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Background and purpose: The direct superior approach (DSA) is a modification of the posterolateral approach (PLA) for total hip arthroplasty (THA). Patient-reported outcome measures (PROMs) of the DSA have not been investigated previously using nationwide data. Our aim was to assess PROMs after THA using the DSA compared with the PLA and, secondarily, with the anterior approach (DAA). Patients and methods: In this population-based cohort study we included 37,976 primary THAs performed between 2014 and 2020 (PLA: n = 22,616; DAA: n = 15,017; DSA: n = 343) using Dutch Arthroplasty Registry data. PROMs (NRS pain, EQ-5D, HOOS-PS, and OHS) were measured preoperatively, and at 3 and 12 months postoperatively. Repeated measurements were analyzed using mixed-effects models, adjusted for confounders, to investigate the association between surgical approach and PROMs over time. Results: From baseline to 3 and 12 months, improvements for NRS pain scores, EQ-5D, and OHS were comparable for the DSA compared with the PLA or DAA. No difference was found in HOOS-PS improvement 3 months postoperatively between DSA and PLA (–0.2, 95% confidence interval [CI] –2.4 to 1.9) and between DSA and DAA (–1.7, CI –3.9 to 0.5). At 12 months postoperatively, patients in the DSA group had improved –2.8 points (CI –4.9 to –0.6) more in HOOS-PS compared with the DAA, but not with the PLA group (–1.0, CI –3.2 to 1.1). Conclusion: Our study showed no clinically meaningful differences between the DSA and either PLA or DAA.

Current diagnostic criteria for myelofibrosis are largely based on bone marrow (BM) biopsy results. However, these have several limitations, including sampling errors. Explorative studies have indicated that imaging might form an alternative for the evaluation of disease activity, but the heterogeneity in BM abnormalities complicates the choice for the optimal technique. In our prospective diagnostic pilot study, we aimed to visualize all BM abnormalities in myelofibrosis before and during ruxolitinib treatment using both PET/CT and MRI. A random sample of patients was scheduled for examinations at baseline and after 6 and 18 months of treatment, including clinical and laboratory examinations, BM biopsies, MRI (T1-weighted, Dixon, dynamic contrast-enhanced (DCE)) and PET/CT ([15O]water, [18F]NaF)). At baseline, all patients showed low BM fat content (indicated by T1-weighted MRI and Dixon), increased BM blood flow (as measured by [15O]water PET/CT), and increased osteoblastic activity (reflected by increased skeletal [18F]NaF uptake). One patient died after the baseline evaluation. In the others, BM fat content increased to various degrees during treatment. Normalization of BM blood flow (as reflected by [15O]water PET/CT and DCE-MRI) occurred in one patient, who also showed the fastest clinical response. Vertebral [18F]NaF uptake remained stable in all patients. In evaluable cases, histopathological parameters were not accurately reflected by imaging results. A case of sampling error was suspected. We conclude that imaging results can provide information on functional processes and disease distribution throughout the BM. Differences in early treatment responses were especially reflected by T1-weighted MRI. Limitations in the gold standard hampered the evaluation of diagnostic accuracy.

Abstract Vaginal inflammation increases the risk for sexual HIV-1 transmission but underlying mechanisms remain unclear. In this study we assessed the impact of immune activation on HIV-1 susceptibility of primary human vaginal Langerhans cells (LCs). Vaginal LCs isolated from human vaginal tissue expressed a broad range of TLRs and became activated after exposure to both viral and bacterial TLR ligands. HIV-1 replication was restricted in immature vaginal LCs as only low levels of infection could be detected. Notably, activation of immature vaginal LCs by bacterial TLR ligands increased HIV-1 infection, whereas viral TLR ligands were unable to induce HIV-1 replication in vaginal LCs. Furthermore, mature vaginal LCs transmitted HIV-1 to CD4 T cells. This study emphasizes the role for vaginal LCs in protection against mucosal HIV-1 infection, which is abrogated upon activation. Moreover, our data suggest that bacterial STIs can increase the risk of HIV-1 acquisition in women.

