Toxoplasma ceramide synthases: Gene duplication, functional divergence, and roles in parasite fitness.

Toxoplasma gondii is an obligate, intracellular apicomplexan protozoan parasite of both humans and animals that can cause fetal damage and abortion and severe disease in the immunosuppressed. Sphingolipids have indispensable functions as signaling molecules and are essential and ubiquitous components of eukaryotic membranes that are both synthesized and scavenged by the Apicomplexa. Ceramide is the precursor for all sphingolipids, and here we report the identification, localization and analyses of the Toxoplasma ceramide synthases TgCerS1 and TgCerS2. Interestingly, we observed that while TgCerS1 was a fully functional orthologue of the yeast ceramide synthase (Lag1p) capable of catalyzing the conversion of sphinganine to ceramide, in contrast TgCerS2 was catalytically inactive. Furthermore, genomic deletion of TgCerS1 using CRISPR/Cas-9 led to viable but slow-growing parasites indicating its importance but not indispensability. In contrast, genomic knock out of TgCerS2 was only accessible utilizing the rapamycin-inducible Cre recombinase system. Surprisingly, the results demonstrated that this "pseudo" ceramide synthase, TgCerS2, has a considerably greater role in parasite fitness than its catalytically active orthologue (TgCerS1). Phylogenetic analyses indicated that, as in humans and plants, the ceramide synthase isoforms found in Toxoplasma and other Apicomplexa may have arisen through gene duplication. However, in the Apicomplexa the duplicated copy is hypothesized to have subsequently evolved into a non-functional "pseudo" ceramide synthase. This arrangement is unique to the Apicomplexa and further illustrates the unusual biology that characterize these protozoan parasites.

'Towards a conceptualization of nurses' support of hospitalised patients' self-management-A modified Delphi study'.

AIM: To determine patients', nurses' and researchers' opinions on the appropriateness and completeness of the proposed conceptualization of nurses' support of hospitalised patients' self-management. DESIGN: A modified Delphi study. METHODS: We conducted a two-round Delphi survey. The panel group consisted of patients, nurses and researchers. The conceptualization of nurses' support of hospitalised patients' self-management presented in the first Delphi round was based on previous research, including a scoping review of the literature. Data was analysed between both rounds and after the second round. Results are reported in accordance with the guidance on Conducting and Reporting Delphi Studies (CREDES). RESULTS: In the first round all activities of the proposed conceptualization were considered appropriate to support the patients' self-management. Panel members' comments led to the textual adjustment of 19 activities, the development of 15 new activities, and three general questions related to self-management support during hospitalisation. In the second round the modified and the newly added activities were also deemed appropriate. The clarification statements raised in the first Delphi round were accepted, although questions remained about the wording of the activities and about what is and what is not self-management support. CONCLUSION: After textual adjustments and the addition of some activities, the proposed conceptualization of nurses' support in patients' self-management while hospitalised have been considered appropriate and complete. Nevertheless, questions about the scope of this concept still remains. The results provide a starting point for further discussion and the development of self-management programs aimed at the hospitalised patient. IMPLICATION FOR THE PROFESSION AND/OR PATIENT CARE: The results can be considered as a starting point for practice to discuss the concept of nurses' support for hospitalised patients' self-management and develop, implement and research self-management programs specific for their patient population. REPORTING METHOD: Results are reported in accordance with the guidance on Conducting and Reporting Delphi Studies (CREDES). PATIENT OR PUBLIC CONTRIBUTION: Patients were involved as expert panellist in this Delphi study. Impact statement What problem did the study address? Self-management support during hospitalisation is understudied, which undermines the development of evidence-based interventions. What were the main findings? A panel, consisting of patients, nurses and researchers, agreed on the appropriateness of a conceptualization of nurses' support of inpatients' self-management, and identified some points for discussion, mainly related to the boundaries of the concept self-management. Where and on whom will the research have an impact? This study is crucial for generating conceptual understanding of how nurses support patients' self-management during hospitalisation. This is necessary for policy, clinical practice, education, and research on this topic.

On the road to comfort: Evaluating the influence of motion predictability on motion sickness in automated vehicles.

