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Craft education in both Finland and Iceland originated over 140 years ago and was influenced by the Scandinavian Sloyd pedagogy. Since then, the subject has moved away from craft and towards technology, with the aim being to increase students' technological abilities. In the beginning, the subject largely focused on the students copying artefacts, using a variety of handicraft tools: the purpose of this was to improve pupils' manual skills, rather than their thinking skills. Today, however, the focus is also on the development of students' thinking skills, which enables them to work through the various handicraft processes (from initial ideas to the final product). This work is based on the idea generation of students and is thus expected to increase their self-esteem and ingenuity. This paper is based on a comparative study of students' attitudes towards craft and technology education in Finland and Iceland, which was undertaken by the University of Iceland and Helsinki University in the years 2011 and 2012. A quantitative survey was distributed to 213 school students and it consisted of 14 questions, which aimed to ascertain students' attitudes towards craft and technology. A literature review was subsequently completed, in order to examine and compare the origins of craft education in Finland and Iceland. The review highlighted that, despite the origins of craft education in Finland and Iceland being similar, the Icelandic national curriculum placed greater emphasis on design and innovation, whereas the Finnish national curriculum focused on the development of students' personalities and gender issues. The survey also showed differences in students' attitudes towards craft and technology education in the two countries: these differences may be explained by differences in the national curriculums and the different pedagogical traditions. However, this finding needs to be examined further through research.

This article builds on earlier research that defined and assessed technological competence among adolescents. It tracks students who took part in a measurements of technical abilities study fifteen years ago. The researcher had no previous knowledge of the test subjects' current employment status, but in favorable circumstances, these test subjects are now professionals in the field of technology. The aim of this research was to examine how technological competence was attained during the test participants' lives. This follow-up study was carried out as a qualitative case study. Data from interviews with three participants were tape-recorded and translated. The research data were then analyzed using content analysis. The analysis was carried out by assessing which of the essential elements in the participants technological competence contributed to success in their lives. These findings were later classified in terms of themes or factors and, finally, reported in the conclusions. The results from each participant interview are shown in a competence curve, which are explained in more detail. The competence curves indicate each person's development in technological competence during their life. (Contains 5 figures and 3 tables.)

The purpose of this study was to determine the elements motivating comprehensive school students to study technology education. The research was carried out as a qualitative case study and the material was collected through individual theme interviews. The study group consisted of two different test groups: novice and technological talents. In each test group there were three test participants, each representing a different case of motivation towards technology education. In choosing individuals for the study the main criteria were gender, negative or positive motivation and competence in the field of technology. This study found that the artifact to be made in school and the student's freedom of choice had the most significant effect on motivation in the novice test group. Instead, curiosity and intellectual challenge seemed to be the main elements in technological talents group. Although, we must be careful with final conclusions as the research group was relatively small, we can conclude that there were more signs of intrinsic motivation in technological talents test group and extrinsic motivation was emphasized in the novice group.

One important theme in technology education is the growing need to develop the type of pedagogies that encourage pupils in authentic and meaningful learning experiences. Often, the teaching strategies of technology education are only a matter of teaching the handling of materials and tools, and the production of mere objects does not consider how to incorporate broader pedagogical connections in comprehensive school technology education. The concept of meaningful learning has been brought into use in technology education of comprehensive school because some generic skills should also be learned in the work process. In this article, learning in technology education is approached from the point of view of meaningful learning. In addition, the realization of practicing the meaningful learning in the teaching of technology is examined.

Social interaction is thought to provide a selection pressure for human intelligence, yet little is known about its neurobiological basis and evolution throughout the primate lineage. Recent advances in neuroimaging have enabled whole brain investigation of brain structure, function, and connectivity in humans and non-human primates (NHPs), leading to a nascent field of comparative connectomics. However, linking social behavior to brain organization across the primates remains challenging. Here, we review the current understanding of the macroscale neural mechanisms of social behaviors from the viewpoint of system neuroscience. We first demonstrate an association between the number of cortical neurons and the size of social groups across primates, suggesting a link between neural information-processing capacity and social capabilities. Moreover, by capitalizing on recent advances in species-harmonized functional MRI, we demonstrate that portions of the mirror neuron system and default-mode networks, which are thought to be important for representation of the other's actions and sense of self, respectively, exhibit similarities in functional organization in macaque monkeys and humans, suggesting possible homologies. With respect to these two networks, we describe recent developments in the neurobiology of social perception, joint attention, personality and social complexity. Together, the Human Connectome Project (HCP)-style comparative neuroimaging, hyperscanning, behavioral, and other multi-modal investigations are expected to yield important insights into the evolutionary foundations of human social behavior.

