912 resultados para Boost
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Dentro del Proyecto Ager Tarraconensis, se han estudiado en el Camp de Tarragona 19 yacimientos con indicios de instalaciones de producción de aceite o vino, que se centran especialmente entre los siglos I a.C. y II d.C. También se han estudiado 22 yacimientos con indicios de alfarería, en siete de los cuales se conoce la producción de ánforas vinarias. El hallazgo de diversas marcas de alfarero dónde identificamos el nombre de M. Clodius Martialis apunta hacia una rica familia de la elite de Tarraco, con la que se han relacionado cuatro yacimientos y quizás un quinto. Entre la época de Augusto y el siglo III, el vino se confirma como el producto principal de una agricultura desarrollada dentro del sistema de la villa, enfocada al mercado de ultramar. El aceite se debió producir para el consumo local. Esta región no volvió a potenciar la producción de vino a nivel de gran negocio de ámbito internacional hasta el siglo XVIII, con el cual se establece una comparación.
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Aim: One standard option in the treatment of stage IIIA/N2 NSCLC is neoadjuvant chemotherapy followed by surgery. We investigated in a randomized trial whether the addition of neoadjuvant radiotherapy would improve the outcome. Here we present the final results of this study. Methods: Patients (pts.) with pathologically proven, resectable stage IIIA/N2 NSCLC, performance status 0-1, and adequate organ function were randomized 1:1 to chemoradiation (CRT) with 3 cycles of neoadjuvant chemotherapy (cisplatin 100 mg/m2 and docetaxel 85 mg/m2 d1, q3weeks) followed by accelerated concomitant boost radiotherapy (RT) with 44 Gy in 22 fractions in 3 weeks, or neoadjuvant chemotherapy alone (CT), with subsequent surgery for all pts. The primary endpoint was event-free survival (EFS). Results: 232 pts. were randomized in 23 centers, the median follow-up was 53 months. Two thirds were men, median age was 60 years (range 37-76). Histology was squamous cell in 33%, adenocarcinoma in 43%. Response rate to CRT was 61% vs. 44% with CT. 85% of all pts. underwent surgery, 30-day postoperative mortality was 1%. The rate of complete resection was 91% (CRT) vs. 81% (CT) and the pathological complete remission (pCR) rate was 16% vs. 12%. The median EFS was 13.1 months (95% CI 9.9 - 23.5) for the CRT group vs. 11.8 months (95% CI 8.4 - 15.2) in the CT arm (p 0.665). The median overall survival (OS) with CRT was 37.1 months (95% CI 22.6 -50), with CT 26.1 months ( 95% CI 26.1 - 52.1, p 0.938). The local failure rate was 23% in both arms. In the CT arm 12 pts. were given postoperative radiotherapy (PORT) for R1 resection, 6 pts. received PORT in violation of the protocol. Pts. with a pCR, mediastinal downstaging to ypN0/1 and complete resection had a better outcome. Toxicity of chemotherapy was substantial, especially febrile neutropenia was common, whereas RT was well tolerated. Conclusions: This is the first completed phase III trial to evaluate the role of induction chemoradiotherapy and surgery, in comparison to neoadjuvant CT alone followed by surgery. RT was active, it increased response, complete resection and pCR rates. However, this failed to translate into an improvement of local control, EFS or OS. Notably, surgery after induction treatment was safe, including pneumonectomy. The overall survival rates of our neoadjuvant regimen are very encouraging, especially for a multicenter setting. Disclosure: M. Pless: Advisory Board for Sanofi; R. Cathomas: Advisory Board Sanofi D.C. Betticher: Advisory Board Sanofi. All other authors have declared no conflicts of interest.
