bluuebunny/crossref_metadata_2025 huggingface dataset:
Facets of Social Innovation in Higher Education
Authors: McDonnell-Naughton Mary , Păunescu Carmen
Published: January 2022

Emphasis on social engagement and innovation for the higher education sector is a priority, despite the various challenges that have arisen as result of Covid-19, for third level providers. It is a conversation that continues to evolve of how the higher education providers can prepare students for global citizenship and societal innovation. There are specific concerns regarding best practice and the contribution of higher education to teaching, research and ultimately public policy. Universities are embedded in teaching and research whereby the onus is to engage collaboratively with outside organisations to develop competences and create products for greater use by society. This chapter aims to explore how the higher education institutions can contribute to transforming teaching and research so that the student, and ultimately each academic community member, experiences the full value of contributing to a successful society, reflecting on sustainable partnerships, engagement, whilst reflecting the whole idea of societal innovation. Its ambition is to define spheres of influence for enhancing social innovation in higher education.
Pathways towards Enhancing HEI’s Role in the Local Social İnnovation Ecosystem
Authors: Baturina Danijel
Published: January 2022

Social innovation as a potential way of looking for new ways to combat the most challenging social problems is underdeveloped in Croatia and Europe. This chapter assesses the contribution of specific Higher education institute (HEI) to developing a social innovation ecosystem in the Zagreb agglomeration area (and beyond) in several dimensions: (a) research and evidence that informed social innovations (SI) and wider policies; (b) education; (c) creating networks and advocating, and (d) community engagement. Additionally, the introduction of the service-learning program is presented to illustrate that contribution. The capacity of the higher education institutions in fostering the development of the social innovation ecosystem is discussed through the prism of the local and national education, science and public (social) policy development in Croatia.
Deep Learning in Multi-step Forecasting of Chaotic Dynamics
Authors: Sangiorgio Matteo
Published: January 2022

The prediction of chaotic dynamical systems’ future evolution is widely debated and represents a hot topic in the context of nonlinear time series analysis. Recent advances in the field proved that machine learning techniques, and in particular artificial neural networks, are well suited to deal with this problem. The current state-of-the-art primarily focuses on noise-free time series, an ideal situation that never occurs in real-world applications. This chapter provides a comprehensive analysis that aims at bridging the gap between the deterministic dynamics generated by archetypal chaotic systems, and the real-world time series. We also deeply explore the importance of different typologies of noise, namely observation and structural noise. Artificial intelligence techniques turned out to provide robust predictions, and potentially represent an effective and flexible alternative to the traditional physically-based approach for real-world applications. Besides the accuracy of the forecasting, the domain-adaptation analysis attested the high generalization capability of the neural predictors across a relatively heterogeneous spatial domain.
Design and Control Recipes for Complex Photonic Integrated Circuits
Authors: Milanizadeh Maziyar
Published: January 2022

In the last decades optical communications contributed to the huge diffusion of the telecommunication market, pushing the development of new technologies to enable higher performances and lower costs.
Modeling of GIDL–Assisted Erase in 3–D NAND Flash Memory Arrays and Its Employment in NOR Flash–Based Spiking Neural Networks
Authors: Malavena Gerardo
Published: January 2022

Since the very first introduction of three-dimensional (3–D) vertical-channel (VC) NAND Flash memory arrays, gate-induced drain leakage (GIDL) current has been suggested as a solution to increase the string channel potential to trigger the erase operation. Thanks to that erase scheme, the memory array can be built directly on the top of a$$n^+$$n+plate, without requiring any p-doped region to contact the string channel and therefore allowing to simplify the manufacturing process and increase the array integration density. For those reasons, the understanding of the physical phenomena occurring in the string when GIDL is triggered is important for the proper design of the cell structure and of the voltage waveforms adopted during erase. Even though a detailed comprehension of the GIDL phenomenology can be achieved by means of technology computer-aided design (TCAD) simulations, they are usually time and resource consuming, especially when realistic string structures with many word-lines (WLs) are considered. In this chapter, an analysis of the GIDL-assisted erase in 3–D VCnandmemory arrays is presented. First, the evolution of the string potential and GIDL current during erase is investigated by means of TCAD simulations; then, a compact model able to reproduce both the string dynamics and the threshold voltage transients with reduced computational effort is presented. The developed compact model is proven to be a valuable tool for the optimization of the array performance during erase assisted by GIDL. Then, the idea of taking advantage of GIDL for the erase operation is exported to the context of spiking neural networks (SNNs) based on NOR Flash memory arrays, which require operational schemes that allow single-cell selectivity during both cell program and cell erase. To overcome the block erase typical ofnorFlash memory arrays based on Fowler-Nordheim tunneling, a new erase scheme that triggers GIDL in the NOR Flash cell and exploits hot-hole injection (HHI) at its drain side to accomplish the erase operation is presented. Using that scheme, spike-timing dependent plasticity (STDP) is implemented in a mainstream NOR Flash array and array learning is successfully demonstrated in a prototype SNN. The achieved results represent an important step for the development of large-scale neuromorphic systems based on mature and reliable memory technologies.
Computational Inference of DNA Folding Principles: From Data Management to Machine Learning
Authors: Nanni Luca
Published: January 2022