Psychomotor performance is fundamental to human existence. It is important in many real world activities and nowadays psychomotor tests are used in several fields of industry, army, and medical sciences in employee selection. This article tries to define psychomotor activity by introducing some psychomotor theories. Furthermore the interrelationship between psychomotor, cognitive, and affective area is researched. It seems that there occurs a significant correlation between psychomotor and cognitive area, but between psychomotor and affective tests only a small correlation was found.

Changes in the economy, nature, production and society together with increasing scientific and technological knowledge make demands of transforming school teaching in the field of technology education. This article analyses current trends in Finnish technology education. The aim of the article is to explore briefly the integration between Science and Craft education and some of the current practices in technology education in Finland. Finnish technology education can be characterized as a design approach that has evolved from the craft-oriented tradition. Additionally, it involves many elements of computer controlling and electronic principles, but still much of the learning is focused on production skills. Approaches that are now dominant in craft education do not prepare students to meet the challenges of modern technology and working life.

In Finland teaching of technology has traveled a long road during its 140-year history. It has gradually gone from the copying of the model series dating back to the 1860s to the building of computer controlled robots. Materials, techniques and technology have developed wildly but the pedagogic contents are restricted regrettably still often only around the product to be made. In technology education subject matter teaching model, which includes motivation, planning, working and evolution is striven for out of narrow minded object thinking and out of merely copying working. In this article subject matter teaching model is approached from the point of view of meaningful learning.

Historically, technology educators have chosen the creation of products or projects as a means to teach technological concepts. Although it is true that technology is most commonly known by its products, in most educational situations technology is best described as a process. This paper describes a technology education course that promotes cooperative and creative problem-solving in primary school teacher education. The purpose of the course was to study creativity through analysing a special method for problem-solving and to create new pedagogical approaches in a learning environment, designed to promote active, co-operative, and problem-centred learning in technology education.

Mycoplasma bovis is an important cattle pathogen affecting animal health, welfare, and productivity. The main disease syndromes are mastitis, pneumonia, and otitis media in young stock, as well as arthritis. Response to antibiotic treatment is poor and no effective vaccine is available. Asymptomatic carriers are common and usually harbor the organism in the airways or mammary glands. Purchase of carrier animals is a major risk for the introduction of infection into naive herds. Following the detection of M. bovis in Finland in 2012, a voluntary control program was established. It aims to prevent the spread of the infection and to help farms attain certification of a low M. bovis risk. Among the diagnostic tools in the program, nasal swabs (NS) from young calves have been tested for M. bovis to indicate the infection status of the herd. In this study, we assessed the suitability of this test method. We analyzed the effectiveness of NS and deep nasopharyngeal swabs (NP) to detect M. bovis in pneumonic and healthy calves in dairy herds recently infected with M. bovis. In pneumonic calves, NP sampling followed by culture and real-time PCR demonstrated a proportion of positive agreement (PPA) of 0.91 compared with bronchoalveolar lavage (BAL), whereas NS showed only 0.5 PPA compared with BAL. Among healthy dairy calves, overall M. bovis prevalence in NS was 29.6%. The highest rate of shedding (43%) occurred in calves 31–60 days old. At the calf level, M. bovis prevalence in NP samples was 47% compared with 33% in NS samples among the 284 studied calves. However, at the herd level, NS sampling classified 51 out of 54 herds with a positive infection status as infected, whereas in NP sampling, the respective figure was 43 out of 54 herds (p = 0.061). In conclusion, NS sampling from calves under 6 months of age and analyzed by real-time PCR is a cost-efficient method for a control program to detect M. bovis in dairy herds, even if no M. bovis mastitis has been detected in the herd. For pneumonic calves, we recommend only NP or BAL sampling.

Recent methodological advances in MRI have enabled substantial growth in neuroimaging studies of non-human primates (NHPs), while open data-sharing through the PRIME-DE initiative has increased the availability of NHP MRI data and the need for robust multi-subject multi-center analyses. Streamlined acquisition and analysis protocols would accelerate and improve these efforts. However, consensus on minimal standards for data acquisition protocols and analysis pipelines for NHP imaging remains to be established, particularly for multi-center studies. Here, we draw parallels between NHP and human neuroimaging and provide minimal guidelines for harmonizing and standardizing data acquisition. We advocate robust translation of widely used open-access toolkits that are well established for analyzing human data. We also encourage the use of validated, automated pre-processing tools for analyzing NHP data sets. These guidelines aim to refine methodological and analytical strategies for small and large-scale NHP neuroimaging data. This will improve reproducibility of results, and accelerate the convergence between NHP and human neuroimaging strategies which will ultimately benefit fundamental and translational brain science.

