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Abstract The motor neuroscience literature suggests that the central nervous system may encode some motor commands in terms of velocity. In this work, we tackle the question: what consequences would velocity commands produce at the behavioral level? Considering the ubiquitous presence of noise in the neuromusculoskeletal system, we predict that velocity commands affected by stationary noise would produce “random walks”, also known as Brownian processes, in position. Brownian motions are distinctively characterized by a linearly growing variance and a power spectral density that declines in inverse proportion to frequency. This work first shows that these Brownian processes are indeed observed in unbounded motion tasks e.g., rotating a crank. We further predict that such growing variance would still be present, but bounded, in tasks requiring a constant posture e.g., maintaining a static hand position or quietly standing. This hypothesis was also confirmed by experimental observations. A series of descriptive models are investigated to justify the observed behavior. Interestingly, one of the models capable of accounting for all the experimental results must feature forward-path velocity commands corrupted by stationary noise. The results of this work provide behavioral support for the hypothesis that humans plan the motion components of their actions in terms of velocity.

In higher education, many students do not complete their studies within the term allotted. A Dutch university implemented an intervention aimed to reduce this form of academic procrastination. The intervention consisted of three measures: (1) requiring students to acquire all first-year credits within their first year in university, (2) reducing the number of resits, and (3) introducing compensation opportunities for insufficient grades. In this study, we investigated which groups of students (if any) benefited most from this intervention. We divided 29,629 students entering the university between 2009 and 2015 into subgroups based on their gender, ethnic background, and level of achievement during pre-university education. For each subgroup, we determined both first-year completion and three-year bachelor graduation rates, both before and after the introduction of the intervention. It was demonstrated that almost all subgroups profited from the intervention. Particularly students from subgroups that in the past performed less well showed much better first-year completion rates and much lower study delay rates. Dropout rates did not change significantly. For most subgroups, an effect of the intervention was still visible after three years: Three-year graduation rates were higher, although the effect was smaller than completion rates in the first academic year.

Abstract Background This study explores patients’ need for information and support in deciding on esophageal cancer treatment, when experimental active surveillance and standard surgery are both feasible. Methods This psychological companion study was conducted alongside the Dutch SANO‐trial (Surgery As Needed for Oesophageal cancer). In‐depth interviews and questionnaires were used to collect data from patients who declined participation in the trial because they had a strong preference for either active surveillance (n = 20) or standard surgery (n = 20). Data were analyzed using both qualitative and quantitative techniques. Results Patients prefer to receive information directly from their doctors and predominantly rely on this information to make a treatment decision. Other information resources are largely used to confirm their treatment decision. Patients highly value support from their loved ones and appreciate emphatic doctors to actively involve them in the decision‐making process. Overall, patients’ needs for information and support during decision‐making were met. Conclusions The importance of shared decision‐making and the role doctors have in this process is underlined. The role of doctors is essential at the initial phase of decision‐making: Once patients seem to have formed their treatment preference for either active surveillance or surgery, the influence of external resources (including doctors) may be limited.

Objectives To determine whether integrated maternity care is associated with reduced preterm births (PTB) and fewer small-for-gestational-age infants (SGA), and whether its implementation leads to a reduction of secondary care consultations.Design Retrospective study.Setting Integrated maternity care organisation in the southwestern region of the Netherlands.Participants All singleton pregnancies (≥24 weeks) within integrated maternity care organisation Annature between 2015 and 2020.Intervention Implementation of a shared maternity record in primary and secondary care.Methods Data of 20 818 women were derived from patient records and from the Netherlands Perinatal Registry. Intervention was the introduction of integrated maternity care in January 2018. Through multivariate logistic regression and segmented regression analysis we assessed the combined prevalence of SGA and PTB (SGA-PTB) before (2015–2017), and after the intervention (2018–2020). Regional rates were contrasted with nationwide rates (n=782 176).Main outcome measures SGA-PTB prevalence and mean number of secondary care consultations per pregnancy.Results SGA-PTB prevalence declined from 618/3443 (17.9%) in 2015 to 560/3501 (16.0%) in 2017 to 507/3459 (14.7%) in 2020 (p

