Search

Study question Is it possible to identify the optimal puncture position by image analysis where oocyte degeneration is reduced in ICSI procedure? Summary answer Visualizing the likelihood of unintentional membrane rupture (UMR) using image analysis can reduce oocyte degeneration and thereby generate more embryos available for treatment. What is known already It is known that the oocyte degeneration after both conventional-ICSI and Piezo-ICSI are often observed when UMR occurs during the puncturing process and the likelihood of UMR may depends on the location of the puncture site on the oolemma. Identifying the appropriate puncturing position may decrease the likelihood of membrane rupture and thus degeneration, however, there are no studies identifying the optimal puncture position during ICSI. Study design, size, duration We have developed the ICSI Position Detector (IPD), which can identify an area where rupture is likely to occur and visualize it on a video monitor. This study included 1,110 mature oocytes retrieved from 190 consenting patients. Matured oocytes were inseminated either by Conventional-ICSI (n = 437, average maternal age: 39.1±4.6 y.o.) or Piezo-ICSI (n = 673, average maternal age: 38.6±4.5 y.o.). ICSI was performed blindly, moving images were recorded and analyzed retrospectively during ICSI using IPD. Participants/materials, setting, methods Inseminated oocytes were subsequently divided into two groups according to IPD results, oocytes on which ICSI was performed at the position with a low chance of UMR (appropriate group), and with a high chance of UMR (non-appropriate group) by IPD. The rates of UMR, degeneration, fertilization (2PN), blastocyst formation, and good-quality blastocyst (Grade 3BB and above on day 5 by the Gardner scoring) were compared between the two groups of both conventional-ICSI and Piezo-ICSI. Main results and the role of chance The areas in which UMR is less likely to occur and more likely to occur are heterogeneously distributed. When ICSI was performed blindly, about half was from the non-appropriate position. In appropriate group of Piezo-ICSI, rates of UMR (4.3% vs. 17.4%, P < 0.001) and degeneration (1.0% vs. 5.7%, P < 0.001) were significantly lower than those of non-appropriate group, whereas rates of fertilization (88.0% vs. 78.4%, P < 0.01) and blastocyst formation (57.8% vs. 45.9%, P < 0.01) were significantly higher than those of non-appropriate group, respectively. The rate of good-quality blastocyst (28.8% vs. 24.9%) was in favor of appropriate group, but not significantly different. In appropriate group of Conventional-ICSI, rates of UMR (6.7% vs. 20.6%, P < 0.001) and degeneration (1.5% vs. 6.6%, P < 0.01) were significantly lower than those of non-appropriate group, whereas rate of fertilization (88.7% vs. 69.5, P < 0.001) was significantly higher than those of non-appropriate group, respectively. The rates of blastocyst formation (37.5% vs. 35.3%), good-quality blastocyst (21.3% vs. 18.7%) were all in favor of appropriate group, but not significantly different. Limitations, reasons for caution This is a single private fertility clinic study. Its reproducibility should be assessed in different laboratory conditions and the hands of different operators. Moreover, specific studies should be addressed on the effect of the other putative confounders under investigation (e.g. kind of ovulation trigger, patient demographics, culture environment, etc.). Wider implications of the findings This study demonstrated that the IPD is useful to identify the optimal puncture location site to prevent UMR on ICSI procedure, resulting in reducing UMR and degeneration of the oocytes and increasing culture results, thereby, generating more embryos available for transfer or cryopreservation. Trial registration number not applicable