Some European countries have successfully implemented country-specific control programs (CPs) for infectious cattle diseases that are not regulated or are regulated only to a limited extent at the European Union (EU) level. Examples of such diseases include bovine viral diarrhea (BVD), infectious bovine rhinotracheitis (IBR), and Johne's disease (JD). The CPs vary between countries in the design and quality of collected data as well as methods used to detect infection and estimate prevalence or probability of freedom from infection. Differences in disease status between countries and non-standardized approaches to assess freedom from infection pose a risk for countries with CPs for non-regulated diseases as infected animals may influence the progress of the disease control or eradication program. The implementation of output-based standards allows estimation and comparison of the probability of freedom for non-regulated cattle diseases in European countries. The aim of the current study was to assess the existence and quality of data that could be used for estimating freedom from infection in European countries. The online data collection tool was sent to 32 countries participating in the SOUND control COST Action and was completed by 24 countries. Data on cattle demographics and data from CPs of IBR and BVD exist in more than 50% of the response countries. However, data describing risk factors and CP of JD was reported as existing in

The COST action “Standardising output-based surveillance to control non-regulated diseases of cattle in the European Union (SOUND control),” aims to harmonise the results of surveillance and control programmes (CPs) for selected cattle diseases to facilitate safe trade and improve overall control of cattle infectious diseases. In this paper we aimed to provide an overview on the diversity of control for these diseases in Europe. A selected cattle disease was defined as an infectious disease of cattle with no or limited control at EU level, which is not included in the European Union Animal health law Categories A or B under Commission Implementing Regulation (EU) 2020/2002. A CP was defined as surveillance and/or intervention strategies designed to lower the incidence, prevalence, mortality or prove freedom from a specific disease in a region or country. Passive surveillance, and active surveillance of breeding bulls under Council Directive 88/407/EEC were not considered as CPs. A questionnaire was designed to obtain country-specific information about CPs for each disease. Animal health experts from 33 European countries completed the questionnaire. Overall, there are 23 diseases for which a CP exists in one or more of the countries studied. The diseases for which CPs exist in the highest number of countries are enzootic bovine leukosis, bluetongue, infectious bovine rhinotracheitis, bovine viral diarrhoea and anthrax (CPs reported by between 16 and 31 countries). Every participating country has on average, 6 CPs (min–max: 1–13) in place. Most programmes are implemented at a national level (86%) and are applied to both dairy and non-dairy cattle (75%). Approximately one-third of the CPs are voluntary, and the funding structure is divided between government and private resources. Countries that have eradicated diseases like enzootic bovine leukosis, bluetongue, infectious bovine rhinotracheitis and bovine viral diarrhoea have implemented CPs for other diseases to further improve the health status of cattle in their country. The control of the selected cattle diseases is very heterogenous in Europe. Therefore, the standardising of the outputs of these programmes to enable comparison represents a challenge.

Background Probody® therapeutics are antibody prodrugs that are activated in the tumor microenvironment by tumor-associated proteases, thereby restricting the activity to the tumor microenvironment and minimizing ‘off-tumor’ toxicity. We report dose-escalation and single-agent expansion phase data from the first-in-human study of CX-072 (pacmilimab), a Probody checkpoint inhibitor directed against programmed death-ligand 1 (PD-L1).Methods In the dose-escalation phase of this multicenter, open-label study (NCT03013491), adults with advanced solid tumors (naive to programmed-death-1/PD-L1 or cytotoxic T-lymphocyte-associated antigen 4 inhibitors) were enrolled into one of seven dose-escalation cohorts, with pacmilimab administered intravenously every 14 days. The primary endpoints were safety and determination of the maximum tolerated dose (MTD). In the expansion phase, patients with one of six prespecified malignancies (triple-negative breast cancer [TNBC]; anal squamous cell carcinoma [aSCC]; cutaneous SCC [cSCC]; undifferentiated pleomorphic sarcoma [UPS]; small bowel adenocarcinoma [SBA]; and thymic epithelial tumor [TET]); or high tumor mutational burden (hTMB) tumors were enrolled. The primary endpoint was objective response (Response Evaluation Criteria In Solid Tumors v.1.1).Results An MTD was not reached with doses up to 30 mg/kg. A recommended phase 2 dose (RP2D) of 10 mg/kg was chosen based on pharmacokinetic and pharmacodynamic findings in the expansion phase. Ninety-eight patients enrolled in the expansion phase: TNBC (n=14), aSCC (n=14), cSCC (n=14), UPS (n=20), SBA (n=14), TET (n=8), and hTMB tumors (n=14). Of 114 patients receiving pacmilimab at the RP2D, grade ≥3 treatment-related adverse events (TRAEs) were reported in 10 patients (9%), serious TRAEs in six patients (5%), and treatment discontinuation due to TRAEs in two patients (2%). Grade ≥3 immune-related AEs occurred in two patients (rash, myocarditis). High PD-L1 expression (ie, >50% Tumor Proportion Score) was observed in 22/144 (19%) patients. Confirmed objective responses were observed in patients with cSCC (n=5, including one complete response), hTMB (n=4, including one complete response), aSCC (n=2), TNBC (n=1), UPS (n=1), and anaplastic thyroid cancer (n=1).Conclusions Pacmilimab can be administered safely at the RP2D of 10 mg/kg every 14 days. At this dose, pacmilimab had a low rate of immune-mediated toxicity and showed signs of antitumor activity in patients not selected for high PD-L1 expression.Trial registration number NCT03013491.

