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Sofie De Leeuw De Sint-Leonarduskerk van Zoutleeuw: kunstschrijn van Brabant.Dat de indrukwekkende sacramentstoren van Zoutleeuw maar één van de vele kunstschatten is van de rijke Sint-Leonarduskerk, wordt door Sofie De Leeuw kort geschetst.Dieter Nuytten De inventie van de sacramentstoren van Zoutleeuw: het oeuvre van Cornelis Floris en de artistieke Nederlanden tijdens de renaissance in de 16de eeuw. [The invention of the Zoutleeuw sacrament tower and the works of Cornelis Floris in the Low Countries art history of 16th century renaissance.]Dieter Nuytten situeert de sacramentstoren van Cornelis Floris binnen de noordelijke renaissance van de 16de eeuw en in het artistieke oeuvre van deze kunstenaar. Cornelis Floris als echte duivel-doet-al, toen uomo universalis genoemd, overschreed met ogenschijnlijk gemak de grenzen van de tot dan toe nauw omschreven ambachten en waagde zich zonder schroom zowel aan architectuur als aan tekeningen, drukwerken en beeldhouwwerken.Valérie Herremans De sacramentstoren als blikvanger in het historische kerkinterieur. [The sacraments tower as an eye-catcher in the historical church interior.]De merkwaardige ontwikkeling van de kleine pyxis, een bescheiden eucharistiedoosje, tot de overweldigende creatie van de Leeuwse sacramentstoren wordt door Valérie Herremans niet alleen vanuit zijn specifieke functie, maar ook vanuit een contextuele invalshoek belicht.Christina Ceulemans De iconografie van de sacramentstoren van Zoutleeuw: een grootse hulde aan het Heilig Sacrament. [The Zoutleeuw sacrament towers iconography: a magnificent hymn to the blessed sacraments.]Niet minder dan 180 beelden gaven, soms node, hun identiteit prijs aan Christina Ceulemans, die de voorstellingen beschrijft als een huldeprocessie aan de eucharistie. Dat een dergelijk ingewikkeld programma werd opgesteld door erudiete kerkgeleerden staat voor haar buiten kijf.Jan Verbeke en Jacques Vereecke Bouwtechniek van de toren. [Building technique of the sacraments tower.]Het gedetailleerde contract tussen Cornelis Floris en de mecenas Maarten Van Wilre levert precieze gegevens op over bouwtechniek en materialen. Toch kon het ervaren oog van de restaurateurs Jacques Vereecke en Jan Verbeke tal van andere bouwspecifieke technieken ontdekken, waarbij het spaarzaam omgaan met het dure materiaal en het onmiskenbare vakmanschap van dit goed georganiseerd atelier de leidraad bleken.Het petrografisch onderzoek van Francis Tourneur bevestigt Cornelis Floris aandacht voor de juiste materiaalkeuze.Summar

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GeneriekGeert Van der Linden Kasseiwegen in de Vlaamse Ardennen, zeldzaam edelgesteente. [Cobbled roads in the Flemish Ardennes, a precious stone.]Rik Vanwalleghem De aantrekkelijkheid van het schaarse. [The attractivity of rare things (annex to: Cobbled roads in the Flemish Ardennes).Winterse toestanden durven wel eens onder de allesverhullende asfaltbekledingen aan hun bestaan herinneren. In de Vlaamse Ardennen behoren kasseiwegen dank zij recente beschermingsmaatregelen daarentegen tot de dagelijkse realiteit, tot grote vreugde overigens van wielersportfanaten.Hoe kinderkoppen en fietsbanden zich intussen tot elkaar verhouden, vertellen ons uit onverdachte hoek landschapsdeskundige Geert Van der Linden en sportredacteur Rik Vanwalleghem.Christina Ceulemans, Daniel De Jonghe en Vera Vereecken Textielvondsten in Limburg. [Discoveries of textile fabrics in Limburg.]Wetenschappelijk onderzoek van Maaslandse reliek-collecties leidden de jongste jaren tot de ontdekking van onvermoede historische textielfragmenten.Bijzonder suggestief zijn hierbij de rijkelijk gestoffeerde reliekschedels uit Tongeren, Sint-Truiden en Herkenrode. De gecoördineerde aanpak door Christina Ceulemans, Daniël De Jonghe en Vera Vereecken opent meteen veelbelovende perspectieven.Marc Mees - Den schoonen constighen eyseren boom. De smeedijzeren boom van Sint-Gummarus uit de Kluizekerk te Lier. [The wrought-iron tree of Saint-Gummarus at the Kluizekerk in Lier.]Toegepast op bomen lijkt het materiaal allesbehalve evident, zelfs in Lier waar Lodewijk Van Boeckel ooit nog de smeedkunst tot zeldzame hoogten tilde.Naar aanleiding van diens restauratie door Aimé Stroobants, wist Marc Mees de Boom van Sint-Gummarus alvast in een vernieuwd daglicht te plaatsen (of is \u27kaarslicht\u27 hier méér op zijn plaats?).Elie Degrande m.m.v. Miek Goossens Gewelfbouw. [Vaulted construction.]Slechts uitzonderlijk kijkt M&L over de landsgrenzen heen. De eenmalige heropbouw van éen volledig kerkgewelf in het Nederlandse Ubbingen, stelde het Brugse Vrij Technisch Instituut nochtans in staat een uitzonderlijke ervaring op te doen.Aan de hand van eigen werkdocumenten, maakt Elie Degrande ons hiervan deelgenoot.SummaryM&L Binnenkran

