Een veelbelovend verbondsprediker : een historisch en homiletisch onderzoek naar de preken van Wilhelmus à Brakel (1635-1711)

In deze scriptie staan de preken van Wilhelmus à Brakel (1635-1711) centraal, een bekende predikant uit de kringen van de Nadere Reformatie. Zijn preken worden zowel historisch als homiletisch onderzocht, omdat gebleken is dat eerder onderzoek hiernaar veel vragen open heeft gelaten. Het eerste onderdeel van de scriptie is authenticiteitsonderzoek naar de zeventien postuum gepubliceerde preken van À Brakel. Hierbij is bijzondere aandacht voor de Dordtse publicist Johan Hofman, die tussen 1710 en 1713 vijftien preken van À Brakel uitgaf. Gebleken is dat twaalf van de vijftien preken authenticiteitsproblemen kennen. Minstens drie van de twaalf preken zijn (vrijwel) volledig vertaalde preken van Engelse puriteinen die Hofman op naam van À Brakel heeft gezet. De negen andere preken zijn in meer of mindere mate aangevuld met vertaalde puriteinse teksten. Hofman gaf echter ook drie preken van À Brakel uit die wel als authentiek bestempeld kunnen worden. Twee andere postuum gepubliceerde preken kennen geen authenticiteitsproblemen. In het tweede onderdeel van de scriptie zijn deze vijf authentieke preken homiletisch onderzocht. Daarbij is op verschillende punten afstand genomen van de conclusies van eerdere onderzoekers. Deze hebben zich veelal gebaseerd op preken waarvan in deze scriptie duidelijk is geworden dat ze niet authentiek zijn. In dit onderdeel is geconcludeerd met een typering van À Brakels prediking. À Brakels prediking kent vijf karakteristieken. Allereerst is het voetiaanse prediking, wat methode betreft. Ten tweede is het verbondsprediking, gezien de centrale rol die het genadeverbond speelt. Dit houdt verband met de derde karakteristiek; het is belofteprediking. Niet alleen wordt het heil beloofd aan allen die willen, begeren en zoeken; bovendien worden er heel concrete beloften gedaan naar onderscheiden staat en stand. Ten vierde is het pastorale prediking; À Brakel had oog voor de pastorale nood in de gemeente, in het bijzonder voor hen die worstelden met de toe-eigening des heils. Ten slotte is het bevindelijke prediking: de toepassing en de beleving van het heil krijgen veel aandacht

Dynamics and equilibria under incremental horizontal differentiation on the Salop circle

We study product differentiation on a Salop circle when firms relocate incrementally due to bounded rationality. We prove that, under common assumptions on demand, firms relocate only when two or more firms target the same niche. In any other case, there is no incentive for any firm to relocate incrementally. We prove that all distributions in which firms are sufficiently far apart in product space are unstable Nash equilibria. We prove, in particular, that the classical equidistant distribution is an unstable Nash equilibrium that cannot emerge from another distribution. However, we show that if each firm is engaged in head-on rivalry with one other competitor, the industry converges to a ’equidistantesque’ equilibrium of clusters of rivals

The Organisation of Floor in Meetings and the Relation with Speaker Addressee Patterns

We present a procedure for conversational floor annotation and discuss floor types and floor switches in face-to-face meetings and the relation with addressing behavior. It seems that for understanding interactions in meetings an agent needs a layered floor model and that turn and floor changes are constrained by the activities and the roles that the agent and his conversational partners play in these activities. We present statistics about the addressee of the speaker and his role in the ongoing activity and a simple method that predicts the addressee using speaker role and floor state. The results support the expectation that information about the activity and the speaker's role will improve detection and interpretation of social signals from speaker addressee patterns in meetings

Pain management in patients with dementia

There are an estimated 35 million people with dementia across the world, of whom 50% experience regular pain. Despite this, current assessment and treatment of pain in this patient group are inadequate. In addition to the discomfort and distress caused by pain, it is frequently the underlying cause of behavioral symptoms, which can lead to inappropriate treatment with antipsychotic medications. Pain also contributes to further complications in treatment and care. This review explores four key perspectives of pain management in dementia and makes recommendations for practice and research. The first perspective discussed is the considerable uncertainty within the literature on the impact of dementia neuropathology on pain perception and processing in Alzheimer’s disease and other dementias, where white matter lesions and brain atrophy appear to influence the neurobiology of pain. The second perspective considers the assessment of pain in dementia. This is challenging, particularly because of the limited capacity of self-report by these individuals, which means that assessment relies in large part on observational methods. A number of tools are available but the psychometric quality and clinical utility of these are uncertain. The evidence for efficient treatment (the third perspective) with analgesics is also limited, with few statistically well-powered trials. The most promising evidence supports the use of stepped treatment approaches, and indicates the benefit of pain and behavioral interventions on both these important symptoms. The fourth perspective debates further difficulties in pain management due to the lack of sufficient training and education for health care professionals at all levels, where evidence-based guidance is urgently needed. To address the current inadequate management of pain in dementia, a comprehensive approach is needed. This would include an accurate, validated assessment tool that is sensitive to different types of pain and therapeutic effects, supported by better training and support for care staff across all settings

