406 research outputs found
Inducing good behavior: Bonuses versus fines in inspection games
We examine the effectiveness of bonuses and fines in an inspection game where an employer can learn the effort of a worker through costly inspection. Standard game theoretic analysis predicts that fines discourage shirking, whereas bonuses encourage shirking. In contrast, ownpayoff effects suggest that both fines and bonuses discourage shirking. In an experiment we find that fines are more effective than bonuses in reducing shirking. However, we do not find that bonuses encourage shirking. Behavioral theories based on Impulse Balance Equilibrium or Quantal Response Equilibrium provide a good account of deviations from Nash equilibrium predictions
Practice-level association between antibiotic prescribing and resistance: an observational study in primary care
A direct relation between antibiotic use and resistance has been shown at country level. We aim to investigate the association between antibiotic prescribing for patients from individual Dutch primary care practices and antibiotic resistance of bacterial isolates from routinely submitted urine samples from their patient populations. Practices’ antibiotic prescribing data were obtained from the Julius Network and related to numbers of registered patients. Practices were classified as low-, middle-or high-prescribers and from each group size-matching practices were chosen. Culture and susceptibility data from submitted urine samples were obtained from the microbiology laboratory. Percentages of resistant isolates, and resistant isolates per 1000 registered patients per year (population resistance) were calculated and compared between the groups. The percentages of resistant Escherichia coli varied considerably between individual practices, but the three prescribing groups’ means were very similar. However, as the higher-prescribing practices requested more urine cultures per 1000 registered patients, population resistance was markedly higher in the higher-prescribing groups. This study showed that the highly variable resistance percentages for individual practices were unrelated to antibiotic prescribing levels. However, population resistance (resistant strains per practice population) was related to antibiotic prescribing levels, which was shown to coincide with numbers of urine culture requests. Whether more urine culture requests in the higher-prescribing groups were related to treatment failures, more complex patient populations, or to general practitioners’ testing behaviour needs further investigation
A Review of the Role of Bioreactors for iPSCs-Based Tissue-Engineered Articular Cartilage
BACKGROUND: Osteoarthritis (OA) is the most common degenerative joint disease without an ultimate treatment. In a search for novel approaches, tissue engineering (TE) has shown great potential to be an effective way for hyaline cartilage regeneration and repair in advanced stages of OA. Recently, induced pluripotent stem cells (iPSCs) have been appointed to be essential stem cells for degenerative disease treatment because they allow a personalized medicine approach. For clinical translation, bioreactors in combination with iPSCs-engineerd cartilage could match patients needs, serve as platform for large-scale patient specific cartilage production, and be a tool for patient OA modelling and drug screening. Furthermore, to minimize in vivo experiments and improve cell differentiation and cartilage extracellular matrix (ECM) deposition, TE combines existing approaches with bioreactors.METHODS: This review summarizes the current understanding of bioreactors and the necessary parameters when they are intended for cartilage TE, focusing on the potential use of iPSCs.RESULTS: Bioreactors intended for cartilage TE must resemble the joint cavity niche. However, recreating human synovial joints is not trivial because the interactions between various stimuli are not entirely understood.CONCLUSION: The use of mechanical and electrical stimulation to differentiate iPSCs, and maintain and test chondrocytes are key stimuli influencing hyaline cartilage homeostasis. Incorporating these stimuli to bioreactors can positively impact cartilage TE approaches and their possibility for posterior translation into the clinics.</p
Clinical management of ovarian small-cell carcinoma of the hypercalcemic type: A proposal for conservative surge
Ovarian small-cell carcinoma of the hypercalcemic type is a rare and highly malignant tumor. In two thirds of the patients, the tumor is associated with asymptomatic paraneoplastic hypercalcemia. The diagnosis may be impeded; the tumor must be distinguished
Discretionary sanctions and rewards in the repeated inspection game