Study question What is the frequency of azoospermia factor (AZF) microdeletions and sperm retrieval rate (SRR) by micro TESE in patients with these deletions? Summary answer AZFc is most frequent of Y chromosome microdeletions and a predictor of micro TESE outcome in Japanese azoospermic men. What is known already After Klinefelter syndrome, Y chromosome microdeletions are the second most frequent genetic cause of male infertility, with a prevalence of 2%-10% in non-obstructive azoospermia (NOA) and three spermatogenesis loci in the Y chromosome long arm (Yq11) have been classified as AZFa, AZFb, and AZFc. The classical correlation of histopathology phenotypes with these three microdeletions comprises of complete absence of germ cells (Sertoli cell-only syndrome) in patients with AZFa microdeletions, maturation arrest of meiosis in patients with AZFb microdeletions, and hypospermatogenesis in patients with AZFc microdeletions, however, individual variation in the extent of deletions has led to various spermatogenic phenotypes. Study design, size, duration We performed a retrospective study based on two reproduction centers in Japan and evaluated 1373 azoospermic patients in our clinics between September 2013 and December 2021. We investigated the frequency of AZF microdeletions and SRR by micro TESE in patients with these microdeletions and therefore aimed to evaluate the correlation between AZF microdeletions and micro TESE results. Participants/materials, setting, methods A total of 1373 azoospermic were enrolled. After the diagnosis of azoospermia, karyotype analysis and detection of Y chromosome microdeletions were performed on peripheral blood lymphocytes of these patients. Y chromosome microdeletions in AZFa, AZFb, and AZFc regions were detected using Promega Y Chromosome AZF Analysis System version 2.0 (Promega Co.). Twenty sequence-tagged sites within the AZF region of Yq11 and the sex-determining region Y gene were targeted for polymerase chain reaction (PCR) amplification. Main results and the role of chance One hundred and fifty-two AZF microdeletions (11.1%) were detected in the azoospermic patients. The most common deleted region was AZFc (60 cases, 4.4%). Among the patients, 17 (1.2%), 1 (0.1%), 42 (3.1%), 13 (1.0%), and 6 (0.5%) had AZFa, AZFa+b, AZFb+c, AZFb, and AZFa+b+c microdeletions, respectively. When the cases were grouped according to causes of infertility that could be detected, no Y chromosome microdeletions were detected in some groups (cases with Klinefelter Syndrome, hypogonadotropic hypogonadism, congenital absence of vas deferens, and 47, XYY karyotype). Fifty-three azoospermic men with AZFc microdeletions underwent micro TESE, and spermatozoa were detected in 88.7% (47/53) of these men. In contrast, we detected spermatozoa in only 20.4% (109/534) of the azoospermic men without AZF microdeletions. The SRR was much higher in patients with AZFc microdeletions than that of patients without AZF deletions. Although three azoospermic men with AZFb+c microdeletions had also undergone micro TESE following patient request, we did not retrieve spermatozoa. Limitations, reasons for caution We excluded post chemotherapy NOA showing 46, XX and AZFa+b+c deletions post bone marrow transplantation from female donor. Additionally, we did not detect AZFc partial deletion including gr/gr deletion. The cohort size of this study is not small, however, our screened population of infertile men may be biased. Wider implications of the findings NOA patients with AZFc microdeletions had a high percentage of successful sperm retrieval by micro TESE. Our study emphasizes that diagnosis of Y chromosome microdeletions is critical for preconception genetic counseling and provides clinically valuable prognostic information to couples considering surgical sperm retrieval. Trial registration number None

Purpose We investigated the clinical results of Japanese men with Y chromosome microdeletions. Methods This study retrospectively examined 2163 azoospermic or severe oligozoospermic patients. We investigated the frequency of azoospermia factor (AZF) deletions and sperm retrieval rate (SRR) by microTESE in patients with these deletions, then analyzed the ICSI outcomes. Results Azoospermia factor deletions were found in 201 patients. SRR was significantly higher than that of the control group (74.0% vs 20.4%, P

Study question Does direct unequal cleavage (DC) affect embryonic development after ICSI with testicular sperm (TESE-ICSI) in patients with non-obstructive azoospermia (NOA) and/or obstructive azoospermia (OA)? Summary answer The incidence of DC at the first cleavage (DC1) was extremely high and DC1 negatively affected embryonic development in NOA patients. What is known already It has been reported that the blastocyst development of embryos with direct cleavage (DC) was significantly lower than that without DC, but the clinical pregnancy rate after blastocyst transfer was not different with or without DC. The incidence of DC has been reported to be significantly higher after ICSI with testicular sperm (TESE-ICSI) than ICSI with ejaculated sperm (Ej), but to our knowledge, there are few reports investigating that the embryos with DC after TESE-ICSI affect embryonic development. Study design, size, duration We conducted a retrospective cohort study using time-lapse incubators (Geri, Genea Biomedx, Australia) from September 2018 to November 2020. Of 1033 two-pronuclear (2PN) embryos from TESE-ICSI, 486 and 547 embryos were from OA (35.9±5.5 years) and NOA (33.7±5.2 years), respectively. As an age matched control, we chose 581 embryos from ICSI using Ej (36.5±4.4 years). Participants/materials, setting, methods DC embryos were classified as DC1 (DC at first cleavage), DC2 (DC at second cleavage), and non-DC (without DC). The incidences of DC1 or DC2 and blastocyst development rates were compared among OA, NOA and Ej groups. In TESE-ICSI group, we compared blastocyst development rates with or without DC between good and poor quality embryos on day 3. Good quality embryos were defined as 8 cells with G3 or more by the Veeck’s classification. Main results and the role of chance DC1 incidence was significantly higher in NOA (37.3%) than OA (27.8%) and Ej (22.7%) (P Limitations, reasons for caution We had a few data about the pregnancy rates after blastocyst transfers with DC, because embryos with DC were seldom transferred due to those lower priority. Although DC might be influenced by the sperm, we did not analyze the incidence of DC by taking the semen factors into account. Wider implications of the findings: The incidence of DC1 was extremely high and DC1 negatively affected embryonic development in NOA patients. Therefore, it is important to observe embryos using time-lapse incubator in order to recognize embryos with/without pregnancy potential, especially for embryos with DC1 in NOA patients. Trial registration number Not applicable

