The variability of ejection fraction (EF) poses a problem in the assessment of left ventricular (LV) function in patients receiving potentially cardiotoxic chemotherapy. We sought to use global ...longitudinal strain (GLS) to compare LV responses to various cardiotoxic chemotherapy regimens and to examine the response to cardioprotection with beta-blockers (BB) in patients showing subclinical myocardial damage.
We studied 159 patients (49 ± 14 year, 127 women) receiving anthracycline (group A, n = 53, 46 ± 17 year), trastuzumab (group T, n = 61, 53 ± 12 year), or trastuzumab after anthracyclines (group AT, n = 45, 46 ± 9 year). LV indices ejection fraction (EF), mitral annular systolic velocity, and GLS were measured at baseline and follow-up (7 ± 7 months). Patients who decreased GLS by ≥11% were followed for another 6 months; initiation of BB was at the discretion of the clinician. Anthracycline dose was similar between group A and group AT (213 ± 118 vs. 216 ± 47 mg/m(2), P = 0.85). Although ΔEF was similar among the groups, attenuation of GLS was the greatest in group AT (group A, 0.7 ± 2.8% shortening; T, 1.1 ± 2.7%; and AT, 2.0 ± 2.3%; P = 0.003, after adjustment). Of 52 patients who decreased GLS by ≥-11%, 24 were treated with BB and 28 were not. GLS improved in BB groups (from -17.6 ± 2.3 to -19.8 ± 2.6%, P < 0.001) but not in non-BB groups (from -18.0 ± 2.0 to -19.0 ± 3.0%, P = 0.08). Effects of BB were similar with all regimens.
GLS is an effective parameter for identifying systolic dysfunction (which appears worst with combined anthracycline and trastuzumab therapy) and responds to cardioprotection in patients administered beta-blockers.
This paper reports the spectroscopic performance improvement of the silicon-on-insulator (SOI) pixel detector for X-ray astronomy, by introducing a double-SOI (D-SOI) structure. For applications in ...X-ray astronomical observatories, we have been developing a series of monolithic active pixel sensors, named as “XRPIXs,” based on SOI pixel technology. The D-SOI structure has an advantage that it can suppress a parasitic capacitance between the sensing node and the circuit layer, due to which the closed-loop gain cannot be increased in our conventional XRPIXs with a single-SOI (S-SOI) structure. Compared to the S-SOI XRPIX, the closed-loop gain is doubled in the D-SOI XRPIX. The readout noise is effectively lowered to 33% (16 e− (rms)), and the energy resolution at 6.4 keV is improved by a factor of 1.7 (290 eV in FWHM). The suppression of the parasitic capacitance is also quantitatively evaluated based on the results of capacitance extraction simulation from the layout. This evaluation provides design guidelines for further reduction of the readout noise.
We designed a versatile analog front-end chip, called LTARS, for TPC-applications, primarily targeted at dual-phase liquid Ar-TPCs for neutrino experiments and negative-ion μ-TPCs for directional ...dark matter searches. Low-noise performance and wide dynamic range are two requirements for reading out the signals induced on the TPC readout channels. One of the development objectives is to establish the analog processing circuits under low temperature operation, which are designed on function block basis as reusable IPs (Intellectual Properties). The newly developed ASIC was implemented in the Silterra 180 nm CMOS technology and has 16 readout channels. We carried out the performance test at room temperature and the results showed an equivalent noise charge of 2695±71 e− (rms) with a detector capacitance of 300 pF. The dynamic range was measured to be 20–100 fC in the low-gain mode and 200–1600 fC in the high-gain mode within 10% integral nonlinearity at room temperature. We also tested the performance at the liquid-Ar temperature and found a deterioration of the noise level with a longer shaper time. Based on these results, we also discuss a unique simulation methodology for future cold-electronics development. This method can be applicable to design the electronics used at low temperature.
We have developed a gating foil for the time projection chamber envisaged as a central tracker for the international linear collider experiment. It has a structure similar to the Gas Electron ...Multiplier (GEM) with a higher optical aperture ratio and functions as an ion gate without gas amplification. The transmission rate for electrons was measured in a counting mode for a wide range of the voltages applied across the foil using an 55Fe source and a laser in the absence of a magnetic field. The blocking power of the foil against positive ions was estimated from the electron transmissions.
Background Quality‐switched (QS) lasers are well‐known effective treatment for removing solar lentigines. However, the high incidence of post‐inflammatory hyperpigmentation (PIH) raises concern in ...darker skin types. This is the first study comparing efficacies and incidences of PIH in Asian skin with different degrees of irradiation between two QS lasers.
