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This study aimed to analyze factors related to adolescent mothers' satisfaction with childbirth.Prospective and cross-sectional study PARTICIPANTS: Fifty adolescent mothers with maternal age from 14 to 19 years and delivery of a single and live newborn at term SETTING: Low-risk maternity hospital INTERVENTION: The participants were invited to answer a questionnaire (North Bristol modified version of the Mackey Childbirth Satisfaction Rating Scale [mMCSRS]) with 18 items measuring childbirth satisfaction. Each item was to be rated on a 5-point Likert scale (very dissatisfied to very satisfied).The main outcome measure was the total score on the questionnaire.The median maternal age was 18 years (95% CI, 11-25), and the median maternal satisfaction score of adolescent mothers was 88 (95% CI, 83-90). There was a significant difference in the total scores on the mMCSRS regarding the following factors: "oral fluid and food intake during labor" (yes = 84.0 vs no = 78.0, P = 0.044); "professional who attended the birth" (physician = 78.0 vs midwife = 86.0, P = 0.022); "skin-to-skin contact" (yes = 83.0 vs no = 71.0, P = 0.004); and "breastfeeding at the first hour" (yes = 84.5 vs no = 75.5, P = 0.008). Multiple regression with a stepwise procedure identified the following independent factors: "gestational age" (coefficient = 2.14, P = 0.03), "oral fluid and food intake during labor" (coefficient = 5.30, P = 0.013), and "skin-to-skin contact" (coefficient = 11.2, P0.001).Satisfaction with childbirth in adolescent mothers is associated with measures that can be easily implemented in the health care system. They are chiefly the provision of oral fluid and food during labor and skin-to-skin contact. Specific strategies are thus needed to increase adolescents' satisfaction with childbirth.

Exposure to prenatal stress increases offspring risk for long-term neurobehavioral impairments and psychopathology, such as Attention Deficit Hyperactivity Disorder (ADHD). Epigenetic regulation of glucocorticoid pathway genes may be a potential underlying mechanism by which maternal conditions 'program' the fetal brain for downstream vulnerabilities. The present study aims to investigate whether mRNA expression of glucocorticoid pathway genes in the placenta predict offspring negative affect during early childhood (between 6 and 24 months). Participants include 318 mother-child dyads participating in a longitudinal birth cohort study. Placental mRNA expression of glucocorticoid pathway genes (HSD11B1, HSD11B2, NR3C1, NCOR2) were profiled and negative affect traits of the offspring were measured at 6, 12, 18, and 24 months. HSD11B1 mRNA expression significantly predicted negative affect (β = -.09, SE = .04; p = .036), and Distress to Limitations trajectories (β = -.13, SE = .06; p = .016). NCOR2 mRNA expression significantly predicted Distress to Limitations (β = .43, SE = .21; p = .047), and marginally predicted Sadness trajectories (β = .39, SE = .21; p = .068). HSD11B2 and NR3C1 did not predict trajectories of Negative Affect or subscale scores. Infant negative affect traits were assessed via maternal self-report, and deviated from linearity across follow-up. mRNA expression of glucocorticoid pathway genes in the placenta may be a potentially novel tool for early identification of infants at greater risk for elevated negative affect. Further study is needed to validate the utility of mRNA expression of glucocorticoid pathway genes in the placenta.

The magnetic ground states of $R_2$Ru$_2$O$_7$ and $A_2$Ru$_2$O$_7$ with $R=$ Pr, Gd, Ho, and Er, as well as $A=$ Ca, Cd are predicted devising a combination of the cluster-multipole (CMP) theory and spin-density-functional theory (SDFT). The strong electronic correlation effects are estimated by the constrained-random-phase approximation (cRPA) and taken into account within the dynamical-mean-field theory (DMFT). The target compounds feature $d$-orbital magnetism on Ru$^{4+}$ and Ru$^{5+}$ ions for $R$ and $A$, respectively, as well as $f$-orbital magnetism on the $R$ site, which leads to an intriguing interplay of magnetic interactions in a strongly correlated system. We find CMP+SDFT is capable of describing the magnetic ground states in these compounds. The cRPA captures a difference in the screening strength between $R_2$Ru$_2$O$_7$ and $A_2$Ru$_2$O$_7$ compounds, which leads to a qualitative and quantitative understanding of the electronic properties within DMFT., Comment: 15 pages, 5 figures, 5 tables

