Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial.

BACKGROUND: The outcome of diffuse large B-cell lymphoma has been substantially improved by the addition of the anti-CD20 monoclonal antibody rituximab to chemotherapy regimens. We aimed to assess, in patients aged 18-59 years, the potential survival benefit provided by a dose-intensive immunochemotherapy regimen plus rituximab compared with standard treatment plus rituximab. METHODS: We did an open-label randomised trial comparing dose-intensive rituximab, doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone (R-ACVBP) with subsequent consolidation versus standard rituximab, doxorubicin, cyclophosphamide, vincristine, and prednisone (R-CHOP). Random assignment was done with a computer-assisted randomisation-allocation sequence with a block size of four. Patients were aged 18-59 years with untreated diffuse large B-cell lymphoma and an age-adjusted international prognostic index equal to 1. Our primary endpoint was event-free survival. Our analyses of efficacy and safety were of the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00140595. FINDINGS: One patient withdrew consent before treatment and 54 did not complete treatment. After a median follow-up of 44 months, our 3-year estimate of event-free survival was 81% (95% CI 75-86) in the R-ACVBP group and 67% (59-73) in the R-CHOP group (hazard ratio [HR] 0·56, 95% CI 0·38-0·83; p=0·0035). 3-year estimates of progression-free survival (87% [95% CI, 81-91] vs 73% [66-79]; HR 0·48 [0·30-0·76]; p=0·0015) and overall survival (92% [87-95] vs 84% [77-89]; HR 0·44 [0·28-0·81]; p=0·0071) were also increased in the R-ACVBP group. 82 (42%) of 196 patients in the R-ACVBP group experienced a serious adverse event compared with 28 (15%) of 183 in the R-CHOP group. Grade 3-4 haematological toxic effects were more common in the R-ACVBP group, with a higher proportion of patients experiencing a febrile neutropenic episode (38% [75 of 196] vs 9% [16 of 183]). INTERPRETATION: Compared with standard R-CHOP, intensified immunochemotherapy with R-ACVBP significantly improves survival of patients aged 18-59 years with diffuse large B-cell lymphoma with low-intermediate risk according to the International Prognostic Index. Haematological toxic effects of the intensive regimen were raised but manageable. FUNDING: Groupe d'Etudes des Lymphomes de l'Adulte and Amgen.

U.S.English is a salad bowl. The Representation of Regionalisms in Standard American English

American English exhibits a great dialectal diversity, easily perceived in lexicon; so that questions are raised about which regionalisms are part of the mythical SAE and which are not. A small sample of regionalisms is checked against three standard dictionaries in order to determine the role regionalisms play in SAE.

Evaluation of an intravitreal fluocinolone acetonide implant versus standard systemic therapy in noninfectious posterior uveitis.

PURPOSE: To evaluate the safety and efficacy of an intravitreal fluocinolone acetonide (FA) implant compared with standard therapy in subjects with noninfectious posterior uveitis (NIPU). DESIGN: Randomized, controlled, phase 2b/3, open-label, multicenter superiority trial. PARTICIPANTS: Subjects with unilateral or bilateral NIPU. METHODS: One hundred forty subjects received either a 0.59-mg FA intravitreal implant (n = 66) or standard of care (SOC; n = 74) with either systemic prednisolone or equivalent corticosteroid as monotherapy (> or =0.2 mg/kg daily) or, if judged necessary by the investigator, combination therapy with an immunosuppressive agent plus a lower dose of prednisolone or equivalent corticosteroid (> or =0.1 mg/kg daily). MAIN OUTCOME MEASURES: Time to first recurrence of uveitis. RESULTS: Eyes that received the FA intravitreal implant experienced delayed onset of observed recurrence of uveitis (P<0.01) and a lower rate of recurrence of uveitis (18.2% vs. 63.5%; P< or =0.01) compared with SOC study eyes. Adverse events frequently observed in implanted eyes included elevated intraocular pressure (IOP) requiring IOP-lowering surgery (occurring in 21.2% of implanted eyes) and cataracts requiring extraction (occurring in 87.8% of phakic implanted eyes). No treatment-related nonocular adverse events were observed in the implant group, whereas such events occurred in 25.7% of subjects in the SOC group. CONCLUSIONS: The FA intravitreal implant provided better control of inflammation in patients with uveitis compared with systemic therapy. Intraocular pressure and lens clarity of implanted eyes need close monitoring in patients receiving the FA intravitreal implant.

