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Climate impact of aviation is expected to increase further. Aircraft routings are an important measure for climate impact reductions. To find an effective aircraft routing strategy for reducing the impact, the first version of the submodel AirTraf has been developed; this submodel can simulate global air traffic in the ECHAM/MESSy Atmospheric Chemistry (EMAC) model. This paper describes the updated submodel AirTraf 2.0. Seven new aircraft routing options are introduced, including contrail avoidance, minimum economic costs, and minimum climate impact. Example simulations of the new routing options are presented by using around 100 north-Atlantic flights of an Airbus A330 aircraft for a typical winter day. The results clearly show that the family of optimum flight trajectories (three-dimensional) varies according to the routing options. The comparison of the results for various routing options reveals characteristics of the routing with respect to air traffic performances. The minimum cost option obtains a trade-off solution between the minimum time and the minimum fuel solutions. The aircraft routings for contrail avoidance and minimum climate impact reduce the potential climate impact, which is estimated by using algorithmic Climate Change Functions, whereas these two routings increase flight operating costs. A trade-off between the aircraft operating costs and the climate impact is confirmed. The simulation results are compared with literature data and the consistency of the submodel AirTraf 2.0 is verified. [ABSTRACT FROM AUTHOR]

Mobility is becoming more and more important to society and hence air transportation is expected to grow further over the next decades. Reducing anthropogenic climate impact from aviation emissions and building a climatefriendly air transportation system are required for a sustainable development of commercial aviation. A climate optimized routing, which avoids climate-sensitive regions by rerouting horizontally and vertically, is an important measure for climate impact reduction. The idea includes a number of different routing strategies (routing options) and shows a great potential for the reduction. To evaluate this, the impact of not only CO2 but also non-CO2 emissions must be considered. CO2 is a long-lived gas, while non-CO2 emissions are short-lived and are inhomogeneously distributed. This study introduces AirTraf (version 1.0) that performs global air traffic simulations, including effects of local weather conditions on the emissions. AirTraf was developed as a new submodel of the ECHAM5/MESSy Atmospheric Chemistry (EMAC) model. Air traffic information comprises Eurocontrol's Base of Aircraft Data (BADA Revision 3.9) and International Civil Aviation Organization (ICAO) engine performance data. Fuel use and emissions are calculated by the total energy model based on the BADA methodology and Deutsches Zentrum für Luft- und Raumfahrt (DLR) fuel flow method. The flight trajectory optimization is performed by a genetic algorithm (GA) with respect to a selected routing option. In the model development phase, benchmark tests were performed for the great circle and flight time routing options. The first test showed that the great circle calculations were accurate to -0.004%, compared to those calculated by the Movable Type script. The second test showed that the optimal solution found by the algorithm sufficiently converged to the theoretical true-optimal solution. The difference in flight time between the two solutions is less than 0.01%. The dependence of the optimal solutions on the initial set of solutions (called population) was analyzed and the influence was small (around 0.01%). The trade-off between the accuracy of GA optimizations and computational costs is clarified and the appropriate population and generation (one iteration of GA) sizing is discussed. The results showed that a large reduction in the number of function evaluations of around 90% can be achieved with only a small decrease in the accuracy of less than 0.1%. Finally, AirTraf simulations are demonstrated with the great circle and the flight time routing options for a typical winter day. The 103 trans-Atlantic flight plans were used, assuming an Airbus A330-301 aircraft. The results confirmed that AirTraf simulates the air traffic properly for the two routing options. In addition, the GA successfully found the time-optimal flight trajectories for the 103 airport pairs, taking local weather conditions into account. The consistency check for the AirTraf simulations confirmed that calculated flight time, fuel consumption, NOx emission index and aircraft weights show good agreement with reference data. [ABSTRACT FROM AUTHOR]

The article focuses on a study that examined the global variation of sonic boom overpressure attributed to seasonal changes in the atmosphere with temperature, pressure and density gradients using radiosonde observations obtained over a period of 10 years. The researchers compared seasonal variations and geographic differences in overpressure due to a nonstandard atmosphere with standard atmospheric conditions. They found three trends of global variation in overpressure.

