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Estonia has since the liberation from the Soviet Union in 1991 successfully branded itself as a digital society and an education nation. This transformation builds on a "sociotechnical imaginary" where the progression of learning and the advancement of future citizens is postulated by a restructuring of the classroom through digital solutions. In this case study, we look at a prototype of a future classroom that was set up at the Estonian pavilion at the world fair EXPO 2020 in Dubai, as part of a nation branding process, promoting the nation's educational system and prosperous ed-tech sector. The future classroom was promoted using slogans and futuristic visuals that targeted foreign investors and policy makers, in a way that suggested that the anticipated digital future already exists in Estonia, and therefore, is available for foreign investment, while at the same time connecting to a national and historical narrative of Estonia as part of the European cultural sphere.

Abstract Corals in marginal reef habitats generally exhibit less bleaching and associated mortality compared to nearby corals in more pristine reef environments. It is unclear, however, if these differences are due to environmental differences, including turbidity, or genomic differences between the coral hosts in these different environments. One particularly interesting case is in the coral genus Porites, which contains numerous morphologically similar massive Porites species inhabiting a wide range of reef habitats, from turbid river deltas and stagnant back reefs to high-energy fore reefs. Here, we generate ddRAD data for 172 Porites corals from river delta and adjacent (

Background Associations between violent victimisation and psychiatric disorders are hypothesised to be bidirectional, but the role of violent victimisation in the aetiologies of psychiatric disorders and other adverse outcomes remains unclear. We aimed to estimate associations between violent victimisation and subsequent common psychiatric disorders, suicidal behaviours, and premature mortality while accounting for unmeasured familial confounders. Methods and findings Using nationwide registers, we identified a total of 127,628 individuals born in Finland (1987 to 2004) and Sweden (1973 to 2004) who had experienced violent victimisation, defined as either hospital admissions or secondary care outpatient visits for assault-related injuries. These were age- and sex-matched with up to 10 individuals in the general population (n = 1,276,215). Additionally, we matched those who had experienced violent victimisation with their unaffected siblings (n = 132,408). Outcomes included depression, anxiety, personality disorders, alcohol use disorders, drug use disorders, suicidal behaviours, and premature mortality. Participants were followed from the victimisation date until the date of the outcome, emigration, death, or December 31, 2020, whichever occurred first. Country-specific associations were estimated using stratified Cox regression models, which also accounted for unmeasured familial confounders via sibling comparisons. The country-specific associations were then pooled using meta-analytic models. Among 127,628 patients (69.0% male) who had experienced violent victimisation, the median age at first violent victimisation was 21 (interquartile range: 18 to 26) years. Incidence of all outcomes was larger in those who were exposed to violent victimisation compared to population controls, ranging from 2.3 (95% confidence interval (CI) [2.2; 2.4]) per 1,000 person-years for premature mortality (compared with 0.6, 95% CI [0.6; 0.6], in controls) to 22.5 (95% CI [22.3; 22.8]) per 1,000 person-years for anxiety (compared with 7.3, 95% CI [7.3; 7.4], in controls). In adjusted models, people who had experienced violent victimisation were between 2 to 3 times as likely as their siblings to develop any of the outcomes, ranging from adjusted hazard ratio [aHR] 1.7 (95% CI [1.7; 1.8]) for depression to 3.0 (95% CI [2.9; 3.1]) for drug use disorders. Risks remained elevated 2 years post-victimisation, ranging from aHR 1.4 (95% CI [1.3; 1.5]) for depression to 2.3 (95% CI [2.2; 2.4]) for drug use disorders. Our reliance on secondary care data likely excluded individuals with milder assault-related injuries and less severe psychiatric symptoms, thus suggesting that our estimates may be conservative. Another limitation is the possibility of residual genetic confounding, as full siblings share on average about half of their co-segregating genes. However, the associations remained robust even after adjusting for both measured and unmeasured familial confounders. Conclusions In this longitudinal cross-national cohort study, we observed that those who had experienced violent victimisation were at least twice as likely as their unaffected siblings to develop common psychiatric disorders (i.e., depression, anxiety, personality disorder, and alcohol and drug use disorders), engage in suicidal behaviours, and to die prematurely. Importantly, these risk elevations remained 2 years after the first victimisation event. Improving clinical assessment, management, and aftercare psychosocial support could therefore potentially reduce rates of common psychiatric disorders, suicidality, and premature mortality in individuals experiencing violent victimisation., Author(s): Amir Sariaslan 1,*, Joonas Pitkänen 2,3, Jonas Forsman 4,5, Ralf Kuja-Halkola 6, Isabell Brikell 6,7,8, Brian M. D'Onofrio 6,9, Mikko Aaltonen 10,11, Henrik Larsson 6,12, Pekka Martikainen 2,3, Paul [...]