Background Probody® therapeutics are antibody prodrugs designed to be activated by tumor-associated proteases. This conditional activation restricts antibody binding to the tumor microenvironment, thereby minimizing ‘off-tumor’ toxicity. Here, we report the phase 1 data from the first-in-human study of CX-072 (pacmilimab), a Probody immune checkpoint inhibitor directed against programmed death-ligand 1 (PD-L1), in combination with the anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) antibody ipilimumab.Methods Adults (n=27) with advanced solid tumors (naive to PD-L1/programmed cell death protein 1 or CTLA-4 inhibitors) were enrolled in the phase 1 combination therapy dose-escalation portion of this multicenter, open-label, phase 1/2 study (NCT03013491). Dose-escalation pacmilimab/ipilimumab followed a standard 3+3 design and continued until the maximum tolerated dose (MTD) was determined. Pacmilimab+ipilimumab was administered intravenously every 3 weeks for four cycles, followed by pacmilimab administered every 2 weeks as monotherapy. The primary objective was identification of dose-limiting toxicities and determination of the MTD. Other endpoints included the rate of objective response (Response Evaluation Criteria In Solid Tumors v.1.1).Results Twenty-seven patients were enrolled in pacmilimab (mg/kg)+ipilimumab (mg/kg) dose-escalation cohorts: 0.3+3 (n=6); 1+3 (n=3); 3+3 (n=3); 10+3 (n=8); 10+6 (n=6); and 10+10 (n=1). Dose-limiting toxicities occurred in three patients, one at the 0.3+3 dose level (grade 3 dyspnea/pneumonitis) and two at the 10+6 dose level (grade 3 colitis, grade 3 increased aspartate aminotransferase). The MTD and recommended phase 2 dose was pacmilimab 10 mg/kg+ipilimumab 3 mg/kg administered every 3 weeks. Pacmilimab-related grade 3–4 adverse events (AEs) and grade 3–4 immune-related AEs were reported in nine (33%) and six (22%) patients, respectively. Three patients (11%) discontinued treatment because of AEs. The overall response rate was 19% (95% CI 6.3 to 38.1), with one complete (anal squamous cell carcinoma) and four partial responses (cancer of unknown primary, leiomyosarcoma, mesothelioma, testicular cancer). Responses lasted for >12 months in four patients.Conclusions The MTD and recommended phase 2 dose of pacmilimab (10 mg/kg)+ipilimumab (3 mg/kg) every 3 weeks is active and has a favorable tolerability profile.

Animal disease control has a long tradition in Finland. The country is free of all EU-regulated cattle diseases of categories A and B. Infectious bovine rhinotracheitis, enzootic bovine leucosis, bovine viral diarrhea, bluetongue, bovine genital campylobacteriosis, and trichomoniasis do not currently exist in the country. The prevalence of paratuberculosis, Mycoplasma bovis, salmonella infection, and Q-fever is low. The geographic location, cold climate, low cattle density, and limited animal imports have contributed to the favorable disease situation. Besides screening for selected regulated diseases, the national disease-monitoring program includes periodic active monitoring of non-regulated diseases, which allows assessment of the need for new control measures. The detection of diseases through efficient passive surveillance also plays an important part in disease monitoring. The Finnish cattle population totals 850,000 animals kept on 9,300 cattle farms, with 62,000 suckler cows in 2,100 herds and 260,000 dairy cows in 6,300 herds. Animal Health ETT, an association owned by the dairy and meat industry, keeps a centralized cattle health care register. Animal Health ETT supervises cattle imports and trade within the country and runs voluntary control programs (CP) for selected diseases. Active cooperation between authorities, the cattle industry, Animal Health ETT, and herd health experts enables the efficient planning and implementation of CPs. CPs have been implemented for cattle diseases such as salmonella, Mycoplasma bovis, ringworm, and Streptococcus agalactiae. The CP for salmonellosis is compulsory and includes all Salmonella serotypes and all cattle types. It has achieved the goal of keeping the salmonella prevalence under 1% of cattle herds. CPs for M. bovis, ringworm, and S. agalactiae are on a voluntary basis and privately funded. The CP for Mycoplasma was designed in collaboration with national experts and has been implemented since 2013. The CP includes observation of clinical signs, nasal swab sampling from calves, and bulk tank milk and clinical mastitis samples for M. bovis. M. bovis-negative herds gradually achieve lower status levels for M. bovis infection. The general challenge facing voluntary CPs is getting farms to join the programs.

