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The present experiments explored the dynamical character of the gaseous jet injected flush into cross-flow for variable jet-to-cross-flow momentum flux ratios$J$(5, 12 and 41) and density ratios$S$(0.35 and 1.0). Contoured nozzle and straight pipe injectors were studied here, with the jet Reynolds number fixed at 1900 as other flow parameters were varied. Simultaneous acetone planar laser-induced fluorescence (PLIF) imaging and stereo particle image velocimetry (PIV) were used to study the relationships between scalar and velocity/vorticity fields, with a special focus on comparing PLIF-based extraction of scalar dissipation rates and local strain rates with PIV-based local strain rates in the upstream and downstream shear layers of the jet. There was remarkable similarity between the scalar and vorticity fields for the jet in cross-flow, spanning conditions for absolutely unstable upstream jet shear layers at low$J$or$S$values to conditions for convectively unstable shear layers for larger$J$, equidensity conditions (Megerianet al.,J. Fluid Mech., vol. 593, 2007, pp. 93–129; Getsingeret al.,Exp. Fluids, vol. 53, 2012, pp. 783–801). Proper orthogonal decomposition applied to both scalar and velocity fields revealed strengthening instabilities in both the upstream shear layer and in the jet’s wake as$J$was reduced. The simultaneous measurements allowed PLIF-extracted scalar dissipation rates and strain rates to be determined via a flamelet-like model and compared with PIV-extracted strain rates, each in the diffusion layer-normal direction. There was generally very good qualitative and quantitative agreement for these metrics in both the jet upstream and downstream shear layers for most flow conditions, with excellent correspondence to locations of shear layer vorticity roll up, although downstream shear layer strain rates in some cases showed lesser correspondence between PLIF- and PIV-based data. Such differences are shown to potentially result from diffusion and resolution effects as well as the influence of three-dimensional and transient effects which can be more significant in the lee side of the jet. Nevertheless, the present results reveal interesting dynamics and demonstrate the importance of strain fields in enhanced diffusion and transport phenomena.

ObjectivesTo investigate the clinical impact of 1-year certolizumab pegol (CZP) therapy added to the first year of 2-year methotrexate (MTX) therapy, compared with 2-year therapy with MTX alone.MethodsMTX-naïve patients with early rheumatoid arthritis (RA) with poor prognostic factors were eligible to enter Certolizumab-Optimal Prevention of joint damage for Early RA (C-OPERA), a multicentre, randomised, controlled study, which consisted of a 52-week double-blind (DB) period and subsequent 52-week post treatment (PT) period. Patients were randomised to optimised MTX+CZP (n=159) or optimised MTX+placebo (PBO; n=157). Following the DB period, patients entered the PT period, receiving MTX alone (CZP+MTX→MTX; n=108, PBO+MTX→MTX; n=71). Patients who flared could receive rescue treatment with open-label CZP.Results34 CZP+MTX→MTX patients and 14 PBO+MTX→MTX patients discontinued during the PT period. From week 52 through week 104, significant inhibition of total modified total Sharp score progression was observed for CZP+MTX versus PBO+MTX (week 104: 84.2% vs 67.5% (pConclusionsIn MTX-naïve patients with early RA with poor prognostic factors, an initial 1 year of add-on CZP to 2-year optimised MTX therapy brings radiographic and clinical benefit through 2 years, even after stopping CZP.Trial registration numberNCT01451203.

