Search

Transplant acquired food allergy (TAFA) is a well-known complication following pediatric liver transplantation, but post-cord blood transplantation (post-CBT) TAFA has rarely been reported. Here, we describe a case of new-onset food anaphylaxis after CBT in an adult patient that demonstrates that post-CBT allergen-challenge is not a risk for long-term allergic sensitization even in adult recipients. The patient was a 39-year-old Japanese man with aggressive NK cell leukemia. He had no previous history of allergies. After receiving CBT, the patient had an unbalanced diet with high preference for bread, bananas, miso-soup, cow's milk, cheese, egg, sesame and buckwheat soba noodles, and experienced repeated diarrhea. Six months later, he developed symptoms such as vomiting, epigastric pain, diarrhea, high fever and hypotension. The condition was initially diagnosed as enterocolitis, but symptoms recurred after consumption of buckwheat. Anaphylaxis induced by buckwheat was confirmed with serum radioallergosorbent tests (RAST), showing allergen-specific IgE for buckwheat (greater than 100 U/mL, Class 6) and egg ovomucoid (Class 4). Nineteen months after a buckwheat and egg-free diet, serum RAST for buckwheat and egg significantly improved. As a result, the patient acquired a tolerance and was able to consume buckwheat and egg without allergic symptoms.

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) has been accepted as a treatment option for aggressive (acute or lymphoma type) adult T cell leukemia/lymphoma (ATLL) patients with a poor prognosis, when a suitable HLA-matched donor is not available. However, haplo-HSCT carries a potential risk of treatment-related mortality including severe graft-versus-host disease (GVHD). Therefore, we conducted a prospective pilot study in order to evaluate the efficacy and safety of reduced-intensity haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) with low-dose thymoglobulin (2.5 mg/kg only on day −2), fludarabine, melphalan, and total body irradiation 4 Gy for aggressive ATLL. Three consecutive acute type ATLL patients, who were ineligible for conventional myeloablative conditioning due to advanced age or comorbidities, were enrolled. One patient received pretransplant mogamulizumab therapy. All the patients were not in complete remission (CR) at the time of transplantation. Our transplantation protocol was safely carried out. CR was achieved in all the patients after transplantation. HTLV-I viral loads became undetectable after transplantation. No severe adverse events such as grade III-IV GVHD or viral/fungal diseases were observed. At a follow-up of 2 years, they were still in CR. However, T cell receptor repertoire diversities were low 1 year after transplantation in next-generation sequencing. Our results show encouraging therapeutic benefits of this pilot approach using reduced-intensity haplo-PBSCT with low-dose thymoglobulin for aggressive ATLL patients.

Currently, allogeneic hematopoietic stem cell transplantation (allo-HCT) is the only available curative modality for patients with adult T-cell leukemia-lymphoma (ATL). When used in conjunction with posttransplantation cyclophosphamide (PTCY) for graft-versus-host disease prophylaxis, allo-HCT from an HLA haplo-identical donor yields promising outcomes for many diseases other than ATL. However, appropriate comparisons with other donor sources, especially cord blood and conventional HLA haplo-identical donors, are needed to validate the safety and efficacy of this modality. In this study, we retrospectively evaluated the outcome of allo-HCT without PTCY in patients with ATL registered in the Japan Society for Hematopoietic Cell Transplantation TRUMP database between 1985 and 2015. During that period, 46 patients received allo-HCT without PTCY and survivors were followed for a median of 2316.5 days (range: 220-3884 days). Although the estimated 1- and 5-year overall survival rates of the entire cohort were 34.5% and 17.7%, respectively, the cumulative 1- and 5-year non-ATL mortality rates of 41.3% and 55.8%, respectively, were high. The results of our study will serve as a platform for discussions of the safety and efficacy of haplo-HCT for future clinical trials in patients with ATL.