In this article, the Creative Technology Education Project (CTEP) is presented, and phases of problem-solving processes in which the participating primary school student teachers generate alternatives and evaluate ideas are analyzed. The aims of this project were to introduce technology education goals and contents to these students, as well as to offer tools for learning and teaching technology, and to facilitate personal growth. One purpose of the project was to encourage the students to become familiar with technology and problem-solving processes and to develop especially creative skills and abilities (e.g., ideation and the evaluation of ideas). For these purposes, a model was introduced, named the Overall Mapping of a Problem Situation (OMPS). This model helps students in ideation (the generation of alternative solutions) and evaluation of ideas when working on project teams. This model was practiced with concrete technology education projects. Thus, the project focus was on collaborative problem solving, with special emphasis on ideation and the positive evaluation of ideas. The purpose of the study presented in this article was to discover how students perceive the creative process and to what extent they learn creative skills, especially those that involve generating alternative ideas and the self-evaluation of these alternatives. This case study indicates that creative problem-solving approaches may be efficiently used to improve teacher education. (Contains 1 figure and 1 table.)

Approximately 15% of patients with prostate cancer are diagnosed with high-risk disease. However, the current definitions of high-risk prostate cancer include a heterogeneous group of patients with a range of prognoses. Some have the potential to progress to a lethal phenotype that can be fatal, while others can be cured with treatment of the primary tumour alone. The optimal management of this patient subgroup is evolving. A refined classification scheme is needed to enable the early and accurate identification of high-risk disease so that more-effective treatment paradigms can be developed. We discuss several principles established from clinical trials, and highlight other questions that remain unanswered. This Review critically evaluates the existing literature focused on defining the high-risk population, the management of patients with high-risk prostate cancer, and future directions to optimize care.

A group of 116 Finnish fifth- through ninth-graders used a problem-solving technology and crafts curriculum with computers; a control group (n=151) used traditional crafts curriculum and instruction. Results for motor skill development, technical knowledge, and emotional engagement suggest that all students should receive a balanced curriculum of technology and crafts education. (Contains 20 references.) (SK)

Abstract Background Brucella is a facultative intracellular pathogen responsible for zoonotic disease brucellosis. Little is known about the molecular basis of Brucella adherence to host cells. In the present study, the possible role of Bp26 protein as an adhesin was explored. The ability of Brucella protein Bp26 to bind to extracellular matrix (ECM) proteins was determined by enzyme-linked immunosorbent assay (ELISA) and biolayer interferometry (BLI). Results ELISA experiments showed that Bp26 bound in a dose-dependent manner to both immobilized type I collagen and vitronectin. Bp26 bound weakly to soluble fibronectin but did not bind to immobilized fibronectin. No binding to laminin was detected. Biolayer interferometry showed high binding affinity of Bp26 to immobilized type I collagen and no binding to fibronectin or laminin. Mapping of Bp26 antigenic epitopes by biotinylated overlapping peptides spanning the entire sequence of Bp26 using anti Bp26 mouse serum led to the identification of five linear epitopes. Collagen and vitronectin bound to peptides from several regions of Bp26, with many of the binding sites for the ligands overlapping. The strongest binding for anti-Bp26 mouse serum, collagen and vitronectin was to the peptides at the C-terminus of Bp26. Fibronectin did not bind to any of the peptides, although it bound to the whole Bp26 protein. Conclusions Our results highlight the possible role of Bp26 protein in the adhesion process of Brucella to host cells through ECM components. This study revealed that Bp26 binds to both immobilized and soluble type I collagen and vitronectin. It also binds to soluble but not immobilized fibronectin. However, Bp26 does not bind to laminin. These are novel findings that offer insight into understanding the interplay between Brucella and host target cells, which may aid in future identification of a new target for diagnosis and/or vaccine development and prevention of brucellosis.