Abstract Background Increasing number of falls and fall-related injuries in an aging society give rise to the need for effective fall prevention and rehabilitation strategies. Besides traditional exercise approaches, new technologies show promising options for fall prevention in older adults. As a new technology-based approach, the hunova robot can support fall prevention in older adults. The objective of this study is to implement and evaluate a novel technology-supported fall prevention intervention using the hunova robot compared to an inactive control group. The presented protocol aims at introducing a two-armed, multi-centre (four sites) randomised controlled trial, evaluating the effects of this new approach on the number of falls and number of fallers as primary outcomes. Methods The full clinical trial incorporates community-dwelling older adults at risk of falls with a minimum age of 65 years. Including a one-year follow-up measurement, all participants are tested four times. The training programme for the intervention group comprises 24-32 weeks in which training sessions are scheduled mostly twice a week; the first 24 training sessions use the hunova robot, these are followed by a home-based programme of 24 training sessions. Fall-related risk factors as secondary endpoints are measured using the hunova robot. For this purpose, the hunova robot measures the participants’ performance in several dimensions. The test outcomes are input for the calculation of an overall score which indicates the fall risk. The hunova-based measurements are accompanied by the timed-up-and-go test as a standard test within fall prevention studies. Discussion This study is expected to lead to new insights which may help establish a new approach to fall prevention training for older adults at risk of falls. First positive results on risk factors can be expected after the first 24 training sessions using the hunova robot. As primary outcomes, the number of falls and fallers within the study (including the one-year follow-up period) are the most relevant parameters that should be positively influenced by our new approach to fall prevention. After the study completion, approaches to examine the cost-effectiveness and develop an implementation plan are relevant aspects for further steps. Trial registration German Clinical Trial Register (DRKS), ID: DRKS00025897. Prospectively registered 16 August 2021, https://drks.de/search/de/trial/DRKS00025897 .

Background: Differentiation between uncomplicated and complicated postoperative wound drainage after arthroplasty is crucial to prevent unnecessary reoperation. Prospective data about the duration and amount of postoperative wound drainage in patients with and without prosthetic joint infection (PJI) are currently absent. Methods: A multicentre cohort study was conducted to assess the duration and amount of wound drainage in patients after arthroplasty. During 30 postoperative days after arthroplasty, patients recorded their wound status in a previously developed wound care app and graded the amount of wound drainage on a 5-point scale. Data about PJI in the follow-up period were extracted from the patient files. Results: Of the 1019 included patients, 16 patients (1.6 %) developed a PJI. Minor wound drainage decreased from the first to the fourth postoperative week from 50 % to 3 %. Both moderate to severe wound drainage in the third week and newly developed wound drainage in the second week after a week without drainage were strongly associated with PJI (odds ratio (OR) 103.23, 95 % confidence interval (CI) 26.08 to 408.57, OR 80.71, 95 % CI 9.12 to 714.52, respectively). The positive predictive value (PPV) for PJI was 83 % for moderate to heavy wound drainage in the third week. Conclusion: Moderate to heavy wound drainage and persistent wound drainage were strongly associated with PJI. The PPV of wound drainage for PJI was high for moderate to heavy drainage in the third week but was low for drainage in the first week. Therefore, additional parameters are needed to guide the decision to reoperate on patients for suspected acute PJI.

The use of computer-based tests (CBTs), for both formative and summative purposes, has greatly increased over the past years. One major advantage of CBTs is the easy integration of multimedia. It is unclear, though, how to design such CBT environments with multimedia. The purpose of the current study was to examine whether guidelines for designing multimedia "instruction" based on the Cognitive Load Theory (CLT) and Cognitive Theory of Multimedia Learning (CTML) will yield similar effects in CBT. In a within-subject design, thirty-three vocational students completed a computer-based arithmetic exam, in which half of the items were presented in an original design format, and the other half was redesigned based on the CTML principles for instructional design (i.e., adapted format). Results showed that applying CTML principles to a CBT decreased the difficulty of the test items, i.e., students scored significantly higher on the adapted test items. Moreover, eye-tracking data showed that the adapted items required less visual search and increased attention for the question and answer. Finally, cognitive load, measured as silent pauses during a secondary think-aloud task, decreased. Mean fixation duration (a different indicator of cognitive load), however, did not significantly differ between adapted and original items. These results indicate that applying multimedia principles to CBTs can be beneficial. It seems to prevent cognitive overload and helps students to focus on important parts of the test items (e.g., the question), leading to better test results.

