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The results are reported of a histological examination by means of serial or multiple sections of 7 malignant lesions of varying type found in a patient with epidermodysplasia verruciformis (E.V.). A number of more or less conspicuous histological features encountered in the various biopsies are recorded; Acantholysis was fairly common. Two of the biopsies showed the picture of an adenoid squamous cell carcinoma, while a keratosis senilis like lesion, if not removed, would also probably have developed into this type of carcinoma. Areas of atypically proliferating epithelium showing Bowenoid features were seen in a number of the examined biopsies. Adjacent to rudimentary pilar structures, distortion and degenerative alterations of hair follicles were found. Unusual cells observed in some of the biopsies are described and discussed. All biopsies showed actinic elastosis in the upper layers of the dermis. No conclusive evidence of a relationship between the malignant changes and the original E.V. lesions could be demonstrated from a histological point of view. This is in contradistinction to the opinion of other authors. Microscopic examination of clinically unaffected skin from the forehead showed, besides atrophy and pigmentation of the basal layer of the epidermis, the occurrence of scattered melanophages and actinic elastosis in the dermis. Serial section of this biopsy additionally revealed at one place a downward proliferation of epithelium suspected of being malignant. Since knowledge of the origin of malignant changes in E.V. must be considered to be still incomplete, more attention should be paid to the unusual actinic damage found at a relatively early age in the exposed skin of these patients. On the histomorphology and origin of malignant cutaneous changes in epidermodysplasia verruciformis. Available from: https://www.researchgate.net/publication/19037140_On_the_histomorphology_and_origin_of_malignant_cutaneous_changes_in_epidermodysplasia_verruciformis [accessed Nov 27 2017].

Background Foetal aortic stenosis (AS) is a challenging congenital heart disease considering its potential to progress during the course of pregnancy. Especially at midgestation, it remains extremely difficult to distinguish the cases that end up biventricular from the cases that will develop into an hypoplastic left heart syndrome. Purpose To test the hypothesis that the degree of myocardial maturation is a possible predictor of biventricular outcome, we present 4 cases of foetal AS with a varying degree of severity and uniquely correlate differences in myocardial function based on prenatal echocardiography to their post-mortem histopathologic maturation. Methods We selected 4 cases with midgestational AS from our tertiary foetal cardiology service between 2018–2020. Speckle tracking recordings of the cardiac four-chamber view were performed during routine foetal echocardiography to quantify myocardial wall motion as a marker for myocardial function. Three cases decided to terminate the pregnancy and donated the cardiac specimen. Immunohistochemical labelling (ICH) against key markers for myocardial maturation (troponin-I, N-cadherin, connexin-43, MLC2A, MLC2V and α-SMA) and fibrosis (Sirius Red) were compared with 2 normal foetal cardiac specimens. Results Two cases with critical AS presented extremely decreased global and segmental longitudinal strain (GLS and SLS) values (GLS −2% and −0.9%) in the left ventricle (LV), indicating an impaired myocardial wall deformation. Post-mortem ICH showed overt endocardial fibro-elastosis (EFE) and pathological fibrosis patterns in the subendocardial layer which was remarkably spatially correlated to the EFE. The cardiomyocytes were disorganised with reduced expression of troponin-I and disturbed expression of connexin-43. The remaining 2 cases had normal LV appearance on foetal echocardiography, showing a mild reduction in left ventricular GLS and SLS (GLS −11.8% and −14.2%). Post-mortem ICH of 1 of these cases showed mild EFE with a milder fibrosis pattern. Cardiomyocytes were less disorganised but also showed a disturbed expression of connexin-43. The 4th case continued the pregnancy and had a biventricular outcome. Conclusions This is a unique case series showing that myocardial function correlates with high extent to histology. The degree of the reduction in myocardial function corresponded with the amount of pathological fibrosis patterns and disorganisation of the cardiomyocyte network. Myocardial wall motion on foetal echocardiography seems to hold promise as a possible marker for cardiac maturation. Funding Acknowledgement Type of funding sources: None. Speckle tracking and fibrosis patterns

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In this paper, the exemplary results of the IEA Wind Task 30 Offshore Code Comparison Collaboration Continuation (OC4) Project - Phase I, focused on the coupled simulation of an offshore wind turbine (OWT) with a jacket support structure, are presented. The focus of this task has been the verification of OWT modeling codes through code-to-code comparisons. The discrepancies between the results are shown and the sources of the differences are discussed. The importance of the local dynamics of the structure is depicted in the simulation results. Furthermore, attention is given to aspects such as the buoyancy calculation and methods of accounting for additional masses (i.e., hydrodynamic added mass). Finally, recommendations concerning the modeling of the jacket are given.