Learning from the public:citizens describe the need to improve end-of-life care access, provision and recognition across Europe

Background: Despite ageing populations and increasing cancer deaths, many European countries lack national policies regarding palliative and end-of-life care. The aim of our research was to determine public views regarding end-of-life care in the face of serious illness. Methods: Implementation of a pan-European population-based survey with adults in England, Belgium (Flanders), Germany, Italy, the Netherlands, Portugal and Spain. Three stages of analysis were completed on open-ended question data: (i) inductive analysis to determine a category-code framework; (ii) country-level manifest deductive content analysis; and (iii) thematic analysis to identify cross-country prominent themes. Results: Of the 9344 respondents, 1543 (17%) answered the open-ended question. Two prominent themes were revealed: (i) a need for improved quality of end-of-life and palliative care, and access to this care for patients and families and (ii) the recognition of the importance of death and dying, the cessation of treatments to extend life unnecessarily and the need for holistic care to include comfort and support. Conclusions: Within Europe, the public recognizes the importance of death and dying; they are concerned about the prioritization of quantity of life over quality of life; and they call for improved quality of end-of-life and palliative care for patients, especially for elderly patients, and families. To fulfil the urgent need for a policy response and to advance research and care, we suggest four solutions for European palliative and end-of-life care: institute government-led national strategies; protect regional research funding; consider within-and between-country variance; establish standards for training, education and service delivery

Sonnius. Bisschop en abt tussen Tongerlo, Antwerpen en 's-Hertogenbosch. Tentoonstellingsgids

status: publishe

Screening for Differences in Early Exposure in the Fasted State with in Vitro Methodologies can be Challenging: Experience with the BioGIT System.

The Biorelevant Gastrointestinal Transfer (BioGIT) system is a useful screening tool for assessing the impact of dose and/or formulation on early exposure after administration of immediate release or enabling drug products with a glass of water in the fasted state. The objective of this study was to investigate potential limitations. BioGIT experiments were performed with five low solubility active pharmaceutical ingredients with weakly alkaline characteristics: mebendazole (tablet and chewable tablet), Compound E (aqueous solutions, three doses), pazopanib-HCl (Votrient™ tablet, crushed Votrient™ tablet and aqueous suspension), Compound B-diHCl (hard gelatin capsule, three doses) and Compound C (hard gelatin capsule containing nanosized drug and hard gelatin capsule containing micronized drug). For all formulation or dose comparisons the ratio of mean BioGIT AUC0-50 min values was not predictive of the ratio of mean plasma AUC0-60 min values which became available after completion of BioGIT experiments. BioGIT experimental conditions have not been designed to simulate the gastrointestinal drug transfer process after administration of chewable tablets or aqueous solutions, therefore, BioGIT may not be useful for the assessment of intraluminal performance early after administration of such drug products. Also, based on this study, BioGIT may not be useful in investigating the impact of dose and/or formulation on early exposure when the dose is not administered with a glass of water to fasted healthy individuals or when BioGIT data are highly variable. Finally, the rapid dissolution of nanocrystals after administration of low solubility weak bases may require adjustment of the pH in the gastric compartment of BioGIT to slightly higher pH values. Limitations identified in this study for the BioGIT system may be also relevant to other in vitro systems proposed for similar evaluations

Usefulness of the BioGIT system in screening for differences in early exposure in the fasted state on an a priori basis

