A wide range of bacterial and viral porcine pathogens are routine

A wide range of bacterial and viral porcine pathogens are routinely isolated from the tonsils [1]. In this study, we identified large numbers of sequences whose MRT67307 closest affiliate in the database were Haemophilus parasuis and Pasteurella multocida (on average 12.8% and 9.3%, respectively, of reads identified at the 97% cutoff), as well as small numbers of sequences closest SB-715992 price to Streptococcus suis (on average 0.4% of reads identified) from almost all

samples. However, we did not find sequences affiliated with Actinobacillus pleuropneumoniae or A. suis, which have been reported to be found in most swine herds in Ontario, Canada [7]. Small numbers of sequences closest to Mycoplasma were found in a few pigs, but these were not identified beyond the Classifier function

of the RDP. Herd 1 has been regularly tested and found to be free of A. pleuropneumoniae, A. suis, and Mycoplasma, which is substantiated by these results. We were surprised not to find sequences consistent with the presence of pathogenic Actinobacillus species in Herd 2, which has had a history of chronic but undefined see more respiratory problems. It is possible that these chronic problems are related to the higher numbers of Pasteurella sequences found in Herd 2, or to the presence of another known respiratory pathogen, Arcanobacterium, found in Herd 2 but not Herd 1. In addition to porcine pathogens, many bacterial agents of foodborne infections of humans have been isolated from pig tonsils, including members of the Enterobacteriaceae such as Salmonella species, Escherichia

PAK5 coli, and Yersinia enterocolitica as well as Campylobacter species and Listeria monocytogenes [9–13]. We found low numbers of Campylobacter (0.17% of total reads) and Escherichia (0.59% of total reads) in most of the pig tonsils in this study. In addition, we found other Enterobacteriaceae (1.9% of the total) that are rarely associated with human foodborne illness, including Citrobacter, Enterobacter, Morganella, Proteus, and Providencia, in one or more pigs. We did not find Salmonella, Yersinia, or Listeria in these tonsil samples from healthy pigs. The only other mammalian system where the tonsillar microbiota has been reported is in humans. Culture-based studies of human tonsils have identified Streptococcus pyogenes; S. pneumoniae; Group C, F, and G β-hemolytic streptococci; several α-hemolytic and non-hemolytic streptococci; Staphylococcus aureus; Haemophilus influenzae; H. parainfluenzae; and Moraxella catarrhalis in aerobic cultures [25–31]. Many species of the Bacteroides-Prevotella-Porphyromonas group, Fusobacterium, Lactobacillus, Peptostreptococcus, and Veillonella have also been isolated using anaerobic cultures.

Spine 27(1):92–98CrossRef Ghaffari M, Alipour A, Farshad AA, Jens

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PH, Staal JB, Heymans MW, Harts CC, Hendriks EJ, de Bie RA (2010) Prognostic factors for perceived recovery or functional improvement in non-specific low back pain: secondary analyses of three randomized clinical trials. Eur Spine J 19(4):650–659CrossRef Heymans MW, de Vet HC, Knol DL, Bongers PM, Koes BW, van MW (2006) Workers’ beliefs and expectations affect return to work over 12 months. J Occup Rehabil 16 (4):685–695 Hoogendoorn WE, van Poppel MN, Bongers PM, Koes BW, Bouter LM (2000) Systematic review of psychosocial factors at work and private life as risk factors for back pain. Spine 25(16):2114–2125CrossRef Hoogendoorn WE, Bongers PM, de Vet HCW, Houtman ILD, Ariens GAM, van Mechelen W, Bouter LM (2001) Psychosocial work characteristics and psychological

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J Clin Microbiol 2000,38(1):382–388 PubMed 9 Schwan TG, Piesman

J Clin Microbiol 2000,38(1):382–388.PubMed 9. Schwan TG, Piesman J, Golde WT, Dolan MC, Rosa PA: Induction of an outer surface protein on Borrelia burgdorferi C188-9 concentration during tick feeding. Proc Natl Acad Sci USA 1995,92(7):2909–2913.PubMedCrossRef 10. Pal U, de Silva AM, Montgomery RR, Fish D, Anguita J, Anderson JF, Lobet Y, Fikrig E: Attachment of Borrelia burgdorferi within Ixodes scapularis mediated by outer surface protein A. J Clin Invest 2000,106(4):561–569.PubMedCrossRef

