation of electron diverters for lobster eye space-based X-ray optics.

Micropore optics have recently been implemented in a lobster eye geometry as a compact X-ray telescope. Fields generated by rare-earth magnets are used to reduce the flux of energetic electrons incident upon the focal plane detector in such a setup. We present the design and implementation of the electron diverters for X-ray telescopes of two upcoming missions: the microchannel X-ray telescope onboard the space-based multiband astronomical variable objects monitor and the soft X-ray instrument onboard the solar wind magnetosphere ionosphere link explorer. Electron diverters must be configured to conform to stringent limits on their total magnetic dipole moment and be compensated for any net moment arising from manufacturing errors. The two missions have differing designs, which are presented and evaluated in terms of the fractions of electrons reaching the detector, as determined by relativistic calculations of electron trajectories. The differential flux of electrons to the detector is calculated, and the integrated electron background is determined for both designs.

Falling through the gap: Dental treatment experiences of patients affected by cleft lip and/or palate.

Introduction: In the UK, one in 600­700 infants is born with a cleft lip and/or palate (CL/P). Previous research has identified patients with CL/P to be at high risk of long-term oral health issues. Yet, few of these patients are currently accessing community dental care. Aims: To assess patients' dental treatment experiences and their suggestions for improving services. Materials and methods: Five focus groups were conducted with 24 adults with CL/P. Thematic analysis was performed on the data. Results: Participants perceived local dental practitioners to lack knowledge about CL/P and its treatment. Consequently, some participants had stopped visiting a dental practice altogether. Participants were also largely unaware of the specialist CL/P services they are entitled to. Discussion: Suggestions are made for the integration of improved training and resources for local dental practitioners. Closer communication between specialist cleft teams and local dental practitioners could also help to bridge the gap in knowledge and improve patients' engagement with dental services. The tertiary sector has a crucial role to play in empowering patients to take more control of their oral health and dental treatment.

Food for thought: pilot randomized controlled trial of lay health trainers supporting dietary change to reduce cardiovascular disease in deprived communities.

BACKGROUND: Cardiovascular disease (CVD) accounts for 30% of UK deaths. It is associated with modifiable lifestyle factors, including insufficient consumption of fruit and vegetables (F&V). Lay health trainers (LHTs) offer practical support to help people develop healthier behaviour and lifestyles. Our two-group pilot randomized controlled trial (RCT) investigated the effectiveness of LHTs at promoting a heart-healthy lifestyle among adults with at least one risk factor for CVD to inform a full-scale RCT. METHODS: Eligible adults (aged 21-78 years), recruited from five practices serving deprived populations, were randomized to health information leaflets plus LHTs' support for 3 months (n = 76) versus health information leaflets alone (n = 38). RESULTS: We recruited 114 participants, with 60% completing 6 month follow-up. Both groups increased their self-reported F&V consumption and we found no evidence for LHTs' support having significant added impact. Most participants were relatively less deprived, as were the LHTs we were able to recruit and train. CONCLUSIONS: Our pilot demonstrated that an LHT's RCT whilst feasible faces considerable challenges. However, to justify growing investment in LHTs, any behaviour changes and sustained impact on those at greatest need should be demonstrated in an independently evaluated, robust, fully powered RCT.

Improvements to Rapfish: a rapid evaluation technique for fisheries integrating ecological and human dimensions.

This paper reports recent developments in Rapfish, a normative, scalable and flexible rapid appraisal technique that integrates both ecological and human dimensions to evaluate the status of fisheries in reference to a norm or goal. Appraisal status targets may be sustainability, compliance with a standard (such as the UN code of conduct for responsible fisheries) or the degree of progress in meeting some other goal or target. The method combines semi-quantitative (e.g. ecological) and qualitative (e.g. social) data via multiple evaluation fields, each of which is assessed through scores assigned to six to 12 attributes or indicators: the scoring method allows user flexibility to adopt a wide range of utility relationships. For assessing sustainability, six evaluation fields have been developed: ecological, technological, economic, social, ethical and institutional. Each field can be assessed directly with a set of scored attributes, or several of the fields can be dealt with in greater detail using nested subfields that themselves comprise multidimensional Rapfish assessments (e.g. the hierarchical institutional field encompasses both governance and management, including a detailed analysis of legality). The user has the choice of including all or only some of the available sustainability fields. For the attributes themselves, there will rarely be quantitative data, but scoring allows these items to be estimated. Indeed, within a normative framework, one important advantage with Rapfish is transparency of the rigour, quality and replicability of the scores. The Rapfish technique employs a constrained multidimensional ordination that is scaled to situate data points within evaluation space. Within each evaluation field, results may be presented as a two-dimensional plot or in a one-dimensional rank order. Uncertainty is expressed through the probability distribution of Monte-Carlo simulations that use the C.L. on each original observation. Overall results of the multidisciplinary analysis may be shown using kite diagrams that compare different locations, time periods (including future projections) and management scenarios, which make policy trade-offs explicit. These enhancements are now available in the R programming language and on an open website, where users can run Rapfish analyses by downloading the software or uploading their data to a user interface.