The use of evidence-based smoking cessation interventions (SCIs) can significantly increase the number of successful smoking cessation attempts. To obtain an overview of the knowledge and viewpoints on the effectiveness and use of SCIs, a three-round online Delphi study was conducted among researchers and primary care professionals (PCPs). The four objectives of this study are to gain an overview of (i) the criteria important for recommending SCIs, (ii) the perceptions of both groups on the effectiveness of SCIs, (iii) the factors to consider when counseling different (high-risk) groups of smokers and (iv) the perceptions of both groups on the use of e-cigarettes as an SCI. We found a high level of agreement within groups on which smoker characteristics should be considered when recommending an SCI to smokers. We also found that PCPs display a lower degree of consensus on the effectiveness of SCIs. Both groups see a value in the use of special protocols for different (high-risk) groups of patients, but the two groups did not reach consensus on the use of e-cigarettes as a means to quit. Making an inventory of PCPs' needs regarding SCIs and their usage may provide insight into how to facilitate a better uptake in the primary care setting.

Abstract Aim Clinical prediction models need to be validated. In this study, we used simulation data to compare various internal and external validation approaches to validate models. Methods Data of 500 patients were simulated using distributions of metabolic tumor volume, standardized uptake value, the maximal distance between the largest lesion and another lesion, WHO performance status and age of 296 diffuse large B cell lymphoma patients. These data were used to predict progression after 2 years based on an existing logistic regression model. Using the simulated data, we applied cross-validation, bootstrapping and holdout (n = 100). We simulated new external datasets (n = 100, n = 200, n = 500) and simulated stage-specific external datasets (1), varied the cut-off for high-risk patients (2) and the false positive and false negative rates (3) and simulated a dataset with EARL2 characteristics (4). All internal and external simulations were repeated 100 times. Model performance was expressed as the cross-validated area under the curve (CV-AUC ± SD) and calibration slope. Results The cross-validation (0.71 ± 0.06) and holdout (0.70 ± 0.07) resulted in comparable model performances, but the model had a higher uncertainty using a holdout set. Bootstrapping resulted in a CV-AUC of 0.67 ± 0.02. The calibration slope was comparable for these internal validation approaches. Increasing the size of the test set resulted in more precise CV-AUC estimates and smaller SD for the calibration slope. For test datasets with different stages, the CV-AUC increased as Ann Arbor stages increased. As expected, changing the cut-off for high risk and false positive- and negative rates influenced the model performance, which is clearly shown by the low calibration slope. The EARL2 dataset resulted in similar model performance and precision, but calibration slope indicated overfitting. Conclusion In case of small datasets, it is not advisable to use a holdout or a very small external dataset with similar characteristics. A single small testing dataset suffers from a large uncertainty. Therefore, repeated CV using the full training dataset is preferred instead. Our simulations also demonstrated that it is important to consider the impact of differences in patient population between training and test data, which may ask for adjustment or stratification of relevant variables.

