In this paper, we describe the development of monolithic pixel detectors using silicon-on-insulator (SOI) technology for a rapid X-ray residual stress measurement system. Conventional two-dimensional ...X-ray detectors are not suitable for rapid X-ray residual stress measurement because of their large pixel size and slow readout. For this reason, we developed highly sensitive SOI monolithic pixel detectors that are made up of smaller pixels and can provide a more rapid X-ray residual stress measurement readout. The detectors are fabricated using a 0.2μm CMOS fully-depleted SOI process (Lapis Semiconductor Co., Ltd). The SOI wafer is made by directly bonding a thick, high-resistivity Si wafer and a low-resistivity Si CMOS wafer. The process does not make use of mechanical bump bonding. We developed an integration-type SOI pixel detector, INTPIX4, for a rapid X-ray residual stress measurement system; it uses a float zone (FZ) or Czochralski (Cz) silicon wafer. Cz SOI detectors have been in use since 2005. After 2011, FZ SOI detectors were successfully fabricated. In this paper, we state recent progresses and test results of the SOI monolithic pixel detector using a FZ silicon and compare them with the results obtained using the Cz detector.
The temperature response functions of the
Yohkoh
/SXT are re-calculated based on the most recent elemental abundances and ionization balance available in the CHIANTI atomic database version 6.0.1. ...The new standard responses are calculated for three types of abundance;
i.e.
, ‘coronal’, ‘hybrid’, and ‘photospheric’ abundances included in the CHIANTI database, and are available in SolarSoft since 2010. Comparison plots of the new and old response functions and filter ratios are available at the Yohkoh Legacy data Archive (
http://solar.physics.montana.edu/ylegacy
). The three new responses generally peak at higher temperatures (at ≈ 10 MK) than the former standard response (at ≈ 5.6 MK) based on Mewe’s spectral model. The new responses with coronal and hybrid abundances have higher peak counts by a factor of 3 and 2, respectively, than those with the photospheric abundances and the former response based on Mewe’s model. The correction of the filter ratios depends on the type of filter and the range of the ratios to be used. In the significant cases, the new filter ratio produces 20 to 30% higher temperatures than the previous calibration. The choice of elemental abundance has a strong influence on the derived temperatures and emission measures, and often produces a variation significantly larger than the statistical and systematic errors considered so far.
Diamond has two crystallographically inequivalent sites in the unit cell. In doped diamond, dopant occupation in the two sites is expected to be equal. Nevertheless, preferential dopant occupation ...during growth under nonequilibrium conditions is of fundamental importance, for example, to enhance the properties of nitrogen-vacancy (N-V) centers; therefore, this is a promising candidate for a qubit. However, the lack of suitable experimental techniques has made it difficult to study the crystal- and chemical-site-resolved local structures of dopants. Here, we confirm the identity of two chemical sites with asymmetric dopant incorporation in the diamond structure, via the photoelectron holography (PEH) of heavily phosphorus (P)-doped diamond prepared by chemical vapor deposition. One is substitutionally incorporated P with preferential site occupations and the other can be attributed to a PV split vacancy complex with preferential orientation. The present study shows that PEH is a valuable technique to study the local structures around dopants with a resolution of crystallographically inequivalent but energetically equivalent sites/orientations. Such information provides strategies to improve the properties of dopant related-complexes in which alignment is crucial for sensing of magnetic field or quantum spin register using N-V centers in diamond.
To provide an update review of the best quality evidence for the clinical effectiveness and cost-effectiveness of donepezil, rivastigmine and galantamine for mild to moderately severe Alzheimer's ...disease (AD) and of memantine for moderately severe to severe AD.
Electronic databases, experts in the field and manufacturer submissions to the National Institute for Health and Clinical Excellence (NICE).
A systematic review of the literature and an economic evaluation were undertaken. The quality of included randomised controlled trials (RCTs) was assessed using criteria developed by the NHS Centre for Reviews and Dissemination. An outline assessment of economic evaluations was undertaken using a standard checklist. The clinical and cost-effectiveness data were synthesised through a narrative review with full tabulation of the results of included studies. Where appropriate, meta-analysis of data was undertaken.
