ハイスイカンツキジャカゴニヨルシャメンアンテイカニカンスルケンキュウ

博士（農学）東京農工大

Nab-paclitaxel monotherapy in refractory pancreatic adenocarcinoma

BACKGROUND: The standard of care in patients with metastatic pancreatic adenocarcinoma is undefined beyond second line of treatment. There have been scant reports of benefit from nab-paclitaxel in patients with refractory pancreatic cancer. MATERIALS AND METHODS: A retrospective review was carried out in patients with pancreatic adenocarcinoma at Siteman Cancer Center, who had received nab-paclitaxel monotherapy after experiencing disease progression on standard treatments. Nab-paclitaxel was given either two out of every three weeks or three out of every four weeks. RESULTS: Twenty patients were identified and included for data analysis. Median age was 63.5 years old. All patients had previously received gemcitabine, while 40% had also received FOLFIRINOX. Median number of prior lines of systemic treatment was 2. Patients were treated for a median of 15 weeks, with a range of 1 to 41.7 weeks. Median dose of nab-paclitaxel was 100 mg/m(2) with range of 75-125 mg/m(2). Best response imaging was available in 17 patients and 11 out of the 17 patients (64.7%) had stable disease. Median progression-free survival (PFS) was 3.7 months and overall survival (OS) were 5.2 months. Most common treatment related toxicities included grade 1 pneumonitis in five patients (25%), grade 3 or 4 neutropenia in three patients (15%), and dehydration resulting in hospitalization in one patient (5%). CONCLUSIONS: Nab-paclitaxel monotherapy had acceptable level of toxicity in a heavily pretreated patient population with pancreatic cancer and appeared to provide a clinical benefit. This agent is worthy of further prospective studies to evaluate extent of benefit after standard therapies have failed

The Role of Palliative Surgery for Malignant Bowel Obstruction and Perforation in Advanced Microsatellite Instability-High Colorectal Carcinoma in the Era of Immunotherapy: Case Report.

The role of palliative surgery in the management of acute complications in patients with disseminated malignancy remains controversial given the complexity of assessing acute surgical risk and long-term oncologic outcome. With the emergence of checkpoint blockade immunotherapy, there appears to be an increasing role for historically palliative procedures as a bridge to systemic immunotherapy. This is especially evident in advanced microsatellite instability-high (MSI-H) colorectal cancer where malignant obstruction and fistula formation are more common and where immunotherapy with checkpoint blockade (anti-PD-1/PD-L1, anti-CTLA-4) has a high response rate with potential for favorable oncologic outcomes. We present a series of three patients with MSI-H metastatic colorectal cancer complicated by malignant bowel obstruction and fistula formation, who having progressed on standard chemotherapy, underwent palliative intervention as a bridge to immune checkpoint blockade with durable and clinically meaningful anti-cancer responses. These cases highlight the need to re-evaluate the role of historically palliative operations in the setting of disease progression for immunotherapy-responsive tumors

A New Dimension Hidden in the Shadow of a Wall

We propose a new way to hide the fifth dimension, and to modify gravity in the far infra-red. A gravitating tensional membrane in five dimensions folds the transverse space into a truncated cone, stoppered by the membrane. For near-critical tension, the conical opening is tiny, and the space becomes a very narrow conical sliver. A very long section, of length comparable to the membrane radius divided by the remaining conical angle, of this sliver is well approximated by a narrow cylinder ending on the membrane. Inside this cylindrical throat we can reduce the theory on the circle. At distances between the circle radius and the length of the cylinder, the theory looks 4D, with a Brans-Dicke-like gravity, and a preferred direction, while at larger distances the cone opens up and the theory turns 5D. The gravitational light scalar in the throat can get an effective local mass term from the interplay of matter interactions and quantum effective potentials on the cone, which may suppress its long range effects. We discuss some phenomenologically interesting consequences.Comment: 8 pages LaTeX, 1 .eps figure; typo fixed, references updated, in press in PL

Know Thy Strengths: Comprehensive Dialogue State Tracking Diagnostics

Recent works that revealed the vulnerability of dialogue state tracking (DST) models to distributional shifts have made holistic comparisons on robustness and qualitative analyses increasingly important for understanding their relative performance. We present our findings from standardized and comprehensive DST diagnoses, which have previously been sparse and uncoordinated, using our toolkit, CheckDST, a collection of robustness tests and failure mode analytics. We discover that different classes of DST models have clear strengths and weaknesses, where generation models are more promising for handling language variety while span-based classification models are more robust to unseen entities. Prompted by this discovery, we also compare checkpoints from the same model and find that the standard practice of selecting checkpoints using validation loss/accuracy is prone to overfitting and each model class has distinct patterns of failure. Lastly, we demonstrate how our diagnoses motivate a pre-finetuning procedure with non-dialogue data that offers comprehensive improvements to generation models by alleviating the impact of distributional shifts through transfer learning.Comment: EMNLP202

Parametric Projection Operator Technique for Second Order Non-linear Response

We demonstrate the application of the recently introduced parametric projector operator technique to a calculation of the second order non-linear optical response of a multilevel molecular system. We derive a parametric quantum master equation (QME) for the time evolution of the excited state of an excitonic system after excitation by the first two pulses in the usual spectroscopic four-wave-mixing scheme. This master equation differs from the usual QME by a correction term which depends on the delay \tau between the pulses. In the presence of environmental degrees of freedom with finite bath correlation time and in the presence of intramolecular vibrations we find distinct dynamics of both the excite state populations and the electronic coherence for different delays \tau.Comment: 15 pages, 8 figure