Abstract Background Neoadjuvant chemoradiotherapy (nCRT) followed by esophagectomy is a standard treatment for potentially curable esophageal cancer. Active surveillance in patients with a clinically complete response (cCR) 12 weeks after nCRT is regarded as possible alternative to standard surgery. The aim of this study is to monitor the safety, adherence and effectiveness of active surveillance in patients outside a randomized trial. Methods This nationwide prospective cohort study aims to accrue operable patients with non-metastatic histologically proven adenocarcinoma or squamous cell carcinoma of the esophagus or esophagogastric junction. Patients receive nCRT and response evaluation consists of upper endoscopy with bite-on-bite biopsies, endoscopic ultrasonography plus fine-needle aspiration of suspicious lymph nodes and 18F-fluorodeoxyglucose positron emission tomography/computed tomography scan. When residue or regrowth of tumor in the absence of distant metastases is detected, surgical resection is advised. Patients with cCR after nCRT are suitable to undergo active surveillance. Patients can consult an independent physician or psychologist to support decision-making. Primary endpoint is the number and severity of adverse events in patients with cCR undergoing active surveillance, defined as complications from response evaluations, delayed surgery and the development of distant metastases. Secondary endpoints include timing and quality of diagnostic modalities, overall survival, progression-free survival, fear of cancer recurrence and decisional regret. Discussion Active surveillance after nCRT may be an alternative to standard surgery in patients with esophageal cancer. Similar to organ-sparing approaches applied in other cancer types, the safety and efficacy of active surveillance needs monitoring before data from randomized trials are available. Trial registration The SANO-2 study has been registered at ClinicalTrials.gov as NCT04886635 (May 14, 2021) – Retrospectively registered.

The purpose of the study reported here was to observe the effects of examination practices on the extent to which university students procrastinate. These examination practices were: (1) limiting the number of resits, (2) compensatory rather than conjunctive decision-making about student progress, and (3) restricting the time available for completing the first bachelor year. Study success in the first academic year (successful completion within one year, delay, or dropout) of 12,432 students entering a Dutch university before the introduction of the new examination practices was compared with that of 17,036 students admitted after its introduction. After the implementation of the new examination practices successful completion increased with 23% and delay decreased with 25%. The data were collected using an interrupted time series design. Three attempts were made to deal with possible threats to its internal validity. (1) Potential confounding variables were demonstrated not to play a role in explaining the effect of the new examination practices. (2) Interrupted time series regression demonstrated that the intervention, not other changes over time, contributed to study success. And (3), extraneous events interfering with the effect of the intervention were shown to be unlikely. In conclusion, the study presented here is the first to demonstrate the effect of examination rules on study delay. The findings indicate that delays, as usually observed in higher education, are not necessarily the result of lack of ability. Nor are they necessarily the effect of some inherent personality disorder.

Abstract Corticotroph macroadenomas are rare but difficult to manage intracranial neoplasms. Mutations in the two Cushing’s disease mutational hotspots USP8 and USP48 are less frequent in corticotroph macroadenomas and invasive tumors. There is evidence that TP53 mutations are not as rare as previously thought in these tumors. The aim of this study was to determine the prevalence of TP53 mutations in corticotroph tumors, with emphasis on macroadenomas, and their possible association with clinical and tumor characteristics. To this end, the entire TP53 coding region was sequenced in 86 functional corticotroph tumors (61 USP8 wild type; 66 macroadenomas) and the clinical characteristics of patients with TP53 mutant tumors were compared with TP53/USP8 wild type and USP8 mutant tumors. We found pathogenic TP53 variants in 9 corticotroph tumors (all macroadenomas and USP8 wild type). TP53 mutant tumors represented 14% of all functional corticotroph macroadenomas and 24% of all invasive tumors, were significantly larger and invasive, and had higher Ki67 indices and Knosp grades compared to wild type tumors. Patients with TP53 mutant tumors had undergone more therapeutic interventions, including radiation and bilateral adrenalectomy. In conclusion, pathogenic TP53 variants are more frequent than expected, representing a relevant amount of functional corticotroph macroadenomas and invasive tumors. TP53 mutations associated with more aggressive tumor features and difficult to manage disease.

Abstract Introduction Malalignment of the Total Ankle Replacement (TAR) has often been postulated as the main reason for the high incidence of TAR failure. As the ankle joint has a small contact area, stresses are typically high, and malalignment may lead to non-homogeneous stress distributions, including stress peaks that may initiate failure. This study aims to elucidate the effect of TAR malalignment on the contact stresses on the bone-implant interface, thereby gaining more understanding of the potential role of malalignment in TAR failure. Methods Finite Element (FE) models of the neutrally aligned as well as malaligned CCI (Ceramic Coated Implant) Evolution TAR implant (Van Straten Medical) were developed. The CCI components were virtually inserted in a generic three-dimensional (3D) reconstruction of the tibia and talus. The tibial and talar TAR components were placed in neutral alignment and in 5° and 10° varus, valgus, anterior and posterior malalignment. Loading conditions of the terminal stance phase of the gait cycle were applied. Peak contact pressure and shear stress at the bone-implant interface were simulated and stress distributions on the bone-implant interface were visualized. Results In the neutral position, a peak contact pressure and shear stress of respectively 98.4 MPa and 31.9 MPa were found on the tibial bone-implant interface. For the talar bone-implant interface, this was respectively 68.2 MPa and 39.0 MPa. TAR malalignment increases peak contact pressure and shear stress on the bone-implant interface. The highest peak contact pressure of 177 MPa was found for the 10° valgus malaligned tibial component, and the highest shear stress of 98.5 MPa was found for the 10° posterior malaligned talar model. High contact stresses were mainly located at the edges of the bone-implant interface and the fixation pegs of the talar component. Conclusions The current study demonstrates that TAR malalignment leads to increased peak stresses. High peak stresses could contribute to bone damage and subsequently reduced implant fixation, micromotion, and loosening. Further research is needed to investigate the relationship between increased contact stresses at the bone-implant interface and TAR failure.

