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Background and Objective: Total mesorectal excision (TME) for rectal cancer (RC) often results in significant bowel symptoms, commonly known as low anterior resection syndrome (LARS). Although pelvic floor muscle training (PFMT) is recommended in noncancer populations for treating bowel symptoms, this has been scarcely investigated in RC patients. The objective was to investigate PFMT effectiveness on LARS in patients after TME for RC. Methods: A multicenter, single-blind prospective randomized controlled trial comparing PFMT (intervention; n=50) versus no PFMT (control; n=54) 1 month following TME/stoma closure was performed. The primary endpoint was the proportion of participants with an improvement in the LARS category at 4 months. Secondary outcomes were: continuous LARS scores, ColoRectal Functioning Outcome scores, Numeric Rating Scale scores, stool diary items, and Short Form 12 scores; all assessed at 1, 4, 6, and 12 months. Results: The proportion of participants with an improvement in LARS category was statistically higher after PFMT compared with controls at 4 months (38.3% vs 19.6%; P=0.0415) and 6 months (47.8% vs 21.3%; P=0.0091), but no longer at 12 months (40.0% vs 34.9%; P=0.3897). Following secondary outcomes were significantly lower at 4 months: LARS scores (continuous, P=0.0496), ColoRectal Functioning Outcome scores (P=0.0369) and frequency of bowel movements (P=0.0277), solid stool leakage (day, P=0.0241; night, P=0.0496) and the number of clusters (P=0.0369), derived from the stool diary. No significant differences were found for the Numeric Rating Scale/quality of life scores. Conclusions: PFMT for bowel symptoms after TME resulted in lower proportions and faster recovery of bowel symptoms up to 6 months after surgery/stoma closure, justifying PFMT as an early, first-line treatment option for bowel symptoms after RC. The authors are grateful to the trial participants and thank all participating centers and collaborating physiotherapists (MW, LDW, LV, RVH) of this trial for their contributions. They also thank Kim Sterckx, Hilde Lemkens, and Lynn Debrun especially, for all of their contributions.

The immunopathophysiological mechanisms underlying chronic inflammatory demyelinating polyneuropathy (CIDP) in an individual patient are largely unknown. Better understanding of these mechanisms may aid development of biomarkers and targeted therapies. Both B- and T-cell dominant mechanisms have been implicated. We therefore investigated whether B-cell and T-cell receptor (BCR/TCR) repertoires might function as immunological biomarkers in CIDP. In this prospective cohort study, we longitudinally sampled peripheral blood of CIDP patients in three different phases of CIDP: starting induction treatment (IT), starting withdrawal from IVIg maintenance treatment (MT), and patients in remission (R). BCR and TCR repertoires were analyzed using RNA based high throughput sequencing. In baseline samples, the number of total clones, the number of dominant BCR and TCR clones and their impact on the repertoire was similar for patients in the IT, MT, and remission groups compared with healthy controls. Baseline samples in the IT or MT did not predict treatment response or potential relapse at follow-up. Treatment responders in the IT group showed a potential IVIg-induced increase in the number of dominant BCR clones and their impact at follow-up (baseline1.0 [IQR 1.0-2.8] vs. 6 m 3.5 [0.3-6.8]; P

Contains fulltext : 292318.pdf (Publisher’s version ) (Open Access) OBJECTIVE: The aim of this systematic review was to evaluate whether exercise prehabilitation programs reduce postoperative complications, postoperative mortality, and length of hospital stay (LoS) in patients undergoing surgery for non-small cell lung cancer (NSCLC), thereby accounting for the quality of the physical exercise program. METHODS: Two reviewers independently selected randomized controlled trials (RCTs) and observational studies and assessed them for methodological quality and therapeutic quality of the exercise prehabilitation program (i-CONTENT tool). Eligible studies included patients with NSCLC performing exercise prehabilitation and reported the occurrence of 90-day postoperative complications, postoperative mortality, and LoS. Meta-analyses were performed and the certainty of the evidence was graded (Grading of Recommendations Assessment, Development and Evaluation (GRADE)) for each outcome. RESULTS: Sixteen studies, comprising 2,096 patients, were included. Pooled analyses of RCTs and observational studies showed that prehabilitation reduces postoperative pulmonary complications (OR 0.45), postoperative severe complications (OR 0.51), and LoS (mean difference -2.46 days), but not postoperative mortality (OR 1.11). The certainty of evidence was very low to moderate for all outcomes. Risk of ineffectiveness of the prehabilitation program was high in half of the studies due to an inadequate reporting of the dosage of the exercise program, inadequate type and timing of the outcome assessment, and low adherence. CONCLUSION: Although risk of ineffectiveness was high for half of the prehabilitation programs and certainty of evidence was very low to moderate, prehabilitation seems to result in a reduction of postoperative pulmonary and severe complications, as well as LoS in patients undergoing surgery for NSCLC.

