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Background: Value-based healthcare (VBHC) is increasingly implemented in healthcare worldwide. Transparent measurement of the outcomes most important and relevant to patients is essential in VBHC, which is supported by a core set of most important quality indicators and outcomes. Therefore, the aim of this study was to develop a VBHC-burns core set for adult burn patients. Methods: A three-round modified national Delphi study, including 44 outcomes and 24 quality indicators, was conducted to reach consensus among Dutch patients, burn care professionals and researchers. Items were rated on a nine-point Likert scale and selected if ≥ 70% in each group considered an item ‘important’. Subsequently, instruments quantifying selected outcomes were identified based on a literature review and were chosen in a consensus meeting using recommendations from the Dutch consensus-based standard set and the Dutch Centre of Expertise on Health Disparities. Time assessment points were chosen to reflect the burn care and patient recovery process. Finally, the initial core set was evaluated in practice, leading to the adapted VBHC-burns core set. Results: Twenty-seven patients, 63 burn care professionals and 23 researchers participated. Ten outcomes and four quality indicators were selected in the Delphi study, including the outcomes pain, wound healing, physical activity, self-care, independence, return to work, depression, itching, scar flexibility and return to school. Quality indicators included shared decision-making (SDM), the number of patients receiving aftercare, determination of burn depth, and assessment of active range of motion. After evaluation of its use in clinical practice, the core set included all items except SDM, which are assessed by 9 patient-reported outcome instruments or measured in clinical care. Assessment time points included are at discharge, 2 weeks, 3 months, 12 months after discharge and annually afterwards. Conclusion: A VBHC-burns core set was devel

Woonplaatskeuze in een notariële akte en stuiting van verjaring, in: Met grootse passen door het recht (red.: W.Burgerhart, J.H.M. ter Haar, B. Hoop, W.D. Kolkman & I. Visser) Ars Notariatus 183, 2024, p. 239t/m 245

Background: The use of patient-reported outcomes to improve burn care increases. Little is known on burn patients’ views on what outcomes are most important, and about preferences regarding online Patient Reported Outcome Measures (PROMs). Therefore, this study assessed what outcomes matter most to patients, and gained insights into patient preferences towards the use of online PROMs. Methods: Adult patients (≥18 years old), 3–36 months after injury completed a survey measuring importance of outcomes, separately for three time periods: during admission, short-term (<6 months) and long-term (6–24 months) after burn injury. Both open and closed-ended questions were used. Furthermore, preferences regarding the use of patient-reported outcome measures in burn care were queried. Results: A total of 140 patients were included (response rate: 27%). ‘Not having pain’ and ‘good wound healing’ were identified as very important outcomes. Also, ‘physical functioning at pre-injury level’, ‘being independent’ and ‘taking care of yourself’ were considered very important outcomes. The top-ten of most important outcomes largely overlapped in all three time periods. Most patients (84%) had no problems with online questionnaires, and many (67%) indicated that it should take up to 15 minutes. Patients’ opinions differed widely on the preferred frequency of follow-up. Conclusions: Not having pain and good wound healing were considered very important during the whole recovery of burns; in addition, physical functioning at pre-injury level, being independent, and taking care of yourself were deemed very important in the short and long-term. These outcomes are recommended to be used in burn care and research, although careful selection of outcomes remains crucial as patients prefer online questionnaires up to 15 minutes.

Comparative cognition research has been largely constrained to isolated facilities, small teams, and a limited number of species. This has led to challenges such as conflicting conceptual definitions and underpowered designs. Here, we explore how Big Team Science (BTS) may remedy these issues. Specifically, we identify and describe four key BTS advantages — increasing sample size and diversity, enhancing task design, advancing theories, and improving welfare and conservation efforts. We conclude that BTS represents a transformative shift capable of advancing research in the field.

