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Background & Aims: Autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) can co-exist in AIH-PBC, requiring combined treatment with immunosuppression and ursodeoxycholic acid (UDCA). The Paris criteria are commonly used to identify these patients; however, the optimal diagnostic criteria are unknown. We aimed to evaluate the use and clinical relevance of both Paris and Zhang criteria. Methods: Eighty-three patients with a clinical suspicion of AIH-PBC who were treated with combination therapy were included. Histology was re-evaluated. Characteristics and long-term outcomes were retrospectively compared to patients with AIH and PBC. Results: Seventeen (24%) patients treated with combination therapy fulfilled the Paris criteria. Fifty-two patients (70%) fulfilled the Zhang criteria. Patients who met Paris and Zhang criteria more often had inflammation and fibrosis on histology compared to patients only meeting the Zhang criteria. Ten-year liver transplant (LT)-free survival was 87.3% (95% CI 78.9–95.7%) in patients with AIH-PBC. This did not differ in patients in or outside the Paris or Zhang criteria (p = 0.46 and p = 0.40, respectively) or from AIH (p = 0.086). LT-free survival was significantly lower in patients with PBC and severe hepatic inflammation – not receiving immunosuppression – compared to those with AIH-PBC (65%; 95% CI 52.2–77.8% vs. 87%; 95% CI 83.2–90.8%; hazard ratio 0.52; p = 0.043). Conclusions: In this study, patients with AIH-PBC outside Paris or Zhang criteria were frequently labeled as having AIH-PBC and were successfully treated with combination therapy with similar outcomes. LT-free survival was worse in patients with PBC and hepatic inflammation than in those treated as having AIH-PBC. More patients may benefit from combination therapy. Impact and implications: This study demonstrated that patients with AIH-PBC variant syndrome treated with combined therapy consisting of immunosuppressants and ursodeoxycholic acid often do not fulfill the Paris criteria. They do however have comparable response to therapy and long-term outcomes as patients who do fulfill the diagnostic criteria. Additionally, patients with PBC and additional signs of hepatic inflammation have poorer long-term outcomes compared to patients treated as having AIH-PBC. These results implicate that a larger group of patients with features of both AIH and PBC may benefit from combined treatment. With our results, we call for improved consensus among experts in the field on the diagnosis and management of AIH-PBC variant syndrome.

The global Covid-19 pandemic exposed the fragility of urban systems and underscored the need to recalibrate regulatory and institutional frameworks for an anticipated crisis-prone future. This article explores the notion of ‘adaptive law and governance’ as a lens through which city authorities can test and modify legal and governance responses to future urban crises. It compares the experiences of managing Covid-19 in the two biggest cities in the Netherlands (Amsterdam and Rotterdam) and in South Africa (Johannesburg and Cape Town). This comparison, between two sets of urban municipal governments functioning under different constitutional systems and in different socio-economic contexts, provides insights pertaining to how adaptive urban governance during the pandemic was constrained or enabled by the interaction between the regulatory and institutional frameworks for and political realities of urban autonomy and intergovernmental relations. The article demonstrates that cities that govern within a flexible and decentralised legal and governance system are better positioned to develop and implement responsive measures to address crises or uncertainty. To enhance resilience, legal systems should promote transparent, risk-responsive, and reflective local governance tools to enable agile, context- specific and decisive crisis responses that can be employed as a matter of course rather than exception.

Few developing countries participate in external educational evaluations. Information gaps on education quality make it imperative to expand such evaluations. Furthermore, international comparability across different evaluations should be improved. In addition, data from evaluations must be combined with data on access or coverage. Finally, educational evaluations reveal social inequalities; socioeconomic status has a systematic influence on educational outcomes, but social gradients vary over countries. Resources alone cannot explain massive performance gaps between developing and developed countries. Large efficiency improvements must occur in classrooms and schools. The need is not for "league tables," but for data that allow countries to judge the appropriateness of their policies and strategies in an international context. Efficient and targeted application of resources and policies to improve education in developing countries requires information on system performance, inequalities, progress and stagnation. International evaluations should be expanded to more countries, should be better anchored and comparable, and should be demystified. Too little international educational evaluation is the enemy of progress.