DNA is the molecular basis of life and would total about three meters if linearly untangled. To fit in the cell nucleus at the micrometer scale, DNA has, therefore, to fold itself into several layers of hierarchical structures, which are thought to be associated with functional compartmentalization of genomic features like genes and their regulatory elements. For this reason, understanding the mechanisms of genome folding is a major biological research problem. Studying chromatin conformation requires high computational resources and complex data analyses pipelines. In this chapter, we first present the PyGMQL software for interactive and scalable data exploration for genomic data. PyGMQL allows the user to inspect genomic datasets and design complex analysis pipelines. The software presents itself as a easy-to-use Python library and interacts seamlessly with other data analysis packages. We then use the software for the study of chromatin conformation data. We focus on the epigenetic determinants of Topologically Associating Domains (TADs), which are region of high self chromatin interaction. The results of this study highlight the existence of a “grammar of genome folding” which dictates the formation of TADs and boundaries, which is based on the CTCF insulator protein. Finally we focus on the relationship between chromatin conformation and gene expression, designing a graph representation learning model for the prediction of gene co-expression from gene topological features obtained from chromatin conformation data. We demonstrate a correlation between chromatin topology and co-expression, shedding a new light on this debated topic and providing a novel computational framework for the study of co-expression networks.
Manchester: The Role of Urban Domestic Gardens in Climate Adaptation and Resilience
Authors: Cavan Gina , Baker Fraser , Tzoulas Konstantinos , Smith Claire L.
Published: January 2022

Urban green infrastructure (GI) is a well-known solution to enhance resilience to climate hazards, particularly through the climate regulating functions of green spaces including cooling the city and moderating runoff, in addition to improving health and wellbeing. Domestic gardens provide a valuable contribution to the larger GI network in cities, however, there is less detailed knowledge about these areas and their role in urban climate regulation, in comparison to publicly accessible spaces such as parks. Environmental models require detailed information relating to GI type, structure, and height, since the functionality of different GI types (e.g. mown grass, rough grass, shrubs, trees) is variable in its influence upon urban microclimate. Whilst remote sensing classification techniques can distinguish broad vegetated and non-vegetated classes, they cannot identify the diverse range of surface types within gardens.

This chapter presents a novel approach to collecting fine-scale high quality information on urban domestic gardens to produce new climate information for planning healthy cities, within the case study city of Manchester, UK. The approach combines citizen science data with high resolution areal imagery and environmental modelling, to quantify and map cooling potential and runoff attenuation under different scenarios. This found that greening gardens could be the solution to reducing future risk of heat wave events and surface water flooding, particularly in neighbourhoods with a high proportion of gardens.

This new climate information was presented in an action plan, co-developed with project partner organisations, embedded within the existing policy framework. Engagement of citizens directly led to positive climate resilient actions within Manchester as residents pledged and implemented climate adaptation solutions within their gardens, such as replacing impervious surfaces with vegetation. This project demonstrates how cross-disciplinary collaboration among scientists, planners, government, non-governmental organizations, the private sector and the general public helps to address the challenges that lie ahead for cities as healthy environments.
Crowd Management in der Lehre
Authors: Axthelm Rebekka , Luppold Stefan , Moroff Marcus
Published: January 2022

Wer schon einmal dicht gedrängt vor der Konzertbühne stand kann sich die aussichtslose Lage, wenn die Stimmung kippt und Panik aufkommt, gut vorstellen. Damit eine öffentliche Veranstaltung reibungslos verläuft ist eine gründliche Planung, also ein qualitativ hochwertiges Crowd Management unabdingbar. Im Studiengang „BWL-, Messe-, Kongress- und Eventmanagement“ der dualen Hochschule Ravensburg Baden-Württemberg (DHBW) ist das Thema Crowd Management ein wichtiger Bestandteil. Für dieses Fachthema wurde im Rahmen des IBH-Labs Seamless Learning das Lernobjekt Cman_event erstellt, das im oben genannten Studiengang entwickelt und erprobt wurde. Die Entwicklung des didaktischen Konzepts basiert auf dem Design Based Research (DBR) Ansatz, wie es im IBH-Lab Seamless Learning entwickelt und definiert wurde. Im Sinne des grenzenlosen Lernens werden in diesem Lernobjekt die Übergänge in den Brüchen „Theorie – Praxis/Realität“ adressiert. Auf verschiedenen Ebenen und in verschiedenen Dimensionen wird neben der Vermittlung theoretischer Kenntnisse den Lernenden ermöglicht, bestimmte Situationen auf verschiedene Weisen zu betrachten, die einer besseren Vorstellung der realen Situation dienen. Dazu gehört das Modellieren in zwei und drei Raumdimensionen auf dem Tisch über Visualisierung durch computergestützte Simulationen bis hin zum Fühlen eines Gedränges am eigenen Leib.
BiLeSA: Mathematik mit digitalen Bildern sichtbar machen
Authors: Axthelm Rebekka
Published: January 2022

Die Frage „Wozu braucht man das?“ vonseiten der Studierenden oder Aussagen wie „Das habe ich im Beruf später nie mehr benötigt.“ von ehemaligen Studierenden ist den meisten Mathematikdozierenden sehr vertraut. Im Projekt BiLeSA wird dem Wunsch nach Integration von Praxisnähe im Mathematikunterricht mithilfe einer Smartphone-App, welche ausgewählte Themen in der Mathematik anhand von digitalen Bildern sichtbar macht, umgesetzt. Bei den ausgewählten Themen handelt es sich um (affin) lineare Abbildungen, Ableitungen in höheren Raumdimensionen und Potenzen von Komplexen Zahlen. Die Konzeptionierung des Lernobjekts erfolgte mit dem Design Based Research (DBR) Ansatz, welches im Basisprojekt des IBH-Labs „Seamless Learning“ konzipiert und entwickelt wurde.
Einleitung
Authors: Wey Santina
Published: January 2022

