bluuebunny/crossref_metadata_2025 huggingface dataset:
Forgetful updating and stubborn decision-makers
Authors: Hu Tai-Wei
Published: March 2022

A decision-maker receives an informative signal each period and is randomly required to make a terminal action based on the signals received so far. The decision-maker is restricted to use a (stochastic) finite automaton no larger than a given size to process information. In contrast to the existing literature that focuses on very low probability of termination, I consider information structures with a (nearly) revealing signal, in which analytical solutions are available for all probability values of termination. Results from that model reveal two robust predictions regarding constrained optimal behaviour. First, it is optimal to ignore small (in terms of informativeness) signals. Second, when deterministic schemes are optimal, big signals with similar strengths should be treated similarly; otherwise, randomization takes a lexicographic order according to the strengths of the signals. I also identify a new behavioural bias, information stubbornness, according to which the decision maker does not respond to further informative signals after seeing a nearly revealing signal. As a result, the decision-maker can persistently choose the wrong action even after an unbounded number of informative signals.
Gesellschaftliche Perspektiven einer fachspezifischen KI für automatisierte Entscheidungen
Authors: Puppe Frank
Published: March 2022

Die künstliche Intelligenz (KI) entwickelt sich rasant und hat bereits eindrucksvolle Erfolge zu verzeichnen, darunter übermenschliche Kompetenz in den meisten Spielen und vielen Quizshows, intelligente Suchmaschinen, individualisierte Werbung, Spracherkennung, -ausgabe und -übersetzung auf sehr hohem Niveau und hervorragende Leistungen bei der Bildverarbeitung, u. a. in der Medizin, der optischen Zeichenerkennung, beim autonomen Fahren, aber auch beim Erkennen von Menschen auf Bildern und Videos oder bei Deep Fakes für Fotos und Videos. Es ist zu erwarten, dass die KI auch in der Entscheidungsfindung Menschen übertreffen wird; ein alter Traum der Expertensysteme, der durch Lernverfahren, Big Data und Zugang zu dem gesammelten Wissen im Web in greifbare Nähe rückt. Gegenstand dieses Beitrags sind aber weniger die technischen Entwicklungen, sondern mögliche gesellschaftliche Auswirkungen einer spezialisierten, kompetenten KI für verschiedene Bereiche der autonomen, d. h. nicht nur unterstützenden Entscheidungsfindung: als Fußballschiedsrichter, in der Medizin, für richterliche Entscheidungen und sehr spekulativ auch im politischen Bereich. Dabei werden Vor- und Nachteile dieser Szenarien aus gesellschaftlicher Sicht diskutiert.
A novel gyrovirus in a common pheasant (Phasianus colchicus) with poult enteritis and mortality syndrome
Authors: Fehér Enikő , Bali Krisztina , Kaszab Eszter , Ihász Katalin , Jakab Szilvia , Nagy Borbála , Ursu Krisztina , Farkas Szilvia L. , Bányai Krisztián
Published: March 2022

A novel gyrovirus was detected in an intestinal specimen of a common pheasant that died due to poult enteritis and mortality syndrome. The genome of the pheasant-associated gyrovirus (PAGyV) is 2353 nucleotides (nt) long and contains putative genes for the VP1, VP2, and VP3 proteins in an arrangement that is typical for gyroviruses. Gyrovirus-specific motifs were identified in both the coding region and the intergenic region of the PAGyV genome. The VP1 of PAGyV shares up to 67.6% pairwise nt sequence identity with reference sequences and forms a distinct branch in the phylogenetic tree. Thus, according to the recently described species demarcation criteria, PAGyV belongs to a novel species in the genus Gyrovirus, family Anelloviridae, for which we propose the name "Gyrovirus phaco 1".
Reducing uncertainty in seismic assessment of multiple masonry buildings based on monitored demolitions
Authors: Martakis Panagiotis , Reuland Yves , Imesch Marco , Chatzi Eleni
Published: March 2022

A significant part of the existing building stock in regions of low to moderate seismic hazard has been designed without modern seismic considerations and is, in the meantime, exceeding its design life span. The assessment of seismic performance poses an engineering challenge, due to unknown material properties, undocumented structural interventions and the scarcity of event-based information. Operational modal analysis has been applied in some cases to verify model assumptions beyond visual inspection. However, masonry buildings exhibit amplitude-dependent stiffness even at very low response amplitudes, raising questions about the validity of such methods. Planned demolitions provide engineers with the opportunity to leverage higher-amplitude vibrations generated during demolition activities to better understand the dynamic behaviour of existing buildings. This paper introduces a Bayesian model-updating framework, which aims at reducing uncertainty in seismic analysis, by fusing dynamic measurements with best-practice structural models. The proposed hybrid framework is applied to nine real masonry buildings, representative of existing residential buildings, as typically encountered in Switzerland, that have been monitored during controlled demolition. A vast reduction in prediction uncertainty is achieved through data-driven model updating, additionally exposing intra- and inter-typological differences in terms of seismic capacity and ductility. In addition, differences between updated model predictions and typical engineering assumptions and generic typological curves are discussed. Overall, this contribution demonstrates, applies and discusses the practical benefits of a straightforward methodology for fusing monitoring data into the seismic evaluation of existing masonry structures.
How to Use Metallurgical Analysis for Fire Investigation: The Case of AISI 316 Stainless Steel
Authors: Casaroli Andrea , Boniardi Marco , Gerosa Riccardo , Rivolta Barbara
Published: March 2022