Pain management in patients with dementia

There are an estimated 35 million people with dementia across the world, of whom 50% experience regular pain. Despite this, current assessment and treatment of pain in this patient group are inadequate. In addition to the discomfort and distress caused by pain, it is frequently the underlying cause of behavioral symptoms, which can lead to inappropriate treatment with antipsychotic medications. Pain also contributes to further complications in treatment and care. This review explores four key perspectives of pain management in dementia and makes recommendations for practice and research. The first perspective discussed is the considerable uncertainty within the literature on the impact of dementia neuropathology on pain perception and processing in Alzheimer’s disease and other dementias, where white matter lesions and brain atrophy appear to influence the neurobiology of pain. The second perspective considers the assessment of pain in dementia. This is challenging, particularly because of the limited capacity of self-report by these individuals, which means that assessment relies in large part on observational methods. A number of tools are available but the psychometric quality and clinical utility of these are uncertain. The evidence for efficient treatment (the third perspective) with analgesics is also limited, with few statistically well-powered trials. The most promising evidence supports the use of stepped treatment approaches, and indicates the benefit of pain and behavioral interventions on both these important symptoms. The fourth perspective debates further difficulties in pain management due to the lack of sufficient training and education for health care professionals at all levels, where evidence-based guidance is urgently needed. To address the current inadequate management of pain in dementia, a comprehensive approach is needed. This would include an accurate, validated assessment tool that is sensitive to different types of pain and therapeutic effects, supported by better training and support for care staff across all settings.publishedVersio

Circumventing the crabtree effect in cell culture: a systematic review

Metabolic reprogramming and mitochondrial dysfunction are central elements in a broad variety of physiological and pathological processes. While cell culture established itself as a versatile technique for the elaboration of physiology and disease, studying metabolism using standard cell culture protocols is profoundly interfered by the Crabtree effect. This phenomenon refers to the adaptation of cultured cells to a glycolytic phenotype, away from aoxidative phosphorylation in glucose-containing medium, and questions the applicability of cell culture in certain fields of research. In this systematic review we aim to provide a comprehensive overview and critical appraisal of strategies reported to circumvent the Crabtree effect.Toxicolog

First-in-human study of the biodistribution and pharmacokinetics of ⁸⁹Zr-CX-072, a novel immunopet tracer based on an anti–PD-L1 probody

Purpose: CX-072, a PD-L1–targeting Probody therapeutic, is engineered to be activated by tumor proteases that remove a masking peptide. To study effects on biodistribution and pharmacokinetics, we performed 89Zr-CX-072 positron emission tomography (PET) imaging. Experimental Design: Patients received 1 mg, 37 MBq 89Zr-CX-072 plus 0, 4, or 9 mg unlabeled CX-072 and PET scans at days 2, 4, and 7. After that, treatment comprised 10 mg/kg CX-072 q2 weeks (n ¼ 7) þ 3 mg/kg ipilimumab q3w 4 (n ¼ 1). Normal organ tracer uptake was expressed as standardized uptake value (SUV)mean and tumor uptake as SUVmax. PD-L1 expression was measured immunohistochemically in archival tumor tissue. Results: Three of the eight patients included received 10-mg protein dose resulting in a blood pool mean SUVmean SD of 4.27 0.45 on day 4, indicating sufficient available tracer. Tumor uptake was highest at day 7, with a geometric mean SUVmax 5.89 (n ¼ 113) and present in all patients. The median follow-up was 12 weeks (4–76þ). One patient experienced stable disease and two patients a partial response. PD-L1 tumor expression was 90% in one patient and ≤1% in the other patients. Mean SUVmean SD day 4 at 10 mg in the spleen was 8.56 1.04, bone marrow 2.21 0.46, and liver 4.97 0.97. Four patients out of seven showed uptake in normal lymph nodes and Waldeyer’s ring. The tracer was intact in the serum or plasma. Conclusions: 89Zr-CX-072 showed tumor uptake, even in lesions with ≤1% PD-L1 expression, and modest uptake in normal lymphoid organs, with no unexpected uptake in other healthy tissues

Preclinical models versus clinical renal ischemia reperfusion injury: a systematic review based on metabolic signatures

Despite decennia of research and numerous successful interventions in the preclinical setting, renal ischemia reperfusion (IR) injury remains a major problem in clinical practice, pointing toward a translational gap. Recently, two clinical studies on renal IR injury (manifested either as acute kidney injury or as delayed graft function) identified metabolic derailment as a key driver of renal IR injury. It was reasoned that these unambiguous metabolic findings enable direct alignment of clinical with preclinical data, thereby providing the opportunity to elaborate potential translational hurdles between preclinical research and the clinical context. A systematic review of studies that reported metabolic data in the context of renal IR was performed according to the PRISMA guidelines. The search (December 2020) identified 35 heterogeneous preclinical studies. The applied methodologies were compared, and metabolic outcomes were semi-quantified and aligned with the clinical data. This review identifies profound methodological challenges, such as the definition of IR injury, the follow-up time, and sampling techniques, as well as shortcomings in the reported metabolic information. In light of these findings, recommendations are provided in order to improve the translatability of preclinical models of renal IR injury.Transplant surger

The ANTARES Optical Beacon System

ANTARES is a neutrino telescope being deployed in the Mediterranean Sea. It consists of a three dimensional array of photomultiplier tubes that can detect the Cherenkov light induced by charged particles produced in the interactions of neutrinos with the surrounding medium. High angular resolution can be achieved, in particular when a muon is produced, provided that the Cherenkov photons are detected with sufficient timing precision. Considerations of the intrinsic time uncertainties stemming from the transit time spread in the photomultiplier tubes and the mechanism of transmission of light in sea water lead to the conclusion that a relative time accuracy of the order of 0.5 ns is desirable. Accordingly, different time calibration systems have been developed for the ANTARES telescope. In this article, a system based on Optical Beacons, a set of external and well-controlled pulsed light sources located throughout the detector, is described. This calibration system takes into account the optical properties of sea water, which is used as the detection volume of the ANTARES telescope. The design, tests, construction and first results of the two types of beacons, LED and laser-based, are presented.Comment: 21 pages, 18 figures, submitted to Nucl. Instr. and Meth. Phys. Res.