Study question To analyze whether microfluidic sperm selection (MSS) by ZyMōt™ improves sperm DNA fragmentation rate and embryonic development compared to density gradient centrifugation with swim-up (DGCS). Summary answer MSS by ZyMōt™ selects sperm for clinical use with less DNA damage significantly compared to DGCS. What is known already Conventional sperm preparation methods, such as density gradient centrifugation and the swim-up method utilize centrifugation during processing, may damage the sperm. MSS may allow for improved selection of normal sperm compared with conventional sperm preparation as it yields sperm with a lower DNA fragmentation rate. However, there are few clinical studies by sibling oocytes study compared to DGCS. Study design, size, duration This prospective study was performed between March 2020 and May 2020 at a reproductive center. All patients involved gave written consent, and institutional review board approval was granted. A total of 575 metaphase II oocytes were collected from 49 cycles. Wife’s age was 34.7 ± 3.9 years old. Raw sperm concentration and motile sperm concentration was 63.1 ± 78.7M/mL, and 41.6 ± 67.7M/mL, respectively. Participants/materials, setting, methods Patients who performed ART for the first or second time were divided into two groups according to MSS and DGCS. Sperm DNA fragmentation rate (SDFR) and motile sperm concentration were compered between MSS and DGCS. SDFR was measured by sperm chromatin structure assay (SCSA) using a flow cytometer. Sibling oocytes were randomized into MSS-IVF, DGCS-IVF, MSS-ICSI, and DGCS-ICSI. Rate of two pronuclear (2PN) oocytes, blastocysts development, and good-quality blastocysts were compared between each group. Main results and the role of chance SDFR was 13.5 ± 11.8% for raw semen. SDFR was significantly lower after MSS (3.6 ± 4.1%) than that for raw semen and after DGCS (17.4 ± 14.8%) (P Limitations, reasons for caution The participants were limited to those who collected semen of 2mL or more and motile sperm concentration of above 1M/mL, because semen sample needed to be divided to MSS and DGCS. Wider implications of the findings: This is the first study to conducted in sibling oosytes study with MSS and DGCS, in both IVF and ICSI. MSS is effective in collecting sperm with less DNA damage compared to DGCS. Motile sperm concentration after using MSS is sufficient to perform IVF as well as DGCS. Trial registration number Not applicable

Purpose Chromosomal abnormalities are a major cause of spontaneous abortion, and conventional G‐banded karyotyping (G‐banding) is mainly utilized for chromosomal analysis. Recently, next‐generation sequencing (NGS) has been introduced for chromosomal analysis. Here, we aimed to investigate the applicability and utility of NGS‐based chromosomal analysis of products of conception (POC) on chorionic villus samples from spontaneous abortion. Methods The results of chromosomal analysis of 7 chorionic villus samples from spontaneous abortion were compared between conventional G‐banding and NGS‐based chromosomal copy number analysis. Age dependency and frequency of each chromosomal aneuploidy were evaluated for 279 cases analyzed by NGS. Results Excluding two cases (culture failure and maternal cell contamination), the results were consistent between G‐banding and NGS. For cases analyzed by NGS, the rate of chromosomal abnormality increased in a maternal age‐dependent manner. The frequency of each chromosomal aneuploidy detected by NGS was almost the same as that previously reported. Finally, NGS analysis was possible for difficult cases by G‐banding analysis, such as culture failure, maternal cell contamination, long‐term storage cases, and low cell number. Conclusions Chromosome analysis using NGS not only obtains comparable results to conventional G‐banding, but also can analyze POC more accurately and efficiently.