Gesellschaftliche Teilhabe ist in Deutschland maßgeblich von der Bildung einer*s jeden abhängig. Diese allerdings ist in Deutschland stark beeinflusst vom sozioökonomischen Hintergrund. Das ist eine Schieflage, die sich besonders evident in den Ergebnissen verschiedener, groß angelegter Schulleistungsstudien der vergangenen Jahre zeigt.
Ein interdisziplinärer Blick auf sprachsensiblen Fachunterricht
Authors: Wey Santina
Published: January 2022

Das vorangegangene Kapitel stellt aus geographiedidaktischer sowie interdisziplinärer Perspektive die Notwendigkeit von Sprachsensibilität im Fachunterricht dar. Einige der einbezogenen Studien geben bereits Hinweise auf fruchtbare Ansätze der fachintegrierten Sprachförderung. Im Folgenden werden Erkenntnisse zu durchgängiger Sprachförderung aus relevanten Bezugsdisziplinen vorgestellt.
Design-Kriterien sprachsensiblen Geographieunterrichts
Authors: Wey Santina
Published: January 2022

Kapitel 2 und 3 legen den Grundstein für die Design-Kriterien und die darauf basierende sprachsensible Unterrichtsreihe zum Thema Schalenbau der Erde und Plattentektonik. Dieses Thema ergibt sich aus dem Rahmenlehrplan der Berliner Schulen für die 7. Jahrgangsstufe.
Forschungsdesign und Methodik
Authors: Wey Santina
Published: January 2022

Ausgehend von grundlegenden Überlegungen zum Forschungsdesign im Rahmen von Design-Based Research begründe ich im Folgenden die verschiedenen methodischen Entscheidungen. Dabei gliedern sich die Ausführungen in die Darstellung der Datenerhebungen mit der Erläuterung der Erhebungsinstrumente, der Datenaufbereitung und der Datenauswertung. Anschließend werden Aspekte des Samplings für die Studie beleuchtet.
Diskussion der Ergebnisse
Authors: Wey Santina
Published: January 2022

In diesem Kapitel wird diskutiert, welchen Beitrag die vorliegende Arbeit zur aktuellen Forschung leistet und welche Grenzen ihr auferlegt sind. Darüber hinaus werden in einem weiteren Unterkapitel alle relevanten Konsequenzen und Empfehlungen für die Unterrichtspraxis erörtert. Zuletzt zeigt ein Ausblick Potenziale für Anschlussforschung, weitere Fragestellungen und Desiderata auf.
Einleitung, Patientengut und Methode
Authors: Eichhorn Thomas
Published: January 2022

Die akut aufgetretene, einseitige, idiopathische sensorineurale Hörminderung (ISSNHL) ist eine Erkrankung, die das Befinden der betroffenen Erkrankten in der Regel erheblich einschränkt und sie meist auch recht schnell dazu veranlasst, ärztliche Hilfe aufzusuchen. Therapeutisch erfolgt derzeit weltweit meistens, zumindest als Erstmaßnahme, eine systemische Kortikoidgabe, sei es in oraler, in der Regel jedoch in parenteraler (intravenöser) Form.
Englische Zusammenfassungen der Kapitel 1–9
Authors: Eichhorn Thomas
Published: January 2022

As a whole the effect of an explorative tympanoscopy with sealing the round/oval window(s) in cases of a profound idiopathic unilateral sudden hearing loss (ISSNHL) has been analyzed (data: own study cases and review of literature) and the results have been compared to that of intratympanal steroid injections published elsewhere. In detail the topics of the chapters focused on: Comparison of epidemiologic data, anamnestic and clinical findings including hearing results of our study group with those published Time course of hearing improvement after explorative tympanoscopyand sealing of the round/oval window Compilation of parameters influencing the extent of the initial hearing loss and the hearing gain after surgical therapy Perilymphatic fistulas as an etilogical factor causing a sudden profound hearing loss Comparison of those cases which have been treated by obliteration of the round/oval window with and without corticoid-soaked connective tissue Comparison of patients (data sampled by literature and own cases) treated with intratympanal corticoid injections on the one side or explorative tympanscopy with sealing of the round/oval window on the other side.
Die Bedeutung des Parameters Zeit bei der Behandlung des fortgeschrittenen Hörsturzes
Authors: Eichhorn Thomas
Published: January 2022

Auch wenn beim Hörsturz über eine hohe Rate an Spontanremissionen berichtet wird, findet man in der Literatur immer wieder Hinweise darauf, dass die Heilungsaussichten bei dieser Erkrankung umso günstiger ausfallen, je rascher nach seinem Auftreten mit einer Behandlung begonnen worden ist [30, 33, 57, 78, 97, 101]. Über den Zeitverlauf der Erholung existieren bislang aber nur vergleichsweise wenige Publikationen [15, 22, 25, 33, 61].
Auswirkung epidemiologischer Daten, anamnestischer Angaben und klinischer Untersuchungsbefunde auf die Hörentwicklung nach explorativer Tympanoskopie mit Abdichtung der runden/ovalen Fensternische bei Hörsturzpatienten
Authors: Eichhorn Thomas
Published: January 2022

