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Search Results: 1 - 10 of 11306 matches for " Walter Taylor "
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Classification of finite-dimensional compact topological algebras, preliminary report
Walter Taylor
Mathematics , 2014,
Abstract: A topological space $A$ is said to be compatible with a set $\Sigma$ of equations (involving operation symbols $F_t$) iff there are continuous operations $\overline F_t$ identically satisfying $\Sigma$ on $A$. The paper's main focus is on the compatibility relation for $A$ a finite simplicial complex. We review and extend the known compatibilities and incompatibilities in this context. Many such spaces are compatible with no non-trivial $\Sigma$. The paper concludes with open questions. For example, if $A$ is compatible with $\Sigma$, can this fact be deduced from the compatibility of $A$ with some $\Gamma$ that involves only ternary operations? If $A$ is compatible with $\Sigma$, can the operations $\overline F_t$ be chosen as piecewise multilinear? Is the compatibility relation (between finite $\Sigma$ and finite complexes $A$) algorithmic? For $A$ a one-simplex (i.e., a closed real interval), is there some simple characterization of the set of all $\Sigma$ compatible with $A$?
Discontinuities in the identical satisfaction of equations
Walter Taylor
Mathematics , 2015,
Abstract: For a metric space $(A,d)$, and a set $\Sigma$ of equations, some quantities are introduced that measure the size of discontinuities that must occur in operations satisfying $\Sigma$ (identically) on $A$. We are able to evaluate these quantities in a few easy cases.}
Approimate satisfaction of identities
Walter Taylor
Mathematics , 2015,
Abstract: For a metric space $(A,d)$, and a set $\Sigma$ of equations, a quantity is introduced that measures how far continuous operations must deviate from satisfying $\Sigma$ on $(A,d)$. }
Therapeutic Use of Dendritic Cells to Promote the Extranodal Priming of Anti-Tumor Immunity
Jennifer L. Taylor,Walter J. Storkus
Frontiers in Immunology , 2013, DOI: 10.3389/fimmu.2013.00388
Abstract: Ectopic lymphoid tissue, also known as tertiary lymphoid organs (TLO) develop adaptively within sites of chronic tissue inflammation, thereby allowing the host to efficiently crossprime specific immune effector cells within sites of disease. Recent evidence suggests that the presence of TLO in the tumor microenvironment (TME) predicts better overall survival. We will discuss the relevance of extranodal T cell priming within the TME as a means to effectively promote anti-tumor immunity and the strategic use of dendritic cell (DC)-based therapies to reinforce this clinically preferred process in the cancer-bearing host.
Effect of Carboxyamidotriazole Orotate, a Modulator of Calcium-Dependent Signaling Pathways, on Advanced Solid Tumors  [PDF]
Matthew H. Taylor, Alan Sandler, Walter J. Urba, Antonio M. P. Omuro, Greg S. Gorman, Rashida A. Karmali
Journal of Cancer Therapy (JCT) , 2015, DOI: 10.4236/jct.2015.64035
Abstract:

Pre-clinical studies suggest carboxyamidotriazole orotate (CTO) demonstrates anti-tumor activity through modulation of multiple tyrosine kinase signaling pathways and interactions with the tumor microenvironment. We determined the safety and tolerability, pharmacokinetic profile, maximum tolerated dose, and recommended Phase II dose of CTO monotherapy in patients with advanced solid tumors. In this first-in-human Phase I clinical trial, eligible patients with advanced solid tumors were enrolled to receive a once-daily dose of CTO following a standard 3 + 3 Phase I design (starting at 50 mg/m2/day) with dose escalations of 30% - 100%. Dose limiting toxicity (DLT) was defined in the first cycle of treatment. Measurable disease and response were defined by RECIST version 1.1. Forty-four patients were evaluable for safety. CTO-related grade 3 toxicities included diarrhea (2.5%), fatigue (5.0%), lymphopenia (2.5%) and transient creatine phosphokinase (CPK) elevation (2.5%). There were no grade 4 or 5 toxicities. Steady state plasma levels of CAI (CTO metabolite) were achieved by day 12 with a half life estimate of 55 hr. Although no objective response rates were observed, nine patients with rapidly progressive and treatment-refractory tumors achieved stable disease (SD) durable for up to 14 months. The maximum tolerated dose for CTO alone was 427 mg/m2/day. The dose-limiting toxicity was grade 3 fatigue. CTO is orally bioavailable, safe, well tolerated and produces disease stabilization in a broad range of heavily treated refractory tumors. Combination trials of CTO with other antineoplastic agents are ongoing.