Cocaine administration produces a protracted decoupling of neural and haemodynamic responses to intense sensory stimuli.

Evidence suggests that for relatively weak sensory stimuli, cocaine elevates background haemodynamic parameters but still allows enhanced neural responses to be reflected in enhanced haemodynamic responses. The current study investigated the possibility that for more intense stimuli, the raised background may produce a protracted attenuation of the haemodynamic response. Three experiments were performed to measure effects of i.v. cocaine administration (0.5 mg/kg) or saline on responses in rat barrel cortex to electrical stimulation of the whisker pad. The first experiment used optical imaging spectroscopy (OIS) and laser Doppler flowmetry (LDF) to measure haemodynamic changes. Cocaine caused an increase in baseline blood flow (peak approximately 90%), which lasted for the duration of the test period (25 min). Haemodynamic responses to whisker stimulation were substantially reduced throughout. The second experiment used a 16-channel multi-electrode to measure evoked potentials at 100 mum intervals through the barrel cortex. Summed neural responses (collapsed across the spatial dimension) after cocaine administration were similar to those after saline. The third experiment extended experiment 1 by examining the effects of cocaine on whisker sensory responses using functional magnetic resonance imaging (and concurrent OIS or LDF). Cocaine caused a similar increase in baseline and reduction in the evoked response to that seen in experiment 1. Together, the results of these three experiments show that cocaine produces a protracted decoupling of neural activity and haemodynamic responses to intense sensory stimulation, which suggests that imaging techniques based on changes in haemodynamic parameters may be unsuitable for studying the effects of cocaine on sensory processing in humans.

Design and initial evaluation of a low-cost 3-Tesla research system for combined optical and functional MR imaging with interventional capability.

A 3-Tesla research system has been developed for functional and interventional magnetic resonance imaging (MRI) procedures on animal models based on a low field niche spectrometer. Use of two stages of fourth harmonic frequency multiplication has allowed us to produce a high-frequency spectrometer with good frequency stability based on a low-frequency direct digital synthesizer. The system has been designed with the ability to introduce interventional tools such as biopsy needles, radiofrequency (RF) electrodes, and fiber optics for optical spectroscopy and thermal ablation as well as drug infusions to allow function to be studied in the presence of external challenges. Full MR-compatible physiologic support capability allows animals to be maintained in a stable condition over extended periods of study. Functional MR images have been acquired by using gradient echoes (TR/TE = 40/12 msec) from the rat whisker barrel cortex using electrical stimulation (5-V, 1.5-mA, 1-msec pulses at 5 Hz via two needle electrodes inserted into the rat whisker pad). Initial results using respiratory gas challenges of 100% N(2), 100% O(2), and 10% CO(2) have shown excellent agreement between single wavelength (633 nm) optical and functional MR time series with subsecond time resolution. The 1-mm copper electrodes for interventional radiofrequency ablation procedures were easily visualized in the superior colliculus by using gradient echo sequences. This novel, low-cost, high field system appears to be a useful research tool for functional and interventional studies of rat brain and allows concurrent optical spectroscopy. J. Magn. Reson. Imaging 2001;13:87-92.

Prospective 153Sm-EDTMP therapy dosimetry by whole-body scintigraphy.

Samarium-153 ethylenediaminetetramethylene phosphonic acid (153Sm-EDTMP) effectively palliates painful bony metastases, but the standard recommended administered activity of 38 MBq.kg-1 may lead to significant myelotoxicity. Prospective individual dosimetry by urine collection and counting allow the bone marrow radiation dose to be limited to 2 Gy. Our novel whole-body scintigraphic method for prospective dosimetry was compared with the 5 h urine collection technique in 10 patients with bone metastases. Anterior and posterior whole-body images were obtained using identical acquisition parameters 10 min and 5 h after the intravenous injection of 740 MBq 153Sm-EDTMP. Total counts in each imaging study were corrected for background activity and time of injection and the bone activity at 5 h was determined. Bone activity was also calculated from a complete urine collection over 5 h, and these two values were compared. MIRD formulae were applied to calculate the radiation absorbed dose to the bone marrow from the injected activity. The total activity delivering a dose of 2 Gy to the bone marrow was then determined and constituted the amount given for therapy. Values for bone activity determined by imaging and by urine counting were concordant in all patients (correlation coefficient = 0.98). The total administered activity of 153Sm-EDTMP predicted on a 2 Gy bone marrow dose varied between 35 and 63% of the standard recommended regimen of 37 MBq.kg-1 and pain relief was experienced by eight of the ten patients. Administration of 153Sm-EDTMP according to the supplier's recommendations would have delivered bone marrow doses of 3.27-5.90 Gy in our patients, doses at which myelotoxicity would have been anticipated.

