45 research outputs found

    Polar molecule reactive collisions in quasi-1D systems

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    We study polar molecule scattering in quasi-one-dimensional geometries. Elastic and reactive collision rates are computed as a function of collision energy and electric dipole moment for different confinement strengths. The numerical results are interpreted in terms of first order scattering and of adiabatic models. Universal dipolar scattering is also discussed. Our results are relevant to experiments where control of the collision dynamics through one dimensional confinement and an applied electric field is envisioned.Comment: 25 pages, 13 figure

    Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): Survival results from an adaptive, multiarm, multistage, platform randomised controlled trial

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    BACKGROUND Long-term hormone therapy has been the standard of care for advanced prostate cancer since the 1940s. STAMPEDE is a randomised controlled trial using a multiarm, multistage platform design. It recruits men with high-risk, locally advanced, metastatic or recurrent prostate cancer who are starting first-line long-term hormone therapy. We report primary survival results for three research comparisons testing the addition of zoledronic acid, docetaxel, or their combination to standard of care versus standard of care alone. METHODS Standard of care was hormone therapy for at least 2 years; radiotherapy was encouraged for men with N0M0 disease to November, 2011, then mandated; radiotherapy was optional for men with node-positive non-metastatic (N+M0) disease. Stratified randomisation (via minimisation) allocated men 2:1:1:1 to standard of care only (SOC-only; control), standard of care plus zoledronic acid (SOC + ZA), standard of care plus docetaxel (SOC + Doc), or standard of care with both zoledronic acid and docetaxel (SOC + ZA + Doc). Zoledronic acid (4 mg) was given for six 3-weekly cycles, then 4-weekly until 2 years, and docetaxel (75 mg/m(2)) for six 3-weekly cycles with prednisolone 10 mg daily. There was no blinding to treatment allocation. The primary outcome measure was overall survival. Pairwise comparisons of research versus control had 90% power at 2·5% one-sided α for hazard ratio (HR) 0·75, requiring roughly 400 control arm deaths. Statistical analyses were undertaken with standard log-rank-type methods for time-to-event data, with hazard ratios (HRs) and 95% CIs derived from adjusted Cox models. This trial is registered at ClinicalTrials.gov (NCT00268476) and ControlledTrials.com (ISRCTN78818544). FINDINGS 2962 men were randomly assigned to four groups between Oct 5, 2005, and March 31, 2013. Median age was 65 years (IQR 60-71). 1817 (61%) men had M+ disease, 448 (15%) had N+/X M0, and 697 (24%) had N0M0. 165 (6%) men were previously treated with local therapy, and median prostate-specific antigen was 65 ng/mL (IQR 23-184). Median follow-up was 43 months (IQR 30-60). There were 415 deaths in the control group (347 [84%] prostate cancer). Median overall survival was 71 months (IQR 32 to not reached) for SOC-only, not reached (32 to not reached) for SOC + ZA (HR 0·94, 95% CI 0·79-1·11; p=0·450), 81 months (41 to not reached) for SOC + Doc (0·78, 0·66-0·93; p=0·006), and 76 months (39 to not reached) for SOC + ZA + Doc (0·82, 0·69-0·97; p=0·022). There was no evidence of heterogeneity in treatment effect (for any of the treatments) across prespecified subsets. Grade 3-5 adverse events were reported for 399 (32%) patients receiving SOC, 197 (32%) receiving SOC + ZA, 288 (52%) receiving SOC + Doc, and 269 (52%) receiving SOC + ZA + Doc. INTERPRETATION Zoledronic acid showed no evidence of survival improvement and should not be part of standard of care for this population. Docetaxel chemotherapy, given at the time of long-term hormone therapy initiation, showed evidence of improved survival accompanied by an increase in adverse events. Docetaxel treatment should become part of standard of care for adequately fit men commencing long-term hormone therapy. FUNDING Cancer Research UK, Medical Research Council, Novartis, Sanofi-Aventis, Pfizer, Janssen, Astellas, NIHR Clinical Research Network, Swiss Group for Clinical Cancer Research