Viele Patienten interessiert recht bald, nachdem ihre Diagnose – in diesem Fall „Hörsturz“ – gestellt worden ist, mit welchen prognostischen Erwartungen sie bezüglich ihrer Hörerholung rechnen können. Der seriös argumentierende Arzt wird antworten, dass dies von einigen Ausgangsbedingungen, nicht zuletzt aber auch von dem auszuwählenden Therapieverfahren abhängig ist, unterscheidet sich also gewöhnlich von angewendetem Behandlungs- zu Behandlungsverfahren. Insofern ist man nach unserer Meinung im Vergleich der in der eigenen Studiengruppe erhobenen Ergebnisse mit denen, die aus der Literatur zusammengetragen werden, darauf angewiesen, sich auf die Auswahl der Publikationen zu beschränken, bei denen nicht nur gleichartige therapeutische Vorgehensweisen gewählt wurden, sondern auch die sonstigen Rahmenbedingungen des Studienprotokolls weitgehend identisch waren.
Auswertung einzelner Subpopulationen unseres Patientengutes mit explorativer Tympanoskopie und Obliteration der runden und ovalen Fensternische
Authors: Eichhorn Thomas
Published: January 2022

In diesem Kapitel sollen einzelne Subpopulationen unseres Patientenkollektives näher ins Auge gefasst werden, bei denen jeweils der Frage nachgegangen wird, ob sie sich bezüglich ihres Hörverhaltens nach der Hörsturztherapie wesentlich vom restlichen Krankengut unterscheiden. Auch mit dieser Analyse wollen wir versuchen, weitere Kenntnisse über prognoserelevante Tatbestände zu erhalten.
Systematischer Überblick über das Hörsturzklientel – eine Mixtur aus Patienten mit und ohne Perilymphfisteln
Authors: Eichhorn Thomas
Published: January 2022

Plötzlich aufgetretene Perilymphfisteln (PLF) unterscheiden sich phänomenologisch oft nicht vom sog. Hörsturz. Neben der akut eingetretenen Hörminderung, die in der Regel sehr ausgeprägt ist – es kommt zum Abfließen von Perilymphe aus dem Innenohr –, tritt oft zeitgleich mit dem Hörverlust ein heftiger Schwindel auf, gelegentlich zusätzlich begleitet von Tinnitus auf dem betroffenen Ohr.
Abdeckung des ovalen/runden Fensters mit und ohne kortisongetränkten autologen Bindegewebspartikeln im Rahmen der Hörsturzbehandlung
Authors: Eichhorn Thomas
Published: January 2022

Die neueste Entwicklung bei der operativen Behandlung der idiopathischen, akuten, sensorineuralen Schwerhörigkeit (ISSNHL) stellt die im Rahmen einer explorativen Tympanoskopie gleichzeitig vorgenommene Obliteration der runden und ovalen Fensternischen mit autologem Bindgewebe dar, das zu Beginn des chirurgischen Eingriffs entnommen und bis zum Einbringen in die Pauke in einer kortisonhaltigen Lösung getränkt wurde. Damit kombiniert dieses Vorgehen gewissermaßen die Effekte der explorativen Tympanoskopie mit Abdeckung der häutigen Membran/en, die den Innenohr- vom Mittelohrraum abtrennt/en, und die einer Applikation von Glukokortikoiden in das Tympanon, wie sie ansonsten bei den intratympanalen Kortikoidinjektionen/-infusionen vorgenommen wird.
The End of Flying: Coronavirus Confinement, Academic (Im)mobilities and Me
Authors: Sheller Mimi
Published: January 2022

This chapter focuses on how the coronavirus pandemic disrupted ‘normal’ academic life and travel through an analysis of my own travel history over the past decade. After contextualising the ways in which quarantines and confinement radically decreased travel, the chapter has three parts. In the first part, I document my own curriculum vitae of academic travel over the past decade and quantitatively measure my estimated CO2 emissions. Next, I seek to situate the value of such academic travel in both quantitative and qualitative terms, through extrinsic measures such as publications and impact and through intrinsic values such as the experience of different cultures and places. Lastly, I look at the transition to virtual events and my own participation in online events during the past nine months and consider the relation between physical and virtual meetings within academic practices. Insofar as the pandemic demonstrated our ability to transform academic travel and accelerate the use of remote meetings within academic practices, a pressing concern is how to find ways of extending this into the post-pandemic phase. Among the questions I ask in conclusion are: What possibilities are there for more seriously extending remote no-fly meetings to address the climate emergency? And what are the implications of such changes, both positive and negative?
Introduction
Authors: Gulati Ashok
Published: January 2022

India has come a long way from being a food scarce nation in the 1960s to a food surplus nation thereafter. The remarkable transformation of the agricultural sector was the result of massive improvements in productivity level owing to the Green Revolution in the case of cereals and the breakthrough that followed in few other agricultural commodities, most notably, dairying. Today, India is the largest producer of milk, pulses, banana, mango, pomegranate, papaya, lemon, okra, ginger and non-food crops like cotton and jute; the second-largest producer of rice, wheat, fruits and vegetables, tea and one of the leading producers of eggs and meat in the world. India produced 281.8 million tonnes of food grains, 307.7 million tonnes of horticulture crops, 176.5 million tonnes of milk, 96 billion eggs and 7.7 million tonnes of meat during TE 2018–19.
Further Strengthening Agri-Value Chains in India—Way Forward
Authors: Gulati Ashok , Sharma Pravesh , Ganguly Kavery
Published: January 2022