Summary Background Standard treatment for untreated advanced-stage follicular lymphoma is rituximab plus chemotherapy. The incidence of histological transformation of follicular lymphoma has been reported only in heterogeneously treated populations and rarely with long-term follow-up. Additionally, the incidence of secondary malignancies after treatment, without high-dose therapy for follicular lymphoma, is largely unknown. The aim of our study was to assess progression-free survival, overall survival, incidence of secondary malignancies, and incidence of histological transformation in a 10-year follow-up analysis of the JCOG0203 trial. Methods In the phase 2–3 randomised JCOG0203 trial, previously untreated patients with stage III or IV indolent B-cell lymphoma, including grades 1–3 follicular lymphoma, from 44 hospital centres in Japan, were randomly assigned (1:1) by use of a minimisation method to receive six cycles of R-CHOP (rituximab [375 mg/m2], given on day 1, plus cyclophosphamide [750 mg/m2], doxorubicin [50 mg/m2], vincristine [1·4 mg/m2, capped at 2·0 mg] given intravenously on day 3, and oral prednisone [100 mg once daily on days 3–7]) every 3 weeks (R-CHOP-21) or every 2 weeks (enabled by mandatory granulocyte-colony stimulating factor administration once daily for 6 days, starting on day 8; R-CHOP-14) without rituximab maintenance. Age, bulky disease (nodal or extranodal mass ≥10 cm in diameter on CT), and institution were used as adjustment factors. Investigators enrolled participants, and assignment to trial groups was done with a computer-assisted randomisation allocation sequence that took place centrally at the Japan Clinical Oncology Group Data Center, without the intervention of investigators. Interventions were not masked for patients or investigators. Data were collected 10 years after enrolment of the last patient. The primary endpoint of the phase 3 part of the study was progression-free survival, and the primary endpoint of the phase 2 part of the study was the proportion of patients who achieved a complete response. Accrual was 4·5 years, and follow-up was 3 years after registration was closed. Data were updated on the cutoff date of Feb 28, 2017. Intention-to-treat analyses (ie, progression-free survival, overall survival, and incidence of secondary malignancies) were predefined, to be done at 10 years after the last patient was enrolled. An additional analysis of the incidence of histological transformation was defined 15 years after the protocol, on May 8, 2017, in a supplementary analysis plan, and assessed at 10 years after the last patient was enrolled. Follow-up is ongoing. This trial is registered with ClinicalTrials.gov, number NCT00147121. Findings Between Sept 1, 2002, and Feb 28, 2007, 300 patients were enrolled, and 149 (50%) were assigned to the R-CHOP-21 group and 151 (50%) were assigned to the R-CHOP-14 group. After eligibility was assessed, one patient was excluded from the R-CHOP-21 group. 10-year progression-free survival was not different between groups (R-CHOP-21 33%, 95% CI 25–41; R-CHOP-14 39%, 31–47; hazard ratio 0·89, 95% CI 0·67–1·17). In 248 patients with grade 1–3a follicular lymphoma, progression-free survival was 39% (33–45) at 8 years and 36% (30–42) at 10 years. The cumulative incidence of histological transformation was 3·2% (95% CI 1·5–6·0) at 5 years, 8·5% (5·4–12·4) at 8 years, and 9·3% (6·1–13·4) at 10 years after enrolment. At 10 years, the cumulative incidence of secondary malignancies was 8·1% (5·1–12·0) and the cumulative incidence of haematological secondary malignancies was 2·9% (1·3–5·5). Interpretation R-CHOP is a viable option for first-line treatment in patients with newly diagnosed advanced follicular lymphoma. Clinicians choosing a first-line treatment for patients with follicular lymphoma should be cautious of secondary malignancies caused by immunochemotherapy and severe complications of infectious diseases in the long-term follow-up—both of which could lead to death. Funding National Cancer Center and Ministry of Health, Labour and Welfare of Japan.

Rod‐like inclusions have rarely been described in cases of monoclonal gammopathy of renal significance or multiple myeloma. The key finding in our case is the strong κ‐light chain positivity of rod‐like inclusions in plasma cells, which confirms their immunoglobulin nature. Therapeutic benefit of bortezomib was also observed.

Optimal management of patients with chronic myeloid leukemia in chronic phase with suboptimal molecular response (MR) to frontline imatinib is undefined. We report final results from SENSOR, which evaluated efficacy/safety of nilotinib in this setting. A substudy assessed whether BIM polymorphisms impacted response to nilotinib. In this single-arm, multicenter study, Japanese patients with suboptimal MR per European LeukemiaNet 2009 criteria (complete cytogenetic response, but not major MR [MMR]) after ≥18 months of frontline imatinib received nilotinib 400mg twice daily for 24 months. MR, BCR-ABL1 mutations/variants, and BIM polymorphisms were evaluated in a central laboratory. Primary endpoint was the MMR rate at 12 months (null hypothesis of 40%). Of 45 patients (median exposure, 22.08 months), 39 completed the study and six discontinued. At 12 and 24 months, 51.1% (95% CI, 35.8%-66.3%) and 66.7% (95% CI, 51.0%-80.0%) achieved MMR, respectively. Cumulative MMR incidence by 24 months was 75.6%. Of 40 patients analyzed, 10 of 12 (83.3%) with and 17 of 28 (60.7%) without BIM polymorphisms achieved MMR at 24 months. The safety profile was manageable with dose reductions and interruptions. Nilotinib provided clinical benefit for patients with suboptimal response to imatinib, and BIM polymorphisms did not influence MMR achievement. ClinicalTrials.gov: NCT01043874.

Display Omitted Triangular fin channel double-gate MOSFETs were fabricated on SOTB.A high threshold voltage shift was obtained in triangular fin devices.A smaller variability was confirmed in triangular fin devices by wet etching.Uniform line edges of a triangular fin were formed by wet etching.A damage-free BOX layer was obtained by the orientation dependent wet etching. Triangular fin (Tri-Fin) channel double-gate (DG) MOSFETs were successfully fabricated on (100) SOTB wafers using orientation dependent wet etching, and their electrical characteristics were systematically compared to the rectangular fin (Rec-Fin) ones by RIE. Thanks to the wide bottom area and the suppressed line edge roughness of Tri-Fins by the wet process, a higher threshold voltage (Vt) tunability and a smaller Vt variation were obtained as compared to the Rec-Fin ones. Moreover, the wet processed Tri-Fin devices provide a damage-free BOX layer, which is useful for the fabrication of multiple Vt devices with an ultrathin BOX layer.

We investigated the impact of fin length ( T fin ) on the threshold voltage ( V th ) modulation by back bias ( V b ) for independent double-gate (IDG) tunnel fin field-effect transistors (tFinFETs). It was found that V th can be tuned by V b for IDG tFinFETs regardless of T fin , which can be explained by the back-gate-effect model of IDG FinFETs. For IDG tFinFETs, the slope (back-gate-effect factor ( γ )) of V th with respect to V b increases with thinning T fin . This means that T fin thinning is effective for tuning V th by V b for IDG tFinFETs. Furthermore, it was demonstrated that this back-bias-effect is consistent with the results of device simulation using an advanced nonlocal band-to-band model.

The scaled charge trapping (CT) type silicon on insulator (SOI) FinFET flash memories with different blocking layer materials of Al2O3 and SiO2 have successfully been fabricated, and their electrical characteristics including short-channel effect (SCE) immunity, threshold voltage (Vt) variability, and the memory characteristics have been comparatively investigated. It was experimentally found that the better SCE immunity and a larger memory window are obtained by introducing a high-k Al2O3 blocking layer instead of a SiO2 blocking layer. It was also confirmed that the variability of Vt before and after one program/erase (P/E) cycle is almost independent of the blocking layer materials.