This letter presents a method to estimate the space-dependent transport coefficients (diffusion, convection, reaction, and source/sink) for a generic scalar transport model, e.g., heat or mass. As the problem is solved in the frequency domain, the complex valued state as a function of the spatial variable is estimated using Gaussian process regression. The resulting probability density function of the state, together with a semi-discretization of the model, and a linear parameterization of the coefficients are used to determine the maximum likelihood solution for these space-dependent coefficients. The proposed method is illustrated by simulations.

After its illegal occupation and annexation of Crimea in 2014 and continued military support for separatists in the Donbas, Russia escalated its war against Ukraine in February 2022 with direct ground attacks by Russian military forces on Ukraine's eastern, northern and southern borders, a blockade of Ukraine's coast and aerial attacks throughout the country. Millions of Ukrainians fled, including thousands of international students residing in Ukraine. Countries around the world responded to the resulting refugee crisis with varying policies. Many of Ukraine's neighboring countries enacted model immigration laws and developed various support schemes. Some governments, such as in Poland and the European Union (EU), immediately granted Ukrainian refugees the right to live, work, obtain access to education and receive benefits comparable to those to which their own citizens are entitled and created a generous and protective immigration model that attempts to prevent human trafficking and other forms of exploitation. Other countries geographically removed from the conflict used different models, including some with a private sponsorship component that, despite the best of intentions, may in retrospect be exposing refugees to the dangers of human trafficking and exploitation. Ukrainian refugees – also referred to as internally displaced persons (IDPs) if still remaining in Ukraine or as parolees if attempting to enter the United States (US) – seeking entry into the United Kingdom (UK) or US are required to find a private sponsor who accepts financial responsibility for them during their stay in their host country. In the UK, private sponsors are paid a monthly stipend, while in the US, private sponsors are not paid but actually contract with the US government to be financially responsible for the persons whom they are sponsoring. By contrast, Ukraine's neighbors, including Poland, with notably less economic and fiscal resources than either the UK or the US, have no private sponsorship requirement. Since the collapse of the Soviet Union in 1991, Ukrainians have been a vulnerable population subjected to human trafficking – a situation exacerbated by Russia's current war against their country. In the first weeks of the war, credible firsthand and in-real-time reports by Ukrainian- and Russian-speaking attorneys and human rights advocates quickly emerged that describe Ukrainian women refugees utilizing online dating platforms, social media sites and online chat rooms to find private sponsors in the UK and the US. While this government policy requiring private sponsorship appeared to be a prudent means for vetting refugees, burden-sharing and shifting the hosting costs away from taxpayers and governments' ledgers, the policy has unintended consequences. Refugee and human trafficking experts state that the private sponsorship requirement compels Ukrainian refugees, 90-plus percent of whom are women and children, to 'market' themselves – often online – to potential private sponsors in the UK and US, thereby exposing themselves to human traffickers. This policy has potentially – albeit unintentionally – increased, exacerbated and even facilitated the human trafficking of Ukrainian refugees, an already vulnerable population experiencing a precariously heightened risk for physical, sexual and economic exploitation due to their growing desperation for physical safety. This article, written from the practitioners' perspective, discusses how the private sponsorship requirement for Ukrainian refugees is potentially increasing the risk of human trafficking for an already at-risk population, unnecessarily jeopardizing their safety and further stripping them of their human dignity. The unintended consequences of private sponsorship demonstrate that such a requirement in a wartime scenario is ill-conceived, inappropriate and dangerous public policy and, dare it be said, potentially exploitative.

Rabies is the deadliest viral infection known, with no reliable treatment, and although it is entirely preventable, rabies continues to kill more than 60,000 people every year, mostly children in countries where dog rabies is endemic. America is only 1 generation away from the time when rabies killed more than 10,000 animals and 50 Americans every year, but 3 to 5 Americans continue to die annually from rabies. Distressingly, > 50,000 Americans undergo rabies prevention therapy every year after exposure to potentially rabid animals. While enormous progress has been made, more must be done to defeat this ancient but persistent, fatal zoonosis. In the US, lack of public awareness and ambivalence are the greatest dangers imposed by rabies, resulting in unnecessary exposures, anxiety, and risk. Veterinarians have a special role in informing and reassuring the public about prevention and protection from rabies. This summary of current facts and future advances about rabies will assist veterinarians in informing their clients about the disease.

Background Scapholunate (SL) ligament injuries are rarely diagnosed in children. This study reports the outcomes of surgically treated SL ligament injuries in patients younger than 18 years. Methods A retrospective review was performed on 20 pediatric patients with SL ligament injuries. Records were reviewed for preoperative and postoperative radiographic data, intraoperative findings, classifications of interosseous ligament injury, and postoperative course. Results Thirteen girls and seven boys sustained SL injuries requiring operative intervention and were followed for an average of 26 months. Magnetic resonance imaging (MRI) was performed in 15 patients, which revealed an SL tear in 7 patients. Arthroscopically, SL injuries were classified as Geissler grade III in 12 patients and grade IV in 5 patients. Based on the Mayo Wrist Score, nine patients had excellent or good results, while six demonstrated fair results. The mean wrist flexion–extension arc was 109 degrees, while the mean grip strength was 82% of the unaffected side. Patients treated >1 year following injury had significantly decreased grip strength and Mayo Wrist Score. Conclusion In this study, worse results were seen in children with a protracted course prior to treatment of an SL injury. A high index of suspicion is necessary to detect an SL injury in the younger age group and should be in the differential for those with persistent dorsal wrist pain, tenderness over the dorsal SL joint, and/or positive Watson's test. MRI may assist in diagnosis but is not definitive to rule out injury. Arthroscopy is valuable to determine the extent of injury.