This study describes the start/unstart characteristics of a finite and rectangular supersonic biplane wing. Two wing models were tested in wind tunnels with aspect ratios of 0.75 (model A) and 2.5 (model B). The models were composed of a Busemann biplane section. The tests were carried out using supersonic and transonic wind tunnels over a Mach number range of 0.3 ≤ M∞≤ 2.3 with angles of attack of 0°, 2°, and 4°. The Schlieren system was used to observe the flow characteristics around the models. The experimental results showed that these models had start/unstart characteristics that differed from those of the Busemann biplane (two dimensional) owing to three-dimensional effects. Models A and B started at lowerMach numbers than the Busemann biplane. The characteristics also varied with aspect ratio: model A (1.3 < M∞≤< 1.5) started at alower Mach number than model B (1.6 < M∞ < 1.8) owing to the lower aspect ratio. Model B was located in the double solution domain for the start/unstart characteristics atM∞ = 1.7, and model B was in either the start or unstart state at M∞ = 1.7. Once the state was determined, either state was stable. [ABSTRACT FROM AUTHOR]

Aviation aims to reduce its climate effect by exploiting the potential of identifying alternative climate optimized aircraft trajectories. Such climate-optimized trajectories require a dedicated meteorological service in order to inform on those regions of the atmosphere where aviation emissions have a large effect on climate, for example, by contrail formation or nitrogen-oxide (NOx)-induced ozone formation. With the algorithmic Climate Change Functions (aCCFs) prototypes of a mathematical formulation for the temporal and spatial climate effects of aviation emissions in the atmosphere is provided, which relies solely on numerical weather prediction at the time and location of emissions. Based on the recently published consistent set of aCCF-V1.0, we here introduce newly derived calibration factors for the individual non-CO2 effects of aviation (NOx, water vapour, contrail cirrus) and establish version V1.0A of aCCFs (aCCF-V1.0A). ACCF-V1.0A represents an updated formulation of aCCF while exploring the current level of scientific understanding of individual climate effects of aviation emissions by evaluating quantitative estimates of climate effects with the state-of-the-art climate-response model AirClim. Individual scaling factors (i.e. AirClim calibration factors) are provided for the respective non-CO2 effects comprising contrail cirrus, water vapour and NOx-induced climate effects on ozone and methane, resulting uniformly in lower estimates in aCCF-V1.0A for all species compared to the earlier version aCCF-V1.0. [ABSTRACT FROM AUTHOR]

Objective: Gestational diabetes (GDM) is considered as mild maternal hyperglycemia during late pregnancy. However, the significance of mild hyperglycemia during early pregnancy (before 20 weeks' gestation) is still controversial. We investigated to identify the characteristics and significance of Japanese women with GDM who were diagnosed before 20 weeks' gestation. Methods: This retrospective study included Japanese women who were diagnosed with GDM before 20 weeks' gestation (the early GDM [e-GDM] group) and those who were diagnosed at 24 weeks' gestation or later (the late GDM [l-GDM] group). We used IADPSG criteria to diagnose GDM. We compared the maternal characteristics and perinatal outcomes between the groups. Results: We included 117 and 351 women in the e- and l-GDM groups, and the mean gestational age (GA) at diagnosis was 13.7±4.3 and 28.0±3.1 weeks, respectively. Maternal prepregnancy body mass index (BMI) in the e-GDM group was significantly higher than that in the l-GDM group (24.7±4.9 vs. 23.0±4.6, p=0.002). Although fasting plasma glucose (PG) levels were also significantly higher in the e-GDM group (88.7±8.9 vs. 84.3±10.8 mg/dl, p<0.0001), there were no significant differences in the 1- and 2-hour PG values between the groups. The mean GA at the beginning of insulin therapy was 21.1±7.3 and 30.0±4.6 weeks in the e- and l-GDM groups, respectively. The rate of insulin therapy was higher in the l-GDM group (41.9% vs. 52.3%, p<0.05). The perinatal outcomes did not differ between the groups. When we compared in the obese subgroups (prepregnancy BMI ≥2 ), we found the prepregnancy BMI was significantly higher in the e-GDM group (31.6±4.7 vs. 29.3±3.4, p=0.0016). However, there were no significant differences in the rate of insulin administration (52.4% vs. 65.6%, ns) or in the perinatal outcomes between the groups. Conclusion: The Japanese women with GDM who were diagnosed before 20 weeks were more frequently obese than those who were diagnosed at 24 weeks or later. The findings suggest that early diagnosis and treatment intervention seemed to be beneficial in obese women with GDM. [ABSTRACT FROM AUTHOR]

