The addition of a 28 m Cherenkov telescope (CT5) to the H.E.S.S. array extended the experiment’s sensitivityto lower energies. The lowest energy threshold is obtained using monoscopic analysis of ...data taken with CT5, providing access to gamma-ray energies below 100 GeV for small zenith angle observations. Such an extension of the instrument’s energy range is particularly beneficial for studies of active galactic nuclei with soft spectra, as expected for those at a redshift ≥0.5. The high-frequency peaked BL Lac objects PKS 2155−304 (z = 0.116) and PG 1553+113 (0.43 < z < 0.58) are among the brightest objects in the gamma-ray sky, both showing clear signatures of gamma-ray absorption at E > 100 GeV interpreted as being due to interactions with the extragalactic background light (EBL).Aims. The aims of this work are twofold: to demonstrate the monoscopic analysis of CT5 data with a low energy threshold, and to obtain accurate measurements of the spectral energy distributions (SED) of PKS 2155−304 and PG 1553+113 near their SED peaks at energies ≈100 GeV.Methods. Multiple observational campaigns of PKS 2155−304 and PG 1553+113 were conducted during 2013 and 2014 using the full H.E.S.S. II instrument (CT1–5). A monoscopic analysis of the data taken with the new CT5 telescope was developed along with an investigation into the systematic uncertainties on the spectral parameters which are derived from this analysis.Results. Using the data from CT5, the energy spectra of PKS 2155−304 and PG 1553+113 were reconstructed down to conservative threshold energies of 80 GeV for PKS 2155−304, which transits near zenith, and 110 GeV for the more northern PG 1553+113. The measured spectra, well fitted in both cases by a log-parabola spectral model (with a 5.0σ statistical preference for non-zero curvature for PKS 2155−304 and 4.5σ for PG 1553+113), were found consistent with spectra derived from contemporaneous Fermi-LAT data, indicating a sharp break in the observed spectra of both sources at E ≈ 100 GeV. When corrected for EBL absorption, the intrinsic H.E.S.S. II mono and Fermi-LAT spectrum of PKS 2155−304 was found to show significant curvature. For PG 1553+113, however, no significant detection of curvature in the intrinsic spectrum could be found within statistical and systematic uncertainties.
We present a catalog of sources detected above 10 GeV by the Fermi Large Area Telescope (LAT) in the first 7 years of data using the Pass 8 event-level analysis. This is the Third Catalog of Hard ...Fermi-LAT Sources (3FHL), containing 1556 objects characterized in the 10 GeV–2 TeV energy range. The sensitivity and angular resolution are improved by factors of 3 and 2 relative to the previous LAT catalog at the same energies (1FHL). The vast majority of detected sources (79%) are associated with extragalactic counterparts at other wavelengths, including 16 sources located at very high redshift (z > 2). Of the sources, 8% have Galactic counterparts and 13% are unassociated (or associated with a source of unknown nature). The high-latitude sky and the Galactic plane are observed with a flux sensitivity of 4.4 to 9.5 × 10$^{−11}$ ph $cm^{−2}$ s$^{−1}$, respectively (this is approximately 0.5% and 1% of the Crab Nebula flux above 10 GeV). The catalog includes 214 new γ-ray sources. The substantial increase in the number of photons (more than 4 times relative to 1FHL and 10 times to 2FHL) also allows us to measure significant spectral curvature for 32 sources and find flux variability for 163 of them. Furthermore, we estimate that for the same flux limit of 10$^{−12}$ erg cm$^{−2}$ s$^{−1}$, the energy range above 10 GeV has twice as many sources as the range above 50 GeV, highlighting the importance, for future Cherenkov telescopes, of lowering the energy threshold as much as possible.
Summary To roughly estimate the incidence of pancreaticobiliary ductal maljunction （PBM） in the Niigata district, a high risk area for biliary tract cancer, amylase activity in gallbladder bile was ...determined in patients with biliary diseases. High amylase activity exceeding 25 times the upper limit of serum amylase（at which level the possibility of PBM increases） was detected in 3. 7% of the patients. This value was not different from those reported from other parts of Japan （Nagasaki, a. relatively high risk area and Hiroshima, a low risk area）. The results suggest that in the relative high occurrence of biliary tract cancer in the Niigata district, PBM does not play an important role. However, a prospective collaborative study between different risk zones is mandatory before a definite conclusion can be reached. For the present, parallel to the study on PBM, multiple factors including environmental pollution should be investigated to elucidate circumstances surrounding the high occurrence of biliary tract cancer.