Y. X. Liu, T. Matsukawa, K. Endo, S. O’uchi, J. Tsukada, H. Yamauchi, Y. Ishikawa, W. Mizubayashi, Y. Morita, S. Migita, H. Ota, and M. Masahara National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba Central 2, 1-1-1 Umezono, Tsukuba-shi, Ibaraki 305-8568, Japan. Tel: +81-29-861-3417, Fax: +81-29-861-5170, E-mail: yx-liu@aist.go.jp Three-dimensional (3D) fin-channel devices provide excellent short-channel effect (SCE) immunity thanks to the strong controllability of channel potential by the multiple gates. Therefore, the scaled charge trapping (CT) type FinFET flash memories have actively been developed in the past few years (1-3). Very recently, we have also developed floating gate (FG) type SOI-FinFET flash memories with different gate structures (4, 5), and experimentally confirmed that tri-gate (TG) structure shows the better SCE immunity and a larger memory window than double-gate (DG) structure. As a further study, in this work, we fabricate CT type TG-structured SOI-FinFET flash memories with different gate materials and different blocking layer materials, and comparatively investigate their electrical characteristics. 1. Device Fabrication In the device fabrication, we used (110)-oriented SOI wafers, and the Si-fin channels were fabricated by using orientation dependent wet etching (6). To fabricate TG structure, the SiO2 fin hard-mask layer was removed by RIE. Then, a 4.3-nm-thick tunnel oxide was formed by thermal oxidation, followed by the deposition of a 10-nm-thick nitride (Si3N4) layer by LPCVD. As the blocking layer, a 10-nm-thick Al2O3 layer or a 9-nm-thick SiO2 layer was deposited on the different sample wafers. As the different gate materials, we used n+-poly-Si and PVD-TiN metal. Figure 1(a) shows the SEM image of the fabricated FinFET flash memory with a scaled gate length (Lg) of 26 nm. The cross-sectional STEM images of the fabricated n+-poly-Si gate SONOS, PVD-TiN metal gate MONOS and MANOS with a high-k Al2O3blocking layer are shown in Figs. 1(b), 1(c) and 1(d), respectively. It is clear that uniform and ultrathin Si-fin channels are successfully fabricated thanks to the orientation dependent wet etching. 2. Gate Material Dependent of Memory Property At first, we measured the initial Id-Vg characteristics of the fabricated SONOS and MONOS type FinFET flash memories, and the threshold voltage (Vt) values were evaluated at a constant drain current of Id = 1 mA. It was experimentally found that almost the same sVt is obtained in the SONOS and MONOS devices. This result indicates that Vt variation is independent of gate material. Then, we measured P/E characteristics of the fabricated SONOS and MONOS devices. It was found that a larger memory window is obtained in the MONOS devices than the SONOS ones due to the higher work function of PVD-TiN gate than the n+-poly-Si gate as shown in Fig. 2. The higher gate work function is effective to the suppression of electron back tunneling during erase operation [7]. 3. Blocking Layer Dependent of Memory Property To investigate blocking layer material dependence on the electrical characteristics of the CT type FinFET flash memories, we fabricated MONOS and MANOS type devices with different blocking layers of SiO2 and Al2O3 as mentioned before. The initial Id-Vg characteristics of the fabricated MONOS and MANOS type FinFET flash memories with different Lg values from 26 to 103 nm were measured and the SCE immunity was systematically evaluated. It was found that the smaller Vt roll-off and the better subthreshold slope (S-slope) are observed in the MANOS devices as compared to the MONOS ones due to the high-k effect of Al2O3 in MANOS devices. The P/E characteristics of the fabricated MONOS and MANOS devices were also comparatively investigated. It was found that a significant memory window increment is obtained by introducing an Al2O3 blocking layer instead of the SiO2 one as shown in Fig. 3. This result is reasonable because a high-k Al2O3blocking layer is effective to enhance the electric field across the tunnel oxide layer and to reduce the electric field across itself. Therefore, electron back tunneling from the gate to nitride layer is effectively suppressed during erase operation. As a result, a deep erase and a large memory window are obtained in the MANOS devices than the MONOS ones. It was also confirmed that the fabricated MONOS and MANOS devices can operate over 100 k cycles, and can maintain a reasonable memory window after 10 years. In summary, we have investigated the gate material and blocking layer material dependences on the electrical characteristics of the fabricated CT type FinFET flash memories. It was experimentally found that a high work function metal gate and a high-k blocking layer are very useful to the enhancement of memory window. Acknowledgment: This work was supported in part by the Nanotechnology Project of NEDO, Japan. [1] P. Xuan et al., IEDM Tech. Dig., 609 (2003). [2] M. Spechi et al., IEDM Tech. Dig., 1083 (2004). [3] S-K. Sung et al., Symp. VLSI Tech. Dig., 106 (2006). [4] Y. X. Liu et al., Ext. Abstract, SSDM, 985 (2011). [5] T. Kamei et al., IEEE EDL 33345 (2012). [6] Y. X. Liu et al., IEEE EDL 24484 (2003). [7] C. H. Lee et al., IEDM Tech. Dig., 613 (2003).