The optimization of aircraft trajectories involves balancing operating costs and climate impact, which are often conflicting objectives. To achieve compromise optimal solutions, higher-level information such as preferences of decision-makers must be taken into account. This paper introduces the SolFinder 1.0 module, a decision-making tool designed to identify eco-efficient aircraft trajectories, which allow to reduce the flights climate impact with limited cost penalties compared to cost-optimal solutions. SolFinder 1.0 offers flexible decision-making options that allow users to select trade-offs between different objective functions, including fuel use, flight time, NOx emissions, contrail distance, and climate impact. The module is included in the AirTraf 3.0 submodel, which optimizes trajectories under atmospheric conditions simulated by the ECHAM/MESSy Atmospheric Chemistry model. This paper focuses on the ability of the module to identify eco-efficient trajectories while solving a bi-objective optimization problem that minimizes climate impact and operating costs. SolFinder 1.0 enables users to explore trajectory properties at varying locations of the Pareto fronts without prior knowledge of the problem results and to identify solutions that limit the cost of reducing the climate impact of a single flight. [ABSTRACT FROM AUTHOR]

The multibeam mask writer MBM-1000 is developed for semiconductor production for the 5-nm technology node. It is designed to accomplish high patterning resolution with a 10-nm beam and high throughput with blanking aperture array supporting data transfer rate of 300 Gbps and an inline real-time data path. It has better beam resolution than the EBM-9500 and has higher throughput at a shot count of more than 500 Gshot/pass. To further improve patterning resolution, pixel-level dose correction (PLDC) is implemented to MBM-1000. It enhances dose contrast by dose modulation pixel by pixel. Correction efficiency of PLDC is evaluated for linearity correction by simulation with a threshold dose model. It is concluded that PLDC corrects critical dimension linearity even without extra dose modulation and improves dose margin with additional dose modulation of 140%. [ABSTRACT FROM AUTHOR]

Background: Although breastfeeding is expected to reduce the incidence of diabetes in women with gestational diabetes, the effect has not been clearly confirmed. We examined whether or not high-intensity breastfeeding reduces the incidence of abnormal glucose tolerance and investigated the effect of high-intensity breastfeeding on insulin resistance during the first year postpartum in Japanese women with current gestational diabetes. Methods: In this retrospective study, we included women with gestational diabetes who underwent postpartum 75 g oral glucose tolerance test during the first year (12-14 months) postpartum from 2009 to 2011 at a single tertiary perinatal care center in Japan. High-intensity breastfeeding was defined as the condition in which infants were fed by breastfeeding alone or 80% or more of the volume. We investigated the effect of high-intensity breastfeeding on the prevalence of postpartum abnormal glucose tolerance and the postpartum homeostasis model of assessment of insulin resistance (HOMA-IR), after controlling for confounders, including prepregnancy obesity and weight changes during pregnancy and postpartum. Results: Among 88 women with gestational diabetes, 46 (52%) had abnormal glucose tolerance during the postpartum period. High-intensity breastfeeding women (n = 70) were significantly less likely to have abnormal glucose tolerance than non-high-intensity breastfeeding women (n = 18) (46% vs. 78%, p = 0.015). High-intensity breastfeeding was also associated with a lower HOMA-IR at 12-14 months postpartum than non-high-intensity breastfeeding (1.41 ± 1.02 vs. 2.28 ± 1.05, p = 0.035). Those associations remained significant after controlling for confounders. At least six months of high-intensity breastfeeding had a significant effect on lowering both the abnormal glucose tolerance prevalence and HOMA-IR compared with non-high-intensity breastfeeding. Conclusions: In Japanese women with gestational diabetes, high-intensity breastfeeding ≥6 months had a protective effect against the development of abnormal glucose tolerance during the first year postpartum through improving insulin resistance, independent of obesity and postpartum weight change. [ABSTRACT FROM AUTHOR]