Abstract Background Malalignment is often postulated as an important reason for the high failure rate of total ankle replacements (TARs). The correlation between TAR malalignment and clinical outcome, however, is not fully understood. Improving and expanding radiographic TAR alignment measurements in the clinic might lead to a better insight into the correlation between malalignment and the clinical outcome. This study aims to develop and validate a tool to semi‐automatic measure TAR alignment, and to improve alignment measurements on radiographs in the clinic. Methods A tool to semi‐automatically measure TAR alignment on anteroposterior and lateral radiographs was developed in MATLAB. Using the principle of edge contouring and the perpendicular relationship between the anteroposterior and lateral radiographs, the exact configuration of the TAR components can be found. Two observers validated the tool by measuring TAR alignment of ten patients using the tool. The Intraclass Coefficient (ICC) was calculated to assess the reliability of the developed method. The results obtained by the tool were compared to clinical results during radiographic follow‐up in the past, and the accuracy of both methods was calculated using three‐dimensional CT data. Results The tool showed an accuracy of 76% compared to 71% for the method used during follow‐up. ICC values were 0.94 (p

Abstract Background Total ankle arthroplasty is increasingly used as a treatment for end stage ankle arthropathy. The aim of this study was to report the mid‐term clinical function and survival results of Ceramic Coated Implant (CCI) ankle replacements and assess the association between the alignment of the CCI total ankle replacements and early functional outcome and complication incidence. Methods Data of 61 patients, who received 65 CCI implants between 2010 and 2016, were obtained from a prospectively documented database. Mean follow‐up time was 85.2 months (range 27–99 months). Clinical function was assessed with AOFAS questionnaire and passive range of motion (ROM). Survival analysis and elaborate radiographic analysis was performed. Furthermore, complications and reoperations were recorded for all patients. Results Progression in ROM was most seen in the first 10 months from 21.8 degrees of passive range of motion preoperative to 27.6 degrees postoperative (p

Background: Adrenocortical carcinoma is a rare malignancy with a poor prognosis. We hypothesized that patients with adrenocortical carcinoma are at high risk for venous thromboembolism, given the numerous risk factors such as malignancy, abdominal surgery, immobility and hormonal excess. The aim of this study was to determine retrospectively the incidence of venous thromboembolisms after surgical treatment in patients with adrenocortical carcinoma. Materials and methods: A retrospective study was performed, collecting data from all patients diagnosed with adrenocortical carcinoma from 2003 to 2018 at the Radboud University Medical Centre, The Netherlands. Results: In 34 patients, eight postoperative venous thromboembolisms, all pulmonary embolisms, were diagnosed in the first 6 months after adrenalect omy (23.5%). In addition, one patient developed pulmonary embolism just prior to surgery and one patient 7 years after surgery. Five of the eight patients with postoperative venous thromboembolisms presented with symptomatic pulmonary embolism whereas the other three pulmonary embolisms were incidentally found on regular follow up CT scans. Seven of the eight venous thromboembolisms occurred within 10 weeks after surgery. Seven of the eight patients had advanced stage adrenocortical carcinoma and four patients already received low-molecular weight heparin during the development of the venous thromboembolism. There was one case of fatal pulmonary embolism in a patient with a cortisol producing tumor with pulmonary metastases, despite the use of a therapeutic dose thromboprophylaxis. Conclusion: Patients with adrenocortical carcinoma are at high risk of developing postoperative venous thromboembolisms. Prolonged postoperative thromboprophylaxis could be considered in these patients.

Autoimmune thyroid diseases (AITD) are common, affecting 2-5% of the general population. Individuals with positive thyroid peroxidase antibodies (TPOAbs) have an increased risk of autoimmune hypothyroidism (Hashimoto's thyroiditis), as well as autoimmune hyperthyroidism (Graves' disease). As the possible causative genes of TPOAbs and AITD remain largely unknown, we performed GWAS meta-analyses in 18,297 individuals for TPOAb-positivity (1769 TPOAb-positives and 16,528 TPOAb-negatives) and in 12,353 individuals for TPOAb serum levels, with replication in 8,990 individuals. Significant associations (P