Abstract Background Cognitions and perceptions of workers with chronic health problems, such as catastrophizing thoughts and fear-avoidance beliefs, can negatively influence work participation. The Progressive Goal Attainment Program (PGAP) is an intervention developed in Canada with the aim of decreasing limiting cognitions and perceptions and increasing work participation. The objective of this protocol article is to describe the design of a randomized controlled superiority trial to study whether PGAP is effective in decreasing limiting cognitions and perceptions and increasing workability and work participation of workers with chronic health problems in the Netherlands. Methods This study is a randomized controlled superiority trial with two (parallel) groups, in which workers on sick leave are randomly assigned to an intervention group (PGAP intervention) or to a waiting-list control group (care as usual). The PGAP intervention consists of a maximum of 10 weekly individual sessions provided by a trained PGAP professional in which the worker learns about staying active, planning activities, and setting goals. Participants in this risk-targeted behavioral activation intervention also learn to be more aware of their cognitions and perceptions and learn about solution-focused problem-solving skills in challenging situations. The primary outcome is the degree of catastrophizing. Secondary outcomes are other personal cognitions and perceptions (e.g., expectations regarding return to work, self-efficacy), health symptoms (e.g., fatigue, depression), work participation (e.g., sick leave status, work hours), and other work-related outcomes (e.g., workability, quality of working life). Discussion Although PGAP shows positive effects in Canada, we do not know whether this intervention is effective in the Netherlands. This study is the first randomized controlled trial to test the effect of PGAP on limiting cognitions and perceptions and on work participation of workers with chronic health problems in the Netherlands. If PGAP is effective it could be implemented in the Netherlands in order to stimulate workability and work participation of workers. Trial registration The protocol of this study is registered in the Netherlands Trial Register (NL9832) in October 2021.

Abstract Background To study the factors associated with the intention of primary care professionals (PCPs) to use or not use a referral aid (RA) for selecting an evidence-based smoking cessation intervention (EBSCI). Methods Participants (n = 85) were recruited from June to September 2020 to complete an online questionnaire based on the I-Change Model to assess the factors associated with the adoption of RA. The differences between PCPs with (n = 37) and without (n = 48) the intention to adopt in terms of demographics, motivational factors, and post-motivational factors were subsequently assessed. Correlation and logistic regression analyses were conducted to investigate the factors associated with the intention to adopt. Results Both groups indicated that they highly appreciated the RA. However, PCPs without the intention to adopt expressed a more negative attitude towards the RA, experienced less social support, showed low self-efficacy, and encountered barriers such as lack of time and skills. The factors most strongly associated with the intention to adopt were advantages, disadvantages, self-efficacy, less barriers, working in a solo practice and age. Conclusions The adoption of RA can be facilitated in two ways. The first one is by increasing the added value of the tool through a second round of co-creation focusing on the adoptability of the RA in practice. The second approach is by communicating the added value of referring to EBSCIS and thereby using the RA by implementing it in smoking cessation training for PCPs, which could also help to improve the attitude, social support, self-efficacy, and perceived skills in terms of RA usage among PCPs. Impact This study is the first work in the Netherlands to investigate the willingness of PCPs to actively refer patients to other EBSCIs in addition to providing face-to-face counseling themselves. Trial registration The study was registered at the Netherlands Trial Register (NL7020, https://www.trialregister.nl/trial/7020 ).

Angst om te vallen komt frequent voor bij ouderen. In het verleden zijn hiervoor verschillende meetmethoden ontwikkeld. Een bekend en veelgebruikt is de Falls Efficacy Scale (FES). De FES blijkt echter (a) met name gericht te zijn op slechter functionerende ouderen en op activiteiten binnenshuis en minder geschikt te zijn voor ouderen uit de algemene populatie, (b) geen betrekking te hebben op sociale activiteiten die verband kunnen houden met valangst, en (c) te zijn ontwikkeld vanuit Amerikaans perspectief waardoor een eenduidige vertaling in verschillende Europese talen wordt bemoeilijkt. Binnen het Prevention of Falls Network Europe (ProFaNE) is de 16-item Falls Efficacy Scale-International (FES-I) ontwikkeld om tegemoet te komen aan deze bezwaren. In dit artikel wordt de Nederlandse versie van de FES-I gepresenteerd en wordt verslag gedaan van de psychometrische kwaliteiten van de FES-I in een Nederlandse steekproef van 213 ouderen van 70 jaar en ouder. De FES-I blijkt unidimensioneel en intern consistent te zijn; de test-hertest betrouwbaarheid is goed. De samenhang met leeftijd, geslacht, valincidenten en bezorgdheid om te vallen wordt zoals verwacht aangetroffen. Het discriminerend vermogen van de FES-I is vergelijkbaar met de oorspronkelijke FES. Geconcludeerd kan worden dat de FES-I een betrouwbaar en valide instrument is om angst om te vallen bij ouderen vast te stellen. Toekomstig onderzoek zal moeten uitwijzen of de FES-I ook gevoeliger is dan de FES voor het vaststellen van veranderingen in angst om te vallen.

