Fryske Akademy

Importance: Mendelian randomization (MR) studies use genetic variation associated with modifiable exposures to assess their possible causal relationship with outcomes and aim to reduce potential bias from confounding and reverse causation. Objective: To develop the STROBE-MR Statement as a stand-alone extension to the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guideline for the reporting of MR studies. Design, Setting, and Participants: The development of the STROBE-MR Statement followed the Enhancing the Quality and Transparency of Health Research (EQUATOR) framework guidance and used the STROBE Statement as a starting point to draft a checklist tailored to MR studies. The project was initiated in 2018 by reviewing the literature on the reporting of instrumental variable and MR studies. A group of 17 experts, including MR methodologists, MR study design users, developers of previous reporting guidelines, and journal editors, participated in a workshop in May 2019 to define the scope of the Statement and draft the checklist. The draft checklist was published as a preprint in July 2019 and discussed on the preprint platform, in social media, and at the 4th Mendelian Randomization Conference. The checklist was then revised based on comments, further refined through 2020, and finalized in July 2021. Findings: The STROBE-MR checklist is organized into 6 sections (Title and Abstract, Introduction, Methods, Results, Discussion, and Other Information) and includes 20 main items and 30 subitems. It covers both 1-sample and 2-sample MR studies that assess 1 or multiple exposures and outcomes, and addresses MR studies that follow a genome-wide association study and are reported in the same article. The checklist asks authors to justify why MR is a helpful method to address the study question and state prespecified causal hypotheses. The measurement, quality, and selection of genetic variants must be described and attempts to assess validity of MR-specific assumptions should be well reported. An item on data sharing includes reporting when the data and statistical code required to replicate the analyses can be accessed. Conclusions and Relevance: STROBE-MR provides guidelines for reporting MR studies. Improved reporting of these studies could facilitate their evaluation by editors, peer reviewers, researchers, clinicians, and other readers, and enhance the interpretation of their results.

This paper focuses on the linguistic landscape of two streets in two multilingual cities in Friesland (Netherlands) and the Basque Country (Spain) where a minority language is spoken, Basque or Frisian. The paper analyses the use of the minority language (Basque or Frisian), the state language (Spanish or Dutch) and English as an international language on language signs. It compares the use of these languages as related to the differences in language policy regarding the minority language in these two settings and to the spread of English in Europe. The data include over 975 pictures of language signs that were analysed so as to determine the number of languages used, the languages on the signs and the characteristics of bilingual and multilingual signs. The findings indicate that the linguistic landscape is related to the official language policy regarding minority languages and that there are important differences between the two settings.

When a biological tissue is illuminated with coherent light, an interference pattern will be formed at the detector, the so-called speckle pattern. Laser speckle contrast imaging (LSCI) is a technique based on the dynamic change in this backscattered light as a result of interaction with red blood cells. It can be used to visualize perfusion in various tissues and, even though this technique has been extensively described in the literature, the actual clinical implementation lags behind. We provide an overview of LSCI as a tool to image tissue perfusion. We present a brief introduction to the theory, review clinical studies from various medical fields, and discuss current limitations impeding clinical acceptance.

(2006). Introduction: The Study of the Linguistic Landscape as a New Approach to Multilingualism. International Journal of Multilingualism: Vol. 3, No. 1, pp. 1-6.

The social dimension of the transition to a low carbon economy is a key challenge to cities. The establishment of local energy initiatives (LEIs) has recently been attracting attention. It is of great importance to draw lessons from best practices when LEIs have been facilitated by local governments and made a substantial contribution to greening local energy systems. The main research questions in this paper are: What lessons can be drawn from successful local low carbon energy transition cases, and which strategies proved successful to support LEIs? We have used analytical notions from the Strategic Niche Management (SNM) and grassroots innovation literature to analyze two best-practice cases: Saerbeck (Germany) and Lochem (The Netherlands). Data collection involved a set of fourteen in-depth interviews and secondary data. The results show that three key factors from SNM (building networks, managing expectations, and facilitation of learning) are of great importance. However, to a great degree it is also strategic, community serving, responsive, reflexive leadership and proper process management by public officials that spurred success, which would not have been possible without close interaction and mutual trust between local government and representatives of the local communities.