Background We previously reported that pulmonary capillary wedge pressure (PCWP) was noninvasively evaluated by 2D speckle tracking echocardiography (STE). Recently, novel software was introduced to examine volume and function of left ventricular and left atrium (LA) by 3D-STE automatically. Purpose We sought to compare the PCWP estimated by conventional 2D-STE (2D-ePCWP) and by novel 3D-STE (3D-ePCWP), and validate those values by cardiac catheterization. Methods Echocardiography and catheterization were performed in 29 patients (age 72±2) (7 ischemic heart disease, 2 hypertensive heart disease, 5 dilated cardiomyopathy, 12 valvular heart disease and 3 primary pulmonary hypertension).The ePCWP (mmHg) is noninvasively obtained as 10.8 − 12.4 x Log (left atrial active emptying function/minimum volume) as we previously reported. Echocardiography was performed just before the catheterization and we analyzed the 2D and 3D data by novel off-line software. 3D data was automatically analyzed and the border settings were fixed at default (ES60, ED30) (Figure). Results 2D-ePCWP and 3D-ePCWP had a good correlation with PCWP invasively obtained by catheterization (r=0.87 and 0.83, respectively, both p Conclusion This study demonstrated that PCWP might be noninvasively assessed by not only 2D-STE but also 3D-STE with reasonable accuracy and 3D-STE might have utility and value in the routine clinical practice.

Background Left ventricular (LV) diastolic function is mainly composed of LV relaxation and LV stiffness. We reported that pulmonary capillary wedge pressure (ePCWP) and LV relaxation assessed by Tau (eTau) are noninvasively evaluated by speckle tracking echocardiography (STE). The minimum LV diastolic pressure (mLVP) was reported to have a strong correlation with Tau. Therefore, LV chamber stiffness (c-stiffness) may be assessed with the use of two LV diastolic pressure-volume coordinates: the mLVP and volume and the end-diastolic pressure (EDP) and volume. Purpose We sought to noninvasively assess LV stiffness using STE and validate the value by cardiac catheterization. Methods Echocardiography and catheterization were performed in 124 patients (age 72±8) (70 angina pectoris, 20 prior myocardial infarction, 19 hypertensive heart disease, 11 congestive heart failure and 4 paroxysmal atrial fibrillation). The ePCWP (mmHg) is noninvasively obtained as 10.8 − 12.4 × Log (left atrial active emptying function/minimum volume) and the eTau (ms) is obtained as isovolumic relaxation time/(ln 0.9 × systolic blood pressure − ln ePCWP) as previously reported. The mLVP (e-mLVP) was estimate using Tau. The estimated EDP (e-EDP) was calculated as 12.3 − 10.1 × Log (left atrial active emptying function / minimum volume). LV c-stiffness (mmHg/ml) was calculated as LV pressure change (from mLVP to EDP) obtained by catheterization divided by LV volume change during diastole which equals to stroke volume by echocardiography. Estimated c-stiffness (e-c-stiffness) was noninvasively obtained using e-mLVP and e-EDP. Furthermore, LV myocardial stiffness (m-stiffness) was calculated by LVED stress / LV longitudinal strain by STE, where LV stress (kdynes/cm2) was calculated as 0.334 × pressure × dimension / [thickness (1 + thickness/dimension)]. The estimated m-stiffness (e-m-stiffness) was calculated using e-EDP. Results The eTau and e-EDP estimated by STE had a good correlation with Tau and EDP invasively obtained by catheterization (r=0.75 and 0.63, respectively, both p Conclusion This study demonstrated that LV stiffness may be noninvasively assessed by STE with reasonable accuracy and may have utility and value in the routine clinical practice for the diagnosis and treatment in patients with diastolic dysfunction.

