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The objective of this study was to investigate the effect of 5-aminolevulinic acid (5-ALA) as a dietary supplement on milk yield and composition as well as iron status and immune response in lactating dairy cows. In this study 13 lactating Holstein cows were randomly assigned to either a control group or a treatment group supplemented with 10 mg of 5-ALA per kilogram of dry matter. During feeding, 5-ALA was mixed with a small amount of the total mixed ration and top-dressed. The experiments followed a crossover design with 2 periods. Each period consisted of an adaptation period of 12 d and a test period of 2 d. Dairy cows fed the diet supplemented with 5-ALA exhibited increased counts of white blood cells and granulocytes compared with the control group. The rate of phagocytosis and mitogen-induced proliferation of peripheral blood mononuclear cells in cows fed 5-ALA were higher than in cows fed a basal diet. However, 5-ALA did not affect iron status or plasma biochemical composition. Supplementation with 5-ALA improved milk protein and milk casein contents; however, it had no effect on milk production, milk fat, lactose, total solids, or solids-not-fat, compared with the control. We conclude that dietary supplementation of 5-ALA to lactating dairy cows may have a positive effect on milk protein synthesis and the immune response.

Limited data are available on Stenotrophomonas maltophilia bloodstream infections (SM-BSIs) and the therapeutic efficacy of trimethoprim–sulfamethoxazole (SXT) against SM-BSI in umbilical cord blood transplant (uCBT) recipients. Medical and microbiological records of adult patients who received uCBTs between December 2008 and December 2015 at Toranomon Hospital (Tokyo, Japan) were reviewed. The efficacy and safety of SXT were evaluated only for recipients who were treated with ≥7 days of intravenous SXT for SM-BSI (evaluation cohort). Of 561 uCBT recipients, 34 developed SM-BSI. Diabetes mellitus (P = .005) and age ≥ 60 years (P = .013) were significant independent risk factors for SM-BSI. Moreover, SM-BSI was identified as an independent risk factor for all-cause mortality up to 100 days following uCBT (P = .025). Of the 34 recipients with SM-BSI, 24 were treated with an intravenous SXT-containing regimen (iSXT-CR). Septic shock (P = .0021), pneumonia (P = .011), neutropenia (P = .0015), and systemic steroid administration (P = .018) were identified as significant independent risk factors for 7-day crude mortality. The evaluation cohort included nine recipients. Doses of SXT were 2.4 to 6.9 mg/kg/day of the trimethoprim component. Of the nine recipients, five developed SM-BSI during the pre-engraftment phase. The 30-day crude-mortality rate and clinical cure rate of the cohort were 22% and 67%, respectively. Only one of the nine recipients experienced significant neutrophil toxicity. In this study, the epidemiology of SM-BSI in uCBT recipients was determined and its negative impact on survival was demonstrated. A low- to moderate-dose iSXT-CR appeared to be a tolerable and important therapeutic option for SM-BSI in the uCBT setting, including during the pre-engraftment phase.

Aggressive therapy-resistant and refractory acute myeloid leukemia (AML) has an extremely poor outcome. By analyzing a large number of genetically complex and diverse, primary high-risk poor-outcome human AML samples, we identified specific pathways of therapeutic vulnerability. Through drug screens followed by extensive in vivo validation and genomic analyses, we found inhibition of cytosolic and mitochondrial anti-apoptotic proteins XIAP, BCL2 and MCL1, and a key regulator of mitosis, AURKB, as a vulnerability hub based on patient-specific genetic aberrations and transcriptional signatures. Combinatorial therapeutic inhibition of XIAP with an additional patient-specific vulnerability eliminated established AML in vivo in patient-derived xenografts (PDXs) bearing diverse genetic aberrations, with no signs of recurrence during off-treatment follow-up. By integrating genomic profiling and drug-sensitivity testing, this work provides a platform for a precision-medicine approach for treating aggressive AML with high unmet need. Ishikawa and colleagues perform integrated genomic and drug-sensitivity screens with extensive PDX modeling and reveal combined XIAP and BCL2 inhibition as a vulnerability hub across AML genetic alterations.

