448 research outputs found
Phase II study of irinotecan with bolus and high dose infusional 5-FU and folinic acid (modified de Gramont) for first or second line treatment of advanced or metastatic colorectal cancer
We investigated the activity of irinotecan given with a more convenient modified bimonthly de Gramont regimen of bolus and infusional 5-fluorouracil [IrMdG] in advanced or metastatic colorectal cancer in the first and second line setting. Irinotecan 180 mg m−2 was infused over 90 min. L-folinic acid 175 mg or d,l folinic acid 350 mg was given over 2 h followed by a bolus of 5-fluorouracil (400 mg m−2) and a 46 h continuous infusion of 5-fluorouracil (2.4–2.8 g m−2). Forty-six previously untreated patients (Group A) and 36 who had received 5-fluorouracil for metastatic disease (Group B) were recruited. Seventy-eight patients were evaluable for response. A partial response was seen in 13 out of 43 (30% [95%CI 28.1–31.9%]) in Group A and 8/35 (23% [95% CI 17.9–28.1%]) in Group B. 40% (95%CI 38.1–41.9%) of Group A and 26% (95% CI 20.9–31.1%) of Group B patients achieved disease stabilisation. The median progression free survival from the start of this treatment was 7 months (95% CI 4.4–9.6 months) in Group A and 5 months (95% CI 2.8–7.2 months) in Group B. Median overall survival was 14 months (95% CI 9.0–18.9) in Group A and 11 months (95% CI 5.9–16.1) in Group B. Grade 3–4 toxicity in both treatment groups were similar; leucopenia 17% and diarrhoea 7–8%. Grade 3–4 mucositis was not seen and severe alopecia affected only three patients. IrMdG is an active and well-tolerated regimen for both the first and second line treatment of advanced colorectal cancer
A ‘modified de Gramont’ regimen of fluorouracil, alone and with oxaliplatin, for advanced colorectal cancer
The standard de Gramont (dG) regimen of fortnightly leucovorin, bolus fluorouracil and 22-h infusion of fluorouracil, d1+2, and the same regimen plus oxaliplatin, are effective but also cumbersome. We therefore present simplified ‘Modified de Gramont’ (MdG) regimens. Forty-six advanced gastrointestinal cancer patients entered a dose-exploring study of MdG, including an expanded cohort of colorectal cancer patients at optimum dose. Treatment (fortnightly) comprised: 2-h i.v.i. leucovorin (350 mg d,l-LV or 175 mg l-LV, not adjusted for patient surface area); bolus fluorouracil (400 mg m−2), then ambulatory 46-h fluorouracil infusion (2000–3600 mg m−2, cohort escalation). Subsequently, 62 colorectal patients (25 unpretreated; 37 fluorouracil-resistant) received MdG plus oxaliplatin (OxMdG) 85 mg m−2. Fluorouracil pharmacokinetics during MdG were compared with dG. The optimum fluorouracil doses for MdG alone were determined as 400 mg m−2 bolus + 2800 mg m−2 46-h infusion. A lower dose of 400 mg m−2 bolus + 2400 mg m−2 infusion which, like dG produces minimal toxicity, was chosen for the OxMdG combination. Fluorouracil exposure (AUC0–48 h) at this lower dose is equivalent to dG. With OxMdG, grade 3–4 toxicity was rare (neutropenia 2.8% cycles; vomiting or diarrhoea <1% cycles), but despite this there were two infection-associated deaths. Oxaliplatin was omitted for cumulative neurotoxicity in 17 out of 62 patients. Objective responses in colorectal cancer patients were: 1st-line MdG (22 assessable): PR=36%, NC=32%, PD=32%. 1st-line OxMdG (24 assessable): CR/PR=72%; NC=20%; PD=8%; 2nd line OxMdG (34 assessable): PR=12%; NC=38%; PD=50%. MdG and OxMdG are convenient and well-tolerated. OxMdG was particularly active as 1st-line treatment of advanced colorectal cancer. Both regimens are being further evaluated in the current UK MRC phase III trial
Electrophysical properties of nanoporous cerium dioxide–water system
The impedance of nanoporous cerium dioxide with adsorbed water is investigated in the frequency range 103–104 Hz at temperatures near the water–ice phase transition. Here we show that the manifestation of impedance peculiarities at phase transition is caused by the dielectric constant of the matrix
Interleaved Parton Showers and Tuning Prospects
General-purpose Monte Carlo event generators have become important tools in
particle physics, allowing the simulation of exclusive hadronic final states.