Background Left ventricular (LV) pressure-strain and pressure-volume (P-V) loop area reflect global myocardial work (MW) and stroke work (SW), but clinical use of these indexes is limited by the need of invasive pressure measurement. A noninvasive method to obtain LV pressure-strain loop area was recently introduced to examine MW by speckle tracking echocardiography (STE). Purpose We sought to evaluate the impact of preload change on MW and SW obtained using this novel method and to examine the utility to assess LV contractile performance by the SW and end-diastolic volume (EDV) relation (SW-VED) in patient with hemodialysis (HD). Methods LV pressure in a cardiac cycle was estimated using systolic blood pressure (SBP), LV minimum diastolic pressure (mDP) and end-diastolic pressure (EDP) in 20 HD patients (age 67±9)and 25 controls (age 67±9) by utilizing the profile of an empiric, normalized reference curve adjusted according to the duration of LV isovolumic and ejection phases as defined by timing of aortic and mitral valve events by echocardiography. Pulmonary capillary wedge pressure (ePCWP) is estimated as 10.8 – 12.4 × Log (left atrial active emptying function/minimum volume): KT index as previously reported. LVEDP were estimated as 12.3 – 10.1 × KT index. We examined the relation between LV pressure decline (Tau) and mDP by catheterization in 126 patients. Tau is estimated as isovolumic relaxation time/(ln 0.9 × systolic BP − ln ePCWP) as previously reported. SW was obtained by P-V loop area using the combination of pressure (SBP, mDP and EDP) and LV volume by 3D-STE. Echo parameters and BP were measured before and after HD and before and after leg up in controls. Results The mDP obtained by catheterization had a good correlation with Tau (Tau = 33.7 + 2.06 × mDP, r=0.70, p Conclusion LVSW noninvasively obtained by P-V loop area was increased in controls associated with increased preload and decreased in HD with decreased preload and SW-VED was deceased in HD. This novel and noninvasive method may be of potential utility to assess LV contractility and have a clinical interest and value to assess LV function.

Introduction Left ventricular (LV) pressure-volume (P-V) loop area reflects stroke work (SW), but clinical use of this index is limited by the need of invasive pressure measurement. A noninvasive method to obtain LV pressure-strain loop was recently introduced to assess myocardial work (MW). The minimum LV diastolic pressure (mLVP) was reported to have a strong correlation with Tau and we reported that Tau was noninvasively evaluated by speckle tracking echocardiography (STE). Purpose We sought to evaluate the impact of preload change by leg lifts on LV SW noninvasively obtained by the novel method and to examine the utility to assess LV contractility by SW and end-diastolic (ED) volume relation (SW-VED). Methods Thirty six controls (age 71±10) and 30 patients with heart failure with reduced ejection fraction (EF) Results LVEF and longitudinal strain in HF before leg up by 3D-STE were lower compared to normal (LVEF; normal: 58±5 vs HF: 39±10*% and strain; −12±3 vs −8±3%*, *p Conclusion LV SW noninvasively obtained by P-V loop area was increased after leg up in both normal and HF but SW-VED in HF was smaller than normal, indicating reduced contractility in HF. This noninvasive method may be a new echocardiographic approach for quantification of LV SW and contractility.

Aim The Certolizumab–Optimal Prevention of joint damage for Early Rheumatoid Arthritis (C‐OPERA) study demonstrated that in methotrexate (MTX)‐naïve early RA patients with poor prognostic factors, 1‐year certolizumab pegol (CZP) therapy added to the first year of 2‐year optimized MTX therapy brings radiographic and clinical benefits through 2 years even after stopping CZP. This exploratory analysis aimed to identify factors at baseline and at CZP discontinuation associated with successful CZP discontinuation. Methods MTX‐naïve early RA patients with poor prognostic factors entered C‐OPERA (NCT01451203), a multicenter, randomized controlled trial. Patients were randomized to CZP + MTX (n = 159) or PBO + MTX (n = 157); those who completed the 1‐year, double‐blind period received MTX alone in Year 2 (CZP + MTX→MTX, n = 108; PBO + MTX→MTX, n = 71). Association between factors at baseline or at discontinuation of CZP and clinical/radiographic outcomes were evaluated by multiple logistic regression analysis. Predictive value cut‐offs were calculated using receiver operating characteristic analysis. Results Sex (male) and low baseline Disease Activity Score of 28 joints – erythrocyte sedimentation rate (DAS28‐ESR) were associated with simple disease activity index (SDAI) remission (≤3.3), whereas high baseline DAS28‐ESR and modified total Sharp score (mTSS) were associated with clinically relevant radiographic progression (yearly progression mTSS > 3) at Week 104 (across both treatment arms). Low DAS28‐ESR (

