Reduced-basis Output Bound Methods for Parametrised Partial Differential Equations

An efficient and reliable method for the prediction of outputs of interest of partial differential equations with affine parameter dependence is presented. To achieve efficiency we employ the reduced-basis method: a weighted residual Galerkin-type method, where the solution is projected onto low-dimensional spaces with certain problem-specific approximation properties. Reliability is obtained by a posteriori error estimation methods - relaxations of the standard error-residual equation that provide inexpensive but sharp and rigorous bounds for the error in outputs of interest. Special affine parameter dependence of the differential operator is exploited to develop a two-stage off-line/on-line blackbox computational procedure. In the on-line stage, for every new parameter value, we calculate the output of interest and an associated error bound. The computational complexity of the on-line stage of the procedure scales only with the dimension of the reduced-basis space and the parametric complexity of the partial differential operator; the method is thus ideally suited for the repeated and rapid evaluations required in the context of parameter estimation, design, optimization, and real-time control. The theory and corroborating numerical results are presented for: symmetric coercive problems (e.g. problems in conduction heat transfer), parabolic problems (e.g. unsteady heat transfer), noncoercive problems (e.g. the reduced-wave, or Helmholtz, equation), the Stokes problem (e.g flow of highly viscous fluids), and certain nonlinear equations (e.g. eigenvalue problems)

A phase I clinical and pharmacological study evaluating vinflunine in combination with doxorubicin as first line treatment in metastatic breast cancer

Vinfunine (VFL) is a novel bifluorinated tubulin-targeted agent of the vinca alkaloids class active in advanced stage breast cancer. We conducted a phase I study combining VFL with doxorubicin (DXR) to define the recommended dose (RD), safety, pharmacokinetic (PK) interaction and efficacy. Two schedules (day 1 every 3weeks; days 1 and 8 every 3weeks) were investigated as first line chemotherapy in metastatic breast cancer patients. Thirty-two patients received a total of 162 cycles of the VFL-DXR combination (median 6). The RDs were VFL 250mg/m2/DXR 40mg/m2 every 3weeks for schedule 1 and VFL 120mg/m2/DXR 25mg/m2 days 1 and 8 every 3weeks for schedule 2. The main dose-limiting toxicity was neutropenia. The most frequent non-hematological adverse events were nausea, fatigue, constipation, vomiting, anorexia, stomatitis and dyspnea. Objective response rate was reached in 47.1% of the patients. No PK interaction was observed. VFL-DXR combination is feasible with manageable toxicity. The antitumor activity was promising and supports further evaluatio

Fungal and Bacterial Loads: Noninvasive Inflammatory Bowel Disease Biomarkers for the Clinical Setting

Malaltia inflamatòria intestinal; Càrrega microbiana; PrediccióEnfermedad inflamatoria intestinal; Carga microbiana; PredicciónInflammatory bowel disease; Microbial load; PredictionMicrobiome sequence data have been used to characterize Crohn's disease (CD) and ulcerative colitis (UC). Based on these data, we have previously identified microbiomarkers at the genus level to predict CD and CD relapse. However, microbial load was underexplored as a potential biomarker in inflammatory bowel disease (IBD). Here, we sought to study the use of fungal and bacterial loads as biomarkers to detect both CD and UC and CD and UC relapse. We analyzed the fecal fungal and bacterial loads of 294 stool samples obtained from 206 participants using real-time PCR amplification of the ITS2 region and the 16S rRNA gene, respectively. We combined the microbial data with demographic and standard laboratory data to diagnose ileal or ileocolonic CD and UC and predict disease relapse using the random forest algorithm. Fungal and bacterial loads were significantly different between healthy relatives of IBD patients and nonrelated healthy controls, between CD and UC patients in endoscopic remission, and between UC patients in relapse and non-UC individuals. Microbial load data combined with demographic and standard laboratory data improved the performance of the random forest models by 18%, reaching an average area under the receiver operating characteristic curve (AUC) of 0.842 (95% confidence interval [CI], 0.65 to 0.98), for IBD diagnosis and enhanced CD and UC discrimination and CD and UC relapse prediction. Our findings show that fecal fungal and bacterial loads could provide physicians with a noninvasive tool to discriminate disease subtypes or to predict disease flare in the clinical setting. IMPORTANCE Next-generation sequence data analysis has allowed a better understanding of the pathophysiology of IBD, relating microbiome composition and functions to the disease. Microbiome composition profiling may provide efficient diagnosis and prognosis tools in IBD. However, the bacterial and fungal loads of the fecal microbiota are underexplored as potential biomarkers of IBD. Ulcerative colitis (UC) patients have higher fecal fungal and bacterial loads than patients with ileal or ileocolonic CD. CD patients who relapsed harbor more-unstable fungal and bacterial loads than those of relapsed UC patients. Fecal fungal and bacterial load data improved prediction performance by 18% for IBD diagnosis based solely on clinical data and enhanced CD and UC discrimination and prediction of CD and UC relapse. Combined with existing laboratory biomarkers such as fecal calprotectin and C-reactive protein (CRP), microbial loads may improve the diagnostic accuracy of IBD and of ileal CD and UC disease activity and prediction of UC and ileal CD clinical relapse.This work was funded by Instituto de Salud Carlos III, grant PI17/00614, cofinanced by the European Regional Development Fund (ERDF) and by the PERIS (SLT002/16). F. Casellas has received research funding from AbbVie, Ferring, MSD, Shire, and Zambon and speaker fees from AbbVie, Chiesi, Ferring, Gebro, MSD, Shire, Takeda, and Zambon. S. Vermeire has received grant support from AbbVie, MSD, Pfizer, J&J, and Takeda; received speaker fees from AbbVie, MSD, Takeda, Ferring, Dr. Falk Pharma, Hospira, Pfizer Inc., and Tillots; and served as a consultant for AbbVie, MSD, Takeda, Ferring, Genentech/Roche, Robarts clinical trials, Gilead, Celgene, Prometheus, Avaxia, Prodigest, Shire, Pfizer Inc, Galapagos, Mundipharma, Hospira, Celgene, Second Genome, and Janssen. C. Manichanh has received financial support for research from Danone