27 februari 2023, Item does not contain fulltext, We present an exact replication of Experiment 2 from Kovács and Mehler's 2009 study, which showed that 7-month-old infants who are raised bilingually exhibit a cognitive advantage. In the experiment, a sound cue, following an AAB or ABB pattern, predicted the appearance of a visual stimulus on the screen. The stimulus appeared on one side of the screen for nine trials and then switched to the other side. In the original experiment, both mono- and bilingual infants anticipated where the visual stimulus would appear during pre-switch trials. However, during post-switch trials, only bilingual children anticipated that the stimulus would appear on the other side of the screen. The authors took this as evidence of a cognitive advantage. Using the exact same materials in combination with novel analysis techniques (Bayesian analyses, mixed effects modeling and cluster based permutation analyses), we assessed the robustness of these findings in four babylabs (N = 98). Our results did not replicate the original findings: although anticipatory looks increased slightly during post-switch trials for both groups, bilingual infants were not better switchers than monolingual infants. After the original experiment, we presented additional trials to examine whether infants associated sound patterns with cued locations, for which we did not find any evidence either. The results highlight the importance of multicenter replications and more fine-grained statistical analyses to better understand child development. HIGHLIGHTS: We carried out an exact replication across four baby labs of the high-impact study by Kovács and Mehler (2009). We did not replicate the findings of the original study, calling into question the robustness of the claim that bilingual infants have enhanced cognitive abilities. After the original experiment, we presented additional trials to examine whether infants correctly associated sound patterns with cued locations, for which we did not find any evidence. The us

Contains fulltext : 246903.pdf (Publisher’s version ) (Open Access), We conducted a close replication of the seminal work by Marcus et al. (1999), which showed that after a brief auditory exposure phase, seven-month-old infants were able to learn and generalize a rule to novel syllables not previously present in the exposure phase. This work became the foundation for the theoretical framework by which we assume that infants are able to learn abstract representations and generalize linguistic rules. While some extensions on the original work have shown evidence of rule learning, the outcomes are mixed, and an exact replication of Marcus et al.'s study has thus far not been reported. A recent meta-analysis (Rabagliati et al., 2019) brings to light that the rule-learning effect depends on stimulus type (e.g., meaningfulness, speech versus nonspeech) and is not as robust as often assumed. In light of the theoretical importance of the issue at stake, it is appropriate and necessary to assess the replicability and robustness of Marcus et al.'s findings. Here we have undertaken a replication across four labs with a large sample of seven-month-old infants (N = 96), using the same exposure patterns (ABA and ABB), methodology (Headturn Preference Paradigm), and original stimuli. As in the original study, we tested the hypothesis that infants are able to learn abstract "algebraic" rules and apply them to novel input. Our results did not replicate the original findings: infants showed no difference in looking time between test patterns consistent or inconsistent with the familiarization pattern they were exposed to.

01 juni 2023, Item does not contain fulltext, Vector-borne diseases, including those transmitted by mosquitoes, account for more than 17% of infectious diseases worldwide. This number is expected to rise with an increased spread of vector mosquitoes and viruses due to climate change and man-made alterations to ecosystems. Among the most common, medically relevant mosquito-borne infections are those caused by arthropod-borne viruses (arboviruses), especially members of the genera Flavivirus and Alphavirus. Arbovirus infections can cause severe disease in humans, livestock and wildlife. Severe consequences from infections include congenital malformations as well as arthritogenic, haemorrhagic or neuroinvasive disease. Inactivated or live-attenuated vaccines (LAVs) are available for a small number of arboviruses; however there are no licensed vaccines for the majority of these infections. Here we discuss recent developments in pan-arbovirus LAV approaches, from site-directed attenuation strategies targeting conserved determinants of virulence to universal strategies that utilize genome-wide re-coding of viral genomes. In addition to these approaches, we discuss novel strategies targeting mosquito saliva proteins that play an important role in virus transmission and pathogenesis in vertebrate hosts. For rapid pre-clinical evaluations of novel arbovirus vaccine candidates, representative in vitro and in vivo experimental systems are required to assess the desired specific immune responses. Here we discuss promising models to study attenuation of neuroinvasion, neurovirulence and virus transmission, as well as antibody induction and potential for cross-reactivity. Investigating broadly applicable vaccination strategies to target the direct interface of the vertebrate host, the mosquito vector and the viral pathogen is a prime example of a One Health strategy to tackle human and animal diseases.