Background:Pulmonary hypertension (PH) is prominent as a vascular involvement of systemic sclerosis (SSc), which remains a leading cause of death in spite of current best treatments. Recently, hemodynamic definition of PH was updated from mPAP≥25mmHg to mPAP>20mmHg and PVR≥3WU. Although new definition may improve the prognosis of PH associated with SSc by giving a chance to start management early, it may be insufficient as more than 2/3 of the pulmonary circulation is already impaired by the time of meeting the definition. Therefore, the ideal therapeutic intervention should be started at the subclinical stage of PH in SSc patients, but little is known about underlying pathological mechanisms at the stage. In this study, we investigate progression to exercise-induced PH (exPH)1), which is considered subclinical PH, in the prospective registry of high-risk population for developing PH associated with SSc.Objectives:To detect the gene expressions in peripheral blood involved in the progression of pulmonary vessel disease (PVD) at the subclinical stage of PH associated with SSc.Methods:Total of 180 patients who had not met PH criteria with Raynaud phenomenon, skin sclerosis or SSc-related autoantibody was registered. To detect the early PVD, exercise Doppler echocardiography (exDE) was carried out every 6 or 12 months for up to 6 years. The definition of exPH was maximum sPAP>40mmHg or increase in sPAP>20mmHg estimated by exDE during exercise. For gene expression analysis, total RNAs from whole peripheral blood cells were extracted by PAXgene system, and then multiplex sequencing was done. To identify candidate genes involved in the progression to exPH, random forest machine learning method was employed. Volcano plots, a scatter plots to visualize fold-changes and p-values of differentially expressed genes (DEGs) between exPH and others (exN), were also used for seeking the important genes for disease progression.Results:At the time of registration, 34.4% of patients met exPH criteria, and 15.6% of patients developed exPH during follow-up period (35.0±18.1 months). Expression of TNF gene was selected as the most useful genes to predict progression to exPH by random forest, and the accuracy of the model was about 87%. Volcano plots indicated that expressions of TMEM176A and TMEM176B were prominent (fold-change >2.4 and -log10 p-value >3.5) in exPH patients. The accuracy was improved to 90% if the expression of TNF and TMEMA/B were used for the prediction of progression to exPH. We found that statistically significant increase in the expression of TNF was eliminated at the time of fulfilling the exPH criteria, while increase in expressions of TMEM A/B were still kept.Conclusion:It was reported that TNFα drives pulmonary arterial hypertension by suppressing the BMP type-II receptor and altering NOTCH signalling2). Our findings suggest that TNFα plays important role only in the period of pre-exPH. On the other hand, increase in expressions of TMEM A/B were observed through the period of pre-exPH to post-exPH. It suggests that there are multiple phases before developing PH associated with SSc. It is very important to understand the phases for the precise treatment to arrest the progression of PVD.References:[1]R. Naeije et al., Am J resp and critical care med 187, 576-583 (2013). 2) LA. Hurst et al., Nat Commun. 13;8:14079 (2017).Disclosure of Interests:Yoshinobu Koyama Speakers bureau: Asahikasei, Ayumi, BMS, Mitsubishi Tanabe, Shin-nihon, Paid instructor for: Asahikasei, Asteras, BMS, Grant/research support from: Eli-Lilly, Yoshiharu Sato: None declared, Tatsuma Shoji: None declared, Soichiro Fuke: None declared, Takatsune Umayahara: None declared, Moe Sakamoto: None declared