Abstract The innate immune system serves as the body's first line of defense, utilizing pattern recognition receptors like Toll‐like receptors to detect pathogens and initiate rapid response mechanisms. Following this initial response, adaptive immunity provides highly specific and sustained killing of pathogens via B cells, T cells, and antibodies. Traditionally, it has been assumed that innate immunity activates adaptive immunity; however, recent studies have revealed more complex interactions. This review provides a detailed dissection of the composition and function of the innate and adaptive immune systems, emphasizing their synergistic roles in physiological and pathological contexts, providing new insights into the link between these two forms of immunity. Precise regulation of both immune systems at the same time is more beneficial in the fight against immune‐related diseases, for example, the cGAS–STING pathway has been found to play an important role in infections and cancers. In addition, this paper summarizes the challenges and future directions in the field of immunity, including the latest single‐cell sequencing technologies, CAR‐T cell therapy, and immune checkpoint inhibitors. By summarizing these developments, this review aims to enhance our understanding of the complexity interactions between innate and adaptive immunity and provides new perspectives in understanding the immune system.

Anthropogenic factors threaten biodiversity of natural habitats globally, including boreal forest habitats of culturally important game species, such as grouse. Forestry and intense draining of wetlands have resulted in landscape fragmentation of the peatlands and the forests in terms of their structure (a mosaic of differently managed small stands), and the loss and alteration of natural grouse habitats, which impacts on fitness parameters are still partly unexamined. We used grouse brood location data from the Finnish wildlife triangle censuses from 2017 to 2020 to study how forest structure and drainage affect breeding success of four grouse species. We calculated environmental characteristics (forest and landscape structure, peatlands and their drainage status) around individual brood observations with different buffer sizes and used them to explain brood size variation and the probability of complete failure (female with no brood). While the most important buffer zones differed by species, brood sizes were generally linked to habitats that offer shelter and food. Black grouse brood size increased when the proportions of deciduous trees and xeric heath forests increased. Hazel grouse broods were largest in spruce-dominated mires and herb-rich forests. Willow grouse brood size decreased with increasing proportion of poorer barren heath forest habitat. Capercaillie brood size decreased as a function of drainage ditch length. In Capercaillie and Black grouse, females without broods were overrepresented (zero-inflation), and the zero excess was related to habitats that differed from those of brooded females. These results suggest that forest management methods and peatland drainage can have a negative effect on offspring production of boreal grouse species. Restoration of natural peatlands and less invasive management such continuous cover forestry should enhance environmental conditions for grouse.

Abstract Introduction Drug courts are criminal justice programs to divert people with substance use disorders from incarceration into treatment. Drug courts have become increasingly popular in the US and other countries. However, their effectiveness in reducing important public health outcomes such as recidivism and substance-related health harms remains ambiguous and contested. We used nationwide register data from Sweden to evaluate the effectiveness of contract treatment sanction, the Swedish version of drug court, in reducing substance misuse, adverse somatic and mental health outcomes, and recidivism. Methods In this prospective cohort study, two quasi-experimental designs were used: difference-in-differences and the within-individual design. In the latter, we compared the risk of outcomes during time on contract treatment to, 1) parole after imprisonment and, 2) probation. Results The cohort included 11,893 individuals (13% women) who underwent contract treatment. Contract treatment was associated with a reduction of 7 percentage points (95% CI: -.088, -.055) in substance misuse, 5 percentage points (-.064, -.034) in adverse mental health events, 9 percentage points (-.113, -.076) in adverse somatic health events, and 3 fewer charges (-3.16, -2.85) for crime in difference-in-differences analyses. Within-individual associations suggested that the same individual had longer times-to-event for all outcomes during contract treatment than on parole or on probation. Conclusions Contract treatment is an effective intervention from both public health and criminal justice perspective. Our findings suggest that it is a superior alternative to incarceration in its target group. Further, we find that an implementation approach that is less punitive and more inclusive than what is typical in the US can be successful.