High-density arrays of silicon wedges bound by {111} planes on silicon (100) wafers have been created by combining convex corner lithography on a silicon dioxide hard mask with anisotropic, crystallographic etching in a repetitive, self-aligned multiplication procedure. A mean pitch of around 30 nm has been achieved, based on an initial pitch of ∼120 nm obtained through displacement Talbot lithography. The typical resolution of the convex corner lithography was reduced to the sub-10 nm range by employing an 8 nm silicon dioxide mask layer (measured on the {111} planes). Nanogaps of 6 nm and freestanding silicon dioxide flaps as thin as 1-2 nm can be obtained when etching the silicon at the exposed apices of the wedges. To enable the repetitive procedure, it was necessary to protect the concave corners between the wedges through "concave" corner lithography. The produced high-density arrays of wedges offer a promising template for the fabrication of large arrays of nanodevices in various domains with relevant details in the sub-10 nm range.

Aims The adult mammalian heart is a post-mitotic organ. Even in response to necrotic injuries, where regeneration would be essential to reinstate cardiac structure and function, only a minor percentage of cardiomyocytes undergo cytokinesis. The gene programme that promotes cell division within this population of cardiomyocytes is not fully understood. In this study, we aimed to determine the gene expression profile of proliferating adult cardiomyocytes in the mammalian heart after myocardial ischaemia, to identify factors to can promote cardiac regeneration. Methods and results Here, we demonstrate increased 5-ethynyl-2’deoxyuridine incorporation in cardiomyocytes 3 days post-myocardial infarction in mice. By applying multi-colour lineage tracing, we show that this is paralleled by clonal expansion of cardiomyocytes in the borderzone of the infarcted tissue. Bioinformatic analysis of single-cell RNA sequencing data from cardiomyocytes at 3 days post ischaemic injury revealed a distinct transcriptional profile in cardiomyocytes expressing cell cycle markers. Combinatorial overexpression of the enriched genes within this population in neonatal rat cardiomyocytes and mice at postnatal day 12 (P12) unveiled key genes that promoted increased cardiomyocyte proliferation. Therapeutic delivery of these gene cocktails into the myocardial wall after ischaemic injury demonstrated that a combination of thymosin beta 4 (TMSB4) and prothymosin alpha (PTMA) provide a permissive environment for cardiomyocyte proliferation and thereby attenuated cardiac dysfunction. Conclusion This study reveals the transcriptional profile of proliferating cardiomyocytes in the ischaemic heart and shows that overexpression of the two identified factors, TMSB4 and PTMA, can promote cardiac regeneration. This work indicates that in addition to activating cardiomyocyte proliferation, a supportive environment is a key for regeneration to occur.

Background Illness after infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant is less severe compared with previous variants. Data on the disease burden in immunocompromised patients are lacking. We investigated the clinical characteristics and outcomes of immunocompromised patients with coronavirus disease 2019 (COVID-19) caused by Omicron. Methods Organ transplant recipients, patients on anti-CD20 therapy, and allogenic hematopoietic stem cell transplantation recipients infected with the Omicron variant were included. Characteristics of consenting patients were collected and patients were contacted regularly until symptom resolution. To identify possible risk factors for hospitalization, a univariate logistic analysis was performed. Results 114 consecutive immunocompromised patients were enrolled. Eighty-nine percent had previously received 3 mRNA vaccinations. While only 1 patient died, 23 (20%) were hospitalized for a median of 11 days. A low SARS-CoV-2 immunoglobulin G (IgG) antibody response ( Conclusions While the mortality in immunocompromised patients infected with Omicron was low, hospital admission was frequent and the duration of symptoms often prolonged. In addition to vaccination, other interventions are needed to limit the morbidity from COVID-19 in immunocompromised patients.

New legal and regulatory challenges are emerging as technology infiltrates every aspect of public and private life on a global scale. The growing dominance of largely unregulated global technology and social media companies presents grave concerns for international and national lawmakers and regulators grappling with health, safety and security issues such as cyber exploitation and discrimination, digital harassment and violence, online human trafficking and cyber sexual exploitation, particularly of vulnerable populations living in conflict zones. Additional issues relate to the biases and discrimination programmed into artificial intelligence and how global technology and social media companies are using powerful algorithms to expand their global audiences without possessing the technical language competency needed to enforce their community standards prohibiting the dissemination of hate speech, illegal content and unlawful activities on their platforms. While social media has benefits, it can also facilitate crimes such as cyber exploitation, sexual terrorism and online human trafficking that especially harm socially marginalized and economically vulnerable people—specifically women and children. This law article focuses on the nexus between cyber exploitation, enslavement, sexual torture and online human trafficking on global technology and social media platforms and its connection to terrorism financing with a detailed discussion of what happened to Yezidi women and children and other religious and ethnic minorities during the rise of the Islamic State of Iraq and Syria (ISIS, ISIL, IS or the Islamic State). This law article will also explore the legal frameworks in the United States, Europe and Iraq that might allow victims of cyber exploitation to pursue criminal and civil accountability against corporate actors.