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BACKGROUND: Postoperative hemithoracic radiotherapy has been used to treat malignant pleural mesothelioma, but it has not been assessed in a randomised trial. We assessed high-dose hemithoracic radiotherapy after neoadjuvant chemotherapy and extrapleural pneumonectomy in patients with malignant pleural mesothelioma. METHODS: We did this phase 2 trial in two parts at 14 hospitals in Switzerland, Belgium, and Germany. We enrolled patients with pathologically confirmed malignant pleural mesothelioma; resectable TNM stages T1-3 N0-2, M0; WHO performance status 0-1; age 18-70 years. In part 1, patients were given three cycles of neoadjuvant chemotherapy (cisplatin 75 mg/m(2) and pemetrexed 500 mg/m(2) on day 1 given every 3 weeks) and extrapleural pneumonectomy; the primary endpoint was complete macroscopic resection (R0-1). In part 2, participants with complete macroscopic resection were randomly assigned (1:1) to receive high-dose radiotherapy or not. The target volume for radiotherapy encompassed the entire hemithorax, the thoracotomy channel, and mediastinal nodal stations if affected by the disease or violated surgically. A boost was given to areas at high risk for locoregional relapse. The allocation was stratified by centre, histology (sarcomatoid vs epithelioid or mixed), mediastinal lymph node involvement (N0-1 vs N2), and T stage (T1-2 vs T3). The primary endpoint of part 1 was the proportion of patients achieving complete macroscopic resection (R0 and R1). The primary endpoint in part 2 was locoregional relapse-free survival, analysed by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00334594. FINDINGS: We enrolled patients between Dec 7, 2005, and Oct 17, 2012. Overall, we analysed 151 patients receiving neoadjuvant chemotherapy, of whom 113 (75%) had extrapleural pneumonectomy. Median follow-up was 54·2 months (IQR 32-66). 52 (34%) of 151 patients achieved an objective response. The most common grade 3 or 4 toxic effects were neutropenia (21 [14%] of 151 patients), anaemia (11 [7%]), and nausea or vomiting (eight [5%]). 113 patients had extrapleural pneumonectomy, with complete macroscopic resection achieved in 96 (64%) of 151 patients. We enrolled 54 patients in part 2; 27 in each group. The main reasons for exclusion were patient refusal (n=20) and ineligibility (n=10). 25 of 27 patients completed radiotherapy. Median total radiotherapy dose was 55·9 Gy (IQR 46·8-56·0). Median locoregional relapse-free survival from surgery, was 7·6 months (95% CI 4·5-10·7) in the no radiotherapy group and 9·4 months (6·5-11·9) in the radiotherapy group. The most common grade 3 or higher toxic effects related to radiotherapy were nausea or vomiting (three [11%] of 27 patients), oesophagitis (two [7%]), and pneumonitis (two [7%]). One patient died of pneumonitis. We recorded no toxic effects data for the control group. INTERPRETATION: Our findings do not support the routine use of hemithoracic radiotherapy for malignant pleural mesothelioma after neoadjuvant chemotherapy and extrapleural pneumonectomy. FUNDING: Swiss Group for Clinical Cancer Research, Swiss State Secretariat for Education, Research and Innovation, Eli Lilly.
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BACKGROUND: Recombinant adenovirus serotype 5 (rAd5)-vectored HIV-1 vaccines have not prevented HIV-1 infection or disease and pre-existing Ad5 neutralizing antibodies may limit the clinical utility of Ad5 vectors globally. Using a rare Ad serotype vector, such as Ad35, may circumvent these issues, but there are few data on the safety and immunogenicity of rAd35 directly compared to rAd5 following human vaccination. METHODS: HVTN 077 randomized 192 healthy, HIV-uninfected participants into one of four HIV-1 vaccine/placebo groups: rAd35/rAd5, DNA/rAd5, and DNA/rAd35 in Ad5-seronegative persons; and DNA/rAd35 in Ad5-seropositive persons. All vaccines encoded the HIV-1 EnvA antigen. Antibody and T-cell responses were measured 4 weeks post boost immunization. RESULTS: All vaccines were generally well tolerated and similarly immunogenic. As compared to rAd5, rAd35 was equally potent in boosting HIV-1-specific humoral and cellular immunity and responses were not significantly attenuated in those with baseline Ad5 seropositivity. Like DNA, rAd35 efficiently primed rAd5 boosting. All vaccine regimens tested elicited cross-clade antibody responses, including Env V1/V2-specific IgG responses. CONCLUSIONS: Vaccine antigen delivery by rAd35 is well-tolerated and immunogenic as a prime to rAd5 immunization and as a boost to prior DNA immunization with the homologous insert. Further development of rAd35-vectored prime-boost vaccine regimens is warranted.