H. Sugai, et al., Recent developments of transition-edge sensors (TESs), based on extensive experience in ground-based experiments, have been making the sensor techniques mature enough for their application on future satellite cosmic microwave background (CMB) polarization experiments. LiteBIRD is in the most advanced phase among such future satellites, targeting its launch in Japanese Fiscal Year 2027 (2027FY) with JAXA’s H3 rocket. It will accommodate more than 4000 TESs in focal planes of reflective low-frequency and refractive medium-and-high-frequency telescopes in order to detect a signature imprinted on the CMB by the primordial gravitational waves predicted in cosmic inflation. The total wide frequency coverage between 34 and 448 GHz enables us to extract such weak spiral polarization patterns through the precise subtraction of our Galaxy’s foreground emission by using spectral differences among CMB and foreground signals. Telescopes are cooled down to 5 K for suppressing thermal noise and contain polarization modulators with transmissive half-wave plates at individual apertures for separating sky polarization signals from artificial polarization and for mitigating from instrumental 1/f noise. Passive cooling by using V-grooves supports active cooling with mechanical coolers as well as adiabatic demagnetization refrigerators. Sky observations from the second Sun–Earth Lagrangian point, L2, are planned for 3 years. An international collaboration between Japan, the USA, Canada, and Europe is sharing various roles. In May 2019, the Institute of Space and Astronautical Science, JAXA, selected LiteBIRD as the strategic large mission No. 2., This work was supported by World Premier International Research Center Initiative (WPI), MEXT, Japan, by JSPS Core-to-Core Program, A. Advanced Research Networks, and by JSPS KAKENHI Grant Numbers JP15H05891, JP17H01115, and JP17H01125. The Italian contribution to the LiteBIRD phase A is supported by the Italian Space Agency (ASI Grant No. 2016-24- H.1-2018) and the National Institute for Nuclear Physics (INFN). The French contribution to the LiteBIRD phase A is supported by the Centre National d’Etudes Spatiale (CNES), by the Centre National de la Recherche Scientifque (CNRS), and by the Commissariat à l’Energie Atomique (CEA). A Concurrent Design Facility study focused on the MHFT and Sub-Kelvin coolers has been led by the European Space Agency (ESA). The Canadian contribution to LiteBIRD is supported by the Canadian Space Agency. The US contribution is supported by NASA Grant no. 80NSSC18K0132

What is known and objective Roxadustat is a hypoxia-inducible factor prolyl hydroxylase inhibitor currently being investigated for the treatment of anemia in chronic kidney disease. Lanthanum carbonate is a phosphate binder that is commonly used to treat hyperphosphatemia in patients with chronic kidney disease. This study investigated the effect of lanthanum carbonate on the pharmacokinetics, safety and tolerability of a single oral dose of roxadustat in healthy non-elderly adult male subjects. Methods This was an open-label, randomized, two-period, two-sequence crossover study in non-elderly healthy adult males. Subjects randomized to Group 1 received roxadustat alone during Period 1 and roxadustat concomitantly with lanthanum carbonate during Period 2; subjects randomized to Group 2 received roxadustat concomitantly with lanthanum carbonate during Period 1 and roxadustat alone during Period 2. All subjects received a single oral dose of 100 mg roxadustat on Day 1 in both periods. Subjects receiving concomitant lanthanum carbonate received 750 mg lanthanum carbonate three times daily on Days 1 and 2. Pharmacokinetic assessments were conducted on Days 1-4 in both periods. The primary study outcomes were the area under the concentration-time curve from the time of dosing extrapolated to infinity (AUCinf ), and maximum concentration (Cmax ); the geometric least squares mean ratio (GMR; roxadustat + lanthanum carbonate/roxadustat alone) and corresponding 90% confidence interval (CI) was calculated for AUCinf and Cmax . Safety was assessed by the occurrence of treatment-emergent adverse events (TEAEs), laboratory test results, vital signs and standard 12-lead electrocardiogram. Results and discussion A total of 18 subjects were enrolled (Group 1, n = 9; Group 2, n = 9); no subjects discontinued from the study. Roxadustat was rapidly absorbed, reaching maximum plasma concentration between 1 and 4 hours. The GMRs for AUCinf and Cmax were 88.00% (90% CI: 84.01, 92.17) and 98.58% (90% CI: 92.92, 104.58), respectively. The 90% CIs for both parameters were within the no-effect boundaries of 80% and 125%, indicating a lack of effect of lanthanum carbonate on roxadustat absorption. No deaths or serious TEAEs occurred. What is new and conclusions Concomitant administration of a single oral dose of 100 mg roxadustat and 750 mg lanthanum carbonate three times daily did not impact the AUCinf or Cmax of roxadustat and was considered safe and well tolerated in non-elderly healthy adult male Japanese subjects.