Healthcare has become more complex in recent years. Such complexity can best be addressed by interprofessional teams. We argue that to ensure successful communication and cooperation in interprofessional teams, it is important to establish interprofessional education in health-related study programs. More precisely, we argue that students in health-related programs need to develop interprofessional competencies and a common language, experience interprofessional contact, build inclusive identities and establish beliefs in the benefit of interprofessional diversity. We give examples how these goals can be implemented in interprofessional education. We also discuss challenges and future avenues for respective research healthcare professionals.

To quantify the subjective and cognitive impairment caused by wearing face masks at work, 20 men and 20 women (median age 47 years, range 19–65) were tested under different ergometer workloads while wearing surgical mask, community mask, FFP2 respirator or no mask in a randomized and partially double-blinded design. Masks were worn also at the workplace for four hours. Subjective impairment was recorded by questionnaires. Cognitive performance was tested before and after the workplace examination. Subjective feeling of heat, humidity, and difficult breathing increased with rising physical exertion and wearing time for all three mask types, most notably for FFP2. Even when blinded, participants with FFP2 reported difficult breathing already at rest. During physical exertion, individuals with low tolerance to discomfort reported significantly stronger impairment (OR 1.14, 95% CI 1.02–1.27). Regarding light work, older subjects (OR 0.95, 95% CI 0.92–0.98) and women (OR 0.84, 95% CI 0.72–0.99) showed significantly lower and atopic subjects stronger impairment (OR 1.16, 95% CI 1.06–1.27). No significant influence of mask wearing was detected on cognitive performance. Wearing a mask had no effect on cognitive performance, but led to discomfort which increased with physical exertion and wearing time. Individuals who tolerate discomfort poorly felt more impaired by wearing a mask during physical exertion.

Background: Atrial functional mitral regurgitation (AFMR) is associated with increased morbidity and mortality. Left atrial (LA) size and function in AFMR are poorly characterized. We aimed to assess LA function by reservoir strain (LASr) and estimated reservoir work (LAWr) and their impact on outcome in AFMR. Methods: Consecutive patients at our institution between 2001 and 2019 and with significant (moderate or greater) AFMR were examined. LAWr was estimated as LASr×LA reservoir volume, and patients were grouped by median LASr and LAWr. Outcomes were all-cause death or heart failure hospitalizations. Results: Five hundred fifteen AFMR patients were followed up for 5 (1–17) years. Patients had previously documented atrial fibrillation (AF; 37%), heart failure with preserved ejection fraction (HFpEF) without AF (24%), or both (HFpEF+AF, 39%). LA volume was largest in AF, while LA function parameters were most impaired in the combined HFpEF+AF group. During follow-up, patients with low LASr or LAWr had higher risk of death ( P P P Conclusions: LA reservoir function but not LA size is a robust predictor of outcome in significant AFMR. This provides mechanistic insights into the interplay of functional versus geometric LA changes in AFMR.

The use of face masks became mandatory during SARS-CoV-2 pandemic. Wearing masks may lead to complaints about laboured breathing and stress. The influence of different masks on cardiopulmonary performance was investigated in a partially double-blinded randomized cross-over design. Forty subjects (19–65 years) underwent body plethysmography, ergometry, cardiopulmonary exercise test and a 4-h wearing period without a mask, with a surgical mask (SM), a community mask (CM), and an FFP2 respirator (FFP2). Cardiopulmonary, physical, capnometric, and blood gas related parameters were recorded. Breathing resistance and work of breathing were significantly increased while wearing a mask. During exercise the increase in minute ventilation tended to be lower and breathing time was significantly longer with mask than without mask. Wearing a mask caused significant minimal decreases in blood oxygen pressure, oxygen saturation, an initial increase in blood and inspiratory carbon dioxide pressure, and a higher perceived physical exertion and temperature and humidity behind the mask under very heavy exercise. All effects were stronger when wearing an FFP2. Wearing face masks at rest and under exercise, changed breathing patterns in the sense of physiological compensation without representing a health risk. Wearing a mask for 4-h during light work had no effect on blood gases.

