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The present study was undertaken to assess whether the odds for incident radiographic osteoarthritis (OA) differ between men and women in regard to body mass index (BMI) and inflammatory magnetic resonance imaging (MRI) markers 1 and 2 years prior, and whether the presence of inflammation on MRI differs between normal-weight and overweight/obese individuals who develop radiographic OA up to 4 years prior. We studied 355 knees from the Osteoarthritis Initiative study that developed incident radiographic OA and 355 matched controls. MRIs were read for effusion-synovitis and Hoffa-synovitis for up to 4 consecutive annual time points. Subjects were classified as normal-weight (BMI

Glutathione-S-transferases (GSTs) not only show cytoprotective role and their involvement in the development of anticancer drug resistance, but also transmit signals that control cell proliferation and apoptosis. However, the role of GST isoforms in chemotherapy resistance remains elusive in pancreatic cancer. Here, we demonstrated that gemcitabine treatment increased the GSTM2 expression in pancreatic cancer cell lines. Knockdown of GSTM2 by siRNA elevated apoptosis and decreased viability of pancreatic cancer cells treated with gemcitabine. Moreover, in vivo experiments further showed that shRNA induced GSTM2 downregulation enhanced drug sensitivity of gemcitabine in orthotopic pancreatic tumor mice. We also found that GSTM2 levels were lower in tumor tissues than in non-tumor tissues and higher GSTM2 expression was significantly associated with longer overall survival. In conclusion, our findings indicate that GSTM2 expression is essential for the survival of pancreatic cancer cells undergoing gemcitabine treatment and leads to chemo resistance. Downregulation of GSTM2 in pancreatic cancer may benefit gemcitabine treatment. GSTM2 expression in patients also shows significant correlation with overall survival. Thus, our study suggests that GSTM2 is a potential target for chemotherapy optimization and prognostic biomarker of pancreatic cancer.

Background: Dental professionals have so many opportunities to use injection needles and sharp instruments during dental treatment that they face an increased risk of needlestick injuries. This retrospective study reports the utilization and clinical outcomes of occupational post-exposure prophylaxis (PEP) with anti-retroviral agents after being potentially exposed to HIV at dental departments of Hiroshima University Hospital. Objective: This study reports the utilization and clinical outcomes of occupational post-exposure prophylaxis (PEP) with anti-retroviral agents after being potentially exposed to HIV at dental departments of Hiroshima University Hospital. Methods: Data on the clinical status of HIV-infected source patients and information on HIV-exposed dental professionals from 2007 to 2018 were collected. Results: Five dentists with an average experience of 5.6 years (1-15 years) were exposed. The averaged CD4-positive cell number and HIV-RNA load were 1176 (768-1898) / l and less than 20 copies/ml, respectively, in all the patients. Two of the five HIV exposed dentists received PEP. Three months after the exposures, all of their results were negative in HIV antibody/antigen tests. Conclusion: These data might support the concept of “undetectable equals untransmittable”, although HIV exposure in this study was not through sexual transmission.

The prognostic value of metabolic tumor volume (MTV) in locally advanced laryngeal or hypopharyngeal cancer is established in the setting of chemoradiotherapy, while it remains unknown in the setting of upfront total laryngectomy.We retrospectively analyzed 88 patients receiving total laryngectomy and neck dissection, using Cox regression models.Variables related to metastatic lymph node were associated with overall survival, whereas those related to primary tumor were not. In multivariable models, MTV of metastatic lymph nodes (N-MTV) as a continuous variable (Akaike's information criterion (AIC), 277.5) was equivalent to pathological nodal status (AIC, 278.2; P = 0.40), and superior to pathological nodal classification as an ordinal variable (AIC, 281.4; P 0.05) in ability of predicting death. The risk of death was increased by 1.2-fold (95% confidence interval (CI), 1.0-1.4; P = 0.03) every 10-ml increment of N-MTV, while patients with pN+ disease were at a higher risk of death by 2.9-fold (95% CI, 1.0-12.2; P 0.05) compared with patients with pN0 disease. Using recursive partitioning analysis (RPA), we classified the patients as having a low, intermediate, or high risk of death on the basis of N-MTV and extranodal extension (ENE). This RPA classification system exhibited greater concordance with overall survival than the classification considering pathological nodal status and ENE (AIC, 275.8 versus 281.4; P = 0.02). In the setting of upfront total laryngectomy, N-MTV is a critical predictor of mortality. A staging system in which N-MTV is incorporated may better inform adjuvant treatment decisions.

Background: Radium-223 dichloride (Ra-223) is a targeted alpha particle-based radiotherapeutic that has a localized cytotoxic effect on bone metastases. We sought to determine whether the circulating tumor cell (CTC) count and the presence of CTCs in epithelial-mesenchymal transition (EMT-CTCs) along with the standardized uptake value (SUV) on positron emission tomography-computed tomography (PET/CT) scans predict the efficacy of combined Ra-223 and hormonal therapy in patients with hormone receptor (HR)-positive bone-dominant metastatic breast cancer. Patients and Methods: In this single-center phase 2 study (NCT02366130), 36 patients received Ra-223 (55 kBq/kg intravenously) on day 1 and then every 4 weeks for six cycles. Patients also received a standard care endocrine monotherapy. One non-bone metastatic site was allowed. The number of prior endocrine therapies was not limited and one prior chemotherapy was allowed for metastasis. Response was evaluated using the PET Response Criteria in Solid Tumors (PERCIST) with PET/CT at baseline, 6 and 9 months (mo) later. The CTC count (CellSearch) and the presence of EMT-CTCs (AdnaTest) was determined at baseline, 6 and 9 mo later. Progression-free survival (PFS) time was calculated to evaluate efficacy. Results: Seven patients (20%) had a non-bone metastatic site. The median number of prior therapies for metastasis was 1 (range, 0-4). Six patients (17%) received chemotherapy. The median CTC count at baseline was 4 (range, 0-306). Only four patients (11%) were positive for EMT-CTCs at baseline. The median follow-up time was 14.7 mo (95% confidence interval [CI], 13.2 mo-not reached [NR]). The disease control rate at 9 mo was 46% in 33 patients who reached 9 mo or progressed up to 9 mo. The tumor response rate at 6 mo was 52% (complete/partialresponse rate; 22/30 %) in 27 patients whose disease was evaluable using PERCIST. The SUV on PET/CT decreased significantly at 6 and 9 mo after baseline (average decreases of 1.5 (p=0.0004) and 2.5 (p=0.0054), respectively). The median PFS duration was 7.4 mo (95% CI, 4.8 mo-NR). The median bone PFS was 16 mo (95% CI, 7.3 mo-NR). Patients with bone-only metastasis (N=28, 80%) had a significantly longer median PFS duration than did patients with non-bone metastases at baseline (N=7, 20%) (13.8 mo versus 4.5 mo; p=0.017). Patients without prior treatment (N=12, 34%) tended to have longer median PFS durations than did those who underwent prior treatment (N=23, 66%) (16.8 mo versus 4.8 mo; p=0.1865). Also, patients with Conclusions: Bone-only metastatic breast cancer and SUV suppression by Ra-223 are predictive of efficacy. Patients with baseline Citation Format: Ueno NT, Tahara RK, Reuben JM, Gao H, Saigal B, Fujii T, Lucci A, Ibrahim NK, Damodaran S, Shen Y, Liu DD, Hortobagyi GN, Tripathy D, Lim B, Chasen BA. CTCs and SUV to predict the efficacy of the bone-specific radiopharmaceutical agent radium-223 dichloride combined with hormonal therapy for hormone receptor-positive bone-dominant breast cancer metastasis [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-18-04.