This paper describes a process to develop and trial new metrics in South Africa to quantify school leadership and management practices or processes that are considered theoretically related to literacy outcomes. The predictive validity of these measures is assessed in challenging contexts, including 60 township and rural primary schools in South Africa. We observe a randomness to how better leadership and management practices are distributed across better and worse performing schools. Regression analyses confirm weak and inconsistent linkages between measured leadership and management dimensions and literacy outcomes across the sample. However, we find evidence of stronger linkages with intermediate outcomes, including monitoring curriculum coverage. This research contributes to a burgeoning, yet underdeveloped literature on educational management and leadership in Africa and the challenges of measurement in this context.

This study analyses information and feedback from matriculation-level continuous assessment in the South African education system in 2005. Continuous assessment (CASS) at the time carried a 25% weight in the final matriculation (Grade 12) mark, and it provided feedback that affected examination preparation and effort. Weak assessment in schools sends wrong signals to learners, which may have important consequences for the way in which they approach the final examination. Moreover, similarly wrong signals earlier in the learners' school careers may also have affected their subject choice and career planning. This study compares CASS data to the externally assessed matric exam marks for a number of subjects. There are two signalling dimensions to inaccurate assessments: (i) inflated CASS marks can give learners a false sense of security and lead to diminished exam effort; and (ii) a weak correlation between CASS and exam marks could mean poor signalling in another dimension: relatively good learners may get relatively low CASS marks. Such low correlations indicate poor assessment reliability, as the examination and continuous assessment should both be testing mastery of the same national curriculum. The paper analyses the prevalence and magnitude of each of these dimensions of weak signalling in South African schools and draws disturbing conclusions for a large part of the school system.

Much hope is placed on education systems to reduce socio-economic learning gaps. However, in South Africa, uneven functioning of the school system widens learning gaps. This paper analyses education performance using ANA data. Weak calibration and inter-temporal or inter-grade comparability of ANA test scores limit their usefulness for measuring learning gains. However, relative performance provides meaningful information on learning gaps and deficits. A reference group that is roughly on track to achieve the TIMSS average is used to estimate the performance required in each grade to perform at TIMSS' low international benchmark. By Grade 4, patterns across quintiles of on-track performance approximate matric exemption patterns. Viewed differently, academic and labour market prospects may be bleak for children who are no longer on track. Improvement in outcomes requires greater emphasis on the Foundation Phase or earlier, before learning deficits have grown to the extreme levels observed by the middle of primary school. This statement is true whether deficits arise from weak early instruction, or simply because a disadvantaged home environment requires early remedial action. The emphasis on the early grades that this analysis of the ANAs suggests is contrary to the conclusions drawn from the ANA results by policy makers that weak test scores in Mathematics in Grade 9 require major interventions in that grade.

The relationship between khôra and mysticism in M.M Walter’s poem ‘Die groot stilte’. In view of M.M. Walters’ recent death (28 Julie 2020), it is timeous to pay homage to him by focusing on a lesser-known aspect of his poetry, namely mysticism. This article aims to demonstrate the relationship between the mysterious and enigmatic Platonic concept khôra and mysticism, and to subsequently indicate how this is expressed in the poem ‘Die groot stilte’ (in the volume Sprekende van God). Walters (1929–2020) was mainly a satirist, but also a poet of religious verse. However, he differentiated himself as an unconventional religious poet and alternative seeker of God. He opposed church dogma and believed that Christ should be sought in ways that go beyond simply accepting the church’s teachings. The article opens with a brief survey of the mystical tradition in Afrikaans poetry, after which the poetry of Walters is briefly described. Subsequently, the reception of his anthology Sprekende van God is discussed. After an introductory discussion of the khôra concept, his poem Die groot stilte is analysed in detail, and the relationship between khôra and mysticism explained. Pieter G.R. de Villiers (2020) maintains that Walters created striking poems with mystical content, and that he was often misunderstood by the clergy and orthodox believers as an enemy of religion and the church. Countering this, De Villiers observes that Walters was driven to seek a genuine, credible spirituality. De Villiers finds it unfortunate that this aspect of Walters’ poetry is not sufficiently recognised. Contribution: Based on the analysis and interpretation of ‘Die groot stilte’, the conclusion is reached that Walters can indeed be described as a mystical poet and that his mystical poetry can be regarded as part of the relatively small yield in mystical Afrikaans literature. This article adds to the equally small corpus of academic literature on mysticism in Afrikaans.