11. Pal U, Li X, Wang T, Montgomery RR, Ramamoorthi N, Desilva AM, Bao F, Yang X, Pypaert M, 17DMAG order Pradhan D, et al.: TROSPA, an Ixodes scapularis receptor for Borrelia burgdorferi . Cell 2004,119(4):457–468.PubMedCrossRef 12. Yang XF, Pal U, Alani SM, Fikrig E, Norgard MV: Essential role for OspA/B in the life cycle of the Lyme disease spirochete. J Exp Med 2004,199(5):641–648.PubMedCrossRef 13. Grimm D, Tilly K, Byram R, Stewart PE, Krum JG, Bueschel DM, Schwan TG, Policastro PF, Elias AF, Rosa PA: Outer-surface protein C of the Lyme disease

spirochete: a protein induced in ticks for infection of mammals. Proc Natl Acad Sci USA 2004,101(9):3142–3147.PubMedCrossRef 14. Pal U, Yang X, Chen M, Bockenstedt LK, Anderson JF, Flavell RA, Norgard MV, Fikrig E: OspC facilitates Borrelia burgdorferi invasion of Ixodes scapularis salivary glands. J Clin Invest 2004,113(2):220–230.PubMed 15. Tilly Pitavastatin mw K, Krum JG, Bestor A, Jewett MW, Grimm D, Bueschel D, Byram R, Dorward D, Vanraden MJ, Stewart P, et al.: Borrelia burgdorferi OspC protein required exclusively in a crucial early stage of mammalian infection. Infect Immun 2006,74(6):3554–3564.PubMedCrossRef 16. Caimano MJ, Eggers CH, Hazlett KR, Radolf JD: RpoS is

not central to the general stress response in Borrelia burgdorferi but does control expression of one or more essential virulence determinants. Infect Immun 2004,72(11):6433–6445.PubMedCrossRef 17. Caimano MJ, Iyer R, Eggers CH, Gonzalez C, Morton EA, Gilbert MA, Schwartz I, Radolf JD: Analysis of the RpoS regulon in Borrelia burgdorferi in response to mammalian host signals provides insight into RpoS function during the enzootic cycle. Mol Microbiol 2007,65(5):1193–1217.PubMedCrossRef 18. Fisher MA, Grimm D, Henion AK, Elias AF, Stewart PE, Rosa PA, Gherardini FC: Borrelia burgdorferi NADPH-cytochrome-c2 reductase sigma54 is required for mammalian infection and vector transmission but not for tick colonization. Proc Natl Acad Sci USA 2005,102(14):5162–5167.PubMedCrossRef 19. Hubner A, Yang X, Nolen DM, Popova TG, Cabello FC, Norgard MV: Expression of Borrelia burgdorferi OspC and DbpA is controlled by a RpoN-RpoS regulatory pathway. Proc Natl Acad Sci USA 2001,98(22):12724–12729.PubMedCrossRef 20. Smith AH, Blevins JS, Bachlani GN, Yang XF, Norgard MV: Evidence that RpoS (sigmaS) in Borrelia burgdorferi is controlled directly by RpoN (sigma54/sigmaN). J Bacteriol 2007,189(5):2139–2144.PubMedCrossRef 21. Samuels DS: Gene regulation in Borrelia burgdorferi .

(PDF 1 MB) Additional file 2: Minimal inhibitory concentrations (

(PDF 1 MB) Selonsertib Additional file 2: Minimal inhibitory concentrations (MICs) of gentamicin for the studied strains. Results of this file show that MICs of gentamicin for SCVs are of 8 μg/ml whereas those of normal strains are below 2 μg/ml. (PDF 45 KB) Additional file 3: Appearance of HQNO-induced SCVs selected on gentamicin-containing agar and streaked back on TSA plates. Pictures are showing CF07-L, CF07-S and HQNO-induced SCVs selected

on gentamicin-containing agar and streaked back on TSA plates. The bottom pictures show streaks of three isolated SCVs on TSA plates. Many more SCVs were similarly tested and our results showed that at least 85% of learn more the SCVs isolated from gentamicin plates were keeping their slow-growth phenotype when subsequently grown on TSA without gentamicin. (PDF 2 MB) Additional file 4: Auxotrophism found among HQNO-induced SCVs. Auxotrophism found among HQNO-induced SCVs generated from the normal cystic fibrosis strains CF07-L and CF1A-L. (PDF 6 KB) Additional file 5: Growth of Newbould hemB in proximity of a well loaded with hemin. Growth of NewbouldhemB in proximity of a well loaded with hemin as an example of a positive auxotrophism