In this work, fire simulations were carried out on AISI 316 austenitic stainless steel sheets (similar to EN X5CrNiMo17-12-2), usually employed for the production of flue pipes. The thermal alteration induced by the fire was simulated by heating samples at different temperatures (from 20°C to 1050°C) and for different exposure times (1 h and 6 h) in a laboratory furnace. The metallurgical investigation concerned the surface coloring by photographic analysis; the morphology and chemical composition of the surface oxides by SEM and EDS; the microstructure as a function of temperature by LOM. The influence of the different parameters was discussed by a statistical ANOVA approach. The obtained results allowed to associate each temperature to one or more alterations in color, to the morphology and the chemical composition assumed by the surface oxides, as well as to the microstructure of the steel.
An active semi-supervised deep learning model for human activity recognition
Authors: Bi Haixia , Perello-Nieto Miquel , Santos-Rodriguez Raul , Flach Peter , Craddock Ian
Published: March 2022

Human activity recognition (HAR), which aims at inferring the behavioral patterns of people, is a fundamental research problem in digital health and ambient intelligence. The application of machine learning methods in HAR has been investigated vigorously in recent years. However, there are still a number of challenges confronting the task, where one significant barrier lies in the longstanding shortage of annotations. To address this issue, we establish a new paradigm for HAR, which integrates active learning and semi-supervised learning into one framework. The main idea is to reduce the annotation cost by actively selecting the most informative samples for annotation, as well as leveraging the unlabelled instances in a semi-supervised way. In particular, we propose to utilize the massive unlabelled data via temporal ensembling of convolutional neural networks (CNN), which yields robust consensus predictions by aggregating the outputs of the training networks on different epochs. We conducted extensive experiments on three public benchmark datasets. The proposed method achieves Macro F1 values of 0.76, 0.45 and 0.91 in a low annotation scenario on PAMAP2, USCHAD and UCIHAR datasets respectively, outperforming a multitude of state-of-the-art deep models. The ablation study proves the effectiveness of the two components of the framework, i.e., active learning-based sample selection and semi-supervised model training with temporal ensembling, in alleviating the issue of insufficient labels. Cross-validation and statistical significance experiments further demonstrate the robustness and generalization ability of the proposed method. The source codes are available at https://github.com/HaixiaBi1982/ActSemiCNNAct.
Open Reading Frame-3a gene of the 2019 novel coronavirus inhibits the occurrence and development of colorectal cancer
Authors: Shuwen Han , Yinhang Wu , Jing Mao , Gong Chen , Xiaohui Hou , Xi Yang , Wei Wu
Published: March 2022

Intestinal microecology is composed of bacteria, fungi and viruses. As a part of intestinal microecology, viruses participate in the occurrence and development of colorectal cancer. The 2019-nCoV was detected in stool samples from patients during COVID-19, suggesting that the 2019-nCoV may be associated with intestinal microecology. However, the relationship of the 2019-nCoV and CRC is unclear. The aim of this study is to explore the role of Open Reading Frame-3a (ORF3a) of the 2019-nCoV in CRC. After the pCDH-CMV-MCS-EF1-Puro vector that provides high expression of ORF3a was transfected into the SW480 CRC cell line, immunofluorescence was used to determine the localization of ORF3a in SW480 cells. The proliferation, migration, invasion, apoptosis, and cell cycle progression of SW480 cells were measured using the Cell Counting Kit-8 (CCK-8), wound healing, Transwell assay, flow cytometry, the TUNEL assay, and propidium iodide single staining. The results showed that ORF3a inhibited the proliferation, invasion, and migration of SW480 cells and induced their apoptosis after 24, 48, 72 h. Meanwhile, ORF3a inhibited the cell cycle and blocked SW480 CRC cells in the G1 phase. In in vivo experiments, high ORF3a expression was associated with decreased tumor volume, tumor weight, relative tumor volume, and tumor activity. ORF3a inhibited the growth and induced apoptosis and necrosis of tumor tissues. Based on this, we demonstrated that ORF3a might play a role in CRC, providing a new direction for the prevention and treatment of CRC.
miR-93-5p suppresses ovarian cancer malignancy and negatively regulate CCND2 by binding to its 3′UTR region
Authors: Chen Guotong , Yan Yiwei , Qiu Xiaojv , Ye Chengfeng , Jiang Xingmei , Song Shuo , Zhang Yibo , Chang Huanhuan , Wang Leqi , He Xuehuan , Tang Lingrong , Zhang Qingyu , Zhang Ying
Published: March 2022

