1,073 research outputs found
Pathological serosa and node-based classification accurately predicts gastric cancer recurrence risk and outcome, and determines potential and limitation of a Japanese-style extensive surgery for Western patients: A prospective with quality control 10-year follow-up study
UICC classification accurately predicts overall survival but not recurrence-risk. We report here data of overall and first site-specific recurrence following curative surgery useful for the development of recurrence-oriented preventive target therapies. Patients who underwent resection for gastric cancer were stratified according to curability of surgery [curative (R0) vs non-curative resection], extent of surgery [limited (D1) vs extended (D2) node dissection] and pathological nodal/serosal status. The intent-to-treat principle, log-rank test and Cox regression analysis were used for statistical analysis of time-to-event (recurrence, death) endpoints. Curative resection only produced a chance of cure whereas survival was very poor following non-curative resection (P < 0.0001). For D2 R0 subgroup of patients, a pathological serosa and a node state-based classification into three groups, proved to be of clinical implication. Risk of recurrence after a median follow-up of 92 months was low among patients with both serosa and node-negative cancer (first group; 11%), moderate among those with either serosa or node-positive cancer (second group; 53%) and very high among those with both serosa and node-positive cancer (third group; 83%). In multivariate analysis, the relative risks of recurrence and death from gastric cancer among patients in the second and third groups, as compared to those in the first, were 7.07 (95% CI, 2.36–21.17;P  = 0.0002) and 16.19 (95% CI, 5.76–45.54;P < 0.0001) respectively. First site-specific recurrence analysis revealed: low rate of loco-regional recurrence alone (12%), serosa state determinant factor of the site-recurrence (peritoneal for serosa-positive and haematogenous for serosa-negative cancers) and dramatic increase of all types of recurrence by the presence of nodal metastases. Our findings demonstrate that a pathological serosa- and node-based classification is very simple and predicts accurately site-specific recurrence-risks. Furthermore they reveal that risk of recurrence following curative D2 surgery alone is low for serosa- and node-negative cancers, but very high in serosa- and node-positive cancers suggesting the need for new therapeutic strategies in this subgroup of patients. © 2001 Cancer Research Campaign http://www.bjcancer.co
Improving the Price of Anarchy for Selfish Routing via Coordination Mechanisms
We reconsider the well-studied Selfish Routing game with affine latency
functions. The Price of Anarchy for this class of games takes maximum value
4/3; this maximum is attained already for a simple network of two parallel
links, known as Pigou's network. We improve upon the value 4/3 by means of
Coordination Mechanisms.
We increase the latency functions of the edges in the network, i.e., if
is the latency function of an edge , we replace it by
with for all . Then an
adversary fixes a demand rate as input. The engineered Price of Anarchy of the
mechanism is defined as the worst-case ratio of the Nash social cost in the
modified network over the optimal social cost in the original network.
Formally, if \CM(r) denotes the cost of the worst Nash flow in the modified
network for rate and \Copt(r) denotes the cost of the optimal flow in the
original network for the same rate then [\ePoA = \max_{r \ge 0}
\frac{\CM(r)}{\Copt(r)}.]
We first exhibit a simple coordination mechanism that achieves for any
network of parallel links an engineered Price of Anarchy strictly less than
4/3. For the case of two parallel links our basic mechanism gives 5/4 = 1.25.
Then, for the case of two parallel links, we describe an optimal mechanism; its
engineered Price of Anarchy lies between 1.191 and 1.192.Comment: 17 pages, 2 figures, preliminary version appeared at ESA 201
THGEM-based detectors for sampling elements in DHCAL: laboratory and beam evaluation
We report on the results of an extensive R&D program aimed at the evaluation
of Thick-Gas Electron Multipliers (THGEM) as potential active elements for
Digital Hadron Calorimetry (DHCAL). Results are presented on efficiency, pad
multiplicity and discharge probability of a 10x10 cm2 prototype detector with 1
cm2 readout pads. The detector is comprised of single- or double-THGEM
multipliers coupled to the pad electrode either directly or via a resistive
anode. Investigations employing standard discrete electronics and the KPiX
readout system have been carried out both under laboratory conditions and with
muons and pions at the CERN RD51 test beam. For detectors having a
charge-induction gap, it has been shown that even a ~6 mm thick single-THGEM
detector reached detection efficiencies above 95%, with pad-hit multiplicity of
1.1-1.2 per event; discharge probabilities were of the order of 1e-6 - 1e-5
sparks/trigger, depending on the detector structure and gain. Preliminary beam
tests with a WELL hole-structure, closed by a resistive anode, yielded
discharge probabilities of <2e-6 for an efficiency of ~95%. Methods are
presented to reduce charge-spread and pad multiplicity with resistive anodes.
The new method showed good prospects for further evaluation of very thin
THGEM-based detectors as potential active elements for DHCAL, with competitive
performances, simplicity and robustness. Further developments are in course.Comment: 15 pages, 11 figures, MPGD2011 conference proceedin
Portable optical blood scattering sensor
Modern non-invasive medical sensors can continuously provide vital information such as blood oxygenation, hemoglobin and glucose, based on substance-specific spectral or electrochemical properties. Cells and other geometrical formations are difficult to observe non-invasively due to the absence of a distinctive substantial signature. Optical scattering angle measurements could provide geometrical information but multiple scattering results in diffusion profiles, limiting their direct applicability. Mie scattering correlation to blood cell size has been demonstrated in the lab and various biomedical optical techniques are under intense investigation towards decoupling direct from indirect scattering, requiring specialized equipment. In this paper, a portable sensor is introduced for in-vitro and potentially in-vivo study of light scattering from blood. A microcontroller-based prototype has been designed and fabricated, with a 650 nm laser source, a 128 × 1 photodiode array and a custom dual-core real-time data acquisition algorithm. The prototype has been evaluated using latex sphere solutions calibrated to emulated red blood cells, white blood cells and platelets. Distinct scattering signatures are demonstrated for the three blood cell sizes. Reproducibility and repeatability tests analyzing data from multiple independent experiments demonstrate the reliability of the demonstration. This device platform provides a flexible and simple means for evaluating optical processing methods towards non-invasive continuous counting of blood cells
Kinome-Wide Synthetic Lethal Screen Identifies PANK4 as a Modulator of Temozolomide Resistance in Glioblastoma
Temozolomide (TMZ) represents the cornerstone of therapy for glioblastoma (GBM). However, acquisition of resistance limits its therapeutic potential. The human kinome is an undisputable source of druggable targets, still, current knowledge remains confined to a limited fraction of it, with a multitude of under-investigated proteins yet to be characterized. Here, following a kinome-wide RNAi screen, pantothenate kinase 4 (PANK4) isuncovered as a modulator of TMZ resistance in GBM. Validation of PANK4 across various TMZ-resistant GBM cell models, patient-derived GBM cell lines, tissue samples, as well as in vivo studies, corroborates the potential translational significance of these findings. Moreover, PANK4 expression is induced during TMZ treatment, and its expression is associated with a worse clinical outcome. Furthermore, a Tandem Mass Tag (TMT)-based quantitative proteomic approach, reveals that PANK4 abrogation leads to a significant downregulation of a host of proteins with central roles in cellular detoxification and cellular response to oxidative stress. More specifically, as cells undergo genotoxic stress during TMZ exposure, PANK4 depletion represents a crucial event that can lead to accumulation of intracellular reactive oxygen species (ROS) and subsequent cell death. Collectively, a previously unreported role for PANK4 in mediating therapeutic resistance to TMZ in GBM is unveiled
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