Endometritis is subdivided into two categories. Acute endometritis is symptomatic and characterized by microabscess formation and neutrophil invasion in the endometrial superficial epithelium, gland lumina, and uterine cavity. Chronic endometritis is rather silent and recognized as unusual plasmacyte infiltration in the endometrial stromal areas. Over the last decade, studies have disclosed the potential association between poor reproductive outcomes and endometritis, particularly chronic endometritis. The aim of this review is to address the current literature surrounding chronic endometritis and highlight recent advances in the research of this long-neglected gynecologic disease.

High-dose cytarabine added to CY/TBI improves the prognosis of cord blood transplantation for acute lymphoblastic leukemia in adults: a retrospective cohort study

Introduction Chromosomal abnormalities are the most common reason for spontaneous abortion. Conventional cytogenetic analysis by G-banded karyotyping is generally performed for chromosomal analysis, but it has a problem with low-resolution, and is needed long term cell culture and enough experience for diagnosis. More recently, next generation sequencing has been introducing and improving for chromosomal analysis as an accurate, high resolution and throughput method. In this study we aimed to compare the consistency between conventional G-banding and NGS-based chromosomal copy number analysis for chorionic villus from spontaneous abortion. In addition, the frequency of each chromosomal aneuploidy was evaluated. Materials and methods From February, 2018, to April, 2018, chromosomal analysis for 7 chorionic villus samples from spontaneous abortions (from 7 to 9 weeks) were carried out both conventional G-banding and NGS (VeriSeq-PGS, Illumia). The frequency of each chromosomal aneuploidy was investigated for 110 cases from February, 2018 to December, 2018. Results NGS was able to analyze all 7 cases, but G-banding was able to detect 6 cases, and one case was cell growth failure. In 6 cases analyzed by G-banding, the results of 5 cases were consistent with the results of NGS, but one case suspected maternal cell contamination. Among 7 cases analyzed by the NGS, 2 cases were normal male karyotype (46, XY) and 5 cases were autosomal trisomy, implying that there were no cases suspected of maternal cell contamination. Among 110 cases, chorionic villus was not observed under microscope from 18 samples, NGS result was obtained from 92 cases. Seventy-one cases were found to have abnormal chromosomes (71/92, 77.2%), and 21 cases were normal karyotype (21/92, 22.8%). Aneuploidy of chromosome 22 (21.8%), chromosome 16 (17.9), chromosome 15 (11.9%), chromosome 21 (10.3%) and Chromosome X (10.3%) were more frequently, consistent with previous report. Conclusions Chromosome analysis using NGS not only obtained comparable results to conventional G-banding, but also is able to analyze more accurately and quickly.

Influence of melphalan plus fludarabine-conditioning regimen in elderly patients aged ⩾ 55 years with hematological malignancies

To assess the impact of minimal residual disease (MRD) and tyrosine kinase inhibitor (TKI) administration on allogeneic hematopoietic cell transplantation (allo-HCT) for Ph-positive ALL (Ph+ALL), we retrospectively analyzed data from a registry database for 432 adult Ph+ALL patients in first CR (CR1) who received pre-transplant TKI administration. Negative MRD (MRD(-)) at allo-HCT was achieved in 277 patients. OS in patients transplanted in MRD(-) was significantly better than that in patients transplanted in MRD(+) (MRD(-): 67% vs MRD(+): 55% at 4 years; P=0.001). MRD(-) at allo-HCT was a significant risk factor for survival along with age at allo-HCT in multivariate analyses. Incidence of relapse in patients transplanted in MRD(-) was significantly lower than that in patients transplanted in MRD(+) (MRD(-): 19% vs MRD(+): 29% at 4 years; P=0.006). In multivariate analyses, MRD(+) at allo-HCT was a significant risk factor for relapse. A post-transplant TKI was administered to 103 patients. In subanalyses regarding the effect of post-transplant TKI administration, post-transplant TKI administration was a significant risk factor for relapse in multivariate analyses (P