Abstract PKAN, CoPAN, MePAN, and PDH‐E2 deficiency share key phenotypic features but harbor defects in distinct metabolic processes. Selective damage to the globus pallidus occurs in these genetic neurodegenerative diseases, which arise from defects in CoA biosynthesis (PKAN, CoPAN), protein lipoylation (MePAN), and pyruvate dehydrogenase activity (PDH‐E2 deficiency). Overlap of their clinical features suggests a common molecular etiology, the identification of which is required to understand their pathophysiology and design treatment strategies. We provide evidence that CoA‐dependent activation of mitochondrial acyl carrier protein (mtACP) is a possible process linking these diseases through its effect on PDH activity. CoA is the source for the 4′‐phosphopantetheine moiety required for the posttranslational 4′‐phosphopantetheinylation needed to activate specific proteins. We show that impaired CoA homeostasis leads to decreased 4′‐phosphopantetheinylation of mtACP. This results in a decrease of the active form of mtACP, and in turn a decrease in lipoylation with reduced activity of lipoylated proteins, including PDH. Defects in the steps of a linked CoA‐mtACP‐PDH pathway cause similar phenotypic abnormalities. By chemically and genetically re‐activating PDH, these phenotypes can be rescued, suggesting possible treatment strategies for these diseases.

Abstract Background Mycoplasma bovis (M. bovis) is an emerging bovine pathogen, leading to significant economic losses in the livestock industry worldwide. Infection can result in a variety of clinical signs, such as arthritis, pneumonia, mastitis and keratoconjunctivitis, none of which are M. bovis-specific. Laboratory diagnosis is therefore important. Serological tests to detect M. bovis antibodies is considered an effective indicator of infection in a herd and often used as a herd test. Combined with clinical judgement, it can also be used to implement control strategies and/or to estimate the disease prevalence within a country. However, due to lack of harmonisation of approaches to testing, and serological tests used by different laboratories, comparisons of prevalence data between countries is often difficult. A network of researchers from six European countries designed and participated in an inter-laboratory trial, with the aim of evaluating the sensitivity (Se) and specificity (Sp) of two commercially available ELISA tests (ID Screen® ELISA (IDvet) and BIO K302 ELISA (BIO-X Diagnostics)) for diagnosis of M. bovis infection. Each laboratory received a blinded panel of bovine sera and tested independently, according to manufacturer’s instructions. Western blot analyses (WB) performed by one of the participating laboratories was used as a third diagnostic test in the statistical evaluation of Se and Sp values using latent class analysis. Results The Se of WB, the ID Screen® ELISA and the BIO K302 ELISA were determined to be 91.8, 93.5 and 49.1% respectively, and corresponding Sp of the three tests were 99.6, 98.6 and 89.6%, respectively. Conclusions The present study is, to our knowledge, the first to present an inter-laboratory comparison of the BIO K302 ELISA and the ID Screen® ELISA. Based on our results, the ID Screen® ELISA showed high consistency with WB and performed with higher precision and accuracy than the BIO K302 ELISA.

Abstract Background Immunosenescence, i.e. the aging-associated decline of the capacity of the immune system, is characterized by several distinct changes in the number and functions of the immune cells. In the case of B cells, the total number of CD19+ B cells is lower in the blood of elderly individuals than in the younger ones. CD19+ B cell population contains several subsets, which are commonly characterized by the presence of CD27 and IgD molecules, i.e. naïve B cells (CD27- IgD+), IgM memory (CD27+ IgD+), switched memory (CD27+ IgD-) and late memory (CD27- IgD-). This late memory, double negative, population represents cells which are nondividing, but are still able to produce inflammatory mediators and in this way maybe contributing to the aging-associated inflammation, inflammaging. Here we have focused on the role of these B cell subsets in elderly individuals, nonagenarians, in the regulation of inflammation and inflammation-associated decline of bodily functions. As the biological aging process demonstrates gender-specific characteristics, the analyses were performed separately in males and female. Results A subcohort of The Vitality 90+ study (67 nonagenarians, 22/45 males/females and 40 young controls, 13/27 males/females) was used. Flow cytometric analysis indicated that the total percentage of the CD19+ cells was ca. 50% lower in the nonagenarians than in the controls in both genders. The proportions of these four B cell subsets within the CD19+ populations were very similar in young and old individuals. Thus, it seems that the aging-associated decline of the total CD19+ cells affects similarly all these B cell subsets. To analyze the role of these subsets in the regulation of inflammation, the correlation with IL-6 levels was calculated. A significant correlation was observed only with the percentage of CD27- IgD- cells and only in males. As inflammation is associated with aging-associated functional performance and frailty, the correlations with the Barthel index and frailty score was analyzed. Again, only the CD27- IgD- population demonstrated a strong male-specific correlation. Conclusions These data show that the CD27- IgD- B cell subset demonstrates a strong pro-inflammatory effect in nonagenarians, which significantly associates with the decline of the bodily functions. However, this phenomenon is only observed in males.

