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Introduction: Antimicrobial resistance (AMR) has emerged as one of the leading threats to public health. AMR possesses a multidimensional challenge that has social, economic, and environmental dimensions that encompass the food production system, influencing human and animal health. The One Health approach highlights the inextricable linkage and interdependence between the health of people, animals, agriculture, and the environment. Antibiotic use in any of these One Health areas can potentially impact the health of other areas. There is a dearth of evidence on AMR from the natural environment, such as the plant-based agriculture sector. Antibiotics, antibiotic-resistant bacteria (ARB), and related AMR genes (ARGs) are assumed to present in the natural environment and disseminate resistance to fresh produce/vegetables and thus to human health upon consumption. Therefore, this study aims to investigate the role of vegetables in the spread of AMR through an agroecosystem exploration from a One Health perspective in Ahmedabad, India.
Protocol: The present study will be executed in Ahmedabad, located in Gujarat state in the Western part of India, by adopting a mixed-method approach. First, a systematic review will be conducted to document the prevalence of ARB and ARGs on fresh produce in South Asia. Second, agriculture farmland surveys will be used to collect the general farming practices and the data on common vegetables consumed raw by the households in Ahmedabad. Third, vegetable and soil samples will be collected from the selected agriculture farms and analyzed for the presence or absence of ARB and ARGs using standard microbiological and molecular methods.
Discussion: The analysis will help to understand the spread of ARB/ARGs through the agroecosystem. This is anticipated to provide an insight into the current state of ARB/ARGs contamination of fresh produce/vegetables and will assist in identifying the relevant strategies for effectively controlling and preventing the spread of AMR.
RELA haploinsufficiency is a recently described autoinflammatory condition presenting with intermittent fevers and mucocutaneous ulcerations. The RELA gene encodes the p65 protein, one of five NF-κB family transcription factors. As RELA is an essential regulator of mucosal homeostasis, haploinsufficiency leads to decreased NF-κB signaling which promotes TNF-driven mucosal apoptosis with impaired epithelial recovery. Thus far, only eight cases have been reported in the literature. Here, we report four families with three novel and one previously described pathogenic variant in RELA. These four families included 23 affected individuals for which genetic testing was available in 16. Almost half of these patients had been previously diagnosed with more common rheumatologic entities (such as Behcet's Disease; BD) prior to the discovery of their pathogenic RELA variants. The most common clinical features were orogenital ulcers, rash, joint inflammation, and fever. The least common were conjunctivitis and recurrent infections. Clinical variability was remarkable even among familial cases, and incomplete penetrance was observed. Patients in our series were treated with a variety of medications, and benefit was observed with glucocorticoids, colchicine, and TNF inhibitors. Altogether, our work adds to the current literature and doubles the number of reported cases with RELA-Associated Inflammatory Disease (RAID). It reaffirms the central importance of the NF-κB pathway in immunity and inflammation, as well as the important regulatory role of RELA in mucosal homeostasis. RELA associated inflammatory disease should be considered in all patients with BD, particularly those with early onset and/or with a strong family history.
Based on the WEF Travel & Tourism Report data, this study deploys k-means cluster analysis to build a global typology of national destination governance. Previous studies have focused on case studies, while this chapter focuses on classification of different destination types, by deploying indicators a set of following relevant indicators: wastewater treatment, fixed broadband internet subscriptions, ground transport efficiency, quality of roads, quality of railroad infrastructure, reliability of police services, ease of finding skilled employees. The results present a four-cluster solution of national destination governance types, as well as their major characteristics. The chapter than provides and discusses important implication for theory and practice of destination governance.
In recent years, the ability of intelligent systems to be understood by developers and users has received growing attention. This holds in particular for social robots, which are supposed to act autonomously in the vicinity of human users and are known to raise peculiar, often unrealistic attributions and expectations. However, explainable models that, on the one hand, allow a robot to generate lively and autonomous behavior and, on the other, enable it to provide human-compatible explanations for this behavior are missing. In order to develop such a self-explaining autonomous social robot, we have equipped a robot with own needs that autonomously trigger intentions and proactive behavior, and form the basis for understandable self-explanations. Previous research has shown that undesirable robot behavior is rated more positively after receiving an explanation. We thus aim to equip a social robot with the capability to automatically generate verbal explanations of its own behavior, by tracing its internal decision-making routes. The goal is to generate social robot behavior in a way that is generally interpretable, and therefore explainable on a socio-behavioral level increasing users' understanding of the robot's behavior. In this article, we present a social robot interaction architecture, designed to autonomously generate social behavior and self-explanations. We set out requirements for explainable behavior generation architectures and propose a socio-interactive framework for behavior explanations in social human-robot interactions that enables explaining and elaborating according to users' needs for explanation that emerge within an interaction. Consequently, we introduce an interactive explanation dialog flow concept that incorporates empirically validated explanation types. These concepts are realized within the interaction architecture of a social robot, and integrated with its dialog processing modules. We present the components of this interaction architecture and explain their integration to autonomously generate social behaviors as well as verbal self-explanations. Lastly, we report results from a qualitative evaluation of a working prototype in a laboratory setting, showing that (1) the robot is able to autonomously generate naturalistic social behavior, and (2) the robot is able to verbally self-explain its behavior to the user in line with users' requests.