Our healthcare system is under increasing pressure, both in terms of financial and human capacity, which forces us into difficult choices. Value-based healthcare offers a theory in which the outcomes of care that matter to patients, relative to the costs incurred, are leading in these choices. Important principles of value-based healthcare are organizing care around the patient and gaining insight into care outcomes that matter to patients. In perinatal care, collaboration around the pregnant woman (integrated maternity care) is already underway, but relatively little insight exists into care results from the patient's perspective. In this thesis, we investigated how structured questionnaires on patient-reported outcomes of perinatal care, such as breastfeeding or incontinence, and experiences, such as satisfaction or autonomy, can contribute to improved care. In clinic, we saw that discussing answers individually as part of regular care contacts helped to identify complaints and personalize care, provided that the questionnaires were properly aligned with the care path. At group level, the insight into outcome data gave healthcare providers motivation for quality improvement. Translating the data into recognizable personas helped to achieve substantive discussion and improvement actions. The network-wide approach to measuring and improving outcomes ensured patient-centeredness but hindered implementation. The iterative, context-specific approach of action research helped to achieve change. The findings in this thesis provide direction for the implementation and application of patient-reported measures around pregnancy and childbirth to strengthen the development towards a healthcare system driven by value for patients.

Rationale: Despite the preferred application of arterial conduits, the greater saphenous vein (SV) remains indispensable for coronary bypass grafting (CABG), especially in multi-vessel coronary artery disease (CAD). The objective of the present work was to address the role of mechanical forces in the activation of maladaptive vein bypass remodeling, a process determining progressive occlusion and recurrence of ischemic heart disease.Methods: We employed a custom bioreactor to mimic the coronary shear and wall mechanics in human SV vascular conduits and reproduce experimentally the biomechanical conditions of coronary grafting and analyzed vein remodeling process by histology, histochemistry and immunofluorescence. We also subjected vein-derived cells to cyclic uniaxial mechanical stimulation in culture, followed by phenotypic and molecular characterization using RNA and proteomic methods. We finally validated our results in vitro and using a model of SV carotid interposition in pigs.Results: Exposure to pulsatile flow determined a remodeling process of the vascular wall involving reduction in media thickness. Smooth muscle cells (SMCs) underwent conversion from contractile to synthetic phenotype. A time-dependent increase in proliferating cells expressing mesenchymal (CD44) and early SMC (SM22α) markers, apparently recruited from the SV adventitia, was observed especially in CABG-stimulated vessels. Mechanically stimulated SMCs underwent transition from contractile to synthetic phenotype. MALDI-TOF-based secretome analysis revealed a consistent release of Thrombospondin-1 (TSP-1), a matricellular protein involved in TGF-β-dependent signaling. TSP-1 had a direct chemotactic effect on SV adventitia resident progenitors (SVPs); this effects was inhibited by blocking TSP-1 receptor CD47. The involvement of TSP-1 in adventitial progenitor cells differentiation and graft intima hyperplasia was finally contextualized in the TGF-β-dependent pathway, and validated in a saphenous vein into carotid interposition pig model.Conclusions: Our results provide the evidence of a matricellular mechanism involved in the human vein arterialization process controlled by alterations in tissue mechanics, and open the way to novel potential strategies to block VGD progression based on targeting cell mechanosensing-related effectors.