Objective Pregnancy after conization is associated with a high risk of preterm delivery. However, because risk factors for preterm delivery after conization remain unknown, we conducted a multicenter observational study to investigate risk factors associated with preterm delivery. Methods We selected patients who had previously undergone conization and reviewed medical records from 18 hospitals in cooperation with Keio University School of Medicine between January 2013 and December 2019. Women were classified as nulliparous and primiparous, and a multiple logistic regression analysis was performed to evaluate the relative contributions of the various maternal risk factors for preterm delivery (i.e. delivery before 37 gestational weeks). Results Among 409 pregnant women after conization, 68 women delivered preterm (17%). The incidence of nulliparity (p = .014) was higher and a history of preterm delivery (p = .0010) was more common in the preterm delivery group than in the term delivery group. Furthermore, the proportion of women diagnosed with adenocarcinoma in situ (AIS) and cervical cancer in the preterm delivery group was higher than that in the term delivery group (p = .0099 and .0004, respectively). In multiple regression models in nulliparous women, cervical cancer or AIS (Odds ratio [OR]: 4.16, 95% CI: 1.26–13.68, p = .019) and a short cervix in the second trimester (OR: 13.41, 95% CI: 3.88–46.42, p < .0001) increased the risk of preterm delivery. Furthermore, a history of preterm delivery (OR: 7.35, 95% CI: 1.55–34.86, p = .012), cervical cancer or AIS (OR: 5.07, 95% CI: 1.24–20.73, p = .024), and a short cervix in the second trimester (OR: 4.29, 95% CI: 1.11–16.62, p = .035) increased the risk of preterm delivery in the multiple regression models in primiparous women. Conclusion Pregnant women who previously underwent conization are at risk for preterm delivery. The histological type of AIS and cervical cancer was evaluated as a risk factor for preterm delivery. KEY MESSAGES Prior preterm delivery, presence of a short cervix, and cervical cancer or AIS were predictors of preterm delivery after conization. The depth of conization in cervical cancer or AIS group was significantly larger than that in the CIN group. [ABSTRACT FROM AUTHOR]

Aviation aims to reduce its climate impact by adopting trajectories, that avoid those regions of the atmosphere where aviation emissions have a large impact. To that end, prototype algorithmic climate change functions (aCCFs) can be used, which provide spatially and temporally resolved information on aviation's climate impact in terms of future near-surface temperature change. These aCCFs can be calculated with meteorological input data obtained from e.g. numerical weather prediction models. We here present the open-source Python Library called CLIMaCCF, an easy to use and flexible tool which efficiently calculates both the individual aCCFs (i.e., water vapour, nitrogen oxide (NOx) induced ozone and methane, and contrail-cirrus aCCFs) and the merged non-CO2 aCCFs that combine all these individual contributions. These merged aCCFs can be only constructed with the technical specification of aircraft/engine parameters, i.e., NOx emission indices and flown distance per kg burnt fuel. These aircraft/engine specific values are provided within CLIMaCCF version V1.0 for a set of aggregated aircraft/engine classes (i.e. regional, single-aisle, wide-body). Moreover, CLIMaCCF allows by a user-friendly configuration setting to choose between a set of different physical climate metrics (i.e. average temperature response for pulse or future scenario emissions over the time horizons of 20, 50 or 100 years). Finally, we demonstrate the abilities of CLIMaCCF by a series of example applications. [ABSTRACT FROM AUTHOR]

Background: Thyroid rupture following blunt trauma is extremely rare, and neck pain without swelling may be the only presenting symptom. However, hemorrhage and hematoma subsequently causes severe tracheal compression and respiratory distress. Case presentation: A 71-year-old Japanese woman visited our emergency room with a complaint of increasing right-sided neck pain at the thyroid cartilage level after she tripped and accidentally hit her neck against a pole 3 h back. On admission, her vital signs were stable. There was no swelling or subcutaneous emphysema. Laryngeal endoscopy revealed mild laryngeal edema, although there was no impairment in vocal fold mobility on either side. Contrast-enhanced computed tomography (CT) revealed rupture of the right lobe of the thyroid gland accompanied by a large hematoma extending from the neck to the mediastinum. Under general anesthesia, the right lobe was resected and the hematoma was evacuated. Conclusion: Only a few isolated cases of thyroid rupture caused by blunt neck trauma have been reported in patients with normal thyroid glands and neck pain without swelling may be the only presenting symptom. When suspected, CT should be performed to confirm the diagnosis determine the optimal treatment. [ABSTRACT FROM AUTHOR]