Time variability of astronomical sources provides crude information on their typical size and on the implied physical mechanisms. PKS1830-211 is a remarkable radio-bright lensed quasar with a foreground molecular absorber at z=0.89. Small-scale morphological changes in the core-jet structure of the quasar -- which is magnified by the lensing -- result in a varying illumination of the absorber screen, which in turn causes variations in the absorption profile. We aim to study the time variations of the system [...] in order to obtain constraints on both the quasar activity and small-scale structures in the ISM of the absorber. We used ALMA to monitor the submm continuum emission, together with the absorption spectra of the H2O and CH molecules, with 17 visits spread over six months in 2016. [...] From the continuum data, we followed the evolution of the flux density, flux-density ratio, spectral index, and differential polarization between the two lensed images of the quasar; all quantities show significant variations related to the intrinsic activity of the quasar. We propose a simple parametric model of a core plus a ballistic plasmon to account for the continuum evolution, from which we constrain a time delay of 25+/-3~days between lensed images. The spectral lines reveal significant variations in the foreground absorption. A PCA highlights apparent wavy time variations, possibly linked to the helical jet precession period of the quasar. From the deep averaged spectra towards the SW image, we detect the absorption of 13CH and estimate an abundance ratio of 12CH/13CH~150. We also measure the oxygen isotopic ratios, 16O/18O=65.3+/-0.7 and 18O/17O=11.5+/-0.5. Finally, we find a remarkable continuous shallow trough in the water absorption spanning a velocity interval of nearly 500 km/s. This broad absorption could be the signature of an extra-planar molecular component. [Abridged], Accepted for publication in A&A

Background: The relation between ventricular arrhythmia and fibrosis in mitral valve prolapse (MVP) is reported, but underlying valve-induced mechanisms remain unknown. We evaluated the association between abnormal MVP-related mechanics and myocardial fibrosis, and their association with arrhythmia. Methods: We studied 113 patients with MVP with both echocardiogram and gadolinium cardiac magnetic resonance imaging for myocardial fibrosis. Two-dimensional and speckle-tracking echocardiography evaluated mitral regurgitation, superior leaflet and papillary muscle displacement with associated exaggerated basal myocardial systolic curling, and myocardial longitudinal strain. Follow-up assessed arrhythmic events (nonsustained or sustained ventricular tachycardia or ventricular fibrillation). Results: Myocardial fibrosis was observed in 43 patients with MVP, predominantly in the basal-midventricular inferior-lateral wall and papillary muscles. Patients with MVP with fibrosis had greater mitral regurgitation, prolapse, and superior papillary muscle displacement with basal curling and more impaired inferior-posterior basal strain than those without fibrosis ( P P 6-month follow-up developed ventricular arrhythmias associated (univariable) with fibrosis, greater prolapse, mitral annular disjunction, and double-peak strain. In multivariable analysis, double-peak strain showed incremental risk of arrhythmia over fibrosis. Conclusions: Basal inferior-posterior myocardial fibrosis in MVP is associated with abnormal MVP-related myocardial mechanics, which are potentially associated with ventricular arrhythmia. These associations suggest pathophysiological links between MVP-related mechanical abnormalities and myocardial fibrosis, which also may relate to ventricular arrhythmia and offer potential imaging markers of increased arrhythmic risk.

The integration of Unmanned Aerial Vehicles (UAVs) is being proposed in a spectrum of applications varying from military to civil. In these applications, UAVs are required to safely navigate in real-time in dynamic and uncertain environments. Uncertainty can be present in both the UAV itself and the environment. Through a literature study, this paper first identifies, quantifies and models different uncertainty sources using bounding shapes. Then, the UAV model, path planner parameters and four scenarios of different complexity are defined. To investigate the effect of uncertainty on path planning performance, uncertainty in obstacle position and orientation and UAV position is varied between 2% and 20% for each uncertainty source first separately and then concurrently. Results show a deterioration in path planning performance with the inclusion of both uncertainty types for all scenarios for both A* and the Rapidly-Exploring Random Tree (RRT) algorithms, especially for RRT. Faster and shorter paths with similar same success rates (>95%) result for the RRT algorithm with respect to the A* algorithm only for simple scenarios. The A* algorithm performs better than the RRT algorithm in complex scenarios.

Aims Arrhythmogenic cardiomyopathy (ACM) is an inherited cardiac disorder that is characterized by progressive loss of myocardium that is replaced by fibro-fatty cells, arrhythmias, and sudden cardiac death. While myocardial degeneration and fibro-fatty replacement occur in specific locations, the underlying molecular changes remain poorly characterized. Here, we aim to delineate local changes in gene expression to identify new genes and pathways that are relevant for specific remodelling processes occurring during ACM. Methods and results Using Tomo-Seq, genome-wide transcriptional profiling with high spatial resolution, we created transmural epicardial-to-endocardial gene expression atlases of explanted ACM hearts to gain molecular insights into disease-driving processes. This enabled us to link gene expression profiles to the different regional remodelling responses and allowed us to identify genes that are potentially relevant for disease progression. In doing so, we identified distinct gene expression profiles marking regions of cardiomyocyte degeneration and fibro-fatty remodelling and revealed Zinc finger and BTB domain-containing protein 11 (ZBTB11) to be specifically enriched at sites of active fibro-fatty replacement of myocardium. Immunohistochemistry indicated ZBTB11 to be induced in cardiomyocytes flanking fibro-fatty areas, which could be confirmed in multiple cardiomyopathy patients. Forced overexpression of ZBTB11 induced autophagy and cell death-related gene programmes in human cardiomyocytes, leading to increased apoptosis. Conclusion Our study shows the power of Tomo-Seq to unveil new molecular mechanisms in human cardiomyopathy and uncovers ZBTB11 as a novel driver of cardiomyocyte loss.