Objectives Uterine leiomyosarcoma (uLMS) is one of rare and aggressive gynecologic malignancies. In this study, we aimed to correlate immune cell profiling with clinical outcomes in uLMS. Methods Total of 6 pathologically diagnosed uLMS patients were enrolled in this study. RNAs were extracted from FFPEs of normal and tumor lesions, and Cell Type Profiling analysis was conducted using nCounter, PanCancer Immune Profiling Panel (NanoString). For evaluating the related pathways, the RNAs were used to conduct microarray analysis using SurePrint G3 Human GE microarray 8 × 60K ver.2.0 (Agilent). Results FIGO stage were IB in 4 patients, IIA in one patient, and IVB in one. We divided these patients into three groups by prognosis; good, no recurrence more than 2 years; intermediate, recurrent within 2 years; poor, recurrent immediately after surgery. In good prognostic group, CD8/regulatory T (Treg) ratio and Mast cell score in tumor lesions were elevated, and TP53 network, and DNA damage response signals were upregulated. In intermediate group, total TIL score in normal uterine were elevated, but CD8/Treg ratio was decreased in tumor lesion. And PI3K/AKT/mTOR signal and STAT3, IL8 signaling were upregulated. Finally, in poor prognostic group, total TIL score were decreased in normal and tumor lesions, and Neutrophil score was elevated in tumor lesions. Upregulation of DNA damage response but downregulated TP53 network. Conclusions Immune cell profiling may predict clinical outcomes in uLMS. Further analyses, such as, correlation with signaling pathways affected to immune cell profiling in larger sample size are needed.

Highlights • Code comparisons build confidence in simulators to model interdependent processes. • International hydrate reservoir simulators are compared over five complex problems. • Geomechanical processes significantly impact response of gas hydrate reservoirs. • Simulators yielded comparable results, however many differences are noted. • Equivalent constitutive models are required to achieve agreement across simulators. Geologic reservoirs containing gas hydrate occur beneath permafrost environments and within marine continental slope sediments, representing a potentially vast natural gas source. Numerical simulators provide scientists and engineers with tools for understanding how production efficiency depends on the numerous, interdependent (coupled) processes associated with potential production strategies for these gas hydrate reservoirs. Confidence in the modeling and forecasting abilities of these gas hydrate reservoir simulators (GHRSs) grows with successful comparisons against laboratory and field test results, but such results are rare, particularly in natural settings. The hydrate community recognized another approach to building confidence in the GHRS: comparing simulation results between independently developed and executed computer codes on structured problems specifically tailored to the interdependent processes relevant for gas hydrate-bearing systems. The United States Department of Energy, National Energy Technology Laboratory, (DOE/NETL), sponsored the first international gas hydrate code comparison study, IGHCCS1, in the early 2000s. IGHCCS1 focused on coupled thermal and hydrologic processes associated with producing gas hydrates from geologic reservoirs via depressurization and thermal stimulation. Subsequently, GHRSs have advanced to model more complex production technologies and incorporate geomechanical processes into the existing framework of coupled thermal and hydrologic modeling. This paper contributes to the validation of these recent GHRS developments by providing results from a second GHRS code comparison study, IGHCCS2, also sponsored by DOE/NETL. IGHCCS2 includes participants from an international collection of universities, research institutes, industry, national laboratories, and national geologic surveys. Study participants developed a series of five benchmark problems principally involving gas hydrate processes with geomechanical components. The five problems range from simple geometries with analytical solutions to a representation of the world's first offshore production test of methane hydrates, which was conducted with the depressurization method off the coast of Japan. To identify strengths and limitations in the various GHRSs, study participants submitted solutions for the benchmark problems and discussed differing results via teleconferences. The GHRSs evolved over the course of IGHCCS2 as researchers modified their simulators to reflect new insights, lessons learned, and suggested performance enhancements. The five benchmark problems, final sample solutions, and lessons learned that are presented here document the study outcomes and serve as a reference guide for developing and testing gas hydrate reservoir simulators.

Two-dimensional layered semiconductor black phosphorus (BP), a promising pressure induced Dirac system as predicted by band structure calculations, has been studied by $^{31}$P-nuclear magnetic resonance. Band calculations have been also carried out to estimate the density of states $D(E)$. The temperature and pressure dependences of nuclear spin lattice relaxation rate $1/T_1$ in the semiconducting phase are well reproduced using the derived $D(E)$, and the resultant pressure dependence of semiconducting gap is in good accordance with previous reports, giving a good confirmation that the band calculation on BP is fairly reliable. The present analysis of $1/T_1$ data with the complemental theoretical calculations allows us to extract essential information, such as the pressure dependences of $D(E)$ and chemical potential, as well as to decompose observed $1/T_1$ into intrinsic and extrinsic contributions. An abrupt increase in $1/T_1$ at 1.63GPa indicates that the semiconducting gap closes, resulting in an enhancement of conductivity., 11 pages, 4 figures

Funding Acknowledgements Department funding Background Mitral valve repair is preferred to valve replacement in cases of degenerative mitral regurgitation (MR) due to the lower risk of valve-related complications and operative mortality. In mitral valve repair, annuloplasty is associated with better clinical outcomes. Sizing of the annuloplasty ring with a ring sizer, which should be performed in the end-systolic phase, is performed in diastole during hyperkalaemia cardioplegic arrest. Three-dimensional transoesophageal echocardiography (3D-TEE) allows measurement of the mitral valve while the heart is beating, which is beneficial since the mitral valve size changes throughout the cardiac cycle. Purpose To investigate whether 3D-TEE measurements of the mitral valve are effective for preventing recurrent mitral regurgitation (MR) in patients who undergo mitral valve repair for degenerative MR. Methods This study retrospectively reviewed 139 patients who underwent mitral annuloplasty for degenerative MR. After 47 patients were excluded, 92 patients were analysed. The inter-commissural (IC) distance and anterior leaflet height of the A2 segment of the mitral valve were measured by 3D-TEE at the end-systolic phase. The annuloplasty ring size and type were selected by surgeons using specific ring sizers. We investigated the association of the IC distance with the size of implanted annulus ring and differences between the size of implanted annulus ring and the IC distance. We also compared the IC distance, the A2 height, and the ratio of A2 height to IC distance between patients with and without recurrent mild-to-moderate MR for 36 months. Results There was a significant correlation between the size of the mitral annuloplasty ring and the IC distance (R²=0.7023, p Conclusions There was a significant correlation between the size of the mitral annuloplasty ring and the IC distance. Our results demonstrated a higher ratio of A2 height to IC distance in patients with recurrent MR. Abstract P1409 Figure1

Poor response to ovarian hyper-stimulation can be difficult to predict prior to stimulation even when factoring in patient age and ovarian reserve testing. When faced with the situation of poor response, patients and providers have the difficult decision to proceed with oocyte retrieval, convert to intrauterine insemination (IUI), or cancel the cycle. Although this is not an uncommon scenario, there is little data available to assist with the counseling of these patients. We performed a systematic review of published studies comparing clinical pregnancy and live births between those patients continuing with in-vitro fertilization (IVF) and those converting to IUI. PubMed and Ovid were searched for all retrospective and randomized studies using the Keywords 'in-vitro fertilization', 'intrauterine insemination', 'poor responders', 'clinical pregnancy' and 'live birth rates'. A total of seven retrospective studies and one randomized control trial were reviewed. When evaluating poor responders as a group, six studies reported higher overall clinical pregnancy rates and five studies reported overall increased live birth rates with continuance of IVF. When stratified by the number of follicles produced, continuance of IVF demonstrated higher clinical pregnancy and live birth rates with ≥ 2 follicles. When only one follicle developed there were no significant differences in clinical pregnancy or live birth rates between the two groups. In patients undergoing IVF with ≤4 follicles, continuance with IVF may lead to higher clinical pregnancy and live birth compared to conversion to IUI except in patients with monofollicular development, although additional randomized controlled trials are needed to confirm these findings.

