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Early detection of colorectal cancer is key to full recovery. This urged governments to start population screening programs for colorectal cancer, often using flexible endoscopes. Flexible endoscopy is difficult to learn and time-consuming. Automation of flexible endoscopes may increase the capacity for the screening programs. The goal of this pilot study is to investigate the clinical and technical feasibility of an assisting automated navigation algorithm for a colonoscopy procedure. Automated navigation (lumen centralization) was implemented in a robotized system designed for conventional flexible endoscopes. Ten novice and eight expert users were asked to perform a diagnostic colonoscopy on a colon model twice: once using the conventional and once using the robotic system. Feasibility was evaluated using time and location data as measures of the system’s added value. Automated target centralization (ATC) was turned on by the novices for a median of 4.2 % of the time during insertion and 0.3 % during retraction. Experts turned ATC on for 4.0 % of the time during insertion and 11.6 % during retraction. Novices and experts showed comparable times to reach the cecum with the conventional or the robotic setup with ATC. The ATC algorithm combined with the robotized endoscope setup works in an experimental setup that closely resembles the clinical environment and is considered feasible, although ATC use was lower than expected. For novices, it was unclear whether the low usage was due to unfamiliarity with the system or because they did not need ATC. Experts used ATC also during the retraction phase of the procedure. This was an unexpected finding and may indicate an added value of the system.

BackgroundPathogenic germline variants in Transient Receptor Potential Vanilloid 4 Cation Channel (TRPV4) lead to channelopathies, which are phenotypically diverse and heterogeneous disorders grossly divided in neuromuscular disorders and skeletal dysplasia. We recently reported in sporadic giant cell lesions of the jaws (GCLJs) novel, somatic, heterozygous, gain-of-function mutations in TRPV4, at Met713.MethodsHere we report two unrelated women with a de novo germline p.Leu619Pro TRPV4variant and an overlapping systemic disorder affecting all organs individually described in TRPV4 channelopathies.ResultsFrom an early age, both patients had several lesions of the nervous system including progressive polyneuropathy, and multiple aggressive giant cell-rich lesions of the jaws and craniofacial/skull bones, and other skeletal lesions. One patient had a relatively milder disease phenotype possibly due to postzygotic somatic mosaicism. Indeed, the TRPV4p.Leu619Pro variant was present at a lower frequency (variant allele frequency (VAF)=21.6%) than expected for a heterozygous variant as seen in the other proband, and showed variable regional frequency in the GCLJ (VAF ranging from 42% to 10%). In silico structural analysis suggests that the gain-of-function p.Leu619Pro alters the ion channel activity leading to constitutive ion leakage.ConclusionOur findings define a novel polysystemic syndrome due to germline TRPV4p.Leu619Pro and further extend the spectrum of TRPV4channelopathies. They further highlight the convergence of TRPV4mutations on different organ systems leading to complex phenotypes which are further mitigated by possible post-zygotic mosaicism. Treatment of this disorder is challenging, and surgical intervention of the GCLJ worsens the lesions, suggesting the future use of MEK inhibitors and TRPV4 antagonists as therapeutic modalities for unmet clinical needs.

Fast and efficient calibration is essential for the effective application of crop models. However, many formulas, parameters, and nonlinear responses in crop models make calibration difficult and time consuming. Using an intelligent optimization algorithm to calibrate the model has advantages in global search ability, optimization speed, and automatic calibration compared to the manual trial and error method, although performance may depend strongly on the objective function used. This study evaluated the use of an improved genetic algorithm, namely elite genetic algorithm (EGA), for calibration of a water‐driven crop model (AquaCrop) using three different objective functions separately, which comprise observed variables from harvest and in‐season data and differ in calculating the weight factors of these variables. Observations of maize (Zea maysL.) and wheat (Triticum aestivumL.) under different irrigation treatments were used for model calibration and validation. The results showed satisfactory calibration performances for the EGA applying the three objective functions, that is, the coefficient of determination and index of agreement were all >0.97 for canopy cover (CC) and biomass of both maize and wheat, and also showed good agreement between simulated and observed soil water storage. The three objective functions differed in calibration speed and performance, since they differ in error source and calculation, moreover, they performed similar or better than manual calibration. The validation results showed that the AquaCrop model calibrated by the EGA can predict CC, biomass, yield, and soil water storage of maize and wheat. In general, calibration of the AquaCrop model using EGA greatly improves the model application efficiency for irrigation management.