Ovarian cancer is the most fatal gynecological cancer worldwide, yet the fundamental mechanism of malignancy acquisition in ovarian cancer remains unknown. miRNA has been implicated to a variety of diseases, including cancer initiation and progression. Cyclin-D2 (CCND2) is ubiquitously implicated in cancer uncontrol cell proliferation. Bioinformatic research revealed that CCND2 is a candidate gene for miR-93-5p with a binding site in its 3′UTR region in the current study. Using our ovarian cancer sample, we verified that miR-93-5p is negatively correlated with CCND2 mRNA and protein levels. Luciferase report assay revealed miR-93-5p inhibits CCND2 production through binding to the 3′UTR region. The expression of miR-93-5p in ovarian cancer patient samples was then determined, and a survival analysis was performed. Our findings showed that miR-93-5p is downregulated in ovarian cancer and is a favorable predictive factor in ovarian cancer patient. CCK8 assay, wound healing assay and flow cytometry-based cell cycle and apoptotic cell analyses were employed here. We found that miR-93-5p suppresses ovarian cancer cell proliferation and migration while enhances cell death. Our research certified that miR-93-5p reduces ovarian cancer malignancy by targeting CCND2.
Was lockdown life worth living?
Authors: Lawford-Smith Holly
Published: March 2022

Lockdowns in Australia have been strict and lengthy. Policy-makers appear to have given the preservation of quantity of lives strong priority over the preservation of quality of lives. But thought-experiments in population ethics suggest that this is not always the right priority. In this paper, I'll discuss both negative impacts on quantity of lives caused by the lockdowns themselves, including an increase in domestic violence, and negative impacts on quality of lives caused by lockdowns, in order to raise the question of whether we each had reason to choose quantity over quality in our own lives in a way that would justify the lockdowns we had.
Marijuana on My Mind
Authors: Cermak Timmen
Published: March 2022

Marijuana is on everyone's mind. Why do so many people enjoy it? What is it doing in our brains? Is it safe for everyone to use? What should we be telling our children? What are the benefits of medical marijuana? How does CBD live up to its hype? Does marijuana have spiritual power? And with so much conflicting information out there, how do we begin to make up our own minds about cannabis? Marijuana on My Mind is for anyone who has ever experienced the mystique of cannabis or wondered exactly how cannabis works. With over 40 years of clinical experience, Dr Timmen Cermak uses science to make sense of the endless debate between advocates and opponents of cannabis and provides answers to some of the greatest mysteries surrounding marijuana.
Flight delay forecasting and analysis of direct and indirect factors
Authors: Wang Fujun , Bi Jun , Xie Dongfan , Zhao Xiaomei
Published: March 2022

The accurate prediction of flight delays is of great significance to airports, airlines and passengers. This paper presents a causal flight delay prediction model developed for a single airport. A long short‐term memory network of delay prediction with an attention mechanism (LSTM‐AM) is established to predict flight delays and analyse their primary causes. In this model, the direct and indirect factors related to delays are comprehensively considered. LSTM‐AM can focus on input data combined with the attention vector to capture the critical time points, which can make the prediction more accurate. The model's performance is verified by actual operational data of Beijing International Airport, one of the busiest airports in the world. Experimental results show that LSTM‐AM has better prediction accuracy than baseline algorithms such as some machine learning methods and deep learning methods. The mean absolute error of LSTM‐AM is about 8.15 min on the test dataset. The study found that using the predicted results of this paper to release delayed information in advance can effectively alleviate the nervousness of passengers. The critical time point captured by LSTM‐AM combined with runway and apron flow control can reduce or eliminate delays of one flight.
Genome-wide mining of B-type cytokinin response regulators in wheat reveals the involvement of
Authors: Hu Yifeng , Cui Hongmei , Xia Pengliang , Liu Gensen , Wu Xingyang , Li Yiting , Yang Yan , Zeng Fansong , Li Yan , Ma Dongfang
Published: March 2022

Context Cytokinin response regulators (RRs) are important components of the two component signal systems that are involved in the regulation of plant growth and development, and in the response to abiotic stresses. Plant cytokinin response regulators (RR) were divided into type A and type B. A-type RR proteins act as negative feedback to regulate cytokinin signals, while B-type RRs could regulate A-type RR gene expression, and B-type RR genes have proved to play important roles in regulating cytokinin signal transduction in various biological processes. Aims We aimed to explore and analyse B-type RR genes in wheat in a preliminary fashion. Methods Using bioinformatics methods, wheat type B RR genes were identified, and type B Triticum aestivum RR (TaRR) genes were analysed using quantitative real-time polymerase chain reaction. In order to further analyse the function of TaRR, staining experiments were performed. Key results Twenty-nine B-type TaRR genes were identified in the wheat genome, divided into three groups according to their phylogenetic relationships. Chromosome mapping showed that 29 TaRRs were evenly distributed on 12 chromosomes, while there were no genes located on the other nine chromosomes, which may have experienced gene loss during evolution. The polymerase chain reaction results showed that TaRRs were significantly up-regulated under polyethylene glycol treatments. Under sodium chloride stress, TaRRs were up-regulated to varying degrees, reaching the maximum at 24 h. The study also found that the expression pattern of TaRRs was different in the root and leaf under different abiotic stresses. In addition, staining experiments also showed that TaRR5.1-6A could induce the self-defence function of leaves. Conclusions These results form the basis for further exploring the role of B-type TaRR genes in plant response to drought stress and salt stress. Implications This study lays the molecular biology foundation for the functional study of the B-type TaRR genes.
Facilitating Safe Discharge Through Predicting Disease Progression in Moderate Coronavirus Disease 2019 (COVID-19): A Prospective Cohort Study to Develop and Validate a Clinical Prediction Model in Resource-Limited Settings
Authors: Chandna Arjun , Mahajan Raman , Gautam Priyanka , Mwandigha Lazaro , Gunasekaran Karthik , Bhusan Divendu , Cheung Arthur T L , Day Nicholas , Dittrich Sabine , Dondorp Arjen , Geevar Tulasi , Ghattamaneni Srinivasa R , Hussain Samreen , Jimenez Carolina , Karthikeyan Rohini , Kumar Sanjeev , Kumar Shiril , Kumar Vikash , Kundu Debasree , Lakshmanan Ankita , Manesh Abi , Menggred Chonticha , Moorthy Mahesh , Osborn Jennifer , Richard-Greenblatt Melissa , Sharma Sadhana , Singh Veena K , Singh Vikash K , Suri Javvad , Suzuki Shuichi , Tubprasert Jaruwan , Turner Paul , Villanueva Annavi M G , Waithira Naomi , Kumar Pragya , Varghese George M , Koshiaris Constantinos , Lubell Yoel , Burza Sakib
Published: March 2022