Introduction: The effect of in vitro fertilization (IVF) on neurodevelopmental outcome is unclear. Probably, IVF does not affect traditional measures of neurological development in infancy, but little is known on long-term effects. Recently a new video-based instrument to evaluate neuromotor development was developed. The Infant Motor Profile (IMP) evaluates neuromotor condition in infants in terms of the quality of spontaneous motor behaviour. The IMP does not only assess traditional neuromotor domains, such as performance, symmetry and movement fluency, but also two novel domains: variation and variability. Movement variation denotes the size of the child's movement repertoire. Previous studies demonstrated that reduced movement variation is associated with early lesions of the periventricular white matter and - more generally - reflects the integrety of cortical connectivity. In addition, reduced variation during infancy is associated with neurodevelopmental disorders in later life and reduced intelligence at school age. Variability denotes the child's ability to select from the repertoire of movements the strategy that suits the situation best. In this prospective, assessor-blinded cohort study, we address the question whether ovarian hyperstimulation and/or the in vitro procedure affect movement variation during infancy. Material and Methods: Singletons born following IVF with conventional controlled ovarian hyperstimulation (COH-IVF, n = 68), following IVF in a modified natural cycle (MNC-IVF, n = 57) and following natural conception born to subfertile couples (Sub-NC, n = 90) were assessed with the IMP at 4, 10 and 18 months. The assessment resulted in a total IMP score and 5 domain scores: variation (i.e. the size of movement repertoire), variability (i.e. the ability to select motor strategies), symmetry, fluency and performance. Primary outcome was the domain score variation. Outcome variables were analyzed with a mixed effects model. Results: The mixed model indicated an overall effect of treatment on variation (p Conclusions: The preliminary data suggest that ovarian hyperstimulation may be associated with reduced movement variation in infancy. These findings stress the need to carefully monitor neurodevelopment in IVF offspring.

Introduction We previously reported an interim analysis of the DADI (dasatinib discontinuation) trial. The results showed that 48% of patients with chronic myeloid leukemia in the chronic phase who maintained a deep molecular response (DMR) for ≥ 1 year could discontinue second- or subsequent-line dasatinib treatment safely at a median follow-up of 20 months. However, the results from longer follow-up periods would be much more useful from a clinical perspective. Patients and Methods The DADI trial was a prospective, multicenter trial conducted in Japan. After confirming a stable DMR for ≥ 1 year, dasatinib treatment subsequent to imatinib or nilotinib was discontinued. After discontinuation, the loss of DMR (even of 1 point) was defined as stringent molecular relapse, thereby triggering therapy resumption. The predictive factors of treatment-free remission (TFR) were analyzed. Results The median follow-up period was 44.0 months (interquartile range, 40.5-48.0 months). The estimated overall TFR rate at 36 months was 44.4% (95% confidence interval, 32.0%-56.2%). Only 2 patients developed a molecular relapse after the 1-year cutoff point. The presence of imatinib resistance was a significant risk factor for molecular relapse. Moreover, high natural killer cell and low γδ+ T-cell and CD4+ regulatory T-cell (CD25+CD127low) counts before discontinuation correlated significantly with successful therapy discontinuation. Conclusion These findings suggest that discontinuation of second- or subsequent-line dasatinib after a sustained DMR of ≥ 1 year is feasible, especially for patients with no history of imatinib resistance. In addition, the natural killer cell count was associated with the TFR.

We report STM/STS measurements at 8 K in underdoped Bi2Sr2CaCu2O8+delta crystals (T-c = 76 K and hole-doping level p similar to 0.12) whose energy spectra around the Fermi level are characterized by a two-gap structure consisting of spatially inhomogeneous pseudogap (PG) and comparatively homogeneous superconducting gap (SCG). Two electronic superstructures, checkerboard modulation (CBM) and Cu-O-Cu bond-centered modulation (BCM), are observed with mapping spectral weights at low energies within the SCG and the ratio of spectral weights at +/-Delta(PG) (PG energy), respectively. On the basis of the present findings, we suggest that the lower-energy scale CBM is an intrinsic property of Cu-O planes and can coexist with the BCM whose characteristic energy is similar to Delta(PG) in identical regions in real space.