A 37-year-old woman was admitted to a hospital due to a prolonged fever and a rash on her legs. She had systemic lymphadenitis and a skin abscess on her left leg. Pathological findings of a left leg skin biopsy revealed abscess formation with granulomatous dermatitis, Mycobacterium abscessus complex was cultured from the resected left supraclavicular lymph node, and disseminated M. abscessus complex infection was diagnosed. She was treated with combination treatment with antimicrobials and percutaneous drainage, and her clinical findings improved. Four months later, she developed acute lymphocytic leukemia. Leukemia is a risk factor for disseminated M. abscessus complex infection, even before developing leukemia.

FinFETs with the low temperature microwave annealing process have been successfully fabricated and the superiority of the microwave annealing process has been precisely studied. For the first time, it is revealed that the microwave annealed FinFET exhibits less Vth variability and lower gate leakage.

We report on performance enhancement of FinFETs with a 25-nm-short extension of the source/drain by using atomic layer deposition (ALD) of SiO 2 thin films for the side-wall spacer (SWS) of the gate electrode. Recently, the higher parasitic resistance ( R para ) of the source/drain region due to the narrow fin width is one of the issues to be solved for the FinFET devices. In this study, the performance of the FinFETs has been successfully improved by the reduction of the parasitic resistance using the ALD-SWS.

ON-current (Ion) variability is comprehensively investigated for fin-shaped FETs (FinFETs) by measurement-based analysis. Variation sources of Ion are successfully extracted as independent contributions of threshold voltage Vt, transconductance Gm, and parasitic resistance Rpara. As well as Vt variability, Gm variation exhibits a linear relationship in the Pelgrom plot. However, the Gm variation is not reduced with scaling the gate dielectric thickness unlike the Vt variation. Perspective for 14-nm FinFETs represents that the Gm variation will be the dominant Ion variation source. A solution to reduce the Gm variation for the FinFET is also proposed.

The crystal-Si and poly-Si fin-channel flash memories with a thin n+-poly-Si floating-gate (FG) layer have successfully been fabricated, and their electrical characteristics have systematically been investigated. It was experimentally found that the better short-channel effect (SCE) immunity, the smaller threshold voltage (Vt) variations and a higher program speed are obtained in the crystal-Si fin-channel tri-gate (TG)-type flash memories than in the double-gate (DG)-type ones. It was also confirmed that split-gate crystal-Si fin-channel flash memories show highly suppressed over-erase as compared to that in stack-gate memories. Moreover, it was found that Vt variation in the poly-Si fin-channel flash memories after a program/erase (P/E) cycle became comparable to that in the crystal-Si fin-channel memories. The measured source-drain breakdown voltage (BVDS) was higher than 3.2 V even the gate length (Lg) was down to 76 nm. The developed technology is very useful for the fabrication of scaled NOR-type flash memory.

We compared the electrical characteristics, including mobility and on -state current Ion, of n+-poly-Si/PVD-TiN stacked-gate FinFETs with different fin heights Hfin. The mobility was enhanced in devices with taller fins due to increased tensile stress. However, as gate length Lg decreases, Ion for devices with tall fins becomes worse, probably due to a high parasitic resistance Rp. Furthermore, Vth variation increased with increasing Hfin due to rough etching of the fin sidewall. Process technologies for reducing Rp and etching technology that yields smooth precise profiles are essential to exploit the high performance of tall FinFETs.

The threshold voltage Vt variability in the scaled crystal channel and poly-Si channel double-gate fin-type metal-oxide-semiconductor field-effect transistors (FinFETs) with different gate oxide thicknesses Tox has been systematically analyzed. By investigating the Tox dependence of Vt variations in crystal channel FinFETs, the gate-stack origin sources, i.e., work function (φm) variation and gate oxide charge (Qox) variation sources, were successfully separated. It was found that the atomically flat Si-fin sidewall channels fabricated by the orientation-dependent wet etching contribute to the reduction of gate-stack origin Vt variations. Moreover, it was experimentally found that the standard Vt deviation (σVt) of poly-Si channel FinFETs is three times higher than that of crystal channel ones, and a good subthreshold slope in the poly-Si channel FinFETs was obtained with gate length Lg down to poly-Si grain size.

This paper presents a precise characterization of high-frequency characteristics of intrinsic channel of FinFET. For the de-embedding of the parasitics attached to the source, drain and gate terminals, it proposes special calibration patterns which can place the reference surface just beside the intrinsic part of the FinFET. It compares the measured S parameter data up to 40GHz with the device simulation and shows good matching. The experimental data of the through pattern also confirms the accuracy of the de-embedded parasitics and extracted intrinsic part of FinFET.

This paper demonstrates a FinFET operational amplifier (opamp), which is suitable to be integrated with digital circuits in a scaled low-standby-power (LSTP) technology and operates at extremely low voltage. The opamp is consisting of an adaptive threshold-voltage (Vt) differential pair and a low-voltage source follower using independent-double-gate- (IDG-) FinFETs. These two components enable the opamp to extend the common-mode voltage range (CMR) below the nominal Vt even if the supply voltage is less than 1.0V. The opamp was implemented by our FinFET technology co-integrating common-DG- (CDG-) and IDG-FinFETs. More than 40-dB DC gain and 1-MHz gain-bandwidth product in the 500-mV-wide input CMR at the supply voltage of 0.7V was estimated with SPICE simulation. The fabricated chip successfully demonstrated the 0.7-V operation with the 480-mV-wide CMR, even though the nominal Vt was 400mV.