BackgroundHouse dust mite (HDM) is a major cause of respiratory allergic diseases. Dendritic cells (DCs) play a central role in orchestrating adaptive allergic immune responses. However, it remains unclear how DCs become activated by HDM. Biochemical functions of the major HDM allergens Der p 1 (cysteine protease) and Der p 2 (MD2-mimick) have been implicated to contribute to DC activation.MethodsWe investigated the immune activating potential of HDM extract and its major allergens Der p 1 and Der p 2 using monocyte-derived DCs (moDCs). Maturation and activation markers were monitored by flow cytometry and cytokine production by ELISA. Allergen depletion and proteinase K digestion were used to investigate the involvement of proteins, and in particular of the major allergens. Inhibitors of spleen tyrosine kinase (Syk), Toll-like receptor 4 (TLR4) and of C-type lectin receptors (CLRs) were used to identify the involved receptors. The contribution of endotoxins in moDC activation was assessed by their removal from HDM extract.ResultsHDM extract induced DC maturation and cytokine responses in contrast to the natural purified major allergens Der p 1 and Der p 2. Proteinase K digestion and removal of Der p 1 or Der p 2 did not alter the immune stimulatory capacity of HDM extract. Antibodies against the CLRs Dectin-1, Dectin-2, and DC-SIGN did not affect cytokine responses. In contrast, Syk inhibition partially reduced IL-6, IL-12 and completely blocked IL-10. Blocking TLR4 signaling reduced the HDM-induced IL-10 and IL-12p70 induction, but not IL-6, while endotoxin removal potently abolished the induced cytokine response.ConclusionOur data strongly suggest that HDM-induced DC activation is neither dependent on Der p 1 nor Der p 2, but depend on Syk and TLR4 activation, which might suggest a crosstalk between Syk and TLR4 pathways. Our data highlight that endotoxins play a potent role in immune responses targeting HDM.

Background: Recently, non-hyperemic pressure ratios (NHPRs) have been validated as a reliable alternative to fractional flow reserve (FFR). However, a discordance between FFR and NHPRs is observed in 20–25% of cases. The aim of this study is to evaluate predictors of discordance between FFR and diastolic Pressure ratio (dPR). Methods: PREDICT is a retrospective, single center, investigator-initiated study including 813 patients (1092vessels) who underwent FFR assessment of intermediate coronary lesions (angiographic 30%-80% stenosis). dPR was calculated using individual pressure waveforms and dedicated software. Clinical, angiographic and hemodynamic variables were compared between patients with concordant and discordant FFR and dPR values. Results: Median age was 65 (IQR:59–73) years and 70% were male. Hemodynamically significant lesions, as defined by FFR ≤ 0.80, and dPR ≤ 0.89, were identified in 29.6% and 30.3% of cases, respectively. Overall, FFR and dPR values were discordant in 22.1% patients (17.4% of the vessels). Discordance was related to FFR+/dPR- and FFR-/dPR + in 11.8% and 10.3% of patients, respectively.In case of FFR-dPR discordance, a higher prevalence of left anterior descending arteries lesions was observed (70.5% vs. 53.1%, p

