Studying the impact of a medication use evaluation for polymedicated older patients by the community pharmacist (SIMENON) : study protocol

Background: Aged polymedicated patients are particularly vulnerable for drug-related problems. A medication review aims to optimize the medication use of patients and improve health outcomes. In this study, the effect of a pharmacist-led medication use review is investigated for polymedicated ambulatory older patients with the aim of implementing this pharmaceutical care intervention across Belgium. Methods: This article describes the study protocol of the SIMENON study and reports the results of the feasibility study, which aimed to test and optimize this study protocol. In the SIMENON intervention study, 75 Belgian community pharmacies each recruit 12 patients for a medication use review. For each patient, the identified drug-related problems and subsequent interventions are registered using the PharmDISC classification. In a subset of Dutch speaking patients, a pretest-posttest single group design is used to measure the impact of this review on patient related outcomes using questionnaires. The main outcome of the study is the type and number of drug-related problems and related interventions. A second outcome is the impact of the medication use review on adherence, objectively measured with dispensing data. Evolution in medication related quality of life is another outcome, measured with the Living with Medicines Questionnaire version 3. Other patient reported outcomes include adherence, self-management, patient satisfaction, fall incidents and use of emergency healthcare services. Discussion: The findings of this study can provide data on the effectiveness of a medication use review in the Belgian primary care setting. Furthermore, it will provide insights in which patients benefit most of this intervention and therefore facilitate the implementation of medication review in Belgium

Beslissingsondersteunende systemen en besluitvorming in marketing management

Nadat eerst kort de complexiteit van de marketing-beslissingssituatie is geschetst, wordt in dit artikel een omschrijving gegeven van zogenaamde beslissingsondersteuningssystemen die een belangrijk hulpmiddel kunnen zijn bij een analytische benadering van marketingbeslissingen. Het artikel laat zien hoe in deze systemen marketingmodellen en marketinginformatiesystemen met elkaar worden geintegreerd, en gaat in op diverse aspecten, zoals het onderscheid in systemen voor strategische versus operationele beslissingen, kwantificering van modellen etc., en geeft een indeling van bestaande modellen. Er worden een aantal concrete ervaringen met deze beslissingsondersteuningssystemen vermeld en het artikel eindigt met een beschouwing over implementatie en de rol die de marktonderzoeker daarin kan spelen

LAI determination in dune vegetation: a comparison of different techniques

Research was conducted in the nature reserve De Westhoek (De Panne, Belgium) in order to determine leaf-area-index (LAI) in different dune vegetation types by both direct (destructively) and indirect optical measurements. The destructive LAI determination was conducted in herbaceous and shrub vegetation types. It was found that the LAI of herbaceous vegetation ranges between 0.87 and 4.60 and the LAI of shrub vegetation between 2.25 and 3.58. Ground-based optical determination of LAI was only conducted in the shrub vegetation, by means of the SunScan (Delta-T Devices Ltd, Cambridge, UK). This indirect LAI method systematically overestimated direct LAI. Another applied optical method is the hemispherical photography (Nikon Coolpix 5000 camera). Airborne remote sensing data are used to establish a relationship between direct LAI and some vegetation indices. Based on the above established relationship a map of the horizontal LAI distribution in the nature reserve De Westhoek will be produced

Structural and Functional Dissection of Mif2p, a Conserved DNA-binding Kinetochore Protein

Mif2p is the budding-yeast orthologue of the mammalian centromere-binding protein CENP-C. We have mapped domains of Saccharomyces cerevisiae Mif2p and studied the phenotyptic consequences of their deletion. Using chromatin immunoprecipitation (ChIP) and electrophoretic mobility shift assays, we have further shown that Mif2p binds in the CDEIII region of the budding-yeast centromere, probably in close spatial association with Ndc10p. Moreover, ChIP experiments show that Mif2p recruits to yeast kinetochores a substantial subset of inner and outer kinetochore proteins, but not the Ndc80 or Spc105 complexes. We have determined the crystal structure of the C-terminal, dimerization domain of Mif2p. It has a "cupin" fold, extremely similar both in polypeptide chain conformation and in dimer geometry to the dimerization domain of a bacterial transcription factor. The Mif2p dimer seems to be part of an enhanceosome-like structure that nucleates kinetochore assembly in budding yeast.Molecular and Cellular Biolog

Robust Model-Checking of Linear-Time Properties in Timed Automata

International audienceFormal verification of timed systems is well understood, but their \emphimplementation is still challenging. Recent works by Raskin \emphet al. have brought out a model of parameterized timed automata that can be used to prove \emphimplementability of timed systems for safety properties. We define here a more general notion of robust model-checking for linear-time properties, which consists in verifying whether a property still holds even if the transitions are slightly delayed or expedited. We provide PSPACE algorithms for the robust model-checking of Büchi-like and LTL properties. We also verify bounded-response-time properties

PARP inhibitor efficacy depends on CD8+ T cell recruitment via intratumoral STING pathway activation in BRCA-deficient models of triple-negative breast cancer.

Combinatorial clinical trials of PARP inhibitors with immunotherapies are ongoing, yet the immunomodulatory effects of PARP inhibition have been incompletely studied. Here, we sought to dissect the mechanisms underlying PARP inhibitor-induced changes in the tumor microenvironment of BRCA1-deficient triple-negative breast cancer (TNBC). We demonstrate that the PARP inhibitor olaparib induces CD8+ T cell infiltration and activation in vivo, and that CD8+ T cell depletion severely compromises anti-tumor efficacy. Olaparib-induced T cell recruitment is mediated through activation of the cGAS/STING pathway in tumor cells with paracrine activation of dendritic cells and is more pronounced in HR-deficient compared to HR-proficient TNBC cells and in vivo models. CRISPR-knockout of STING in cancer cells prevents proinflammatory signaling and is sufficient to abolish olaparib-induced T cell infiltration in vivo. These findings elucidate an additional mechanism of action of PARP inhibitors and provide rationale for combining PARP inhibition with immunotherapies for the treatment of TNBC