result. The auxotrophism of NewbouldhemB for hemin is seen by observing normal growth only within the diffusion zone of a well loaded with hemin. (PDF 3 MB) Additional mTOR inhibitor file 6: Non-normalized absorbance values at 560 nm representing biofilm production for each of the strains used in Fig. 2. Non-normalized absorbance values at 560 nm representing biofilm production for each of the strains used in Fig. 2. Results show that MycoClean Mycoplasma Removal Kit strains vary in their relative production of biofilms but that for each related pairs of normal and SCV strains, SCV counterparts always produce

more biofilm than their respective normal strains. (PDF 659 KB) References 1. Lyczak JB, Cannon CL, Pier GB: Lung infections associated with cystic fibrosis. Clin Microbiol Rev 2002,15(2):194–222.PubMedCrossRef 2. Hoffman LR, Deziel E, D’Argenio DA, Lepine F, Emerson J, McNamara S, Gibson RL, Ramsey BW, Miller SI: Selection for Staphylococcus aureus small-colony variants due to growth in the presence of Pseudomonas aeruginosa . Proc Natl Acad Sci USA 2006,103(52):19890–19895.PubMedCrossRef 3. Harrison F: Microbial ecology of the cystic fibrosis lung. Microbiology 2007,153(Pt 4):917–923.PubMedCrossRef 4. Brogden KA, Guthmiller JM, Taylor CE: Human polymicrobial infections. Lancet 2005,365(9455):253–255.PubMed 5. Duan K, Dammel C, Stein J, Rabin H, Surette MG: Modulation of Pseudomonas aeruginosa gene expression by host microflora through interspecies communication. Mol Microbiol 2003,50(5):1477–1491.PubMedCrossRef 6.

Proteomics 2009,9(23):5389–5393 PubMedCrossRef Competing interest

Proteomics 2009,9(23):5389–5393.PubMedCrossRef Competing interests The authors declare that they have no competing interests. Authors’ contributions MM and BC had equal contribution. All authors read and approved the final manuscript.”
“Erratum to: Int J Clin Oncol (2009) 14:534–536

DOI 10.1007/s10147-009-0875-6 In the printed version of the article, the accepted date was incorrectly shown. The correct date should be January 10, 2009, not 2008. The publisher sincerely MLN4924 mouse apologizes for the error.”
“Background Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is an emerging global problem with very similar clinical presentations across different clones, despite significant genetic diversity [1]. Many CA-MRSA strains carry lukSF-PV in the accessory genome, which encodes the Panton-Valentine leukocidin (PVL), an exotoxin that causes neutrophil lysis [1]. Although there has been considerable controversy as to the role of this toxin in CA-MRSA pathogenesis, some of this may be explained by a variable, species dependent susceptibility to PVL – human and rabbit neutrophils are lysed by PVL at very low concentrations whilst mouse and monkey neutrophils are less susceptible, making the interpretation

of animal model data difficult in some cases [2]. Additionally, Fenbendazole the importance of PVL is also likely to be dependent on the site of infection. In the rabbit pneumonia model, PVL has been demonstrated to have a clear GS-1101 manufacturer role in mediating severe lung necrosis and inflammation

[3]. In contrast, in skin infection, even in the rabbit model, its role remains less clear [4, 5]. Notwithstanding PVL, the increased expression of other core genome virulence determinants also contributes significantly to the increased virulence of CA-MRSA strains [6, 7]. These include α-hemolysin (Hla) and α-type phenol soluble modulins (PSMs). Hla is a pore-forming exotoxin that lyses many cells including red cells, platelets, monocytes and endothelial cells [8]. Hla has been demonstrated to be an important mediator of virulence in skin infection and pneumonia [9, 10]. The α-type PSMs have been recently characterized and they lyse neutrophils and red cells [11, 12]. The α-type PSMs also mediate virulence in skin infection and septicemia and of these, PSMα3 is the most potent [11]. The study of unique, distantly related CA-MRSA clones that also demonstrate enhanced virulence, may provide insights into the emergence of the global CA-MRSA phenomenon, and also help define the RG7112 purchase genomic determinants of enhanced virulence.