This paper focuses on the linguistic landscape of two streets in two multilingual cities in Friesland (Netherlands) and the Basque Country (Spain) where a minority language is spoken, Basque or Frisian.The paper analyses the use of the minority language (Basque or Frisian), the state language (Spanish or Dutch) and English as an international language on language signs.It compares the use of these languages as related to the differences in language policy regarding the minority language in these two settings and to the spread of English in Europe.The data include over 975 pictures of language signs that were analysed so as to determine the number of languages used, the languages on the signs and the characteristics of bilingual and multilingual signs.The findings indicate that the linguistic landscape is related to the official language policy regarding minority languages and that there are important differences between the two settings.

Intentions have been identified as one of the main drivers of sustainable entrepreneurial opportunity recognition and ultimately activity. However, research has not provided sufficient explanation for how the inherent complexities of simultaneously generating social, environmental and economic value as well as considering the needs of future generations might influence the intention formation process of sustainable entrepreneurs. The aim of this study is therefore to investigate the impacts of values and future orientation on said intention formation process. This study uses structural equation modeling to quantitatively analyze an adapted model of the theory of planned behavior based on survey data of 407 students collected within two European countries. The empirical results highlight the importance of self-transcending values and future orientation to understand attitudes towards sustainable entrepreneurship. Attitudes and perceived behavioral control, in turn, positively influence intentions to become a sustainable entrepreneur. On a practical note, the results suggest that educational and other practitioners could stimulate sustainable entrepreneurial intentions through value activation strategies to raise attitudes. It is further recommended that, as a matter of policy, governmental programs should help strengthen subjective norms as a different route to stimulating intention formation.

The replacement of natural lands with urban structures has multiple environmental consequences, yet little is known about the magnitude and extent of albedo-induced warming contributions from urbanization at the global scale in the past and future. Here, we apply an empirical approach to quantify the climate effects of past urbanization and future urbanization projected under different shared socioeconomic pathways (SSPs). We find an albedo-induced warming effect of urbanization for both the past and the projected futures under three illustrative scenarios. The albedo decease from urbanization in 2018 relative to 2001 has yielded a 100-year average annual global warming of 0.00014 [0.00008, 0.00021] °C. Without proper mitigation, future urbanization in 2050 relative to 2018 and that in 2100 relative to 2018 under the intermediate emission scenario (SSP2-4.5) would yield a 100-year average warming effect of 0.00107 [0.00057,0.00179] °C and 0.00152 [0.00078,0.00259] °C, respectively, through altering the Earth's albedo.

Increasing pressure on farming systems due to rapid urbanization and population growth has severely affected soil health and fertility. The need to meet the growing food demands has also led to unsustainable farming practices with the intensive application of chemical fertilizers and pesticides, resulting in significant greenhouse gas emissions. Biochar, a multifunctional carbon material, is being actively explored globally for simultaneously addressing the concerns related to improving soil fertility and mitigating climate change. Reviews on biochar, however, mainly confined to lab-scale studies analyze biochar production and its characteristics, its effects on soil fertility, and carbon sequestration. The present review addresses this gap by focusing on biochar field trials to enhance the current understanding of its actual impact on the field, w.r.t. agriculture and climate change. The review presents an overview of the effects of biochar application as observed in field studies on soil health (soil’s physical, chemical, and biological properties), crop productivity, and its potential role in carbon sequestration. General trends from this review indicate that biochar application provides higher benefits in soil properties and crop yield in degraded tropical soils vis-a-vis the temperate regions. The results also reveal diverse observations in soil health properties and crop yields with biochar amendment as different studies consider different crops, biochar feedstocks, and local climatic and soil conditions. Furthermore, it has been observed that the effects of biochar application in lab-scale studies with controlled environments are not always distinctly witnessed in corresponding field-based studies and the effects are not always synchronous across different regions. Hence, there is a need for more data, especially from well-designed long-term field trials, to converge and validate the results on the effectiveness of biochar on diverse soil types and agro-climatic zones to improve crop productivity and mitigate climate change.