Synthetic jets, whose size and weight can be reduced easily, have become an attractive alternative to continuous jets. Many experimental and numerical studies have been conducted on synthetic jets to investigate their fundamental flow characteristics, including jet structure, for applied research such as boundary layer control and enhanced fluid mixing. However, few studies have focused on fluid transportation devices using synthetic jets as a driving source. Therefore, several issues concerning fluid transport characteristics still need to be resolved. In addition, although optimum operation of devices using synthetic jets is essential for their practical use, few studies have focused on this issue. The present study experimentally demonstrates the influence of the dimensionless stoke L on the performance characteristics of a synthetic jet fan under Reynolds number Re = 1800 and the same fan geometry; here, the stroke l is nondimensionalized by the primary slot width b. Furthermore, numerical simulations are conducted to complement the experiment. Velocity and pressure measurements are performed using a hot-wire anemometer, differential pressure manometer, and pressure transducer. The influence of the dimensionless stroke L on the performance/efficiency curves, static pressure distribution on the duct surface, and unsteady flow characteristics are investigated. Moreover, the flow field inside the duct is observed through numerical simulation. The results show that the performance characteristics and pressure recovery process depend on the dimensionless stroke L, and an optimum range of dimensionless stroke L exists for operation.

Purpose/Objective(s) Radiation therapy treatment planning has traditionally been a time-consuming process with potentially high inter-planner variability. The Pareto optimal projection search (POPS) algorithm, which produces Pareto optimal and clinically acceptable plans, provides a fully automated framework for treatment planning without requiring any active planning. Materials/Methods The POPS algorithm searches the feasibility boundary for desirable plans, as defined by a scoring function. Overall, POPS has two main components—gradient-free search in the decision variable space and projection of decision variables to the Pareto front using the bisection method. As treatment plan evaluation is highly nuanced with many candidate scoring functions available in literature, we evaluate the performance of the POPS automated plans under the following two conditions: 1) when POPS performs plan scoring using a normalized equivalent uniform dose (NEUD) metric and 2) when POPS performs plan scoring using a scoring function (SF) based on dose-volume histogram (DVH) limits. Results Treatment plans were generated automatically using the POPS algorithm for a dataset of 21 prostate cases collected as part of clinical workflow. Dose conformity, dose homogeneity, and sparing of organs-at-risk are assessed using a Wilcoxon signed-rank test. In general, plans generated using the POPS algorithm were of high quality. Plans scored using the NEUD metric had improved conformity and comparable homogeneity as compared to plans scored using the SF score. Sparing of organs-at-risk for POPS generated plans was also comparable when using either of the scoring functions. Conclusion The POPS algorithm allows for fully automated treatment planning and produces plans that are pareto optimal and clinically acceptable. We anticipate that POPS will substantially improve treatment planning workflow.

Heating and domestic hot water for family houses represents a notable share of energy consumption. However, sufficient space for the installation of thermal energy storage (TES) components may not be available in family houses or urban areas, where space may be restricted and expensive. Sorption TES devices seem to be a promising means of replacing conventional TES devices and reducing the occupied space for its high energy density. In this paper, a 10 kWh short-term sorption TES device was developed and investigated. The employed composite sorbent was formed from lithium chloride (LiCl) with the addition of expanded graphite (EG). The principle of sorption TES for the LiCl/water working pair is first illustrated. This prototype was tested under conditions representative of transition or winter seasons. Under the conditions used (charging temperature Tcha at 85 °C, discharging temperature Tdis at 40 °C, condensing temperature Tc at 18 °C, and evaporating temperature Te at 30 °C), the heat storage capacity can reach 10.25 kWh, of which sorption heat accounts for approximately 60%. The heat storage density obtained was 873 Wh per kg of composite sorbent or 65.29 kWh/m3, while the heat storage density of hot water tank was about 33.02 kWh/m3.

In Japan in October 2016, the Pharmaceuticals and Medical Devices Agency (PMDA) began to receive electronic data in new drug applications (NDAs). These electronic data are useful to conduct regulatory assessment of sponsors' submissions and contribute to the PMDA's research. In this article, we summarize the number of submissions of quantitative modeling and simulation (M&S) documents in NDAs in Japan, and we describe our current thinking and activities about quantitative M&S in PMDA.

The aim was to assess adolescent satisfaction with childbirth and compare it with that of adult women.An observational comparative study was conducted during the period of October 2016 and April 2017 in a public maternity hospital in São Paulo, Brazil. The population included 50 adolescents (14-19 years) and 51 adults (20-35 years) mothers in post-partum after a term live birth. Maternal satisfaction was assessed by the North Bristol modified Mackey Childbirth Satisfaction Rating Scale questionnaire with 18 items divided into five subscales (self, partner, baby, physician and overall) and two items on birth experience. Each item was rated on a 5-point Likert scale and a total score was calculated. The main outcome measure was a total score on questionnaire.The mean maternal age of adolescents was 18 years (95% confidence interval [CI] 11-25) and for adults, 28.3 years (95% CI 26.1-30.7). Primiparity was more common among adolescents than adults (92% vs 43.1%, P 0.001). The median maternal satisfaction score of adolescents (88; 95% CI 83-90) was lower than that of adult women (90; 95% CI 87-93, P = 0.046). Adolescents also scored lower than adult women on the following subscales: satisfaction with baby (median 14 vs 15, P = 0.004) and satisfaction concerning care provided by doctors/midwives (median 33 vs 35, P = 0.006).Adolescents were statistically less satisfied with their childbirth experience. More dissatisfaction was seen among them specifically concerning their baby and the care provided by doctors/midwives. This shows that different strategies need to be developed for this specific group of women.