16 februari 2022, Item does not contain fulltext, We conducted a close replication of the seminal work by Marcus et al. (1999), which showed that after a brief auditory exposure phase, seven-month-old infants were able to learn and generalize a rule to novel syllables not previously present in the exposure phase. This work became the foundation for the theoretical framework by which we assume that infants are able to learn abstract representations and generalize linguistic rules. While some extensions on the original work have shown evidence of rule learning, the outcomes are mixed, and an exact replication of Marcus et al.'s study has thus far not been reported. A recent meta-analysis (Rabagliati et al., 2019) brings to light that the rule-learning effect depends on stimulus type (e.g., meaningfulness, speech versus nonspeech) and is not as robust as often assumed. In light of the theoretical importance of the issue at stake, it is appropriate and necessary to assess the replicability and robustness of Marcus et al.'s findings. Here we have undertaken a replication across four labs with a large sample of seven-month-old infants (N = 96), using the same exposure patterns (ABA and ABB), methodology (Headturn Preference Paradigm), and original stimuli. As in the original study, we tested the hypothesis that infants are able to learn abstract "algebraic" rules and apply them to novel input. Our results did not replicate the original findings: infants showed no difference in looking time between test patterns consistent or inconsistent with the familiarization pattern they were exposed to.

Background and aims: Pancreatic cancer has a dismal prognosis. So far, imaging has been proven incapable of establishing an early enough diagnosis. Thus, biomarkers are urgently needed for early detection and improved survival. Our aim was to evaluate the pooled diagnostic performance of DNA alterations in pancreatic juice. Methods: A systematic literature search was performed in EMBASE, MEDLINE Ovid, Cochrane CENTRAL and Web of Science for studies concerning the diagnostic performance of DNA alterations in pancreatic juice to differentiate patients with high-grade dysplasia or pancreatic cancer from controls. Study quality was assessed using QUADAS-2. The pooled prevalence, sensitivity, specificity and diagnostic odds ratio were calculated. Results: Studies mostly concerned cell-free DNA mutations (32 studies: 939 cases, 1678 controls) and methylation patterns (14 studies: 579 cases, 467 controls). KRAS, TP53, CDKN2A, GNAS and SMAD4 mutations were evaluated most. Of these, TP53 had the highest diagnostic performance with a pooled sensitivity of 42% (95% CI: 31–54%), specificity of 98% (95%-CI: 92%–100%) and diagnostic odds ratio of 36 (95% CI: 9–133). Of DNA methylation patterns, hypermethylation of CDKN2A, NPTX2 and ppENK were studied most. Hypermethylation of NPTX2 performed best with a sensitivity of 39–70% and specificity of 94–100% for distinguishing pancreatic cancer from controls. Conclusions: This meta-analysis shows that, in pancreatic juice, the presence of distinct DNA mutations (TP53, SMAD4 or CDKN2A) and NPTX2 hypermethylation have a high specificity (close to 100%) for the presence of high-grade dysplasia or pancreatic cancer. However, the sensitivity of these DNA alterations is poor to moderate, yet may increase if they are combined in a panel.