    Addition of Docetaxel to First-line Long-term Hormone Therapy in Prostate Cancer (STAMPEDE): Modelling to Estimate Long-term Survival, Quality-adjusted Survival, and Cost-effectiveness

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    BACKGROUND: Results from large randomised controlled trials have shown that adding docetaxel to the standard of care (SOC) for men initiating hormone therapy for prostate cancer (PC) prolongs survival for those with metastatic disease and prolongs failure-free survival for those without. To date there has been no formal assessment of whether funding docetaxel in this setting represents an appropriate use of UK National Health Service (NHS) resources OBJECTIVE: To assess whether administering docetaxel to men with PC starting long-term hormone therapy is cost-effective in a UK setting. DESIGN, SETTING AND PARTICIPANTS: We modelled health outcomes and costs in the UK NHS using data collected within the STAMPEDE trial, which enrolled men with high-risk, locally advanced metastatic or recurrent PC starting first-line hormone therapy. INTERVENTION: SOC was hormone therapy for ≥2 yr and radiotherapy in some patients. Docetaxel (75 mg/m2) was administered alongside SOC for six three-weekly cycles. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The model generated lifetime predictions of costs, changes in survival duration, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). RESULTS AND LIMITATIONS: The model predicted that docetaxel would extend survival (discounted quality-adjusted survival) by 0.89 yr (0.51) for metastatic PC and 0.78 yr (0.39) for nonmetastatic PC, and would be cost-effective in metastatic PC (ICER £5514/QALY vs SOC) and nonmetastatic PC (higher QALYs, lower costs vs SOC). Docetaxel remained cost-effective in nonmetastatic PC when the assumption of no survival advantage was modelled. CONCLUSIONS: Docetaxel is cost-effective among patients with nonmetastatic and metastatic PC in a UK setting. Clinicians should consider whether the evidence is now sufficiently compelling to support docetaxel use in patients with nonmetastatic PC, as the opportunity to offer docetaxel at hormone therapy initiation will be missed for some patients by the time more mature survival data are available. PATIENT SUMMARY: Starting docetaxel chemotherapy alongside hormone therapy represents a good use of UK National Health Service resources for patients with prostate cancer that is high risk or has spread to other parts of the body

    Addition of Docetaxel to First-line Long-term Hormone Therapy in Prostate Cancer (STAMPEDE) : Modelling to Estimate Long-term Survival, Quality-adjusted Survival, and Cost-effectiveness

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    Background Results from large randomised controlled trials have shown that adding docetaxel to the standard of care (SOC) for men initiating hormone therapy for prostate cancer (PC) prolongs survival for those with metastatic disease and prolongs failure-free survival for those without. To date there has been no formal assessment of whether funding docetaxel in this setting represents an appropriate use of UK National Health Service (NHS) resources. Objective To assess whether administering docetaxel to men with PC starting long-term hormone therapy is cost-effective in a UK setting. Design, setting, and participants We modelled health outcomes and costs in the UK NHS using data collected within the STAMPEDE trial, which enrolled men with high-risk, locally advanced metastatic or recurrent PC starting first-line hormone therapy. Intervention SOC was hormone therapy for ≥2 yr and radiotherapy in some patients. Docetaxel (75 mg/m2) was administered alongside SOC for six three-weekly cycles. Outcome measurements and statistical analysis The model generated lifetime predictions of costs, changes in survival duration, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). Results and limitations The model predicted that docetaxel would extend survival (discounted quality-adjusted survival) by 0.89 yr (0.51) for metastatic PC and 0.78 yr (0.39) for nonmetastatic PC, and would be cost-effective in metastatic PC (ICER £5514/QALY vs SOC) and nonmetastatic PC (higher QALYs, lower costs vs SOC). Docetaxel remained cost-effective in nonmetastatic PC when the assumption of no survival advantage was modelled. Conclusions Docetaxel is cost-effective among patients with nonmetastatic and metastatic PC in a UK setting. Clinicians should consider whether the evidence is now sufficiently compelling to support docetaxel use in patients with nonmetastatic PC, as the opportunity to offer docetaxel at hormone therapy initiation will be missed for some patients by the time more mature survival data are available. Patient summary Starting docetaxel chemotherapy alongside hormone therapy represents a good use of UK National Health Service resources for patients with prostate cancer that is high risk or has spread to other parts of the body.This study was supported by the UK Medical Research Council (delegation to Swiss Group for Cancer Clinical Research [SAKK] in Switzerland) grant number MRC_MC_UU_12023/25 and the following funders: Cancer Research UK (grant number CRUK_A12459), Medical Research Council, Astellas, Clovis Oncology, Janssen, Novartis, Pfizer, and Sanofi-Aventis. The sponsors played no direct role in the study

    Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

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    Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

    Modèles théoriques pour collisions ultra froids entre atomes-ions dans les géométries confinées

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    Les systèmes composés d'atomes et d'ions ultrafroids ont étés un sujet d'intérêt pour les physiciens atomiques et, plus récemment, pour la communauté des ions froids (simulation et calcul quantique avec des ions piégés). Ils sont considéré la possibilité d'utiliser un gaz d'atomes ultrafroids pour refroidir sympathiquement les ions car la modulation intrinsèque du mouvement, le micromouvement, représente une source de décohérence dans les applications des ions froids. L'intérêt envers ce système mixte est aussi motivé par l'étude de la physique d'impuretés et par une meilleure compréhension des réactions entre espèces ioniques et neutre ayant pour but la création d'ions moléculaires. Cette thèse a pour objectif d'étudier les effets du micromouvement dans les collisions atome-ion. Nous traitons au préalable les collisions à 1D d'une particule dans un piège harmonique (un ion) et d'un particule libre (une atome) en utilisant différentes approches numériques. Ce système est intéressant en soi en raison de la dimensionnalité mixte 0D-1D. Le potentiel atome-ion est modélisé par une interaction à portée nulle tout au cours de ce travail. Par la suite, nous traitons un problème similaire mais dans le cas d'une particule dans un piège harmonique décrivant un piège de Paul. Enfin, nous généralisons l'étude du micromouvement à un système modèle 3D avec un ion dans un piège de Paul sphérique 3D et un atome lourd au centre du piège. Nous discutons de l'influence du micromouvement en vue d'applications potentielles de ce système telle que la porte logique de phase.Ultracold atom-ion systems have been a topic of interest for atomic physicists studying chemical reactions and since recently, the cold ion community (ion trap quantum computation and simulation). They have been looking at the possibility of using an ultracold atom gas to sympathetically cool ions since intrinsic motional modulation i.e micromotion is an inherent cause of decoherence in coherent applications of cold ions. Interest is also piqued by the possibility of using this hybrid system for studying impurity physics and to better understand ion-neutral reactions aimed at creation of molecular ions. In this thesis, we aim to study the effect of ion micromotion in atom-ion collision. As a prelude, we treat the 1D collision of a particle in a harmonic trap (ion) and a free particle (atom) using different numerical schemes. This system is of interest in its own right due to the mixed 0D-1D dimensionality. Atom-ion potential is simplified to a zero range potential all through out the work. Next we deal with a similar problem but with the trapped particle in a time dependent harmonic trap identical to an ion Paul trap. Finally we extend the study of micromotion to a model system in 3D with an ion in a 3D spherical Paul trap and a heavy atom at the trap centre. We discuss the effect micromotion has on potential applications of such a system, like a quantum phase gate

    Sujet de thèse en cours : Theoretical models for ultracold atom-ion collisions in confined geometries [Soutenance 30.03.2015]

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    supervisors Andrea Simoni and Jean-Michel Launay (department of molecular physics)sous la direction de Andrea Simoni et de Jean-Michel Launay dans le département de physique moléculair

    Modèles théoriques pour collisions ultra froids entre atomes-ions dans les géométries confinées