Background In some patients, non-tuberculous mycobacteria (NTM) infections manifest in solitary nodules (solitary nodular [SN] type) generally caused by Mycobacterium avium complex (MAC). In patients treated using surgical resection, the American Thoracic Society guidelines state that postoperative chemotherapy is not necessary in the absence of lesions, although there have been a few reports of such cases. Methods Twenty-eight patients diagnosed with NTM who underwent solitary pulmonary nodule resection at Toneyama Hospital, Osaka, Japan, between January 2000 and October 2012 were enrolled. We evaluated the influence of the surgical procedure and chemotherapy on outcomes in this retrospective study. Results Of the 28 patients, 12 were males and 16 were females; the mean age was 58.6 ± 13.2 years. Twenty-five patients were asymptomatic and bronchoscopy was performed in 18; only 2 had a definitive diagnosis of NTM. The pathogen responsible was MAC in 27 patients and M. kansasii in 1. The surgical procedure used was wedge resection in 22 patients, segmentectomy in 1 and lobectomy in 5. Postoperative chemotherapy was administered to 9 patients. Twenty-six patients had no recurrence. Conclusion We believe that wedge resection is a valid surgical intervention for SN type NTM; additional postoperative chemotherapy is unnecessary in cases with no residual lesions in the operated lung lobe.

Background Patients with sensitive gene mutations could achieve better overall survival by taking targeted drugs. Many trials have shown that non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EFGR) mutation responded to PD-1/PD-L1 inhibitors worse than EGFR wild-type. And subgroups of trials have also reported the efficacy of PD-1/PD-L1 inhibitors in the treatment of NSCLC patients with other sensitive gene mutations. So, we conducted a complementary systematic review and meta-analysis to compare efficacy of PD-1/PD-L1 inhibitors for NSCLC patients with sensitive gene mutations. Methods PubMed, EMBASE, Web of Science and the Cochrane Central Register of Controlled Trials (Central) databases were searched for all clinical trials in NSCLC until 5th of January 2019. Eligible studies included randomized controlled trials (RCTs) comparing PD-1/PD-L1 inhibitors with chemotherapy in NSCLC patients with sensitive gene mutations. The hazard ratio (HR) and 95% confidence intervals (CIs) of overall survival (OS) or progression-free survival (PFS) were used. Results We analyzed 193 patients in this study. Among cumulative total of 210 patients, 197 were treated with PD-1 or PD-L1 inhibitors. Another 8 and 5 patients were treated with CTLA-4 inhibitor alone and combination with PD-1 inhibitor, respectively. This study included non-small cell lung cancer (n = 106; 50.5%), kidney (n = 23; 10.9%), melanoma (n = 30; 14.3%), gastric (n = 19; 9.0%), Hodgkin lymphoma (n = 11; 5.2%), urothelial carcinoma (n = 10; 4.8%) and others (n = 10; 4.8%). Any grade of irAEs occurred in 73 (34.8%) cumulative patients, and among them, 28 (13.3%) were classified as grade 3-5. The most common irAEs in any grade were skin disorders (n = 29) and endocrine disorders including thyroid dysfunction and adrenal insufficiency (n = 28). Eosinophilia occurred in 57 cumulative patients (27.1%), and 21 patients out of them had eosinophilia from baseline. Among the clinical and laboratory factors, only eosinophilia was significantly associated with the occurrence of any grade of irAEs in both univariate (p = 0.010) and multivariate (p = 0.0463) analyses. Notably, endocrine irAEs were significantly related to eosinophilia (p = 0.0287). Conclusions Eosinophilia after the initiation of treatment with ICIs predicts succeeding onset of irAEs. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure Y. Miura: Honoraria (self): Ono; Honoraria (self): Bristol-Myers Squibb Japan; Honoraria (self): Chugai. T. Takano: Honoraria (self): Daiichi Sankyo; Honoraria (self): Kyowa Hakko Kirin; Honoraria (self): Eisai; Research grant / Funding (self): MSD; Research grant / Funding (self): Ono; Research grant / Funding (self): Merck Serono; Research grant / Funding (self): Taiho; Research grant / Funding (self): Novartis; Research grant / Funding (self): Chugai. All other authors have declared no conflicts of interest.

To determine whether a difference in donor source affects the outcome of transplantation for patients with primary myelofibrosis (PMF), a retrospective study was conducted using the national registry data on patients who received first allogeneic hematopoietic cell transplantation (HCT) with related BM (n=19), related PBSCs (n=25), unrelated BM (n=28) or unrelated umbilical cord blood (UCB; n=11). The 5-year OS rates after related BM, related PBSC and unrelated BM transplantation were 63%, 43% and 41%, respectively, and the 2-year OS rate after UCB transplantation was 36%. On multivariate analysis, the donor source was not a significant factor for predicting the OS rate. Instead, performance status (PS) ⩾2 (vs PS 0–1) predicted a lower OS (P=0.044), and RBC transfusion ⩾20 times before transplantation (vs transfusion ⩽9 times) showed a trend toward a lower OS (P=0.053). No advantage of nonmyeloablative preconditioning regimens in terms of decreasing nonrelapse mortality or increasing OS was found. Allogeneic HCT, and even unrelated BM and UCB transplantation, provides a curative treatment for PMF patients.