The value chain analysis undertaken in this study reveals their varying performance against the conceptual framework of CISS-F. This research has helped understand the functioning of the value chains and implications of key policy reforms on the ground. There are examples of successful agricultural value chains, which clearly indicate how policies have worked in the interests of the farmers and contributed towards making the chain more efficient. However, there are several challenges confronting these value chains that need serious policy attention. Each value chain study concludes with a proposed list of desirable interventions, and way forward, very specific to the commodity. These proposed interventions are by no means exhaustive. Rather, they represent a set of critical and urgent actions which are necessary for the growth and development of that particular value chain.
Classification of CRISPR/Cas system and its application in tomato breeding
Authors: Chaudhuri Abira , Halder Koushik , Datta Asis
Published: January 2022

Remarkable diversity in the domain of genome loci architecture, structure of effector complex, array of protein composition, mechanisms of adaptation along with difference in pre-crRNA processing and interference have led to a vast scope of detailed classification in bacterial and archaeal CRISPR/Cas systems, their intrinsic weapon of adaptive immunity. Two classes: Class 1 and Class 2, several types and subtypes have been identified so far. While the evolution of the effector complexes of Class 2 is assigned solely to mobile genetic elements, the origin of Class 1 effector molecules is still in a haze. Majority of the types target DNA except type VI, which have been found to target RNA exclusively. Cas9, the single effector protein, has been the primary focus of CRISPR-mediated genome editing revolution and is an integral part of Class 2 (type II) system. The present review focuses on the different CRISPR types in depth and the application of CRISPR/Cas9 for epigenome modification, targeted base editing and improving traits such as abiotic and biotic stress tolerance, yield and nutritional aspects of tomato breeding.
Machine learning algorithm to predict anterior cruciate ligament revision demonstrates external validity
Authors: Martin R. Kyle , Wastvedt Solvejg , Pareek Ayoosh , Persson Andreas , Visnes Håvard , Fenstad Anne Marie , Moatshe Gilbert , Wolfson Julian , Lind Martin , Engebretsen Lars
Published: January 2022

Purpose

External validation of machine learning predictive models is achieved through evaluation of model performance on different groups of patients than were used for algorithm development. This important step is uncommonly performed, inhibiting clinical translation of newly developed models. Machine learning analysis of the Norwegian Knee Ligament Register (NKLR) recently led to the development of a tool capable of estimating the risk of anterior cruciate ligament (ACL) revision (https://swastvedt.shinyapps.io/calculator_rev/). The purpose of this study was to determine the external validity of the NKLR model by assessing algorithm performance when applied to patients from the Danish Knee Ligament Registry (DKLR).

Methods

The primary outcome measure of the NKLR model was probability of revision ACL reconstruction within 1, 2, and/or 5 years. For external validation, all DKLR patients with complete data for the five variables required for NKLR prediction were included. The five variables included graft choice, femur fixation device, KOOS QOL score at surgery, years from injury to surgery, and age at surgery. Predicted revision probabilities were calculated for all DKLR patients. The model performance was assessed using the same metrics as the NKLR study: concordance and calibration.

Results

In total, 10,922 DKLR patients were included for analysis. Average follow-up time or time-to-revision was 8.4 (± 4.3) years and overall revision rate was 6.9%. Surgical technique trends (i.e., graft choice and fixation devices) and injury characteristics (i.e., concomitant meniscus and cartilage pathology) were dissimilar between registries. The model produced similar concordance when applied to the DKLR population compared to the original NKLR test data (DKLR: 0.68; NKLR: 0.68–0.69). Calibration was poorer for the DKLR population at one and five years post primary surgery but similar to the NKLR at two years.

Conclusion

The NKLR machine learning algorithm demonstrated similar performance when applied to patients from the DKLR, suggesting that it is valid for application outside of the initial patient population. This represents the first machine learning model for predicting revision ACL reconstruction that has been externally validated. Clinicians can use this in-clinic calculator to estimate revision risk at a patient specific level when discussing outcome expectations pre-operatively. While encouraging, it should be noted that the performance of the model on patients undergoing ACL reconstruction outside of Scandinavia remains unknown.

Level of evidence

III.
Pharmacological inhibition of MERTK induces in vivo retinal degeneration: a multimodal imaging ocular safety assessment
Authors: Hamm Gregory , Maglennon Gareth , Williamson Beth , Macdonald Ruth , Doherty Ann , Jones Stewart , Harris Jayne , Blades James , Harmer Alexander R. , Barton Peter , Rawlins Philip B. , Smith Paul , Winter-Holt Jon , McMurray Lindsay , Johansson Julia , Fitzpatrick Paul , McCoull William , Coen Muireann
Published: January 2022

The receptor tyrosine kinase, MERTK, plays an essential role in homeostasis of the retina via efferocytosis of shed outer nuclear segments of photoreceptors. The Royal College of Surgeons rat model of retinal degeneration has been linked to loss-of-function of MERTK, and together with the MERTK knock-out mouse, phenocopy retinitis pigmentosa in humans with MERTK mutations. Given recent efforts and interest in MERTK as a potential immuno-oncology target, development of a strategy to assess ocular safety at an early pre-clinical stage is critical. We have applied a state-of-the-art, multi-modal imaging platform to assess the in vivo effects of pharmacological inhibition of MERTK in mice. This involved the application of mass spectrometry imaging (MSI) to characterize the ocular spatial distribution of our highly selective MERTK inhibitor; AZ14145845, together with histopathology and transmission electron microscopy to characterize pathological and ultra-structural change in response to MERTK inhibition. In addition, we assessed the utility of a human retinal in vitro cell model to identify perturbation of phagocytosis post MERTK inhibition. We identified high localized total compound concentrations in the retinal pigment epithelium (RPE) and retinal lesions following 28 days of treatment with AZ14145845. These lesions were present in 4 of 8 treated animals, and were characterized by a thinning of the outer nuclear layer, loss of photoreceptors (PR) and accumulation of photoreceptor outer segments at the interface of the RPE and PRs. Furthermore, the lesions were very similar to that shown in the RCS rat and MERTK knock-out mouse, suggesting a MERTK-induced mechanism of PR cell death. This was further supported by the observation of reduced phagocytosis in the human retinal cell model following treatment with AZ14145845. Our study provides a viable, translational strategy to investigate the pre-clinical toxicity of MERTK inhibitors but is equally transferrable to novel chemotypes.
Harmonic extension through conical surfaces
Authors: Gardiner Stephen J. , Render Hermann
Published: January 2022