166Ho-microsphere liver radiotherapy: a preclinical SPECT dosimetry study in the pig.

Liver metastases cause the majority of deaths from colorectal cancer and response to chemotherapy is poor. Intrahepatic arterial 90Y-microspheres may induce tumour regression but the beta-radiation dose is variable and cannot be determined in patients. The 81 keV gamma emission of holmium-166 (166Ho) was used to determine, by single photon emission computed tomographic (SPECT) imaging, the beta-radiation absorbed dose to normal liver in pigs following intrahepatic arterial administration of 166Ho-microspheres. The SPECT system was calibrated with anthropomorphic liver phantoms containing known activity concentrations of 166Ho-chloride. The relationship of SPECT counts to phantom activity concentration was linear with a correlation coefficient of r = 0.996. The SPECT pattern of liver distribution following successive administrations of tracer activities of 166Ho-microspheres was similar. The ratio of initial to total SPECT estimates of mean activity concentration in regions of interest, from which anatomically matched biopsy samples were later obtained and counted in an ionization chamber, showed good correlation (r = 0.924). Prospective SPECT dosimetry performed on a tracer activity of 166Ho-microspheres predicted the total administered activity required to deliver a prescribed radiation absorbed dose of 25 Gy to the liver within an error of +/- 8%. This study demonstrates the feasibility of prospective control of the absorbed radiation dose to the critical normal organ by SPECT dosimetry on a tracer dose of 166Ho-microspheres prior to administration of a therapy dose.

Medial collateral ligament knee sprains in college football. Effectiveness of preventive braces.

This is the second of 2 articles on a 3-year investigation of medial collateral ligament sprains of the knee to assess the effectiveness of prophylactic knee braces in NCAA Division I college football players. Position, string, type of session, and daily brace wear were recorded. The injury rates for braced and unbraced knees were used to create an incidence density ratio. The data were stratified and simultaneously controlled for position, string, and session and evaluated for their statistical significance. The 987 Big Ten players generated 155,772 knee exposures over the study period (50% braced). Noticeable differences existed in the rates of injury for the braced and unbraced knees in almost every position during practices, depending on player or nonplayer status. When the influential factors of position, string, and session are considered, there is a consistent but not statistically significant tendency for the players wearing preventive knee braces to experience a lower injury rate than for their unbraced counterparts. For starters and substitutes in the line positions, as well as the linebackers and tight ends, there was a consistent trend toward a lower injury rate in both practices and games. The braced players in the skill positions (backs/kickers), at least during games, exhibited a higher injury rate.

Medial collateral ligament knee sprains in college football. Brace wear preferences and injury risk.

In this prospective, multiinstitutional analysis of medial collateral ligament sprains in college football players, we categorized 987 previously uninjured study subjects according to frequency of wearing preventive knee braces, studied the patterns by which 47 of 100 injuries occurred to unbraced knees, and identified several extrinsic, sport-specific risk factors shared for both braced and unbraced knees. The attendance, brace wear choice, position, string, and session of each participant were recorded daily; medial collateral ligament sprains were reported whenever tissue damage was confirmed. Both the likelihood of wearing braces and risk of injury without them was highly dependent on session (games/practices), position group (line, linebacker/tight end, skill), and string group (players/nonplayers). Subjects wearing braces often faced a high injury risk to their unbraced knees, a finding compatible with the opinion that braces were a necessary evil, best worn when concern over danger of injury outweighed desire for speed and agility. It is concluded that to avoid misinterpretations due to the confounding influence of brace wear selection bias, accurate investigation of daily brace wear patterns is required. Then, before considing the impact of preventive knee braces, a repartitioning of the data base is essential to assure that only similar groups will be compared.

153Sm-EDTMP and melphalan chemoradiotherapy regimen for bone marrow ablation prior to marrow transplantation: an experimental model in the rat.