PSR B0950+08 is a bright non-recycled pulsar whose single-pulse fluence variability is reportedly large. Based on observations at two widely separated frequencies, 55 MHz (NenuFAR) and 1.4 GHz (Westerbork Synthesis Radio Telescope), we review the properties of these single pulses. We conclude that they are more similar to ordinary pulses of radio emission than to a special kind of short and bright Giant Pulses, observed from only a handful of pulsars. We argue that temporal variation of properties of interstellar medium along the line of sight to this nearby pulsar, namely the fluctuating size of decorrelation bandwidth of diffractive scintillation makes important contribution to observed single-pulse fluence variability. We further present interesting structures in the low-frequency single-pulse spectra that resemble the "sad trombones" seen in Fast Radio Bursts (FRBs); although for PSR B0950+08 the upward frequency drift is also routinely present. We explain these spectral features with radius-to-frequency mapping, similar to the model developed by Wang et al. (2019) for FRBs. Finally, we speculate that microsecond-scale fluence variability of the general pulsar population remains poorly known, and that its further study may bring important clues about the nature of FRBs., Accepted by A&A. This version includes a number of minor corrections, including corrected FRB luminosities on the time-luminosity phase-space plot for radio pulses from neutron stars and repeating FRBs

Supermassive black holes at the centres of galaxies can cycle through periods of activity and quiescence. Characterising the duty cycle of active galactic nuclei is crucial for understanding the impact of the energy they release on the host galaxy. For radio AGN, this can be done by identifying dying (remnant) and restarted radio galaxies from their radio spectral properties. Using the combination of images at 1400 MHz produced by Apertif, the new phased-array feed receiver installed on the Westerbork Synthesis Radio Telescope, and images at 150 MHz provided by LOFAR, we have derived resolved spectral index images (at a resolution of ~15 arcsec) for all the sources within ~6 deg^2 area of the Lockman Hole region. We were able to select 15 extended radio sources with emission (partly or entirely) characterised by extremely steep spectral indices (steeper than 1.2). These objects represent radio sources in the remnant or the restarted phases of their life cycle. Our findings suggest this cycle to be relatively fast. They also show a variety of properties relevant for modelling the evolution of radio galaxies. For example, the restarted activity can occur while the remnant structure from a previous phase of activity is still visible. This provides constraints on the duration of the 'off' (dying) phase. In extended remnants with ultra-steep spectra at low frequencies, the activity likely stopped a few hundred megayears ago, and they correspond to the older tail of the age distribution of radio galaxies, in agreement with simulations of radio source evolution. We find remnant radio sources with a variety of structures (from double-lobed to amorphous), suggesting different types of progenitors. The present work sets the stage for exploiting low-frequency spectral index studies of extended sources by taking advantage of the large areas common to the LOFAR and the Apertif surveys., Accepted for publication in A&A. This paper is part of the 1st data release of the LoTSS Deep Fields. 17 pages, 10 figures

Despite recent advances, the synthesis of colloidal InSb quantum dots (QDs) remains underdeveloped, mostly due to the lack of suitable precursors. In this work, we use Lewis acid–base interactions between Sb(III) and In(III) species formed at room temperature in situ from commercially available compounds (viz., InCl3, Sb[NMe2]3 and a primary alkylamine) to obtain InSb adduct complexes. These complexes are successfully used as precursors for the synthesis of colloidal InSb QDs ranging from 2.8 to 18.2 nm in diameter by fast coreduction at sufficiently high temperatures (≥230 °C). Our findings allow us to propose a formation mechanism for the QDs synthesized in our work, which is based on a nonclassical nucleation event, followed by aggregative growth. This yields ensembles with multimodal size distributions, which can be fractionated in subensembles with relatively narrow polydispersity by postsynthetic size fractionation. InSb QDs with diameters below 7.0 nm have the zinc blende crystal structure, while ensembles of larger QDs (≥10 nm) consist of a mixture of wurtzite and zinc blende QDs. The QDs exhibit photoluminescence with small Stokes shifts and short radiative lifetimes, implying that the emission is due to band-edge recombination and that the direct nature of the bandgap of bulk InSb is preserved in InSb QDs. Finally, we constructed a sizing curve correlating the peak position of the lowest energy absorption transition with the QD diameters, which shows that the band gap of colloidal InSb QDs increases with size reduction following a 1/d dependence.