In this paper we describe the historical background and contents of the DUMIRA vegetation plot database (GIVD-code EU-NL-003). It contains 13,046 relevés, collected between 1995 and 2018 at military ranges in the Netherlands, and it is updated regularly with new data. Historical circumstances led to the placement of military ranges at the most nutrient poor, dry, sandy soils, and as a result, the database is built up mainly by plots of Calluno-Ulicetea and Nardetea heathlands, Koelerio-Corynephoretea grasslands, and Quercetea robori-petraeae woodlands. These classes account for more than 50% of the database. Coastal communities (e.g. from the Juncetea maritimae and the Therosalicornietea) and scrubs (e.g. the Lonicero-Rubetea plicati and Salicetea arenariae) are other important sources. Notably, throughout the database, Rubus species are identified to species level. Although the DUMIRA database was initially used for management related vegetation mapping projects, the data gave rise to several more scientific studies and papers. Taxonomic reference: Van der Meijden (2005) for vascular plants; Van de Beek et al. (2014) for Rubus; Kleukers et al. (2004) for Orthoptera. Syntaxonomic reference: Mucina et al. (2016). Abbreviations: DUMIRA = Vegetation plot database of Dutch Military Ranges; GIVD = Global Index of Vegetation-plot Databases; MoD = Ministry of Defence.

Genetic modification techniques, in particular novel gene editing technologies, hold the yet unfulfilled promise of altering genetic traits in farm animals more efficiently than by crossbreeding, allowing for a more rapid development of new cattle breeds with distinct traits. Gene editing technologies allow for the directed alteration of specific traits and thereby have the potential to enhance, for instance, disease resilience, production yield and the production of desired substances in milk. The potential implications of these technological advancements, which are often combined with animal cloning methods, are discussed both for animal health and for consumer safety, also with consideration of available methods for the detection and identification of the related products in the food supply chain. Finally, an overview is provided of current regulatory approaches in the European Union (EU) and major countries exporting beef to the EU, for products from animals bred through established practices as well as modern biotechnologies.

The growing digitization puts more pressure on brick-and-mortar businesses in the retail sector by creating new and more complex customer demands that increase the need for cooperative and trustful exchange relationships between supervisors and salespeople. A promising approach to tackle these challenges lies in implementing less hierarchical leadership structures. While sharing leadership on the team level gains traction among practitioners as a viable form of horizontal leadership, research provides little evidence on the conditions and mechanisms that enable a shared leadership work environment for retail salespeople. Especially the role of formal leaders in such a transition remains unclear. To fill this void, we followed a two-study design. We conducted a large-scale survey with 1,527 salespeople of a German fashion retailer to analyze how formal leadership contributes to the existence of a less hierarchically structured work environment for retail salespeople. Our multiple mediation analysis provides in-depth and context-sensitive insights into conditions and mechanisms that facilitate a shared leadership environment. A subsequent online-based scenario experiment confirms that transformational leadership is a driver for a shared leadership environment. We contribute to the literature by showing that transformational leadership matters not only in business-to-business (B2B) settings but also in traditionally more transactional business-to-consumer (B2C) retail sales settings to create a shared leadership environment. [ABSTRACT FROM AUTHOR]