Background Radium-223 dichloride (Ra-223) is a therapeutic alpha particle-emitting radiopharmaceutical compound which have antitumor effect targeted on bone metastases. Alpha particles induces double strand DNA breaks and localized cytotoxic effect to cancer cells with limiting harm on normal tissues. We are conducting a phase II clinical trial of combination of Ra-223, hormonal therapy, and denosumab treatment in patients with hormone receptor (HR)-positive bone-dominant metastatic breast cancer (NCT02366130). In this preliminary analysis of the study, we aimed to evaluate the feasibility and safety of this combination therapy. Methods This single-center phase II study seeks to determine the efficacy and safety of Ra-223 in combination with hormonal therapy and denosumab. Major eligibility criteria include HR-positive breast cancer with bone and/or marrow predominant metastases. Patients with two or more visceral metastases were not eligible. There was no limit in the number of prior hormonal therapies in the metastatic setting. Patients received Ra-223 injection (55 kBq/kg intravenously) on day 1 of the study and then every 4 weeks thereafter for 6 cycles. Patients were also administered a single hormonal agent (i.e., tamoxifen, aromatase inhibitor, or fulvestrant at standard doses) daily and denosumab (120 mg subcutaneously) every 4 weeks. For this analysis, adverse events (AEs) were summarized using descriptive statistics. Results A total of 25 patients were enrolled and 22 were evaluable between March 2015 and December 2016. Median age was 58.5 years (range 31-79), and 59% of patients were postmenopausal. ECOG performance status was 0 in 16 patients (73%), and 1 in six patients (27%). HER2/neu was positive in only one patient. Four patients (18%) were de novo metastasis, no patients had visceral metastasis, and multiple bone metastases in 20 patients (91%) vs. focal metastasis in 2 (9%). Median time from diagnosis of bone metastasis was 4.8 months (range 0.5-96.6). Prior therapy for metastatic disease consisted of hormonal therapy in 50% of the patients (eight patients with one line and three patients with two lines), chemotherapy (9%), palbociclib (14%), radiation to bone metastasis (50%), and bone-supportive therapy (27% with zoledronic acid, 27% with denosumab). The median number of cycles of Ra-223 administered was 6 (range 4-6). The median follow-up time was 4 months (range 2-8). There were no grade 3 or 4 AEs. Major non-hematological grade 1 and 2 AEs were bone pain (77%), fatigue (45%), nausea (36%), diarrhea (32%), AST/ALT elevation (23%), hot flashes (23%), and headache (18%). The most common hematological AEs were grade 1 or 2 neutropenia (23%), anemia (14%), and thrombocytopenia (18%). There was no treatment delay or discontinuation due to AEs. Conclusion Our results suggest that the addition of Ra-223 to hormonal therapy and denosumab is a feasible and safe combination therapy in patients with HR-positive breast cancer with bone-dominant metastasis. We continue to enroll patients in the phase II trial to evaluate the efficacy of the treatment. Citation Format: Tahara RK, Fujii T, Saigal B, Ibrahim NK, Damodaran S, Barcenas CH, Murray JL, Chasen BA, Shen Y, Liu DD, Hortobagyi GN, Tripathy D, Ueno NT. Phase II study of the feasibility and safety of radium-223 dichloride in combination with hormonal therapy and denosumab for the treatment of patients with hormone receptor-positive breast cancer with bone-dominant metastasis [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-16-02.

Background: The number of patients worldwide with metastatic breast cancer (MBC) who participate in therapeutic clinical trials has remained so far low. One of the reasons is a lack of opportunity, whereas another is fear of health care providers and patients of poor outcome of the use of new drugs. We therefore investigated whether survival in patients with MBC who participated in first-line therapeutic clinical trials is worse than that in patients who received only standard care and never enrolled in a clinical trial. We hypothesized that first-line therapeutic clinical trials do not negatively affect survival outcome. Methods: We reviewed the records of 5501 patients with MBC treated at The University of Texas MD Anderson Cancer Center from January 2000 to December 2010. We extracted a first cohort of 285 patients enrolled in a therapeutic clinical trial for the first time for first-line systemic MBC treatment. The second cohort, referred to as the eligible control population, consisted of 367 patients without comorbidities who did not participate in a clinical trial at any stage of their disease; these patients lived in Harris County, in which MD Anderson is located, and thus could be potentially eligible for MD Anderson's financial assistance program. To limit confounding factors, we excluded male patients and patients with known brain metastasis from both cohorts. Results: The median follow-up duration in our cohort was 7.16 years (95% confidence interval [CI], 6.53-7.64 years). We observed discrepancies in race (minorities were less represented in the clinical trial arm), estrogen receptor (ER) status (more ER-positive than ER-negative patients participated in clinical trials), and metastatic disease site (fewer patients with bone metastasis participated in clinical trials) between the two groups. Overall, we observed no significant differences in progression-free survival (PFS) or overall survival (OS) duration between the treatment arms. Specifically, in the clinical trial cohort, the median PFS duration was 7.00 months (95% CI, 5.72-8.71 months), and the median OS duration was 28.48 months (95% CI, 22.70-34.60 months). In the control cohort, the median PFS duration was 10.02 months (95% CI, 7.13-11.99 months), and the median OS duration was 28.71 months (95% CI, 24.41-31.31 months) (P = .089 and .335, respectively). Conclusion: In MBC patients, enrolling in first-line therapeutic clinical trials does not result in worse survival than does never enrolling in a clinical trial. This study should reassure health care providers in demonstrating that enrollment in a clinical trial does not negatively affect survival in MBC patients. Citation Format: Le Du F, FUJII T, Park M, Liu D, Hsu L, Gonzalez-Angulo A-M, Ueno NT. Impact of enrollment in clinical trials on survival of metastatic breast cancer patients [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-10-07.

Hydrosalpinx, the blockage of fallopian tubes, can result from pelvic inflammatory disease. Hydrosalpinx is a cause of infertility and negatively impacts in vitro fertilization. To better understand the pathobiology of hydrosalpinx, we compared the proteome of lavages from disease vs. healthy fallopian tubes. Results indicate a disruption of redox homeostasis and activation of the complement system, immune cell infiltration, and phagocytosis; pathways that may drive tubal injury. To our surprise among the most prominent proteins with hydrosalpinx was mesothelin (MSLN), which until now has only been associated with epithelial malignancies. Analogous to mesothelioma and ovarian carcinoma, a significant increase of MSLN was detected in plasma from patients with hydrosalpinx. This finding suggests MSLN may provide clinical diagnosis in lieu of the current approaches that require invasive imaging. Importantly, these findings implicate MSLN in a benign disease, indicating that the activation and role of MSLN is not restricted to cancer.