For mild to moderately severe AD, the results of the study suggested that all three treatments were beneficial when assessed using cognitive outcome measures. Global outcome measures were positive for donepezil and rivastigmine, but mixed for galantamine. Results for measures of function were mixed for donepezil and rivastigmine, but positive for galantamine. Behaviour and mood measures were mixed for donepezil and galantamine, but showed no benefit for rivastigmine. For memantine, two published RCTs were included; in one of these trials the participants were already being treated with donepezil. The results suggest that memantine is beneficial when assessed using functional and global measurements. The effect of memantine on cognitive and behaviour and mood outcomes is, however, less clear. Literature on the cost-effectiveness of donepezil, rivastigmine and galantamine was dominated by industry-sponsored studies, and studies varied in methods and results. Of the three UK studies, two report donepezil as not cost-effective, whereas a third study reports an additional cost (1996 pounds sterling) of between 1200 pounds sterling and 7000 pounds sterling per year in a non-severe AD health state (concerns over these estimates are raised, suggesting that they may underestimate the true cost-effectiveness of donepezil). Cost-effectiveness analysis undertaken in this review suggests that donepezil treatment has a cost per quality-adjusted life-year (QALY) in excess of 80,000 pounds sterling, with donepezil treatment reducing the mean time spent in full-time care (delays progression of AD) by 1.42-1.59 months (over a 5-year period). From four published cost-effectiveness studies, two UK studies report additional costs associated with rivastigmine treatment. Cost-effectiveness analysis undertaken in the current review suggests that rivastigmine treatment has a cost per QALY in excess of 57,000 pounds sterling, with rivastigmine treatment reducing the mean time spent in full-time care (delays progression) by 1.43-1.63 months (over a 5-year period). From five published cost-effectiveness studies, one UK study reports a cost per QALY of 8693 pounds sterling for 16-mg galantamine treatment and 10,051 pounds sterling for 24-mg galantamine treatment (concerns raised suggest that this may underestimate the true cost-effectiveness of galantamine). Cost-effectiveness analysis undertaken in the present review suggests that galantamine treatment has a cost per QALY in excess of 68,000 pounds sterling, with galantamine reducing the time spent in full-time care (delays progression) by 1.42-1.73 months (over a 5-year period). From two published cost-effectiveness studies, one reports analysis for the UK, finding that memantine treatment results in cost savings and benefits in terms of delaying disease progression (concerns raised suggest that this may underestimate the true cost-effectiveness of memantine). In the current review, the cost-effectiveness of memantine has not been modelled separately, but where alternative parameter inputs on the cost structure and utility values have been used in a reanalysis using the industry model, the cost-effectiveness is reported at between 37,000 pounds sterling and 52,000 pounds sterling per QALY, with this alternative analysis still based on what is regarded as an optimistic or favourable effectiveness profile for memantine.
Although results from the clinical effectiveness review suggest that these treatments may be beneficial, a number of issues need to be considered when assessing the results of the present review, such as the characteristics of the participants included in the individual trials, the outcome measures used, the length of study duration, the effects of attrition and the relationship between statistical significance and clinical significance. Many included trials were sponsored by industry. For donepezil, rivastigmine and galantamine, the cost savings associated with reducing the mean time spent in full-time care do not offset the cost of treatment sufficiently to bring estimated cost-effectiveness to levels generally considered acceptable by NHS policy makers. It is difficult to draw conclusions on the cost-effectiveness of memantine; it is suggested that further amendments to the potentially optimistic industry model (measure of effect) would offer higher cost per QALY estimates. Future research should include: information on the quality of the outcome measures used; development of quality of life instruments for patients and carers; studies assessing the effects of these interventions of durations longer than 12 months; comparisons of benefits between interventions; and research on the prediction of disease progression.