Chemoradiotherapy with melphalan and 153Sm-ethylenediaminetetramethylene phosphonate (EDTMP) was used to ablate bone marrow in WAG rats which were subsequently rescued by marrow transplantation. Internal irradiation of bone marrow with high doses of up to 3.5 GBq kg-1 153Sm-EDTMP alone produced profound, but self-limiting, myelosuppression and all animals recovered spontaneously. Melphalan alone in doses of 9.5 mg kg-1 also caused transient myelosuppression without mortality. However, the combination of 9.5 mg kg-1 melphalan and 555 MBq kg-1 153Sm-EDTMP caused marrow ablation and death in 80% of animals. The mortality of this chemoradiotherapy regimen was reduced to 7% by sequential administration of 153Sm-EDTMP on day 0 and melphalan on day 5 followed by marrow transfusion of 7.5 x 10(7) cells on day 6. These results were comparable to those obtained following bone marrow transplantation 24 h after lethal total body external beam irradiation. In the inbred WAG rat experimental model the sequential chemoradiotherapeutic regimen of internal irradiation with 153Sm-EDTMP followed by chemotherapy with melphalan was demonstrated to ablate bone marrow effectively whilst preserving the capacity for recovery following marrow transplantation.

A phase I study of samarium-153 ethylenediaminetetramethylene phosphonate therapy for disseminated skeletal metastases.

Thirty-five patients with disseminated skeletal metastases from a variety of tumor types underwent clinical trial of samarium-153 ethylenediaminetetramethylene phosphonate (153Sm-EDTMP) on a day-patient basis. Individual beta radiation dosimetry was based on pharmacokinetic studies of a 20 mCi tracer dose of 153Sm-EDTMP. The retained skeletal activity varied unpredictably from 40% to 95% of the administered dose, but in all patients greater than 98% of the nonosseous activity was cleared in the urine within 6 hours. Prospective calculation of radiation dosimetry in each patient permitted an accurate dosage schedule based upon total red marrow exposure, starting at 100 cGy and escalating to 280 cGy to define the dose-limiting myelotoxicity. Pain was relieved in 22 of 34 evaluable patients (65%) for periods ranging from 4 to 35 weeks, following a single administration of 153Sm-EDTMP. Recurrence of pain responded to retreatment with 153Sm-EDTMP in five of nine patients. The dose-limiting toxicity was myelosuppression manifested particularly by delayed thrombocytopenia. Platelet counts less than 100 x 10(9)/L occurred in 42% of courses when bone marrow radiation absorbed dose exceeded 200 cGy. Myelosuppression was transient and platelet counts had recovered to pretreatment levels within 10 weeks of treatment. 153Sm-EDTMP is effective for the amelioration of pain due to disseminated skeletal metastases particularly with carcinoma of breast or prostate where 83% of patients experienced pain relief. In 15 of the 34 evaluable patients there was evidence of stabilization or regression of skeletal metastases on radiographs and follow-up technetium-99m methylene diphosphonate (99mTc-MDP) bone scans.

Samarium-153 EDTMP therapy of disseminated skeletal metastasis.

153Sm-EDTMP (ethylenediaminetetramethylene phosphonate), prepared from a kit, was administered to 28 patients in a clinical trial of therapy for painful skeletal metastases unresponsive to all conventional treatment. The 103 keV gamma emission of 153Sm was utilized for prospective individual estimation of beta radiation absorbed dose to red marrow to minimize myelotoxicity and provide optimum internal radiotherapy to skeletal metastases in each patient. Pain relief occurred within 14 days of administration of 153Sm-EDTMP in 15 of 19 patients (79%) who could be evaluated at 6 weeks, when clinical response was maximal. Duration of response ranged from 4 to 35 weeks. Recurrence of pain responded to retreatment with 153Sm-EDTMP in five of eight cases. No dose-response relationship was apparent for pain relief but reversible myelotoxicity was frequently observed at radiation absorbed doses to bone marrow greater than or equal to 270 cGy. Dosimetry calculation was based on pharmacokinetic studies of a tracer administration of 153Sm-EDTMP in each patient. Assumptions inherent in this prospective method of predicting dose to bone marrow were validated experimentally. Biodistribution studies in rats demonstrated rapid skeletal uptake and long term retention of 153Sm-EDTMP in bone over 5 days. Urinary clearance accounted for 40% of injected dose, and less than 1.0% of administered activity was retained in non osseous tissue. Microdensitometry of autoradiographs of sheep vertebra and femur confirmed surface uptake of 153Sm-EDTMP in cortical bone and demonstrated relatively high trabecular bone activity which is the major component of radiation absorbed dose to bone marrow. Haematological studies in rabbits showed 153Sm-EDTMP-induced myelotoxicity to be transient and no histopathological abnormalities were demonstrable with doses ten times greater than those administered to patients.