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The effect of intramyocellular lipids (IMCLs) on endurance performance with high skeletal muscle glycogen availability remains unclear. Previous work has shown that a lipid-supplemented high-carbohydrate (CHO) diet increases IMCLs while permitting normal glycogen loading. The aim of this study was to assess the effect of fat supplementation on fat oxidation (Fox) and endurance performance. Twenty-two trained male cyclists performed 2 simulated time trials (TT) in a randomized crossover design. Subjects cycled at ∼53% maximal voluntary external power for 2 h and then followed 1 of 2 diets for 2.5 days: a high-CHO low-fat (HC) diet, consisting of CHO 7.4 g·kg(-1)·day(-1) and fat 0.5 g·kg(-1)·day(-1); or a high-CHO fat-supplemented (HCF) diet, which was a replication of the HC diet with ∼240 g surplus fat (30% saturation) distributed over the last 4 meals of the diet period. On trial morning, fasting blood was sampled and Fox was measured during an incremental exercise; a ∼1-h TT followed. Breath volatile compounds (VOCs) were measured at 3 time points. Mental fatigue, measured as reaction time, was evaluated during the TT. Plasma free fatty acid concentration was 50% lower after the HCF diet (p < 0.0001), and breath acetone was reduced (p < 0.05) "at rest". Fox peaked (∼0.35 g·kg(-1)) at ∼42% peak oxygen consumption, and was not influenced by diet. Performance was not significantly different between the HCF and HC diets (3369 ± 46 s vs 3398 ± 48 s; p = 0.39), nor were reaction times to the attention task and VOCs (p = NS for both). In conclusion, the short-term intake of a lipid supplement in combination with a glycogen-loading diet designed to boost intramyocellular lipids while avoiding fat adaptation did not alter substrate oxidation during exercise or 1-hour cycling performance.
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Simple Heuristics in a Social World invites readers to discover the simple heuristics that people use to navigate the complexities and surprises of environments populated with others. The social world is a terrain where humans and other animals compete with conspecifics for myriad resources, including food, mates, and status, and where rivals grant the decision maker little time for deep thought, protracted information search, or complex calculations. Yet, the social world also encompasses domains where social animals such as humans can learn from one another and can forge alliances with one another to boost their chances of success. According to the book's thesis, the undeniable complexity of the social world does not dictate cognitive complexity as many scholars of rationality argue. Rather, it entails circumstances that render optimization impossible or computationally arduous: intractability, the existence of incommensurable considerations, and competing goals. With optimization beyond reach, less can be more. That is, heuristics--simple strategies for making decisions when time is pressing and careful deliberation an unaffordable luxury--become indispensible mental tools. As accurate as or even more accurate than complex methods when used in the appropriate social environments, these heuristics are good descriptive models of how people make many decisions and inferences, but their impressive performance also poses a normative challenge for optimization models. In short, the Homo socialis may prove to be a Homo heuristicus whose intelligence reflects ecological rather than logical rationality.
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Abstract Objective: To perform a comparative dosimetric analysis, based on computer simulations, of temporary balloon implants with 99mTc and balloon brachytherapy with high-dose-rate (HDR) 192Ir, as boosts to radiotherapy. We hypothesized that the two techniques would produce equivalent doses under pre-established conditions of activity and exposure time. Materials and Methods: Simulations of implants with 99mTc-filled and HDR 192Ir-filled balloons were performed with the Siscodes/MCNP5, modeling in voxels a magnetic resonance imaging set related to a young female. Spatial dose rate distributions were determined. In the dosimetric analysis of the protocols, the exposure time and the level of activity required were specified. Results: The 99mTc balloon presented a weighted dose rate in the tumor bed of 0.428 cGy.h-1.mCi-1 and 0.190 cGyh-1.mCi-1 at the balloon surface and at 8-10 mm from the surface, respectively, compared with 0.499 and 0.150 cGyh-1.mCi-1, respectively, for the HDR 192Ir balloon. An exposure time of 24 hours was required for the 99mTc balloon to produce a boost of 10.14 Gy with 1.0 Ci, whereas only 24 minutes with 10.0 Ci segments were required for the HDR 192Ir balloon to produce a boost of 5.14 Gy at the same reference point, or 10.28 Gy in two 24-minutes fractions. Conclusion: Temporary 99mTc balloon implantation is an attractive option for adjuvant radiotherapy in breast cancer, because of its availability, economic viability, and similar dosimetry in comparison with the use of HDR 192Ir balloon implantation, which is the current standard in clinical practice.