Background: General health checks are an established component of preventive health care in many countries. Declining participation rates have raised concerns in health care providers. Understanding the reasons for attendance and non-attendance is necessary to improve the preventive health care system. The aim of this study was to examine health- and study-related factors associated with university entrants’ health check attendance. Methods: Since 2009, an electronic health questionnaire (eHQ) has been conducted yearly to all Finnish university entrants by the Finnish Student Health Service (FSHS) to screen students for a general health check. The questionnaire comprises 26 questions about health, health habits and studying. The study population consisted of the 3346 entrants from the 2011–2012 academic year who were referred to a health check based on their eHQ responses. The eHQ data were linked with health check attendance information. Multivariable logistic regression was used to study the associations between the questionnaire responses and non-attendance of the health check. Results: Male sex (OR 1.6, 95% CI % 1.4–1.9) and low engagement with studies (OR 1.5, 95% CI 1.2–2.0) were the variables most strongly associated with non-attendance. Having low state of mind was negatively associated with health check non-attendance thus enhanced the health-check attendance (OR 0.6, 95% CI 0.5–0.8). Conclusions: The results suggest that providing health checks in student health care may serve as a way of reaching students with health concerns. However, motivating males and smokers to attend general health checks continue to be a challenge also in a university student population. That low engagement with studies associates with health check non-attendance points to need to improve collaboration between universities and student health care.

Small vertebral size is a well-known risk factor for vertebral fractures. To help understanding the factors behind vertebral size, we aimed to investigate whether physical activity and participation in high-impact exercise are associated with the growth rate of the vertebral cross-sectional area (CSA) among young adults. To conduct our study, we utilized the Northern Finland Birth Cohort 1986 as our study population (n = 375). Questionnaire data about physical activity was obtained at 16, 18 and 19 years of age and lumbar magnetic resonance imaging scans at two timepoints, 20 and 30 years of age. We used generalized estimating equation (GEE) models to conduct the analyses. We did not find any statistically significant associations between vertebral CSA, physical activity, and high-impact exercise in our study sample. We conclude that neither physical activity nor high-impact sports seem to influence the change in vertebral CSA among young adults.

Multi-modal neuroimaging projects such as the Human Connectome Project (HCP) and UK Biobank are advancing our understanding of human brain architecture, function, connectivity, and their variability across individuals using high-quality non-invasive data from many subjects. Such efforts depend upon the accuracy of non-invasive brain imaging measures. However, ‘ground truth’ validation of connectivity using invasive tracers is not feasible in humans. Studies using nonhuman primates (NHPs) enable comparisons between invasive and non-invasive measures, including exploration of how “functional connectivity” from fMRI and “tractographic connectivity” from diffusion MRI compare with long-distance connections measured using tract tracing. Our NonHuman Primate Neuroimaging & Neuroanatomy Project (NHP_NNP) is an international effort (6 laboratories in 5 countries) to: (i) acquire and analyze high-quality multi-modal brain imaging data of macaque and marmoset monkeys using protocols and methods adapted from the HCP; (ii) acquire quantitative invasive tract-tracing data for cortical and subcortical projections to cortical areas; and (iii) map the distributions of different brain cell types with immunocytochemical stains to better define brain areal boundaries. We are acquiring high-resolution structural, functional, and diffusion MRI data together with behavioral measures from over 100 individual macaques and marmosets in order to generate non-invasive measures of brain architecture such as myelin and cortical thickness maps, as well as functional and diffusion tractography-based connectomes. We are using classical and next-generation anatomical tracers to generate quantitative connectivity maps based on brain-wide counting of labeled cortical and subcortical neurons, providing ground truth measures of connectivity. Advanced statistical modeling techniques address the consistency of both kinds of data across individuals, allowing comparison of tracer-based and non-invasive MRI-based connectivity measures. We aim to develop improved cortical and subcortical areal atlases by combining histological and imaging methods. Finally, we are collecting genetic and sociality-associated behavioral data in all animals in an effort to understand how genetic variation shapes the connectome and behavior.