Highlights: • Standardised questionnaires are used to measure the outcomes of citizenship education. • A prerequisite for cross-group comparisons based on these questionnaires is an assessment of measurement invariance. • This study used data from 6035 students from 87 Dutch primary schools to examine the measurement invariance of citizenship knowledge, attitude, and skill across sex, socioeconomic position and migration background. • The measurement invariance was sufficient in most cases. • Periodic assessment of measurement invariance in instruments measuring citizenship competences is important due to the dynamic nature of the construct. Purpose: Standardised questionnaires are used to measure the outcomes of citizenship education. These outcomes are often compared across groups to document different outcomes, for example, between boys and girls. A prerequisite for cross-group comparisons is an assessment of measurement invariance. Methodology: This study used data from 6035 students from 87 Dutch primary schools to examine the measurement invariance of the Citizenship Competences Questionnaire (Ten Dam et al., 2011). Dutch schools use this questionnaire to gain insight into students’ citizenship knowledge, attitudes, and skills. Measurement invariance was assessed across sex, socioeconomic position, and migration background. Findings: Measurement invariance was sufficient in most cases, allowing for cross-group comparisons of associations between latent constructs and their indicators, and in some cases, for cross-group comparisons of the latent means. We conclude by emphasising that periodic assessment of measurement invariance in instruments measuring citizenship competences is important due to the dynamic nature of the construct.

The hydrogen recombination lines H30 α , H40 α , H42 α , H50 β , and H57 γ and the underlying bremsstrahlung continuum emission were detected with ALMA in the bipolar nebula Mz3. The source was not spatially resolved, but the velocity profile of the H30 α line shows clear indication of maser amplification, confirming previous reports of laser amplification in the far-infrared H recombination lines observed with Herschel Space Observatory. Comparison between the flux densities of the H50 β , H40 α , and H42 α lines show overcooling, or darkness amplification by stimulated absorption (dasar effect) at the LSR velocity of about −25 km s ^−1 , which constrains the density of the absorbing region to about 10 ^3 cm ^−3 . The H30 α line, on the other hand, presents maser lines at LSR velocities of −69 and −98 km s ^−1 , which indicates ionized gas with densities close to 10 ^7 cm ^−3 . Although the source of emission was not resolved, it was possible to find the central position of the images for each velocity interval, which resulted in a well defined position–velocity distribution.

We present the first detection of the ground-state OH emission line at 1612 MHz toward the prototypical carbon-rich planetary nebula (PN) NGC 7027, utilizing the newly installed ultrawideband (UWB) receiver of the Five-hundred-meter Aperture Spherical radio Telescope (FAST). This emission is likely to originate from the interface of the neutral shell and the ionized region. The other three ground-state OH lines at 1665, 1667, and 1721 MHz are observed in absorption and have velocities well matched with that of HCO ^+ absorption. We infer that the OH absorption is from the outer shell of NGC 7027, although the possibility that they are associated with a foreground cloud cannot be completely ruled out. All the OH lines exhibit a single blueshifted component with respect to the central star. The formation of OH in carbon-rich environments might be via photodissociation-induced chemical processes. Our observations offer significant constraints for chemical simulations, and they underscore the potent capability of the UWB receiver of FAST to search for nascent PNe.

We present point-source photometry from the Spitzer Space Telescope's final survey of the Small Magellanic Cloud (SMC). We mapped nearly 30 deg ^2 in two epochs in 2017, with the second extending to early 2018 at 3.6 and 4.5 μ m using the Infrared Array Camera. This survey duplicates the footprint from the SAGE-SMC program in 2008. Together, these surveys cover a nearly 10 yr temporal baseline in the SMC. We performed aperture photometry on the mosaicked maps produced from the new data. We did not use any prior catalogs as inputs for the extractor in order to be sensitive to any moving objects (e.g., foreground brown dwarfs) and other transient phenomena (e.g., cataclysmic variables or FU Ori–type eruptions). We produced a point-source catalog with high-confidence sources for each epoch as well as a combined-epoch catalog. For each epoch and the combined-epoch data, we also produced a more complete archive with lower-confidence sources. All of these data products will be made available to the community at the Infrared Science Archive.