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Les mécanismes qui régulent le processus de guérison de la peau lésée ne sont pas entièrement compris. Nous avons précédemment montré que les cellules dendritiques plasmocytoïdes (pDCs) sont normalement absentes de la peau saine mais infiltrent rapidement la peau humaine ainsi que celle des souris après une blessure cutanée. Après avoir infiltré la peau, ces pDCs sont capables de détecter les acides nucléiques par l'expression des récepteurs de type Toll 7 et 9 ce qui les active à produire de 1' interféron (IFN) de type I. Ce processus est primordial pour la re- épithélisation des blessures cutanées. Cependant, les mécanismes conduisant à l'infiltration et à 1'activation des pDCs restent inconnus. Dans notre projet, nous montrons que la chimiokine CxcllO est responsable de l'infiltration des pDCs. De façon importante, nous démontrons que les neutrophiles qui infiltrent également la peau lésée sont la source majeure de cette chimiokine. La déplétion des neutrophiles abolit d'ailleurs le recrutement des pDCs confirmant ainsi que CxcllO produit par les neutrophiles est responsable de l'infiltration des pDCs dans la peau endommagée. De façon intéressante, nous avons trouvé que CxcllO en plus de son activité chimiotactique, est capable de former des complexes avec l'ADN et d'activer ainsi les pDCs à produire de l'IFN de type I. De plus, nous avons observé que les neutrophiles qui infiltrent la peau forment des Neutrophil Extracellular Traps (NETs). Ces NETs sont constitués de filaments extracellulaires d'ADN recouverts par de nombreuses protéines principalement d'origine granulaire. D'une manière frappante, le blocage de la NETose ou l'utilisation de souris déficientes pour la formation de NETs altère le recrutement et l'activation des pDCs ainsi que la réponse inflammatoire qui en découle ainsi que le processus de re-epithélisation qui s'ensuit. En prenant en compte toutes ces données, nos résultats démontrent que suite à une blessure de la peau, les neutrophiles par la production de CxcllO contrôlent l'infiltration des pDCs dans la peau lésée et par la formation de NETs, promeuvent l'activation des pDCs. Notre étude fournit donc de nouvelles informations sur les mécanismes de guérison de la peau et ouvre de nouvelles perspectives thérapeutiques quant à la réparation tissulaire de la peau soit dans le but de l'amplifier ou de l'inhiber. -- The mechanisms that regulate healing of the injured skin are not well understood. We have previously shown that plasmacytoid dendritic cells (pDCs) are normally absent from the healthy skin, but rapidly infiltrate both murine and human skin upon injury. Upon skin infiltration, pDCs sense nucleic acids via TLR7/TLR9 and are activated to produce type I interferon (IFN), a process that is crucial for re-epithelialisation of skin wounds. However, the mechanisms that drive pDCs recruitment and activation in injured skin remain unclear. We show that CxcllO is responsible for pDCs infiltration. Importantly, we demonstrate that skin infiltrating neutrophils are the major source of this chemokine. Neutrophils depletion completely abrogated pDCs recruitment confirming that CxcllO- driven pDCs recruitment is controlled by neutrophils. Interestingly, CxcllO was also found to form complexes with DNA and to activate pDCs to produce Type I IFN in addition to its chemotactic activity. Moreover, we observed that infiltrating neutrophils release Neutrophils Extracellular Traps (NETs) composed of DNA filaments decorated with neutrophils-derived proteins. Strikingly, blocking NETosis or using mice deficient for NETs production impaired pDCs recruitment and activation as well as the subsequent inflammatory response and the re-epithelialisation process. Altogether, these data demonstrate that upon skin injury, neutrophils control pDCs infiltration into the injured skin by the release of CxcllO and via the production of NETs, they allow complex formation between CxcllO and NET-DNA leading to pDCs activation. Our findings provide new insights into the mechanisms of wound healing and open new avenues for potential therapeutic interventions to boost or inhibit wound repair in the skin.