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    Ultracold atom-ion systems have been a topic of interest for atomic physicists studying chemical reactions and since recently, the cold ion community (ion trap quantum computation and simulation). They have been looking at the possibility of using an ultracold atom gas to sympathetically cool ions since intrinsic motional modulation i.e micromotion is an inherent cause of decoherence in coherent applications of cold ions. Interest is also piqued by the possibility of using this hybrid system for studying impurity physics and to better understand ion-neutral reactions aimed at creation of molecular ions. In this thesis, we aim to study the effect of ion micromotion in atom-ion collision. As a prelude, we treat the 1D collision of a particle in a harmonic trap (ion) and a free particle (atom) using different numerical schemes. This system is of interest in its own right due to the mixed 0D-1D dimensionality. Atom-ion potential is simplified to a zero range potential all through out the work. Next we deal with a similar problem but with the trapped particle in a time dependent harmonic trap identical to an ion Paul trap. Finally we extend the study of micromotion to a model system in 3D with an ion in a 3D spherical Paul trap and a heavy atom at the trap centre. We discuss the effect micromotion has on potential applications of such a system, like a quantum phase gate.Les systèmes composés d'atomes et d'ions ultrafroids ont étés un sujet d'intérêt pour les physiciens atomiques et, plus récemment, pour la communauté des ions froids (simulation et calcul quantique avec des ions piégés). Ils sont considéré la possibilité d'utiliser un gaz d'atomes ultrafroids pour refroidir sympathiquement les ions car la modulation intrinsèque du mouvement, le micromouvement, représente une source de décohérence dans les applications des ions froids. L'intérêt envers ce système mixte est aussi motivé par l'étude de la physique d'impuretés et par une meilleure compréhension des réactions entre espèces ioniques et neutre ayant pour but la création d'ions moléculaires. Cette thèse a pour objectif d'étudier les effets du micromouvement dans les collisions atome-ion. Nous traitons au préalable les collisions à 1D d'une particule dans un piège harmonique (un ion) et d'un particule libre (une atome) en utilisant différentes approches numériques. Ce système est intéressant en soi en raison de la dimensionnalité mixte 0D-1D. Le potentiel atome-ion est modélisé par une interaction à portée nulle tout au cours de ce travail. Par la suite, nous traitons un problème similaire mais dans le cas d'une particule dans un piège harmonique décrivant un piège de Paul. Enfin, nous généralisons l'étude du micromouvement à un système modèle 3D avec un ion dans un piège de Paul sphérique 3D et un atome lourd au centre du piège. Nous discutons de l'influence du micromouvement en vue d'applications potentielles de ce système telle que la porte logique de phase

    Individuality of Fingerprints: Comparison of Models and Measurements Abstract

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    Over a hundred years, several attempts have been made to quantitatively establish the degree of individuality of fingerprints. Measurements have been made using models based on grids, ridges, fixed probabilities, relative measurements and generative distributions. This paper is a survey and assessment of various fingerprint individuality models proposed to-date. Models starting from that of Galton to recently proposed generative models are described. The models are described in terms of their attributes, similarities and differences. A detailed discussion of generative models for fingerprints, which are based on modeling the distributions of fingerprint features from a database, is given. Generative models with and without ridge information are compared. The probabilities of random correspondence arrived at by all the models are summarized. Finally, recent studies of fingerprints of twins, which strengthen the individuality argument, are discussed

    On the automatic scoring of handwritten essays

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    Automating the task of scoring handwritten student essays is a challenging problem of AI. The goal is to assign scores which are comparable to those of human scorers even though both human and machine handwriting recognition do not achieve perfect transcription. The research described is a first attempt based on coupling two AI technologies: optical handwriting recognition and automated essay scoring. The test-bed is that of essays written by children in statewide reading comprehension tests in schools. The process involves several image-level operations: removal of pre-printed matter, segmentation of handwritten text lines and extraction of words. Constraints provided by the reading passage, the question and the answer rubric help recognize handwritten words. The method of essay scoring is based on using a vector space model and a machine learning approach to learn scoring parameters from a set of human-scored samples. System performance is compared to scoring done by human raters. Testing on test-bed of 96 handwritten answers indicate that system performance is comparable to that of automatic scoring based on perfect manual transcription.
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