Feasibility and Efficacy of Definitive Radiotherapy with 66 Gy and Concurrent Carboplatin-Paclitaxel Chemotherapy for Stage III Non-Small Cell Lung Cancer.

Purpose/Objectives : This study was conducted to assess the feasibility and efficacy of definitive radiotherapy (RT) with a total dose of 66 Gy and concurrent carboplatin-paclitaxel chemotherapy for patients (pts) with stage Ⅲ non-small celllung cancer. Materials/Methods : Between April 2007 and December 2013，99 pts with non-small cell lung cancer were treated using RT with concurrent carboplatin-paclitaxel chemotherapy in our hospital. Sixty-eight of them received RT with a total dose of 66 Gy. We analyzed 46 Stage Ⅲ pts who had been treated with RT using three-dimensional radiotherapy treatment planning. The prophylactic mediastinal lymph nodes were included in the clinical target volume for RT. The survival rate after the start of RT was estimated using the Kaplan-Meier method. We estimated the cumulative local failure and distant metastasis rates with the Fine-Gray method. Adverse events were evaluated according to the CTCAE (v.4.0). Results : The median age of the pts was 70.9 (52.8-78.7) years old (y.o.). The performance status (PS) of each pt was fairly good (ECOG PS 0: 25, PS 1: 20, PS 3:1), and their clinical stages (UICC 7th) were twenty-nine Ⅲ A and seventeen Ⅲ B. Diagnoses were pathologically confirmed in 32 pts. The median follow-up period was 35.7 (2.0-82.2) months among all pts, and 55.9 (40.1-82.2) months among survivors. The 3- and 5-year Kaplan-Meier overall survival rates were 52.2 and 34.0%，respectively, and the median survival time was 36.6 months. The 3- and 5-year Kaplan-Meier progression-free survival rates were 29.1 and 21.9%，respectively, and the median progression-free survival time was 9.9 months. The 5-year local failure rate was 37.6%, and the 5-year distant metastasis rate was 49.7%. Sixteen (34.8%) pts required steroid administration because of radiation pneumonitis (CTCAE Grade 2 or higher) and two of them died (Grade 5). No other severe non-hematologic toxicity (Grade 3 or higher) was observed. Conclusion : These results suggest that definitive RT with a total dose of 66 Gy and concurrent carboplatin-paclitaxel chemotherapy is feasible and may be promising for pts with Stage Ⅲ non-small cell lung cancer

Correspondence of topological classification between quantum graph extra dimension and topological matter

In this paper, we study a classification of boundary conditions with symmetries for a five-dimensional Dirac fermion on a quantum graph. We find that there is a nontrivial correspondence between the classification of boundary conditions at the vertex on the quantum graph and that of the symmetry-protected topological phases of gapped free-fermion systems, which are classified into ten symmetry classes by the time-reversal symmetry, particle-hole symmetry and chiral symmetry. A Hermitian matrix which specifies the boundary conditions in our model corresponds to a zero-dimensional Hamiltonian in the gapped free-fermion systems. Furthermore, symmetries in our model give the condition that restricts the parameter space of the boundary conditions. These conditions are identical to the ones in the gapped free-fermion systems that the Hamiltonian with the symmetries should satisfy. We also show that the topological number for each symmetry class in our model implies the presence of 4d massless fields localized at the vertex of the quantum graph, like gapless boundary states for the free-fermion systems from the bulk-boundary correspondence.Comment: 39 pages, 7 figures, 5 table

Characteristics of physicians, their migration patterns and distance: a longitudinal study in Hiroshima, Japan

Introduction: Although some characteristics of physicians are known to be associated with their recruitment in rural and remote areas, the factors that predict mobility of physicians, and in particular, their mobility to rural and distant areas are largely unknown. Methods: Flows of all physicians (n=4268) among municipalities in Hiroshima Prefecture, Japan, between 2002 and 2008 were analysed. Physician data were obtained from the National Physician Census. Municipality-level population data derived from the National Basic Resident Register were merged with the physician data. Information on the road distances of two municipalities measured with a geographic information system (GIS) was added to the physician cohort. Results: During the period of study, 24.8% of physicians crossed municipal borders, and among them, 66.6% moved distances of less than 60 min travel time. The number of migrated physicians decreased as the distance increased, which held true for both migration to urban and rural areas. In the univariate analysis, female, younger, and hospital physicians were more mobile to rural areas than were male, older, and clinic physicians. Male and younger (≤40 years) physicians moved a longer distance than female and older physicians. Multivariate analysis revealed that age was a negative predictor (odds ratio [OR] per 10 years 0.62, 95% confidence interval [CI] 0.55-0.70]), and affiliation with a hospital was a positive predictor of migration to rural areas (OR 6.19 [95% CI 4.21-9.10]). Male sex (OR 1.67 [95% CI 1.11-2.50]) and hospital affiliation (OR 5.61 [95% CI 3.33-9.45]) were positive predictors, and age (OR per 10 years 0.39 [95% CI 0.33-0.46]) was a negative predictor of migrating a long distance. Conclusion: In order to attract physicians to rural and remote areas, health workforce policies need to set a target population of physicians who are highly mobile to such places. Combining known predictors of rural practice, such as physicians with rural background and primary care physicians, and the mobility predictors shown in this study (ie young, hospital and male physicians) would make the target more appropriate and policies more effective.The Ministry of Education, Culture, Sports, Science and Technology (Tokyo, Japan) and Satake Education and Research Fund (Hiroshima, Japan) sponsored this research