Objectives: To compare the efficacy and safety of certolizumab pegol (CZP) with and without loading dose (LD) in a post-hoc analysis of two Japanese clinical studies. Methods: Data from the double-blind trials (DBT) J-RAPID and HIKARI, and their open-label extension (OLE) studies, were used. Patients randomized to CZP 200 mg every 2 weeks (Q2W) groups starting with LD (400 mg Weeks 0/2/4; LD group; J-RAPID: n = 82, HIKARI: n = 116) and patients randomized to placebo groups who subsequently started CZP Q2W without LD in the OLEs (No-LD group; J-RAPID: n = 61, HIKARI: n = 99) were analyzed. Efficacy and pharmacokinetics were assessed during 24 weeks. Adverse events were reported from all studies. Results: In both trials, the LD groups showed more rapid initial ACR20/50/70 kinetics, and maintained higher ACR50/70 responses until 24 weeks, compared with the No-LD groups. Anti-CZP antibody development was less frequent in the LD groups (J-RAPID: 1.2% versus 4.9%; HIKARI: 17.2% versus 27.3%). Similar safety profiles were reported between LD and No-LD groups (any AEs: 281.8 versus 315.7 [J-RAPID], 282.6 versus 321.3 [HIKARI] [incidence rate/100 patient-years]). Conclusions: Despite limitations, including comparing DBT and OLE studies, these results suggest that a CZP LD improves clinical response in active rheumatoid arthritis without altering the safety profile.

The benefits of laparoscopic splenectomy (LS) over open splenectomy (OS) for normal-sized spleens have been well documented. However, the role of laparoscopy for moderate and massive splenomegaly is debated.A retrospective review of patients undergoing elective splenectomy at one institution from 1997 to 2017 was conducted. Moderate and massive splenomegaly was defined as splenic weight of 500-1000 g and greater than 1000 g, respectively. We performed a 1:2 matching of laparoscopic to open splenectomy to control for differences in splenic weight. Differences in perioperative morbidity (infection, thromboembolism, reoperation, readmission), intraoperative factors (blood loss, operative time), length of stay, and mortality were examined.A total of 491 elective splenectomies were identified. 268 cases were for splenic weights greater than 500 g. After a 1:2 matching of LS:OS, we identified 22 LS and 44 matched OS for moderate splenomegaly. The LS group had longer mean operative times (178 vs. 107 min, p 0.01), with similar length of stay and blood loss. For massive splenomegaly, 26 LS were identified and matched to 52 OS. LS had longer mean operative times (171 vs. 112 min, p 0.01) and higher readmission rates (27% vs. 6%, p 0.05). Other factors and outcomes did not differ between LS and OS for moderate or massive splenomegaly. The conversion rate for LS was higher for massive versus moderate splenomegaly, but was not statistically significant (35% vs. 14%, p = 0.09).LS for moderate and massive splenomegaly is associated with longer operative times. Other perioperative outcomes were comparable to OS, with no demonstrated benefits for LS. Although LS may be a feasible approach to moderate and massive splenomegaly, its benefits require further clarification in this patient population.

Objectives To evaluate efficacy and safety of combination therapy using certolizumab pegol (CZP) and methotrexate (MTX) as first-line treatment for MTX-naive, early rheumatoid arthritis (RA) with poor prognostic factors, compared with MTX alone. Methods MTX-naive, early RA patients with ≤12 months persistent disease, high anti-cyclic citrullinated peptide, and either rheumatoid factor positive and/or presence of bone erosions were enrolled in this multicentre, double-blind, randomised placebo (PBO)-controlled study. Patients were randomised 1:1 to CZP+MTX or PBO+MTX for 52 weeks. Primary endpoint was inhibition of radiographic progression (change from baseline in modified Total Sharp Score (mTSS CFB)) at week 52. Secondary endpoints were mTSS CFB at week 24, and clinical remission rates at weeks 24 and 52. Results 316 patients randomised to CZP+MTX (n=159) or PBO+MTX (n=157) had comparable baseline characteristics reflecting features of early RA (mean disease duration: 4.0 vs 4.3 months; Disease Activity Score 28-joint assessment (DAS28)) (erythrocyte sedimentation rate (ESR)): 5.4 vs 5.5; mTSS: 5.2 vs 6.0). CZP+MTX group showed significantly greater inhibition of radiographic progression relative to PBO+MTX at week 52 (mTSS CFB=0.36 vs 1.58; p