When proteins in aqueous solutions are exposed to solid substrates, they adsorb due to the dynamic interplay of electrostatic, van der Waals, and hydration interactions and do so in a rather irreversible fashion, which makes protein recovery troublesome. Here, we use a gold electrode as the solid substrate and modulate the surface potential to systematically induce protein adsorption as well as partial desorption. We use different methods such as surface plasmon resonance, atomic force microscopy, and electrowetting and show that biasing the electrode to more negative potentials (by -0.4 V compared to the open-circuit potential at pH 6) results in an increased adsorption barrier of 6 kJ mol-1 for the negatively charged protein β-lactoglobulin. Further, we clearly demonstrate that this is due to an increased double layer potential of -0.06 V and an increase in hydration repulsion. This indicates that an electric potential can directly influence surface interactions and thus induce partial β-lactoglobulin desorption. These observations can be the basis for biosensors as well as separation technologies that use only one trigger to steer protein ad- and desorption, which is low in energy requirement and does not generate large waste streams, as is the case for standard protein separation technologies.

Purpose: To investigate the performance of two microwave ablation (MWA) systems regarding ablation volume, ablation shape and variability. Materials and Methods: In this ex vivo study, the Emprint and Amica MWA systems were used to ablate porcine livers at 4 different settings of time and power (3 and 5 minutes at 60 and 80 Watt). In total, 48 ablations were analysed for ablation size and shape using Vitrea Advanced Visualization software after acquisition of a 7T MRI scan. Results: Emprint ablations were smaller (11,1 vs. 21,1 mL p < 0.001), more spherical (sphericity index of 0.89 vs. 0.59 p < 0.001) and showed less variability than Amica ablations. In both systems, longer ablation time and higher power resulted in significantly larger ablation volumes. Conclusion: Emprint ablations were more spherical, and the results showed a lower variability than those of Amica ablations. This comes at the price of smaller ablation volumes., Medical Instruments & Bio-Inspired Technology

Most data analyses rely on models. To complement statistical models, psychologists have developed cognitive models, which translate observed variables into psychologically interesting constructs. Response time models, in particular, assume that response time and accuracy are the observed expression of latent variables including 1) ease of processing, 2) response caution, 3) response bias, and 4) non-decision time. Inferences about these psychological factors hinge upon the validity of the models' parameters. Here, we use a blinded, collaborative approach to assess the validity of such model-based inferences. Seventeen teams of researchers analyzed the same 14 data sets. In each of these two-condition data sets, we manipulated properties of participants' behavior in a two-alternative forced choice task. The contributing teams were blind to the manipulations, and had to infer what aspect of behavior was changed using their method of choice. The contributors chose to employ a variety of models, estimation methods, and inference procedures. Our results show that, although conclusions were similar across different methods, these "modeler's degrees of freedom" did affect their inferences. Interestingly, many of the simpler approaches yielded as robust and accurate inferences as the more complex methods. We recommend that, in general, cognitive models become a typical analysis tool for response time data. In particular, we argue that the simpler models and procedures are sufficient for standard experimental designs. We finish by outlining situations in which more complicated models and methods may be necessary, and discuss potential pitfalls when interpreting the output from response time models.

Most data analyses rely on models. To complement statistical models, psychologists have developed cognitive models, which translate observed variables into psychologically interesting constructs. Response time models, in particular, assume that response time and accuracy are the observed expression of latent variables including 1) ease of processing, 2) response caution, 3) response bias, and 4) non-decision time. Inferences about these psychological factors, hinge upon the validity of the models’ parameters. Here, we use a blinded, collaborative approach to assess the validity of such model-based inferences. Seventeen teams of researchers analyzed the same 14 data sets. In each of these two-condition data sets, we manipulated properties of participants’ behavior in a two-alternative forced choice task. The contributing teams were blind to the manipulations, and had to infer what aspect of behavior was changed using their method of choice. The contributors chose to employ a variety of models, estimation methods, and inference procedures. Our results show that, although conclusions were similar across different methods, these "modeler’s degrees of freedom" did affect their inferences. Interestingly, many of the simpler approaches yielded as robust and accurate inferences as the more complex methods. We recommend that, in general, cognitive models become a typical analysis tool for response time data. In particular, we argue that the simpler models and procedures are sufficient for standard experimental designs. We finish by outlining situations in which more complicated models and methods may be necessary, and discuss potential pitfalls when interpreting the output from response time models.

