Development of a UV-transparent Lens Array for Enlarging the Effective Area of Multichannel SiPMs

We developed a UV-transparent lens array that can increase the photon detection efficiency of a silicon photomultiplier (SiPM) array comprising of 64 pixels ($3\times3$ mm$^2$ each) and 0.2-mm gaps. Through the plano-convex spherical lens on each $3.2\times3.2$ mm$^2$ region, we showed that the loss of photon detection efficiency due to the pixel gaps could be recovered as the incident photons get concentrated on the sensitive regions of the SiPM array. By using a prototype lens array, we achieved approximately 10%-30% relative increase in photon detection efficiency in our target angles of incidence of 30-60 deg.Comment: Accepted for publication in the Proceedings of the 5th International Workshop on New Photon-Detectors (PD18

Photosensor Characterization for the Cherenkov Telescope Array: Silicon Photomultiplier versus Multi-Anode Photomultiplier Tube

Photomultiplier tube technology has been the photodetector of choice for the technique of imaging atmospheric Cherenkov telescopes since its birth more than 50 years ago. Recently, new types of photosensors are being contemplated for the next generation Cherenkov Telescope Array. It is envisioned that the array will be partly composed of telescopes using a Schwarzschild-Couder two mirror design never built before which has significantly improved optics. The camera of this novel optical design has a small plate scale which enables the use of compact photosensors. We present an extensive and detailed study of the two most promising devices being considered for this telescope design: the silicon photomultiplier and the multi-anode photomultiplier tube. We evaluated their most critical performance characteristics for imaging gamma-ray showers, and we present our results in a cohesive manner to clearly evaluate the advantages and disadvantages that both types of device have to offer in the context of GeV-TeV gamma-ray astronomy.Comment: submitted to SPIE Optics+Photonics proceeding

Protein C activity as a potential prognostic factor for nursing home-acquired pneumonia

[Introduction] Despite the poor prognosis for nursing home acquired pneumonia (NHAP), a useful prognostic factor is lacking. We evaluated protein C (PC) activity as a predictor of in-hospital death in patients with NHAP and community-acquired pneumonia (CAP). [Methods] This prospective, observational study included all patients hospitalized with pneumonia between July 2007 and December 2012 in a single hospital. We measured PC activity at admission and investigated whether it was different between survivors and non-survivors. We also examined whether PC activity 20 mg/dL, respiratory rate >30/min, and blood pressure 65). When it was a useful prognostic factor for pneumonia, we combined PC activity with the existing prognostic scores, the pneumonia severity index (PSI) and CURB-65, and analyzed its additional effect by comparing the areas under the receiver operating characteristic curves (AUCs) of the modified and original scores. [Results] Participants comprised 75 NHAP and 315 CAP patients. PC activity was lower among non-survivors than among survivors in NHAP and all-pneumonia (CAP+NHAP). PC activity <55% was a useful prognostic predictor for NHAP (Odds ratio 7.39 (95% CI; 1.59–34.38), and when PSI or CURB-65 was combined with PC activity, the AUC improved (from 0.712 to 0.820 for PSI, and 0.657 to 0.734 for CURB-65). [Conclusions] PC activity was useful for predicting in-hospital death of pneumonia, especially in NHAP, and became more useful when combined with the PSI or CURB-65

Recruitment of Young Medical Apprentices (RYOMA) Project: A Comprehensive Surgical Education Program at a Local Academic Institute in Japan

Objectives The number of young surgeons in Japan has significantly decreased in recent years, which may lead to future problems in the medical field. Therefore, comprehensive training programs for young surgeons are needed. Design Retrospective study Setting We developed a specific education program called the "Recruitment of Young Medical Apprentices" (RYOMA) project. Participants We performed this project between January 2008 and August 2013 on fourth- to sixth-year medical students and internship doctors. The RYOMA project included step-by-step surgical education programs on open and scopic procedures as dry, wet, and animal laboratory training. Our goal was to increase the number of young and specialist surgeons. Results Based on an interview questionnaire answered by 90 medical students, most young students were interested in surgical training and several chose to become surgeons in the future. The most positive opinions regarding the field of surgery were the impressive results achieved with surgery, whereas negative opinions included the difficulty of the surgical skill, physical concerns related to difficult work environments, and the severity of surgical procedures. The present program has begun to resolve negative opinions through adequate training or simulations. Of the 19 medical students and internship doctors who attended the RYOMA project in 2008, 17 trainees (90%) were satisfied with this special surgical program and 16 (88%) showed interest in becoming surgeons. The number of participants considering the field of surgery increased between 2008 and 2013. Of 23 participants, 19 (83%) had a positive opinion of the program after the training. Conclusions Gaining experience in surgical training from an early stage in medical school and step-by-step authorized education by teaching staff are important for recruiting students and increasing the number of young surgeons

Accuracy and prognostic impact of a vessel invasion grading system for stage IA non-small cell lung cancer.