Background The hand is the most frequently involved site in rheumatoid arthritis (RA). The treatment aim of RA is achieving and maintaining remission (REM) or low disease activity (LDA) via tight medical control. However, despite remarkable advances in medication, progressive deterioration and/or deformity of the hand, if adequate medication is not administered in the early stage. Surgical reconstruction is still required in hands with functional loss and/or a grotesque appearance caused by joint deterioration or tendon rupture. Recently, patients have expressed a desire to achieve functional REM with a higher quality of life (QOL) and improved mental wellness. Objectives The objective of this study was to clarify the systemic effects of surgical intervention in the impaired hand, even in patients with well-controlled disease who have achieved REM or LDA. Methods A prospective cohort study was performed in 119 hands of 119 patients with functional loss and/or a grotesque appearance due to RA who underwent primary elective surgery between October 2012 and September 2014. A total of 42 hands in 42 patients (males: 2, females: 40) had a disease activity of REM or LDA just before surgery. In the REM/LDA group, the average (range) age was 61 (29–82) years, and the average (range) disease duration was 15 (2–35) years. The procedures performed included Darrach procedure (ulnar head resection) in 17 hands, radiolunate arthrodesis in 10, extensor tendon reconstruction in 6, thumb/finger metacarpophalangeal joint arthroplasty (Swanson) in 14, proximal interphalangeal (interphalangeal) joint fusion in 4, and thumb CM joint arthroplasty (Thompson) in 4 and so on. The patient-reported outcome (PRO) was assessed using the Health Assessment Questionnaire-Disability Index (HAQ-DI), EuroQol-5 Dimensions (EQ-5D), Beck Depression Inventory-II (BDI-II), Patient9s General Health using visual analogue scale of 100 mm (Pt-GH), and the Disabilities of the Arm, Shoulder and Hand (DASH). The 28-joint Disease Activity Score using C reactive protein (DAS28-CRP) and Grip power (GP) were also examined. All of these items were investigated just before surgery (baseline) and again at 6 and 12 months after surgery. Results On the whole, the physical function (HAQ-DI, DASH, GP), QOL (HAQ-DI, EQ-5D, Pt-GH), mental wellness (BDI-II, Pt-GH), and disease activity (DAS28-CRP) were significantly improved at 6 and 12 months after surgery compared to baseline (p Conclusions Achieving REM or LDA is not the ultimate goal of treatment for patients with functional loss and/or a grotesque appearance of their hands. Further “wellness” can be achieved by surgical intervention in the affected hand, even for patients with well-controlled RA. Such intervention can also ameliorate the disease activity. References Ishikawa H, Murasawa A, Nakazono K, et al. The patient-based outcome of upper-extremity surgeries using the DASH questionnaire and the effect of disease activity of the patients with rheumatoid arthritis. Clin Rheumatol. 2008;27:967–973. Disclosure of Interest None declared

Background The treatment aim of rheumatoid arthritis (RA) is achieving and maintaining remission (REM) or low disease activity (LDA) via tight medical control 1) . However, despite remarkable advances in medication, progressive deterioration and deformity of the forefoot sometimes occur if adequate medication is not administered in the early stage. Surgical reconstruction is still required in patients with painful callosity and footwear problems caused by typical forefoot deformity. Recently, patients have expressed a desire to achieve functional REM with a higher quality of life (QOL) and improved mental wellness. Objectives The objective of this study was to clarify the systemic effects of forefoot reconstruction on the impaired foot, even in patients who have achieved REM or LDA. Methods A prospective cohort study was performed for 63 feet of 50 patients (males: 6, females: 44) with RA who underwent primary elective surgery between October 2012 and September 2014. Both feet underwent surgery on the same day in 13 patients. The average (range) age was 64 (42–89) years, and the average (range) disease duration was 20 (2–36) years. The procedures performed included shortening oblique osteotomy at the metatarsal neck of the lessor toes in 47 feet, first metatarsophalangeal joint arthroplasty (Swanson) in 44 feet, correction shortening osteotomy (modified Mitchell) at the first metatarsal in 4 feet, and fusion at the first interphalangeal joint in 7 feet, among others. A total of 30 feet in 27 patients (males: 5, females: 22) had a disease activity of REM or LDA just before surgery. The patient-reported outcomes (PROs) were assessed using the Health Assessment Questionnaire-Disability Index (HAQ-DI), EuroQol-5 Dimensions (EQ-5D), Beck Depression Inventory-II (BDI-II), and Patient9s General Health using a visual analogue scale of 100 mm (Pt-GH). The 28-joint Disease Activity Score using C reactive protein (DAS28-CRP), the Japanese Society of Surgery of the Foot (JSSF) standard rating system (JSSF) for the RA foot and ankle scale 2) , and the Time Up&Go test (TUG) were also evaluated. All of these items were investigated just before surgery (baseline) and again at 6 and 12 months after surgery. Results Overall, the physical function (JSSF, TUG), QOL (EQ-5D), and mental wellness (depression) (BDI-II) were significantly improved at 6 and 12 months after surgery compared to the baseline values (p Conclusions Achieving REM or LDA is not the ultimate goal of treatment for patients with painful callosity and footwear problem functional loss. A higher QOL and improved function can be achieved by surgical intervention in the deformed forefoot. References Smolen JS, Breedveld FC, Burmester GR, et al. Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force. Ann Rheum Dis. 2016;75(1):3–15. Niki H, Aoki H, Inokuchi S, et al. Development and reliability of a standard rating system for outcome measurement of foot and ankle disorders I: development of standard rating system. J Orthop Sci. 2005:10:457–465. Disclosure of Interest None declared