Few studies have evaluated the risk factors for chronic GVHD and organ involvement associated with different graft types, including unrelated cord blood (U-CB). We retrospectively studied 4818 adult patients who received their first allogeneic transplantation and survived for at least 100 days. The incidence of chronic GVHD at 2 years was 37%. The following factors were associated with the development of chronic GVHD: female donor/male recipient, CMV-Ab seropositivity, matched related peripheral blood grafts vs matched related BM grafts, no in vivo T-cell depletion and the occurrence of grade II-IV acute GVHD. Among these factors, the association with acute GVHD occurrence was consistently significant across donor subtypes. The use of U-CB was not associated with chronic GVHD, but was associated with a low incidence of extensive chronic GVHD. Chronic GVHD patients who had received U-CB transplants showed less frequent involvement of the oral cavity (28% vs 55%), eye (12% vs 26%), liver (20% vs 44%), lung (11% vs 25%) and joint (0% vs 6%) than those with matched related BM grafts. In conclusion, we found that U-CB transplants were associated with a low incidence of extensive chronic GVHD and less frequent involvement of the oral cavity, eye, liver, lung and joints.

Cryptogenic organizing pneumonia (COP), previously known as bronchiolitis obliterans organizing pneumonia (BOOP), is a significant complication after allogeneic hematopoietic SCT (HCT). However, the pathogenesis of this complication has not yet been elucidated. Therefore, we identified the pre-transplant risk factors for the development of COP/BOOP using the Japan transplant registry database between 2005 and 2009. Among 9550 eligible recipients, 193 experienced COP/BOOP (2%). HLA disparity (odds ratio (OR) 1.51, P=0.05), female-to-male HCT (OR 1.53, P=0.023), and PBSC transplant (OR 1.84, P=0.0076) were significantly associated with an increased risk of COP/BOOP. On the other hand, BU-based myeloablative conditioning (OR 0.52, P=0.033), or fludarabine-based reduced-intensity conditioning (OR 0.50, P=0.0011) in comparison with a TBI-based regimen and in vivo T-cell depletion (OR 0.46, P=0.055) were associated with a lower risk. Of the 193 patients with COP/BOOP, 77 died, including non-relapse death in 46 (59%). Pulmonary failure and fatal infection accounted for 41% (n=19) and 26% (n=12) of the non-relapse death. Allogeneic immunity and conditioning toxicity could be associated with COP/BOOP. Prospective studies are required to elucidate the true risk factors for COP/BOOP and to develop a prophylactic approach.

In this study, outcomes for 575 adult ALL patients aged ≥45 years who underwent first allo-SCT in CR were analyzed according to the type of conditioning regimen (myeloablative conditioning (MAC) for 369 patients vs reduced-intensity conditioning (RIC) for 206 patients). Patients in the RIC group were older (median age, 58 vs 51 years, P

Radiation monitoring at high energy proton accelerators poses a considerable challenge due to the complexity of the encountered stray radiation fields. These environments comprise a wide variety of different particle types and span from fractions of electron-volts up to several terra electron-volts. As a consequence the use of Monte Carlo simulation programs like FLUKA is indispensable to obtain appropriate field-specific calibration factors. At many locations of the LHC a large contribution to the particle fluence is expected to originate from high-energy neutrons and thus, benchmark experiments with mono-energetic neutron beams are of high importance to verify the aforementioned detector response calculations. This paper summarizes the results of a series of benchmark experiments with quasi mono-energetic neutrons of 100, 140, 200, 250 and 392 MeV that have been carried out at RCNP - Osaka University, during several campaigns between 2006 and 2014.

Estimation of joint torque is an important objective in the analyses of human motion. In particular, many applications seek to discern torque during a desired human motion, which is equivalent to solving the inverse dynamics. The computed torque method is a conventional means of calculating inverse dynamics. The obtained torque, however, invariably includes errors resulting from inexact inertial and viscoelastic parameters. This paper presents a method for solving the inverse dynamics of a human arm passively during tracking. To achieve precise human motion tracking, iterative learning control is used for motion generation. Some experiments that target a human arm are executed to validate the proposed method.

We investigated the efficacy of cord blood transplantation (CBT) for adult acute lymphoblastic leukemia (ALL) by reviewing medical records of 256 patients reported to the Japan Cord Blood Bank Network between June 1997 and August 2006. Cumulative incidence of neutrophil engraftment at day 100 was 78%. Infused CD34-positive cell dose (1 × 10(5) cells/kg) was associated with successful neutrophil engraftment. Cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) at day 100 was 37%. A 2-year disease-free and overall survival (OS) rates were 36% and 42%, respectively. Multivariate analysis showed that age (51 or older vs younger than 50) (hazard ratio 1.9, 95% confidence interval (CI), 1.3-2.8, P=0.001), disease status (non-remission vs remission) (hazard ratio 2.2, 95% CI, 1.5-3.2, P0.0001), grade III-IV acute GVHD (hazard ratio 2.0, 95% CI, 1.2-3.2, P=0.006) and absence of chronic GVHD (hazard ratio 2.4, 95% CI, 1.1-5.1, P=0.02) were negatively associated with OS. CBT is effective for some patients with advanced ALL. It is worth considering for further evaluation.