Abstract??The mushroom genusAmanitahas a spectrum of chemical compounds affecting survival and performance of animals. Ibotenic acid is one of such compounds found in someAmanitamushrooms. We studied the effects of ibotenic acid and its derivative, muscimol, on egg-to-pupa survival, pupation time, and pupal size in fiveDrosophilaspecies (Diptera: Drosophilidae),Drosophila bizonata,Drosophila angularis,Drosophila brachynephros,Drosophila immigrans, andDrosophila melanogaster. The first three species are mycophagous and use a wide range of mushrooms for breeding, whereasD. immigransandD. melanogasterare frugivorous. We reared fly larvae on artificial medium with 500, 250, 125, and 62.5??g/ml of ibotenic acid and/or musimol. The three mycophagous species were not susceptible to ibotenic acid, whereas the two frugivorous species were affected. In experiments withD. melanogaster, muscimol was less toxic than ibotenic acid. [ABSTRACT FROM AUTHOR]

MALT (Micro-Analysis Laboratory, Tandem accelerator) at The University of Tokyo is a research and service facility for elemental and isotopic analysis using a tandem accelerator for AMS, PIXE and NRA. Among these, AMS is the most promising technique at MALT. After the AMS-8 conference in 1999, the overall performance was greatly improved for 10Be-, 26Al- and 14C-AMS. For 10Be-AMS, the negative ion current was considerably increased by a new Cs-ionizer system and the replacement of the compound powder (Nb instead of Ag) for the BeO target. More than 3 μA current of BeO− ions can be extracted while it had been typically 1 μA before. For 26Al-AMS, by examining the sample ignition process, the negative ion gain was increased more than 200 nA (typically 100 nA before), which greatly improved the overall efficiency. For 14C-AMS, the 12C− current dependency problem has been moderated substantially by installing a fine controllable Cs oven and careful beam tuning. As a consequence, the precision is now better than 0.5% for modern carbon. In addition, systems for 36Cl-AMS and 129I-AMS are currently being developed for future research programs at MALT. [Copyright &y& Elsevier]

Objective: Gestational diabetes (GDM) is one of the most common complications during pregnancy, up to 12% or more of all pregnant women. It is well established evidence that women affected by GDM during pregnancy are high risk of the development of diabetes after delivery. Several studies showed that breastfeeding has a protective effect against the development of diabetes in general population and in women with GDM during pregnancy. However, underlying mechanism regarding the protective effect has not been clearly understood. Therefore, in this study, we investigated the effect of breastfeeding on insulin resistance during the first year postpartum in Japanese women with current gestational diabetes. Methods: In this retrospective study, we included women who were diagnosed as having GDM after 24 weeks' gestation during pregnancy and underwent postpartum 75g oral glucose tolerance test (OGTT) during the first year postpartum at a single tertiary perinatal care center in Japan. We used IADPSG criteria and WHO criteria to make a diagnosis of GDM during pregnancy and abnormal glucose tolerance (AGT) after delivery, respectively. We defined AGT as impaired glucose intolerance and diabetes by WHO criteria. Regarding breastfeeding conditions, we defined highintensity breastfeeding (HIB) as the condition in which infants were fed by breastfeeding alone or 80% or more of the volume, and other statuses, including partial and non-breastfeeding, as non-HIB. We investigated the effect of HIB on the prevalence of postpartum abnormal glucose tolerance and the postpartum homeostasis model of assessment of insulin resistance (HOMA-IR), after controlling for confounders, including prepregnancy obesity and weight changes during pregnancy and postpartum. Results: We included 88 women affected by GDM during pregnancy, and among them, 46 (52%) women had AGT during the postpartum period. Among the all participants, 70 (79.5%) women fed their infants by HIB at least 6 weeks or more during postpartum period (HIB group), and the other 18 (20.5%) women were in the non-HIB group. HIB women were significantly less likely to have AGT than non-HIB women (46% vs. 78%, p<0.02). Women in the HIB group were also associated with a lower HOMA-IR at one year postpartum than those in the non-HIB group (1.41±1.02 vs. 2.28±1.05, p=0.035). Regarding the duration of breastfeeding, we found that at least six months of HIB had a significant effect of both reducing the prevalence of the AGT and improving HOMA-IR during one year postpartum, in comparison with non-HIB. Conclusions: In Japanese women with GDM, HIB at least 6 months or more had a protective effect against the development of AGT during the first year postpartum through improving insulin resistance, independent of obesity and postpartum weight change. [ABSTRACT FROM AUTHOR]