This paper develops an event-triggered optimal control method that can deal with asymmetric input constraints for nonlinear discrete-time systems. The implementation is based on an explainable global dual heuristic programming (XGDHP) technique. Different from traditional GDHP, the required derivatives of cost function in the proposed method are computed by explicit analytical calculations, which makes XGDHP more explainable. Besides, the challenge caused by the input constraints is overcome by the combination of a piece-wise utility function and a bounding layer of the actor network. Furthermore, an event-triggered mechanism is introduced to decrease the amount of computation, and the stability analysis is provided with fewer assumptions compared to most existing studies that investigate event-triggered discrete-time control using adaptive dynamic programming. Two simulation studies are carried out to demonstrate the applicability of the constructed approach. The results present that the developed event-triggered XGDHP algorithm can substantially save the computational load, while maintain comparable performance with the time-based approach.

The supplementary figures file contains additional data that are not provided in the main text (because of space constraints). Fig. S1, Data on the miR-520f expression models, incl. phase-contrast images; Fig. S2, Schematic representation of SOEing PCR; Fig. S3, Reporter and cell line models to study EMT-reversal; Fig. S4, Membranous E-cadherin staining in PANC-1 cells; Fig. S5, Overview of the 3'-UTR reporter vectors; Fig. S6, Additional data on the in vivo (mouse) experiments.

The supplementary materials and methods file contains a more detailed description of methods (cell culture, real-time and stem loop RT-PCR, Western blot analysis, and 3'-UTR reporter assays) that are described in the main text in brief. Methods that have not been described in the main text, because the data are not shown or only provided in the supplementary figures (Sanger DNA sequence analysis, phase-contrast imaging, and immunocytochemisty) are also described here.

The supplementary table file contains a table with the names and origin of the cell lines used in this study (Suppl. Table S1). It also contains four tables with nucleotide sequences of primers and oligonucleotides used for qPCR and DNA sequence analysis, and for vector cloning (Suppl. Tables S2, S3, S5 and S6), and a table describing the origin of the miRNA mimics and siRNAs used in this study (Suppl. Table S4).

OBJECTIVES Patients undergoing surgical mitral valve repair (MVr) for degenerative mitral regurgitation are at risk of even late postoperative atrial fibrillation (AF). Left atrial (LA) function has been shown superior to LA volume in evaluating the risk of AF in diverse cardiac conditions. We therefore investigated the prognostic value of LA function and volume in predicting mid-to-late postoperative AF after MVr (>30 days postoperatively). METHODS We retrospectively identified all patients who underwent MVr for degenerative mitral regurgitation between 2012 and 2019 at our institution. Exclusion criteria were preoperative AF, concomitant procedures, re-operations, missing or insufficiently processable preoperative echocardiograms and missing follow-up. LA function and volume measurements were conducted using speckle-tracking strain echocardiographic analysis. Postoperative LA function was measured in a subgroup with sufficient postoperative echocardiograms. RESULTS We included 251 patients, of whom 39 (15.5%) experienced AF in the mid-to-late postoperative period. Reduced LA strain parameters and more than mild preoperative tricuspid regurgitation were independently associated with mid-to-late postoperative AF. LA volume index had no association with mid-to-late postoperative AF in univariable analysis and did not improve the performance of multivariable models. Patients with mid-to-late AF exhibited diminished improvement in LA function after surgery. CONCLUSIONS In MVr patients, LA function (but not volume) showed independent predictive value for mid-to-late postoperative AF. Including LA function into surgical decision-making and approach may identify patients who will benefit from earlier intervention with the aim to prevent irreversible LA damage with consequent risk of postoperative AF.

BackgroundPatients with mitral valve prolapse (MVP) requiring surgical repair (MVr) are increasingly operated using minimally invasive strategies. Skill acquisition may be facilitated by a dedicated MVr program. We present here our institutional experience in establishing minimally invasive MVr (starting in 2014), laying the foundation to introduce robotic MVr.MethodsWe reviewed all patients that had undergone MVr for MVP via sternotomy or mini-thoracotomy between January 2013 and December 2020 at our institution. In addition, all cases of robotic MVr between January 2021 and August 2022 were analyzed. Case complexity, repair techniques, and outcomes are presented for the conventional sternotomy, right mini-thoracotomy and robotic approaches. A subgroup analysis comparing only isolated MVr cases via sternotomy vs. right mini-thoracotomy was conducted using propensity score matching.ResultsBetween 2013 and 2020, 799 patients were operated for native MVP at our institution, of which 761 (95.2%) received planned MVr (263 [34.6%] via mini-thoracotomy) and 38 (4.8%) received planned MV replacement. With increasing proportions of minimally invasive procedures (2014: 14.8%, 2020: 46.5%), we observed a continuous growth in overall institutional volume of MVP (n = 69 in 2013; n = 127 in 2020) and markedly improved institutional rates of successful MVr, with 95.4% in 2013 vs. 99.2% in 2020. Over this period, a higher complexity of cases were treated minimally-invasively and increased use of neochord implantation ± limited leaflet resection was observed. Patients operated minimally invasively had longer aortic cross-clamp times (94 vs. 88 min, p = 0.001) but shorter ventilation times (4.4 vs. 4.8 h, p = 0.002) and hospital stays (5 vs. 6 days, p via sternotomy, with no significant differences in other outcome variables. A total of 16 patients underwent robotically assisted MVr with successful repair in all cases.ConclusionA focused approach towards minimally invasive MVr has transformed the overall MVr strategy (incision; repair techniques) at our institution, leading to a growth in MVr volume and improved repair rates without significant complications. On this foundation, robotic MVr was first introduced at our institution in 2021 with excellent outcomes. This emphasizes the importance of building a competent team to perform these challenging operations, especially during the initial learning curve.