BACKGROUND: The optimum method of defining cognitive impairment in virally suppressed people living with HIV is unknown. We evaluated the relationships between cognitive impairment, including using a novel multivariate method (NMM), patient- reported outcome measures (PROMs), and neuroimaging markers of brain structure across 3 cohorts. METHODS: Differences in the prevalence of cognitive impairment, PROMs, and neuroimaging data from the COBRA, CHARTER, and POPPY cohorts (total n = 908) were determined between HIV-positive participants with and without cognitive impairment defined using the HIV-associated neurocognitive disorders (HAND), global deficit score (GDS), and NMM criteria. RESULTS: The prevalence of cognitive impairment varied by up to 27% between methods used to define impairment (eg, 48% for HAND vs 21% for NMM in the CHARTER study). Associations between objective cognitive impairment and subjective cognitive complaints generally were weak. Physical and mental health summary scores (SF-36) were lowest for NMM-defined impairment ( P < .05).There were no differences in brain volumes or cortical thickness between participants with and without cognitive impairment defined using the HAND and GDS measures. In contrast, those identified with cognitive impairment by the NMM had reduced mean cortical thickness in both hemispheres ( P < .05), as well as smaller brain volumes ( P < .01). The associations with measures of white matter microstructure and brain-predicted age generally were weaker. CONCLUSION: Different methods of defining cognitive impairment identify different people with varying symptomatology and measures of brain injury. Overall, NMM-defined impairment was associated with most neuroimaging abnormalities and poorer self-reported health status. This may be due to the statistical advantage of using a multivariate approach.

Contains fulltext : 190194.pdf (publisher's version ) (Open Access), Eye-trackers are a popular tool for studying cognitive, emotional, and attentional processes in different populations (e.g., clinical and typically developing) and participants of all ages, ranging from infants to the elderly. This broad range of processes and populations implies that there are many inter- and intra-individual differences that need to be taken into account when analyzing eye-tracking data. Standard parsing algorithms supplied by the eye-tracker manufacturers are typically optimized for adults and do not account for these individual differences. This paper presents gazepath, an easy-to-use R-package that comes with a graphical user interface (GUI) implemented in Shiny (RStudio Inc 2015). The gazepath R-package combines solutions from the adult and infant literature to provide an eye-tracking parsing method that accounts for individual differences and differences in data quality. We illustrate the usefulness of gazepath with three examples of different data sets. The first example shows how gazepath performs on free-viewing data of infants and adults, compared to standard EyeLink parsing. We show that gazepath controls for spurious correlations between fixation durations and data quality in infant data. The second example shows that gazepath performs well in high-quality reading data of adults. The third and last example shows that gazepath can also be used on noisy infant data collected with a Tobii eye-tracker and low (60 Hz) sampling rate.

Item does not contain fulltext, IMPORTANCE: Patients with treatment-resistant depression (TRD) do not respond sufficiently to several consecutive treatments for major depressive disorder. Deep brain stimulation (DBS) is a promising treatment for these patients, but presently placebo effects cannot be ruled out. OBJECTIVE: To assess the efficacy of DBS of the ventral anterior limb of the internal capsule (vALIC), controlling for placebo effects with active and sham stimulation phases. DESIGN, SETTING, AND PARTICIPANTS: Twenty-five patients with TRD from 2 hospitals in the Netherlands were enrolled between March 22, 2010, and May 8, 2014. Patients first entered a 52-week open-label trial during which they received bilateral implants of 4 contact electrodes followed by optimization of DBS until a stable response was achieved. A randomized, double-blind, 12-week crossover phase was then conducted with patients receiving active treatment followed by sham or vice versa. Response and nonresponse to treatment were determined using intention-to-treat analyses. INTERVENTIONS: Deep brain stimulation targeted to the vALIC. MAIN OUTCOMES AND MEASURES: The change in the investigator-rated score of the 17-item Hamilton Depression Rating Scale (HAM-D-17) was the main outcome used in analysis of the optimization phase. The primary outcome of the crossover phase was the difference in the HAM-D-17 scores between active and sham DBS. The score range of this tool is 0 to 52, with higher scores representing more severe symptoms. Patients were classified as responders to treatment (>/=50% decrease of the HAM-D-17 score compared with baseline) and partial responders (>/=25 but <50% decrease of the HAM-D-17 score). RESULTS: Of 25 patients included in the study, 8 (32%) were men; the mean (SD) age at inclusion was 53.2 (8.4) years. Mean HAM-D-17 scores decreased from 22.2 (95% CI, 20.3-24.1) at baseline to 15.9 (95% CI, 12.3-19.5) (P = .001), Montgomery-Asberg Depression Rating Scale scores from 34.0 (95% CI, 31.8-36.3) to

