Background
Neoadjuvant chemotherapy (NAC) represents a promising alternative to pancreatic ductal adenocarcinoma (PDAC) planned resection, but the survival impact remains undefined. To assess the ...feasibility and survival outcomes of NAC with gemcitabine and S1 (GS) for PDAC planned resection by prospective study.
Methods
Patients with resectable or borderline resectable PDAC received 2 cycles of NAC-GS and were offered curative resection followed by gemcitabine adjuvant. The primary endpoint was 2-year overall survival (OS). Adverse events during NAC, radiological and tumor marker responses, resection rate, and surgical safety were evaluated as secondary endpoints (UMIN000004148).
Results
We enrolled 104 patients between 2010 and 2012, with 101 patients treated using NAC-GS as the full analysis set (FAS). Of the 101 patients, 88% received the planned 2 cycles of NAC. Grade 3 neutropenia was common (35%). Radiological partial response and decreased carbohydrate antigen 19-9 concentration (> 50% decrease) were noted in 13% and 41%, respectively. R0/1 resections with M0 were performed in 65 patients without surgical mortality. Of the 65 patients, 44 received planned gemcitabine adjuvant for 6 months as the on-protocol cohort. The primary endpoint for the 2-year OS rate was 55.9% in the FAS (
n
= 101) and 74.6% in the on-protocol cohort (
n
= 44).
Conclusions
NAC-GS was feasible and actively prolonged survival following PDAC planned resection. Randomized control trials are needed to further clarify the survival benefit of NAC-GS in addition to surgery followed by adjuvant therapy.
For research on cosmic gamma rays with energies in the range of several tens of teraelectronvolts or more, we investigated a method to improve the angular resolution of an air shower. In an air ...shower, the density of secondary gamma rays is several times higher than that of electrons and those measurement is important for determining the shower direction. It was found that the angular resolution in the shower front-fit method decreases in inverse proportion to the square root of the number of measured particles. Even if the total number of measured particles is the same, secondary gamma rays contribute more to the improvement of angular resolution than electrons. If secondary gamma rays could be measured at an altitude of 4,740 m with a sensitivity of 100 %, an improvement of approximately 40 % was determined for a 500 TeV shower. A water Cherenkov detector with high gamma-ray sensitivity was investigated through Monte Carlo simulation. Detection efficiencies of approximately 0.38 and 0.76 were obtained for vertically incident gamma rays and electrons, respectively, using 19 8-inch diameter PMTs inside a detector installed in a water tank of radius 4.5 m and water depth 1.6 m. The detection time error for secondary gamma rays is approximately 2.18 ns at an incident angle of 0
∘
and the standard error in the detection time for shower front particles was found to be approximately 10 times lower than that obtained by using a plastic scintillation detector with an area of 1 m
2
.
A major quantitative trait locus (QTL) controlling response to photoperiod, Hd1, was identified by means of a mapbased cloning strategy. High-resolution mapping using 1505 segregants enabled us to ...define a genomic region of ∼12 kb as a candidate for Hd1. Further analysis revealed that the Hd1 QTL corresponds to a gene that is a homolog of CONSTANS in Arabidopsis. Sequencing analysis revealed a 43-bp deletion in the first exon of the photoperiod sensitivity 1 (se1) mutant HS66 and a 433-bp insertion in the intron in mutant HS110. Se1 is allelic to the Hd1 QTL, as determined by analysis of two se1 mutants, HS66 and HS110. Genetic complementation analysis proved the function of the candidate gene. The amount of Hd1 mRNA was not greatly affected by a change in length of the photoperiod. We suggest that Hd1 functions in the promotion of heading under short-day conditions and in inhibition under long-day conditions.
A model of the cosmic-ray energy spectrum is proposed that assumes various acceleration limits at multiple sources. The model describes the broken power-law energy spectrum of cosmic rays by ...superposition of multiple sources; a diffusive shock acceleration mechanism plays an essential role. The maximum energy of galactic cosmic rays is discussed based on a comparison of experimental data with calculations done using the proposed model. The model can describe the energy spectrum at very high energies of up to several times 10{sup 18} eV, but the observed highest-energy cosmic rays deviate from the model predictions, indicating a different origin, such as an extragalactic source. This model describes the steepening of the power index at the so-called knee. However, it was found that additional assumptions are needed to explain the sharpness of the knee. Two possible explanations for the structure of the knee are discussed in terms of nearby source(s) and the hard energy spectrum suggested by nonlinear effects of cosmic-ray acceleration mechanisms.
PDF