Automated vehicles could increase the risk of motion sickness because occupants are not involved in driving and do not watch the road. This paper aimed to investigate the influence of motion predictability on motion sickness in automated vehicles, as better motion anticipation is believed to mitigate motion sickness. In a simulator-based study, twenty participants experienced two driving conditions differing only in turn directions. The repetitive condition featured a repeating turn direction pattern. The non-repetitive condition contained pseudo-randomly ordered turn directions. To mimic an 'eyes-off-the-road' setting and prevent visual motion anticipation, road visuals were omitted. No significant differences in sickness or head motion, a metric for motion anticipation, were found between the conditions. No participant recognised the repeating turn pattern. This suggests no increased motion anticipation in the repetitive condition, possibly due to a reduced ability to recognise a repeating motion pattern in one degree of freedom within more complex motion.

Motion anticipation is believed to mitigate motion sickness. However, in this simulator-based study on automated vehicles, no significant differences in motion anticipation or sickness were observed between repetitive and non-repetitive turn directions. Recognition of a repeating motion pattern in one degree of freedom might be diminished when it is part of more complex motion.

MUC1 Glycopeptide Vaccine Modified with a GalNAc Glycocluster Targets the Macrophage Galactose C-type Lectin on Dendritic Cells to Elicit an Improved Humoral Response.

Mucin expression and glycosylation patterns on cancer cells differ markedly from healthy cells. Mucin 1 (MUC1) is overexpressed in several solid tumors and presents high levels of aberrant, truncated O-glycans (e.g., Tn antigen). Dendritic cells (DCs) express lectins that bind to these tumor-associated carbohydrate antigens (TACAs) to modulate immune responses. Selectively targeting these receptors with synthetic TACAs is a promising strategy to develop anticancer vaccines and to overcome TACA tolerance. In this work, we prepared, via a solid phase peptide synthesis approach, a modular tripartite vaccine candidate, incorporating a high-affinity glycocluster based on a tetraphenylethylene scaffold, to target the macrophage galactose-type lectin (MGL) on antigen presenting cells. MGL is a C-type lectin receptor that binds Tn antigens and can route them to human leukocyte antigen class II or I, making it an attractive target for anticancer vaccines. Conjugation of the glycocluster to a library of MUC1 glycopeptides bearing the Tn antigen is shown to promote uptake and recognition of the TACA by DCs via MGL. In vivo testing revealed that immunization with the newly designed vaccine construct bearing the GalNAc glycocluster induced a higher titer of anti-Tn-MUC1 antibodies compared to the TACAs alone. Additionally, the antibodies obtained bind a library of tumor-associated saccharide structures on MUC1 and MUC1-positive breast cancer cells. Conjugation of a high-affinity ligand for MGL to tumor-associated MUC1 glycopeptide antigens has a synergistic impact on antibody production.

Antisense Inhibition of Prekallikrein to Control Hereditary Angioedema.

Hereditary angioedema is characterized by recurrent and unpredictable episodes of subcutaneous and mucosal swelling that can be life threatening. IONIS-PKK-LRx is a ligand-conjugated antisense oligonucleotide designed for receptor-mediated delivery to hepatocytes. In a compassionate-use pilot study, two patients with severe bradykinin-mediated angioedema were initially administered weekly subcutaneous injections of the unconjugated parent drug, IONIS-PKKRx, for 12 to 16 weeks, after which they received IONIS-PKK-LRx at a dose of 80 mg every 3 to 4 weeks for 7 to 8 months. Treatment was accompanied by a reduction in the angioedema attack rate. (Funded by Amsterdam UMC.).

Membrane damage and repair: a thin line between life and death.

Bilayered membranes separate cells from their surroundings and form boundaries between intracellular organelles and the cytosol. Gated transport of solutes across membranes enables cells to establish vital ion gradients and a sophisticated metabolic network. However, an advanced compartmentalization of biochemical reactions makes cells also particularly vulnerable to membrane damage inflicted by pathogens, chemicals, inflammatory responses or mechanical stress. To avoid potentially lethal consequences of membrane injuries, cells continuously monitor the structural integrity of their membranes and readily activate appropriate pathways to plug, patch, engulf or shed the damaged membrane area. Here, we review recent insights into the cellular mechanisms that underly an effective maintenance of membrane integrity. We discuss how cells respond to membrane lesions caused by bacterial toxins and endogenous pore-forming proteins, with a primary focus on the intimate crosstalk between membrane proteins and lipids during wound formation, detection and elimination. We also discuss how a delicate balance between membrane damage and repair determines cell fate upon bacterial infection or activation of pro-inflammatory cell death pathways.