Background

In locations where few people have received coronavirus disease 2019 (COVID-19) vaccines, health systems remain vulnerable to surges in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Tools to identify patients suitable for community-based management are urgently needed.

Methods

We prospectively recruited adults presenting to 2 hospitals in India with moderate symptoms of laboratory-confirmed COVID-19 to develop and validate a clinical prediction model to rule out progression to supplemental oxygen requirement. The primary outcome was defined as any of the following: SpO2 < 94%; respiratory rate > 30 BPM; SpO2/FiO2 < 400; or death. We specified a priori that each model would contain three clinical parameters (age, sex, and SpO2) and 1 of 7 shortlisted biochemical biomarkers measurable using commercially available rapid tests (C-reactive protein [CRP], D-dimer, interleukin 6 [IL-6], neutrophil-to-lymphocyte ratio [NLR], procalcitonin [PCT], soluble triggering receptor expressed on myeloid cell-1 [sTREM-1], or soluble urokinase plasminogen activator receptor [suPAR]), to ensure the models would be suitable for resource-limited settings. We evaluated discrimination, calibration, and clinical utility of the models in a held-out temporal external validation cohort.

Results

In total, 426 participants were recruited, of whom 89 (21.0%) met the primary outcome; 257 participants comprised the development cohort, and 166 comprised the validation cohort. The 3 models containing NLR, suPAR, or IL-6 demonstrated promising discrimination (c-statistics: 0.72–0.74) and calibration (calibration slopes: 1.01–1.05) in the validation cohort and provided greater utility than a model containing the clinical parameters alone.

Conclusions

We present 3 clinical prediction models that could help clinicians identify patients with moderate COVID-19 suitable for community-based management. The models are readily implementable and of particular relevance for locations with limited resources.
Shakespeare’s Othello and Colour-Blindness among Saudi Readers
Authors: AlShalan Amjad
Published: March 2022

This article discusses the perception of race among Middle Eastern readers, especially Saudi students, who are studying English literature, with focus on Shakespeare’s Othello, to demonstrate the complexity of perceiving race among Saudi readers by linking it to the concept of ‘colour-blindness’. The article highlights the importance of acknowledging one’s own identity in relation to teaching and reading literature, since interpreting the text is based on the position the reader holds in relation to the narrative in front of him/her, and the apprehension of the cultural context of the text. Shakespeare’s Othello is a work that poses an interesting challenge to Saudi students since they do not realise the linguistic cues used by Shakespeare to denote the racial inequality the protagonist of the play is facing. Such phenomenon is explored in the article as an example of colour-blindness as their initial reading of the text did not count for Othello’s position in the play as a ‘person of colour’. The concept of decolonization is explored through how, after focusing on the element of race, Saudi students became acutely aware of their position as a reader of an English literary text that is part of a different culture than theirs.
Shakespeare Through Decolonization
Authors: Karim-Cooper Farah
Published: March 2022

In this article, I ask what Shakespeare’s position is in the ongoing debate about how we present our cultural past today. This debate includes not just efforts to decolonize curricula in universities, but broader polemics within the culture/heritage sector and higher education, notably a right-wing backlash against scholarly efforts, in universities and elsewhere, to re-evaluate, and recontextualize Britain’s past. I note that the construction of Shakespeare as the ‘Bard’ was itself instrumentalized within the British colonial project, as a national poet and as an icon of white heritage and excellence: the conception of the man as Bard is, I argue, endemic to coloniality. Contemporary theatre historiography has markedly de-centralized Shakespeare, and I suggest that we need to introduce further consideration of race, identity and early modern constructions of ‘otherness’ into its wide-ranging theatrical reconstruction of the past. I finish with a few strategies as a way of decolonizing Shakespeare and/or early modern literature.
Decolonizing the Home at Home in the Pandemic: Articulating Women’s Experience
Authors: Abhaya N B
Published: March 2022