JPEG standard uniform quantization error modeling with applications to sequential and progressive operation modes

In this paper we propose a method for computing JPEG quantization matrices for a given mean square error or PSNR. Then, we employ our method to compute JPEG standard progressive operation mode definition scripts using a quantization approach. Therefore, it is no longer necessary to use a trial and error procedure to obtain a desired PSNR and/or definition script, reducing cost. Firstly, we establish a relationship between a Laplacian source and its uniform quantization error. We apply this model to the coefficients obtained in the discrete cosine transform stage of the JPEG standard. Then, an image may be compressed using the JPEG standard under a global MSE (or PSNR) constraint and a set of local constraints determined by the JPEG standard and visual criteria. Secondly, we study the JPEG standard progressive operation mode from a quantization based approach. A relationship between the measured image quality at a given stage of the coding process and a quantization matrix is found. Thus, the definition script construction problem can be reduced to a quantization problem. Simulations show that our method generates better quantization matrices than the classical method based on scaling the JPEG default quantization matrix. The estimation of PSNR has usually an error smaller than 1 dB. This figure decreases for high PSNR values. Definition scripts may be generated avoiding an excessive number of stages and removing small stages that do not contribute during the decoding process with a noticeable image quality improvement.

Building Environmental Management System for Laboratory Products Manufacturing Company according ISO 14001-standard

Tutkielman tavoitteena on rakentaa toimiva ympäristöjärjestelmä Thermo Fisher Scientific Oy:lle. Tutkimuksen tarkoituksena on myös löytää kahdelle täysin erilaiselle toiminnalle yhtenäinen ympäristöjärjestelmä, jonka avulla pystytään ottamaan huomioon molempien toimipaikkojen hieman erilaiset vaatimukset. Lisäksi tavoitteena on muodostaa ympäristöjärjestelmälle oma organisaatio, jonka avulla ympäristöjärjestelmän integrointi yrityksen prosesseihin voidaan suorittaa sujuvasti. Aluksi tutkimusongelmaa lähestytään teoreettisesta näkökulmasta,jossa tarkastellaan ympäristöjärjestelmän historiaa, rakennetta, etuja sekä ISO 14001–standardin rakennetta ja sen etenemistä ympäristöjärjestelmän rakentamisen yhteydessä aina kolmannen osapuolen sertifiointiin asti. Empiria osa alkaa alustavalla ympäristökatselmuksella, jossa selvitetään ympäristöasioiden hoidon nykytaso ja luodaan pohja koko ympäristöjärjestelmän luomiselle, jonka vankimpana perustana on ympäristöpolitiikka. Johdon hyväksymä ympäristöpolitiikka varmistaa johdon sitoutumisen järjestelmään. Ympäristöjärjestelmän toimintarakenteen muodostaminen kahdelle erilaiselle toiminnalle onnistui tutkimuksessa kiitettävästi. Se miten ympäristöjärjestelmä toimii todellisuudessa, tullaan näkemään käytännön kokemuksien yhteydessä.

Accounting system for activity standard costs formulation in ERP environment

Toiminnanohjausjärjestelmän implementointi ja sen mukanaan tuomat muutokset tuotekustannuslaskentaan asettavat haasteita yritykselle. Metallitoimialalla toimivassa yrityksessä on havaittu samat haasteet implementoitaessa SAP R/3 toiminnanohjausjärjestelmää ja sen tuotekustannuslaskentatoiminnallisuutta. SAP R/3 tuotekustannuslogiikka tarvitsee tietoa järjestelmän ulkopuolelta, minkä huomioimatta jättäminen vaikuttaa suoraan laskentatarkkuuteen. Diplomityössä kehitetään sekä standardoitu prosessi että laskentajärjestelmä, joiden avulla pystytään laskemaan tarvittavat niin toimintokustannukset eri teräspalvelukeskuksen kuormituspisteille kuin kustannustenvyörytysarvot. Lasketut arvot muodostavat tarvittavat tekijät SAP R/3 tuotekustannuslaskennan master dataan. Tavoitteena on edesauttaa läpinäkyvän kustannustiedon muodostumista. Diplomityö pohjautuu ns. vesiputousmalliin (SDLC). Ensin tunnistetaan reunaehdot ympäristöstä, jossa tuotekustannuslaskenta toteutetaan. Tämä asettaa joustamattomia komponentteja kehitettävälle laskentajärjestelmälle. Joustavat komponentit sen sijaan antavat vapautta laskentajärjestelmälle. Yhdistämällä joustamattomat ja joustavat komponentit saavutetaan järjestelmä, jolla voidaan täydentää SAP R/3 tuotekustannuslaskennan puutteellisuutta.