RationalePaediatric laryngotracheal stenosis (LTS) is often successfully corrected with open airway surgery. However, respiratory and vocal sequelae frequently remain. Clinical care and surgical interventions could be improved with better understanding of these sequelae.ObjectiveThe objective of this cross-sectional study was to develop an upper airway MRI protocol to obtain information on anatomical and functional sequelae post-LTS repair.MethodsForty-eight patients (age 14.4 (range 7.5–30.7) years) and 11 healthy volunteers (15.9 (8.2–28.8) years) were included. Spirometry and static and dynamic upper airway MRI (3.0 T, 30 min protocol) were conducted. Analysis included assessment of postoperative anatomy and airway lumen measurements during static and dynamic (inspiration and phonation) acquisitions.Main resultsGood image quality without artefacts was achieved for static and dynamic images in the majority of MRIs. MRI showed vocal cord thickening in 80.9% of patients and compared with volunteers, a significant decrease in vocal cord lumen area (22.0 (IQR 17.7–30.3) mm2vs 35.1 (21.2–54.7) mm2, p=0.03) but not cricoid lumen area (62.3±27.0 mm2vs 66.2±34.8 mm2, p=0.70). Furthermore, 53.2% of patients had an A-frame deformation at site of previous tracheal cannula, showing lumen collapse during inspiration. Dynamic imaging showed incomplete vocal cord abduction during inspiration in 42.6% and incomplete adduction during phonation in 61.7% of patients.ConclusionsStatic and dynamic MRI is an excellent modality to non-invasively image anatomy, tissue characteristics and vocal cord dynamics of the upper airways. MRI-derived knowledge on postsurgical LTS sequelae might be used to improve surgery.

Abnormalities of the hyoid bone are associated with impairment of oropharyngeal functions including feeding, swallowing, and breathing. Few studies have characterized anatomic abnormalities of the hyoid in patients with Robin sequence (RS), e.g. a less mineralized and voluminous hyoid. The purpose of this study was to compare normal hyoid bone morphology and hyoid bone morphology in children with isolated RS.

Objective To reflect upon our non-surgical respiratory management by evaluating clinical outcomes regarding airway, feeding, and growth during the first year of life in patients with Robin Sequence.Design Prospective study.Setting Sophia Children's Hospital, Rotterdam, the Netherlands.Patients/ Participants 36 patients with Robin Sequence who were treated between 2011 and 2021.Interventions Positional therapy and respiratory support.Main Outcome Measure(s) Data on respiratory outcomes included polysomnography characteristics and capillary blood gas values. Feeding outcomes were based on the requirement of additional tube feeding. Outcomes on growth were expressed as standard-deviation-scores (SDS) for weight-for-age (WFA) and height-for-age (HFA).Results Twenty patients were treated with positional therapy (PT), whilst the other 16 patients required respiratory support. Twenty-two patients presented with non-isolated Robin Sequence (RS). During the first year of life, obstructive apnea hypopnea index decreased, oxygen levels enhanced, and capillary blood gas values improved. Eighty-six percent (31/36) experienced feeding difficulties, which completely resolved in 71% (22/31) during their first year of life. From start treatment, to stop treatment, to the age of 1 year, the SDS WFA worsened from −0.40 to −0.33 to −1.03, respectively.Conclusions Non-surgical respiratory treatment resulted in an improvement of respiratory outcomes to near normal during the first year of life in patients with RS. These patients often experience feeding difficulties and endure impaired weight gain up to 1 year of age, despite near normalization of breathing. The high prevalence of feeding difficulties and impaired weight for age indicate the urgency for early recognition and adequate treatment to support optimal growth.

Methane fluxes (FCH4) vary significantly across wetland ecosystems due to complex mechanisms, challenging accurate estimations. The interactions among environmental drivers, while crucial in regulating FCH4, have not been well understood. Here, the interactive effects of six environmental drivers on FCH4were first analyzed using 396,322 half-hourly measurements from 22 sites across various wetland types and climate zones. Results reveal that soil temperature, latent heat turbulent flux, and ecosystem respiration primarily exerted direct effects on FCH4, while air temperature and gross primary productivity mainly exerted indirect effects by interacting with other drivers. Significant spatial variability in FCH4regulatory mechanisms was highlighted, with different drivers demonstrated varying direct, indirect, and total effects among sites. This spatial variability was then linked to site-specific annual-average air temperature (17.7%) and water table (9.0%) conditions, allowing the categorization of CH4sources into four groups with identified critical drivers. An improved estimation approach using a random forest model with three critical drivers was consequently proposed, offering accurate FCH4predictions with fewer input requirements. By explicitly accounting for environmental interactions and interpreting spatial variability, this study enhances our understanding of the mechanisms regulating CH4emissions, contributing to more efficient modeling and estimation of wetland FCH4.