Feminism bears the promise of liberation of and equality for women. Reading and teaching feminist texts, within the academia and in activist spaces, has provided the opportunity to explore what it means to become and be a woman. This article explores the experience of teaching a course on women’s writing at the undergraduate level during the COVID-19 pandemic. Normally, a course on feminist writings is an occasion for self-reflection, thereby providing an opportunity to establish a dialogue between the domestic and the public. Such dialogues took place in secure institutional spaces such as classrooms or conference halls, without the intrusion of the domestic. However, as the teacher–student interaction shifted to an online mode during the pandemic, all the participants in this dialogue, including the instructor and the students, found themselves in domestic spaces, with family members listening. The article chronicles the anxieties of a woman instructor, as she teaches feminist texts from home to learners who are sitting behind computer screen in their homes and the possible impact of feminist ideas on the domestic spaces of all participants.
China's new historical statecraft: reviving the Second World War for national rejuvenation
Authors: Chang Vincent K L
Published: March 2022

There is a common perception that the Chinese state promotes fabricated accounts of the Second World War and the Communist Party's role in that conflict. Despite a growing scholarly interest in the history and collective memory of China's war experience, this perception has rarely been scrutinized, and the field has been slow to recognize recent shifts in China's memoryscape. This study draws on the concept of historical statecraft to compare official accounts with the historical record and explore how the Chinese party-state uses war memory for political purposes. It finds that its desire for national unity and international recognition have led Beijing to espouse a narrative of the Second World War that, despite significant gaps, is more representative and historically accurate than ever before. Simultaneously, the analysis shows that the Chinese leadership, at what it sees as a high-stakes juncture in China's nation-building project, increasingly monopolizes and mobilizes the memory of the war for the purposes of self-legitimation, control and strategic posturing. Although there are signs of China normalizing and globalizing its history, its official war memory reinforces an inwardly-directed form of Chinese nationalism. Analysts should take Chinese war memory seriously and study the implications of Beijing's new historical statecraft.
The futility of the pandemic treaty: caught between globalism and statism
Authors: Wenham Clare , Eccleston-Turner Mark , Voss Maike
Published: March 2022

In November 2021, the World Health Assembly (WHA) is hosting a special session to discuss the proposed plans for a pandemic treaty. Despite the fact that there are scant details concerning the treaty, the proposal has gained considerable support in both the academic community, and at the international level. While we agree that in the wake of the numerous governance failures during COVID-19, we need to develop appropriate global solutions to be able to prevent, detect, respond to, and recover from future global health crises—and that such mechanisms should be rooted in global equity—we disagree, however, that this pandemic treaty, currently, is the most appropriate way in which to achieve this. Indeed, notions of global community, solidarity, fairness are far removed from the reality that we have seen unfolding in the actions of states responding to the pandemic. This is the crux of the tension with the proposed treaty: the balance between the ideal cosmopolitan worldview held by those in power in global health, and the practice of national security decision-making witnessed in the last 18 months. Indeed, we do not believe that a pandemic treaty will deliver what is being extolled by its proponents, and it will not solve the multiple problems of global cooperation in global health that supporters believe it will.
Global health diplomacy and North Korea in the COVID-19 era
Authors: Kim Dong Jin , Kim Andrew Ikhyun
Published: March 2022

The COVID-19 pandemic has exposed increasing global inequality in responding to the issues of health. How do we resolve the tension between normative concerns for global responsibility and strategic concerns for national interest in facilitating health aid to vulnerable populations in low-income countries in the COVID-19 era? This article presents global health diplomacy as a conceptual framework that could overcome the dichotomy of humanitarianism and international politics, using health aid to North Korea during COVID-19 as a case-study. Health is a critical component of human dignity and can be a normative motivation for cooperation beyond sovereign borders. However, health is also an important element of national interest and can be a strategic motivation for transnational cooperation. The overlap between the moral and rational spaces in global health diplomacy demonstrates how COVID-19 assistance to North Korea's vulnerable population is in the enlightened self-interest of donors to prevent resurgences of new COVID-19 variants. Moreover, this framework imbues all parties, including aid recipients such as North Korea, with the global cooperative responsibility to address health. In this sense, global health diplomacy can reframe the tensions between humanitarianism and politics, morality and rationality, and cosmopolitanism and nationalism, from antithetical to complementary.
Compensation or Competitive Advantage? Reconciling Investment Arbitration with EU State Aid Law
Authors: Fahner Johannes Hendrik
Published: March 2022

—International investment law and EU State aid law have clashed on multiple occasions, most famously in the Micula case but also in disputes over subsidies in the renewable energy sector. In the view of the European Commission, investors should not be able to use investment arbitration to obtain compensation for the withdrawal of unlawful State aid, as this would jeopardize the effectiveness of EU State aid law. For this reason, the Commission has intervened in numerous investment arbitrations, arguing that investors cannot have legitimate expectations in respect of State aid that was granted in violation of EU law, and that any compensation awarded by a tribunal in such circumstances would also constitute State aid. This article argues that while EU State aid law should inform an assessment of the investor’s legitimate expectations, tribunals need to conduct a comprehensive evaluation that also considers other relevant factors, such as the respondent State’s representations and the foreseeability of the State aid qualification. If a tribunal determines that an investor was entitled to legitimate expectations despite EU State aid law, any compensation awarded by the tribunal should be accepted as damages that fall outside the scope of EU State aid law. In this way, a conflict between the two fields of law, which only encourages investors to seek enforcement outside the European Union, can be avoided.
Longitudinal profiling of metabolic ageing trends in two population cohorts of young adults
Authors: Mäkinen Ville-Petteri , Karsikas Mari , Kettunen Johannes , Lehtimäki Terho , Kähönen Mika , Viikari Jorma , Perola Markus , Salomaa Veikko , Järvelin Marjo-Riitta , Raitakari Olli T , Ala-Korpela Mika
Published: March 2022

Background

Quantification of metabolic changes over the human life course is essential to understanding ageing processes. Yet longitudinal metabolomics data are rare and long gaps between visits can introduce biases that mask true trends. We introduce new ways to process quantitative time-series population data and elucidate metabolic ageing trends in two large cohorts.