Background The treatment aim of rheumatoid arthritis (RA) is achieving and maintaining remission (REM) or low disease activity (LDA) via tight medical control. However, despite remarkable advances in medication, progressive deterioration and/or deformity of the joint sometimes occurs, if adequate medication is not administered in the early stage. Surgical reconstruction is still required in the joints with functional loss caused by structural damage. Recently, patients have expressed a desire to achieve functional REM with a higher quality of life (QOL) and improved mental wellness. Objectives The objective of this study was to clarify the effectiveness of intensive combination therapy with medication and orthopedic surgical intervention in patients who have already achieved REM or LDA. Methods A prospective cohort study was performed on 294 sites in 276 patients with functional loss due to RA scheduled to undergo primary elective surgery between October 2012 and September 2014. There were 99 sites in 96 patients (males: 10, females: 86) whose disease activity was REM or LDA just before surgery. In the REM/LDA group, the average age was 63 (29–82) years, and the average disease duration was 17 (2–60) years. The surgical site was the shoulder in 1 patient, elbow in 7, wrist in 21, hand in 24, hip in 5, knee in 10, ankle in 4, and forefoot in 27. The procedures performed included 38 alloarthroplasties, 41 arthroplasties without prosthesis, 19 arthrodesis, and 9 synovectomies. The patient-reported outcome (PRO) was assessed using the Health Assessment Questionnaire-Disability Index (HAQ-DI), EuroQol-5 Dimensions (EQ-5D), Beck Depression Inventory-II (BDI-II), Patient9s General Health using visual analogue scale of 100 mm (Pt-GH), and the Disabilities of the Arm, Shoulder and Hand (DASH) for the upper extremity surgery. The Time Up &Go test (TUG) was administered for patients receiving lower extremity surgery. The disease activity was assessed based on the 28-joint Disease Activity Score using C reactive protein (DAS28-CRP). All of these items were investigated just before surgery (baseline) and again at 6 and 12 months after surgery. Results On the whole, the physical function (HAQ-DI, DASH, TUG), QOL (HAQ-DI, EQ-5D, Pt-GH), mental wellness (BDI-II, Pt-GH), and disease activity (DAS28-CRP)1) were significantly improved at 6 and 12 months after surgery compared to baseline (p Conclusions Achieving REM or LDA is not the ultimate goal of treatment for patients with functional loss caused by structural damage. Further “wellness” can be achieved by surgical intervention. Intensive combination therapy with medication and orthopedic surgical intervention is effective in improving the QOL and mental health as well as the physical function. Such intervention can also ameliorate the disease activity. References Oh K, Ishikawa H, Abe A, et al. Effects of surgical intervention on disease activity of rheumatoid arthritis: cases of surgery for rheumatoid arthritis of the lower limbs treated with biologics. Mod Rheumatol. 2014;24(4):606–11. Disclosure of Interest None declared