Background: When the new coronavirus rapidly spread across the globe, the impact of the virus on children was still unclear, and closing schools seemed the responsible thing to do. But much has been learnt since about coronavirus disease 2019 (COVID-19) and the effects of lockdown and school closures, both in South Africa and internationally. Aim: It shows that the mortality risk of the virus is extremely small for children, even when assuming an extremely pessimistic scenario for total COVID-19 deaths. Setting: We review the evidence at a national level in South Africa using nationally-representative datasets. Methods: This article offers evidence drawn from nationally representative household surveys, school surveys and administrative datasets, as well as research reports. Results: International evidence predominantly shows that children are not important transmitters of this virus, which is different from the case for influenza, for example. We show that there are considerable costs to the lockdown for children. These relate to foregone leaning opportunities, mental health, nutrition and physical health. Conclusion: We show that re-opening the economy whilst keeping schools closed results in many unintended consequences, including that children are at higher risk of being left home alone. Considering all of this, we propose that all children should return to schools, crèches and early childhood development (ECD)centres without any further delay.

No abstract available.

Background Arterial stiffness is an independent risk factor for cardiovascular disease and can be beneficially influenced by physical activity. However, it is not clear how an individual’s physical activity pattern over a week is associated with arterial stiffness. Therefore, we examined the associations of the amount and pattern of higher intensity physical activity with arterial stiffness. Methods and Results Data from the Maastricht Study (n=1699; mean age: 60±8 years, 49.4% women, 26.9% type 2 diabetes mellitus) were used. Arterial stiffness was assessed by carotid‐to‐femoral pulse wave velocity and carotid distensibility. The amount (continuous variable as h/wk) and pattern (categorical variable) of higher intensity physical activity were assessed with the activPAL3. Activity groups were: inactive (150 min/wk in ≤2 sessions), and regularly active (>150 min/wk in ≥3 sessions). In the fully adjusted model (adjusted for demographic, lifestyle, and cardiovascular risk factors), higher intensity physical activity was associated with lower carotid‐to‐femoral pulse wave velocity (amount: β = −0.05, 95% CI, −0.09 to −0.01; insufficiently active: β = −0.33, 95% CI, −0.55 to −0.11; weekend warrior: β = −0.38, 95% CI, −0.64 to −0.12; and regularly active: β = −0.46, 95% CI, −0.71 to −0.21 [reference: inactive]). These associations were stronger in those with type 2 diabetes mellitus. There was no statistically significant association between higher intensity physical activity with carotid distensibility. Conclusions Participating in higher intensity physical activity was associated with lower carotid‐to‐femoral pulse wave velocity, but there was no difference between the regularly actives and the weekend warriors. From the perspective of arterial stiffness, engaging higher intensity physical activity, regardless of the weekly pattern, may be an important strategy to reduce the risk of cardiovascular disease, particularly in individuals with type 2 diabetes mellitus.

Certain estrogen metabolites have been implicated in the pathophysiology of breast cancer. Moreover, the estrogen metabolite profiles of healthy women and those with (a high risk of) breast cancer differ significantly. The development of an analytical method to determine the relative levels of all the estrogen biotransformation products has been described in van der Berg et al. [1]. An improvement on previously developed methods was the ability to also detect molecules such as sulphate and glucuronide conjugates as well as progesterone, estradiol precursors, and metabolites from the 16-hydroxylation metabolic pathway of estrogens simultaneously with all other estrogen metabolites. The data presented here describe the optimisation of a solid phase extraction method with different fractionation steps for LC-MS/MS analysis of 27 estrogen-related metabolites from small urine volumes. Conditions that were optimised include the elution and washing solvent concentration, the urine, loading, washing, and elution volumes, as well as pH. All raw data used to construct the bar graphs presented in this article are included in the supplementary data file. The data indicated that fractionation was necessary in order to elute estrogen metabolites with different chemical properties at different eluate compositions. Only one of the fractions (containing the less water-soluble metabolites) underwent derivatisation before LC-MS/MS analysis. Keywords: Estrogen metabolism, Solid phase extraction, LC-MS/MS, Method optimisation