[18F]Fluoride PET provides distinct information on disease activity in ankylosing spondylitis as compared to MRI and conventional radiography.

PURPOSE: To relate [18F]fluoride uptake on PET with abnormalities on magnetic resonance imaging (MRI) and conventional radiography (CR) in ankylosing spondylitis (AS) patients. METHODS: Ten clinically active AS patients (female 6/10, age 38 ± 11 years) were included, and both spine and SI-joints were examined. PET scans were dichotomously scored for enhanced [18F]fluoride uptake, MRI scans were scored for fatty lesions, erosions, ankylosis, and bone marrow edema (BME), and CR was scored for erosions, syndesmophytes, and ankylosis. The overlap of lesions across all modalities was evaluated through univariate and multivariate analyses using a generalized mixed model. RESULTS: In the spine, 69 lesions with enhanced [18F]fluoride uptake, 257 MRI lesions, and 88 CR lesions were observed. PET lesions were mostly located in costovertebral and facet joints, outside the field of view (FOV) of the MRI and CR. However, PET lesions inside the FOV of MRI and CR partially showed no abnormality on MRI and CR. In lesions with abnormalities on multiple modalities, both univariate and multivariate analysis showed that PET activity had the strongest association with BME on MRI and ankylosis on CR. In the SI joints, 15 lesions (75%) with PET uptake were found, with 87% showing abnormalities on MRI and CR. CONCLUSION: [18F]fluoride PET lesions are often found outside the scope of MRI and CR, and even in the same location show only partial overlap with abnormalities on MRI (especially BME) and CR (especially ankylosis). This suggests that [18F]fluoride PET partially visualizes aspects of AS separate from MRI and CR, providing novel information. CLINICAL TRIAL REGISTRATION: NL43223.029.13 registered at 02-05-2013.  https://www.toetsingonline.nl/to/ccmo_search.nsf/fABRpop?readform&unids=C1257BA2002CC066C1257B4E0049A65A.

Anti-high-mobility group box-1 treatment strategies improve trauma-induced coagulopathy in a mouse model of trauma and shock.

BACKGROUND: Trauma-induced coagulopathy is associated with platelet dysfunction and contributes to early mortality after traumatic injury. Plasma concentrations of the damage molecule high-mobility group box-1 (HMGB-1) increase after trauma, which may contribute to platelet dysfunction. We hypothesised that inhibition of HMGB-1 with a monoclonal antibody (mAb) or with recombinant thrombomodulin (rTM) improves trauma-induced coagulopathy in a murine model of trauma and shock. METHODS: Male 129S2/SvPasOrlRJ mice were anaesthetised, mechanically ventilated, and randomised into five groups: (i) ventilation control (VENT), (ii) trauma/shock (TS), (iii) TS+anti-HMGB-1 mAb (TS+AB), (iv) TS+rTM (TS+TM), and (v) TS+anti-HMGB-1 mAb+rTM (TS+COMBI). Primary outcome was rotational thromboelastometry EXTEM. Secondary outcomes included tail bleeding time, platelet count, plasma HMGB-1 concentration, and platelet activation. RESULTS: Trauma and shock resulted in a hypocoagulable thromboelastometry profile, increased plasma HMGB-1, and increased platelet activation markers. TS+AB was associated with improved clot firmness after 5 min compared with TS (34 [33-37] vs 32 [29-34] mm; P=0.043). TS+COMBI was associated with decreased clot formation time (98 [92-125] vs 122 [111-148] s; P=0.018) and increased alpha angle (77 [72-78] vs 69 [64-71] degrees; P=0.003) compared with TS. TS+COMBI also reduced tail bleeding time compared with TS (P=0.007). The TS+TM and TS+COMBI groups had higher platelet counts compared with TS (P=0.044 and P=0.041, respectively). CONCLUSIONS: Inhibition of HMGB-1 early after trauma in a mouse model improves clot formation and strength, preserves platelet count, and decreases bleeding time.