BACKGROUND: Despite the recognition that lymphatic and blood vessel invasion is an important prognostic factor in lung cancer, there is no common definition for pathological evaluation of vessel invasion. The aim of the present study was to determine whether D2-40 immunostaining can increase the accuracy of detection of lymphatic vessel invasion and whether our new grading system of vessel invasion by "degree" could be used instead of conventional evaluation by "presence" for pathological stage IA non-small cell lung cancer (NSCLC). METHODS: The vessel invasion classification was re-evaluated in 221 recent paraffin-embedded sections of p-stage IA NSCLC stained by Hematoxylin-Eosin (HE), Elastica-Van-Gieson (EVG), and D2-40. RESULTS: After re-assessment using D2-40 immunostaining, 41.2% (31 of 75) of ly1 cases by HE/EVG changed to ly0, and 14.9% (17 of 114) of ly0 cases by HE/EVG changed to ly1. Overall, 4 of 28 ly2 cases on conventional staining were changed to ly1, and 2 were changed to ly0 using D2-40 immunostaining. When the patients were divided into two groups by the presence of vessel invasion (v/ly0 vs. 1, 2, 3), there was no significant difference in cancer-specific survival (p=0.1107, 0.0875, respectively), while when they were divided according to degree of vessel invasion (v/ly0, 1 vs. 2, 3), there was a statistically significant difference (p=0.0038, p=0.0002, respectively). On multivariate analysis, lymphatic vessel invasion had a significant impact on cancer-specific survival (p=0.0061). CONCLUSION: Our results suggest that D2-40 immunostaining provides a precise diagnosis of lymphatic vessel invasion, and our new grading system of vessel invasion by "degree" is accurate and has prognostic value in early lung cancer

Polymorphisms and expression of genes encoding Argonautes 1 and 2 in autoimmune thyroid diseases

The microRNA (miRNA) biogenesis pathway is regulated by specific proteins and enzymes, including Dicer, Drosha, DGCR8, Exportin 5 and the Argonaute (AGO) family. In this study, we investigated the AGO family, which is the primary component of RISC (RNA-induced silencing complex) and directly binds to microRNA. We examined the association of polymorphisms in AGO family genes with AGO expression and with the development and prognosis of autoimmune thyroid diseases. We genotyped AGO1 rs636832A/G, AGO2 rs7005286C/T, AGO2 rs11166985A/G and AGO2 rs2292779C/G polymorphisms in 184 Graves’ disease (GD) patients, 195 Hashimoto’s disease (HD) patients and 122 healthy volunteers using the polymerase chain reaction-restriction fragment length polymorphism method. We also examined the expression of AGO1 and AGO2 mRNAs in peripheral blood mononuclear cells (PBMC) obtained from 52 GD patients, 41 HD patients, and 25 healthy volunteers using quantitative RT-PCR methods. The G allele of AGO1 rs636832 and the A allele of AGO2 rs11166985 polymorphisms were significantly more frequent in GD patients than in healthy controls. The A allele of AGO2 rs11166985 was also significantly more frequent in intractable GD patients than in controls. The C carrier (CC + CG genotypes) and C allele of AGO2 rs2292779 polymorphism were significantly more frequent in intractable GD patients than in patients with GD in remission. Expression of AGO1 mRNA in PBMC was significantly higher in AITD patient than in controls, and that of AGO2 mRNA in PBMC was significantly higher in intractable GD patients than in patients with GD in remission. Furthermore, the expression levels of both the AGO1 and AGO2 genes were significantly correlated with the proportions of Th17 cells in PBMC. In conclusion, the polymorphisms of the AGO1 and AGO2 genes, the expression levels of which correlated with the proportion of Th17 cells, were associated with the development and prognosis of GD. The AGO2 rs2292779 C carrier and C allele were associated with the intractability of GD

Association of IL6 gene methylation in peripheral blood cells with the development and prognosis of autoimmune thyroid diseases

Autoimmune thyroid diseases (AITDs), including Hashimoto’s disease (HD) and Graves’ disease (GD), are archetypes of organ-specific autoimmune diseases, but the prognosis of patients with AITD varies. Autoimmune diseases, including AITDs, are believed to develop in response to both genetic and environmental factors. Interleukin (IL)-6 plays a major role in B cell differentiation and T cell proliferation, and methylation of the IL6 gene is associated with IL-6 production. To clarify the role of IL6 gene methylation in the pathogenesis and prognosis of AITDs, we measured the methylation levels of −666, −664, −610, −491 and −426 CpG sites in the IL6 gene. We measured the methylation levels of 5 CpG sites in 29 patients with HD, 31 patients with GD and 16 healthy volunteers using pyrosequencing. The methylation level at each of the −664, −491 and −426 CpG sites was negatively correlated with the age at the time of sampling. Multiple regression analysis indicated that patients with HD, including severe or mild HD, showed higher methylation levels at the −426 CpG site than control subjects. Patients with intractable GD showed lower methylation levels at the −664 and −666 CpG sites than patients with GD in remission. In conclusion, IL6 gene methylation levels were related to the susceptibility to HD and the intractability of GD