In this article we examine the Pythia 8 generator, in particular focusing on
its parton-shower algorithms. Some relevant new additions to the code are
introduced, that should allow for a better description of data. We also
implement and compare with 2 to 3 real-emission QCD matrix elements, to check
how well the shower algorithm fills the phase space away from the soft and
collinear regions. A tuning of the generator to Tevatron data is performed for
two PDF sets and the impact of first new LHC data is examined
Coherent Parton Showers with Local Recoils
We outline a new formalism for dipole-type parton showers which maintain
exact energy-momentum conservation at each step of the evolution. Particular
emphasis is put on the coherence properties, the level at which recoil effects
do enter and the role of transverse momentum generation from initial state
radiation. The formulated algorithm is shown to correctly incorporate coherence
for soft gluon radiation. Furthermore, it is well suited for easing matching to
next-to-leading order calculations.Comment: 24 pages, 3 figure
Where the Sidewalk Ends: Jets and Missing Energy Search Strategies for the 7 TeV LHC
This work explores the potential reach of the 7 TeV LHC to new colored states
in the context of simplified models and addresses the issue of which search
regions are necessary to cover an extensive set of event topologies and
kinematic regimes. This article demonstrates that if searches are designed to
focus on specific regions of phase space, then new physics may be missed if it
lies in unexpected corners. Simple multiregion search strategies can be
designed to cover all of kinematic possibilities. A set of benchmark models are
created that cover the qualitatively different signatures and a benchmark
multiregion search strategy is presented that covers these models.Comment: 30 pages, 8 Figures, 3 Tables. Version accepted at JHEP. Minor
changes. Added figur
SerpinB2 regulates stromal remodelling and local invasion in pancreatic cancer
Pancreatic cancer has a devastating prognosis, with an overall 5-year survival rate of ~8%, restricted treatment options and characteristic molecular heterogeneity. SerpinB2 expression, particularly in the stromal compartment, is associated with reduced metastasis and prolonged survival in pancreatic ductal adenocarcinoma (PDAC) and our genomic analysis revealed that SERPINB2 is frequently deleted in PDAC. We show that SerpinB2 is required by stromal cells for normal collagen remodelling in vitro, regulating fibroblast interaction and engagement with collagen in the contracting matrix. In a pancreatic cancer allograft model, co-injection of PDAC cancer cells and SerpinB2(-/-) mouse embryonic fibroblasts (MEFs) resulted in increased tumour growth, aberrant remodelling of the extracellular matrix (ECM) and increased local invasion from the primary tumour. These tumours also displayed elevated proteolytic activity of the primary biochemical target of SerpinB2-urokinase plasminogen activator (uPA). In a large cohort of patients with resected PDAC, we show that increasing uPA mRNA expression was significantly associated with poorer survival following pancreatectomy. This study establishes a novel role for SerpinB2 in the stromal compartment in PDAC invasion through regulation of stromal remodelling and highlights the SerpinB2/uPA axis for further investigation as a potential therapeutic target in pancreatic cancer
Bigger, Better, Faster, More at the LHC
Multijet plus missing energy searches provide universal coverage for theories
that have new colored particles that decay into a dark matter candidate and
jets. These signals appear at the LHC further out on the missing energy tail
than two-to-two scattering indicates. The simplicity of the searches at the LHC
contrasts sharply with the Tevatron where more elaborate searches are necessary
to separate signal from background. The searches presented in this article
effectively distinguish signal from background for any theory where the LSP is
a daughter or granddaughter of the pair-produced colored parent particle
without ever having to consider missing energies less than 400 GeV.Comment: 26 pages, 8 Figures. Minor textual changes, typos fixed and
references adde
Prehospital intravenous access and fluid resuscitation in severe sepsis: an observational cohort study
Scaling Patterns for QCD Jets
Jet emission at hadron colliders follows simple scaling patterns. Based on
perturbative QCD we derive Poisson and staircase scaling for final state as
well as initial state radiation. Parton density effects enhance staircase
scaling at low multiplicities. We propose experimental tests of our theoretical
findings in Z+jets and QCD gap jets production based on minor additions to
current LHC analyses.Comment: 36 pages, 16 figure
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