Statistical analysis Pearson’s Chi-Square test or Fisher’s Exact

Statistical analysis Pearson’s Chi-Square test or Fisher’s Exact test were used, when appropriate, to evaluate associations between the variables. The Odds PFT�� Ratio (OR) and the 95% confidence intervals (95% CI) were estimated for each variable. A multivariate logistic regression model was also developed using stepwise regression (forward selection) to compare the predictive power for modulation of different factors. Enter limit and remove limit were p = 0.10 and p = 0.15, respectively. The Blasticidin S clinical trial assessment of interactions

between significant investigation variables was taken into account when developing the multivariate model. Multivariate models based on regression tree analysis were explored to establish the most discriminative check details combination of variables to identify MSI-H. Recursive partitioning programs build classification or regression models of a very general structure using a 2-stage procedure; the resulting models can be represented as binary trees. Performance characteristics, accuracy, sensitivity,

specificity, positive (PPV) and negative (NPV) predictive values and areas under the curves (AUC) were evaluated with respect to the presence of MSI–H on tumor specimen by computing Receiver Operating Characteristic (ROC) curves. The SPSS®(20.0) statistical program was used for all the analyses. Results Patients 117 early onset CRC cases were recruited in the study and were categorized in three groups: Group A, 70 cases with CRC diagnosed at age ≤ 50 and no family history of CRC and/or other malignancies of LS spectrum.

Group B, 40 cases with CRC diagnosed at age ≤ 50 and Amsterdam II Criteria fulfilled. Group C, 7 Methocarbamol cases with CRC diagnosed at age ≤ 50 and family history of CRC, not fulfilling the Amsterdam II criteria. The median age at diagnosis of CRC was 42 years (range 20–50 years) in group A, 45 years (range 28–50 years) in group B and 39 years in group C (range 36–46 years); gender distribution (male/female) was 26/44 in group A, 19/21 in group B and 3/4 in group C (p = 0.57). 16 out of 70 patients of group A (22.9%), 21 out of 40 of group B (52.5%) and 2 out of 7 (28.6%) patients of group C had a right-sided colorectal cancer (proximal to the splenic flexure) (p = 0.006). There was no significant difference in staging at diagnosis between the three groups: an advanced stage (III, IV) was present in 38 out of 70 pts from group A (54.3%) vs 17 out of 40 patients from group B (44.7%) and 4 out of 7 from group C (57.1%) (p = 0.61).

Weeks and Breeuwer [48] showed that Wolbachia is involved in caus

Weeks and Breeuwer [48] showed that Wolbachia is involved in causing asexuality in at least two species: B. praetiosa and an unidentified species. Wolbachia is possibly causing asexuality in the other infected asexual Bryobia species as well. The general observation is that all individuals within the asexual Bryobia species are infected with Wolbachia. No males have ever been observed, neither in cultures nor in the field, and additional lab experiments including at least 20 individuals per species (except for B. berlesei) show a fixed infection

with Wolbachia (unpublished data). Moreover, Weeks and Breeuwer [48] analyzed 240 B. kissophila, 144 B. praetiosa, and 24 B. rubrioculus individuals and found all individuals infected with Wolbachia. We detected selleck chemicals llc Cardinium in one asexual species, B. rubrioculus. This species is doubly infected with both Wolbachia and Cardinium, although Cardinium was not found in all individuals.

www.selleckchem.com/products/bb-94.html It is unclear if Cardinium is having an effect on the host species, but it is unlikely that it induces the asexuality as not all individuals are infected. We detected both Wolbachia and Cardinium in the sexually reproducing species B. sarothamni and T. urticae. Both species appear polymorphic Necrostatin-1 molecular weight for infection with both bacteria. Cardinium induces strong CI in B. sarothamni, while no effect for Wolbachia has been found so far [47]. Previously, Wolbachia was found inducing CI in T. urticae [66–69], but no effect of Cardinium on T. urticae was found so far [68]. We detected only Cardinium in P. harti, but Weeks et al. [2] also report Wolbachia from P. harti. The effects of both Wolbachia and Cardinium in P. harti, and T. urticae require further investigation. Conclusions We found a relatively high rate of recombination for Wolbachia strains