Background In Japan, rituximab (RTX) has become one of the dominant alternatives for ANCA associated vasculitis (AAV) even for elderly patients. Objectives The efficacy and safety of RTX for AAV patients was determined at our hospital. Methods Nineteen patients with AAV, including 14 newly diagnosed patients and 6 relapsed patients, had been treated with RTX. There were 10 males and 9 females. They were all MPO-ANCA positive; 16 were diagnosed with microscopic polyangiitis (MPA), 2 with granulomatosis with polyangiitis (GPA), and 1 with undifferentiated, according to the EMA classification of AAV. The mean age at RTX induction was 71.3 years (range: 40 – 82 years). The efficacy was evaluated by the BVAS score at the time of first induction and after 6 month treatment. Adverse events were recorded during the 6-month treatment. Results The mean of BVAS decreased from 17.3 (range: 7–35) at the first induction to 1.2 (0–4) at 6 month of RTX treatment. Of the 10 patients who could be followed-up for over 6 months, 7 patients achieved remission (BVAS=0) (remission rate: 70.0%). The titer of mean MPO-ANCA decreased 136.1 IU/mL (9.9–300 IU/mL) to 44.4 IU/mL (1.0–114.0 IU/mL) at 6 month. The dose of prednisolone decreased from 34.4mg/day (5–60mg/day) at baseline to 5.5mg/day (0–10 mg/day) at 6 month. The adverse events were as follows: 3 patients experienced reactivation of cytomegalovirus (CMV) with a CMV colitis, one patient with sepsis following urinary-tract infection, and one patient with bacterial pneumonia. One patient with PMA died of exacerbation of the disease itself. Conclusions In Japan, AAV, mostly MPO-ANCA-positive PMA, affects elderly persons. The results suggest that RTX may provide a therapeutic option for elderly patients at the age of over 70 years with severe MPA, with an acceptable safety profile and rapid glucocorticoid tapering. However, careful monitoring for infectious diseases will be needed. Disclosure of Interest None declared

Background Although the biological disease-modifying antirheumatic drugs (bDMARDs) are the most effective treatment for rheumatoid arthritis (RA), the costs are much higher than those of conventional synthetic DMARDs. A number of studies on discontinuation, dose reduction and/or spacing of bDMARDs have been performed, but there have been few reports on increased spacing time between tocilizumab (TCZ) administrations so far. Objectives To analyze the efficacy of spacing of the intravenous (IV) administration of TCZ in patients with RA. Methods 63 patients (11 M, 52 F) who were administered IV TCZ for more than 1 year were enrolled. Eleven patients had shifted to subcutaneous injection and the data at the last IV infusion were analyzed. Results Mean age was 57.4 years old (30–78), mean body weight was 55.5kg (37–85.5), mean duration of illness was 10.7yrs (0–32), The number of the bDMARDs previously administered were 0.9 (0–3), and duration of TCZ treatment was 46.9 months (13–83). The intervals between administrations were 4 weeks: 28.6%, 5 weeks: 38.1%, 6 weeks: 17.5%, 7 weeks: 6.0%, 8 weeks: 7.9%, and 10 weeks: 1.6%. Tender joint count, swollen joint count, erythrocyte sedimentation rate (ESR), C-reactive protein, matrix metalloproteinase-3 (MMP-3), patient9s visual analogue scale (VAS), doctor9s VAS, disease activity score (DAS) 28-ESR, simplified disease activity index (SDAI), clinical DAI (CDAI) were significantly improved. All of patients remission rates were 90.5% for DAS28-ESR, 44.4% for CDAI, and 42.9% for SDAI. Patients with prednisolone (PSL) decreased from 50 to 38 (p=0.031), at doses of 5.3 (2–10) to 2.7 (0.5–5) mg/day (p Conclusions TCZ treatment was associated with significantly reduced disease activity and reduced use of PSL and MTX. Increased spacing between administrations was used in 71.4% of the patients. TCZ was able to reduce PSL and MTX even after spacing. MMP-3 might be a useful marker to decide the spacing period. TCZ is the most inexpensive bDMARD in Japan, but with increased spacing, it is possible to reduce the cost even further with acceptable control of RA symptoms. Disclosure of Interest None declared

We set out to examine the relations between prenatal exposure to the natural disaster Superstorm Sandy, maternal depression, and offspring electrodermal activity (EDA). EDA was measured via skin conductance response (SCR) magnitude in 198 children (M = 42.54 months, SD = 12.76) during a startle paradigm. In keeping with prior research, we expected prenatal depression to be associated with hyporeactive EDA and prenatal stress to be associated with hyperreactive EDA. SCR magnitude was lower in children prenatally exposed to depression alone, when compared to Superstorm Sandy, and controls. SCR magnitude of children prenatally exposed to both maternal depression and the storm was lower than that of all other groups. Our results emphasize the influence of maternal prenatal mental health, support targeted risk assessment for children who experienced an adverse prenatal environment, and highlight the need for a deeper understanding of the interactions between maternal mood and stress on the developing child.