Methods

Eligible participants included 1672 individuals from the Cardiovascular Risk in Young Finns Study and 3117 from the Northern Finland Birth Cohort 1966. Up to three time points (ages 24–49 years) were analysed by nuclear magnetic resonance metabolomics and clinical biochemistry (236 measures). Temporal trends were quantified as median change per decade. Sample quality was verified by consistency of shared biomarkers between metabolomics and clinical assays. Batch effects between visits were mitigated by a new algorithm introduced in this report. The results below satisfy multiple testing threshold of P < 0.0006.

Results

Women gained more weight than men (+6.5% vs +5.0%) but showed milder metabolic changes overall. Temporal sex differences were observed for C-reactive protein (women +5.1%, men +21.1%), glycine (women +5.2%, men +1.9%) and phenylalanine (women +0.6%, men +3.5%). In 566 individuals with ≥+3% weight gain vs 561 with weight change ≤−3%, divergent patterns were observed for insulin (+24% vs −10%), very-low-density-lipoprotein triglycerides (+32% vs −6%), high-density-lipoprotein2 cholesterol (−6.5% vs +4.7%), isoleucine (+5.7% vs −6.0%) and C-reactive protein (+25% vs −22%).

Conclusion

We report absolute and proportional trends for 236 metabolic measures as new reference material for overall age-associated and specific weight-driven changes in real-world populations.
Towards achievement of Sustainable Development Goal 3: multilevel analyses of demographic and health survey data on health insurance coverage and maternal healthcare utilisation in sub-Saharan Africa
Authors: Amu Hubert , Aboagye Richard Gyan , Dowou Robert Kokou , Kongnyuy Eugene Justine , Adoma Prince Owusu , Memiah Peter , Tarkang Elvis Enowbeyang , Bain Luchuo Engelbert
Published: March 2022

Background

Improving maternal health and achieving universal health coverage (UHC) are important expectations in the global Sustainable Development Goals (SDGs) agenda. While health insurance has been shown as effective in the utilisation of maternal healthcare, there is a paucity of literature on this relationship in sub-Saharan Africa (SSA). We examined the relationship between health insurance coverage and maternal healthcare utilisation using demographic and health survey data.

Methods

This was a cross-sectional study of 195 651 women aged 15–49 y from 28 countries in SSA. We adopted bivariable and multivariable analyses comprising χ2 test and multilevel binary logistic regression in analysing the data.

Results

The prevalence of maternal healthcare utilisation was 58, 70.6 and 40.7% for antenatal care (ANC), skilled birth attendance (SBA) and postnatal care (PNC), respectively. The prevalence of health insurance coverage was 6.4%. Women covered by health insurance were more likely to utilise ANC (adjusted OR [aOR]=1.48, 95% CI 1.41 to 1.54), SBA (aOR=1.37, 95% CI 1.30 to 1.45) and PNC (aOR=1.42, 95% CI 1.37 to 1.48).

Conclusion

Health insurance coverage was an important predictor of maternal healthcare utilisation in our study. To accelerate progress towards the achievement of SDG 3 targets related to the reduction of maternal mortality and achievement of UHC, countries should adopt interventions to increase maternal insurance coverage, which may lead to higher maternal healthcare access and utilisation during pregnancy.
Competency for Japanese Novice Medical Laboratory Scientists: A Delphi Method
Authors: Maekawa Kiriko , Kotera Sayaka , Ohsaki Hiroyuki
Published: March 2022

Introduction

Competency is used to channel abilities into successful processes and is employed in the medical field. Worldwide, many laboratory competencies are available, but little evidence-based information about the competency of novice medical laboratory scientists exists in Japan. This study aimed to clarify competencies by various expert opinions around Japan.

Methods

The Delphi method was used to achieve an expert consensus on the competencies of novice medical laboratory scientists. We asked the participants to evaluate the importance of each item using the Likert scale and set 70% as the final consensus rate. The participants comprised medical laboratory scientists who met the following inclusion criteria: (1) qualified Japanese national medical laboratory scientists, (2) practised with >10 years of experience and (3) were heads of medical laboratory scientists in a clinical setting.

Results

We obtained 106 responses from 400 (26.5%) participants in round one and 95 from 106 (89.6%) participants in round two. Their professional experience mean ± standard deviation was 32.4 ± 6.0 years (range: 13–41). The average of each category consensus rate was >99.1%. The opinions of 95 experts converged, who agreed that competency comprised 8 categories and 54 items.