A directional coupler using a CoFeB magnetic/polyimide dielectric hybrid transmission line was fabricated and evaluated under a large-signal transmission condition from 0.5 to 2 W. The device consists of a [polyimide (1μm)/CoFeB (1μm)/polyimide (1μm)] sandwich between upper Cu coupled lines (3μm thick and 12μm wide) and a lower Cu ground plane (3μm). The electromagnetic coupling between the top main line and the sub-line is composed of the electric field coupling due to the stub capacitors and the magnetic field coupling through the inner magnetic film. The fabricated CoFeB magnetic thin film directional coupler exhibited excellent large-signal transmission characteristics even at a rating power of 2 W in a real cellular phone application. In addition, such a large-signal characteristic was acceptable for a wideband frequency of 0.8 to 2.4 GHz, which was mainly due to the non-resonance operation.

YBa2Cu3O7 (YBCO) film was prepared by fluorine-free metalorganic deposition (MOD) on a 2-inch-diameter CeO2-buffered yttria-stabilized zirconia (CbYSZ) substrate. The MOD-YBCO films on a flat CbYSZ prepared using a metal acetylacetonate-based coating solution demonstrated high critical current density (Jc), the average being higher than 4 MA/cm2 at 77.3 K and in a self field using an inductive method. The Jc distribution was uniform in the whole area of the MOD-YBCO films on the large size substrates. Cross sectional transmission electron microscopic images of the MOD-YBCO film exhibited a very smooth CeO2/ YSZ and CeO2 buffer layer/ YBCO film interfaces. Both the buffer and the YBCO layers were dense; however, a small amount of (100)-oriented YBCO occurred inside the matrix of (001)-oriented YBCO layers. Also, some distinct dislocations were observed at the CeO2/ YBCO interface. From around the stepped surface of the CeO2 buffer layer there seemed to grow a slightly distorted (001)-oriented YBCO domain, however, the domain restored its (001)-oriented periodicity in the region at some distance above the steps. Such growth mode is considered to correlate the high Jc of the MOD-YBCO film with very small average roughness of CeO2 buffer layer.

Epitaxial YBa/sub 2/Cu/sub 3/O/sub 7/ (Y123) films were obtained by metal-organic deposition (MOD) using a simple, low-cost vacuum technique without gas flowing. The total pressure and oxygen partial pressure in the furnace were controlled to be 10 kPa and 10 Pa, respectively, by evacuation with a rotary pump followed by refilling with a mixture of O/sub 2/ and N/sub 2/ (O/sub 2/ content: 1000 ppm). XRD analyses exhibited that c-axis-oriented epitaxial Y123 films have successfully been obtained on CeO/sub 2/-buffered YSZ (100) (CbZ) and CeO/sub 2/-buffered sapphire (012) (CbS) substrates. In-plane alignments of these films were as high as that of the CeO/sub 2/ buffer layer. The film on the CbZ demonstrated a high critical current density J/sub c/ of /spl sim/2.1 MA/cm/sup 2/ at 77 K all over the film; the fluctuation of J/sub c/ being within /spl plusmn/10% of the average. Inductive T/sub c/ measurement showed a very sharp peak with T/sub c/=90.5 K. Inductive-J/sub c/ and T/sub c/ of the Y123 film on CbS were 1.1 MA/cm/sup 2/ and 89.6 K, respectively, whereas the T/sub c/ of the Y123 film on LaAlO/sub 3/ was lower than 77 K owing to the occurrence of the a-axis grains.

Distribution of J/sub c/ in the two-dimensional large-size YBa/sub 2/Cu/sub 3/O/sub 7/ (YBCO) film was investigated by an inductive method for the application to fault current limiter elements. The YBCO films were prepared by metal-organic deposition (MOD) using a fluorine-free acetylacetonate-based complex solution on R-plane sapphire with an evaporated-CeO/sub 2/ buffer layer. The average J/sub c/ values of 1-3 MA/cm/sup 2/ at 77 K were obtained for 1 cm /spl times/ 12 cm-, 3 cm /spl times/ 12 cm-, and 10 cm /spl times/ 30 cm-rectangular YBCO films as well as on 2-inch-diameter films. In contrast with the TFA-MOD method via BaF/sub 2/ precursor, the fluctuation of J/sub c/ in the present films was fairly small; no significant size effects or shape effects were recognized on the fluctuation of J/sub c/. Instead, fluctuation of J/sub c/ depended on the average J/sub c/ values; higher-J/sub c/ films tended to exhibit more uniform J/sub c/ distribution.