This paper provides an overview of learning losses and altered schooling patterns in South Africa during the COVID-19 pandemic (2020–2021). Five major trends emerge from a review of the evidence. These include significant learning losses (38–118% of a year of learning), widened learning inequality, lowered grade repetition rates, increased secondary school enrolments and an unprecedented rise in candidates writing and passing the National Senior Certificate (NSC) examination. School completion significantly increased in 2021 and 2022, spurred by COVID-19 adjusted assessment and promotion practices in Grades 10 and 11. Larger numbers of youth also achieved a NSC pass or Bachelor's pass enabling access to university. With twin pandemic shocks of learning losses and secondary school enrolment increases, remediating losses and realigning progression rules to effective assessment practices should be prioritised. [ABSTRACT FROM AUTHOR]

Abstract CC Chemokine Receptor 2 (CCR2) and its endogenous ligand CCL2 are involved in a number of diseases, including atherosclerosis. Several CCR2 antagonists have been developed as potential therapeutic agents, however their in vivo clinical efficacy was limited. In this report, we aimed to determine whether 15a, an antagonist with a long residence time on the human CCR2, is effective in inhibiting the development of atherosclerosis in a mouse disease model. First, radioligand binding assays were performed to determine affinity and binding kinetics of 15a on murine CCR2. To assess the in vivo efficacy, western-type diet fed apoE−/− mice were treated daily with 15a or vehicle as control. Treatment with 15a reduced the amount of circulating CCR2+ monocytes and the size of the atherosclerotic plaques in both the carotid artery and the aortic root. We then showed that the long pharmacokinetic half-life of 15a combined with the high drug concentrations ensured prolonged CCR2 occupancy. These data render 15a a promising compound for drug development and confirms high receptor occupancy as a key parameter when targeting chemokine receptors.

Objective Combined paediatric and forensic medical expertise to interpret physical findings is not available in Dutch healthcare facilities. The Dutch Expertise Centre for Child Abuse (DECCA) was founded in the conviction that this combination is essential in assessing potential physical child abuse. DECCA is a collaboration between the three paediatric hospitals and the Netherlands Forensic Institute. DECCA works with Bayes’ theorem and uses likelihood ratios in their conclusions.Design We present the implementation process of DECCA and cross-sectional data of the first 4 years.Participants Between 14 December 2014 and 31 December 2018, a total of 761 advisory requests were referred, all of which were included in this study. An advisee evaluation over the year 2015 was performed using a self-constructed survey to gain insight in the first experiences with DECCA.Results 761 cases were included, 381 (50.1%) boys and 361 (47.4%) girls (19 cases (2.5%) sex undisclosed). Median age was 1.5 years (range 1 day to 20 years). Paediatricians (53.1%) and child safeguarding doctors (21.9%) most frequently contacted DECCA. The two most common reasons for referral were presence of injury/skin lesions (n=592) and clinical history inconsistent with findings (n=145). The most common injuries were bruises (264) and non-skull fractures (166). Outcome of DECCA evaluation was almost certainly no or improbable child abuse in 35.7%; child abuse likely or almost certain in 24.3%, and unclear in 12%. The advisee evaluations (response rate 50%) showed that 93% experienced added value and that 100% were (very) satisfied with the advice.Conclusion Data show growing interest in the expertise of DECCA through the years. DECCA seems to be a valuable addition to Dutch child protection, since advisee value the service and outcome of DECCA evaluations. In almost half of the cases, DECCA concluded that child abuse could not be substantiated.

Genome editing is an emerging, new breeding technology with numerous potential applications in plant breeding. In Europe, genome editing is regarded, in legal terms, as a genetic modification technique, hence plants obtained using these methods fall under the legislation for genetically modified organisms (GMOs). Despite the opportunities that genome editing brings to the plant sector, it also poses challenges to the regulatory system. For example, the enforcement of labelling and traceability requirements for GM foods and feeds may be impossible for small genome edits that are indistinguishable from natural mutations. In order to discuss potential adaptations of EU legislation with stakeholders from the Dutch plant breeding sector, five different scenarios of future regulation of plants obtained by means of genome editing were elaborated. These scenarios were discussed in depth, along with the potential applications of genome editing in plant breeding, as well as challenges and opportunities. Stakeholders particularly indicated their preference for new, future-proof legislation in the long term, which will also include products of novel technologies. Finally, we discuss potential short-term amendments to current legislation, including the exemption of certain small mutations, that would make it align with regulation of genome edited plants in non-EU countries.