Long-term outcomes after obturator hernia surgery remain unclear. Between 1979 and 2012, 80 consecutive operations for obturator hernia were performed for 70 patients at our hospital. Their charts were retrospectively reviewed, and the patients were contacted by telephone to check for the presence of an episode of recurrence. Including bilateral cases, a total of 104 obturator hernia repairs were divided by type into either mesh repair (n = 29) or non-mesh repair (n = 75). Recurrence rate was then calculated and compared between groups. Median age at the time of initial surgery was 84 years. Postoperative complications occurred in 31 operations (39 %), including four in-hospital deaths (5 %). After the initial obturator hernia surgery, the 2- and 5-year survival rates were 74 and 55 %, respectively. Seventeen recurrences were detected, all after non-mesh repairs. Recurrence rates at 3 years after obturator hernia repair were 0 % for mesh repair and 22 % for non-mesh repair (P = 0.048). Once patients recover from an incarcerated obturator hernia, they may still enjoy their super-aged lives. To prevent the recurrence, mesh repair is preferable if no contraindications are present.

Background Three-dimensional (3D) imaging has facilitated liver resection with excision of hepatic veins by estimating the liver volume of portal and hepatic venous territories. However, 3D imaging cannot be used for real-time navigation to determine the liver transection line. This study assessed the value of indocyanine green (ICG) fluorescence imaging with hepatic vein clamping for navigation during liver transection. Methods Consecutive patients who underwent liver resection with excision of major hepatic veins between 2012 and 2013 were evaluated using ICG fluorescence imaging after clamping veins and injecting ICG. Regional fluorescence intensity (FI) values of non-veno-occlusive regions (FINon), veno-occlusive regions (FIVO) and ischaemic regions (FIIS) were calculated using luminance analysing software. Results Of the 21 patients, ten, four and seven underwent limited resection, monosegmentectomy/sectionectomy and hemihepatectomy respectively, with excision of major hepatic veins. Median veno-occlusive liver volume was 80 (range 30–458) ml. Fluorescence imaging visualized veno-occlusive regions as territories with lower FI compared with non-veno-occlusive regions, and ischaemic regions as territories with no fluorescence after intravenous ICG injection. Median FIIS/FINon was lower than median FIVO/FINon (0·22 versus 0·59; P = 0·002). There were no deaths in hospital or within 30 days, and only one major complication. Conclusion ICG fluorescence imaging with hepatic vein clamping visualized non-veno-occlusive, veno-occlusive and ischaemic regions. This technique may guide liver transection by intraoperative navigation, enhancing the safety and accuracy of liver resection.

Adipocyte responses to adrenergic and s-adrenoceptor(-AR) (adrenoceptor) regulation are not sufficiently understood, and information helpful for elucidating the adrenoceptor-responsive machinery is insufficient. Here we show by using immunoprecipitated kinase analysis with a phosphatidylinositol 3-kinase (PI3K) p85 antibody that PI3K activation was induced by treatment with 10 or 100 µM norepinephrine (NE) for 15 min or with 10 mM aluminum fluoride (AF, a guanosine triphosphate (GTP)-binding (G) protein activator) for 20 min in white adipocytes (rat epididymal adipocytes) and that treatment with pertussis toxin (PTX, a G-protein inactivator) inhibited PI3K activation induced by the 20-min treatment with AF in the cells. In addition, western blot analysis revealed that glucose transporter 4 (GLUT4) level in the adipocyte plasma membrane (PM) fraction was increased by treatment with 10 µM NE, 100 µM dobutamine (DOB, a s1-AR agonist), or 0.1 µM CL316243 (CL, a s3-AR agonist) for 30 min or with 10 mM AF for 20 min. NE or AF treatment triggered 2-deoxyglucose (2-DG) uptake into adipocytes under the above conditions. Our results advance the understanding of responses to adrenoceptor regulation in white adipocytes and provide possible clues for clarifying the machinery involved in adrenergic and s-AR responses in the cells.

The effect of beta(3)-adrenoceptor (beta(3)-AR) agonists on adipocytes treated or not treated with signaling modulators has not been sufficiently elucidated. Using rat epididymal adipocytes (adipocytes) labeled with [(32)P]orthophosphate, we found that treatment with the selective beta(3)-AR agonist CL316243 (CL; 1 microM) induces phosphatidylinositol (PI) 3,4,5-triphosphate (PI[3,4,5]P(3)) production and that this response is inhibited by adenosine deaminase (ADA, an adenosine-degrading enzyme; 2 U/ml), pertussis toxin (PTX, an inactivator of inhibitory guanine-nucleotide-binding protein; 1 microg/ml), or wortmannin (WT, a PI-kinase inhibitor; 3 microM). The results showed that CL induced PI(3,4,5)P(3) production in intact adipocytes and that this production was affected by signaling modulators. Taken together, our findings indicate that CL produces PI(3,4,5)P(3) in an ADA-sensitive, PTX-sensitive, or WT-sensitive manner and will advance understanding of the effect of beta(3)-AR agonists on adipocytes.