Objectives: This study aimed to investigate the association between drug exposure and adverse events (AEs) during the standardized multidrug-resistant tuberculosis (MDR-TB) treatment, as well as to identify predictive drug exposure thresholds. Methods: We conducted a prospective, observational multicenter study among participants receiving standardized MDR-TB treatment between 2016 and 2019 in China. AEs were monitored throughout the treatment and their relationships to drug exposure (e.g., the area under the drug concentration-time curve from 0 to 24 h, AUC0-24 h) were analyzed. The thresholds of pharmacokinetic predictors of observed AEs were identified by boosted classification and regression tree (CART) and further evaluated by external validation. Results: Of 197 study participants, 124 (62.9%) had at least one AE, and 15 (7.6%) experienced serious AEs. The association between drug exposure and AEs was observed including bedaquiline, its metabolite M2, moxifloxacin and QTcF prolongation (QTcF >450 ms), linezolid and mitochondrial toxicity, cycloserine and psychiatric AEs. The CART-derived thresholds of AUC0-24 h predictive of the respective AEs were 3.2 mg·h/l (bedaquiline M2); 49.3 mg·h/l (moxifloxacin); 119.3 mg·h/l (linezolid); 718.7 mg·h/l (cycloserine). Conclusions: This study demonstrated the drug exposure thresholds predictive of AEs for key drugs against MDR-TB treatment. Using the derived thresholds will provide the knowledge base for further randomized clinical trials of dose adjustment to minimize the risk of AEs.

Forests are pivotal for biodiversity, food webs, and human economies, and as carbon sinks their climate change mitigation potential is undisputed. However, whether trees continue to efficiently accumulate biomass at an increasing rate with age, how growth trajectories respond to climate change, and vary with latitude at species range margins is under debate. Here, we combine tree-ring data with biometric equation modeling to analyze how annual biomass increment varies according to tree age, species, latitude, and germination year. We generated 26,225 estimates of annual biomass increments for 136 individual trees, representing two evergreen gymnosperm conifer species (Picea abies (L.) H.Karst., and Pinus sylvestris L.) and two deciduous angiosperm species (Quercus spp. L. and Fagus sylvatica L.). Our dataset includes some old trees (range 150 - 405 years), and samples from locations spanning >10° latitude (55.0 - 66.3 °N) in Sweden. Annual biomass increments varied considerably between species, years and among individual trees within stands. On average, biomass increment remained positive throughout the lifespan across trees, species, and latitudes. Age-specific biomass increment was higher in the deciduous than in the evergreen species and declined with increasing latitude within species. For spruce and beech, biomass increment increased significantly with germination year, possibly reflecting faster growth in recent times in response to a warmer climate. The findings have implications for forestry practices aimed at productivity, biodiversity conservation, and climate change mitigation.

ABSTRACTThis review gives an overview of the protective role of CD8+ T cells in SARS-CoV-2 infection. The cross-reactive responses intermediated by CD8+ T cells in unexposed cohorts are described. Additionally, the relevance of resident CD8+ T cells in the upper and lower airway during infection and CD8+ T-cell responses following vaccination are discussed, including recent worrisome breakthrough infections and variants of concerns (VOCs). Lastly, we explain the correlation between CD8+ T cells and COVID-19 severity. This review aids in a deeper comprehension of the association between CD8+ T cells and SARS-CoV-2 and broadens a vision for future exploration.