Suivi neurodéveloppemental à 5ans des extrêmes prématurés et détection des difficultés sur le plan des fonctions exécutives [Detection of executive function disorders with a standard neurodevelopmental follow-up of premature children].

INTRODUCTION: A significant proportion of prematurely born children encounter behavioral difficulties, such as attention deficit or hyperactivity, which could be due to executive function disorders. AIMS: To examine whether the standard neurodevelopmental assessment offered to premature children in Switzerland recognizes executive function disorders. METHODS: The study population consisted of 49 children born before 29 weeks of gestation who were examined between 5 and 6 years of age with a standard assessment, with additional items to assess executive functioning. Children with severe neurodevelopmental impairment were excluded (mental retardation, cerebral palsy, autism). Standard assessment consisted in the Kaufman Assessment Battery for Children (K-ABC), which comprises three subscales: sequential processes (analysis of sequential information), simultaneous processes (global analysis of visual information), and composite mental processes (CMP) (result of the other two scales), as well as a behavioral evaluation using the standardized Strengths and Difficulties Questionnaire (SDQ). Executive functioning was assessed with tasks evaluating visual attention, divided attention, and digit memory as well as with a specialized questionnaire, the Behavior Rating Index of Executive Functions (BRIEF), which evaluates several aspects of executive function (regulation, attention, flexibility, working memory, etc). RESULTS: Children were divided according to their results on the three K-ABC scales (< or>85), and the different neuropsychological tasks assessing executive function were compared between the groups. The CMP did not differentiate children with executive difficulties, whereas a score<85 on the sequential processes was significantly associated with worse visual and divided attention. There was a strong correlation between the SDQ and the BRIEF questionnaires. For both questionnaires, children receiving psychotherapy had significantly higher results. Children who presented behavioral problems assessed with the SDQ presented significantly higher scores on the BRIEF. CONCLUSION: A detailed analysis of the standard neurodevelopmental assessment allows the identification of executive function disorders in premature children. Children who performed below 85 on the sequential processes of the K-ABC had significantly more attentional difficulties on the neuropsychological tasks and therefore have to be recognized and carefully followed. Emotional regulation had a strong correlation with behavioral difficulties, which were suitably assessed with the SDQ, recognized by the families, and treated.

Supplier Evaluation on the Standard Material and Component Markets in the Electronic Manufacturing Equipment Industry

Työn tavoitteena oli arvioida ja selvittää toimittajasuhteeseen vaikuttavia tekijöitä JOT Automation Group Oyj.n ja sen alihankkijoiden välisessä yhteistyössä ja muodostaa yrityksen kilpailukykyä parantava toimittaja-arviointiprosessi. Työssä keskityttiin tarkastelemaan yleisillä materiaali- ja komponenttimarkkinoilla toimivia toimittajia elektroniikkateollisuuden tuotantojärjestelmien valmistuksessa. Ensin tutustuttiin toimittajasuhdetta ja sen arviointia käsitelleeseen kirjallisuuteen. Teorian tueksi tehtiin haastatteluja ja kartoitettiin ensisijaisia tarpeita ja tavoitteita arviointiprosessille. Valmis prosessi testattiin käytännössä kahden eri case-esimerkin avulla. Prosessista muodostui kahteen eri työkaluun jakautunut kokonaisuus, joista auditointi arvioi toimittajan kyvykkyyttä vastatta sille asetettuihin vaatimuksiin. Toimittajan suorituskyvyn mittaaminen puolestaan testaa ja vertaa jatkuvasti toiminnan todellista tasoa auditoinnissa saatuihin tuloksiin. Työ sisältää selvityksen ja ohjeistuksen toimittaja-arviointiprosessin käytöstä. Prosessin käyttö alentaa toimittajaan kohdistuvaa materiaalien saatavuuteen ja hankintaan liittyviä riskejä. Esimerkeistä saadut kokemukset osoittivat, että prosessin avulla päästään pureutumaan tärkeisiin ydinalueisiin ja kehittämään niitä sekä toimittajalle, että ostajayritykselle edullisella tavalla. Toimittaja-arviointiprosessista kehittyy toimintatapa yrityksen ja sen toimittajan välisen suhteen ylläpitämiseksi.