A multicenter phase III study for untreated multiple myeloma was conducted to investigate a switch-induction chemotherapy with melphalan-prednisolone and vincristine-doxorubicin-dexamethasone followed by randomization on maintenance therapy for patients achieving plateau. Between November 2002 and November 2005, 34 patients were registered. The study was closed early because of poor accrual. Thirty-three eligible patients, with a median age of 65 years (range: 47-77 years) were analyzed for the secondary purpose. For induction therapy, 16 patients were treated with vincristine-doxorubicin-dexamethasone and 17 with melphalan-prednisolone initially. In eight cases, induction therapy was switched because of a poor response. Both regimens were well tolerated, but neutropenia, anorexia, constipation and infection with neutropenia were more frequent for vincristine-doxorubicin-dexamethasone. Best response rates were 44% (95% confidence interval, 20-70) and 47% (95% confidence interval, 23-72), respectively, for vincristine-doxorubicin-dexamethasone and melphalan-prednisolone. Vincristine-doxorubicin-dexamethasone/melphalan-prednisolone switch-induction therapy might be feasible and effective for Japanese patients with multiple myeloma.

[Figure][1] A 68-year-old man with a history of adult T-cell leukemia/lymphoma (ATLL) presented to our outpatient clinic complaining of painful hand swelling of 3 weeks’ duration. Neither enlarged lymph nodes nor skin lesions were observed. The total leukocyte count was normal (5.2 × 109/

Objective The efficacy of pirarubicin (THP)-COP was previously compared with cyclophophamide + doxorubicin + vincristine + prednisolone (CHOP) in elderly patients with lymphoma. The subset analysis showed that T-cell lymphoma had a significantly better response with THP-COP, whereas no such difference was observed in B-cell lymphoma. The aim of this study is to confirm the efficacy of THP-COP in the treatment of T-cell lymphoma. Methods We underwent a multicenter phase II study of THP-COP as a first-line treatment for T-cell lymphoma. The overall response rate, survival period, and toxicity were analyzed. Results Fifty-three patients were enrolled in this study. Seventeen patients had peripheral T-cell lymphoma (PTCL), including nine of PTCL not otherwise specified (PTCL-NOS) and eight of angioimmunoblastic T-cell lymphoma (AITL). Thirty-six patients had adult T-cell leukemia/lymphoma (ATLL), including 20 of acute type and 16 of lymphoma type. A treatment response was obtained in 35 (66%) patients, including 17 (32%) complete responses. Median overall survival (OS) and progression-free survival (PFS) times were 14.3 months and 5.2 months, respectively. Patients with ATLL showed a tendency to obtain low response rate (61% vs. 77%, P = 0.27) and had a significantly inferior OS (13.3 vs. 28.6 months, P = 0.04) and PFS (4.6 vs. 8.1 months, P = 0.01) in comparison with PTCL. Grade 3 to 4 neutropenia, anemia, and thrombocytopenia occurred in 72%, 34%, and 58% of the patients, respectively. Febrile neutropenia was observed in 51% and grade 3 non-hematological toxicities in 2-9% of the patients. Conclusion The efficacy of THP-COP is equivalent to that of CHOP for the first-line therapy in T-cell lymphoma.

Background The diagnosis of myelodysplastic syndromes is not always straightforward when patients lack specific diagnostic markers, such as blast excess, karyotype abnormality, and ringed sideroblasts.Design and Methods We designed a flow cytometry protocol applicable in many laboratories and verified its diagnostic utility in patients without those diagnostic markers. The cardinal parameters, analyzable from one cell aliquot, were myeloblasts (%), B-cell progenitors (%), myeloblast CD45 expression, and channel number of side scatter where the maximum number of granulocytes occurs. The adjunctive parameters were CD11b, CD15, and CD56 expression (%) on myeloblasts. Marrow samples from 106 control patients with cytopenia and 134 low-grade myelodysplastic syndromes patients, including 81 lacking both ringed sideroblasts and cytogenetic aberrations, were prospectively analyzed in Japan and Italy.Results Data outside the predetermined reference range in 2 or more parameters (multiple abnormalities) were common in myelodysplastic syndromes patients. In those lacking ringed sideroblasts and cytogenetic aberrations, multiple abnormalities were observed in 8/26 Japanese (30.8%) and 37/55 Italians (67.3%) when the cardinal parameters alone were considered, and in 17/26 Japanese (65.4%) and 42/47 Italians (89.4%) when all parameters were taken into account. Multiple abnormalities were rare in controls. When data from all parameters were used, the diagnostic sensitivities were 65% and 89%, specificities were 98% and 90%, and likelihood ratios were 28.1 and 8.5 for the Japanese and Italian cohorts, respectively.Conclusions This protocol can be used in the diagnostic work-up of low-grade myelodysplastic syndromes patients who lack specific diagnostic markers, although further improvement in diagnostic power is desirable.

In this paper, Ta/Mo interdiffusion dual metal-gate technology, which has an advantage in realizing dual gate work functions without etching of metals from the gate dielectrics, has been introduced for a FinFET. Gate-first fabrication of the FinFET was successfully implemented by optimizing the deposition and patterning of the Mo and Ta/Mo metal gates on the ultra- thin fin channels. The Ta/Mo-gated n-MOS and Mo-gated p-MOS FinFET exhibit symmetrical values of Vth (0.31/-0.36 V), which are desirable for FinFET CMOS circuit operation with enhanced current drivability, because the threshold voltage (Vth) is reduced due to Ta diffusion in the Ta/Mo gate. It was experimentally found that the Ta/Mo interdiffusion process causes no degradation in integrity of the gate dielectric or the carrier mobility. It was also confirmed that the Ta/Mo interdiffusion process is appropriate for a scaled gate length down to 100 nm.