Chlamydia trachomatis is the most common sexually transmitted bacterial infection in the United States. Within the U.S. military, the age- and race-adjusted chlamydia infection rates among female service members are consistently higher than civilian rates, with a 20% annual acquisition rate among young active-duty women. The sequelae of chlamydia disproportionately impact women in terms of severity and cost. Untreated chlamydia progresses to pelvic inflammatory disease in 40% of cases, and is a leading cause of fallopian tube damage and pelvic adhesive disease resulting in ectopic pregnancy, tubal infertility, and acute and chronic pelvic pain. Tubal infertility is among the leading indications for in vitro fertilization (IVF) nationally and rates among couples undergoing IVF at military treatment centers are double the national average. Collectively, chlamydia infection represents a significant resource burden to the military health care system and, in view of the serious gynecologic health sequelae, a significant threat to the readiness of servicewomen. In this review, we discuss the gynecologic impact of chlamydia infection within the military, the critical gaps for research funding, and opportunities for intervention.

BACKGROUND AND PURPOSE: The flow-diverter device has been established as a treatment procedure for large unruptured intracranial aneurysms. The purpose of this study was to compare the usefulness of Silent MR angiography and time-of-flight MRA to assess the parent artery and the embolization state of the aneurysm after a flow-diverter placement. MATERIALS AND METHODS: Seventy-eight large, unruptured internal carotid aneurysms in 78 patients were the subjects of this study. After 6 months of treatment, they underwent follow-up digital subtraction angiography, Silent MRA, and TOF-MRA, performed simultaneously. All images were independently reviewed by 2 neurosurgeons and 1 radiologist and rated on a 4-point scale from 1 (not visible) to 4 (excellent) to evaluate the parent artery. The aneurysmal embolization status was assessed with 2 ratings: complete or incomplete occlusion. RESULTS: The mean scores of Silent MRA and TOF-MRA regarding the parent artery were 3.18 ± 0.72 and 2.31 ± 0.86, respectively, showing a significantly better score with Silent MRA (P < .01). In the assessment of the embolization of aneurysms on Silent MRA and TOF-MRA compared with DSA, the percentages of agreement were 91.0% and 80.8%, respectively. CONCLUSIONS: Silent MRA is superior for visualizing blood flow images inside flow-diverter devices compared with TOF-MRA. Furthermore, Silent MRA enables the assessment of aneurysmal embolization status. Silent MRA is useful for assessing the status of large and giant unruptured internal carotid aneurysms after flow-diverter placement.

Background:An all-case post marketing surveillance (PMS) of baricitinib (Bari), that started in Sep 2017, collects safety and effectiveness for the first 24 wks of treatment and continues to collect serious adverse events (SAEs) for 3 yrs.Objectives:To evaluate Bari safety in RA patients (pt) in clinical practice.Methods:We report pt baseline demographics and adverse events (AEs) up to 24 wks for pts whose case report files for 24-wk data were completed as of Jun 2020.Results:Data from 3445 pts were analyzed (females=80%, mean age=64yr, mean RA duration 12yr). Bari dose regimen was as follows: 4mg, 60%, 2mg, 27%, 4mg→2mg, 5%, 2mg→4mg, 5%, and others, 2%. Concomitant use of MTX and glucocorticoid was 65% and 48%, respectively. 74% continued treatment for 24 wks. AE and SAE were recognized in 887 (26%) and 122 pts (4%), respectively. 6 pts died of pneumonia, aspiration pneumonia, bacterial pneumonia, cerebral infarction/ILD/aspiration pneumonia, adenocarcinoma, and colorectal cancer. Major AEs were as follows: herpes zoster=3%, liver dysfunction=3%, serious infection=1%, anemia=1%, hyperlipidemia=1%, malignancy=0.3%, interstitial pneumonia=0.2%, MACE=0.1%, and VTE=0.1%.Conclusion:Data do not show new safety concerns and encourage guideline-compliant use of Bari.Disclosure of Interests:Takao Fujii Speakers bureau: Chugai Pharmaceutical Co. Ltd.; Eisai Co. Ltd; Eli Lilly Japan K.K.; Janssen Pharmaceutical K.K.; Ono Pharmaceutical Co. Ltd., Consultant of: Asahikasei Pharma Corp, Grant/research support from: Asahikasei Pharma Corp; AbbVie Japan GK; Chugai Pharmaceutical Co. Ltd., Eisai Co. Ltd; Eli Lilly Japan K.K.; Mitsubishi-Tanabe Pharma Co.; Ono Pharmaceutical Co., Ltd., Tatsuya Atsumi Speakers bureau: AbbVie Japan GK; Astellas Pharma Inc.; Bristol-Myers Squibb Co. Ltd; Chugai Pharmaceutical Co. Ltd.; Daiichi Sankyo Co. Ltd.; Eisai Co. Ltd.; Eli Lilly Japan K.K.; Mitsubishi Tanabe Pharma Co.; Pfizer Japan Inc.; Takeda Pharmaceutical Co. Ltd., UCB Japan Co. Ltd., Consultant of: AbbVie Japan GK; AstraZeneca plc.; Boehringer Ingelheim Co. Ltd.; Medical & Biological Laboratories Co. Ltd.; Novartis Pharma K.K.; Ono Pharmaceutical Co. Ltd.; Pfizer Japan Inc., Grant/research support from: Astellas Pharma Inc., Alexion Inc.; Chugai Pharmaceutical Co. Ltd., Daiichi Sankyo Co. Ltd., Mitsubishi Tanabe Pharma Co., Otsuka Pharmaceutical Co., Ltd.Pfizer Japan Inc.; Takeda Pharmaceutical Co. Ltd., Nami Okamoto Speakers bureau: AbbVie Japan GK; Asahikasei Pharma Co.; AYUMI Pharmaceutical Co.Eisai Co. Ltd; Bristol-Myers Squibb Co. Ltd.; Eli Lilly Japan K.K.; Mitsubishi-Tanabe Pharma Co.; Pfizer Japan Inc.Sanofi K.K.; Chugai Pharmaceutical Co. Ltd.; Novartis Pharma Co.; Teijin Pharma Ltd.; Torii Pharmaceutical Co., Ltd., Nobunori Takahashi Speakers bureau: AbbVie Japan GK; Eisai Co. Ltd.; Mitsubishi Tanabe Pharma Co.; Pfizer Japan Inc.; Chugai Pharmaceutical Co., Ltd.; Eli Lilly Japan K.K.; Janssen Pharmaceutical K.K.; UCB Japan Co. Ltd.; Astellas Pharma Inc.; Bristol Myers Squibb Co. Ltd., Grant/research support from: Bristol Myers Squibb Co. Ltd., Naoto Tamura Speakers bureau: AbbVie Japan GK; Bristol Myers Squibb Co. Ltd.; Chugai Pharmaceutical Co. Ltd.; Eisai Co. Ltd.; Eli Lilly Japan K.K.; Glaxo Smith Kline K.K.; Janssen Pharmaceutical K.K.; Mitsubishi-Tanabe Pharma Co.; Novartis Pharma Co., Atsuo Nakajima: None declared, Ayako Nakajima Speakers bureau: AbbVie Japan GK; Actelion Pharmaceuticals Japan Ltd., Asahi Kasei Pharma Co., Astellas Pharma Inc., Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd.,Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., Glaxo Smith Kline K.K., Hisamitsu Pharmaceutical Co. Inc., Kyorin Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Co., Otsuka Pharmaceutical Co. Ltd., Pfizer Japan Inc., Teijin Pharma Ltd., Grant/research support from: Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Hiroaki Matsuno Speakers bureau: Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Eli Lilly Japan K.K., Consultant of: Mochida Pharmaceutical Co., Ltd., Grant/research support from: Astellas Pharma Inc., Eli Lilly Japan K.K.; Janssen Pharmaceutical K.K, Naoto Tsujimoto Shareholder of: Eli Lilly, Employee of: Eli Lilly Japan K.K., Atsushi Nishikawa Shareholder of: Eli Lilly, Employee of: Eli Lilly Japan K.K., Taeko Ishii Shareholder of: Eli Lilly, Employee of: Eli Lilly Japan K.K., Tsutomu Takeuchi Speakers bureau: AbbVie Japan GK, Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co, Ltd. Daiichi Sankyo Co., Ltd. Eisai Co., Ltd. Eli Lilly Japan K.K.; Gilead Sciences, Inc. Janssen Pharmaceutical K.K.; Mitsubishi-Tanabe Pharma Co.; Novartis Pharma Co.; Pfizer Japan Inc.; Sanofi K.K.; UCB Japan Co., Ltd., Consultant of: AbbVie Japan GK, Astellas Pharma, Inc.; Chugai Pharmaceutical Co, Ltd.; Eli Lilly Japan K.K.; Eisai Co., Ltd.; Gilead Sciences, Inc.; Janssen Pharmaceutical K.K.; Mitsubishi-Tanabe Pharma Corp., Pfizer Japan Inc., Grant/research support from: AbbVie Japan GK, Asahikasei Pharma Corp., Chugai Pharmaceutical Co, Ltd., DNA Chip Research Inc.; Eisai Co., Ltd., Eli Lilly Japan K.K.; Mitsubishi-Tanabe Pharma Corp., UCB Japan Co., Ltd., Masataka Kuwana Speakers bureau: AbbVie Japan GK, Astellas Pharma Inc., Asahi Kasei Pharma Co., Boehringer-Ingelheim, Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Janssen Pharmaceutical K.K., Medical &Biological Laboratories Co., Ltd.; Mitsubishi Tanabe Pharma Co.; Mochida Pharmaceutical Co., Ltd., Nippon Shinyaku Co., Ltd.; Ono Pharmaceutical Co., Ltd.; Pfizer Japan Inc., Consultant of: Boehringer-Ingelheim, Chugai Pharmaceutical Co., Ltd., Corbus Pharmaceuticals Holdings, Inc.; Medical &Biological Laboratories Co., Ltd.; Mochida Pharmaceutical Co., Ltd., Grant/research support from: Boehringer-Ingelheim, Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Medical &Biological Laboratories Co., Ltd; Mitsubishi Tanabe Pharma Co., Ono Pharmaceutical Co., Ltd., Michiaki Takagi Speakers bureau: Yes, but sponsored lectures without COI in the academic meetings, only.