The purpose of this study is to investigate the association of cigarette smoking with gastric cancer.Over 215,000 men and women, representing five ethnic groups (African Americans, Japanese Americans, Latino Americans, Native Hawaiians, and Whites), completed a mailed questionnaire, 1993-1996. After an average follow-up of 7.3 years, 454 men and 242 women were diagnosed with gastric adenocarcinoma. Cox proportional hazard models were used to calculate multivariate-adjusted hazard ratios and 95% confidence intervals.Current cigarette smokers had elevated hazard ratios compared with never smokers among men (HR = 1.98; 95% CI 1.46-2.70) and women (HR = 1.78; 95% CI 1.23-2.57). This positive association was consistent across all five ethnicities. Former smokers had an elevated risk among men, but not among women. There was a significant trend by intensity (cigarettes per day) and duration (years) of smoking among all current smokers. After separation by anatomic location of their tumor, ever smokers had a higher risk for gastric cardia cancer (HR = 2.86; 95% CI 1.66-4.93) than for distal gastric cancer (HR = 1.52; 95% CI 1.25-1.86) among men and women combined. Analysis by histologic tumor type showed a stronger association between current smoking and the intestinal type.Overall, this study shows an association of current cigarette smoking with gastric cancer in both sexes, consistency of this effect across five ethnic groups, evidence for a dose-response effect of smoking in both sexes, a stronger effect for cardia than for distal gastric cancer, and a stronger association for intestinal than for diffuse gastric cancer.

Upper gastrointestinal (GI) cancers of the stomach and esophagus have high incidence and mortality worldwide, but they are uncommon in Western countries. Little information exists on the association between vitamin D and risk of upper GI cancers. This study examined the association between circulating 25-hydroxyvitamin D (25(OH)D) and upper GI cancer risk in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. Concentrations of 25(OH)D were measured from 1,065 upper GI cancer cases and 1,066 age-, sex-, race-, and season-of blood draw-matched controls from 8 prospective cohort studies. In multivariate-adjusted models, circulating 25(OH)D concentration was not significantly associated with upper GI cancer risk. Subgroup analysis by race showed that among Asians, but not Caucasians, lower concentrations of 25(OH)D (

The objective of this study was to examine the association of urinary phytoestrogens with the risk of postmenopausal breast cancer. Participants in the Multiethnic Cohort Study included 36,458 postmenopausal women who provided blood or urine specimens. A nested case-control study of breast cancer with biospecimens was created in which cases diagnosed after specimen collection were matched to two controls. Two hundred fifty-one women with breast cancer and 462 controls had urine available for analysis of urinary phytoestrogens. Odds ratios (OR) and 95% confidence intervals (CI) were obtained using conditional logistic regression. A nonmonotonic inverse trend (P = 0.04) in breast cancer risk was associated with increasing urinary excretion of genistein (OR 25th-75th percentile, 0.88; 95% CI, 0.78-0.99) and total isoflavones (OR 25th-75th percentile, 0.80; 95% CI, 0.65-0.99). A significant reduction in breast cancer risk in Japanese-American women was associated with the highest compared with the lowest quartile excretion of urinary daidzein (OR, 0.41; 95% CI, 0.19-0.89; Ptrend, 0.005). The risk of breast cancer was reduced among White women with the highest compared with the lowest quartile excretion of equol (OR, 0.27; 95% CI, 0.08-0.95), although the trend in risk was not significant (P = 0.07). Our results provide some support to the hypothesis that a diet rich in isoflavones from soy products reduces the risk of postmenopausal breast cancer, particularly in populations with comparatively high excretion of phytoestrogens.

Achievement of CO2 emission reductions in the automobile sector is a complex problem because of the difficulties in regulating consumer behavior. The approach of the present study is not government regulation of consumer CO2 emissions but the encouragement of responsible environmental behavior using the bounded rationality of consumers based on behavioral economics. Currently, greenhouse gas (GHG) emission credits are mainly traded among corporations. However, the use of small-lot emission credits is expected to begin spreading to consumers. We propose a system through which small-lot emission credits can be purchased by the consumers during the purchase or renewal of automobile insurance. Drivers can offset vehicle CO2 emissions by purchasing emission credits. In the present study, we analyzed the market potential for small-lot GHG emission credits attached to automobile insurance. A consumer survey of 351 drivers was conducted in Japan. Consumer preferences are evaluated using conjoint analysis and the contingent valuation method (CVM). The average value of the marginal willingness to pay (WTP) for GHG emission credits is estimated to be approximately 2171 yen per ton-CO2. The median WTP for GHG emission credits is estimated to be approximately 2260 yen per year. Assuming that the average driver in Japan travels a distance of 10,000 kilometers per year and the vehicle fuel efficiency is 10 kilometers per liter, the WTP for GHG emission credits corresponds to approximately 30 percent of each driver's CO2 emissions.