We have investigated dual-work-function metal gates based on Mo and stacked Ta/Mo fabricated by an interdiffusion method that does not require a metal etching process from the gate dielectrics. The diffusion of Ta into the Mo layer provides a markedly reduced work function for the Ta/Mo gate (4.42 eV) in comparison with that for the single Mo gate (5.04 eV). The metal–oxide–semiconductor field-effect transistors (MOSFETs) with the Mo and Ta/Mo gates on 4-nm-thick SiO2 were fabricated by the gate-first process with dopant activation annealing at 850 °C. The Ta/Mo-gate n-MOSFET with the reduced gate work function and the Mo-gate p-MOSFET exhibited almost symmetrical threshold voltages (+0.53/-0.45 V). It was also confirmed that the Ta/Mo interdiffusion process did not degrade the gate dielectric integrity and electron mobility in contrast to the case of the single Mo gate.

Cancer chemotherapy regimens which had been used at a ward and outpatient chemotherapy in various departments were collected and made available to everybody in October, 2003. However, it was difficult to manage cancer chemotherapy regimens in real time, from the viewpoint of risk management. Then, the Cancer Chemotherapy Center took the leading part and established a chemotherapy exploratory committee, which consists of 4 doctors, 2 nurses and 2 pharmacists, in June, 2006. The department of pharmacy could control all cancer chemotherapy regimens by this system, and lead the proper use of increasing anticancer agents. Inquiries on prescription by the pharmacist contributed to proper medical treatment. The role of the cancer chemotherapy exploratory committee and its outcome are described for the purpose of the prevention of medical accidents in this paper.

This paper presents the fin-height controlled TiN-gate FinFET CMOS technology based on the experimental carrier mobility data. The good current matching by tuning the N-channel fin-height and the excellent transfer performance in the fabricated TiN-gate CMOS inverter are demonstrated. The developed technologies are attractive to materialize the high-performance FinFET CMOS circuits.

A novel resist etch-back process for fabrication of separated-gate four-terminal FinFETs has been investigates. This process enabled co-fabrication of three-terminal (3T) and four-terminal (4T) FinFETs on a same chip. The fabricated 3T-FinFET shows excellent sub-threshold characteristics and drain induced barrier lowering (DIBL) value whereas the 4T-FinFET provides efficient Vth controllability. The effective Vth controllability with keeping a small sub-threshold slope has been confirmed in the synchronized double gate (DD) operation mode

This paper presents a robust and compact SRAM physically-unclonable-function (PUF) cell using a polycrystalline-Si channel (poly-Si) FinFET, for the first time. Its process is identical to that of a crystalline-Si FinFET except channel material. A systematic comparison between poly- and crystalline-Si FinFET PUF cells, reveals that the poly-Si cell improves the intra-PUF hamming distance to 1/3.4 of that of the crystalline-Si cell and 15k logic-transistors for stabilizing PUF reproducibility are reduced with keeping the same stability. For this analysis, a newly defined noise margin for SRAM PUFs, which is different from the SRAM static noise margin, is introduced.

We systematically investigated the NBTI degradation of Si-channel p-type tunnel FETs (pTFETs). The NBTI degradation mechanism of pTFETs is almost the same as that of pFETs. It was clarified that the NBTI degradation of pTFETs is only caused by the trap charge and the interface state degradation located in the tunneling region near the n+ source/gate edge. Furthermore, in terms of the BTI degradation of n- and p-type TFETs, although the injection sources of carriers inducing PBTI and NBTI are different, applying a drain bias corresponding to the operation conditions has an effect on the BTI lifetime improvement of n- and p-type TFETs.

This paper demonstrates a 0.8-V rail-to-rail operational amplifier (op-amp) for ultra-low-power Internet-of-Things (IoT) sensor nodes. To suppress the leakage current in the logic part, a FinFET technology with 0.4-V threshold voltage (V t ), is chosen. To realize the rail-to-rail operation in the small common-mode (CM) voltage headroom, V DD –V t , a 4-stage chopper-stabilized topology with high-pass filters, multi-path hybrid-nested Miller compensation, and a push-pull output stage are introduced. A near-V t amplifier is also introduced to the second stage to boost the gain. The fabricated op-amp shows 1MHz Gain-Bandwidth in whole of the CM voltage range.

This paper reports the positive bias temperature instability (PBTI) characteristics for n-type fin-channel tunnel field-effect transistors (TFETs) with high-k gate stacks. The subthreshold slope (SS) is not degraded at all while the threshold voltage (V th ) shifts in the positive direction by the PBTI stress. The activation energy of ΔV th for TFETs is almost the same as FinFETs, indicating that the PBTI mechanism for TFETs is almost the same as FinFETs. It was found that by applying a positive bias to the n+-drain, the PBTI lifetime is dramatically improved as compared with that in the conventional stress test. This is because carrier injection from the n+-drain is the main cause of the PBTI, especially for n-type TFETs. Thus, to accurately predict the PBTI lifetime of n-type TFETs, it is necessary to apply a drain bias for the reliability test.

Polycrystalline-silicon (poly-Si) and crystalline-silicon (crystal-Si) channel FinFET CMOS inverters were successfully fabricated and the variations of threshold voltage (V t ) for their individual n- and p-channel transistors and the logic gate V t (V Thc ) for the inverters were systematically investigated. It was found that poly-Si n- and p-channel devices show about 3 and 5 times larger σV t values, respectively and about 2 times larger σV Thc as compared to those in crystal-Si channel ones. The calculated σV THC values by using the error propagation low are good agreement with experimental results.

Breast cancer is a hormone responsive disease, and its proliferation and progression correlate with estrogen. Estrogen binds to estrogen receptor and induces various target genes, thus promoting proliferation of breast cancer cells. Therefore, the strategy of endocrine therapy is the blockade of estrogen action. We can use a luteinizing hormone releasing hormone agonist and aromatase inhibitor as an interruptor of supply, tamoxifen as an inhibitor of estrogen receptor, and medroxyprogesterone acetate with an anti-estrogen action. In this article, we review endocrine therapy for breast cancer patients based on recent clinical trials.