An electrostatic time-of-flight detector named E-MCP has been developed for quick diagnostics of circulating beam and timing measurement in mass spectrometry at the Rare-RI Ring in RIKEN. The E-MCP detector consists of a conversion foil, potential grids, and a microchannel plate. Secondary electrons are released from the surface of the foil when a heavy ion hits it. The electrons are accelerated and deflected by 90$^\circ$ toward the microchannel plate by electrostatic potentials. A thin carbon foil and a thin aluminum-coated mylar foil were used as conversion foils. We obtained time resolutions of 69(1) ps and 43(1) ps (standard deviation) for a $^{84}$Kr beam at an energy of 170 MeV/u when using the carbon and the aluminum-coated mylar foils, respectively. A detection efficiency of approximately 90% was obtained for both foils. The E-MCP detector equipped with the carbon foil was installed inside the Rare-RI Ring to confirm particle circulation within a demonstration experiment on mass measurements of nuclei around $^{78}$Ge produced by in-flight fission of uranium beam at the RI Beam Factory in RIKEN. Periodic time signals from circulating ions were clearly observed. Revolution times for $^{78}$Ge, $^{77}$Ga, and $^{76}$Zn were obtained. The results confirmed successful circulation of the short-lived nuclei inside the Rare-RI Ring.

EUSO-Balloon is a pathfinder mission for the Extreme Universe Space Observatory onboard the Japanese Experiment Module (JEM-EUSO). It was launched on the moonless night of the 25th of August 2014 from Timmins, Canada. The flight ended successfully after maintaining the target altitude of 38 km for five hours. One part of the mission was a 2.5 hour underflight using a helicopter equipped with three UV light sources (LED, xenon flasher and laser) to perform an inflight calibration and examine the detectors capability to measure tracks moving at the speed of light. We describe the helicopter laser system and details of the underflight as well as how the laser tracks were recorded and found in the data. These are the first recorded laser tracks measured from a fluorescence detector looking down on the atmosphere. Finally, we present a first reconstruction of the direction of the laser tracks relative to the detector., 0, SCOPUS: ar.j, info:eu-repo/semantics/published

This paper reports the structural and optical investigations of the structural colour of the weevil Lamprocyphus augustus . The photonic crystal structure within the weevil's scales was investigated using sequential focused ion-beam milling and scanning electron microscopy imaging. We carefully analysed the reconstructed three-dimensional structure to determine the unit cell of the photonic crystal. It was found that the cuticle network of the cubic unit cell perfectly matches the previously reported diamond-based network. However, different results were obtained for the crystal orientations of the small crystal domains that comprise the entire photonic crystal structure in the scales: directions are highly preferred along the surface normal of the scale. This finding explains the fact that the scale is almost uniformly coloured despite the multi-domain structure. It is confirmed experimentally and theoretically that the wavelength range of the reflection band corresponds to the gap of the photonic band.