Introduction. The experience of pain is regularly accompanied by facial expressions. The gold standard for analyzing these facial expressions is the Facial Action Coding System (FACS), which provides so-called action units (AUs) as parametrical indicators of facial muscular activity. Particular combinations of AUs have appeared to be pain-indicative. The manual coding of AUs is, however, too time- and labor-intensive in clinical practice. New developments in automatic facial expression analysis have promised to enable automatic detection of AUs, which might be used for pain detection. Objective. Our aim is to compare manual with automatic AU coding of facial expressions of pain. Methods. FaceReader7 was used for automatic AU detection. We compared the performance of FaceReader7 using videos of 40 participants (20 younger with a mean age of 25.7 years and 20 older with a mean age of 52.1 years) undergoing experimentally induced heat pain to manually coded AUs as gold standard labeling. Percentages of correctly and falsely classified AUs were calculated, and we computed as indicators of congruency, "sensitivity/recall," "precision," and "overall agreement (F1)." Results. The automatic coding of AUs only showed poor to moderate outcomes regarding sensitivity/recall, precision, and F1. The congruency was better for younger compared to older faces and was better for pain-indicative AUs compared to other AUs. Conclusion. At the moment, automatic analyses of genuine facial expressions of pain may qualify at best as semiautomatic systems, which require further validation by human observers before they can be used to validly assess facial expressions of pain.
IT-Governance, Prüfung & Revision mal agil gedacht! Herausforderungen und Notwendigkeit eines Perspektivwechsels für IT-Governance, Prüfung & Revision viele Fallbeispiele zeigen die praktische Umsetzbarkeit auf Agilität und der Einsatz agiler Methoden sind heute nicht mehr nur auf IT-Projekte begrenzt, sondern prägen zunehmend ganze Organisationen. Dieses Buch zeigt auf, wie sich IT-Governance, Prüfung & Revision erfolgreich dem durch Agilität ausgelösten Wandel stellen können und wie sich der Umgang mit den Kernthemen Risiko & Unsicherheit verändert. Zum einen werden Ansätze für eine agile IT-Governance und eine agile Prüfung & Revision beschrieben, indem sie sich agile Werte und Vorgehensweisen zu eigen machen. Zum anderen werden IT-Governance, Prüfung & Revision befähigt, agile Projekte angemessen steuern und wirksam prüfen zu können.
Die soziale Netzwerkanalyse versucht menschliche Interaktion in einen analytischen und auswertbaren Zusammenhang zu bringen. Sie hat sich als Methode in den letzten Jahrzehnten über die Sozialwissenschaften hinaus in die Geschichtswissenschaften, Archäologie und Religionswissenschaften verbreitet. Dabei fanden verschiedene Paradigmenwechsel statt, zum Beispiel vom statischen Netzwerken mit dem Schwerpunkt auf quantitativ-struktureller Analyse hin zu heterogenen Handlungsnetzwerken wie zum Beispiel in der der Actor Network Theory (ANT) gewandelt. Der Fokus liegt aktuell eher auf der Frage des Informationsaustauschs und der Dynamik nicht statischer Netzwerke.
This paper gives an overview of how we can benefit from using container technology in our academic work. It aims to be a starting point for fellow researchers which also think about applying these technologies. Hence, we focus on decribing our own experiences and motivations instead of proving hard scientific facts.
Open-Source Software spielt sowohl zur Ausgestaltung von Lehr- und Lernszenarien (bspw. Organisation mit Editoren und Groupware, Kollaboration und Kommunikation via Chats und Webblogs), als auch für die Umsetzung von Forschunsprojekten (zum Beispiel Auswertung großer Datenbestände, Erprobung realer Situationen in vituellen Laboren, Evaluation neuer Oberflächenentwicklungen) eine wichtige Rolle. Um eine bestmögliche Passung der Software herzustellen, erfolgt Softwareentwicklung im Hochschulbereich entweder forschungsprojektbezogen oder Disziplin- und Einrichtungsübergreifend.