Objectives. A post-hoc analysis was performed to determine the relationship between the timing and magnitude of DAS28(ESR) response and long term outcomes in Japanese patients after 1 year of CZP treatment. Methods. Our analysis included 82 J-RAPID trial patients treated with CZP 200 mg and methotrexate, and 116 HIKARI trial patients treated with CZP 200 mg alone or with disease-modifying agents other than methotrexate. Remission rates and changes in mTSS at year 1 were compared to the DAS28(ESR) response at week 12 of CZP treatment. Results. After 1 year of treatment, remission was achieved in 41.3% of the J-RAPID and 34.9% of the HIKARI patients with a week 12 DAS28(ESR) response of ≥ 1.2. In comparison, patients with a DAS28(ESR) response of < 1.2 at week 12 only had a < 7% probability of achieving remission and displayed higher change in mTSS after 1-year treatment. Conclusions. The likelihood of remission and extent of radiographic progression after 1 year was associated with the week 12 DAS28(ESR) response. The DAS28(ESR) response at 12 weeks could be beneficial for identifying patients that are unlikely to respond to prolonged CZP treatment.

A 4.36-mm-thick pixelated thallium bromide (TlBr) detector with Tl electrodes was fabricated from a crystal grown by the traveling molten zone method using zone-purified material. The detector had four 1×1 mm2 pixelated anodes. The detector performance was characterized at room temperature. The mobility-lifetime products of electrons for each pixel of the TlBr detector were measured to be >2.8×10−3 cm2/V. The four pixelated anodes of the detector exhibited energy resolutions of 1.5–1.8% full width at half maximum (FWHM) for 662-keV gamma rays for single-pixel events with the depth correction method. An energy resolution of 4.5% FWHM for 662-keV gamma rays was obtained from a reconstructed energy spectrum using two-pixel events from the two pixelated anodes on the detector.

The biological filter capable of simultaneous nitrification and denitrification was constructed for aquatic animal experiments in the International Space Station (ISS). The biological filter will be used to remove harmful ammonia excreted from aquatic animals in a closed water circulation system (Aquatic Habitat). The biological filter is a cylindrical tank packed with porous glass beads for nitrification and dual plastic bags for denitrification. The porous beads are supporting media for Nitrosomonas europaea and Nitrobacter winogradskyi. The N. europaea cells and N. winogradskyi cells on the porous beads, oxidize the excreted ammonia to nitrate via nitrite. On the other hand, the dual bag is composed of an outer non-woven fabric bag and an inner non-porous polyethylene film bag. The outer bag is supporting media for Paracoccus pantotrophus. The inner bag, in which 99.5% ethanol is packed, releases the ethanol slowly, since ethanol can permeate through the non-porous polyethylene film. The P. pantotrophus cells on the outer bag reduce the produced nitrate to nitrogen gas by using the released ethanol as an electron donor for denitrification. The biological filter constructed in this study consequently removed the ammonia without accumulating nitrate. Most of the excess ethanol was consumed and did not affect the nitrification activity of the N. europaea cells and N. winogradskyi cells severely. In accordance with the aquatic animal experiments in the ISS, small freshwater fish had been bred in the closed water circulation system equipped with the biological filter for 90 days. Ammonia concentration daily excreted from fish is assumed to be 1.7 mg-N/L in the recirculation water. Under such conditions, the harmful ammonia and nitrite concentrations were kept below 0.1 mg-N/L in the recirculation water. Nitrate and total organic carbon concentrations in the recirculation water were kept below 5 mg-N/L and 3 mg-C/L, respectively. All breeding fish were alive and ate the feed well. The results show that the nitrification and denitrification abilities of the biological filter sufficed to keep water quality for aquatic animal experiments in the ISS. This simple and effective system is certainly applicable to aquarium systems and aquaculture systems.

