The algebraic square peg problem

The square peg problem asks whether every continuous curve in the plane that starts and ends at the same point without self-intersecting contains four distinct corners of some square. Toeplitz conjectured in 1911 that this is indeed the case. Hundred years later we only have partial results for curves with additional smoothness properties. The contribution of this thesis is an algebraic variant of the square peg problem. By casting the set of squares inscribed on an algebraic plane curve as a variety and applying Bernshtein's Theorem we are able to count the number of such squares. An algebraic plane curve defined by a polynomial of degree m inscribes either an infinite amount of squares, or at most (m4 - 5m2 + 4m)= 4 squares. Computations using computer algebra software lend evidence to the claim that this upper bound is sharp for generic curves. Earlier work on Toeplitz's conjecture has shown that generically an odd number of squares is inscribed on a smooth enough Jordan curve. Examples of real cubics and quartics suggest that there is a similar parity condition on the number of squares inscribed on some topological types of algebraic plane curves that are not Jordan curves. Thus we are led to conjecture that algebraic plane curves homeomorphic to the real line inscribe an even number of squares

Today's Mistakes and Tomorrow's Wisdom in Endoscopic Imaging of Barrett's Esophagus

Background: Esophageal adenocarcinoma (EAC) is one of the main causes of cancer-related deaths worldwide and its incidence is rising. Barrett's esophagus (BE) can develop low- and high-grade dysplasia which can progress to EAC overtime. The golden standard to detect dysplastic BE (DBE) or EAC is surveillance with high-definition white-light endoscopy (HD-WLE) and random biopsies according to the Seattle protocol. However, this method is time-consuming and associated with a remarkable miss rate. Therefore, there is great need for the development of novel reliable techniques to optimize surveillance strategies and improve detection rates.Summary: Optical chromoendoscopy (OC) techniques like narrow-band imaging have shown improved detection of DBE and EAC compared to HD-WLE and random biopsies. Most recent OC techniques, including the iSCAN optical enhancement system and linked color imaging, showed improved characterization of DBE and EAC retrospectively. Fluorescence molecular endoscopy (FME) presented promising results to highlight DBE and EAC. Moreover, with the establishment of well-performing delineation computer-aided detection (CAD) algorithms and the first real-time CAD system for EAC, we expect clinical application of CAD in the near future.Key Messages: Despite impressive progress made in the development of advanced endoscopic techniques, combined HD-WLE/OC followed by random biopsies remains the golden standard for BE surveillance. Surveillance depends on appropriate mucosal cleansing, sufficient inspection time, and competence of the performing gastroenterologist to improve detection of EAC. In addition, to facilitate the clinical implementation of advanced endoscopic techniques, multicenter prospective clinical studies are demanded for OC and FME. Meanwhile, further optimization of CAD algorithms, the education of gastroenterologists, and analysis of the interaction between the clinician and the computer should be performed.</p

Improvement of exercise capacity following neonatal respiratory failure: A randomized controlled trial

Exercise capacity deteriorates in school-aged children born with major anatomical foregut anomalies and/or treated with extracorporeal membrane oxygenation. The aim of the present study was to evaluate whether exercise capacity can be improved in the short term and long term in children born with anatomical foregut anomalies and/or treated with extracorporeal membrane oxygenation. Therefore, we evaluated two different interventions in this single-blinded randomized controlled trial. Forty participants were randomly assigned to group A: standardized anaerobic high-intensity interval training plus online lifestyle coaching program, B: online lifestyle coaching program only, or C: standard of care. Inclusion criteria were as follows: score ≤−1 standard deviation (SD) on the Bruce protocol. Exercise capacity was assessed at baseline (T0), after 3 months (T1), and after 12 months (T2). Exercise capacity improved over time: mean (SD) standard deviation score (SDS) endurance time: T0 −1.91 (0.73); T1 −1.35 (0.94); T2 −1.20 (1.03): both P <.001. No significant differences in maximal endurance time were found at T1 (group A-C: estimated mean difference (SDS): 0.06 P =.802; group B-C: −0.17 P =.733) or T2 (group A-C: −0.13 P =.635; group B-C: −0.18 P =.587). Exercise capacity improved significantly over time, irrespective of the study arm. Not only residual morbidities may be responsible for reduced exercise capacity. Parental awareness of reduced exercise capacity rather than specific interventions may have contributed. Monitoring of exercise tolerance and providing counseling on lifestyle factors that improve physical activity should be part of routine care, and aftercare should be offered on an individual basis