The capabilities of Artificial Intelligence (AI) evolve rapidly and affect almost all sectors of society. AI has been increasingly integrated into criminal and harmful activities, expanding existing vulnerabilities, and introducing new threats. This article reviews the relevant literature, reports, and representative incidents which allows to construct a typology of the malicious use and abuse of systems with AI capabilities. The main objective is to clarify the types of activities and corresponding risks. Our starting point is to identify the vulnerabilities of AI models and outline how malicious actors can abuse them. Subsequently, we explore AI-enabled and AI-enhanced attacks. While we present a comprehensive overview, we do not aim for a conclusive and exhaustive classification. Rather, we provide an overview of the risks of enhanced AI application, that contributes to the growing body of knowledge on the issue. Specifically, we suggest four types of malicious abuse of AI (integrity attacks, unintended AI outcomes, algorithmic trading, membership inference attacks) and four types of malicious use of AI (social engineering, misinformation/fake news, hacking, autonomous weapon systems). Mapping these threats enables advanced reflection of governance strategies, policies, and activities that can be developed or improved to minimize risks and avoid harmful consequences. Enhanced collaboration among governments, industries, and civil society actors is vital to increase preparedness and resilience against malicious use and abuse of AI.

Supplementary key words liver humanized mouse model cholesterol transintestinal cholesterol excretion cytochrome P450 family 2 subfamily c polypeptide 70 Bile acids (BAs) are amphipathic steroids, produced exclusively by the liver from cholesterol, that act as soaps to facilitate solubilization and absorption of dietary cholesterol, fats, and fat-soluble vitamins in the small intestine (1). Whereas cholesterol is virtually not absorbed in the absence of BAs, fatty acid absorption decreases from 97% to 70% when no BAs are present within the intestinal lumen (2). The capacity to solubilize cholesterol, but also other lipids, in the intestine is largely determined by the size and composition of the circulating BA pool that consists of several species differing in number, position, and orientation of hydroxyl groups (Table BAs also act as signaling molecules by activating the nuclear farnesoid X receptor (FXR; NR1H4) (3, 4) and the membrane-bound Takeda Abstract Bile acids (BAs) facilitate intestinal absorption of lipid-soluble nutrients and modulate various metabolic pathways through the farnesoid X receptor (FXR) and Takeda G-protein-coupled receptor 5. These receptors are targets for therapy in cholestatic and metabolic diseases. However, dissimilarities in BA metabolism between humans and mice complicate translation of preclinical data. Cytochrome P450 family 2 subfamily c polypeptide 70 (CYP2C70) was recently proposed to catalyze the formation of rodent-specific muricholic acids (MCAs). With CRISPR/Cas9-mediated somatic genome editing, we generated an acute hepatic Cyp2c70 knockout mouse model (Cyp2c70 ako ) to clarify the role of CYP2C70 in BA metabolism in vivo and evaluate whether its activity modulates effects of pharmacologic FXR activation on cholesterol homeostasis. In Cyp2c70 ako mice, chenodeoxycholic acid (CDCA) increased at the expense of MCA, resulting in a more hydrophobic human-like BA pool. Tracer studies demonstrated that, in vivo, CYP2C70 catalyzes the formation of MCA primarily by sequential 6-hydroxylation and C7-epimerization of CDCA, generating MCA as an intermediate metabolite. Physiologically, the humanized BA composition in Cyp2c70 ako mice blunted the stimulation of fecal cholesterol disposal in response to FXR activation compared with WT mice, predominantly due to reduced stimulation of transintestinal cholesterol excretion. Thus, deletion of hepatic Cyp2c70 in adult mice translates into a human-like BA pool composition and impacts the response to pharmacologic FXR activation. This Cyp2c70 ako mouse model may be a useful tool for future studies of BA signaling and metabolism that informs human disease development and treatment.-