Background It has been well known that anti-TNF-α treatment for patients with rheumatoid arthritis (RA) is associated with anti-nuclear antibody (ANA) development. Using data of 110 RA patients treated with infliximab (IFX), we previously reported that ANA development along with ANA levels at base line were associated with poor outcomes of IFX. 1 However, no replication studies have been reported. In addition, whether the findings are true to general biological disease-modifying anti-rheumatic drugs (bDMARDs) is uncertain. Objectives To replicate an association between poor response and development of ANA during IFX treatment in patients with RA. To analyse whether the association is found in other bDMARDs. Methods We analysed a data of Japanese RA patients treated with (n=721) or without (bDMARDs-naive; n=1050) bDMARDs (IFX, etanercept ETN, adalimumab ADA, golimumab GLM, certolizumab pegol CZP, tocilizumab TCZ, abatacept ABT) as a first line bDMARD from a single comprehensive RA cohort. All of the participants were not included in our previous study. We conducted multiple logistic linear regression analysis to assess effects of ANA development on treatment outcomes. We further analysed correlates of ANA development. ANAs were determined by indirect immunofluorescence with HEp-2 cells, and ANA development was defined as more than two times increase from baseline values. Results We found that ANA development at 3 months after starting bDMARDs was significantly associated with cessation of bDMARDs due to insufficient response within a year (OR 3.70, p=0.037). We further found that RA patients who did not develop ANA at 3 months but developed ANA within a year showed a significant association with treatment failure between 12 and 24 months (OR 7.11, p=0.044). ANA levels at baseline showed significant association with or tendency of insufficient response in both situations (OR 1.21 and 1.69, respectively), independently on ANA development. We still found associations of ANA development after conditioning on IFX usage, indicating that the associations are not limited to IFX. Female was associated with ANA development (OR 1.85) and high levels of ANA at baseline (OR 2.41, p=0.006), which is consistent with previous data in healthy population. 2 bDMARDs use (OR 2.09, p=0.056) was also a risk for ANA development. Among bDMARDs, anti-TNF agents, especially IFX, were risk factors of ANA development (OR 6.34, p Conclusions ANA development during treatment is associated with poor response to bDMARDs, which is not limited to IFX. Female and IFX usage are risk factors for ANA development. References [1] Yukawa N, et al. Arthritis Research & Therapy2011;13:R213. [2] Kuramoto N, et al. Sci Rep2017;7:6911. Disclosure of Interest Y. Ishikawa: None declared, M. Hashimoto: None declared, H. Ito Grant/research support from: Pfizer Japan Inc., Mitsubishi Tanabe Pharma Corporation, Astellas Pharma Inc., Chugai Co., Ltd., Bristol-Myers Squibb, M. Tanaka: None declared, N. Yukawa: None declared, T. Fujii Grant/research support from: Pfizer Japan Inc., Ono Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Eisai Co.,Ltd., Astellas Pharma Inc., T. Mimori Grant/research support from: Pfizer Japan Inc., Mitsubishi Tanabe Pharma Corporation, Eisai Co.,Ltd., Astellas Pharma Inc., AYUMI Pharmaceutical Co., Chugai Co., Ltd., Bristol-Myers Squibb, Daiichi Sankyo Company, Ltd., Nippon Shinyaku Co., Ltd., Takeda Pharmaceutical Company, Ltd., C. Terao: None declared

The Telescope Array experiment studies ultra high energy cosmic rays using a hybrid detector. Fluorescence telescopes measure the longitudinal development of the extensive air shower generated when a primary cosmic ray particle interacts with the atmosphere. Meanwhile, scintillator detectors measure the lateral distribution of secondary shower particles that hit the ground. The Middle Drum (MD) fluorescence telescope station consists of 14 telescopes from the High Resolution Fly’s Eye (HiRes) experiment, providing a direct link back to the HiRes measurements. Using the scintillator detector data in conjunction with the telescope data improves the geometrical reconstruction of the showers significantly, and hence, provides a more accurate reconstruction of the energy of the primary particle. The Middle Drum hybrid spectrum is presented and compared to that measured by the Middle Drum station in monocular mode. Further, the hybrid data establishes a link between the Middle Drum data and the surface array. A comparison between the Middle Drum hybrid energy spectrum and scintillator Surface Detector (SD) spectrum is also shown.

Summary Introduction The aim of this study was to determine whether loss of ACL integrity in an older cohort precedes the onset of radiographic OA (ROA). Methods Participants in this nested case–control study were selected from the Osteoarthritis Initiative (OAI) study who had risk factors for OA development but did not have ROA (Kellgren–Lawrence grading (KLG) of 0 or 1) in both knees at baseline. The MRIs were assessed for the presence of ACL tears. Case knees were defined by the development of ROA on knee radiographs between the 12 and 48 month visits. Their radiographs were assessed at P0 (time of onset of radiographic knee OA), 1 year prior to P0 (P-1) and at baseline. Controls were selected from amongst those who did not develop incident ROA and were matched to cases. Results 355 persons who developed ROA were matched to 355 controls. No relationship between loss of ACL integrity and incident ROA was found at any assessment time point. Odds ratios (OR) for baseline, 1 year prior to incident ROA (P1) and at point of occurrence of incident ROA (P0) were 2.00 (0.66–6.06), 2.5 (0.76–8.24) and 2.75 (0.85–8.88) respectively. A significant risk of incident ROA was found in participants who had a history of knee injury with an OR of 1.51 (1.05–2.16). Conclusion Loss of ACL integrity does not confer a significantly increased risk of incident ROA in an older adult cohort. In contrast, a history of knee injury was associated with an increased risk of incident ROA.

Objective To assess whether the presence of structural osteoarthritis (OA) features over as many as 4 years prior to incident radiographic OA increases the risk of radiographic OA in a nested, case–control design. Methods We studied 355 knees from the Osteoarthritis Initiative cohort that developed radiographic OA before the 48-month visit. They were matched one-to-one by sex, age, and contralateral knee radiographic status with a control knee. Magnetic resonance images (MRIs) were read for bone marrow lesions (BMLs), cartilage damage, meniscal damage (including tears and extrusion), Hoffa synovitis, and effusion synovitis. Conditional logistic regression was applied to assess the risk of radiographic OA with regard to the presence of BMLs (score ≥2), cartilage lesions (score ≥1.1), meniscal damage (any) and extrusion of ≥3 mm ± (score ≥2), and Hoffa and effusion synovitis (any). Time points were defined as incident radiographic OA visit (P0), 1 year prior to the detection of radiographic OA (P −1), 2 years prior to the detection of radiographic OA (P −2), etc. Results The presence of Hoffa synovitis (hazard ratio [HR] 1.76 [95% confidence interval (95% CI) 1.18–2.64]), effusion synovitis (HR 1.81 [95% CI 1.18–2.78]), and medial meniscal damage (HR 1.83 [95% CI 1.17–2.89]) at P −2 predicted radiographic OA incidence. At P −1, all features but meniscal extrusion predicted radiographic OA, with highest odds for medial BMLs (HR 6.50 [95% CI 2.27–18.62]) and effusion synovitis (HR 2.50 [95% CI 1.76–3.54]). The findings at P −3 and P −4 did not reach statistical significance. Conclusion Our findings indicate that the presence of specific structural features of MRI-detected joint damage 2 years prior to incident radiographic OA increases the risk of incident radiographic OA. However, 1 year prior to radiographic OA, the presence of almost any abnormal morphologic feature increases the risk of radiographic OA in the subsequent year.