Mitral valve prolapse (MVP) is a cardiac valve disease that not only affects the mitral valve (MV), provoking mitral regurgitation, but also leads to maladaptive structural changes in the heart. Such structural changes include the formation of left ventricular (LV) regionalized fibrosis, especially affecting the papillary muscles and inferobasal LV wall. The occurrence of regional fibrosis in MVP patients is hypothesized to be a consequence of increased mechanical stress on the papillary muscles and surrounding myocardium during systole and altered mitral annular motion. These mechanisms appear to induce fibrosis in valve-linked regions, independent of volume-overload remodeling effects of mitral regurgitation. In clinical practice, quantification of myocardial fibrosis is performed with cardiovascular magnetic resonance (CMR) imaging, even though CMR has sensitivity limitations in detecting myocardial fibrosis, especially in detecting interstitial fibrosis. Regional LV fibrosis is clinically relevant because even in the absence of mitral regurgitation, it has been associated with ventricular arrhythmias and sudden cardiac death in MVP patients. Myocardial fibrosis may also be associated with LV dysfunction following MV surgery. The current article provides an overview of current histopathological studies investigating LV fibrosis and remodeling in MVP patients. In addition, we elucidate the ability of histopathological studies to quantify fibrotic remodeling in MVP and gain deeper understanding of the pathophysiological processes. Furthermore, molecular changes such as alterations in collagen expression in MVP patients are reviewed.

This paper proposes an extension to the traditional flight path reconstruction filter to simultaneously reconstruct the aircraft rigid body states together with modal amplitudes and velocities of the structure. To achieve this, the filter makes use of additional accelerometers, gyroscopes and strain gauges placed across the aircraft structure. These measurements are used in a Kalman filter together with kinematic equations of a flexible aircraft and structural mode shapes. First a simulation model is used to evaluate the filter performance on reference signals where the true state is known. Finally, flight test measurements obtained using an instrumented Diana 2 scaled glider are used to validate the filter.

Recent research on the Flying V - a flying-wing long-range passenger aircraft - shows that its airframe design is 25% more aerodynamically efficient than a conventional tube-and-wing airframe. The Flying V is therefore a promising contribution towards reduction in climate impact of long-haul flights. However, some design aspects of the Flying V still remain to be investigated, one of which is automatic flight control. Due to the unconventional airframe shape of the Flying V, aerodynamic modelling cannot rely on validated aerodynamic-modelling tools and the accuracy of the aerodynamic model is uncertain. Therefore, this contribution investigates how an automatic flight controller that is robust to aerodynamic-model uncertainty can be developed, by utilising Twin-Delayed Deep Deterministic Policy Gradient (TD3) - a recent deep-reinforcement-learning algorithm. The results show that an offline-trained single-loop altitude controller that is fully based on TD3 can track a given altitude-reference signal and is robust to aerodynamic-model uncertainty of more than 25%.

This is a Preregistration-As-Code. In line with the Workflow for Open Reproducible Code in Science (WORCS), a fully reproducible, version controlled repository has been created with the intended analysis code. The code has been verified to run on a synthetic dataset. After preregistration, the code will be evaluated on the real data, and any necessary changes will be tracked in the version controlled project history. The preregistered repository is available on Zenodo here: https://doi.org/10.5281/zenodo.7541044

The injection of electron cyclotron (EC) waves fulfills a number of important tasks in nuclear fusion devices for which detailed knowledge of the spatial power deposition profile is critical. This deposition profile is commonly determined using forward models such as beam or ray tracing. Recent numerical and experimental studies have shown that small-angle scattering of the EC beam as it passes through the turbulent plasma edge can cause significant broadening of the effective deposition profile, leading to considerable underestimation of the deposition width by forward methods. However, traditional inverse methods to determine the deposition profile from measurements overestimate the deposition profile width due to transport broadening. In this work, we implement three novel methods to resolve the EC power deposition profile from measurements that counteract transport broadening by simultaneously resolving transport and power deposition. We validate their assumptions and compare the results from these methods to the traditional break-in-slope method as well as to the TORAY ray-tracing code in a set of DIII-D discharges spanning five different confinement modes. We show that the four different inverse methods, novel and established, paint a consistent picture of deposition broadening. Specifically, we show that the measured power deposition profile is between 1.6 and 3.6 times wider than the TORAY profiles. Moreover, we show the considerable consequences that this level of broadening can have for ITER.