Epitaxial cerium oxide (CeO/sub 2/; thickness: 40 nm) buffer layers were deposited on large area (maximum size 10/spl times/30 cm/sup 2/) R-cut single-crystal sapphire (/spl alpha/-Al/sub 2/O/sub 3/) substrates by double electron-beam guns. Substrate heater-and-holder system was modified to maintain the substrate temperature uniform over the large area during deposition. Oxygen gas of a pressure 4/spl times/10/sup -2/ Pa was introduced to keep radio frequency plasma. When the substrate temperature was controlled in the range 640/spl deg/-700/spl deg/C, the CeO/sub 2/ buffer showed a complete [001] orientation and very smooth surfaces by x-ray diffraction analysis and atomic force microscopic observations, respectively, in the whole area of the large size substrates. These buffer layers without post-deposition annealing were quite suitable for preparing YBa/sub 2/Cu/sub 3/O/sub 7/ (YBCO) films by a metal-organic deposition (MOD) using a metal acetylacetonate-based solution. The average critical current density of the 210-nm-thick MOD-YBCO film was in excess of 2.6 MA/cm/sup 2/ measured by an inductive method at 77.3 K.

Large-size, two-dimensional Y Ba2Cu3O7 (YBCO) films were successfully prepared by a chemical solution-based coating pyrolysis (CP) process on 30 × 10 cm2 R-plane sapphire substrates with a vacuum-deposited CeO2 buffer layer. The CeO2 layer was very smooth and uniform with an average roughness (Ra) of 0.48 nm by atomic force microscopic observations and highly (001)-oriented by large-area x-ray diffraction θ–2θ scans. The c-axis-oriented YBCO films were prepared by a CP process using a fluorine-free, metal acetylacetonate-based coating solution. A 30 × 10 cm2-rectangular c-axis-oriented YBCO film annealed in a large-diameter tube furnace demonstrated high inductive-Jc values, for which the distribution was fairly uniform, with an average 1.0 MA cm−2 at 77 K.

Epitaxial films of vanadium(III) oxide V2O3 were prepared on the C-, A-, and R-planes of α-Al2O3 substrates by a coating-pyrolysis process. The final heat treatment was carried out at 1000°C in a precisely controlled gas flow of a CO–CO2 mixture (pCO/pCO2=10−1) at ambient pressure. This condition corresponds to an oxygen partial pressure of ~10−12 atm. The X-ray diffraction θ–2θ scanning and pole-figure analysis showed that the 0.5-μm-thick V2O3 films chiefly comprise the grains grown epitaxially to the substrate surfaces and a small amount of uniaxially oriented crystallites with the c-axis perpendicular to the substrate surfaces. In the films grown on the C- and A-planes of α-Al2O3, epitaxial grains grown 60°-rotated in the basal plane relative to the substrates (or 180° domains) were also present. The occurrence of the uniaxially c-axis-oriented and 180° domains may be attributed to the crystallization from the film surface accompanying the reduction of the precursors, which contain higher-valence vanadium ions, by the CO–CO2 mixed gas, whereas the epitaxial grains grow from the film/substrate interface.

Epitaxially grown hematite (α-Fe 2 O 3 ) films were obtained on the R -, A - and C -planes of sapphire (α-Al 2 O 3 ) substrates by a coating-pyrolysis process in air and in an argon atmosphere. The X-ray diffraction θ –2 θ scanning and pole-figure analysis showed that the films have grown epitaxially to the substrate surfaces after heat treatment at 500°C and higher. The crystallinity of the films was evaluated in terms of a full width at half maximum (FWHM) of the α-Fe 2 O 3 104 peak in the φ scans. The crystallinity of the films increased after annealing in air up to 1000°C, while the highest epitaxy was obtained at 600°C in argon. The degraded crystallinity of the films prepared in argon at higher temperatures is attributed to the reaction between the film and the substrate due to a decrease in local oxygen partial pressure caused by an organic residue in the prefired films.