Objectives. This 24-week, multicenter, double-blind, randomized, placebo-controlled study (NCT00791999) compared efficacy and safety of certolizumab pegol (CZP) in combination with methotrexate (MTX) vs placebo plus MTX in Japanese rheumatoid arthritis (RA) patients with inadequate response to MTX. Methods. In total, 316 patients were randomized 1:1:1:1 to subcutaneous CZP 100, 200, or 400 mg (induction dose: 200 mg or 400 mg CZP at Weeks 0, 2, and 4) plus MTX or placebo plus MTX every 2 weeks. Primary endpoint was ACR20 response at Week 12. Results. ACR20 response rates were 62.5%, 76.8%, 77.6%, and 28.6% at Week 12, and 61.1%, 73.2%, 71.8%, and 24.7% at Week 24 for CZP 100, 200, and 400 mg, and placebo groups, respectively, with statistical significance between each CZP group and placebo. Change in Total Sharp Score over 24 weeks was significantly smaller in CZP 200 and 400 mg groups vs placebo. Improvements in health-related quality of life (HRQoL) were observed in all three CZP groups vs placebo. Incidence of adverse events was similar between CZP groups. Conclusions. CZP plus MTX resulted in rapid, sustained reductions in RA signs and symptoms in Japanese patients with inadequate response to MTX, with significant inhibition of radiographic progression and improved HRQoL.

Objectives. To evaluate the long-term efficacy and safety of certolizumab pegol (CZP) plus methotrexate treatment and to assess the efficacy of two CZP maintenance dosing schedules in Japanese rheumatoid arthritis (RA) patients with an inadequate response to methotrexate. Methods. J-RAPID double-blind patients were entered into an open-label extension (OLE) study. Patients withdrawn due to lack of efficacy at 16 weeks and double-blind completers without a week-24 American College of Rheumatology (ACR) 20 response received CZP 200 mg every other week (Q2W) plus methotrexate. Double-blind completers with week-24 ACR20 responses were randomized to CZP 200 mg Q2W plus methotrexate or CZP 400 mg every 4 weeks plus methotrexate. Results. The ACR20/ACR50/ACR70 response rates of double-blind completers (n = 204) were 89.7%/67.2%/36.3% at OLE entry and 95.6%/84.8%/58.3% at 52 weeks, respectively. Other clinical, functional and radiographic outcomes were sustained with long-term CZP plus methotrexate. Long-term treatment with CZP was well-tolerated with no new unexpected adverse events observed. The efficacy and safety of CZP treatment were similar between the two dosing schedules. Conclusions. Continued CZP administration with methotrexate maintained efficacy over 52 weeks and was well-tolerated for Japanese RA patients. No obvious differences in clinical efficacy and safety were observed between the two dosing schedules, giving flexibility in maintenance administration schedules.

Thallium bromide (TlBr) is a promising compound semiconductor for fabrication of gamma-ray detectors. The attractive physical properties of TlBr lie in its high photon stopping power, high resistivity and good charge transport properties. Gamma-ray detectors fabricated from TlBr crystals have exhibited excellent spectroscopic performance. In this paper, advances in TlBr radiation detector development are reviewed with emphasis on crystal growth, detector fabrication, physical properties and detector performance.

The timing performance of TlBr detectors was evaluated at room temperature (22 °C). 0.5-mm-thick planar TlBr detectors with Tl circular electrodes with a diameter of 3 mm were fabricated from TlBr crystals grown by the traveling molten zone method using a zone-purified material. The pulse rise time of the TlBr detector was measured using a digital oscilloscope as the cathode surface of the device was irradiated with a 22Na gamma-ray source. Coincidence timing spectra were obtained between the TlBr detector and a BaF2 scintillation detector when both detectors were irradiated with 511 keV positron annihilation gamma-rays. The timing resolution of the TlBr detector was found to be inversely proportional to the applied bias voltage. The TlBr detector, in coincidence with the BaF2 detector, exhibited timing resolutions characterized by a 6.5 ns full width at half maximum (FWHM) and an 8.5 ns FWHM with and without an energy window of 350 keV-560 keV, respectively.