Discussion

Here, Japanese novice medical laboratory scientists required not only basic laboratory competencies but also other competencies, such as ‘medical safety management’, ‘interpersonal relationships’, ‘professional development’ and ‘ethics’, and some items were characteristic of Japan. Further research is warranted to explore assessments tools through the scale development of competencies, thus helping clarify the differences between ability and correlated factors.
An investigation into the wellbeing of optometry students
Authors: Vorster Anne , Hamlett Barbara M , Roux Janike le , Blount Janke , Knoesen Jane , Coetzee Lauren S
Published: March 2022

Introduction

Wellbeing is synonymous with positive mental health and impacts the efficacy of student learning. The wellbeing of optometry students is an understudied topic. The wellbeing of optometry students studying in a blended undergraduate course during the COVID-19 pandemic was also unknown. The aim of this study was to determine the status of optometry students’ wellbeing during COVID-19, by identifying their experiences of symptoms of anxiety and depression. Moreover, to determine to what extent students experience these symptoms and what specific factors influenced their wellbeing.

Methodology

Participants from four year groups completed online questionnaires. The response rate was 78.38% (n=87). Zung self-rating depression and anxiety scale questionnaires were used to determine whether students identified with a given list of symptoms commonly linked to anxiety or depression. Through open ended questions students’ wellbeing was further investigated.

Results

Participants experienced normal levels of anxiety symptoms and most participants experienced mild to moderate depression symptoms. Of concern is the severe depression symptoms identified in the third and fourth year student cohorts. Mental health, Academics, Lifestyle, Relationships and Sleep were main themes identified that had an influence on the students’ general wellbeing. Uncertainty and Physical Health themes were additional influences of wellbeing specifically related to COVID-19.

Contribution

This preliminary study into wellbeing of optometry students was undertaken in a unique timeframe, due to the COVID-19 pandemic. The results provide a platform to determine baseline wellbeing in the future student cohorts and the exploratory identification of factors causing stress and anxiety. The impact of COVID-19 on the wellbeing of students is evident.

Conclusion

Optometry students do experience symptoms of depression. COVID-19 has had considerable impact on their academic experience and their wellbeing.
Potency and Breadth of Neutralization after 3 doses of mRNA vaccines in COVID-19 Convalescent and Naïve individuals
Authors: Luczkowiak Joanna , Rivas Gonzalo , Labiod Nuria , Lasala Fátima , Rolo Marta , Lora-Tamayo Jaime , Mancheno-Losa Mikel , Rial-Crestelo David , Pérez-Rivilla Alfredo , Folgueira María D. , Delgado Rafael
Published: March 2022

Third doses of mRNA COVID-19 vaccines induced a significant increase in neutralizing potency and breadth in naïve individuals comparable with convalescents who restored levels after the first two doses. These results suggest a limit to elicit neutralization in the number of stimuli by infection or vaccination with ancestral SARS-CoV-2 sequences
Interpreting Changes in Life Expectancy During Temporary Mortality Shocks
Authors: Heuveline Patrick
Published: March 2022

Life expectancy is the most popular mortality indicator with demographers. Unless specified otherwise, it implicitly refers to the value at birth (age 0) of one of the functions derived through a period life table, a key tool of demographic and actuarial analysis. Demographers tend to favor life expectancy because it is a pure measure of the mortality conditions faced by a population, unaffected by that population’s age structure. Life expectancy also has an intuitive interpretation, conditional on the assumption that mortality conditions remain unchanged, as the expected age at death of an average newborn. If life table construction might be limited to an inner circle of demographers and actuaries, this interpretative ease gives life expectancy a much broader appeal.
Fine oculomotor knowledge enhances high-acuity vision
Authors: Zhao Zhetuo , Ahissar Ehud , Victor Jonathan D. , Rucci Michele
Published: March 2022

It has long been debated how humans resolve fine details and perceive a stable visual world despite the fixational motion of their eyes, the incessant ocular jitter that occurs in the intervals between voluntary gaze shifts. Current theories assume these processes to rely solely on the visual input to the retina, without contributions from motor and/or proprioceptive sources. Here we show that contrary to this widespread assumption, the visual system has access to high-resolution extra-retinal knowledge of fixational eye motion and uses it to deduce spatial relations. Building on recent advances in gaze-contingent display control, we created a spatial discrimination task in which the stimulus configuration was entirely determined by oculomotor activity. Our results show that humans correctly infer geometrical relations even when no spatial information is delivered to the retina and accurately combine high-resolution extraretinal monitoring of gaze displacement with retinal signals. These findings reveal a multimodal strategy for encoding spatial details, in which fine oculomotor knowledge is used to interpret the fixational input to the retina.
Evidence-based calibration of computational tools for missense variant pathogenicity classification and ClinGen recommendations for clinical use of PP3/BP4 criteria
Authors: Pejaver Vikas , Byrne Alicia B. , Feng Bing-Jian , Pagel Kymberleigh A. , Mooney Sean D. , Karchin Rachel , O’Donnell-Luria Anne , Harrison Steven M. , Tavtigian Sean V. , Greenblatt Marc S. , Biesecker Leslie G. , Radivojac Predrag , Brenner Steven E. ,   ClinGen Sequence Variant Interpretation Working Group
Published: March 2022