BackgroundLonger treatment time has been shown to be associated with lower crime recidivism among forensic psychiatric patients, but it is not known if this applies also to mortality. In this study, we aim to research whether treatment time is associated with risk of post-discharge mortality in Finnish forensic psychiatric patients.Materials and methodsThe study population consisted of 989 patients committed to compulsory forensic psychiatric hospital treatment in Finland from 1980 to 2009 who were released from care by the end of 2018. Each patient included in the cohort was linked with the Statistics Finland register, which includes all data on dates and causes of deaths in Finland. Crude cumulative rate of mortality were estimated using Kaplan–Meier method and compared using logrank-test. Adjusted cumulative rate analyzed using Cox regression model. A possible nonlinear relationship between the treatment time and the hazard of death was assessed by using 3-knot-restricted cubic spline regression. Adjusted models included age, sex, and SUD (substance use disorder) as covariates.ResultsThe mean duration of care was 7.1 (SD 6) years. The duration of treatment variable was divided into tertiles of treatment duration less than 3.5 years, 3.5–7.9 years and equal or more than 8 years. The risk of mortality was highest in the first tertile, and lowest in the last tertile. The risk of mortality was higher for patients suffering from SUD, for patients of male sex and for those released at younger age.ConclusionsLonger treatment time is associated with reduced post-discharge mortality in forensic psychiatric patients in Finland. Especially males and individuals with SUD are at higher mortality risk after release, but longer treatment duration may mitigate these risks. Longer periods of hospitalization have to be, however, viewed against the backdrop of institutionalization and loss of self-determination.

Abstract Maturation of the secondary antibody repertoire requires class‐switch recombination (CSR), which switches IgM to other immunoglobulins (Igs), and somatic hypermutation, which promotes the production of high‐affinity antibodies. Following immune response or infection within the body, activation of T cell‐dependent and T cell‐independent antigens triggers the activation of activation‐induced cytidine deaminase, initiating the CSR process. CSR has the capacity to modify the functional properties of antibodies, thereby contributing to the adaptive immune response in the organism. Ig CSR defects, characterized by an abnormal relative frequency of Ig isotypes, represent a rare form of primary immunodeficiency. Elucidating the molecular basis of Ig diversification is essential for a better understanding of diseases related to Ig CSR defects and could provide clues for clinical diagnosis and therapeutic approaches. Here, we review the most recent insights on the diversification of five Ig isotypes and choose several classic diseases, including hyper‐IgM syndrome, Waldenström macroglobulinemia, hyper‐IgD syndrome, selective IgA deficiency, hyper‐IgE syndrome, multiple myeloma, and Burkitt lymphoma, to illustrate the mechanism of Ig CSR deficiency. The investigation into the underlying mechanism of Ig CSR holds significant potential for the advancement of increasingly precise diagnostic and therapeutic approaches.

Introduction The large reservoir of tuberculosis (TB) infections is one of the main reasons for the persistent incidence of TB. Accurate diagnostic tests are crucial to correctly identify and treat people with TB infection, which is vital to eliminate TB globally. The rdESAT-6 and rCFP-10 (Cy-Tb) injection (‘Cy-Tb’), a TB-specific antigen skin test and STANDARD F TB-Feron FIA (‘Standard F TB’) measuring interferon-gamma by fluorescence immunoassay assay are two novel tools for the diagnosis of TB infection which offer advantages compared with current tests in low-resource settings and reduced costs to both health systems and TB-affected people. The proposed study aims to evaluate the diagnostic accuracy of these two new tests for TB infection diagnosis.Methods and analysis This cross-sectional study aims to assess the diagnostic accuracy for TB infection of the Cy-Tb skin test and Standard F TB assay (investigational tests) compared with the QuantiFERON-TB Gold Plus (QFT-Plus) assay as the immunological reference standard. Three different cohorts of study participants will be recruited at the Vietnam National Lung Hospital: adults with bacteriologically confirmed pulmonary TB (n=100), household contacts of people with TB (n=200) and people without TB infection (n=50). All consenting participants will undergo simultaneous testing with Cy-Tb, Standard F TB and QFT-Plus. The primary endpoint is the diagnostic accuracy of the Cy-Tb skin test and Standard F TB assay, expressed as sensitivity and specificity against the reference standard.Ethics and dissemination Ethical approval was granted by the Vietnam National Lung Hospital Institutional Review Board (65/23/CN-HDDD-BVPTU) and the Swedish Ethical Review Authority (Dnr 2023-04271-01). Study results will be disseminated to the scientific community and policymakers through scientific publications.Trial registration number NCT06221735.