We experimentally investigate a repeated “inspection game” where, in the stage game, an employee can either work or shirk and an employer simultaneously chooses to inspect or not inspect. The unique equilibrium of the stage game is in mixed strategies with positive probabilities of shirking/inspecting while combined payoffs are maximized when the employee works and the employer does not inspect. We examine the effects of allowing the employer discretion to sanction or reward the employee after observing stage game payoffs. When employers have limited discretion, and can only apply sanctions and/or rewards following an inspection, we find that both instruments are equally effective in reducing shirking and increasing joint earnings. When employers have discretion to reward and/or sanction independently of whether they inspect we find that rewards are more effective than sanctions. In treatments where employers can combine sanctions and rewards employers rely mainly on rewards and outcomes closely resemble those of treatments where only rewards are possible
Phosphocreatine interacts with phospholipids, affects membrane properties and exerts membrane-protective effects
A broad spectrum of beneficial effects has been ascribed to creatine (Cr), phosphocreatine (PCr) and their cyclic analogues cyclo-(cCr) and phospho-cyclocreatine (PcCr). Cr is widely used as nutritional supplement in sports and increasingly also as adjuvant treatment for pathologies such as myopathies and a plethora of neurodegenerative diseases. Additionally, Cr and its cyclic analogues have been proposed for anti-cancer treatment. The mechanisms involved in these pleiotropic effects are still controversial and far from being understood. The reversible conversion of Cr and ATP into PCr and ADP by creatine kinase, generating highly diffusible PCr energy reserves, is certainly an important element. However, some protective effects of Cr and analogues cannot be satisfactorily explained solely by effects on the cellular energy state. Here we used mainly liposome model systems to provide evidence for interaction of PCr and PcCr with different zwitterionic phospholipids by applying four independent, complementary biochemical and biophysical assays: (i) chemical binding assay, (ii) surface plasmon resonance spectroscopy (SPR), (iii) solid-state (31)P-NMR, and (iv) differential scanning calorimetry (DSC). SPR revealed low affinity PCr/phospholipid interaction that additionally induced changes in liposome shape as indicated by NMR and SPR. Additionally, DSC revealed evidence for membrane packing effects by PCr, as seen by altered lipid phase transition. Finally, PCr efficiently protected against membrane permeabilization in two different model systems: liposome-permeabilization by the membrane-active peptide melittin, and erythrocyte hemolysis by the oxidative drug doxorubicin, hypoosmotic stress or the mild detergent saponin. These findings suggest a new molecular basis for non-energy related functions of PCr and its cyclic analogue. PCr/phospholipid interaction and alteration of membrane structure may not only protect cellular membranes against various insults, but could have more general implications for many physiological membrane-related functions that are relevant for health and disease
Neuronal integration in an abuttingretinas culture system
PURPOSE. Limited integration is consistently observed between subretinal transplants and host retinas. In the current study, an in vitro model system for studying connections forming between two abutting retinas was developed. METHODS. Neuroretinas were dissected from normal wild-type (WT) mice and green fluorescent protein (GFP) transgenic mice (obtained at postnatal days [P]0, P5, or P60), as well as from adult rd mice. Pieces from two different retinas (WT-WT, GFP-WT, GFP-rd) were placed side-by-side (contacting each other at the margins) or overlapping each other in organ cultures for 7 or 12 days. The abutting retinal pieces derived from animals of the same age (P5-P5; P60-P60) or of different ages (P0-P60; P5-P60). Retinal cells and fibers were visualized in wholemount preparations and in cross sections by immunocytochemistry using antibodies against neurofilament (NFϩ), neuronal nitric oxide synthase (NOSϩ), and protein kinase C (PKCϩ) and by GFP fluorescence (GFPϩ). RESULTS. In side-by-side pairs (WT-WT, GFP-WT), numerous horizontal cell fibers (NFϩ) and amacrine cell fibers (NOSϩ) crossed the interface between the two pieces, forming continuous plexiform layers. In overlapping pairs, NFϩ, NOSϩ, and PKCϩ fibers displayed parallel plexiform layers, and no crossover of fibers was observed in any of the pair combinations examined (WT-WT, GFP-WT, GFP-rd). Some integration was seen only in small areas where the structure of both retinal pieces was disrupted at the interface. CONCLUSIONS. The results demonstrate the ability of neurites to extend between abutting retinas and to make appropriate target choices when they are placed side-by-side. However, this ability is limited when they overlap each other, similar to that observed in subretinal transplantation. (Invest Ophthalmol Vis Sci. 2003;44:4936 -4946 ). Prompted by the problem of poor graft-host integration, we developed a modified culture system in which the outgrowth of fibers between two retinal pieces could be analyzed. The system consists of two abutting retinal pieces, placed overlapping each other, which is analogous to the in vivo situation of subretinal transplantation, or side by side. Using specific neuronal markers, we examined in wholemount preparations and in transverse sections, whether neuronal fibers can extend from one retinal piece into the abutting piece. Pairs were formed using retinal pieces derived from 5-day-old (P5) mice and cultured for 7 days, thus encompassing a time window (P5-P12) during which, in normal mouse development, substantial outgrowth of retinal cell processes occurs within the synaptic layers, and synaptic maturation is initiated. 