To assess the clinical effectiveness and cost-effectiveness of ranibizumab and pegaptanib for subfoveal choroidal neovascularisation (CNV) associated with wet age-related macular degeneration (AMD).
...Electronic databases were searched from inception to September 2006. Experts in the field were consulted and manufacturers' submissions were examined.
The quality of included studies was assessed using standard methods and the clinical effectiveness data were synthesised through a narrative review with full tabulation of results. A model was developed to estimate the cost-effectiveness of ranibizumab and of pegaptanib (separately), compared with current practice or best supportive care, from the perspective of the NHS and Personal Social Services. Two time horizons were adopted for each model. The first adopted time horizons determined by the available trial data. The second analysis extrapolated effects of treatment beyond the clinical trials, adopting a time horizon of 10 years.
The combined analysis of two randomised controlled trials (RCTs) of pegaptanib 0.3 mg (licensed dose), 1.0 mg and 3.0 mg versus sham injection in patients with all lesion types was reported by three publications (the VISION study). Three published RCTs of ranibizumab were identified (MARINA, ANCHOR, FOCUS), and an additional unpublished RCT was provided by the manufacturer (PIER). Significantly more patients lost less than 15 letters of visual acuity at 12 months when taking pegaptanib (0.3 mg: 70% of patients; 1.0 mg: 71% of patients; 3.0 mg: 65% of patients) or ranibizumab (0.3 mg: 94.3-94.5%; 0.5 mg: 94.6-96.4%) than sham injection patients (55% versus pegaptanib and 62.2% versus ranibizumab) or, in the case of ranibizumab, photodynamic therapy (PDT) (64.3%). The proportion of patients gaining 15 letters or more (a clinically important outcome having a significant impact on quality of life) was statistically significantly greater in the pegaptanib group for doses of 0.3 and 1.0 mg but not for 3.0 mg, and for all ranibizumab groups compared to the sham injection groups or PDT. This was also statistically significant for patients receiving 0.5 mg ranibizumab plus PDT compared with PDT plus sham injection. Pegaptanib patients lost statistically significantly fewer letters after 12 months of treatment than the sham group mean letters lost: 7.5 (0.3 mg), 6.5 (1.0 mg) or 10 (3.0 mg) vs 14.5 (sham). In the MARINA and ANCHOR trials, ranibizumab patients gained letters of visual acuity at 12 months whereas patients with sham injection or PDT lost about 10 letters (p<0.001) and in the PIER study, ranibizumab patients lost significantly fewer than the sham injection group. Significantly fewer patients receiving pegaptanib or ranibizumab deteriorated to legal blindness compared with the control groups. Adverse events were common for both pegaptanib andranibizumab but most were mild to moderate. Drug costs for 1 year of treatment were estimated as 4626 pounds for pegaptanib and 9134 pounds for ranibizumab. Non-drug costs accounted for an additional 2614 pounds for pegaptanib and 3120 pounds for ranibizumab. Further costs are associated with the management of injection-related adverse events, from 1200 pounds to 2100 pounds. For pegaptanib compared with usual care, the incremental cost-effectiveness ratio (ICER) ranged from 163,603 pounds for the 2-year model to 30,986 pounds for the 10-year model. Similarly, the ICERs for ranibizumab for patients with minimally classic and occult no classic lesions, compared with usual care, ranged from 152,464 pounds for the 2-year model to 25,098 pounds for the 10-year model.
Patients with AMD of any lesion type benefit from treatment with pegaptanib or ranibizumab on measures of visual acuity when compared with sham injection and/or PDT. Patients who continued treatment with either drug appeared to maintain benefits after 2 years of follow-up. When comparing pegaptanib and ranibizumab, the evidence was less clear due to the lack of direct comparison through head-to-head trials and the lack of opportunity for indirect statistical comparison due to heterogeneity. The cost-effectiveness analysis showed that the two drugs offered additional benefit over the comparators of usual care and PDT but at increased cost. Future research should encompass trials to compare pegaptanib with ranibizumab and bevacizumab, and to investigate the role of verteporfin PDT in combination with these drugs. Studies are also needed to assess adverse events outside the proposed RCTs, to consider the optimal dosing regimes of these drugs and the benefits of re-treatment after initial treatment, and to review costing in more detail. Health state utilities and their relationship with visual acuity and contrast sensitivity, the relationship between duration of vision loss and the quality of life and functional impact of vision loss, behavioural studies of those genetically at risk are other topics requiring further research.