Background and Objective We compared the hemoglobin-maintaining effects between continuous erythropoietin receptor activator (CERA) and darbepoetin-α (DA) in patients with chronic kidney disease (CKD) during the 3 months before dialysis initiation. Methods This study was conducted with 37 CERA-administered patients and 26 DA-administered patients who had initiated dialysis at a participating facility between January 2012 and December 2014. We investigated clinical laboratory data 3 months before and at dialysis initiation, and compared these data between the CERA and DA groups. Results No significant differences in hemoglobin level or reticulocyte count were found between the two groups 3 months before dialysis initiation. However, at dialysis initiation, the hemoglobin level (CERA 9.82 ± 1.52 vs. DA 8.79 ± 1.07 g/dL; P = 0.003) and the reticulocyte count (CERA 5.21 ± 2.95 vs. DA 3.15 ± 1.62 9 104/µL; P = 0.004) were significantly higher in the CERA group than in the DA group. Moreover, the extent of changes in the erythropoietin resistance index during the 3 months before dialysis initiation was significantly increased in the DA group compared with the CERA group. Conclusions Our results suggest that CERA may be more effective than DA in maintaining hemoglobin levels in patients with CKD during 3 months before dialysis initiation. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the differences between acoustic trauma (AT) and other types of acute noise-induced hearing loss (ANIHL), we performed a literature search and case reviews. Methods: The literature search based on online databases was completed in September 2016. Articles on ANIHL and steroid treatment for human subjects were reviewed. The source sounds and treatment sequelae of our accumulated cases were also reviewed. Hearing loss caused by gun-shots and explosions was categorized into the AT group, while hearing loss caused by concerts and other noises was categorized into the ANIHL group. Results: Systemic steroid treatment did not appear to be effective, at least in the AT group, based on both the literature and our case reviews. However, effective recovery after treatment including steroids was observed in the ANIHL group. The difference in hearing recovery between the AT and ANIHL groups was statistically significant (p = .030), although differences in age, days from the onset to treatment and pretreatment hearing levels were not significant. Conclusions: Hearing recovery from AT is very poor, whereas, ANIHL is recoverable to some extent. Therefore, it is essential to differentiate between these two groups for accurate prediction of the hearing prognosis and evaluation of treatment effects. [ABSTRACT FROM AUTHOR]

Objectives: This study used Tsumura Suzuki Obese Diabetes (TSOD) mice as a spontaneous type 2 diabetes model and Tsumura Suzuki Non-obesity (TSNO) mice as controls to investigate factors involved in the onset of hearing impairment. Method: Body weight, blood glucose levels, and auditory brainstem responses (ABRs) were measured. The cochleae were excised and evaluated histopathologically. Results: The TSOD mice showed significant hyperglycemia at 2-7 months and severe obesity at 5-10 months; significantly elevated ABR thresholds at 8-10 months; and the capillary lumens in the cochlea stria vascularis were narrower in the TSOD mice than in the TSNO mice. At 17 months, India ink vascular staining of the TSOD mice's cochleae revealed decreased capillary density in the stria vascularis. The vascular area of capillaries in the stria vascularis and the vascular area were significantly smaller in TSOD mice. Histopathological analysis showed vessel wall thickening in the modiolus and narrowed capillaries in the stria vascularis, suggesting reduced blood flow to the inner ear. Conclusion: The diabetes mice model used in our study showed early age-associated hearing loss, and histopathology showed findings of vessel wall thickening in the modiolus, narrowing of capillaries in the stria vascularis, and chronically reduced blood flow in the cochlea. [ABSTRACT FROM AUTHOR]