Recommendations from the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) for interpreting sequence variants specify the use of computational predictors as Supporting level of evidence for pathogenicity or benignity using criteria PP3 and BP4, respectively. However, score intervals defined by tool developers, and ACMG/AMP recommendations that require the consensus of multiple predictors, lack quantitative support. Previously, we described a probabilistic framework that quantified the strengths of evidence (Supporting, Moderate, Strong, Very Strong) within ACMG/AMP recommendations. We have extended this framework to computational predictors and introduce a new standard that converts a tool’s scores to PP3 and BP4 evidence strengths. Our approach is based on estimating the local positive predictive value and can calibrate any computational tool or other continuous-scale evidence on any variant type. We estimate thresholds (score intervals) corresponding to each strength of evidence for pathogenicity and benignity for thirteen missense variant interpretation tools, using carefully assembled independent data sets. Most tools achieved Supporting evidence level for both pathogenic and benign classification using newly established thresholds. Multiple tools reached score thresholds justifying Moderate and several reached Strong evidence levels. One tool reached Very Strong evidence level for benign classification on some variants. Based on these findings, we provide recommendations for evidence-based revisions of the PP3 and BP4 ACMG/AMP criteria using individual tools and future assessment of computational methods for clinical interpretation.
Altered PVN-to-CA2 hippocampal oxytocin pathway and reduced number of oxytocin-receptor expressing astrocytes in heart failure rats
Authors: Althammer Ferdinand , Roy Ranjan K. , Lefevre Arthur , Najjar Rami , Schoenig Kai , Bartsch Dusan , Eliava Marina , Feresin Rafaela , Hammock Elizabeth , Murphy Anne Z. , Charlet Alexandre , Grinevich Valery , Stern Javier E.
Published: March 2022

Oxytocinergic actions within the hippocampal CA2 are important for neuromodulation, memory processing and social recognition. However, the source of the OTergic innervation, the cellular targets expressing the OT receptors (OTRs) and whether the PVN-to-CA2 OTergic system is altered during heart failure (HF), a condition recently associated with cognitive and mood decline, remains unknown. Using immunohistochemistry along with retrograde monosynaptic tracing, RNAscope and a novel OTR-Cre rat line, we show that the PVN (but not the supraoptic nucleus) is an important source of OTergic innervation to the CA2. These OTergic fibers were found in many instances in close apposition to OTR expressing cells within the CA2. Interestingly, while only a small proportion of neurons were found to express OTRs (∼15%), this expression was much more abundant in CA2 astrocytes (∼40%), an even higher proportion that was recently reported for astrocytes in the central amygdala. Using an established ischemic rat heart failure (HF) model, we found that HF resulted in robust changes in the PVN-to-CA2 OTergic system, both at the source and target levels. Within the PVN, we found an increased OT immunoreactivity, along with a diminished OTR expression in PVN neurons. Within the CA2 of HF rats, we observed a blunted OTergic innervation, along with a diminished OTR expression, which appeared to be restricted to CA2 astrocytes. Taken together, our studies highlight astrocytes as key cellular targets mediating OTergic PVN inputs to the CA2 hippocampal region. Moreover, provides the first evidence for an altered PVN-to-CA2 OTergic system in HF rats, which could potentially contribute to previously reported cognitive and mood impairments in this animal model.
Beneficial effects of prolonged 2-phenylethyl alcohol inhalation on chronic distress-induced anxio-depressive-like phenotype in female mice
Authors: Ramadan Bahrie , Cabeza Lidia , Cramoisy Stéphanie , Houdayer Christophe , Andrieu Patrice , Millot Jean-Louis , Haffen Emmanuel , Risold Pierre-Yves , Peterschmitt Yvan
Published: March 2022

Chronic distress-induced hypothalamic-pituitary-adrenal axis deregulations have been associated with the development of neuropsychiatric disorders such as anxiety and depression. Currently available drugs treating such pathological conditions have limited efficacy and diverse side effects, revealing the need of new safer strategies. Aromatic plant-based compounds are largely used in herbal medicine due to their therapeutic properties on mood, physiology, and general well-being. The purpose of this study was to investigate the effects of 2-phenylethyl alcohol (PEA), one of the pharmacologically active constituents of rose essential oil, on chronic corticosterone (CORT)-induced behavioral and neurobiological changes in female mice. Animals followed a prolonged PEA inhalation exposure (30 min per day) for 15 consecutive days prior to behavioral evaluation with open-field, forced swim and novelty-suppressed feeding tests. CORT treatment induced an anxio-depressive-like phenotype, evidenced by a reduced locomotor activity in the open-field, and an increased latency to feed in the novelty-suppressed feeding paradigms. To elucidate the neural correlates of our behavioral results, cerebral cFos expression analysis was further performed to provide a global map of neuronal activity. The altered feeding behavior was accompanied by a significant decrease in the number of cFos-positive cells in the olfactory bulb, and altered brain connectivity as shown by cross-correlation-based network analysis. CORT-induced behavioral and neurobiological alterations were reversed by prolonged PEA inhalation, suggesting a therapeutic action that allows regulating the activity of neural circuits involved in sensory, emotional and feeding behaviors. These findings might contribute to better understand the therapeutic potential of PEA on anxio-depressive symptoms.