Responses to Raven matrices: Governed by visual complexity and centrality.

Raven matrices are widely considered a pure test of cognitive abilities. Previous research has examined the extent to which cognitive strategies are predictive of the number of correct responses to Raven items. This study examined whether response times can be explained directly from the centrality and visual complexity of the matrix cells (edge density and perceived complexity). A total of 159 participants completed a 12-item version of the Raven Advanced Progressive Matrices. In addition to item number (an index of item difficulty), the findings demonstrated a positive correlation between the visual complexity of Raven items and both the mean response time and the number of fixations on the matrix (a strong correlate of response time). Moreover, more centrally placed cells as well as more complex cells received more fixations. It is concluded that response times on Raven matrices are impacted by low-level stimulus attributes, namely, visual complexity and eccentricity.

Modeling, Fabrication, and Testing of a 3D-Printed Coriolis Mass Flow Sensor.

This paper presents the modeling, fabrication, and testing of a 3D-printed Coriolis mass flow sensor. The sensor contains a free-standing tube with a circular cross-section printed using the LCD 3D-printing technique. The tube has a total length of 42 mm, an inner diameter of about 900 µm, and a wall thickness of approximately 230 µm. The outer surface of the tube is metalized using a Cu plating process, resulting in a low electrical resistance of 0.5 Ω. The tube is brought into vibration using an AC current in combination with a magnetic field from a permanent magnet. The displacement of the tube is detected using a laser Doppler vibrometer (LDV) that is part of a Polytec MSA-600 microsystem analyzer. The Coriolis mass flow sensor has been tested over a flow range of 0-150 g/h for water, 0-38 g/h for isopropyl alcohol (IPA), and 0-50 g/h for nitrogen. The maximum flow rates of water and IPA resulted in less than a 30 mbar pressure drop. The pressure drop at the maximum flow rate of nitrogen is 250 mbar.

'Nurses' self-management support to hospitalised patients: A scoping review.

AIMS AND OBJECTIVES: To review the current literature to map and explore the interventions that have been considered or used by nurses to support adult patients' self-management during hospitalisation. BACKGROUND: Nurses can play an important role in supporting patients' self-management. Currently, however, it is unclear how nurses perform this task during a patient's stay in hospital. Traditionally, nurses take the primary role in managing patients' care during hospitalisation. Ideally, patients should have the opportunity to continue applying strategies to manage their health conditions as much as possible while in the hospital. This can increase patients' self-efficacy and decrease unnecessary readmissions. DESIGN: Scoping review informed by the Joanna Briggs Institute methodology. METHODS: A database search was undertaken using Pubmed, CINAHL, PsycInfo, Cochrane, Embase and grey literature sources. Data from the included studies were mapped and summarised in a narrative summary. To synthesise the information that was given about each intervention, we conducted a qualitative inductive content analysis. Results are reported in accordance with the guidelines for reporting Items for systematic review and meta-analyses extension for scoping review (PRISMA-ScR) (Supplementary File 1). RESULTS: 83 documents were included in this review. Based on the information about the interventions, three themes were identified: 'self-management support activities', 'focus of self-management support' and the 'intervention procedure'. Five self-management support activities can be distinguished: 'giving education', 'counselling and coaching', 'enhancing responsibility', 'engaging family-caregivers' and 'supporting transition from hospital to home'. The interventions focused on improving disease-related knowledge and on strengthening several self-management skills. Information about the procedure, development and the theoretical underpinning of the intervention was often limited. CONCLUSIONS: Most activities within the nursing interventions to support adult patients' self-management during hospitalisation are the part of regular nursing care. However, the transfer of responsibility for care task to the patient is relatively new. Further research could focus on developing interventions addressing all aspects of self-management and that are embedded in the patient's care pathway across settings. RELEVANCE TO CLINICAL PRACTICE: Clinical nurses may improve nursing care by supporting all aspects of patients' self-management and facilitate patients as much as possible for taking responsibility for self-management tasks during hospitalisation.

The effect of an occlusion-induced delay on braking behavior in critical situations: A driving simulator study.