11,12 MATERIALS AND METHODS Animals and Tissue Culture Preparation The experiments were conducted with the approval of the local animal experimentation and ethics committee. Animals were handled according to the guidelines on care and use of experimental animals set forth by the Government Committee on Animal Experimentation at the University of Lund and the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. The organ culture condition has been described in detail. 13 Retinas were dissected from normal mice (C57BL/6), from GFP mice (harboring a transgene consisting of enhanced GFP [EGFP] cDNA under the control of a chicken -actin promoter and a cytomegalovirus enhancer), After the superior and nasal cornea were marked, the eyes were enucleated under sterile conditions and transferred to a dish containing serum-free medium (R16; Invitrogen-Gibco, Gaithersburg, MD). 15 Retinas were dissected from the retinal pigment epithelium (RPE) and from hyaloid vessels. Each retina was cut under fresh medium into four pieces along the superior-inferior and the nasal-temporal axes (Fig
Optimized Preoperative Planning of Double Outlet Right Ventricle Patients by 3D Printing and Virtual Reality:A Pilot Study
OBJECTIVES: In complex double outlet right ventricle (DORV) patients, the optimal surgical approach may be difficult to assess based on conventional two-dimensional (2D) ultrasound (US) and computed tomography (CT) imaging. The aim of this study is to assess the added value of 3D printed and 3D Virtual Reality (VR) models of the heart used for surgical planning in DORV patients, supplementary to the gold standard 2D imaging modalities.METHODS: Five patients with different DORV-subtypes and high-quality CT scans were selected retrospectively. 3D prints and 3D-VR models were created. Twelve congenital cardiac surgeons and paediatric cardiologists, from three different hospitals, were shown 2D-CT first, after which they assessed the 3D print and 3D-VR models in random order. After each imaging method, a questionnaire was filled in on the visibility of essential structures and the surgical plan.RESULTS: Spatial relationships were generally better visualized using 3D methods (3D printing/3D-VR) than in 2D. The feasibility of VSD patch closure could be determined best using 3D-VR reconstructions (3D-VR 92%, 3D print 66%, and US/CT 46%, P < 0.01). The percentage of proposed surgical plans corresponding to the performed surgical approach was 66% for plans based on US/CT, 78% for plans based on 3D printing, and 80% for plans based on 3D-VR visualization.CONCLUSIONS: This study shows that both 3D printing and 3D-VR have additional value for cardiac surgeons and cardiologists over 2D imaging, because of better visualization of spatial relationships. As a result, the proposed surgical plans based on the 3D visualizations matched the actual performed surgery to a greater extent.</p
Port: A software tool for digital data donation
Recently, a new workflow has been introduced that allows academic researchers to partner with individuals interested in donating their digital trace data for academic research purposes (Boeschoten, Ausloos, et al., 2022). In this workflow, the digital traces of participants are processed locally on their own devices in such a way that only the subset of participants’ digital trace data that is of legitimate interest to a research project are shared with the researcher, which can only occur after the participant has provided their informed consent. This data donation workflow consists of the following steps: First, the participant requests a digital copy of their personal data at the platform of interest, such as Google, Meta, Twitter and other digital platforms, i.e., their Data Download Package (DDP). Platforms, as data controllers, are required as per the European Union’s General Data Protection Regulation (GDPR) to share a digital copy with each participant requesting such a copy. Second, they download the DDP onto their personal device. Third, by means of local processing, only the data points of interest to the researcher are extracted from that DDP. Fourth, the participant inspects the extracted data points after which the participant can consent to donate. Only after providing this consent, the donated data is sent to a storage location and can be accessed by the researcher, which would mean that the storage location can be accessed for further analysis. In this paper, we introduce Port. Port is a software tool that allows researchers to configure the local processing step of the data donation workflow, allowing the researcher to collect exactly the digital traces needed to answer their research question. When using Port, a researcher can decide: • Which digital platforms are investigated; • Which digital traces are collected; • How the extracted digital traces are visually presented to the participant; • What is communicated to the participant
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