obtained from host species of the family Tetranychidae. Considering the fact that Wolbachia is widely distributed among arthropods, we investigated strains from a restrictive Thiamet G host range. It remains to be investigated if our findings present a general pattern and if similar recombination rates will be found among strains from other restricted host ranges. Our study of diversity within Cardinium revealed incongruencies among host and bacterial phylogenies, confirming earlier findings. Analysis of additional genes is needed to investigate recombination rates within this reproductive parasite. Methods DNA isolation, amplification, and sequencing We analyzed Wolbachia and Cardinium strains from seven Bryobia species (34 populations), T. urticae (three populations), and P. harti (one population) (Figure 1 and Additional file 1). Samples were collected between May 2004 and November 2006 from eight European countries, and from South Africa, the United States, and China. For each host population, information on mitochondrial (part of the COI gene) and nuclear (part of the 28S rDNA gene) diversity was obtained as described in Ros et al.

One of the


One of the

predominant GDC 0032 C-terminal phosphorylation sites of EGFR is Tyr1068, which used to represent ligand-induced activation of EGFR. Another site, Tyr1173, provides conflicting and confusing information of its correlation with EGFR mutations and predictive value to TKIs therapy [29–31]. Based on the fact that at least 10% of patients with EGFR wild-type respond to TKIs, it is critical to identify potential biomarkers which are click here helpful to select this subgroup of patients for EGFR-TKIs therapy. In this study, we hypothesized that activation of phosphorylated EGFR could provide predictive information to clinicians and serve as supplement to EGFR mutations for screening patients eligible for TKIs therapy, especially those without EGFR mutations. Patients and method Patients 205 patients with locally advanced and advanced NSCLC(stage IIIb and IV) treated in Beijing Cancer Hospital from January 2005 to June 2010 were enrolled. All patients had tumor tissues available for biomarkers analysis. Nineteen patients Smad inhibition got samples from surgical resection, and others from biopsy. 194 patients received EGFR-TKIs as monotherapy (including 148 in gefitinib therapy and 57 in erlotinib

therapy), and had complete clinicopathologic documents. Treatment of Gefitinib (250 mg) or Erlotinib (150 mg) alone daily continued until disease progression, unacceptable toxicity, or patients’ refusal. All patients provided written informed consent and a separate consent for optional provision of tumor samples

for biomarker analysis. The study protocol was approved by the Institutional Ethic Committee at Beijing Cancer Hospital. Study design The study was designed to explore potential value of EGFR phosphorylation in predicting clinical response to EGFR-TKIs treatment. Tumor specimens were obtained at initial diagnosis. Clinical data were sealed during laboratory analysis until all data were evaluated. Recorded variables included age, sex, smoking history, pathology, eastern cooperative oncology group (ECOG) performance status, stage at diagnosis, treatments, and toxicities. Efficacy evaluation included best response, objective response rate (ORR), disease Staurosporine mw control rate (DCR), progression-free survival (PFS) and overall survival (OS). Assessments Tumor assessments were performed at baseline and every eight weeks until investigators documented disease progression or unacceptable toxicity. Clinical responses to TKIs including complete response (CR), partial response (PR), stable disease (SD) and disease progression (PD) were evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) [32]. PFS was defined as time from beginning of TKIs treatment to PD or death, and OS was defined as time from beginning of TKIs to death. An independent radiologist (Dr. N.W.) assessed all films, who was blind to EGFR biomarker status.

Clustering was visualized for weighted and unweighted UniFrac dat

Clustering was visualized for weighted and unweighted UniFrac data using principal coordinates analysis. We use the distance based Permutational Multivariate Analysis of Variance (NPMANOVA) to perform overall test of the difference between the two gold standards (samples taken 1 cm apart from the same piece of stool) and between gold standards and other sampling methods using both the weighted and unweighted UniFrac distance matrix. If the overall test gave significant results, then we used signed rank test on the proportion data to pinpoint

the taxonomic groups that showed significant differences in abundance between the two sampling methods. Acknowledgements We are grateful Luminespib to members of the Wu and Bushman laboratories for help and suggestions. This work was supported by Human Microbiome Roadmap Demonstration Project UH2DK083981 Combretastatin A4 mw (Wu, Bushman, Lewis, Co-PIs). We also acknowledge the Penn Genome Frontiers Institute and a grant with the Pennsylvania Department of Health; the Department of Health specifically disclaims responsibility