ObjectiveIt is difficult to predict the presence of histological risk factors for lymph node metastasis (LNM) before endoscopic treatment of T1 colorectal cancer (CRC). Therefore, endoscopic therapy is propagated to obtain adequate histological staging. We examined whether secondary surgery following endoscopic resection of high-risk T1 CRC does not have a negative effect on patients' outcomes compared with primary surgery.DesignPatients with T1 CRC with one or more histological risk factors for LNM (high risk) and treated with primary or secondary surgery between 2000 and 2014 in 13 hospitals were identified in the Netherlands Cancer Registry. Additional data were collected from hospital records, endoscopy, radiology and pathology reports. A propensity score analysis was performed using inverse probability weighting (IPW) to correct for confounding by indication.Results602 patients were eligible for analysis (263 primary; 339 secondary surgery). Overall, 34 recurrences were observed (5.6%). After adjusting with IPW, no differences were observed between primary and secondary surgery for the presence of LNM (OR 0.97; 95% CI 0.49 to 1.93; p=0.940) and recurrence during follow-up (HR 0.97; 95% CI 0.41 to 2.34; p=0.954). Further adjusting for lymphovascular invasion, depth of invasion and number of retrieved lymph nodes did not alter this outcome.ConclusionsOur data do not support an increased risk of LNM or recurrence after secondary surgery compared with primary surgery. Therefore, an attempt for an en-bloc resection of a possible T1 CRC without evident signs of deep invasion seems justified in order to prevent surgery of low-risk T1 CRC in a significant proportion of patients.

Background Most post-colonoscopy colorectal cancers (PC-CRCs) are thought to develop from missed or incompletely resected adenomas.Aims We aimed to assess the incidence rate of PC-CRC overall and per colorectal segment, as a proxy for PC-CRC due to incomplete adenoma resection, and to identify adenoma characteristics associated with these PC-CRCs.Methods We performed a nationwide, population-based cohort study, including all patients with a first colorectal adenoma between 2000–2010 in the Dutch Pathology Registry (PALGA). Outcomes were the incidence rate of PC-CRC overall and of PC-CRC in the same colorectal segment, occurring between six months and five years after adenoma resection. A multivariable Cox proportional hazard analysis was performed to identify factors associated with PC-CRCs in the same segment.Results We included 107,744 patients (mean age 63.4 years; 53.6% male). PC-CRC was detected in 1031 patients (0.96%) with an incidence rate of 1.88 per 1000 person years. PC-CRC in the same segment was found in 323 of 133,519 adenomas (0.24%) with an incidence rate of 0.56 per 1000 years of follow-up. High-grade dysplasia (hazard ratio (HR) 2.54, 95% confidence interval (CI) 1.99–3.25) and both villous (HR 2.63, 95% CI 1.79–3.87) and tubulovillous histology (HR 1.80, 95% CI 1.43–2.27) were risk factors for PC-CRC in the same segment.Conclusions Approximately one-third of PC-CRCs are found in the same colorectal segment after adenoma resection and could therefore be a consequence of incomplete adenoma resection, occurring in one in 400 adenomas. The risk of PC-CRC in the same segment is increased in adenomas with high-grade dysplasia or (tubulo)villous histology.

Most post-colonoscopy colorectal cancers (PC-CRCs) are thought to develop from missed or incompletely resected adenomas. We aimed to assess the incidence rate of PC-CRC overall and per colorectal segment, as a proxy for PC-CRC due to incomplete adenoma resection, and to identify adenoma characteristics associated with these PC-CRCs. We performed a nationwide, population-based cohort study, including all patients with a first colorectal adenoma between 2000–2010 in the Dutch Pathology Registry (PALGA). Outcomes were the incidence rate of PC-CRC overall and of PC-CRC in the same colorectal segment, occurring between six months and five years after adenoma resection. A multivariable Cox proportional hazard analysis was performed to identify factors associated with PC-CRCs in the same segment. We included 107,744 patients (mean age 63.4 years; 53.6% male). PC-CRC was detected in 1031 patients (0.96%) with an incidence rate of 1.88 per 1000 person years. PC-CRC in the same segment was found in 323 of 133,519 adenomas (0.24%) with an incidence rate of 0.56 per 1000 years of follow-up. High-grade dysplasia (hazard ratio (HR) 2.54, 95% confidence interval (CI) 1.99–3.25) and both villous (HR 2.63, 95% CI 1.79–3.87) and tubulovillous histology (HR 1.80, 95% CI 1.43–2.27) were risk factors for PC-CRC in the same segment. Approximately one-third of PC-CRCs are found in the same colorectal segment after adenoma resection and could therefore be a consequence of incomplete adenoma resection, occurring in one in 400 adenomas. The risk of PC-CRC in the same segment is increased in adenomas with high-grade dysplasia or (tubulo)villous histology.