OBJECTIVE: To share results of an experiment that used visual occlusion for a new purpose: inducing a waiting time. BACKGROUND: Senders was a leading figure in human factors. In his research on the visual demands of driving, he used occlusion techniques. METHODS: In a simulator experiment, we examined how drivers brake for different levels of urgency and different visual conditions. In three blocks (1 = brake lights, 2 = no brake lights, 3 = occlusion), drivers followed a vehicle at 13.4 or 33.4 m distance. At certain moments, the lead vehicle decelerated moderately (1.7 m/s2) or strongly (6.5 m/s2). In the occlusion condition, the screens blanked for 0.4 s (if 6.5 m/s2) or 2.0 s (if 1.7 m/s2) when the lead vehicle started to decelerate. Participants were instructed to brake only after the occlusion ended. RESULTS: The lack of brake lights caused a delayed response. In the occlusion condition, drivers adapted to the instructed late braking by braking harder. However, adaptation was not always possible: In the most urgent condition, most participants collided with the lead vehicle because the ego-vehicle's deceleration limits were reached. In non-urgent conditions, some drivers braked unnecessarily hard. Furthermore, while waiting until the occlusion cleared, some drivers lightly touched the brake pedal. CONCLUSION: This experimental design demonstrates how drivers (sometimes fail to) adjust their braking behavior to the criticality of the situation. APPLICATION: The phenomena of biomechanical readiness and (inappropriate) dosing of the brake pedal may be relevant to safety, traffic flow, and ADAS design.

Animal Models for Studying Protein-Bound Uremic Toxin Removal-A Systematic Review.

Protein-bound uremic toxins (PBUTs) are associated with the progression of chronic kidney disease (CKD) and its associated morbidity and mortality. The conventional dialysis techniques are unable to efficiently remove PBUTs due to their plasma protein binding. Therefore, novel approaches are being developed, but these require validation in animals before clinical trials can begin. We conducted a systematic review to document PBUT concentrations in various models and species. The search strategy returned 1163 results for which abstracts were screened, resulting in 65 full-text papers for data extraction (rats (n = 41), mice (n = 17), dogs (n = 3), cats (n = 4), goats (n = 1), and pigs (n = 1)). We performed descriptive and comparative analyses on indoxyl sulfate (IS) concentrations in rats and mice. The data on large animals and on other PBUTs were too heterogeneous for pooled analysis. Most rodent studies reported mean uremic concentrations of plasma IS close to or within the range of those during kidney failure in humans, with the highest in tubular injury models in rats. Compared to nephron loss models in rats, a greater rise in plasma IS compared to creatinine was found in tubular injury models, suggesting tubular secretion was more affected than glomerular filtration. In summary, tubular injury rat models may be most relevant for the in vivo validation of novel PBUT-lowering strategies for kidney failure in humans.

Perception of recently graduated Dutch dentists of their education.

INTRODUCTION: The curriculum of the three dental schools in the Netherlands consists of a three-year bachelor's and three-year master's course. The education programmes focus inter alia on clinical dental reasoning, thinking and acting scientifically, general oral healthcare activities, and communication and (inter)professional cooperation. This study examined how recently graduated dentists, in the light of their work experience, evaluate their education in retrospect. MATERIALS AND METHODS: All 1074 dentists who graduated between 2012 and mid-2017 were invited by e-mail to answer a web survey. Of those, 314 (29%) took part in the study. RESULTS: The majority of dentists were positive about their knowledge of general and clinical oral healthcare fields when they graduated (70% and 68%, respectively). Fewer dentists were satisfied with their skills in terms of some specific procedures (50%) and clinical professional areas (33%). By far, the majority (85%) were satisfied with the educational skills of their teachers. The majority (70%) felt that their education fitted in well with their professional practice. Nevertheless, 60% thought a year's trainee work experience would be a good idea. The overall evaluation of dentists who have their own practices was less positive than those who do not. CONCLUSION: Knowledge and skills relating to managing a practice were not sufficiently addressed in the programme. The introduction of a practical internship would be desirable, preferably during the education. But when they look back, the majority of recently graduated dentists in the Netherlands are generally positive about the education they received.

Biofunctional Nanodot Arrays in Living Cells Uncover Synergistic Co-Condensation of Wnt Signalodroplets.