At present, one-third of people die of cancer and the number is still increasing in Japan. A safe and effective treatment system is critically required. Recently, the discovery of new drugs and the development of medical oncology promotes out-patient treatment for cancer patients. Out-patient treatment in the cancer chemotherapy center of the University of Occupational and Environmental Health Hospital has been started, and many chemotherapy regimens were verified in this center. Not only different organ-specific chemotherapies but also summarizing the oncology team are necessary for performance of the mission. We describe in this review the characteristics of the cancer chemotherapy center.

Hypercalcemia is observed in >80% of ATL. Serum MIP-1 levels were elevated in all 24 ATL with hypercalcemia but undetectable in all 10 patients with humoral hypercalcemia of malignancy with solid tumors and in 34 of 37 ATL without hypercalcemia. We propose that serum MIP-1 is a clinical hallmark for hypercalcemia in ATL. Introduction: High serum cytokines levels are not always associated with hypercalcemia in patients with adult T-cell leukemia (ATL), suggesting that other factors are involved in the pathogenesis of ATL patients with hypercalcemia. This study was designed to determine the role of macrophage inflammatory protein-1 (MIP-1), a chemokine recently described as an osteoclast stimulatory factor, in ATL-associated hypercalcemia. Materials and Methods: We measured serum interleukin (IL)-1, IL-6, TNF-, parathyroid hormone-related protein (PTHrP), and MIP-1 levels in ATL patients by enzyme-linked immunosorbent assays. FACScan was used to measure the expression of RANKL on ATL cells. Osteoclast formation in cocultures of ATL cells and peripheral blood mononuclear cells (PBMCs) was evaluated by TRACP staining. Results: High serum MIP-1 levels were noted in all 24 ATL patients with hypercalcemia and in 3 of 37 ATL patients without hypercalcemia. The elevated levels of MIP-1 and calcium in ATL patients decreased after effective chemotherapy, emphasizing the role of MIP-1 in ATL hypercalcemia. ATL cells spontaneously produced MIP-1. MIP-1 significantly enhanced human monocyte (precursor cells of osteoclasts) migration and induced RANKL expression on ATL cells. ATL cell-induced osteoclast formation from PBMCs was inhibited by anti-MIP-1 antibody and osteoprotegerin. Conclusion: Our results suggest that MIP-1 can induce RANKL on ATL cells in autocrine fashion and that RANKL seems to mediate the hypercalcemic effect of MIP-1 in ATL. We propose that MIP-1 is the clinical hallmark of hypercalcemia in ATL and could be a potentially useful therapeutic target. J Bone Miner Res 2004;19:1105-1111. Published online on March 15, 2004; doi: 10.1359/JBMR.040314 DULT T-CELL LEUKEMIA (ATL) is a mature CD4 T-cell malignancy caused by infection with human T-lymphotrophic virus (HTLV)-I and is associated with a marked increase of peripheral leukemic cells and monoclo- nal growth during the acute phase. Mechanisms of hyper- calcemia in malignancy have been explored recently. The high frequency of hypercalcemia is the most striking feature of ATL; 70% of ATL patients have hypercalcemia during the clinical course of the disease, particularly during the aggressive stage of ATL. (1) Such a frequency is the highest among malignancies, and hypercalcemia is more severe in patients with ATL than in those with other malignancies. (2) Several pathological studies of ATL patients with hyper- calcemia have indicated that the latter is caused by in

Although imatinib mesylate has shown encouraging activity in chronic myelogenous leukemia (CML), disease progression during therapy has been observed, manifested by clonal expansion of imatinib mesylate-resistant leukemia cells. On the other hand, myelosuppression related to treatment of imatinib mesylate is often managed with temporary interruption of treatment or dose reduction. We here report two CML patients who had imatinib mesylate-sensitive blast crisis (BC) immediately after discontinuation of imatinib mesylate therapy. The patients discontinued therapy because of neutropenia. Although there was no evidence of blastic phase during therapy, BC occurred 2 weeks after the withdrawal of treatment in both cases. Interestingly, additional chromosomal abnormalities were detected following the withdrawal of imatinib mesylate and disappeared by re-introduction of this agent. The same doses of imatinib mesylate was still effective and remission was sustained with imatinib mesylate alone again. Our report suggests the possibility that withdrawal of imatinib mesylate may lead to proliferation of blast clones even in patients showing good responses to imatinib mesylate without signs of disease progression.

A 58-year-old right-handed man presented with 3 months gradual worsening of twitching in his left hand. He had no remarkable medical or family history. Examination demonstrated continuous twitching in his left upper limb and dystonic posture of his left hand (videos 1 and 2 at [Neurology.org][1]). Superficial, deep, and cortical sensations were not disturbed in his left upper limb. Acknowledgment: The authors thank Drs. Shigeru Nishizawa and Mayu Takahashi from the Department of Neurosurgery, University of Occupational and Environmental Health School of Medicine, for performing open brain biopsy. [1]: http://neurology.org/lookup/doi/10.1212/WNL.0000000000003515

The functional split-gate type trigate flash memory cell transistors have successfully been fabricated for the first time, and their threshold voltage (Vt) variations before and after NOR-mode program/erase cycle have systematically been compared with the stack-gate ones. It was experimentally found that split-gate type cell transistors with the same control gate length (LCG) of 176 nm show much smaller Vt distribution after erase compared to those of stack-gate ones. Moreover, the measured source-drain breakdown voltage (BVDS) is higher than 3.1 V even the LCG was down to 76 nm. This indicates that the developed split-gate type trigate flash memory is very effective for scaled NOR-type flash memory with highly suppressed over-erase.