Artemisinin-based combination therapy for uncomplicated Plasmodium falciparum malaria in Colombia
Lyda Osorio, Iveth Gonzalez, Piero Olliaro, Walter RJ Taylor
Malaria Journal , 2007, DOI: 10.1186/1475-2875-6-25
Abstract: A randomized, double-blind, placebo-controlled, clinical trial of the efficacy, effect on gametocytes and safety of the addition of artesunate/placebo (4 mg/kg/day × 3 d) to amodiaquine (10 mg/kg/day × 3 d) was conducted in Choco department, a low intensity transmission area in northwest Colombia.From 2,137 screened subjects, 85 entered the study: 43 in the amodiaquine plus placebo and 42 in the amodiaquine plus artesunate groups. Potentially eligible cases failed to qualify mostly because they were not available for follow-up visits (73%). Based on a per protocol analysis, the therapeutic response to both treatments was high: amodiaquine/placebo 35/36, 97.2% (95% CI 85.5–99.9), and amodiaquine/artesunate 32/32, 100% (89.1–100) after PCR genotyping. The Kaplan-Meier survival estimates based on all eligible patients enrolled (amodiaquine/placebo: n = 42; amodiaquine/artesunate: n = 41) were similar in the two study groups (P = 0.3). The addition of artesunate significantly decreased gametocyte carriage on Day 4 (OR = 0.1 95% CI 0.02–0.6), Day 7 (OR = 0.2 95%CI 0.04–0.9), Day 14 (OR = 0.09 95% CI 0–0.8), and Day 21 (OR95%CI 0–0.9). Most subjects in both groups (81% in amodiaquine/placebo and 75.6% in amodiaquine/artesunate) reported at least one drug related adverse event. Symptoms were generally mild and self-limiting and there was no serious adverse event. Two patients on amodiaquine/artesunate voluntarily withdrew from study because they could not tolerate the medication.Both drug regimens were effective in this area of Colombia. The addition of artesunate reduced gametocyte carriage and did not adversely affect tolerability. In this set of patients, the rate of adverse events was higher than in other studies. Patients' follow-up is problematic in areas with dispersed population and affects the conduct of clinical studies and monitoring of treatment effects. The results are discussed in the light of concurrent increase resistance to amodiaquine in other endemic are
Malaria treatment failures after artemisinin-based therapy in three expatriates: could improved manufacturer information help to decrease the risk of treatment failure ?
Yves Jackson, Fran?ois Chappuis, Louis Loutan, Walter Taylor
Malaria Journal , 2006, DOI: 10.1186/1475-2875-5-81
Abstract: Manufacturers information and drug content included in twenty-five artemisinin-containing specialities were reviewed.A substantial number of manufacturers do not follow current WHO recommendations regarding treatment duration and doses.This study shows that drug packaging and their inserts should be improved.Artemisinin derivatives, such as artesunate, artemether and dihydroartemisinin, are the most parasiticidal of all the antimalarial drugs against Plasmodium falciparum [1]. Their pharmacokinetic (rapid absorption, short half life ~1 hour) and pharmacodynamic (high parasite reduction ratio) properties mitigate against the development of resistance. In vivo resistance to this drug class has not yet been described [2]. However, several challenges remain, including the limited availability of GMP quality drugs, the emergence of fake drugs, and their optimal deployment in malaria-endemic countries. Artemisinin-based drugs are easily available in several malaria-endemic countries and are sold as mono- or combination therapies. They are manufactured in several countries, packaged differently and contain package inserts of varying quality and accuracy. WHO currently recommends malaria-endemic countries to use three days of an artemisinin-based combination treatment (ACT) e.g. artemether/lumefantrine (A/L), artesunate (4 mg/kg/day) plus an effective, longer acting partner drug, such as amodiaquine or mefloquine [3]. If used alone, seven days of treatment of an artemisinin derivative is necessary because shorter courses result in unacceptably high rates of recrudescence. Most recently, WHO has called drug manufacturers to switch the production of artemisinin monotherapies towards combined therapies because of the risk of developing drug resistance. Artesunate monotherapy of ≤ 5 days duration in South-East Asian and African patients is associated with a failure rate of up to 50% and the four doses regimen of artemether/lumefantrine has resulted in failure rates of between 1
Predictors of elevated tumour necrosis factor level in obstructive sleep apnoea syndrome