Das Kernanliegen des Datenschutzes ist es, natürliche Personen vor nachteiligen Effekten der Speicherung und Verarbeitung der sie betreffenden Daten zu schützen. Aber viele Personen scheinen gar nicht geschützt werden zu wollen. Im Gegenteil, viele Endanwender willigen “freiwillig“ – bewusst oder unbewusst – in eine umfassende Verarbeitung ihrer personenbezogenen Daten ein. Warum tun Menschen dies? Es werden verschiedene Ursachen diskutiert (beispielsweise in [79]), hierzu gehören Uninformiertheit, mangelnde Sensibilität, das Gefühl der Hilflosigkeit, mangelnde Zahlungsbereitschaft und mangelnde Alternativen. Auch wenn dies in Einzelfällen zutrifft, so gibt es oft sehr wohl datenschutzfreundliche Alternativen. Beispielsweise existiert zu WhatsApp (als Instant Messaging App) die Alternative Threema. Threema gilt als EU-DS-GVO-konform und funktional durchaus mit WhatsApp vergleichbar [62]. Allerdings ist inzwischen die aktuelle Netzwerkgröße ein entscheidendes Auswahlkriterium: Im Januar 2018 hatte Threema 4,5 Millionen Nutzer [172], WhatsApp dagegen 1,5 Milliarden [171]. Dies ist ein Indiz dafür, dass WhatsApp sich quasi zum De-facto-Standard entwickelt hat und es für die einzelne Person nur schwer möglich ist, viele andere “zum Wechsel auf ein anderes Produkt zu bewegen. [. . . ] Bei Diensten mit Nutzerzahlen im Milliardenbereich kann von ’Freiwilligkeit’ nur noch bedingt gesprochen werden.“ [9]
Experience made with free and open source software (FOSS) in the public research is shared with the community. The motivation for using and publishing FOSS is to increase visibility, transparancy and feedback quality while at the same time lowering software licensing costs. Also, the idea of giving back and returning a value plays a role. The most frequently given counter arguments are discussed. In the end, it’s important to embed FOSS publishing into the company’s strategy for the exploitation of scientific research results. To help with this, a checklist of criteria to indicate FOSS publishing is suggested. On the backround of wireless sensor networks, some case studies of FOSS contribution are detailed. The emphasis is on checking the original motivation and the spirit of FOSS back with the reality. Finally, further potential of publishing FOSS in the context of scientific research is identified.
Cancer is one of the leading causes of death worldwide [183], with lung tumors being the most frequent cause of cancer deaths in men as well as one of the most common cancers diagnosed in woman [40]. As symptoms often arise in advanced stages, an early diagnosis is especially important to ensure the best and earliest possible treatment. In order to achieve this, Computed Tomography (CT) scans are frequently used for tumor detection and diagnosis. We will present examples of publicly available CT image data of lung cancer patients and discuss possible methods to realize an automatic system for automated cancer diagnosis. We will also look at the recent SPIE-AAPM Lung CT Challenge [10] data set in detail and describe possible methods and challenges for image segmentation and classification based on this data set.
Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies (NEDDFL), defined primarily by developmental delay/intellectual disability, speech delay, postnatal microcephaly, and dysmorphic features, is a syndrome resulting from heterozygous variants in the dosage-sensitive bromodomain PHD finger chromatin remodeler transcription factor BPTF gene. To date, only 11 individuals with NEDDFL due to de novo BPTF variants have been described. To expand the NEDDFL phenotypic spectrum, we describe the clinical features in 25 novel individuals with 20 distinct, clinically relevant variants in BPTF, including four individuals with inherited changes in BPTF. In addition to the previously described features, individuals in this cohort exhibited mild brain abnormalities, seizures, scoliosis, and a variety of ophthalmologic complications. These results further support the broad and multi-faceted complications due to haploinsufficiency of BPTF.
BACKGROUND
Biallelic loss-of-function variants in NCF1 lead to reactive oxygen species deficiency and chronic granulomatous disease (CGD). Heterozygosity for the p.Arg90His variant in NCF1 has been associated with susceptibility to systemic lupus erythematosus, rheumatoid arthritis, and Sjögren's syndrome in adult patients. This study demonstrates the association of the homozygous p.Arg90His variant with interferonopathy with features of autoinflammation and autoimmunity in a pediatric patient.