for any analyses, interpretations, or conclusions; NIH AI39368 (GDW); the Molecular Biology Core of The Center for Molecular MK0683 Studies in Digestive and Liver Diseases (P30 DK050306); and The Joint Penn-CHOP Center for Digestive, Liver, and Pancreatic Medicine. We also acknowledge NIH instrument grant S10RR024525 and NIH CTSA grant UL1RR024134 from the National Center for Research Resources, and the Crohn’s and Colitis Foundation of America and the Howard Hughes Medical Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. Electronic supplementary material Additional file 1: Table S1. Samples analyzed in the study of methods

for Selleckchem Docetaxel storage and DNA isolation. This table summarizes the samples studied comparing methods for storage and DNA isolation. (XLS 44 KB) Additional file 2: Table S2. Samples analyzed in the study of variable region primers. This table summarizes the samples used specifically in the analysis of different variable region primers. (XLS 30 KB) Additional file 3: Table S3. Sequences of primers used for amplification. This table contains the sequences of primers used for PCR amplification. (XLS 30 KB) Additional file 4: Table S4. Samples analyzed in the study of the cloned DNA mock community. This table summarizes the samples used in the study of the cloned DNA mock community. (XLS 34 KB) References 1. Savage DC: Microbial ecology of the gastrointestinal tract. Annu Rev Microbiol 1977, 31:107–133.PubMedCrossRef 2. Zaneveld J, Turnbaugh PJ, Lozupone C, Ley RE, Hamady M, Gordon JI, Knight R: Host-bacterial coevolution and the search for new drug targets. Current opinion in chemical biology 2008,12(1):109–114.PubMedCrossRef 3.

Furthermore, administration of landiolol hydrochloride showed a p

Furthermore, administration of landiolol hydrochloride showed a positive correlation between the image quality score and heart rate. 4.1 Study Limitations In the present study, we did not compare landiolol hydrochloride with placebo. We also investigated the usefulness and safety of landiolol in a small population (n = 39), despite a huge number of suspected ischemic heart MK-8776 research buy disease cases in Japan. Calcium scoring was not employed as an inclusion or exclusion

criterion in the present study, which excluded subjects whose heart rate was higher than 90 beats/min before CCTA (regardless of the heart rate immediately before administration of the study drug) and subjects expected to develop arrhythmia during CCTA. 5 Conclusions Landiolol hydrochloride was confirmed to lower

heart rate significantly and rapidly after intravenous injection, suggesting that it is a safe and useful agent for improving the image quality of CCTA by 16-slice MDCT. Acknowledgments This study was supported by a grant from Ono Pharmaceutical Co., Ltd., Osaka, Japan, the manufacturer of landiolol hydrochloride. Masaharu Hirano, Kazuhiro https://www.selleckchem.com/products/S31-201.html Hara, Yuji Ikari, Masahiro Jinzaki, Misako Iino, Takuhiro Yamaguchi, and Sachio Kuribayashi received consulting fees from Ono Pharmaceutical Co., Ltd. We gratefully acknowledge the contributions of the www.selleckchem.com/products/sis3.html members of the Landiolol Hydrochloride Study Group (listed in the Appendix) to this study, as well as DAPT solubility dmso of Dr. Hiroshi Higashino, Dr. Masahiro Higashi, and Dr. Teruhito Kido (Central Coronary Visualization Judgment Committee). Open AccessThis

article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited. Appendix: Principal Investigators Seiji Fukushima, Nerima-ku, Tokyo; Ichiro Michishita, Yokohama-city, Kanagawa; Shogo Miyake, Ebina-city, Kanagawa; Shinji Ookubo, Inashiki-gun, Ibaraki; Yuji Hisamatsu, Shimonoseki-city, Yamaguchi; Norimoto Houda, Matsuzaka-city, Mie; Koushi Mawatari, Kagoshima-city, Kagoshima; Masayuki Ueeda, Kannonji-city, Kagawa; Ken Kusaba, Yame-city, Fukuoka. Ono Pharmaceutical clinical development team: Mitsunobu Tanimoto, Tatsuaki Okamura, Masaya Takahashi, Hiroshi Inose, Akira Tsuchiya (data manager), Masahiro Yoshizaki (statistician), and Shinichi Kikawa. References 1. Bluemke DA, Achenbach S, Budoff M, et al.