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L’objectiu general d’aquest treball és definir les competències i limitacions del perfil del gestor del patrimoni cultural en el context de nous projectes de gestió del patrimoni que tenen l’objectiu de dinamitzar econòmica i socialment el territori. Per a fer-ho es parteix de l’avaluació del paper del gestor patrimonial en un projecte concret de recuperació d’oficis
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Kiristyvät markkinat ajavat yritykset tehostamaan toimintaansa. Suorituskyvyn mittaaminen on jo olennainen osa suomalaista yrityskulttuuria. Mittaamisen päätehtävä on tuottaa yritysjohdolle relevanttia informaatiota yrityksen tilasta ja auttaa valvomaan ja kehittämään toimintaa. Tämän tutkimuksen kohteena on palvelukonsernin Iiiketoimintayksikön suorituskyvyn mittaaminen. Tutkimuksen päätavoitteina on 1. valita palvelukonsernin liiketoimintayksikölle sopiva suorituskyvyn mittausjärjestelmä, 2. valita käytännöllinen implementointimalli sekä 3. laatia suorituskykymittaristo palvelukonsernin liiketoimintayksikölle. Tämä tutkimus jakautuu kahteen vaiheeseen. Ensimmäisessä vaiheessa tutkimuksen kohteena on suorituskyvyn teoria ja neljä erilaista mittausmenetelmää, joista valitaan yksi Iiiketoimintayksikön suorituskyvyn mittausjärjestelmäksi sekä syvempää tarkastelua varten. Tutkimuksen toisessa vaiheessa tutkitaan valitun mittausjärjestelmän ominaisuuksia strategisena johtamisjärjestelmänä sekä sen implementointimalleja. Toisen vaiheen keskeisin tutkimusosuus on suorituskykymittausjärjestelmän laadinta. Työn lopputuloksena syntyy palvelukonsernin Iiiketoimintayksikön suorituskyvyn mittausjärjestelmä sekä jatkotoimenpide-ehdotus Balanced Scorecardin laajentamiseksi Iiiketoimialan ohjausjärjestelmäksi.
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Hyötysuhteen merkitys tehoelektroniikan järjestelmissä kasvaa jatkuvasti kun käytössä olevien järjestelmien määrä lisääntyy ja toisaalta energian hinta kallistuu. Hyötysuhteen lisäksi verkkovirran käyrämuotovaatimukset asettavat omat haasteensa sähköverkkoon liitettävien tehoelektroniikkajärjestelmien suunnittelulle. Tässä työssä tutkitaan häviöiden syntyyn vaikuttavia tekijöitä hakkuriteholähteissä ja pyritään löytämään keinoja hyötysuhteen parantamiseksi. Työssä analysoidaan 300 W – 2 kW tehoalueelle soveltuvat, tehokerroinkorjattujen AC/DC-hakkuriteholähteiden topologiavaihtoehdot ja arvioidaan niiden soveltuvuutta tavanomaisen boost-topologian korvaajaksi. Tarkastelussa otetaan huomioon kustannukset, toimivuus sekä saavutettu hyötysuhteen parantuminen verrattuna perinteisellä topologialla toteutettuun teholähteeseen. Tarkasteltavat topologiat valitaan kirjallisuustutkimuksen perusteella. Valittujen topologioiden häviöt ja hyötysuhde selvitetään analyyttisin menetelmin sekä simuloimalla. Käytännön testausta varten suunnitellaan ja rakennetaan prototyyppi valitusta topologiasta.
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Diplomityö on osa KaskiTec 2010 projektia. Työn tavoitteena oli tehostaa Lametal Oy:n hitsausrobotin käyttöä. Tehostamisella pyrittiin robotin käyttöasteen ja tuottavuuden kohottamiseen ja sitä kautta parantamaan investoinnin kannattavuutta. Työ on jaettu teoriaosaan ja soveltavaan osaan. Teoriaosassa käsitellään yleisesti robottihitsausta ja hitsauksen tuottavuutta. Lähdeaineistona on käytetty alan kirjallisuutta. Soveltavassa osassa käsitellään työn käytännön osuutta yrityksessä. Työn alkuvaiheessa kartoitettiin yrityksen lähtötilanne, selvitettiin pahimmat ongelmakohdat ja etsittiin ongelmiin parannuskeinoja. Tutkimusmenetelminä yrityksessä käytettiin havainnointia, henkilöhaastatteluita sekä tilastollisia ja laskennallisia menetelmiä. Seurattavaksi valittiin tuottavuuden tunnuslukuja, joiden perusteella voitiin arvioida tehostamistoimenpiteiden vaikutuksia. Yrityksessä kartoitettujen ongelmien perusteella ryhdyttiin nostamaan robotin käyttöastetta, kehittämään tuotannonohjausta, robotin materiaalivirtoja ja layoutia. Käyttöastetta nostettiin viemällä robotille uusia hitsattavia tuotteita. Työssä selvitettiin yrityksessä jo olemassa oleva tuotannonohjausjärjestelmän soveltuvuus hitsausrobotin ohjaukseen. Materiaalivirtojen sujuvuutta ja layoutia kehitettiin yhdessä muiden KaskiTec- projektin osapuolten kanssa.