I.v. BU/fludarabine plus melphalan or TBI in unrelated cord blood transplantation for high-risk hematological diseases

IntroductionHypothyroidism psychocognitive key features may include melancholia, memory impairment, depression and dementia which could be misdiagnosed as a psychiatric disorder.ObjectiveTo study the incidence of hypothyroidism in psychiatric patients.MethodsThis retrospective study included 232 psychiatric patients with mean age of 43.39 ± 10 years old weight mean of 79.81 ± 19.07 kg, BIM of 29.55 ± 6.83, enrolled in a public mental health service.ResultsTwenty point twenty-one percent (39) patients presented hypothyroidism with thyroid-stimulating hormone (TSH) levels above 5 mIU/L and Free T4 levels below 0.7 ng/dl.Comparing the incidence of hypothyroidism in Brazilian population estimated rate of until 10% [1] with this psychiatric patients population we observed a significant difference with p value of 2.28 E-6. Neuroleptics 92%(36), biperiden 62%(24) and benzodiazepines 38% (15) were the most frequent prescribed drugs for these hypothyroidism patients.ConclusionSignificant difference in the incidence of hypothyroidism between general Brazilian population and the studied psychiatric patients was observed [2,3].Disclosure of interestThe authors have not supplied their declaration of competing interest.

BACKGROUND AND PURPOSE Hydrogen sulphide (H2S), a potentially toxic gas, is also involved in the neuroprotection, neuromodulation, cardioprotection, vasodilatation and the regulation of inflammatory response and insulin secretion. We have recently reported that H2S suppresses pancreatic β-cell apoptosis induced by long-term exposure to high glucose. Here we examined the protective effects of sodium hydrosulphide (NaHS), an H2S donor, on various types of β-cell damage. EXPERIMENTAL APPROACH Isolated islets from mice or the mouse insulinoma MIN6 cells were cultured with palmitate, cytokines (a mixture of tumour necrosis factor-α, interferon-γ and interleukin-1β), hydrogen peroxide, thapsigargin or tunicamycin with or without NaHS. We examined DNA fragmentation, caspase-3 and -7 activities and reactive oxygen species (ROS) production in the treated cells thereafter. Apoptotic cell death in isolated islets was also assessed by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling (TUNEL) method. KEY RESULTS NaHS suppressed DNA fragmentation and the activities of caspase-3 and -7 induced by palmitate, the cytokines or hydrogen peroxide. In contrast, NaHS failed to protect islets and MIN6 cells from apoptosis induced by thapsigargin and tunicamycin, both of which cause endoplasmic reticulum stress. NaHS suppressed ROS production induced by cytokines or hydrogen peroxide but it had no effect on ROS production in thapsigargin-treated cells. NaHS increased Akt phosphorylation in MIN6 cells treated with cytokines but not in cells treated with thapsigargin. Treatment with NaHS decreased TUNEL-positive cells in cytokine-exposed islets. CONCLUSIONS AND IMPLICATIONS H2S may prevent pancreatic β-cells from cell apoptosis via an anti-oxidative mechanism and the activation of Akt signalling.

In complex perovskite-type oxides, which have been studied as cathode materials, the thermal expansion coefficient (TEC) increases with the increase in the oxygen ionic conductivity. The aim of the present study is to explain such a behavior from a chemical bond point of view. For the perovskite oxides expressed as A1-x A′ x B1-y B′ y O3-δ and ABO3, the ionicity of A‒O and B‒O bonds and the thermal expansion coefficient were evaluated theoretically by using semiempirical methods. It is found that the thermal expansion coefficient and the oxygen ionic conductivity decrease with the increase in the difference of the ionicity between A‒O and B‒O bonds.

We demonstrate the in vivo effects of bacterially synthesized, N-methionine-free recombinant human granulocyte-macrophage colony stimulating factor (rh GM-CSF) using a crab-eating monkey model. Monkeys were treated with cyclophosphamide (60 mg/kg) and administered with rh GM-CSF (30 micrograms/kg/d) subcutaneously (s.c.) for 7 days. Within 12 h, a transient increase of neutrophils (greater than 15.0 x 10(9)/l) was observed, and complete recovery of WBC counts was obtained by d 9 (d 16 in control monkeys). Neutrophils and eosinophils were absolutely increased (greater than 8 x 10(9)/l) on d 10. Readministration of rh GM-CSF (30 micrograms/kg/d, s.c.) for 3 d (including control monkeys) revealed absolute increases of neutrophils, eosinophils, monocytes and platelets. A two-fold increase of granulocyte/macrophage colony-forming units was also seen in the bone marrow, while the number of burst-forming units-erythroid was not affected. These data indicate that rh GM-CSF of this type stimulates granulopoiesis and thrombopoiesis in vivo.