Qualitative and quantitative analysis of transient signaling platforms in the plasma membrane has remained a key experimental challenge. Here, biofunctional nanodot arrays (bNDAs) are developed to spatially control dimerization and clustering of cell surface receptors at the nanoscale. High-contrast bNDAs with spot diameters of ≈300 nm are obtained by capillary nanostamping of bovine serum albumin bioconjugates, which are subsequently biofunctionalized by reaction with tandem anti-green fluorescence protein (GFP) clamp fusions. Spatially controlled assembly of active Wnt signalosomes is achieved at the nanoscale in the plasma membrane of live cells by capturing the co-receptor Lrp6 into bNDAs via an extracellular GFP tag. Strikingly, co-recruitment is observed of co-receptor Frizzled-8 as well as the cytosolic scaffold proteins Axin-1 and Disheveled-2 into Lrp6 nanodots in the absence of ligand. Density variation and the high dynamics of effector proteins uncover highly cooperative liquid-liquid phase separation (LLPS)-driven assembly of Wnt "signalodroplets" at the plasma membrane, pinpointing the synergistic effects of LLPS for Wnt signaling amplification. These insights highlight the potential of bNDAs for systematically interrogating nanoscale signaling platforms and condensation at the plasma membrane of live cells.

How Do Laboratories Perform von Willebrand Disease Diagnostics and Classification of von Willebrand Disease Patients? Results from External Quality Data and an International Survey.

BACKGROUND: Reduced or dysfunctional von Willebrand factor (VWF) may lead to von Willebrand disease (VWD), which is a common inherited bleeding disorder. VWD is classified into three major types: type 1 is a partial quantitative deficiency of VWF, type 3 is a complete quantitative deficiency of VWF, and type 2 consists of qualitative abnormalities of VWF. To arrive at a correct VWD diagnosis, multiple tests and a correct interpretation of these tests are needed. AIM: The aim of the present study was to gain insight into the approach of laboratories toward VWD diagnosis. METHODS: Data from four samples of the external quality assessment (EQA) VWF surveys of the ECAT (External Quality Control for Assays and Tests) were evaluated. Furthermore, results were analyzed of a questionnaire that was sent to hemostasis laboratories about VWD diagnostic approaches. RESULTS: For most EQA samples, the majority of participants indicated the correct classification. However, 6 to 60% indicated another classification. For all samples, significant differences in VWF results were observed between the correct and incorrect classifications. The questionnaire demonstrated that the testing approach varied between the laboratories, especially for parameters that were essential for discrimination between VWD type 1 and healthy individuals, as well as the cutoff values used to discriminate VWD types 1 and 2. CONCLUSIONS: Diagnosis of VWD is heterogeneous in diagnostic approach, guidelines, and cutoff values within large ranges of VWF results between laboratories. Harmonization of approaches and increased accuracy of VWF measurements may help to establish a correct diagnosis.

How Do Laboratories Perform von Willebrand Disease Diagnostics and Classification of von Willebrand Disease Patients? Results from External Quality Data and an International Survey.

BACKGROUND: Reduced or dysfunctional von Willebrand factor (VWF) may lead to von Willebrand disease (VWD), which is a common inherited bleeding disorder. VWD is classified into three major types: type 1 is a partial quantitative deficiency of VWF, type 3 is a complete quantitative deficiency of VWF, and type 2 consists of qualitative abnormalities of VWF. To arrive at a correct VWD diagnosis, multiple tests and a correct interpretation of these tests are needed. AIM: The aim of the present study was to gain insight into the approach of laboratories toward VWD diagnosis. METHODS: Data from four samples of the external quality assessment (EQA) VWF surveys of the ECAT (External Quality Control for Assays and Tests) were evaluated. Furthermore, results were analyzed of a questionnaire that was sent to hemostasis laboratories about VWD diagnostic approaches. RESULTS: For most EQA samples, the majority of participants indicated the correct classification. However, 6 to 60% indicated another classification. For all samples, significant differences in VWF results were observed between the correct and incorrect classifications. The questionnaire demonstrated that the testing approach varied between the laboratories, especially for parameters that were essential for discrimination between VWD type 1 and healthy individuals, as well as the cutoff values used to discriminate VWD types 1 and 2. CONCLUSIONS: Diagnosis of VWD is heterogeneous in diagnostic approach, guidelines, and cutoff values within large ranges of VWF results between laboratories. Harmonization of approaches and increased accuracy of VWF measurements may help to establish a correct diagnosis.