Method In total, 355 solar lentigines in 193 cases, skin types III–V, were randomly divided into four groups. All cases received single laser treatment. Clinical results were evaluated after 4 weeks. Groups 1 and 3 were treated ‘aggressively’ with endpoints of very obvious immediate whitening (IW) of the lesion. Groups 2 and 4 were treated ‘mildly’ with endpoints of slight IW of the lesion. Groups 1 and 2 were irradiated with the QS ruby, and groups 3 and 4 with the QS frequency doubled Nd:YAG laser.
Results There were no statistically significant differences in degrees of clearance among the four groups. However, PIH incidences were very different: 33.33%, 7.47%, 23.18% and 8.47% in groups 1, 2, 3 and 4 respectively. The difference between aggressively and mildly irradiated groups (1 and 3 vs. 2 and 4) was statistically significant (P < 0.001). However, there was no statistical difference between the two aggressively or the two mildly irradiated groups. There were no significant differences between skin types.
Conclusion Aggressive irradiation using QS lasers resulted in a high PIH incidence, while having no advantage in efficacy. For darker skin types, mild irradiation reduces the PIH risk with no disadvantage in efficacy.
Fibrates, the PPARα ligand-like compounds increase the expression of proximal tubule liver fatty acid binding protein (L-FABP) and significantly decrease cisplatin-induced acute kidney injury. To ...study whether the bezafibrate-mediated upregulation of renal L-FABP was involved in this cytoprotective effect we treated transgenic mice of PPAR agonists inducible human L-FABP expression with cisplatin in the presence or absence of bezafibrate. Blood urea nitrogen was unchanged in the first day but increased 3 days after cisplatin. While urinary L-FABP increased over 100-fold 1 day after cisplatin treatment in the transgenic mice it was significantly reduced when these transgenic mice were pretreated with bezafibrate. Cisplatin-induced renal necrosis and apoptosis were significantly reduced in bezafibrate pretreated transgenic mice and this correlated with decreased accumulation of lipid and lipid peroxidation products. Immunohistochemical analysis of kidney tissue of bezafibrate-cisplatin-treated transgenic mice showed preservation of cytoplasmic L-FABP in the proximal tubule, but this was reduced in transgenic mice treated only with cisplatin. L-FABP mRNA and protein levels were significantly increased in bezafibrate-cisplatin-treated transgenic mice when compared to mice not fibrate treated. Our study shows that the bezafibrate-mediated upregulation of proximal tubule L-FABP plays a pivotal role in the reduction of cisplatin-induced acute kidney injury.
Previous studies from our laboratory showed that increased fatty acid oxidation by the kidney is cytoprotective during cisplatin (CP)-mediated nephrotoxicity. In this study, we determined the effects ...of CP and fibrates on peroxisome proliferation and the expression of liver fatty acid-binding protein (L-FABP) in normal mice, and in mice transgenically overexpressing human L-FABP (h-L-FABP). Labeling of peroxisomes demonstrated reduced peroxisomal staining in the proximal tubule of CP-treated mice compared with control mice. There was increased peroxisomal labeling in the proximal tubules of both control and CP-treated mice when either was treated with fibrate; a known peroxisome proliferator-activated receptor-α ligand. L-FABP protein expression, not detected in control or CP-treated mice, was significantly increased in the proximal tubules of fibrate-treated mice of either group. In the transgenic mice, CP increased the shedding of h-L-FABP in the urine, which was decreased by fibrate as was the acute renal failure. A cytosolic pattern of h-L-FABP expression was found in the proximal tubules of untreated transgenic mice with a nuclear presence in CP-treated mice. Fibrate pretreatment restored the cytosolic expression pattern in CP-treated mice. Our study shows that fibrate may improve CP-induced acute renal failure due to both peroxisome proliferation and increased L-FABP in the cytosol of the proximal tubule.
We have been developing the X-ray silicon-on-insulator (SOI) pixel sensor called XRPIX for future astrophysical satellites. XRPIX is a monolithic active pixel sensor consisting of a high-resistivity ...Si sensor, thin SiO2 insulator, and CMOS pixel circuits that utilize SOI technology. Since XRPIX is capable of event-driven readouts, it can achieve high timing resolution greater than ∼10 μs, which enables low background observation by adopting the anti-coincidence technique. One of the major issues in the development of XRPIX is the electrical interference between the sensor layer and circuit layer, which causes nonuniform detection efficiency at the pixel boundaries. In order to reduce the interference, we introduce a Double-SOI (D-SOI) structure, in which a thin Si layer (middle Si) is added to the insulator layer of the SOI structure. In this structure, the middle Si layer works as an electrical shield to decouple the sensor layer and circuit layer. We measured the detector response of the XRPIX with D-SOI structure at KEK. We irradiated the X-ray beam collimated with 4 μmφ pinhole, and scanned the device with 6 μm pitch, which is 1/6 of the pixel size. In this paper, we present the improvement in the uniformity of the detection efficiency in D-SOI sensors, and discuss the detailed X-ray response and its physical origins.
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