This paper establishes extension results for harmonic functions which vanish on a conical surface. These are based on a detailed analysis of expansions for the Green function of an infinite cone.
Prevalence of Paediatric Surgical Conditions in Eastern Uganda: A Cross‐Sectional Study
Authors: Ajiko Mary Margaret , Weidman Viking , Nordin Pär , Wladis Andreas , Löfgren Jenny
Published: January 2022

Background

The role of surgery in global health has gained greater attention in recent years. Approximately 1.8 billion children below 15 years live in low‐ and middle‐income countries (LMIC). Many surgical conditions affect children. Therefore, paediatric surgery requires specific emphasis. Left unattended, the consequences can be dire. Despite this, there is a paucity of data regarding prevalence of surgical conditions in children in LMIC. The present objective was to investigate the prevalence of paediatric surgical conditions in children in a defined geographical area in Eastern Uganda.

Method

A cross‐sectional study was carried out in the Iganga‐Mayuge Health and Demographic Surveillance Site located in Eastern Uganda. Through a two‐stage, cluster‐based sampling process, 490 households from 49 villages were randomly selected, generating a study population of 1581 children. The children's caregivers were interviewed, and the children were physically examined by two medical doctors to identify any surgical conditions.

Results

The interview was performed with 1581 children, and 1054 were physically examined. Among these, the overall prevalence of any surgical condition was 16.0 per cent (n = 169). Of these, 39 per cent had an unmet surgical need (66 of 169). This is equivalent to a 6.3 per cent prevalence of current unmet surgical need. The most common groups of surgical condition were congenital anomalies and trauma‐related conditions.

Conclusion

Surgical conditions in children are common in eastern Uganda. The unmet need for surgery is high. With a growing population, the need for paediatric surgical capacity will increase even further. The health care system must be reinforced to provide services for children with surgical conditions if United Nations Sustainability Development Goal 3 is to be achieved by 2030.
The burden of illness in patients with paroxysmal nocturnal hemoglobinuria receiving treatment with the C5-inhibitors eculizumab or ravulizumab: results from a US patient survey
Authors: Dingli David , Matos Joana E. , Lehrhaupt Kerri , Krishnan Sangeeta , Yeh Michael , Fishman Jesse , Sarda Sujata P. , Baver Scott B.
Published: January 2022

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare and life-threatening disease with symptoms of hemolysis and thrombosis. Current therapies for this complement-mediated disease rely predominantly on inhibition of the C5 complement protein. However, data on treatment responses and quality of life in C5-inhibitor (C5i)-treated PNH patients are scarce. The objective of this study was to determine C5i treatment effects on clinical parameters, PNH symptoms, quality of life, and resource use for PNH patients. This cross-sectional study surveyed 122 individuals in the USA receiving treatment for PNH with C5-targeted monoclonal antibodies, eculizumab (ECU) or ravulizumab (RAV). Despite most patients receiving C5i therapy for ≥ 3 months (ECU 100%, n = 35; RAV 95.4%, n = 83), many patients remained anemic with hemoglobin levels ≤ 12 g/dL in 87.5% (n = 28/32) and 82.9% (n = 68/82) of ECU and RAV recipients, respectively. A majority of patients on ECU (88.6%; n = 31/35) and RAV (74.7%; n = 65/87) reported fatigue symptoms. Among PNH patients receiving C5i therapy for ≥ 12 months, some still reported thrombotic events (ECU, 10.0%, n = 1/10; RAV, 23.5%, n = 4/17) and required transfusions within the past year (ECU, 52.2%, n = 12/23; RAV, 22.6%, n = 7/31). Other patient-reported PNH symptoms included breakthrough hemolysis, shortness of breath, and headaches. Patients reported scores below the average population norms on the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) scales. Overall, this study found that PNH patients receiving ECU or RAV therapy demonstrated a significant burden of illness, highlighting the need for improved PNH therapies.
Validation of an automatic tool for the rapid measurement of brain atrophy and white matter hyperintensity: QyScore®
Authors: Cavedo Enrica , Tran Philippe , Thoprakarn Urielle , Martini Jean-Baptiste , Movschin Antoine , Delmaire Christine , Gariel Florent , Heidelberg Damien , Pyatigorskaya Nadya , Ströer Sébastian , Krolak-Salmon Pierre , Cotton Francois , dos Santos Clarisse Longo , Dormont Didier
Published: January 2022

Objectives

QyScore® is an imaging analysis tool certified in Europe (CE marked) and the US (FDA cleared) for the automatic volumetry of grey and white matter (GM and WM respectively), hippocampus (HP), amygdala (AM), and white matter hyperintensity (WMH). Here we compare QyScore® performances with the consensus of expert neuroradiologists.