Two cilengitide regimens in combination with standard treatment for patients with newly diagnosed glioblastoma and unmethylated MGMT gene promoter: results of the open-label, controlled, randomized phase II CORE study.

BACKGROUND: Survival outcomes for patients with glioblastoma remain poor, particularly for patients with unmethylated O(6)-methylguanine-DNA methyltransferase (MGMT) gene promoter. This phase II, randomized, open-label, multicenter trial investigated the efficacy and safety of 2 dose regimens of the selective integrin inhibitor cilengitide combined with standard chemoradiotherapy in patients with newly diagnosed glioblastoma and an unmethylated MGMT promoter. METHODS: Overall, 265 patients were randomized (1:1:1) to standard cilengitide (2000 mg 2×/wk; n = 88), intensive cilengitide (2000 mg 5×/wk during wk 1-6, thereafter 2×/wk; n = 88), or a control arm (chemoradiotherapy alone; n = 89). Cilengitide was administered intravenously in combination with daily temozolomide (TMZ) and concomitant radiotherapy (RT; wk 1-6), followed by TMZ maintenance therapy (TMZ/RT→TMZ). The primary endpoint was overall survival; secondary endpoints included progression-free survival, pharmacokinetics, and safety and tolerability. RESULTS: Median overall survival was 16.3 months in the standard cilengitide arm (hazard ratio [HR], 0.686; 95% CI: 0.484, 0.972; P = .032) and 14.5 months in the intensive cilengitide arm (HR, 0.858; 95% CI: 0.612, 1.204; P = .3771) versus 13.4 months in the control arm. Median progression-free survival assessed per independent review committee was 5.6 months (HR, 0.822; 95% CI: 0.595, 1.134) and 5.9 months (HR, 0.794; 95% CI: 0.575, 1.096) in the standard and intensive cilengitide arms, respectively, versus 4.1 months in the control arm. Cilengitide was well tolerated. CONCLUSIONS: Standard and intensive cilengitide dose regimens were well tolerated in combination with TMZ/RT→TMZ. Inconsistent overall survival and progression-free survival outcomes and a limited sample size did not allow firm conclusions regarding clinical efficacy in this exploratory phase II study.

PROTETOR SOLAR DIMINUI A INCIDÊNCIA DAS PODRIDÕES ‘OLHO-D-BOI’ E ‘BRANCA’ EM MAÇÃS ‘FUJI STANDARD’ E ‘PINK LADY’

RESUMO A podridão-olho-de-boi (Cryptosporiosis perennans) e a podridão-branca (Botryosphaeria dothidea) estão entre as principais doenças de verão da macieira no Brasil. O objetivo deste trabalho foi avaliar o efeito de uma película protetora constituída de cera de carnaúba e argilas (Raynox® ), nas doses de 2,5 e 5,0%, na infecção por C. perennans e por B. dothidea em maçãs das cultivares Fuji Standard e Pink Lady. As macieiras foram pulverizadas cinco vezes de dezembro de 2007 a março de 2008, conforme previsão de condições adequadas para ocorrência dos danos e crescimento dos frutos. Na colheita, as maçãs foram inoculadas com os dois patógenos e avaliadas quanto à incidência das podridões. Indiferente à dose, o uso de Raynox® reduziu a incidência da podridão-branca e da podridão-olho-de-boi em 67% e 42% na ‘Fuji Standard’, e 43% e 42% na ‘Pink Lady’, respectivamente. O incremento da dose aumentou a eficiência do produto para o controle da podridão-olho-de-boi. Na dose de 2,5%, o controle da podridão-olho-de-boi foi de 19% e 20%, respectivamente, em maçãs ‘Fuji Standard’ e ‘Pink Lady’, enquanto para as mesmas cultivares, mas com a dose de 5,0%, estes valores foram de 65% e 63%. Mais estudos são necessários para o ajuste de dose e critérios de aplicação para que o protetor solar possa ser recomendado.