Samarium-153 chelate localization in malignant melanoma.

153Sm, a radiolanthanide of half life 46.27 h, has a gamma emission of 0.103 MeV which is well suited to imaging, it is also a moderate energy beta emitter and tumour localization of various 153Sm chelates was evaluated in B16 murine melanoma to assess their endoradiotherapeutic potential. 153Sm was prepared from enriched 152Sm in the Australian Nuclear Science and Technology Organization reactor. 153Sm chelates were prepared from 153Sm-chloride and their chromatographic behaviour characterized. Tumour and organ uptake of 153Sm-chloride, 153Sm-citrate and the 153Sm chelates, DTPA, HEDTA, HIDA, BZ, PBH, PIH and NTA were measured at 1, 6, 24 and 48 h after intravenous administration to C57 black mice bearing either melanotic or amelanotic B16 melanoma of mean size 0.75 cm3. Histopathological examination of the tumours at each passaging assured comparability of the degree of melanogenesis and the absence of necrosis. 153Sm-chloride was immobile on chromatography and the rapid hepatic accumulation of both 153Sm-chloride and 153Sm-citrate was attributed to in vivo formation of a colloid. In contrast, 153Sm-DTPA, moving at the solvent front on chromatography, showed no reticuloendothelial accumulation in vivo and was rapidly excreted by the kidneys without tumour uptake. The other 153Sm chelates were of intermediate stability and all localized in both melanotic and amelanotic tumours, although to a significantly lesser degree than 67Ga-citrate. The relatively high 153Sm-HIDA activity in liver and 153Sm-NTA activity in bone impaired tumour definition, but on imaging of all the 153Sm chelates only 153Sm-DTPA failed to demonstrate the B16 melanoma and the best tumour delineation was obtained using 153Sm-HEDTA.

Technetium-99m antimony colloid for bone-marrow imaging.

Technetium-99m antimony colloid was prepared in our laboratory for bone-marrow imaging. Optimal production of colloid particles of size range 1-13 nm was achieved by the use of polyvinylpyrrolidone of mol. wt. 44,000. Electron microscopy was used to size the particles. Studies in rabbits showed exclusive concentration in the subendothelial dendritic phagocytes of the bone marrow. Pseudopods from these cells were found to traverse interendothelial junctions and concentrate colloid from the sinusoids. Imaging studies of bone marrow in rabbits showed the superiority of the Tc-99m antimony colloid over the much larger colloidal particles of Tc-99m sulfur colloid. Tissue distribution studies in the rat confirmed that bone-marrow uptake of Tc-99m antimony colloid was greater than that of Tc-99m sulfur colloid, although blood clearance was much slower.

Taking a closer look: time sampling and measurement error.

A person manufactured his in-seat behavior for 15, 30-min sessions so that there were three blocks of five sessions where the behavior occurred 20%, 50%, and 80% of the time. Whole interval, partial interval, and momentary time-sample measures of the behavior were taken and compared to the continuous measure of the behavior i.e., per cent of time the behavior occurred. For interval time sampling, the difference between the continuous and sample measures i.e., measurement error, was: (1) extensive, (2) unidirectional, (3) a function of the time per response, and (4) inconsistent across changes in the continuous measure. A procedural analysis demonstrated that the frequency and duration of behavior are confounded in interval time sampling. Momentary time sampling was found to be superior to interval time sampling in estimating the duration a behavior occurs.

An evaluation of time-sample measures of behavior.

Continuous and time-sample measures of the in-seat behavior of a secretary were obtained. Measurement error, i.e., the extent to which the sample measures deviated from the continuous measure, was a function of the frequency of the sample measurements and the criterion used to score an example of the behavior. If the behavior had to be exhibited throughout the observational interval (whole-interval time sampling), there was a consistent underestimate of the continuous measure. If the behavior had to be exhibited only briefly within the observational interval (partial-interval time sampling), there was a consistent overestimate of the continuous measure. And, if the behavior had to be exhibited at the end of the observational interval (momentary time sampling), overestimations and underestimations of the continuous measure occurred about equally often. As expected, the more frequently the sample measures were made the closer was the agreement between the sample and continuous measures. Two conclusions concerning measurement error in interval time sampling were made. The first was that the error will be a function of the mean time per response. The second is that this error will not be consistent across experimental conditions.