Objectives. This study investigated the clinical course of myeloperoxidase-antineutrophil cytoplasm autoantibody (MPO-ANCA)-associated vasculitis after starting dialysis. Methods. A retrospective review was conducted of the clinical charts of dialysis-dependent patients with MPO-ANCA-associated vasculitis who attended one of 8 associated clinics over the past 21 years. Results. Eighty-nine patients were included in the study; 88 had microscopic polyangiitis (MPA) and 1 had granulomatosis with polyangiitis. Of the 88 patients with MPA, 18 had renal-limited vasculitis. Twenty-one relapses occurred among 13 patients (frequency, 0.05 relapses/person-year; 95% confidence interval, 0.03 - 0.08). Mean time from start of dialysis to relapse was 65 - 59 months. Cox multivariate analysis showed that pulmonary involvement was a predictor of relapse (hazard ratio [HR], 21.4) and mortality (HR, 4.60), and that patient age (HR, 1.10) and cyclophosphamide use (HR, 0.20) were significant predictors of mortality. Postdialysis 1- and 5-year survival rates were 83.0% and 65.6%, respectively; infection was the most frequent cause of death. Conclusion. Pulmonary involvement was a predictor of relapse and mortality. Although relapse can occur long after the start of dialysis, incidence was low among dialysis-dependent patients. Prolonged maintenance immunosuppressive therapy might be limited to patients with pulmonary involvement in dialysis-dependent ANCA-associated vasculitis. [ABSTRACT FROM AUTHOR]

Body weight is tightly regulated by food intake and energy dissipation, and obesity is related to decreased energy expenditure (EE). Herein, we show that nucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2, autotaxin) is an adipose-derived, secreted enzyme that controls adipose expansion, brown adipose tissue (BAT) function, and EE. In mice, Enpp2 was highly expressed in visceral white adipose tissue and BAT and is downregulated in hypertrophied adipocytes/adipose tissue. Enpp2+/- mice and adipocyte-specific Enpp2 knockout mice fed a high-fat diet showed smaller body weight gains and less insulin resistance than control mice fed the same diet. BAT was functionally more active and EE was increased in Enpp2-deficient mice. In humans, ENPP2 expression in subcutaneous fat and ENPP2 levels in serum were reduced in obese subjects. Taken together, our results establish ENPP2 as an adipose-derived, secreted enzyme that regulates adipose obesity and systemic metabolism. They also suggest ENPP2 could be a useful therapeutic target for the treatment of metabolic disease. [ABSTRACT FROM AUTHOR]

Background: Early induction with biologics can reduce complications in patients with Crohn’s disease (CD) and improve their quality of life. The safety of biologics, however, is uncertain. Granulocyte and monocyte adsorptive apheresis (GMAA) is a natural biologic therapy that selectively removes granulocytes and monocytes/macrophages and has few severe adverse effects. The effects of GMAA on patients with early-diagnosed CD are unclear. We investigated the effects of GMAA combined with thiopurines on patients with early-diagnosed CD. Methods: Twenty-two corticosteroid- and biologic-naïve patients with active early-diagnosed CD were treated with intensive GMAA (twice per week) combined with thiopurines administration. Active early-diagnosed CD was defined as follows: (i) within 2years after diagnosis of CD, (ii) with no history of both surgical treatment and endoscopic dilation therapy, and (iii) Crohn’s Disease Activity Index (CDAI) was higher than 200. We investigated the ratios of clinical remission defined as CDAI was less than or equal to 150 at 2, 4, 6 and 52weeks and mucosal healing defined as a Simplified Endoscopic Activity Score for Crohn’s Disease (SES-CD) as 0 at 6 and 52weeks. Adverse events were recorded at each visit. Results: The ratios of clinical remission at 2, 4, and 6 weeks were 6 of 22 (27.2%), 12 of 22 (54.5%), and 17 of 22 (77.2%), respectively. At 52 weeks, 18 of 21 patients (81.8%) were in clinical remission. The ratios of mucosal healing at 6 and 52 weeks were 5 of 22 (22.7%) and 11 of 22 (50%), respectively. The difference in the mucosal healing ratio was significant between 6 and 52 weeks (p = 0.044). No serious adverse effects were observed during this study. Conclusions: Combination therapy with intensive GMAA and thiopurines administration rapidly induced high remission in patients with active early-diagnosed CD without serious adverse effect. Mucosal healing was observed in 50.0% of enrolled patients. This combination therapy might be a rational option for patients with early-diagnosed CD. [ABSTRACT FROM AUTHOR]