Aging of hospital physicians in rural Japan: A longitudinal study based on national census data

Background The disparity in the number of urban and rural physicians is a social problem in Japan. There may also be a disparity in the age of physicians. This study longitudinally examines both geographic and age distributions of physicians. Methods Individual data from the Survey of Physicians, Dentists and Pharmacists in 1994, 2004 and 2014 and municipality data from the National Population Census were used. The 2015 municipality border was applied to all years, and all municipalities were classified into equalsize quintiles based on population density. Both municipalities and physicians were longitudinally observed. Results Between 1994 and 2014, the number of physicians per 100,000 population increased by 31.8% in the most urban group of municipalities and 17.4% in the most rural group. The average age of physicians was highest in the most rural and lowest in the most urban group. The difference in average age between the urban and rural physicians widened from 2.1 years in 1994 to 6.0 years in 2014. This disparity is particularly pronounced among hospital physicians (from 1.5 years in 1994 to 7.6 years in 2014). In the most rural group, the number of hospital physicians younger than 40 years old has decreased by 59.4%, while the number of those 55±70 has grown by 153% and the number older than 70 years old by 41.0%. Between 1994 and 2004, only 23.0% of hospital physicians younger than 40 years old were retained in the most rural group; the retention rate fell to 19.3% between 2004 and 2014, while the rates increased in older physicians. Conclusions The uneven distribution of physicians is increasing in Japan, as is the aging of rural hospital physicians. Shortage of physicians in rural areas may be more serious than that shown as their headcount.This research was supported by Japan Society for the Promotion of Science (JSPS) KAKENHI Grant Number 16K09145 (http://www.jsps.go.jp/english/e-grants/index.html) (KI)

Carboplatin-Paclitaxel Chemoradiotherapy With 66 Gy For Elderly Patients With Locally Advanced Non-Small-Cell Lung Cancer.

Background/ Aim: The common radiation dose administered with chemoradiotherapy for stage III non-small-cell lung cancer (NSCLC) is 60 Gy. We aimed to examine the feasibility and effectiveness of carboplatin-paclitaxel chemoradiotherapy with 66 Gy for elderly NSCLC patients. Patients and Methods: Forty-five patients with stage III NSCLC were enrolled from 2011 to 2014 at our hospital. They were divided into three groups according to their status and underwent different treatments. Overall survival (OS), progression-free survival (PFS), and local control (LC) were determined. Toxicity was evaluated with NCI-CTCAE ver. 4.0; intergroup differences were analysed statistically. Results: The group receiving carboplatin-paclitaxel chemotherapy with 66 Gy showed the longest median OS (40.4 months), PFS (17.9 months), and LC (44.3 months). Toxicity was acceptable in all groups. Conclusion: For elderly patients with stage III NSCLC, carboplatin-paclitaxel chemoradiotherapy with 66 Gy is suggested to be feasible and effective

Three-dimensional structure of monoanionic methionine-enkephalin: X-ray structure of tert-butyloxycarbonyl-Tyr-Gly-Gly-(4-bromo)Phe-Met-OH

AbstractThe conformation of tert-butyloxycarbonyl-Tyr-Gly-Gly-(4-bromo)Phe-Met-OH, as a monoanionic derivative of Met-enkephalin, was elucidated by X-ray crystal analysis. The molecule took an extended conformation which was bended at the Phe residue. The implication of the dimer formation caused by 4 intermolecular hydrogen bonds was discussed in the relation with the opiate receptor

Follow-up study of the regional quota system of Japanese medical schools and prefecture scholarship programmes: a study protocol

Introduction: Given the shortage of physicians, particularly in rural areas, the Japanese government has rapidly expanded the number of medical school students by adding chiikiwaku (regional quotas) since 2008. Quota entrants now account for 17% of all medical school entrants. Quota entrants are usually local high school graduates who receive a scholarship from the prefecture government. In exchange, they temporarily practise in that prefecture, including its rural areas, after graduation. Many prefectures also have scholarship programmes for non-quota students in exchange for postgraduate in-prefecture practice. The objective of this cohort study, conducted by the Japanese Council for Community-based Medical Education, is to evaluate the outcomes of the quota admission system and prefecture scholarship programmes nationwide. Methods and analysis: There are 3 groups of study participants: quota without scholarship, quota with scholarship and non-quota with scholarship. Under the support of government ministries and the Association of Japan Medical Colleges, and participation of all prefectures and medical schools, passing rate of the National Physician License Examination, scholarship buy-out rate, geographic distribution and specialties distribution of each group are analysed. Participants who voluntarily participated are followed by linking their baseline information to data in the government’s biennial Physician Census. Results to date have shown that, despite medical schools’ concerns about academic quality, the passing rate of the National Physician License Examination in each group was higher than that of all medical school graduates. Ethics and dissemination: The Ethics Committee for Epidemiological Research of Hiroshima University and the Research Ethics Committee of Nagasaki University Graduate School of Biomedical Sciences permitted this study. No individually identifiable results will be presented in conferences or published in journals. The aggregated results will be reported to concerned government ministries, associations, prefectures and medical schools as data for future policy planning.This study is funded by the Ministry of Education, Culture, Sports, Science and Technology KAKENHI Grant-in-Aid for Scientific Research (C), grant number (25460803)