Methods

Dice similarity coefficient (DSC) and the relative volume difference (RVD) for GM, WM volumes were calculated on 50 3DT1 images. DSC and the F1 metrics were calculated for WMH on 130 3DT1 and FLAIR images. For each index, we identified thresholds of reliability based on current literature review results. We hypothesized that DSC/F1 scores obtained using QyScore® markers would be higher than the threshold. In contrast, RVD scores would be lower. Regression analysis and Bland–Altman plots were obtained to evaluate QyScore® performance in comparison to the consensus of three expert neuroradiologists.

Results

The lower bound of the DSC/F1 confidence intervals was higher than the threshold for the GM, WM, HP, AM, and WMH, and the higher bounds of the RVD confidence interval were below the threshold for the WM, GM, HP, and AM. QyScore®, compared with the consensus of three expert neuroradiologists, provides reliable performance for the automatic segmentation of the GM and WM volumes, and HP and AM volumes, as well as WMH volumes.

Conclusions

QyScore® represents a reliable medical device in comparison with the consensus of expert neuroradiologists. Therefore, QyScore® could be implemented in clinical trials and clinical routine to support the diagnosis and longitudinal monitoring of neurological diseases.

Key Points

• QyScore® provides reliable automatic segmentation of brain structures in comparison with the consensus of three expert neuroradiologists.

• QyScore® automatic segmentation could be performed on MRI images using different vendors and protocols of acquisition. In addition, the fast segmentation process saves time over manual and semi-automatic methods.

• QyScore® could be implemented in clinical trials and clinical routine to support the diagnosis and longitudinal monitoring of neurological diseases.
Drivers and physical processes of drought events over the State of São Paulo, Brazil
Authors: Abatan Abayomi A. , Tett Simon F. B. , Dong Buwen , Cunningham Christopher , Rudorff Conrado M. , Klingaman Nicholas P. , de Abreu Rafael C.
Published: January 2022

The State of São Paulo, Brazil (SSP) was impacted by severe water shortages during the intense austral summer drought of 2013/2014 and 2014/2015 (1415SD). This study seeks to understand the features and physical processes associated with these summer droughts in the context of other droughts over the region during 1961–2010. Thus, this study examines the spatio-temporal characteristics of anomalously low precipitation over SSP and the associated large-scale dynamics at seasonal timescales, using an observation-based dataset from the Climatic Research Unit (CRU) and model simulation outputs from the Met Office Hadley Centre Global Environment Model (HadGEM3-GA6 at N216 resolution). The study analyzes Historical and Natural simulations from the model to examine the role of human-induced climate forcing on droughts over SSP. Composites of large-scale fields associated with droughts are derived from ERA-20C and ERA-Interim reanalysis and the model simulations. HadGEM3-GA6 simulations capture the observed interannual variability of normalized precipitation anomalies over SSP, but with biases. Drought events over SSP are related to subsidence over the region. This is associated with reduced atmospheric moisture over the region as indicated by the analysis of the vertically integrated moisture flux convergence, which is dominated by reduced moisture flux convergence. The Historical simulations simulate the subsidence associated with droughts, but there are magnitude and location biases. The similarities between the circulation features of the severe 1415SD and other drought events over the region show that understanding of the dynamics of the past drought events over SSP could guide assessment of changes in risk of future droughts and improvements of model performance. The study highlights the merits and limitations of the HadGEM3-GA6 simulations. The model possesses the skills in simulating the large-scale atmospheric circulations modulating precipitation variability, leading to drought conditions over SSP.
Assessment of thoron contribution to indoor radon exposure in Canada
Authors: Chen Jing
Published: January 2022

From 2007 to 2013, simultaneous radon (222Rn) and thoron (220Rn) measurements were conducted in a total of 3534 residential homes in 34 metropolitan areas covering 71% of the Canadian population. While radon levels were above the detector’s detection limit in almost all homes, thoron concentrations were measurable in only 1738 homes. When analysis was limited to homes where thoron concentrations exceeded the detection limit, a pooled analysis confirmed that thoron is log-normally distributed in the indoor environment, and the distribution was characterized by a population-weighted geometric mean of 13 Bq/m3 and a geometric standard deviation of 1.89. Thoron contribution to indoor radon dose varied widely, ranging from 1.3 to 32% geographically. This study indicated that on average, thoron contributes 4% of the radiation dose due to total indoor radon exposure (222Rn and 220Rn) in Canada.
Pre-emptive active drainage of reflux (PARD) in Ivor-Lewis oesophagectomy with negative pressure and simultaneous enteral nutrition using a double-lumen open-pore film drain (dOFD)
Authors: Loske Gunnar , Müller Johannes , Schulze Wolfgang , Riefel Burkhard , Müller Christian Theodor
Published: January 2022

Background

Postoperative reflux can compromise anastomotic healing after Ivor-Lewis oesophagectomy (ILE). We report on Pre-emptive Active Reflux Drainage (PARD) using a new double-lumen open-pore film drain (dOFD) with negative pressure to protect the anastomosis.

Methods

To prepare a dOFD, the gastric channel of a triluminal tube (Freka®Trelumina, Fresenius) is coated with a double-layered open-pore film (Suprasorb®CNP drainage film, Lohmann & Rauscher) over 25 cm. The ventilation channel is blocked. The filmcoated segment is placed in the stomach and the intestinal feeding tube in the duodenum. Negative pressure is applied with an electronic vacuum pump (− 125 mmHg, continuous suction) to the gastric channel. Depending on the findings in the endoscopic control, PARD will either be continued or terminated.

Results

PARD was used in 24 patients with ILE and started intraoperatively. Healing was observed in all the anastomoses. The median duration of PARD was 8 days (range 4–21). In 10 of 24 patients (40%) there were issues with anastomotic healing which we defined as “at-risk anastomosis”. No additional endoscopic procedures or surgical revisions to the anastomoses were required.