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Peering into the field of Alzheimer's disease (AD), the outsider realizes that many of the therapeutic strategies tested (in animal models) have been successful. One also may notice that there is a deficit in translational research, i.e., to take a successful drug in mice and translate it to the patient. Efforts are still focused on novel projects to expand the therapeutic arsenal to 'cure mice.' Scientific reasons behind so many successful strategies are not obvious. This article aims to review the current approaches to combat AD and to open a debate on common mechanisms of cognitive enhancement and neuroprotection. In short, either the rodent models are not good and should be discontinued, or we should extract the most useful information from those models. An example of a question that may be debated for the advancement in AD therapy is: In addition to reducing amyloid and tau pathologies, would it be necessary to boost synaptic strength and cognition? The debate could provide clues to turn around the current negative output in generating effective drugs for patients. Furthermore, discovery of biomarkers in human body fluids, and a clear distinction between cognitive enhancers and disease modifying strategies, should be instrumental for advancing in anti-AD drug discovery.
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The aim of the thesis is to devise a framework for analyzing simulation games, in particular introductory supply chain simulation games which are used in education and process development. The framework is then applied to three case examples which are introductory supply chain simulation games used at Lappeenranta University of Technology. The theoretical part of the thesis studies simulation games in the context of education and training as well as of process management. Simulation games can be seen as learning processes which comprise of briefing, micro cycle, and debriefing which includes observation and reflection as well as conceptualization. The micro cycle, i.e. the game itself, is defined through elements and characteristics. Both briefing and debriefing ought to support the micro cycle. The whole learning process needs to support learning objectives of the simulation game. Based on the analysis of the case simulation games, suggestions on how to boost the debriefing and promote long term effects of the games are made. In addition, a framework is suggested to be used in designing simulation games and characteristics of introductory supply chain simulation games are defined. They are designed for general purposes, are simple and operated manually, are multifunctional interplays, and last about 2.5 4 hours. Participants co operate during a game run and competition arises between different runs or game sessions.
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Metaheuristic methods have become increasingly popular approaches in solving global optimization problems. From a practical viewpoint, it is often desirable to perform multimodal optimization which, enables the search of more than one optimal solution to the task at hand. Population-based metaheuristic methods offer a natural basis for multimodal optimization. The topic has received increasing interest especially in the evolutionary computation community. Several niching approaches have been suggested to allow multimodal optimization using evolutionary algorithms. Most global optimization approaches, including metaheuristics, contain global and local search phases. The requirement to locate several optima sets additional requirements for the design of algorithms to be effective in both respects in the context of multimodal optimization. In this thesis, several different multimodal optimization algorithms are studied in regard to how their implementation in the global and local search phases affect their performance in different problems. The study concentrates especially on variations of the Differential Evolution algorithm and their capabilities in multimodal optimization. To separate the global and local search search phases, three multimodal optimization algorithms are proposed, two of which hybridize the Differential Evolution with a local search method. As the theoretical background behind the operation of metaheuristics is not generally thoroughly understood, the research relies heavily on experimental studies in finding out the properties of different approaches. To achieve reliable experimental information, the experimental environment must be carefully chosen to contain appropriate and adequately varying problems. The available selection of multimodal test problems is, however, rather limited, and no general framework exists. As a part of this thesis, such a framework for generating tunable test functions for evaluating different methods of multimodal optimization experimentally is provided and used for testing the algorithms. The results demonstrate that an efficient local phase is essential for creating efficient multimodal optimization algorithms. Adding a suitable global phase has the potential to boost the performance significantly, but the weak local phase may invalidate the advantages gained from the global phase.