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Oxidative stress induced interactions between fatty acid (FA) and one-carbon metabolism may be involved in co-occurrence of major depressive disorder (MDD) and cardiovascular disease (CVD), which have been scarcely studied together. In 137 recurrent MDD-patients vs. 73 age- and sex-matched healthy controls, we simultaneously measured key components of one-carbon metabolism in plasma (homocysteine, folate, vitamins B6 and B12), and of FA-metabolism in red blood cell membranes [main polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA) and structural FA-indices (chain length, unsaturation, peroxidation)]. Results show significant positive associations of folate with EPA, DHA, and the peroxidation index, which were similar in patients and controls. After correction for confounders, these associations were lost except for EPA. Associations between B-vitamins and FA-parameters were non-significant, but also similar in patients and controls. Homocysteine and DHA were significantly less negatively associated in patients than in controls. In conclusion, these data indicate similarities but also differences in associations between parameters of one-carbon and FA-metabolism in recurrent MDD patients vs. controls, which may reflect differences in handling of oxidative stress. Further research should test the consequences of these differences, particularly the premature development of CVD in MDD.

Item does not contain fulltext, BACKGROUND: Major depressive disorder (MDD) has been associated with low dehydroepiandrosterone-sulphate (DHEAS), - particularly relative to high cortisol - although conflicting findings exist. Moreover, it is unclear whether low DHEAS is only present during the depressive state, or manifests as a trait that may reflect vulnerability for recurrence. Therefore, we longitudinally tested whether low DHEAS and high cortisol/DHEAS-ratio in recurrent MDD (I) reflects a trait, and/or (II) varies with depressive state. In addition, we tested associations with (III) previous MDD-episodes, (IV) prospective recurrence, and (V) effects of cognitive therapy. METHODS: At study-entry, we cross-sectionally compared morning and evening salivary DHEAS and molar cortisol/DHEAS-ratio of 187 remitted recurrent MDD-patients with 72 matched controls. Subsequently, patients participated in an 8-week randomized controlled cognitive therapy trial. We repeated salivary measures after 3 months and 2 years. We measured clinical symptoms during a 10-year follow-up. RESULTS: Remitted patients showed steeper diurnal DHEAS-decline (p<.005) and a flatter diurnal profile of cortisol/DHEAS-ratio (p<.001) than controls. We found no state-effect in DHEAS or cortisol/DHEAS-ratio throughout follow-up and no association with number of previous episodes. Higher morning cortisol/DHEAS-ratio predicted shorter time till recurrence over the 10-year follow-up in interaction with the effects of cognitive therapy (p<.05). Finally, cognitive therapy did not influence DHEAS or cortisol/DHEAS-ratio. CONCLUSIONS: Diurnal profiles of DHEAS and cortisol/DHEAS-ratio remain equally altered in between depressive episodes, and may predict future recurrence. This suggests they represent an endophenotypic vulnerability trait rather than a state-effect, which provides a new road to understand recurrent depression and its prevention. TRIAL REGISTRATION: www.isrctn.com/ISRCTN68246470.