Evidence on continuous flow peritoneal dialysis: A review.

Clinical application of continuous flow peritoneal dialysis (CFPD) has been explored since the 1960s, but despite anticipated clinical benefits, CFPD has failed to gain a foothold in clinical practice, among others due to the typical use of two catheters (or a dual-lumen catheter) and large dialysate volumes required per treatment. Novel systems applying CFPD via the existing single-lumen catheter using rapid dialysate cycling may solve one of these hurdles. Novel on-demand peritoneal dialysate generation systems and sorbent-based peritoneal dialysate regeneration systems may considerably reduce the storage space for peritoneal dialysate and/or the required dialysate volume. This review provides an overview of current evidence on CFPD in vivo. The available (pre)clinical evidence on CFPD is limited to case reports/series with inherently nonuniform study procedures, or studies with a small sample size, short follow-up, and no hard endpoints. Small solute clearance appears to be higher in CFPD compared to conventional PD, in particular at dialysate flows ≥100 mL/min using two single-lumen catheters or a double-lumen catheter. Results of CFPD using rapid cycling via a single-lumen catheter are too preliminary to draw any conclusions. Continuous addition of glucose to dialysate with CFPD appears to be effective in reducing the maximum intraperitoneal glucose concentration while increasing ultrafiltration efficiency (mL/g absorbed glucose). Patient tolerance may be an issue since abdominal discomfort and sterile peritonitis were reported with continuous circulation of the peritoneal dialysate. Thus, well-designed clinical trials of longer duration and larger sample size, in particular applying CFPD via the existing catheter, are urgently required.

How do people distribute their attention while observing The Night Watch?

This study explored how people look at The Night Watch (1642), Rembrandt's masterpiece. Twenty-one participants each stood in front of the painting for 5 min, while their eyes were recorded with a mobile eye-tracker and their thoughts were verbalized with a think-aloud method. We computed a heatmap of the participants' attentional distribution using a novel markerless mapping method. The results showed that the participants' attention was mainly directed at the faces of the two central figures, the bright mascot girl in the painting, and detailed elements such as the apparel of the key figures. The eye-movement analysis and think-aloud data also showed that participants' attention shifted from the faces of the key figures to other elements of the scene over the course of the 5 min. Our analyses are consistent with the theory that Rembrandt used light and texture to capture the viewer's attention. Finally, the robustness of the eye-tracking method was demonstrated by replicating the study on a smaller replica.

Collaboration between general dental practitioners and dental hygienists: a qualitative study.

BACKGROUND: Influenced by governmental measures, collaboration in oral health care practices in the Netherlands has increased in recent decades. Previous studies on this subject have mainly concerned the composition of the staff or have been normative rather than descriptive. Based on the existing literature, four aspects were expected to be of significant influence on the collaboration on oral health care practices: goals, leadership, the allocation of tasks and responsibilities and formalization. METHODS: The aim of this study was to describe a classification of collaboration between general dental practitioners and dental hygienists within oral health care practices in the Netherlands. Eighteen semi-structured face-to-face interviews were conducted in nine oral health care practices, which differed with regard to both practice characteristics and characteristics of the principal general dental practitioner. In all practices, the principal general dental practitioner and one dental hygienist were consulted. The interviews were conducted in the practices of the respondents and were held between October 2019 and July 2020. The interviews were analyzed through theoretical thematic analysis using Microsoft Word 2010 and Atlas.ti 8. Three researchers coded and analyzed three practices, and discussed their results. Based on their mutual conclusions, one researcher analysed all practices. The final results were reviewed and approved by the other two researchers. RESULTS: Different factors influencing the collaboration between general dental practitioners and dental hygienist in the Netherlands were found. The most important factors seemed to be leadership style and goals for collaboration. Leadership style varied from very directive to very supportive and seemed to be connected to the allocation of responsibilities. Goals for collaboration varied from predominantly patient-related to mostly practice-related. Formalization appeared to be more present in larger practices and practices that are affiliated to a dental chain. CONCLUSIONS: Based on leadership style and goals for collaboration, a classification was identified. This classification is recommended as a starting point for further research on directive and supportive leadership in oral health care practices.