We devised a linear discriminant function to predict the outcome for patients with acute subdural hematoma (ASDH) based on a consecutive series of 170 ASDH cases with mild to severe head injury ...Glasgow Coma Scale (GCS) 3-15. Functional recovery was achieved in 50.0% of patients and the mortality was 36.5%. The relationship between initial clinical and radiological signs and the outcome 3 months after admission was studied retrospectively by Mann-Whitneys U-test and Pearsons chisquared test. Fourteen factors (GCS, pupillary response, motor paresis, age, hematoma volume and thickness, midline shift, association with cerebral contusion and subarachnoid hemorrhage, obliteration of the basal, ambient, or quadrigeminal cistern on computed tomography, fibrin-fibrinogen degradation product level, and intracranial pressure) were found to correlate significantly (p <0.01) with outcome. Linear discriminant functions were formulated by multivariate analysis to investigate the relationship between these factors and recovery or poor prognosis. The following formula was obtained： Z=-0.110 + 0.013 (Age) - 0.108 (GCS) + 0.397 (Eye) + 0.003 (Shift) + 0.268 (Ambient). Functional recovery could be predicted by a negative Z value, with an accuracy of 90.59%. This simple discriminant function is useful for predicting the outcome of ASDH.
Real-world bargainings often proceed step-by-step: the agents make intermediate agreements today and continue to negotiate tomorrow to reach a final agreement. We consider two natural properties of ...the bargaining solutions in such step-by-step negotiations and show that the Nash solution is the only solution that satisfies either of them, a very weak axiom of individual rationality, and Nash’s axioms except for Pareto optimality.
•We consider two new properties of bargaining solutions in step-by-step negotiations.•We provide two characterizations of the Nash solution using each of them.•We also show that all the axioms are independent.
In the classical bargaining problem, we propose a very mild axiom of individual rationality, which we call
possibility of utility gain
. This requires that for at least one bargaining problem, there ...exists at least one player who reaches a higher utility level than their disagreement utility. This paper shows that the Nash solution (Nash in Econometrica 18(2):155–162, 1950) is characterized by
possibility of utility gain
and continuity with respect to feasible sets together with Nash’s axioms except
weak Pareto optimality
. We also show that in Nash’s theorem,
weak Pareto optimality
can be replaced by
conflict-freeness
(introduced by Rachmilevitch in Math Soc Sci 76(C):107–109, 2015). This demands that when the agreement most preferred by all players is feasible, this should be chosen. Furthermore, we provide alternative and unified proofs for other efficiency-free characterizations of the Nash solution. This clarifies the role of each axiom in the related results.
Purpose: Determination of optimal treatment strategies for HER2-positive advanced gastric cancer (AGC) in randomized trials is necessary despite difficulties in direct comparison between trastuzumab ...deruxtecan (T-DXd) and nivolumab as third or later-line treatments. Materials and Methods: This single-institution, retrospective study aimed to describe the real-world efficacy and safety of T-DXd and nivolumab as ≥ third line treatments for HER2-positive AGC between March 2016 and May 2022. Overall, 58 patients (median age, 64 years; 69% male) were eligible for the study (T-DXd group, n=20; nivolumab group, n=38). Results: Most patients exhibited a HER2 3+ status (72%) and presented metastatic disease at diagnosis (66%). The response rates of 41 patients with measurable lesions in the T-DXd and nivolumab groups were 50% and 15%, respectively. The T-DXd and nivolumab groups had a median progression-free survival of 4.8 months (95% confidence interval CI, 3.3, 7.0) and 2.3 months (95% CI, 1.5, 3.5), median overall survival (OS) of 10.8 months (95% CI, 6.9, 23.8) and 11.7 months (95% CI, 7.6, 17.1), and grade 3 or greater adverse event rates of 50% and 2%, respectively. Overall, 64% patients received subsequent treatment. Among 23 patients who received both regimens, the T-DXd-nivolumab and nivolumab-T-DXd groups had a median OS of 14.0 months (95% CI, 5.0, not reached) and 19.3 months (95% CI, 9.5, 25.1), respectively. Conclusions: T-DXd and nivolumab showed distinct efficacy and toxicity profiles as ≥ third line treatments for HER2-positive AGC. Considering the distinct features of each regimen, they may help clinicians personalize optimal treatment approaches for these patients.