Orientation-controlled epitaxial thin films of bismuth layer-structured ferroelectrics, SrBi2Ta2O9 (SBT) and SrBi2Nb2O9 (SBN), were prepared on single-crystal SrTiO3 (STO) substrates by the coating-pyrolysis process. Most of the SBT (SBN) films showed the (106) and (001) orientations on STO(110) and (001), respectively. The degree of orientation, in terms of the ratio of peak intensity to the background level in the x-ray diffraction φ-scan profile for the film, greatly increased with a decrease in the oxygen partial pressure, p(O2), of annealing atmosphere at 800 °C. Interestingly, coexistence of the (110)-oriented grains with the (106)-oriented ones on STO(110) [and the (100)-oriented grains with the (001)-oriented ones on STO(001)] was observed exclusively in the SBT films annealed at 700–750 °C under p(O2) of 10 Pa. Atomic force microscopy observations showed that the surface morphology of the SBT films remained almost unchanged, i.e., comprising round-shaped grains of submicrometer size, whereas that of the SBN films drastically changed, according to the variation in orientation of substrate surfaces or in annealing conditions, i.e., temperature, p(O2), and time.

Contraception is recommended during imatinib therapy based on the teratogenicity data in rats. However, patients may become pregnant and here we describe a successful pregnancy and labor without any congenital anomaly in a patient with chronic myeloid leukemia (CML) under treatment with imatinib. The patient had received imatinib for 53 months before she became pregnant, with a complete cytogenetic response achieved after 6 months of therapy and a major molecular response (MMR) after 28 months. CML was in MMR at discovery of pregnancy and the fetus had been exposed to imatinib for 5 weeks. Treatment was discontinued, but MMR persisted during gestation.

An understanding of the effects of long-term, low-dose-rate radiation on core components is critical to light-water reactor plant life extension. Following reactor shutdown, materials that had experienced long exposures to low-dose-rate irradiation were retrieved from the EBR-II research reactor for analysis. These components are being analyzed to provide insight into pressurized water reactor life extension. In this work, three examples of EBR-II materials analyses are highlighted: radiation-induced segregation in 304 stainless steel, stress relaxation in Inconel X750, and swelling in 316 stainless steel.

We have investigated whether the extent of residual leukemia at bone marrow harvest can predict subsequent relapse after autologous bone marrow transplantation (BMT). A total of 29 pre- and post-purged marrow samples from 15 patients with high-risk common acute lymphoblastic leukemia were examined. An accurate quantitation of residual disease was achieved by phage library assay using polymerase chain reaction to amplify the third complementarity determining region of the immunoglobulin gene. The estimated rate of disease-free survival at 3 years was significantly higher for the patients with less than 5% residual disease among total B cells than for those with greater than 5% before purging (87.5% vs 0%, P = 0. 0013). Furthermore, among patients with subsequent relapse, there was a linear correlation between the quantitated residual tumor burden of pre-purged marrow and remission duration after BMT (r2 = 0. 888). An accurate quantitative assessment of residual disease in the autograft has a high predictive value for subsequent relapse. A serial assay of residual disease would help us to individualize the treatment for each patient after induction or consolidation therapy.

Non-c-axis oriented epitaxial films of bismuth layer-structured ferroelectrics, SrBi2Ta2O9 (SBT) and SrBi2Nb2O9 (SBN), were prepared on SrTiO3(110) by coating-pyrolysis process. These films were found to be (106)-oriented (pseudo-tetragonal indices). Interestingly, this orientation is ‘stealthy’ or unseen in the conventional XRD θ–2θ scans due to extinction rule so that its presence was revealed by XRD pole-figure measurement and reciprocal-space mapping. The crystallographic relationship of the films and substrates was SBT, SBN (106)∥SrTiO3 (110) and SBT, SBN [010]∥SrTiO3 [001]. This epitaxial relationship was also discussed from the standpoint of ion arrangement.

Epitaxial and polycrystalline thin films of bismuth layer-structured ferroelectrics, SrBi2Nb2O9 (SBN) and SrBi2Ta2O9 (SBT), were prepared on single-crystal SrTiO3(001) and polycrystalline yttria-stabilized zirconia substrates, respectively, by the coating-pyrolysis process. The epitaxial relationship of the films and substrates was SBN, SBT (001)//SrTiO3(001) and SBN, SBT [100]//SrTiO3[100],[010], where pseudotetragonal indices were adopted for SBN and SBT. The lattices of the epitaxial films were found to be slightly strained owing to stress from the substrate. Atomic force microscopy observations showed that the epitaxial films as well as polycrystalline films consisted of round-shaped, islandlike grains of submicrometer size.