The Grevé cheese, a semi-hard Swedish cheese, is well-known for its characteristic flavor and shape of eye formation. The size and distribution of the eyes play a crucial role for the sensory attributes, aesthetic value and quality of the cheese. This article focuses on investigating the feasibility of using computed tomography (CT) scanning as a non-destructive tool to observe early-stage eye formation in Grevé cheese within an industrial trial. It is crucial to achieve a perfect combination of small and big sized eyes, evenly distributed within the cheese wheel, without having cracks/splits for optimal quality. Such variations could be visualized using CT-scanning of cheeses at a young and mature stage by providing high-resolution, three-dimensional CT-scanning images of the cheese's internal structure, without the need for physical dissection. Further, the distribution of eyes, their shape and number, could be visualized and compared for the same cheese scanned at young and mature stages. Thus, the importance of monitoring eye formation through non-destructive techniques is emphasized to ensure consistent product quality.

The world’s oceans are challenged by climate change linked warming with typically highly populated coastal areas being particularly susceptible to these effects. Many studies of climate change on the marine environment use large, short-term temperature manipulations that neglect factors such as long-term adaptation and seasonal cycles. In this study, a Baltic Sea ‘heated’ bay influenced by thermal discharge since the 1970s from a nuclear reactor (in relation to an unaffected nearby ‘control’ bay) was used to investigate how elevated temperature impacts surface water microbial communities and activities. 16S rRNA gene amplicon based microbial diversity and population structure showed no difference in alpha diversity in surface water microbial communities, while the beta diversity showed a dissimilarity between the bays. Amplicon sequencing variant relative abundances between the bays showed statistically higher values for, e.g., Ilumatobacteraceae and Burkholderiaceae in the heated and control bays, respectively. RNA transcript-derived activities followed a similar pattern in alpha and beta diversity with no effect on Shannon’s H diversity but a significant difference in the beta diversity between the bays. The RNA data further showed more elevated transcript counts assigned to stress related genes in the heated bay that included heat shock protein genes dnaKJ, the co-chaperonin groS, and the nucleotide exchange factor heat shock protein grpE. The RNA data also showed elevated oxidative phosphorylation transcripts in the heated (e.g., atpHG) compared to control (e.g., atpAEFB) bay. Furthermore, genes related to photosynthesis had generally higher transcript numbers in the control bay, such as photosystem I (psaAC) and II genes (psbABCEH). These increased stress gene responses in the heated bay will likely have additional cascading effects on marine carbon cycling and ecosystem services.

BACKGROUND: Optimal drug dosing is important to ensure adequate response to treatment, prevent development of drug resistance and reduce drug toxicity. The aim of these clinical standards is to provide guidance on 'best practice´ for dosing and management of TB drugs.METHODS: A panel of 57 global experts in the fields of microbiology, pharmacology and TB care were identified; 51 participated in a Delphi process. A 5-point Likert scale was used to score draft standards. The final document represents the broad consensus and was approved by all participants.RESULTS: Six clinical standards were defined: Standard 1, defining the most appropriate initial dose for TB treatment; Standard 2, identifying patients who may be at risk of sub-optimal drug exposure; Standard 3, identifying patients at risk of developing drug-related toxicity and how best to manage this risk; Standard 4, identifying patients who can benefit from therapeutic drug monitoring (TDM); Standard 5, highlighting education and counselling that should be provided to people initiating TB treatment; and Standard 6, providing essential education for healthcare professionals. In addition, consensus research priorities were identified.CONCLUSION: This is the first consensus-based Clinical Standards for the dosing and management of TB drugs to guide clinicians and programme managers in planning and implementation of locally appropriate measures for optimal person-centred treatment to improve patient care.