Silke Ryan,Cormac. T. Taylor,Walter. T. McNicholas
European Respiratory Review , 2006,
Abstract: Circulating levels of TNF-alpha are elevated in Obstructive Sleep Apnoea Syndrome (OSAS) and likely contribute to associated cardiovascular diseases. Furthermore, TNF-alpha has been suggested as a mediator of excessive daytime sleepiness (EDS). We investigated the predictors of TNF-alpha in OSAS in large, well-selected patient and control cohorts. We undertook a prospective study of 30 non-OSAS (including 22 non-sleepy controls and 8 sleepy non-apnoeic snorers), 36 mild-moderate OSAS and 31 severe OSAS male subjects. All groups were closely matched in age, BMI, smoking status, blood pressure and lipid profile. All subjects were free of other disease and were not taking regular medication. Serum for TNF-alpha assay was drawn following polysomnography (PSG) in all subjects. 49 patients were commenced on CPAP therapy within one week following PSG; sleep studies and TNF-alpha measurements were repeated 6 weeks later. TNF-alpha was higher in OSAS patients than controls (p<0.001). In multivariate analysis, TNF-alpha was independently associated with the desaturation index (r = 0.399, p<0.001), the Epworth Sleepiness Score (ESS) (r = 0.243, p = 0.005) and total cholesterol (r = 0.216, p = 0.018). Furthermore, levels were higher in sleepy non-OSAS patients than in controls (4.49[3.35,6.94] pg·ml–1 vs 2.46[1.66,3.40]; p = 0.002) but lower than in severe OSAS patients (6.32[5.70,8.17]; p = 0.03). CPAP significantly lowered TNF-alpha (from 5.56±2.10 to 4.13±2.99 pg·ml–1; p = 0.004). The severity of intermittent hypoxia is the strongest predictor of TNF-alpha level supporting a key role of inflammation in the cardiovascular pathophysiology of OSAS. Furthermore, TNF-alpha is independently associated with EDS.
Drug resistant falciparum malaria and the use of artesunate-based combinations : focus on clinical trials sponsored by TDR
Walter R.J. Taylor, Jean Rigal & Piero L. Olliaro
Journal of Vector Borne Diseases , 2003,
Abstract: Antimalarial drug resistance has now become a serious global challenge and is the principal reasonfor the decline in antimalarial drug efficacy. Malaria endemic countries need inexpensive and efficaciousdrugs. Preserving the life spans of antimalarial drugs is a key part of the strategy for rollingback malaria. Artemisinin-based combinations offer a new and potentially highly effective way tocounter drug resistance. Clinical trials conducted in African children have attested to the good tolerabilityof oral artesunate when combined with standard antimalarial drugs. The cure rates of thedifferent combinations were generally dependent on the degree of resistance to the companiondrug. They were high for amodiaquine-artesunate, variable for sulfadoxine/pyrimethamine-artesunate,and poor for chloroquine-artesunate.
The Interaction between the ISM and Star Formation in the Dwarf Starburst Galaxy NGC 4214
F. Walter,C. Taylor,S. Huettemeister,N. Scoville,V. McIntyre
Physics , 2000, DOI: 10.1086/318775
Abstract: We present the first interferometric study of the molecular gas in the metal-poor dwarf starburst galaxy NGC 4214. Our map of the 12CO(1-0) emission, obtained at the OVRO millimeter array, reveals an unexpected structural wealth. We detected three regions of molecular emission in the north-west (NW), south-east (SE) and centre of NGC 4214 which are in very different and distinct evolutionary stages (total molecular mass: 5.1 x 10^6 M_sun). These differences are apparent most dramatically when the CO morphologies are compared to optical ground based and HST imaging: massive star formation has not started yet in the NW region; the well-known starburst in the centre is the most evolved and star formation in the SE complex started more recently. We derive a star formation efficiency of 8% for the SE complex. Using high--resolution VLA observations of neutral hydrogen HI and our CO data we generated a total gas column density map for NGC 4214 (HI + H_2). No clear correlation is seen between the peaks of HI, CO and the sites of ongoing star formation. This emphasizes the irregular nature of dwarf galaxies. The HI and CO velocities agree well, so do the H-alpha velocities. In total, we cataloged 14 molecular clumps in NGC 4214. Our results from a virial mass analysis are compatible with a Galactic CO-to-H_2 conversion factor for NGC 4214 (lower than what is usually found in metal-poor dwarf galaxies).
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