T0 monitoringplan voor effectmeting van VIBEG maatregelen in natura 2000 gebied Noordzeekustzone

In december 2011 is door vertegenwoordigers van de visserijsector, de natuurorganisaties en het ministerie (momenteel: Economische Zaken) het ‘VIBEG-akkoord’ gesloten. In dit akkoord wordt een ruimtelijke zonering van visserij-activiteit gegeven en is een tijdschema aangegeven voor wanneer welke maatregelen in werking treden. Voor het evalueren van de effecten van de maatregelen is monitoring nodig. Dit monitoringplan beschrijft de nulmeting voor de benodigde monitoring. Het vormt een onderdeel van de T0 bemonstering van het benthische ecosysteem in de Noordzeekustzone en Vlakte van de Raan in het kader van de Vogel- en Habitatrichtlijn. Het doel van specifiek dit onderdeel is het opstellen van een plan voor het verzamelen van een dataset waarmee later (in T1 en T2) de effecten van de ruimtelijke zonering van visserij in de Noordzeekustzone op het benthische ecosysteem in beeld kunnen worden gebracht

Discards Sampling of the Dutch and German Brown shrimp fisheries in 2009 - 2012

In the European Union the collection of discard data is enforced trough the Data Collection Regulation or Framework (DCF) of the European Commission (EC). To comply with this ruling, shrimp trawlers have been monitored since 2008 for the Netherlands and since 2006 for Germany. This report presents the information of both sampling programmes from 2009 to 2012. The initiative to describe the methods and results of the monitoring of brown shrimp fisheries in a joint report anticipates on the harmonised regional sampling of commercial fisheries as described in the DCF

Netinnovatie Kottervisserij

Als reactie op de aanlandplicht heeft de kottersector via de Coöperatieve Visserij Organisatie (CVO) het initiatief opgepakt om de selectiviteit van de vistuigen te verhogen om zo weinig mogelijk discards te vangen en aan te landen. Na een ontwerpfase met modelonderzoek in de flume tank van SINTEF te Hirtshals, Denemarken, en met ervaringen uit eerdere projecten werden op verscheidene schepen netinnovaties uitgeprobeerd. Er werd onderzoek gedaan op een schip met boomkor, verschillende schepen vissend met pulsvistuigen en op twinriggers. Hierbij werd aanvankelijk gewerkt op ‘trial-and error’ basis met in sommige gevallen zelfmonitoring. Vervolgens werden enkele uitgebreide vangst- en bijvangstvergelijkingen gedaan met medewerkers van IMARES aan boord

Long-term response to second-line afatinib in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC): Analysis of the LUX-Head & Neck 1 (LHN1) trial

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Managing cancer patients during the COVID-19 pandemic: an ESMO multidisciplinary expert consensus.

We established an international consortium to review and discuss relevant clinical evidence in order to develop expert consensus statements related to cancer management during the severe acute respiratory syndrome coronavirus 2-related disease (COVID-19) pandemic. The steering committee prepared 10 working packages addressing significant clinical questions from diagnosis to surgery. During a virtual consensus meeting of 62 global experts and one patient advocate, led by the European Society for Medical Oncology, statements were discussed, amended and voted upon. When consensus could not be reached, the panel revised statements until a consensus was reached. Overall, the expert panel agreed on 28 consensus statements that can be used to overcome many of the clinical and technical areas of uncertainty ranging from diagnosis to therapeutic planning and treatment during the COVID-19 pandemic

Effecten voor de visserij bij de aanleg van windmolenparken binnen de 12 mijlszone

In 2020 moet 16% van de Nederlandse energievoorzieing duurzaam worden opgewekt. Windenergie op zee is een van de duurzame energiebronnen die Nederland gaat gebruiken om deze doelstelling te halen. Begin 2013 is besloten om een Haalbaarheidsstudie naar de (on)mogelijkheden van windenergie binnen de 12 mijlszone uit te voeren. In deze haalbaarheidsstudie worden de mogelijke effecten op de opbrengstwaarde voor de beroeps- en recreatieve visserij - indien windmolenparken worden aangelegd binnen vijf geselecteerde zoekgebieden - in kaart gebracht