Purpose: Liver metastasis (LM) is reported in approximately 40% of patients with advanced/metastatic gastric/gastroesophageal junction adenocarcinoma (metastatic esophagogastric adenocarcinoma; mGEA) ...and is associated with a worse prognosis. This post-hoc analysis from the RAINBOW trial reported the efficacy, safety, and biomarker outcomes of ramucirumab and paclitaxel combination treatment (RAM+PAC) in patients with (LM+) and without (LM-) LM at baseline. Materials and Methods: Patients (n=665) were randomly assigned on a 1:1 basis to receive either RAM+PAC (LM+: 150, LM-: 180) or placebo and paclitaxel (PL+PAC) (LM+: 138, LM-: 197). The overall survival (OS) and progression-free survival (PFS) were evaluated using stratified Kaplan-Meier and Cox regression models. The correlation of dichotomized biomarkers (VEGF-C, D; VEGFR-1,2) with efficacy in the LM+ versus LM- subgroups was analyzed using the Cox regression model with reported interaction P-values. Results: The presence of LM was associated with earlier progression than those without LM, particularly in patients receiving PL+PAC (hazard ratio HR, 1.68). RAM+PAC treatment improved OS and PFS irrespective of LM status but showed greater improvement in LM+ than that in LM- (OS HR, 0.71 LM+ vs. 0.88 LM-; PFS HR, 0.47 LM+ vs. 0.76 LM-). Treatment-emergent adverse events were similar between patients with and without LM. No predictive relationship was observed between biomarker levels (VEGF-C, D; VEGFR-1,2) and efficacy outcome (OS, PFS) (all interaction P-values >0.05). Conclusions: RAM provided a significant benefit, irrespective of LM status; however, its effect was numerically stronger in patients with LM. Therefore, RAM+PAC is a clinically meaningful therapeutic option for patients with mGEA and LM.
Background/Aims: Multiple white and flat elevated lesions (MWFL) that develop from the gastric corpus to the fornix may be strongly associated with oral antacid intake. Therefore, this study aimed to ...determine the association between the occurrence of MWFL and oral proton pump inhibitor (PPI) intake and clarify the endoscopic and clinicopathological characteristics of MWFL.
Methods: The study included 163 patients. The history of oral drug intake was collected, and serum gastrin levels and anti-Helicobacter pylori immunoglobulin G antibody titers were measured. Upper gastrointestinal endoscopy was performed. The primary study endpoint was the association between MWFL and oral PPI intake.
Results: In the univariate analyses, MWFL were observed in 35 (49.3%) of 71 patients who received oral PPIs and 10 (10.9%) of 92 patients who did not receive oral PPIs. The occurrence of MWFL was significantly higher among patients who received PPIs than in those who did not (p<0.001). Moreover, the occurrence of MWFL was significantly higher in patients with hypergastrinemia (p=0.005). In the multivariate analyses, oral PPI intake was the only significant independent factor associated with the presence of MWFL (p=0.001; odds ratio, 5.78; 95% confidence interval, 2.06-16.2).
Conclusions: Our findings suggest that oral PPI intake is associated with the presence of MWFL (UMINCTR 000030144).
Colorectal cancer (CRC) is currently the most common type of cancer in Japan, and its prognosis has improved because of development of diagnosis and advancement in treatments including surgery and ...chemotherapy. However, because of intratumor heterogeneity and clonal evolution, tumors often develop resistance to treatment. Genotyping tumor tissue in search of somatic genetic alterations for actionable information has become routine examination in clinical practice. However, the inherent molecular heterogeneity of metastatic tumors and the ability of cancer genomes to dynamically evolve are not properly captured by tissue specimens only. Circulating tumor DNA (ctDNA) carrying tumor‐specific genetic or epigenetic alterations is released into the circulation from tumor cells undergoing apoptosis or necrosis. Analysis of ctDNA has the potential to change clinical practice by exploiting blood rather than tissue, as a source of information. Here, we provide an overview of the characteristics of ctDNA and focus on detection methods for ctDNA, and the feasibility of use of ctDNA to monitor tumor dynamics for patients with colorectal cancer.
Circulating tumor DNA (ctDNA) carrying tumor‐specific genetic or epigenetic alterations is released into the circulation from tumor cells undergoing apoptosis or necrosis. Analysis of ctDNA has the potential to change clinical practice by exploiting blood rather than tissue, as a source of information. In this article, we provide an overview of the characteristics of ctDNA and focus on detection methods for ctDNA, and the feasibility of the use of ctDNA to monitor tumor dynamics for patients with colorectal cancer.
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