The patient was a 45-year-old man with underlying alcoholic liver cirrhosis. Two years prior, he was repeatedly hospitalized for liver failure symptoms and requested a living-donor liver transplantation (LDLT) because of end-stage cirrhosis. A pretransplantation blood test revealed a high 1,3-beta-d-glucan (BDG) value of 102.0 pg/mL (reference value

Aims To investigate the relationship between the progression of anaemia and renal pathological findings in patients with diabetic nephropathy. Methods A total of 223 patients with diabetes underwent renal biopsy from 1985 to 2010 and were confirmed to have pure diabetic nephropathy according to the recent classification, of whom 113 (baseline haemoglobin ≥ 11 g/dl) were enrolled in the study. Linear regression analysis was used to estimate the changes in haemoglobin levels during the follow-up period. Results In a multivariate model adjusted for clinical and histopathological variables, higher interstitial fibrosis and tubular atrophy scores were more strongly associated with a decrease in haemoglobin levels than were lower scores. Compared with an interstitial fibrosis and tubular atrophy score of 0, the standardized coefficients for interstitial fibrosis and tubular atrophy scores of 1, 2 and 3 were 0.20 (95% CI −0.31 to 0.93), 0.34 (95% CI −0.22 to 1.34) and 0.47 (95% CI 0.07 to 1.96), respectively, whereas a higher glomerular class, a higher vascular lesion score and the presence of exudative lesions were not strongly correlated with the decrease in haemoglobin. Conclusions Tubulointerstitial lesions that are more advanced are significantly associated with the progression of anaemia in patients with diabetic nephropathy after adjustment for numerous covariates. This finding suggests that tubulointerstitial lesions may be a useful prognostic indicator for anaemia in patients with diabetic nephropathy, and that decreased erythropoietin production attributable to the progression of tubulointerstitial lesions is a major cause of anaemia in these patients.

A bone biopsy specimen in a long-term hemodialysis patient with sarcoidosis coexisting with severe hypoparathyroidism has demonstrated that a persistent near physiological level of 1,25-dihydroxyvitamin D3 contributes to the preservation of bone remodeling and has the potential to retard the development of vascular calcification and atherosclerosis. Sarcoidosis-related hypercalcemia and hypoparathyroidism, which is characterized by 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) overproduction, is rarely seen in hemodialysis patients. Herein, we describe a 60-year-old Japanese woman on hemodialysis for 35 years who presented with malaise and hypercalcemia. Severe hypoparathyroidism without parathyroidectomy and a preserved 1,25(OH)2D3 level were detected. Computed tomography showed bilateral axillary lymphadenopathy and minimal aortic and soft tissue calcification. The axillary node biopsy led to a definite diagnosis of sarcoidosis. A bone biopsy specimen obtained from the right iliac crest showed remodeling of normal lamellar bone with scalloped cement lines and clear double labeling by tetracycline on fluorescence microscopy. Histomorphometric analysis revealed that the bone formation rate was preserved (30.0 %/year), together with a decrease of osteoid volume (5.75 %) and fibrous volume (0 %), indicating that the patient did not have adynamic bone disease and only showed mild disease. This is the first documented case of sarcoidosis-related hypercalcemia associated with severe hypoparathyroidism in a long-term hemodialysis patient who underwent bone histomorphometry. Our findings suggest that, in hemodialysis patients with sarcoidosis coexisting with severe hypoparathyroidism, a persistent near physiological level of 1,25(OH)2D3 contributes to the preservation of bone remodeling and has the potential to retard the development of vascular calcification and atherosclerosis.

The stability of the gain of the photomultiplier (PMT) camera for the Fluorescence Detector (FD) of the Telescope Array experiment was monitored using an 241 Am loaded scintillator pulsers (YAP) and a diffused xenon flasher (TXF) for a selected set of 35 PMT-readout channels. From the monitoring of YAP pulses over four years of FD operation, we found slow monotonic drifts of PMT gains at a rate of −1.7~+1.7%/year. An average of the PMT gains over the 35 channels stayed nearly constant with a rate of change measured at −0.01±0.31(stat)±0.21(sys)%/year. No systematic decrease of the PMT gain caused by the night sky background was observed. Monitoring by the TXF also tracked the PMT gain drift of the YAP at 0.88±0.14(stat)%/year.

Objective To assess structural progression in knees with no/mild radiographic osteoarthritis (OA) (i.e., Kellgren/Lawrence [K/L] grades 0-2) that will undergo knee replacement during a 5-year period; to assess differences in structural damage on magnetic resonance imaging (MRI) in knees with no/mild radiographic OA versus those with severe radiographic OA (i.e., K/L grades 3 and 4) at baseline; and to assess differences in pain levels between those groups. Methods All participants who underwent knee replacement from baseline to 60 months were drawn from the Osteoarthritis Initiative. MRIs were assessed for bone marrow lesions (BMLs), Hoffa synovitis, and effusion synovitis (i.e., hyperintensity signal changes in the fat pad and abnormal amount of capsular distension due to intraarticular joint fluid and/or synovial thickening) at baseline and at the time point before knee replacement (T0). The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Knee Injury and Osteoarthritis Outcome Score (KOOS) pain were used for pain characterization. WOMAC activities of daily living and KOOS quality of life were applied to characterize functional status of the included participants. Logistic regression was used to assess the association of no/mild radiographic OA with these MRI features and pain. Results Based on inclusion criteria, 181 knees were selected. Participants were predominantly female (57.8%) with a mean age of 64.4 years. A total of 51 knees (28.2%) had no/mild radiographic OA at baseline. Of these, 51.0% progressed to severe radiographic OA. No/mild radiographic OA knees showed higher odds of BMLs in the patellofemoral joint at baseline (odds ratio [OR] 7.92 [95% confidence interval (95% CI) 3.45-18.16]) and T0 (OR 9.44 [95% CI 4.00-22.28]) compared to severe radiographic OA knees. In addition, no/mild radiographic OA knees were associated with change from no pain to pain from baseline to T0 (adjusted OR 5.48 [95% CI 1.25-24.00]). Conclusion More than half of the knees with no/mild radiographic OA before knee replacement progressed to severe radiographic OA during 4 years of follow-up. BMLs in the patellofemoral joint were more often seen among knees that had no/mild radiographic OA. Worsening pain status may contribute to knee replacement in knees with no/mild radiographic OA.

Turoctocog alfa pegol (N8-GP) is a novel glycoPEGylated extended half-life recombinant factor VIII (FVIII) product developed for prophylaxis and treatment of bleeds in patients with haemophilia A, to enable higher activity levels with less frequent injections compared with standard FVIII products. This phase III (NCT01480180), multinational, open-label, non-randomised trial evaluated the safety and clinical efficacy of N8-GP when administered for treatment of bleeds and for prophylaxis, in previously treated patients aged ≥12 years with severe haemophilia A. Patients were allocated to receive N8-GP for prophylaxis or on-demand treatment for up to 1.8 years. Patients on prophylaxis were administered one dose of 50 IU/kg of N8-GP every fourth day. Bleeds were treated with doses of 20-75 IU/kg. Total exposure to N8-GP in the trial was 14,114 exposure days (159 patient-years). For the prophylaxis arm (n=175), the median annualised bleeding rate (ABR) was 1.33 (interquartile range, 0.00-4.61), the mean ABR was 3.70 (95 % confidence interval 2.94-4.66) and 70 (40 %) patients had no bleeds during the trial. Across treatment arms, 83.6 % of bleeds resolved with one injection and 95.5 % with up to two injections. N8-GP had a favourable safety profile and was well tolerated. The frequency and types of adverse events reported were as expected in this population. One patient developed inhibitory antibodies against FVIII (≥0.6 Bethesda units [BU]) after 93 N8-GP exposure days. No clinically significant safety concerns were identified and N8-GP was effective for prophylaxis and treatment of bleeds in previously treated patients. Turoctocog alfa pegol (N8-GP) is a novel glycoPEGylated extended half-life recombinant factor VIII (FVIII) product developed for prophylaxis and treatment of bleeds in patients with haemophilia A, to enable higher activity levels with less frequent injections compared with standard FVIII products. This phase III (NCT01480180), multinational, open-label, non-randomised trial evaluated the safety and clinical efficacy of N8-GP when administered for treatment of bleeds and for prophylaxis, in previously treated patients aged ≥12 years with severe haemophilia A. Patients were allocated to receive N8-GP for prophylaxis or on-demand treatment for up to 1.8 years. Patients on prophylaxis were administered one dose of 50 IU/kg of N8-GP every fourth day. Bleeds were treated with doses of 20-75 IU/kg. Total exposure to N8-GP in the trial was 14,114 exposure days (159 patient-years). For the prophylaxis arm (n=175), the median annualised bleeding rate (ABR) was 1.33 (interquartile range, 0.00-4.61), the mean ABR was 3.70 (95 % confidence interval 2.94-4.66) and 70 (40 %) patients had no bleeds during the trial. Across treatment arms, 83.6 % of bleeds resolved with one injection and 95.5 % with up to two injections. N8-GP had a favourable safety profile and was well tolerated. The frequency and types of adverse events reported were as expected in this population. One patient developed inhibitory antibodies against FVIII (≥0.6 Bethesda units [BU]) after 93 N8-GP exposure days. No clinically significant safety concerns were identified and N8-GP was effective for prophylaxis and treatment of bleeds in previously treated patients.