Many studies have shown that bilingual children outperform monolinguals on tasks testing executive functioning, but other studies have not revealed any effect of bilingualism. In this study we compared three groups of bilingual children in the Netherlands, aged 6-7 years, with a monolingual control group. We were specifically interested in testing whether the bilingual cognitive advantage is modulated by the sociolinguistic context of language use. All three bilingual groups were exposed to a minority language besides the nation's dominant language (Dutch). Two bilingual groups were exposed to a regional language (Frisian, Limburgish), and a third bilingual group was exposed to a migrant language (Polish). All children participated in two working memory tasks (verbal, visuospatial) and two attention tasks (selective attention, interference suppression). Bilingual children outperformed monolinguals on selective attention. The cognitive effect of bilingualism was most clearly present in the Frisian-Dutch group and in a subgroup of migrant children who were relatively proficient in Polish. The effect was less robust in the Limburgish-Dutch sample. Investigation of the response patterns of the flanker test, testing interference suppression, suggested that bilingual children more often show an effect of response competition than the monolingual children, demonstrating that bilingual children attend to different aspects of the task than monolingual children. No bilingualism effects emerged for verbal and visuospatial working memory.

An outbreak of tuberculosis (TB) in sea lions occurred recently in a zoo in the Netherlands. The disease was detected in a captive colony consisting of 29 animals kept in an open air basin with an indoor night house. Approximately 25 animal keepers were in close contact with the animals.The sea lions were investigated using the tuberculin skin test (TST) with avian and bovine purified protein derivative (PPD) and, in case of positivity, necropsied. A survey was conducted among the animal keepers including TSTs with Mycobacterium tuberculosis complex PPD tuberculin, a chest X-ray and an interferon-gamma release assay (IGRA).Necropsy was positive for TB in 13 of the 29 sea lions. Three cases of pulmonary involvement were found. Only one of these was infectious and it was therefore regarded as the source case. The causative mycobacterium was identified as M. pinnipedii. Six of the 25 animal keepers were TST-positive; in five of these, infection was confirmed by a positive IGRA.Transmission of M. pinnipedii infection from sea lions to humans was established by TST. IGRA results largely agreed with the TST results. Nebulisation when cleaning the sea lions' enclosure was most likely the main cause of transmission to humans.

How does language change take place and could developments be predictable? In this study, Arjen Versloot evaluates these questions, supported by analysis of the decline in the use of unstressed vowels in the Frisian language between 1300 and 1550. This decline is found, for example, in the words: Old Frisian sitta ‘to sit’ > Modern Frisian sitte and Old Frisian sone ‘son’ > Modern Frisian soan. The study presents two models of language change. Model one considers the duration and intensity of vowels in individual words, rather than abstract, underlying phonemes. The order and timing of vowel reduction can thus be predicted with 95% accuracy over a period of 200 years. In the second model, the language user is regarded as a ‘calculating speaker’, evaluating what he hears from others, estimating the reception by listeners, and a little lazy in his articulation. With an accuracy of over 90%, the model predicts the order and timing of changes in verbal and nominal endings where vowel reduction is involved. These results of the study support the hypothesis of language as a deterministic, dynamic system, where the ‘grammar’ and its change are the outcome of self-organization in the language system. The models are fed with detailed data from late-mediaeval Frisian texts, providing a significant amount of new information about Open Syllable Lengthening, Vowel Balance, Vowel Harmony and Apocope/Syncope. One of the remarkable conclusions is that 15th and 16th centuries Frisian was probably a tonal language, just like modern Norwegian.

The COVID-19 pandemic leads governments around the world to resort to tracking technology and other data-driven tools in order to monitor and curb the spread of SARS-CoV-2. Such large-scale incursion into privacy and data protection is unthinkable during times of normalcy. However, in times of a pandemic the use of location data provided by telecom operators and/or technology companies becomes a viable option. Importantly, legal regulations hardly protect people's privacy against governmental and corporate misuse. Established privacy regimes are focused on individual consent, and most human rights treaties know derogations from privacy and data protection norms for states of emergency. This leaves little safeguards nor remedies to guarantee individual and collective autonomy. However, the challenge of responsible data use during a crisis is not novel. The humanitarian sector has more than a decade of experience to offer. International organisations and humanitarian actors have developed detailed guidelines on how to use data responsibly under extreme circumstances. This article briefly addresses the legal gap of data protection and privacy during this global crisis. Then it outlines the state of the art in humanitarian practice and academia on data protection and data responsibility during crisis.