The main objective of the present study was to confirm the usefulness of BioGIT data in the evaluation of the impact of dose and/or formulation on early exposure after administration of immediate release (IR) or enabling drug products of low solubility active pharmaceutical ingredients (APIs) with a glass of water in the fasted state. BioGIT experiments were performed with four APIs: Compound Α (tablet, three dose levels), Compound E (capsule PiC1, capsule PiC2 and tablet), fenofibrate (Lipidil® capsule and Lipidil 145 ONE® tablet) and bedaquiline (HP-β-CD aqueous solution and tablet). Based on mean plasma AUC0-60min values which became available after completion of the BioGIT experiments, mean BioGIT AUC0-50min values were useful for the evaluation of the impact of dose and/or formulation on early exposure. Furthermore, the log-transformed mean BioGIT AUC0-50min ratios of two doses and/or two formulations calculated from data collected in this study and in a recent study with two diclofenac potassium products (Cataflam® tablet and Voltfast® sachet, same dose) (n=7 pairs of ratios), and the corresponding log-transformed mean plasma AUC0-60min ratios calculated from clinical data were included in a previously established correlation between log-transformed mean plasma AUC0–60min ratios with log-transformed mean BioGIT AUC0–50min ratios (n=9 pairs of ratios). The correlation between log-transformed plasma AUC0–60min ratios vs. log-transformed BioGIT AUC0–50min ratios was confirmed (n=16 pairs of ratios, R=0.90). Compared with the previously established correlation the statistical characteristics were improved. Based on this study, the BioGIT system could be useful as a screening tool for assessing the impact of dose and/or formulation differences on early exposure, after administration of immediate release or enabling drug products with a glass of water in the fasted state, on an a priori basis

Variants in PRKAR1B cause a neurodevelopmental disorder with autism spectrum disorder, apraxia, and insensitivity to pain.

PurposeWe characterize the clinical and molecular phenotypes of six unrelated individuals with intellectual disability and autism spectrum disorder who carry heterozygous missense variants of the PRKAR1B gene, which encodes the R1β subunit of the cyclic AMP-dependent protein kinase A (PKA).MethodsVariants of PRKAR1B were identified by single- or trio-exome analysis. We contacted the families and physicians of the six individuals to collect phenotypic information, performed in vitro analyses of the identified PRKAR1B-variants, and investigated PRKAR1B expression during embryonic development.ResultsRecent studies of large patient cohorts with neurodevelopmental disorders found significant enrichment of de novo missense variants in PRKAR1B. In our cohort, de novo origin of the PRKAR1B variants could be confirmed in five of six individuals, and four carried the same heterozygous de novo variant c.1003C>T (p.Arg335Trp; NM_001164760). Global developmental delay, autism spectrum disorder, and apraxia/dyspraxia have been reported in all six, and reduced pain sensitivity was found in three individuals carrying the c.1003C>T variant. PRKAR1B expression in the brain was demonstrated during human embryonal development. Additionally, in vitro analyses revealed altered basal PKA activity in cells transfected with variant-harboring PRKAR1B expression constructs.ConclusionOur study provides strong evidence for a PRKAR1B-related neurodevelopmental disorder

FOXP1-related intellectual disability syndrome : a recognisable entity

Background: Mutations in forkhead box protein P1 (FOXP1) cause intellectual disability (ID) and specific language impairment (SLI), with or without autistic features (MIM: 613670). Despite multiple case reports no specific phenotype emerged so far. Methods: We correlate clinical and molecular data of 25 novel and 23 previously reported patients with FOXP1 defects. We evaluated FOXP1 activity by an in vitro luciferase model and assessed protein stability in vitro by western blotting. Results: Patients show ID, SLI, neuromotor delay (NMD) and recurrent facial features including a high broad forehead, bent downslanting palpebral fissures, ptosis and/or blepharophimosis and a bulbous nasal tip. Behavioural problems and autistic features are common. Brain, cardiac and urogenital malformations can be associated. More severe ID and NMD, sensorineural hearing loss and feeding difficulties are more common in patients with interstitial 3p deletions (14 patients) versus patients with monogenic FOXP1 defects (34 patients). Mutations result in impaired transcriptional repression and/or reduced protein stability. Conclusions: FOXP1-related ID syndrome is a recognisable entity with a wide clinical spectrum and frequent systemic involvement. Our data will be helpful to evaluate genotype-phenotype correlations when interpreting next-generation sequencing data obtained in patients with ID and/or SLI and will guide clinical management