Conclusions

PARD with dOFD contributes to the protection of anastomosis after ILE. Negative pressure applied to the dOFD (a nasogastric tube) enables enteral nutrition to be delivered simultaneously with permanent evacuation and decompression.
A convolution neural network approach for fall detection based on adaptive channel selection of UWB radar signals
Authors: Wang Ping , Li Qimeng , Yin Peng , Wang Zhonghao , Ling Yu , Gravina Raffaele , Li Ye
Published: January 2022

According to the World Health Organization and other authorities, falls are one of the main causes of accidental injuries among the elderly population. Therefore, it is essential to detect and predict the fall activities of older persons in indoor environments such as homes, nursing, senior residential centers, and care facilities. Due to non-contact and signal confidentiality characteristics, radar equipment is widely used in indoor care, detection, and rescue. This paper proposes an adaptive channel selection algorithm to separate the activity signals from the background using an ultra-wideband radar and to generalize fused features of frequency- and time-domain images which will be sent to a lightweight convolutional neural network to detect and recognize fall activities. The experimental results show that the method is able to distinguish three types of fall activities (i.e., stand to fall, bow to fall, and squat to fall) and obtain a high recognition accuracy up to 95.7%.
Efficacy and safety of esketamine nasal spray by sex in patients with treatment-resistant depression: findings from short-term randomized, controlled trials
Authors: Jones Robyn R. , Freeman Marlene P. , Kornstein Susan G. , Cooper Kimberly , Daly Ella J. , Canuso Carla M. , Nicholson Susan
Published: January 2022

The objective of this analysis was to determine if there are sex differences with esketamine for treatment-resistant depression (TRD). Post hoc analyses of three randomized, controlled studies of esketamine in patients with TRD (TRANSFORM-1, TRANSFORM-2 [18–64 years], TRANSFORM-3 [≥ 65 years]) were performed. In each 4-week study, adults with TRD were randomized to esketamine or placebo nasal spray, each with a newly initiated oral antidepressant. Change from baseline to day 28 in Montgomery-Åsberg Depression Rating Scale (MADRS) total score was assessed by sex in pooled data from TRANSFORM-1/TRANSFORM-2 and separately in data from TRANSFORM-3 using a mixed-effects model for repeated measures. Use of hormonal therapy was assessed in all women, and menopausal status was assessed in women in TRANSFORM-1/TRANSFORM-2. Altogether, 702 adults (464 women) received ≥ 1 dose of intranasal study drug and antidepressant. Mean MADRS total score (SD) decreased from baseline to day 28, more so among patients treated with esketamine/antidepressant vs. antidepressant/placebo in both women and men: TRANSFORM-1/TRANSFORM-2 women—esketamine/antidepressant -20.3 (13.19) vs. antidepressant/placebo -15.8 (14.67), men—esketamine/antidepressant -18.3 (14.08) vs. antidepressant/placebo -16.0 (14.30); TRANSFORM-3 women—esketamine/antidepressant -9.9 (13.34) vs. antidepressant/placebo -6.9 (9.65), men—esketamine/antidepressant -10.3 (11.96) vs. antidepressant/placebo -5.5 (7.64). There was no significant sex effect or treatment-by-sex interaction (p > 0.35). The most common adverse events in esketamine-treated patients were nausea, dissociation, dizziness, and vertigo, each reported at a rate higher in women than men. The analyses support antidepressant efficacy and overall safety of esketamine nasal spray are similar between women and men with TRD. The TRANSFORM studies are registered at clinicaltrials.gov (identifiers: NCT02417064 (first posted 15 April 2015; last updated 4 May 2020), NCT02418585 (first posted 16 April 2015; last updated 2 June 2020), and NCT02422186 (first posted 21 April 2015; last updated 29 September 2021)).
Biophysical Determinants of Shifting Tundra Vegetation Productivity in the Beaufort Delta Region of Canada
Authors: Seider Jordan H. , Lantz Trevor C. , Hermosilla Txomin , Wulder Michael A. , Wang Jonathan A.
Published: January 2022

Temperature increases across the circumpolar north have driven rapid increases in vegetation productivity, often described as ‘greening’. These changes have been widespread, but spatial variation in their pattern and magnitude suggests that biophysical factors also influence the response of tundra vegetation to climate warming. In this study, we used field sampling of soils and vegetation and random forests modeling to identify the determinants of trends in Landsat-derived Enhanced Vegetation Index, a surrogate for productivity, in the Beaufort Delta region of Canada between 1984 and 2016. This region has experienced notable change, with over 71% of the Tuktoyaktuk Coastlands and over 66% of the Yukon North Slope exhibiting statistically significant greening. Using both classification and regression random forests analyses, we show that increases in productivity have been more widespread and rapid at low-to-moderate elevations and in areas dominated by till blanket and glaciofluvial deposits, suggesting that nutrient and moisture availability mediate the impact of climate warming on tundra vegetation. Rapid greening in shrub-dominated vegetation types and observed increases in the cover of low and tall shrub cover (4.8% and 6.0%) also indicate that regional changes have been driven by shifts in the abundance of these functional groups. Our findings demonstrate the utility of random forests models for identifying regional drivers of tundra vegetation change. To obtain additional fine-grained insights on drivers of increased tundra productivity, we recommend future research combine spatially comprehensive time series satellite data (as used herein) with samples of high spatial resolution imagery and integrated field investigations.