Generally, point-to-point control for a completely restrained (CR) parallel-wire-driven system requires a balancing internal force to prevent slackening of wires, along with a feedback term based on some displacement sensor. This paper specifically describes CR systems' internal force properties, then presents the possibility of motion convergence at a desired position when the internal force balancing at a position is given as sensorless feedforward input. Subsequently, we use the property of internal force positively for sensorless position control. This positioning method is applicable for low-cost manipulation, which does not require high accuracy, and for emergency positioning of systems when sensors malfunction.

The features of lightning shielding of transmission lines have been calculated using the electrogeometric model (EGM) proposed by Armstrong and Whitehead. Discrepancies, however, have been found in the case of ultra-high voltage (UHV)-designed transmission lines. UHV-designed transmission lines often pass through high-altitude mountain areas, where foggy or rainy conditions are common when there is lightning. While the electrogeometric model determines the striking distance based on the lightning stroke current, environmental conditions, and how they might affect lightning discharge paths, they are not considered. It is possible, therefore, that foggy conditions may cause differences in the performance of transmission-line lightning shielding. This study used scale models of transmission lines for discharge tests with a 1-m air gap and analyzed differences in discharge paths and locations in dry and foggy conditions. The results showed that the polarity of the discharge had a significant influence, but differences in dry and foggy tests were negligible.

The electric geometry model suggested by Armstrong and Whitehead was used to calculate the performance of lightning-shielded transmission lines. However, since the ultra high voltage (UHV) designed transmission lines were brought into 500 kV operation, it has become evident that their actual performance is different from the calculated predictions in terms of their actual faults, lightning observation results, etc. It is thought that the UHV designed transmission lines are subjected to foggy or rainy conditions when lightning strikes, because they often pass through mountainous areas at higher altitudes. However, according to the electric geometry model, the striking distance is determined by the lightning-stroke current value only, and the model does not consider the environment of discharge path for the relevant lightning strokes. These considerations suggest that foggy conditions may affect transmission line lightning shielding performance. In this study, discharge tests were conducted using a scaled-down transmission line with a 5 m air gap. The discharge point to the simulated conductor was analyzed in both dry and foggy conditions. Tests were also conducted with a DC bias applied to the simulated power lines, to take the operating voltage of the lines into consideration. These experiments have shown that the effect of fog on the discharge ratio to the conductors is negligible.

The electrogeometric model has been used to calculate the transmission line lightning shielding characteristics. However, actual UHV design transmission line accidents and the lightning observation results indicate that there are differences between what actually happens and theoretical results. In this paper, long-gap discharge tests were conducted to better understand lightning shielding characteristics, mainly of UHV design transmission lines. As far as the test method is concerned, the arrangements of transmission line conductors were reduced, and simulated as ground electrodes, and a switching impulse voltage was applied to rod electrodes. As a result, discharges occurred most frequently to the conductors with the smallest gaps with the rod electrodes. On the other hand, it was seen that the electric field strength of the transmission lines and their position with respect to ground might have some influence. These results might also be valuable for long air gap dielectrics.

The electrogeometric model (EGM) proposed by Armstrong and Whitehead has been used to calculate the lightning shielding features of transmission lines. While the striking distance equation in the EGM uses the 50% flashover voltage characteristics of negative switching impulses for rod-rod gaps, those characteristics for long air gaps have not been sufficiently examined. The present study has therefore focused on clarifying the 50% flashover characteristics of negative switching impulses for long air gaps. Consequently, saturating characteristics have been obtained for rod-plane gaps compared with almost linear characteristics for rod-rod and rod-conductor gaps. Furthermore, new knowledge was obtained indicating that, for air gaps of around 4 to 5 m, the 50% flashover voltage may possibly be lower for rod-plane gaps than for rod- rod and rod-conductor gaps.