Several dietary patterns and nutritional supplements have been linked to the development, progression, and symptomatic treatment of Parkinson's disease (PD). Most of the evidence, at this point, is preliminary and based largely on observational studies. Interventional studies are scarce, so the evidence on effectiveness remains inconclusive. Dietary interventions could, analogous to exercise, potentially have a beneficial effect on disease symptoms as well as on the progression of the disease and should therefore be researched in high quality studies. Further work is also needed to study whether dietary interventions, when applied to an at-risk population, have any potential to postpone the onset of manifest PD. In this paper, we summarize all ongoing clinical trials on dietary interventions in PD. We found 10 ongoing studies, all aimed at a different intervention. These studies are mostly exploratory in nature or represent phase I or phase II trials focusing on safety, biological responses, and symptomatic effects. Taken together, we conclude that research on dietary interventions in persons with PD is still in its early days. The results of the various ongoing trials are expected to generate new hypotheses and will help to shape the agenda for future research on this important topic. [ABSTRACT FROM AUTHOR]

The global Covid-19 pandemic exposed the fragility of urban systems and underscored the need to recalibrate regulatory and institutional frameworks for an anticipated crisis-prone future. This article explores the notion of 'adaptive law and governance' as a lens through which city authorities can test and modify legal and governance responses to future urban crises. It compares the experiences of managing Covid-19 in the two biggest cities in the Netherlands (Amsterdam and Rotterdam) and in South Africa (Johannesburg and Cape Town). This comparison, between two sets of urban municipal governments functioning under different constitutional systems and in different socio-economic contexts, provides insights pertaining to how adaptive urban governance during the pandemic was constrained or enabled by the interaction between the regulatory and institutional frameworks for and political realities of urban autonomy and intergovernmental relations. The article demonstrates that cities that govern within a flexible and decentralised legal and governance system are better positioned to develop and implement responsive measures to address crises or uncertainty. To enhance resilience, legal systems should promote transparent, riskresponsive, and reflective local governance tools to enable agile, context- specific and decisive crisis responses that can be employed as a matter of course rather than exception. [ABSTRACT FROM AUTHOR]

Traditionally, meat and dairy products have been important protein sources in the human diet. Consumers are eating more plant-based proteins, which is reflected in current market trends. Assessing how alternative proteins are processed and their impact on food safety helps realize market opportunities while ensuring food safety. In this review, an analysis of the food safety hazards, along with current industry trends and processing methods associated with alternative proteins for meat and dairy products for the European Union market is described. Understanding the effects of processing and safety alternative proteins is paramount to ensuring food safety and understanding the risks to consumers. However, the data here is limited. With the expected further increase in protein alternatives in consumers' diets, the risk of food allergens is apparent. The occurrence of processing contaminants in plant-based alternatives may occur, along with anti-nutritional compounds, which interfere with the absorption of nutrients. Further, typical food safety hazards related to the plant, the product itself, or processing are relevant. Although hazards in insects and seaweed are being addressed, other protein alternatives like cultured meat and SCPs warrant attention. Our findings can aid industry and governmental authorities in understanding current trends and prioritizing hazards for future monitoring. [ABSTRACT FROM AUTHOR]

Early childhood development (ECD) access and quality inequalities can manifest as school and labour market outcomes that are persistently unequal by race, gender and geography. Using the General Household Survey 2019 and Early Childhood Development Census 2009–2014 data, we find that household socio-economic status, proximity to ECD centres and the mother’s educational attainment are positively associated with ECD enrolment. Having an economically inactive or unemployed adult in the household is negatively associated with enrolment rates. This paper also evaluates the programme gains (value added) of five ECD programmes in the large-scale cross-sectional the Early Learning Outcomes Measure study. We find gains that are surprisingly large, considering that these programmes served mainly poorer children, and because contact time per week for three of the programmes was only 2½ to 8 hours. [ABSTRACT FROM AUTHOR]