Tunable Full-Color Electroluminescence from All-Organic Optical Upconversion Devices by Near-Infrared Sensing

Full-color all-organic optical upconversion devices that can directly convert incident near-infrared (NIR) light into tunable visible light were developed by integrating an organic light-emitting diode (OLED) on an NIR-sensitizing organic photodetector. Thermally activated delayed fluorescence (TADF) emitters were utilized for the first time in the upconversion devices for achieving high electroluminescence (EL) efficiency in the OLED unit and high overall upconversion efficiency. The emission color of upconversion EL can be varied across the entire visible region ranging from blue to red and white by judicious selection of the incorporating TADF emitters. These all-organic optical upconversion devices have a great potential for low-cost, large-area, pixelless NIR imaging applications

PD-1 gene polymorphisms and thyroid expression of PD-1 ligands differ between Graves’ and Hashimoto’s diseases

The programmed cell death-1 (PD-1)/PD ligand pathway plays a key role in the maintenance of peripheral tolerance by enhancing the suppressive activity of regulatory T (Treg) cells. The promoter activity of the A allele of PD1 rs36084323 G/A polymorphism is lower than that of the G allele. We examined the association of PD1 gene polymorphisms, PD-1 expression on Treg cells, and thyroid PD-1/PD-1 ligand (PD-L1) expression with the pathogenesis of autoimmune thyroid disease (AITD). We classified patients and genotyped PD-1 polymorphisms by using the PCR-RFLP method in a total of 176 Graves’ disease (GD) patients, 150 Hashimoto’s disease (HD) patients with different disease severities and 99 healthy controls. PD-1 expression on Treg cells was analysed by flow cytometry. Indirect immunofluorescence staining was performed in thyroid tissue to detect PD-1, PD-L1, and PD-L2. The frequencies of the A allele and the AA + AG genotypes of the PD1 rs36084323 polymorphism were lower in HD patients than in GD patients, and the frequencies of the AA genotype of the PD1 rs36084323 and of the TT genotype of the PD1 rs2227982 were lower in mild HD patients than in severe HD patients. In patients with severe HD, the titres of TgAb at the onset were higher in patients with the PD1 rs36084323 AA genotype than in patients with the GG genotype. Peripheral PD1+ Treg cells tended to decrease in individuals with the PD1 rs36084323 AA genotype than with the G carrier genotype. Peripheral PD-1+ Treg cells were increased in HD, especially in mild HD. PD-1, PD-L1, and PD-L2 were expressed in thyroid-infiltrating mononuclear cells (TIMCs), and PD-L1 and PD-L2 were expressed in thyroid epithelial cells (TECs) in AITD patients but not in normal controls. Expression of PD-L1 in TIMCs and expression of PD-L2 in TECs were predominant in HD and GD patients, respectively. In conclusion, the functional PD1 rs36084323 polymorphism and the thyroid PD-1/ PD-L1s expression which may enhance the suppressive activity of Treg cells differ between GD and HD, and the PD1 rs36084323 and rs2227982 polymorphisms and PD1+ Treg cells are related to the severity of HD

Association of the polymorphisms in the gene encoding thyroglobulin with the development and prognosis of autoimmune thyroid disease

Graves’ disease (GD) and Hashimoto’s disease (HD) are autoimmune thyroid diseases (AITDs), and the prognosis of AITDs is different for each patient. We examined the association of polymorphisms in the Thyroglobulin (TG) gene with the pathogenesis of AITD. We genotyped TG rs180195G/A, rs853326G/A, rs2076740C/T, rs2703013G/T, rs2958692C/T and rs733735A/G polymorphisms in 137 HD patients, 131 GD patients and 89 healthy controls and also examined the levels of TG mRNA expression and serum TG. The TG rs180195 GG genotype was more frequent in HD patients (p = .0277), and the proportion of CD4+ cells with high levels of TG mRNA was greater in individuals with the GG genotype than in A carriers (p = .0107). The TG rs2703013 TT genotype was less frequent in AITD (p = .0186), and serum TG levels were lower in individuals with the TT genotype than in G carriers (p = .0170). In the TG rs2958692 polymorphism, the T allele was more frequent in intractable GD than in GD in remission (p = .0055), and serum titres of anti-thyroglobulin antibody (TgAb) were lower in GD patients with the TT genotype than in C carriers (p = .0151). In the TG rs2076740 polymorphism, serum titres of TgAb were higher in HD patients who were T carriers than in those with the CC genotype (p = .0359). SNPs in the TG gene were associated with the development of HD and GD, the intractability of GD, and the levels of TG mRNA expression, serum TG, and serum TgAb