This brief describes a control strategy for the throwing motion of an underactuated two-link planar robot called the Pendubot. The springed Pendubot is built based on the concept of unstable zero dynamics, and our investigation uses it as a dynamic model of superior limbs to imitate human throwing motion. In the proposed control strategy, the zero dynamics is intentionally destabilized when a ball held by the end-effector is constrained on a geometric path in a vertical plane, using output zeroing control for the deviation between the ball and geometric path. The unstable zero dynamics drives the ball along the geometric path to achieve fast and accurate throw in a desired direction. The unstable zero dynamics is analytically derived to guarantee the dynamic acceleration of the ball along the geometric path. Numerical simulations and experimental results confirm the effectiveness of the proposed control strategy.

Titanium oxide-based composites containing (1) Nb, (2) Nb and Sr, and (3) Sr and La were fabricated by a combination of wet processing and reactive spark plasma sintering in which the metal oxide components were reduced by reaction with titanium nitride. If only TiO2 was used as the starting material, several Magneli-type phases of oxygen-deficient titanium oxides were obtained. When mixed with Nb ions with Ti:Nb = 0.9:0.1, microsegregation of Nb ions was observed (case 1). If Sr was added, a perovskite, SrTiO3 (STO) phase occurred (case 2), which contained La ions in the case of La addition (case 3). The sintered compacts consisted largely of grains of about 1 μm in size. In the case of Ti-Nb combination (case 1), a unique stripe pattern also appeared inside the grains. The electrical conductivity increased monotonically with increasing temperature in the case of the pure Magneli phases and the Nb-containing composite, whereas bow-shaped temperature dependences with a maximum were observed in the case of the composites containing STO phases. The Seebeck coefficients were commonly negative, and the absolute values increased with temperature. The thermal conductivity was between 2 W m−1 K−1 and 4 W m−1 K−1 in the temperature range from room temperature to 800°C. A maximum ZT of 0.34 was achieved at 800°C (case 2).

Capacitive Frisch grid detectors with the dimensions of 2 mm × 2 mm × 4.4 mm were fabricated from TlBr crystals grown by the travelling molten zone method using zone-purified materials. Spectroscopic performance of the detectors was evaluated at room temperature (24°C), - 5°C and - 20°C. The TlBr detector exhibited an energy resolution of 1.6% FWHM at 662 keV with a peak-to-Compton ratio of 8.7 with the depth correction at room temperature. Improvement of the detector performance was achieved by cooling the detector-preamplifier system. The energy resolutions of 3.4%, 1.5%, 1.0% and 0.9% FWHM at 122 keV, 356 keV, 662 keV and 1332 keV, respectively, were recorded with the TlBr detector without the depth correction at - 5°C. An energy resolution of 0.9% FWHM at 662 keV with a peak-to-Compton ratio of 18.2 was obtained from the TlBr detector with the depth correction at -20°C. An upper limit for the Fano factor of TlBr was estimated to be 0.43 at -20°C.

Phosphate glass with composition of 35NaO1/2–20WO3–45PO5/2 prepared by a conventional melt-quenching method was treated by a positive corona discharging at room temperature. It was found that the OH concentration in the top surface layer of the glass increased by the treatment of +6.0–7.5 kV, for 10 h in 5%H2-95%N 2 atmosphere and 5.0 mm in positive electrode and glass surface distance. On the other hand, the Na ion in the same area of 15 μm thickness diffused and precipitated to the bottom surface. It was found by the infrared and Raman spectra that the Na was replaced by implanted proton without notable structural change.

We demonstrate the first phase-stabilized, fully monolithic mode-locked solid-state laser operating at 1 GHz fundamental repetition rate. The offset frequency is stabilized to an RF reference with a residual integrated phase noise of < 50 mrad.