Physiological significance of synaptic Zn(2+) signaling was examined in the CA1 of young rats. In vivo CA1 long-term potentiation (LTP) was induced using a recording electrode attached to a ...microdialysis probe and the recording region was locally perfused with artificial cerebrospinal fluid (ACSF) via the microdialysis probe. In vivo CA1 LTP was inhibited under perfusion with CaEDTA and ZnAF-2DA, extracellular and intracellular Zn(2+) chelators, respectively, suggesting that the influx of extracellular Zn(2+) is required for in vivo CA1 LTP induction. The increase in intracellular Zn(2+) was chelated with intracellular ZnAF-2 in the CA1 1h after local injection of ZnAF-2DA into the CA1, suggesting that intracellular Zn(2+) signaling induced during learning is blocked with intracellular ZnAF-2 when the learning was performed 1h after ZnAF-2DA injection. Object recognition was affected when training of object recognition test was performed 1h after ZnAF-2DA injection. These data suggest that intracellular Zn(2+) signaling in the CA1 is required for object recognition memory via LTP. Surprisingly, in vivo CA1 LTP was affected under perfusion with 0.1-1μM ZnCl2, unlike the previous data that in vitro CA1 LTP was enhanced in the presence of 1-5μM ZnCl2. The influx of extracellular Zn(2+) into CA1 pyramidal cells has bidirectional action in CA1 LTP. The present study indicates that the degree of extracellular Zn(2+) influx into CA1 neurons is critical for LTP and cognitive performance.
A search for dark matter using an underground single-phase liquid xenon detector was conducted at the Kamioka Observatory in Japan, particularly for Weakly Interacting Massive Particles (WIMPs). We ...have used 705.9 live days of data in a fiducial volume containing 97kg of liquid xenon at the center of the detector. The event rate in the fiducial volume after the data reduction was (4.2±0.2)×10−3day−1kg−1keVee−1 at 5keVee, with a signal efficiency of 20%. All the remaining events are consistent with our background evaluation, mostly of the “mis-reconstructed events” originated from 210Pb in the copper plates lining the detector's inner surface. The obtained upper limit on a spin-independent WIMP-nucleon cross section was 2.2×10−44cm2 for a WIMP mass of 60GeV/c2 at the 90% confidence level, which was the most stringent limit among results from single-phase liquid xenon detectors.
Highlights • After spinal injury of goldfish, fibrous scar was formed in the lesion site. • Regenerating axons entering the fibrous scar were usually accompanied by glial processes. • Regenerating ...axons pass the fibrous scar through laminin-coated tubular structures. • Invasion of glial processes into the tubular structures reduces the fibrous scar area. • Regenerating axons increase in parallel with the reduction of fibrous scar area.
Abstract
The behaviour of I in soil depends on its chemical form in soil solution. Stable I (127I) in the soil solution under actual soil conditions was investigated as a natural analogue of ...long-lived radioiodine (129I). Soil samples were collected at 5-cm depth intervals down to 20 cm from forests and grasslands in Rokkasho, where the Japanese first commercial nuclear fuel reprocessing plant is located, and the soil solution was extracted by centrifugation. Almost half of total I in the soil solution was iodide, and the other half was dissolved organic I (DOI), with iodate under the detection limit. The proportion of DOI in total I at 0–5 cm depth was larger than the proportions at 5–20 cm depth. The concentration of DOI was positively correlated with that of DOC in the soil solution, suggesting that the behaviour of DOI in the surface soil is affected by labile organic matter dynamics.
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