Invasive fungal infection (IFI) is a significant complication after allogeneic hematopoietic stem cell transplantation (HSCT); however, we have little information on its clinical features after reduced intensity cord blood transplantation (RICBT) for adults. We reviewed medical records of 128 patients who underwent RICBT at Toranomon Hospital between March 2002 and November 2005. Most of the patients received purine-analogbased preparative regimens. Graft-versus-host disease (GVHD) prophylaxis was a continuous infusion of either tacrolimus 0.03 mg/kg or cyclosporine 3 mg/kg. IFI was diagnosed according to the established EORTC/NIH-MSG criteria. IFI was diagnosed in 14 patients. Thirteen of the 14 had probable invasive pulmonary aspergillosis and the other had fungemia resulting from Trichosporon spp. Median onset of IFI was day 20 (range: 1-82), and no patients developed IFI after day 100. Three-year cumulative incidence of IA was 10.2%. Four of the 13 patients with invasive aspergillosis (IA) developed grade II-IV acute GVHD, and their IA was diagnosed before the onset of acute GVHD. The mortality rate of IFI was 86%. Multivariate analysis revealed that the use of prednisolone >0.2 mg/kg (relative risk 7.97, 95% confidence interval 2.24-28.4, P = .0014) was a significant risk factor for IA. This study suggests that IFI is an important cause of deaths after RICBT, and effective strategies are warranted to prevent IFI.

Magellanic penguins, Spheniscus magellanicus, are the most abundant penguins living in temperate regions of South America and are good indicators of environmental pollution in the region. Persistent organic pollutants (POPs) were detected in the liver of Magellanic penguins found debilitated or dead on the beaches of Brazil (states of Rio de Janeiro, Sao Paulo, Santa Catarina and Rio Grande do Sul) between 2008 and 2012 as well as in Uruguay and Chile in 2011. Polychlorinated biphenyls (PCBs) were more prevalent than organochlorine pesticides (DDTs ∼ HCB ∼ Drins) and polybrominated diphenyl ethers (PBDEs). Among PCBs, penta-, hexa- and hepta-chlorinated congeners were predominant. Concentrations of POPs were similar between the Pacific and Atlantic penguin populations, except for PCBs, which were relatively higher in the Pacific population. During the study years (2008-2012), large variations were found in organochlorine pesticides and PCBs tended to decline. Overall, the southern portion of South America has low concentrations of POPs, with either a constant trend or evidence of decline.

The authors have developed a solenoid model coil used for superconducting magnetic energy storage (SMES) for power system control, aimed at drastically reducing the costs of the SMES system. The single solenoid model coil of 2.9 MJ is designed with the rated current of 9.6 kA, a maximum magnetic field of 5.5 T and coil charge rates equivalent to those of the practical 100 MW/54 MJ class SMES. The coil is characterized by the use of an aluminum stabilized NbTi CIC (Cable-in-conduit) conductor. The experimental SMES consists mainly of a 2.9 MJ coil, the cooling system for the CIC conductor and the 1 MW class AC/DC converter. The SMES is connected to 6 kV distribution lines at a substation. In the field test, the SMES's 17 ms responses for the step input of active and reactive power were ascertained. Furthermore, its function of compensating for load fluctuation in the 6 kV distribution line was confirmed. The test results show the realization of a practical SMES system for power line control

Superconducting technology has conventionally been used in magnetic separation using high DC field as its industrial application. In the field of electromagnetic processing of materials (EPM), on the other hand, it has a lot of advantages in the production of high quality, high value-added materials, such as uniformity in crystals, faster refining speed, facilitation of separation of inclusions, and attracts considerable attention. In the present study, we intended to lay a new path to industrial application of superconducting technology, and aimed at applying AC superconducting technology to high AC field as is expected in EPM. We examined thermal insulation technology regarding high temperature metals and low temperature superconducting magnets, and showed a path to solutions. We also designed magnets for applied stirring field, and made a prototype of magnets in which effective countermeasures are adopted against the shape of magnets and electromagnetic oscillation

We conducted a nation-wide survey of 112 adult Japanese patients who underwent reduced-intensity stem cell transplantation (RIST) from 1999 to 2002. Underlying diseases included indolent (n=45), aggressive (n=58) and highly aggressive lymphomas (n=9). Median age of the patients was 49 years. A total of 40 patients (36%) had relapsed diseases after autologous stem cell transplantation and 36 patients (32%) had received radiotherapy. RIST regimens were fludarabine-based (n=95), low-dose total body irradiation-based (n=6) and others (n=11). Cumulative incidences of grade II-IV acute graft-versus-host disease (GVHD) and chronic GVHD were, respectively, 49 and 59%. Cumulative incidences of progression and progression-free mortality were 18 and 25%, respectively. With a median follow-up of 23.9 months, 3-year overall survival rates were 59%. A multivariate analysis identified three significant factors for progression, which are history of radiation (relative risk (RR) 3.45, confidential interval (CI) 1.12-10.0, P=0.03), central nervous system involvement (RR 6.25, CI 2.08-20.0, P=0.001) and development of GVHD (RR 0.28, CI 0.090-0.86, P=0.026). RIST may have decreased the rate of transplant-related mortality, and GVHD may have induced a graft-versus-lymphoma effect. However, whether or not these potential benefits can be directly translated into improved patient survival should be evaluated in further studies.