1998, a consensus meeting was held in Miyazaki, Japan, to develop an approach to management of febrile neutropenia (FN). The K-HOT study group decided to examine whether this proposal was applicable to clinical practice in a multicenter study. Patients who developed fever with neutrophil counts

We systematically investigated the bias temperature instability (BTI) of tunnel field-effect transistors (TFETs). The positive BTI and negative BTI mechanisms in TFETs are the same as those in metal–oxide–semiconductor FETs (MOSFETs). In TFETs, although traps are generated in high-k gate dielectrics by the bias stress and/or the interface state is degraded at the interfacial layer/channel interface, the threshold voltage (V th) shift due to BTI degradation is caused by the traps and/or the degradation of the interface state locating the band-to-band tunneling (BTBT) region near the source/gate edge. The BTI lifetime in n- and p-type TFETs is improved by applying a drain bias corresponding to the operation conditions.

The positive bias temperature instability (PBTI) characteristics for n-type fin-channel tunnel FETs (TFETs) with high-k gate stacks have been thoroughly investigated and compared with conventional FinFETs. The subthreshold slope (SS) is not degraded at all while the threshold voltage (V th ) shifts in the positive direction by the PBTI stress. The activation energy of ?Vth for TFETs is almost the same as FinFETs, indicating that the PBTI mechanism for TFETs is almost the same as FinFETs. It was found that, by applying a positive bias to the n+-drain (normal operation condition), the PBTI lifetime is dramatically improved as compared with that in the conventional stress test (both the p+-source and n+-drain are grounded). This is because carrier injection from the n+-drain is the main cause of the PBTI, especially for n-type TFETs. Thus, the realistic impact of the PBTI is significantly mitigated for n-type TFETs.

The effectiveness of amorphous metal gate (MG) in suppressing low-frequency noise (LFN) for FinFETs has been thoroughly investigated. It was demonstrated that the amorphous TaSiN MGs with various atomic compositions provide flexible tuning of threshold voltage (V t ) as well as small V t variability, namely AVt. It was found that the TaSiN-MG FinFETs exhibit drastic reduction of LFN in comparison to the poly-crystalline TiN MG case. Modelling by 3D-TCAD reveals that work function variation (WFV) of the MG has a significant impact on LFN generation. Suppression of A Vt and LFN is highly beneficial to conduct further scaling of analog/digital components in SoC.

The 3D fin-channel charge-trapping (CT) type flash memories with a high-k Al 2 O 3 blocking layer (MANOS) have successfully been fabricated by scaling down L g to 22 nm, and their electrical characteristics including variability of threshold voltage (V t ), endurance and retention characteristics have systematically been investigated. Thanks to the high-k effect of an Al 2 O 3 blocking layer, it was found that the better short-channel effect (SCE) immunity and a larger memory window are obtained in the fabricated MANOS type flash memories than the MONOS ones with a SiO 2 blocking layer.

FinFETs with an amorphous metal gate (MG) are fabricated on silicon-on-thin-buried-oxide (SOTB) wafers for realizing both low variability and tunable threshold voltage (V t ) necessary for multiple V t solution. The FinFETs with an amorphous TaSiN MG record the lowest on-state drain current (I on ) variability (0.37 %μm) in comparison to bulk and SOI planar MOSFETs thanks to the suppressed variability of V t (A Vt =1.32 mVμm), drain induced barrier lowering (DIBL) and trans-conductance (G m ). Back-biasing through the SOTB provides excellent V t controllability keeping the low V t variability in contrast to V t tuning by fin channel doping.

Chronic lymphocytic leukemia (CLL) is a rare disease in Japan. Recent advances in molecular biology, diagnostic criteria and classification of CLL have reinforced the concept of each category of CLL as a distinct entity. Since there have been no recent studies on the incidence and prevalence of CLL in Japan, the Kyushu Hematology Organization for Treatment (K-HOT) Study Group conducted two studies of CLL. One study is a prospective registration of newly diagnosed hematological disorders, which gave us some idea of the incidence of CLL in our region (Kyushu island) where adult T-cell leukemia is endemic. A total of 677 patients with hematological disorders were registered over a 6-month period and 11 patients were diagnosed as having CLL among 182 leukemia patients. This amounts to 6% of all leukemias, which is twice as frequent as previously reported in Japan. The other study is a retrospective analysis of CLL. Eleven institutions of the K-HOT Group analysed their diagnostic records of chronic lymphoid leukemia, and 145 patients with CLL were found over a period of 3-12 yr. After the data were reviewed 11 patients were excluded through having a different type of leukemia. The proportion of chronic B-cell lymphoid leukemia was 73% (98/134), while that of T-cell leukemia was 18% (24/134). The proportion of T-cell chronic leukemia was 5-6 times higher than that in Western countries. Two institutions had a complete database on hematological disorders. From this database, the annual incidence of CLL was estimated to be 0.48 per 100 000. Thus, the incidence of CLL in Japan is at least 4-5 times lower than that in Western countries, suggesting that chronic B-cell leukemia is really rare, but chronic leukemia of T-cell lineage develops in Japan as frequently as in Western societies. Further investigation is required to delineate why the incidence of B-CLL is so low in Japan.

Variability of TiN FinFET performance is comprehensively studied. It is found that the variation of the in the FinFET occurs and the standard deviations of the of nMOS and pMOS FinFETs are almost the same. From the analytical results, it is found that the variation of the TiN FinFET is due to the work function variation (WFV) of TiN metal gate. The WFV is also responsible for the on-current variation.