The current paper describes a study that sought to determine the beliefs, practices, and needs of parents living in Montreal, Quebec, who were raising their children bi/multilingually. The parents (N = 27) participated in a total of nine focus group and individual interviews in which they discussed their family language policies (language ideologies, practices, and actions taken to maintain a language). Through rounds of deductive and inductive coding and analysis, family language policies regarding English and/or French were compared with policies regarding heritage languages. The participants’ family language policies were further examined in light of Quebec’s official language policy of interculturalism. Findings indicate a complex co-existence of family and official language policy in which parents both support Quebec’s official language policy by converging towards French as a common public language and questioning the policy’s stance on official institutional support for heritage languages.

BACKGROUND: Asthma and rhinitis may represent two manifestations of the same airway disease. Genetic research can increase our understanding of their common or distinct pathogenesis. IL13 and IL4R polymorphisms are associated with asthma and show gene-gene interaction in asthma. Their role in rhinitis has not been extensively studied. METHODS: Association of IL13 and IL4R polymorphisms in relation to rhinitis, asthma, serum IgE and skin test response was studied in: (1) 188 trios ascertained through a proband with rhinitis who were clinically not affected by asthma; (2) 407 trios with an asthmatic proband, and (3) 118 asthma cases and 102 unrelated healthy controls using family-based association testing, logistic regression, and analysis of variance as appropriate. Gene-gene interaction was evaluated using logistic regression analysis. RESULTS: IL13 C-1111T (rs1800925) was significantly associated with rhinitis and atopic phenotypes in rhinitis trios that were not affected by clinical asthma. IL13 Arg130Gln (rs20541) and G870A (rs1295685) were consistently associated with asthma and serum IgE in both asthma populations. IL4R Glu375Ala (rs1805011) and Ser411Leu (rs1805013) were associated with asthma in the asthma case-control population. Combining risk genotypes of IL13 Arg130Gln with IL4R Glu375Ala, and IL13 C-1111T with IL4R Ser478Pro yielded increased risks for asthma compared to their separate effects. CONCLUSION: IL13 polymorphisms were associated with asthma and rhinitis without clinical asthma; thus, these polymorphisms may constitute a common etiologic pathway for their development. In addition, the study replicates a previously reported interaction of IL13 and IL4R polymorphisms in asthma.

Societies at large still grapple to categorize digital space as a phenomenon. At the same time, scientists and developers are searching for innovative methods to better understand how the fundamental shifts caused by digital change will affect the future of humanity over the coming decades. Interdisciplinary governance research at the intersection of technological and environmental foresight is urgently needed to minimize the risks of technological change and explore how digitalization may support, hinder or re-shape sustainability transformations. In this article, we focus on the case of ‘blockchain’ or distributed-ledger technology (DLT) to investigate how recent digital technologies may support the implementation of sustainable development initiatives. Our investigation is centered on areas of public administration and governance which will most likely see an adoption of DLT over the next two decades, such as digital identity, social service provision, and innovative climate finance. To allow for a meaningful comparison of various use cases, we propose four guiding questions that can help researchers, decision-makers and practitioners to determine whether DLT might be an appropriate choice for the sustainability-related task at hand. Moreover, we illustrate how the initial design and subsequent implementation of DLTs may support more centralized or networked modes of governance.

This study investigates the link between the perception and production in sound change in progress, both at the regional and the individual level. Two devoicing processes showing regional variation in Dutch are studied: the devoicing of initial labiodental fricatives and of initial bilabial stops. Five regions were selected, to represent different stages of change in progress. For each region, 20 participants took part in production (Study 1) and perception (Study 2) experiments. First, the results of the production tasks give additional insight in the regional and individual patterns of sound change. Second, the regional perceptual patterns in fricatives match the differences in production: perception is the most categorical in regions where the devoicing process is starting, and the least categorical in regions where the process of devoicing is almost completed. Finally, a clear link is observed between the production and perception systems undergoing sound change at the individual level. Changes in the perceptual system seem to precede changes in production. However, at the sound change completion, perception lags behind: individuals still perceive a contrast they no longer produce.

To investigate whether genome sequencing yields more useful markers than those currently used to study the epidemiology of tuberculosis, it was applied to three Mycobacterium tuberculosis isolates of the Harlingen outbreak. Our findings suggest that single nucleotide polymorphisms can be used to identify transmission chains in restriction fragment length polymorphism clusters.