Since the introduction of reduced-intensity stem-cell transplantation (RIST), allogeneic stem-cell transplantation has become available for elderly patients. While pharmacokinetics of cyclosporine might differ according to age or other factors, cyclosporine is uniformly started at an oral dose of 6 mg/kg/day. We retrospectively reviewed medical records of 35 patients aged between 32 and 65 (median 52) years who had undergone RIST. Doses of cyclosporine were adjusted to the target blood trough level of 150-250 ng/ml. Cyclosporine dosages were changed in 33 patients (94%). Dose reduction was required in 32 patients because of high blood levels (n=25), renal dysfunction (n=3), hepatic dysfunction (n=2), and hypertension (n=2). Cyclosporine doses were increased in one because of the suboptimal level. The median of the achieved stable doses was 3.1 mg/kg/day (range, 1.0-7.4). Five patients sustained Grade III toxicities according to NCI-CTC version 2.0: renal dysfunction (n=4), hyperbilirubinemia (n=2), and hypertension (n=2). No patients developed grade IV toxicity. There was no statistically significant difference in the frequency and severity of cyclosporine toxicities between patients aged 50 years and above and those below 50 years. The initial oral cyclosporine dose of 6 mg/kg/day was unnecessarily high irrespective of age. The possible overdose of cyclosporine might have aggravated regimen-related toxicities.

Efficacy of reduced-intensity stem-cell transplantation (RIST) for acute lymphoblastic leukemia (ALL) was investigated in 33 patients (median age, 55 years). RIST sources comprised 20 HLA-identical related donors, five HLA-mismatched related, and eight unrelated donors. Six patients had undergone previous transplantation. Disease status at RIST was first remission (n=13), second remission (n=6), and induction failure or relapse (n=14). All patients tolerated preparatory regimens and achieved neutrophil engraftment (median, day 12.5). Acute and chronic graft-versus-host disease (GVHD) developed in 45 and 64%, respectively. Six patients received donor lymphocyte infusion (DLI), for prophylaxis (n=1) or treatment of recurrent ALL (n=5). Nine patients died of transplant-related mortality, with six deaths due to GVHD. The median follow-up of surviving patients was 11.6 months (range, 3.5-37.3 months). The 1-year relapse-free and overall survival rates were 29.8 and 39.6%, respectively. Of the 14 patients transplanted in relapse, five remained relapse free for longer than 6 months. Cumulative rates of progression and progression-free mortality at 3 years were 50.9 and 30.4%, respectively. These findings suggest the presence of a graft-versus-leukemia effect for ALL. RIST for ALL is worth considering for further evaluation.

Allogeneic hematopoietic stem cell transplantation (allo-SCT) recipients are prone to infections. The incidences of mycobacterial infections after allo-SCT in several case series vary from less than 0.1-5.5%. However, no study has been published on tuberculosis following unrelated cord blood transplantation (UCBT). We retrospectively reviewed medical records of 113 adult patients with a median age of 54 years who underwent reduced-intensity UCBT (RI-UCBT) at Toranomon Hospital from March 2002 to May 2004. Mycobacterium tuberculosis infections were diagnosed in three patients (2.7%), of these two patients developed primary infection and one patient developed reactivation of latent tuberculosis. The interval between RI-UCBT and the diagnosis of tuberculosis was 34, 41 and 61 days. All the patients had disseminated disease at diagnosis. Histological examination showed the lack of granuloma in caseous necrosis. Combination antituberculous treatments showed limited efficacy, and two patients died immediately after diagnosis. M. tuberculosis caused life-threatening illness, rapidly progressing in RI-UCBT recipients. The lack of granuloma in caseous necrosis suggests the impaired T-cell function in early post transplant phase of RI-UCBT. We should consider M. tuberculosis in the differential diagnoses of fever of unknown source after RI-UCBT.

Since 1999, a Japanese national project to realize commercially feasible SMES for designated applications has been promoted. Model coils for power system stabilization, load fluctuation compensation and frequency control have been fabricated and tested. In this paper, we introduce the present status of the project, including feasibility studies of an HTS SMES.