Computed tomography-colonography is a diagnostic modality that can be used when the colon is not completely intubated during colonoscopy. It may have the additional advantage that information on extracolonic lesions can be obtained.

Chimpanzees are knuckle walkers, with forelimbs contacting the ground by the dorsum of the finger's middle phalanges. As these muscular apes are given to high-velocity motions, the question arises of how the ground reaction forces are buffered so that no damage ensues in the load-bearing fingers. In the literature, it was hypothesized that the finger flexors help buffer impacts because in knuckle stance the metacarpophalangeal joints (MCPJs) are strongly hyperextended, which would elongate the finger flexors. This stretching of the finger flexor muscle–tendon units would absorb impact energy. However, EMG studies did not report significant finger flexor activity in knuckle walking. Although these data by themselves question the finger flexor impact buffering hypothesis, the present study aimed to critically investigate the hypothesis from a biomechanical point of view. Therefore, various aspects of knuckle walking were modeled and the finger flexor tendon displacements in the load-bearing fingers were measured in a chimpanzee cadaver hand, of which also an MRI was taken in knuckle stance. The biomechanics do not support the finger flexor impact buffering hypothesis. In knuckle walking, the finger flexors are not elongated to lengths where passive strain forces would become important. Impact buffering by large flexion moments at the MCPJs from active finger flexors would result in impacts at the knuckles themselves, which is dysfunctional for various biomechanical reasons and does not occur in real knuckle walking. In conclusion, the current biomechanical analysis in accumulation of previous EMG findings suggests that finger flexors play no role in impact buffering in knuckle walking.

The Reflux Finding Score for Infants (RFS-I) was developed to objectively assess signs of laryngopharyngeal reflux (LPR). Based on review of flexible laryngoscopic videos, only moderate inter- and highly variable intraobserver reliability was found. We hypothesized that examination of the infant larynx with rigid laryngoscopy would provide better agreement. AIM: to assess the validity of the RFS-I in the detection of LPR-related findings using flexible versus rigid laryngoscopy. Thirty consecutive infants underwent flexible and rigid laryngoscopy. Based on the recorded videos, RFS-I was scored by 4 otorhinolaryngologists, 2 otorhinolaryngology fellows, and 2 inexperienced observers. Videos were presented in a randomized order, blinded for clinical profile and findings during initial examination. Observers were provided an instruction sheet prior to evaluation. For categorical data, agreement was calculated using Cohen's kappa (2 observers) and Fleiss’ kappa (>2 observers). For ordinal data the intraclass correlation coefficient (ICC) was used. Of 30 included patients (17?M; median age 7.5 (0–19.8) months), main reasons for referral were: stridor (n?=?15,50%), ALTE/apneas (n?=?7,23.3%), follow-up of laryngeal abnormalities (n?=?6,20%), aspiration (n?=?5,16.7%), and other indications (n?=?7,23.3%). Overall interobserver agreement of the RFS-I was moderatefor both flexible (ICC?=?0.60, [95%CI 0.44–0.76]) and rigid (ICC?=?0.42, [95%CI 0.26–0.62] laryngoscopy. There were no significant differences in agreement on overall RFS-I scores and individual RFS-I items for flexible versus rigid laryngoscopy. We did observe higher overall agreement amongst the 2 inexperienced observers for rigid (ICC?=?0.40, [95%CI 0.03–0.67]), compared to flexible (ICC?=?0.11, [95%CI 0.17–0.41]) laryngoscopy, albeit not significant. Comparing RFS-I results for flexible versus rigid laryngoscopy perobserver, agreement ranged from noto substantialagreement (k?=?-0.16–0.63, mean k?=?0.22) and the observed agreement (not adjusted for chance) was 0.08–0.35%. Interobserver agreement of the RFS-I was only moderate and did not differ between flexible and rigid laryngoscopy. This indicates that the RFS-I should not be used with flexible, nor rigid laryngoscopy to detect signs of LPR.