The circumgalactic medium (CGM) is a crucial component of galaxy evolution, but thus far its physical properties are highly unconstrained. As of yet, no cosmological simulation has reached convergence when it comes to constraining the cold and dense gas fraction of the CGM. Such components are also challenging to observe, and require sub-millimeter instruments with a high sensitivity to extended, diffuse emission, like the proposed Atacama Large Aperture Sub-millimetre telescope (AtLAST). We present a state-of-the-art theoretical effort at modeling the [CII], [CI](1-0), [CI](2-1), CO(3-2), and [OIII] line emissions of galaxies. We use the high-resolution cosmological zoom-in simulation Ponos, representing a star forming galaxy system at z = 6.5 ($M_*=2\times10^9~M_{\odot}$), undergoing a major merger. We adopt different modeling approaches based on the photoionisation code Cloudy. Our fiducial model uses radiative transfer post-processing with RamsesRT and Krome to create realistic FUV radiation fields, which we compare to sub-grid modeling approaches adopted in the literature. We find significant differences in the luminosity and in the contribution of different gas phases and galaxy components between the different modeling approaches. [CII] is the least model-dependant gas tracer, while [CI](1-0) and CO(3-2) are very model-sensitive. In all models, we find a significant contribution to the emission of [CII] (up to $\sim$10%) and [OIII] (up to $\sim$20%) from the CGM. [CII] and [OIII] trace different regions of the CGM: [CII] arises from an accreting filament and from tidal tails, while [OIII] traces a puffy halo surrounding the main disc, probably linked to SN feedback. We discuss our results in the context of current and future sub-mm observations with ALMA and AtLAST., Comment: Submitted for publication to A&A. 25 pages, 17 figures. Abstract summarised for arXiv submission

This paper presents a modeling framework to optimize the two-dimensional placement of powertrain elements inside the vehicle, explicitly accounting for the rotation, relative placement and alignment. Specifically, we first capture the multi-level nature of the system mathematically, and construct a model that captures different powertrain component orientations. Second, we include the relative element placement as variables in the model and derive alignment constraints for both child components and parent subsystems to automatically connect mechanical ports. Finally, we showcase our framework on a four-wheel driven electric vehicle. Our results demonstrate that our framework is capable of efficiently generating system design solutions in a fully automated manner, only using basic component properties., Comment: Submitted to VPPC 2023

We have measured the angular auto-correlation function of near-infrared galaxies in SERVS+DeepDrill, the Spitzer Extragalactic Representative Volume Survey and its follow-up survey of the Deep Drilling Fields, in three large fields totalling over 20 sq. deg on the sky, observed in two bands centred on 3.6 and 4.5 micron. We performed this analysis on the full sample as well as on sources selected by [3.6]-[4.5] colour in order to probe clustering for different redshift regimes. We estimated the spatial correlation strength as well, using the redshift distribution from S-COSMOS with the same source selection. The strongest clustering was found for our bluest subsample, with z~0.7, which has the narrowest redshift distribution of all our subsamples. We compare these estimates to previous results from the literature, but also to estimates derived from mock samples, selected in the same way as the observational data, using deep light-cones generated from the SHARK semi-analytical model of galaxy formation. For all simulated (sub)samples we find a slightly steeper slope than for the corresponding observed ones, but the spatial clustering length is comparable in most cases., Comment: 20 pages, 15 figures, 6 tables, accepted for publication in MNRAS

The American Concrete Institute has published ACI 440.11-22, Building Code Requirements for Structural Concrete Reinforced with Glass Fiber-Reinforced Polymer (GFRP) Bars—Code and Commentary. This new code was developed by an American National Standards Institute–approved consensus process and addresses structural systems, members, and connections, including cast-in-place, precast, nonprestressed, and composite concrete construction. ACI 440.11-22 is the first comprehensive building code covering the use of nonmetallic, GFRP reinforcing bars in structural concrete applications. This article provides background on this new code and discusses potential uses for precast concrete components and structures.

Design ManifesT.O. 2020 is a Participatory Action Research project currently underway in Toronto, Canada and is working with communities to uncover stories of grassroots placemaking and community building done through creative practice. An unexpected discovery during data collection highlighted how communities are still being left out of decision-making processes that directly affect their collective values and living conditions and are being disrespected by designers and researchers — exposing very large gaps in the education of designers in terms of values-based learning, design ethics, and informed methods for working with communities. This paper interrogates design pedagogy and practice in order to stimulate further discourse and investigation into how to successfully integrate ethical and responsible protocols into design curriculum to support co-design practices where social justice and equity becomes normalized in practice. In other words: giving students the tools to “work with, not for” communities. Demonstrating social conscience is ethically desirable in design education but if students are not given the tools required to work with communities through respectful and collaborative processes then we are training the next generation of designers to continue a form of hegemony in design practice that is undesirable.