Increase in treatment of retinopathy of prematurity in the Netherlands from 2010 to 2017

Purpose: Compare patients treated for Retinopathy of Prematurity (ROP) in two consecutive periods. Methods: Retrospective inventory of anonymized neonatal and ophthalmological data of all patients treated for ROP from 2010 to 2017 in the Netherlands, subdivided in period (P)1: 1-1-2010 to 31-3-2013 and P2: 1-4-2013 to 31-12-2016. Treatment characteristics, adherence to early treatment for ROP (ETROP) criteria, outco

Detection of Early Esophageal Neoplastic Barrett Lesions with Quantified Fluorescence Molecular Endoscopy Using Cetuximab-800CW

Esophageal adenocarcinoma causes 6% of cancer-related deaths worldwide. Near-infrared fluorescence molecular endoscopy (NIR-FME) uses a tracer that targets overexpressed proteins. In this study, we aimed to investigate the feasibility of an epidermal growth factor receptor (EGFR)–targeted tracer, cetuximab-800CW, to improve detection of early-stage esophageal adenocarcinoma. Methods: We validated EGFR expression in 73 esophageal tissue sections. Subsequently, we topically administered cetuximab-800CW and performed high-definition white-light endoscopy (HD-WLE), narrow-band imaging, and NIR-FME in 15 patients with Barrett esophagus (BE). Intrinsic fluorescence values were quantified using multidiameter single-fiber reflectance and single-fiber fluorescence spectroscopy. Back-table imaging, histopathologic examination, and EGFR immunohistochemistry on biopsy samples collected during NIR-FME procedures were performed and compared with in vivo imaging results. Results: Immunohistochemical preanalysis showed high EGFR expression in 67% of dysplastic tissue sections. NIR-FME visualized all 12 HD-WLE–visible lesions and 5 HD-WLE–invisible dysplastic lesions, with increased fluorescence signal in visible dysplastic BE lesions compared with nondysplastic BE as shown by multidiameter single-fiber reflectance/single-fiber fluorescence, reflecting a target-to-background ratio of 1.5. Invisible dysplastic lesions also showed increased fluorescence, with a target-to-background ratio of 1.67. Immunohistochemistry analysis showed EGFR overexpression in 16 of 17 (94%) dysplastic BE lesions, which all showed fluorescence signal. Conclusion: This study has shown that NIR-FME using cetuximab-800CW can improve detection of dysplastic lesions missed by HD-WLE and narrow-band imaging.</p

MKL1 deficiency results in a severe neutrophil motility defect due to impaired actin polymerization

Megakaryoblastic leukemia 1 (MKL1) promotes the regulation of essential cell processes, including actin cytoskeletal dynamics, by coactivating serum response factor. Recently, the first human with MKL1 deficiency, leading to a novel primary immunodeficiency, was identified. We report a second family with 2 siblings with a homozygous frameshift mutation in MKL1. The index case died as an infant from progressive and severe pneumonia caused by Pseudomonas aeruginosa and poor wound healing. The younger sibling was preemptively transplanted shortly after birth. The immunodeficiency was marked by a pronounced actin polymerization defect and a strongly reduced motility and chemotactic response by MKL1-deficient neutrophils. In addition to the lack of MKL1, subsequent proteomic and transcriptomic analyses of patient neutrophils revealed actin and several actin-related proteins to be downregulated, confirming a role for MKL1 as a transcriptional coregulator. Degranulation was enhanced upon suboptimal neutrophil activation, whereas production of reactive oxygen species was normal. Neutrophil adhesion was intact but without proper spreading. The latter could explain the observed failure in firm adherence and transendothelial migration under flow conditions. No apparent defect in phagocytosis or bacterial killing was found. Also, monocyte-derived macrophages showed intact phagocytosis, and lymphocyte counts and proliferative capacity were normal. Nonhematopoietic primary fibroblasts demonstrated defective differentiation into myofibroblasts but normal migration and F-actin content, most likely as a result of compensatory mechanisms of MKL2, which is not expressed in neutrophils. Our findings extend current insight into the severe immune dysfunction in MKL1 deficiency, with cytoskeletal dysfunction and defective extravasation of neutrophils as the most prominent features