Experimental and theoretical works are conducted on the first-order and second-order wave interactions among an array of two rows of vertical circular cylinders. We show that both the first-order and the second-order resonance of dynamic free-surface displacement could in some cases be quite relevant among an array of two rows of vertical cylinders not only in theory but also in real phenomena. In some cases, on the other hand, we show that large free-surface displacement predicted theoretically is quite attenuated in reality probably due to viscous dissipation.

A 33-year-old woman presented for a preoperative examination prior to an upcoming operative hysteroscopy. During the examination, a firm 1 cm mass in her right labia minora was noted. The mass was excised in the operating room without difficulty. Pathological examination revealed a benign phyllodes tumour of the vulva. Phyllodes tumours are uncommon fibroepithelial tumours primarily found in the breast although rarely may present as a vulvar lesion. Phyllodes tumours of the vulva are rarely reported in the literature, with only 17 previously reported cases. This case represents the first reported case of a phyllodes tumour occurring in the labia minora. While most of these tumours are benign, it is important to keep these and other rare tumours in the differential diagnosis of vulvar masses. Even with benign tumours, continued surveillance for recurrence should be performed.

Low-pressure multi-wire drift chambers have been developed to track high-intensity radioactive isotope beams at the energies of around 200 MeV/nucleon. In order to minimize the effect of multiple scattering by radioactive isotope beam, the thickness of the detectors were minimized by using isobutane gas at low pressure (10 kPa). The performance of the position resolution, the tracking efficiency, and the beam intensity capability were evaluated as a function of atomic number and applied voltage. As a result, an overall position resolution of 300 μm was achieved for radioactive isotope beams with an intensity of 1 MHz. The details of the design specifications and performances of the low-pressure multi-wire drift chambers are described.

The SHARAQ spectrometer and High-Resolution Beamline, which began operation in March 2009, have been put into use for six experiments using charge exchange reactions with radioactive isotope beams. For experiments at SHARAQ, detector developments and ion optics studies continue to improve performance in high-resolution nuclear spectroscopy. We have introduced improved timing resolution with CVD diamond detectors, high count-rate beamline tracking detectors and development of multi-particle detection by cathode-readout drift chambers. Ion-optics studies for the high-resolution achromatic (HA) and dispersion-matching (DM) transport modes are also reported here. Momentum tagging in the HA mode demonstrated an improvement in spectroscopic resolution with respect to the momentum spread of the radioactive beam. For the DM transportation mode, a momentum resolution of 1 / 8100 (FWHM) was achieved by taking into account the positions and angles of the beam at the third focal plane of BigRIPS.

The incidence of hot flashes under hormone manipulation therapy is so high that this symptom caused by sex hormone blocking agents has been bothering patients and has a negative impact on their quality of life. Venlafaxine and gabapentin are most promising novel nonestrogenic agents to control the symptom. We seek to quatitatively summarize the efficacy of these novel agents. We conducted a meta-analysis of randomized controlled studies on the efficacy of venlafaxine/gabapentin to hot flashes in cancer patient under hormone deprivation therapies. A search for Medline, Embase, Cochrane Central Register of Controlled Trials, Ichushi, and Google Scholar yielded 733 citations, which were independently assessed by two authors. We estimated overall effect sizes and its 95 % confidence intervals (CI) for the efficacy of these agents compared with the controls with standardized mean difference. A total of 5 studies involving 588 cancer patients with hot flashes finally fulfilled the predefined inclusion criteria. Overall effect size of the efficacy of venlafaxine/gabapentin was −0.630 (95 % CI [−0.801, −0.459]). Venlafaxine/gabapentin significantly improved hot flashes in cancer patients under hormone manipulation therapies.

We present a measurement of the energy spectrum of ultra-high-energy cosmic rays performed by the Telescope Array experiment using monocular observations from its two new FADC-based fluorescence detectors. After a short description of the experiment, we describe the data analysis and event reconstruction procedures. Since the aperture of the experiment must be calculated by Monte Carlo simulation, we describe this calculation and the comparisons of simulated and real data used to verify the validity of the aperture calculation. Finally, we present the energy spectrum calculated from the merged monocular data sets of the two FADC-based detectors, and also the combination of this merged spectrum with an independent, previously published monocular spectrum measurement performed by Telescope Array’s third fluorescence detector [T. Abu-Zayyad et al., The energy spectrum of Telescope Array’s middle drum detector and the direct comparison to the high resolution fly’s eye experiment, Astroparticle Physics 39 (2012) 109-119, http://dx.doi.org/10.1016/j.astropartphys.2012.05.012 , Available from: ]. This combined spectrum corroborates the recently published Telescope Array surface detector spectrum [T. Abu-Zayyad, et al., The cosmic-ray energy spectrum observed with the surface detector of the Telescope Array experiment, ApJ 768 (2013) L1, http://dx.doi.org/10.1088/2041-8205/768/1/L1 , Available from: ] with independent systematic uncertainties.

In this paper, a simple experimental technique for the measurement of the Poisson's ratio of a small-sized specimen is described. When two equal and opposite bending moments are applied to a rectangular solid structure, the structure deforms like a saddlelike shape on the basis of the linear elastic theory. The contour line on the structure middle portion is represented as a family of hyperbolas, and the angle between the asymptote and the structure's width direction is related to the Poisson's ratio. We applied the principle to a microspecimen. Based on Searle's analysis, the specimen was designed by means of finite element analysis. Single crystal silicon (SCS) was chosen as the first target material, and the specimen was manufactured by conventional micromachining technologies. The test equipment with a loading mechanism and a contour line measurement function using an optical interference method was developed. After precise alignment between the loading point and the center of the loading lever, normal loading was applied. From the obtained optical interference patterns, the mean angle of 14.5° was obtained in the penetration depth ranging from 25 to 100 μm. The angle provided the Poisson's ratio, 0.068, which was in very good agreement with the ideal value of the in-plane Poisson's ratio, 0.064, for SCS(001)[110]. The developed technique has the potential for evaluating the Poisson's ratio of small-sized specimens.