Purpose: The purpose of this research was to evaluate the feasibility of reduced-intensity unrelated cord-blood transplantation (RI-UCBT) in adult patients with advanced hematological diseases. Experimental Design: Thirty patients (median age, 58.5 years; range, 20–70 years) with advanced hematological diseases underwent RI-UCBT at Toranomon Hospital between September 2002 and August 2003. Preparative regimen composed of fludarabine 25 mg/m2 on days −7 to −3, melphalan 80 mg/m2 on day −2, and 4 Gy total body irradiation on day −1. Graft-versus-host disease prophylaxis was composed of cyclosporin alone. Results: Twenty-six patients achieved primary neutrophil engraftment after a median of 17.5 days. Median infused total cell dose was 3.1 × 107/kg (range, 2.0–4.3 × 107/kg). Two transplant-related mortalities occurred within 28 days of transplant, and another 2 patients displayed primary graft failure. Cumulative incidence of complete donor chimerism at day 60 was 93%. Grade II-IV acute graft-versus-host disease occurred in 27% of patients, with median onset 36 days. Primary disease recurred in 3 patients, and transplant-related mortality within 100 days was 27%. Estimated 1-year overall survival was 32.7%. Excluding 7 patients with documented infection, 19 patients displayed noninfectious fever before engraftment (median onset, day 9). Manifestations included high-grade fever, eruption, and diarrhea. The symptoms responded well to corticosteroid treatments in 7 of 13 treated patients. Conclusion: This study demonstrated the feasibility of RI-UCBT in adults.

With the increasing frequency of haploidentical transplantation, it is becoming more important to establish the degree of HLA mismatch that can be accepted. We retrospectively analyzed clinical data of 50 adult Japanese patients with high-risk hematologic malignancies who underwent allogeneic peripheral blood stem cell transplantation (PBSCT) from two- or three-loci-mismatched related donors with HLA class I and II gene disparities in the graft-versus-host direction. They were treated at 20 transplant centers between 1996 and 2002. In all, 18 patients received unmanipulated PBSC, while 32 received purified CD34+ blood cells. Conventional (n=31) or reduced-intensity (n=19) conditioning regimens were used. Of the 39 patients (78%) who survived for > or =28 days after transplant, 37 (95%) achieved neutrophil engraftment, while graft failure and rejection occurred in two of 39 (5%) and three of 37 (8%) patients, respectively. Stepwise Cox regression analysis revealed a significantly lower incidence of grades II-IV acute GVHD in patients receiving purified CD34+ cells (hazard ratio 0.32; 95% CI 0.12-0.84; P=0.022). By 1 year post transplant, 28 patients (56%) had died of transplant-related problems, including infectious complications (30%). Although the number of patients is small, our data suggest that transplant-related problems, particularly infectious complications, are major obstacles to the success of this therapy.

We investigated effects of variations in the cellular composition of G-CSF-mobilized peripheral blood progenitor cell (G-PBPC) allografts on clinical outcomes of allogeneic PBPC transplantation. We retrospectively analyzed transplanted doses of various immunocompetent cells from 27 HLA-identical sibling donors in relation to engraftment, incidence of graft-versus-host disease (GVHD), and survival. Significant variability was documented in both absolute numbers and relative proportions of CD34+, CD2+, CD3+, CD4(high)+, CD4+25+, CD8(high)+, CD19+, CD56+, and CD56+16+ cells contained in these allografts. Stepwise Cox regression analysis revealed that the CD56+ cell dose was significantly inversely correlated with the incidence of GVHD. Thus, there was a significantly higher incidence of grade II acute GVHD in patients receiving a lower CD56+16+ cell dose (hazard ratio (HR) 0.0090; 95% confidence interval (CI)

A prospective study was conducted to test the utility of the motor evoked potentials (MEPs) from the erector spinae muscles as a measure to estimate the motor level of thoracic compression myelopathies in 13 consecutive patients.To confirm whether this test is a useful addition to the neurological examination in non-invasively localizing the level responsible for the main functional change in mild to moderate thoracic myelopathy.Department of Orthopaedic Surgery, Kochi Medical School, Kochi, Japan.This electrophysiological study consisted of transcranial magnetic stimulation (TMS) of the brain and surface recording of MEPs from voluntarily contracted erector spinae muscles with the patient in the prone position. The recordings were obtained unilaterally from the same side as the lower-limb affected at 12 serial interspinous levels from T5-6 to L4-5. The results were compared to the MEP data from normal subjects and to neurological and MRI findings.Multisegmental MEP studies demonstrated a focal conduction block in one patient, a single site of conduction delay in seven, and normal conduction in five. The conduction block was characterized by an abrupt reduction in amplitude of the MEPs. Examination of the sites conduction delay showed that the latency difference between the two adjacent levels was longer than the corresponding normal upper limit by 1.00+/-0.40 ms (range, 0.62-1.61 ms). The site of conduction abnormalities approximated to the compressive lesion site shown by MRI. All five patients with false-negative MEP findings had the lesion site at or caudal to the T10-11 vertebral level.This method has the advantage of instantaneously testing multisegments of the thoracic spinal cord. The technique is of particular value in estimating the motor level of the lesions rostral to T10-11 vertebral level, which can not be achieved by clinical examinations or MEP recordings from the lower limb.