CASE PRESENTATION
A 5-year old female of Indian ancestry with early-onset recurrent fever and headache, and persistently elevated antinuclear, anti-Ro, and anti-La antibodies was found to carry the homozygous p.Arg90His variant in NCF1 through exome sequencing. Her unaffected parents and three other siblings were carriers for the mutant allele. Because the presence of two NCF1 pseudogenes, this variant was confirmed by independent genotyping methods. Her intracellular neutrophil oxidative burst and NCF1 expression levels were normal, and no clinical features of CGD were apparent. Gene expression analysis in peripheral blood detected an interferon gene expression signature, which was further supported by cytokine analyses of supernatants of cultured patient's cells. These findings suggested that her inflammatory disease is at least in part mediated by type I interferons. While her fever episodes responded well to systemic steroids, treatment with the JAK inhibitor tofacitinib resulted in decreased serum ferritin levels and reduced frequency of fevers.
CONCLUSION
Homozygosity for p.Arg90His in NCF1 should be considered contributory in young patients with an atypical systemic inflammatory antecedent phenotype that may evolve into autoimmunity later in life. The complex genomic organization of NCF1 poses a difficulty for high-throughput genotyping techniques and variants in this gene should be carefully evaluated when using the next generation and Sanger sequencing technologies. The p.Arg90His variant is found at a variable allele frequency in different populations, and is higher in people of South East Asian ancestry. In complex genetic diseases such as SLE, other rare and common susceptibility alleles might be necessary for the full disease expressivity.
Somatic Mutations in UBA1 Define a Distinct Subset of Relapsing Polychondritis Patients With VEXAS
(2021)
The deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessively inherited disease that has undergone extensive phenotypic expansion since being first described in patients with fevers, recurrent strokes, livedo racemosa, and polyarteritis nodosa in 2014. It is now recognized that patients may develop multisystem disease that spans multiple medical subspecialties. Here, we describe the findings from a large single center longitudinal cohort of 60 patients, the broad phenotypic presentation, as well as highlight the cohort's experience with hematopoietic cell transplantation and COVID-19. Disease manifestations could be separated into three major phenotypes: inflammatory/vascular, immune dysregulatory, and hematologic, however, most patients presented with significant overlap between these three phenotype groups. The cardinal features of the inflammatory/vascular group included cutaneous manifestations and stroke. Evidence of immune dysregulation was commonly observed, including hypogammaglobulinemia, absent to low class-switched memory B cells, and inadequate response to vaccination. Despite these findings, infectious complications were exceedingly rare in this cohort. Hematologic findings including pure red cell aplasia (PRCA), immune-mediated neutropenia, and pancytopenia were observed in half of patients. We significantly extended our experience using anti-TNF agents, with no strokes observed in 2026 patient months on TNF inhibitors. Meanwhile, hematologic and immune features had a more varied response to anti-TNF therapy. Six patients received a total of 10 allogeneic hematopoietic cell transplant (HCT) procedures, with secondary graft failure necessitating repeat HCTs in three patients, as well as unplanned donor cell infusions to avoid graft rejection. All transplanted patients had been on anti-TNF agents prior to HCT and received varying degrees of reduced-intensity or non-myeloablative conditioning. All transplanted patients are still alive and have discontinued anti-TNF therapy. The long-term follow up afforded by this large single-center study underscores the clinical heterogeneity of DADA2 and the potential for phenotypes to evolve in any individual patient.
Dieses Dokument präsentiert eine Zusammenfassung der Dissertation der Autorin. In dieser Dissertation [Ha20] wurde ein neuartiger und hybrider Ansatz für die Scha ̈tzung der Intensität von Gesichtsmuskelbewegungen (Action Unit (AU)) vorgeschlagen und validiert. Dieser Ansatz basiert auf einer Gauß’schen Zustandsschätzung und kombiniert ein verformbares, AU-basiertes Gesichtsformmodell, ein viskoelastisches Modell der Gesichtsmuskelbewegung, mehrere erscheinungsbasierten AU-Klassifikatoren und eine Methode zur Erkennung von Gesichtspunkten. Es wurden mehrere Erweiterungen vorgeschlagen und in das Zustandsschätzungs-Framework integriert, um mit den personenspezifischen Eigenschaften sowie technischen und praktischen Herausforderungen umzugehen.Die mit der vorgeschlagenen Methode erzeugten AU-Intensitätsschätzungen wurden für die automatische Erkennung von Schmerzen und für die Analyse von Fahrerablenkung eingesetzt.