Two cell lines were generated by CRISPR/Cas9 mediated knockout of MKK7 (MAP2K7) by removal of exon 1 or exons 4 through 7. These knockouts were confirmed at the transcript and protein levels. These hESCs are pluripotent and maintain tri-lineage differentiation capacity. These cell lines are a useful resource for studying MKK7 function in humans.

Psychiatric and neurological disorders are afflictions of the brain that can affect individuals throughout their lifespan. Many brain magnetic resonance imaging (MRI) studies have been conducted; however, imaging-based biomarkers are not yet well established for diagnostic and therapeutic use. This article describes an outline of the planned study, the Brain/MINDS Beyond human brain MRI project (BMB-HBM, FY2018 ~ FY2023), which aims to establish clinically-relevant imaging biomarkers with multi-site harmonization by collecting data from healthy traveling subjects (TS) at 13 research sites. Collection of data in psychiatric and neurological disorders across the lifespan is also scheduled at 13 sites, whereas designing measurement procedures, developing and analyzing neuroimaging protocols, and databasing are done at three research sites. A high-quality scanning protocol, Harmonization Protocol (HARP), was established for five high-quality 3 T scanners to obtain multimodal brain images including T1 and T2-weighted, resting-state and task functional and diffusion-weighted MRI. Data are preprocessed and analyzed using approaches developed by the Human Connectome Project. Preliminary results in 30 TS demonstrated cortical thickness, myelin, functional connectivity measures are comparable across 5 scanners, suggesting sensitivity to subject-specific connectome. A total of 75 TS and more than two thousand patients with various psychiatric and neurological disorders are scheduled to participate in the project, allowing a mixed model statistical harmonization. The HARP protocols are publicly available online, and all the imaging, demographic and clinical information, harmonizing database will also be made available by 2024. To the best of our knowledge, this is the first project to implement a prospective, multi-level harmonization protocol with multi-site TS data. It explores intractable brain disorders across the lifespan and may help to identify the disease-specific pathophysiology and imaging biomarkers for clinical practice.

Objective To evaluate the association between health and study-related factors measured by an Electronic Health Questionnaire (eHQ), participation in a health examination process and graduation in a university student population.Design Nationwide, retrospective, register-based cohort study with a 6-year follow-up.Setting Student health care in Finland. Finnish Student Health Service (FSHS) provides statutory student health services to university students in Finland. The health examination process of FSHS includes the eHQ provided annually to university entrants and a subsequent health check when necessary based on students’ eHQ response.Participants A national cohort of university entrants from the 2011–2012 academic year (n=14 329, n (female)=8075, n (male)=6254).Outcome measures The primary outcome measure was graduation, measured based on whether a student had completed a bachelor’s, licentiate or master’s degree during the 6-year follow-up.Results Some 72% of the women and 60% of the men had graduated during the follow-up. The predictors in the eHQ associated with non-graduation differed by sex. Among the women’s low enthusiasm about studies (OR 2.6, 95% CI 1.9 to 3.6), low engagement with studies (OR 2.5, 95% CI 1.8 to 3.4) and daily smoking (OR 1.9, 95% CI 1.4 to 2.6) were the strongest predictors to non-graduation. Among the men, low engagement with studies (OR 3.7, 95% CI 2.5 to 5.5) and obesity (body mass index≥35) (OR 4.0, 95% CI 1.9 to 8.8) were the strongest predictors to non-graduation. Not attending the health check when referred was associated with non-graduation in both sexes: the OR for not graduating was 1.6 (95% CI 1.3 to 1.9) in women and 1.3 (95% CI 1.0 to 1.6) in men.Conclusions Engagement and enthusiasm about studying in the first year are important predictors of graduation and therefore a potential intervention target. Health promotion initiatives conducted early in the studies may have a positive effect on students’ academic achievement.

Macaque monkeys are an important animal model where invasive investigations can lead to a better understanding of the cortical organization of primates including humans. However, the tools and methods for noninvasive image acquisition (e.g. MRI RF coils and pulse sequence protocols) and image data preprocessing have lagged behind those developed for humans. To resolve the structural and functional characteristics of the smaller macaque brain, high spatial, temporal, and angular resolutions combined with high signal-to-noise ratio are required to ensure good image quality. To address these challenges, we developed a macaque 24-channel receive coil for 3-T MRI with parallel imaging capabilities. This coil enables adaptation of the Human Connectome Project (HCP) image acquisition protocols to the in-vivo macaque brain. In addition, we adapted HCP preprocessing methods to the macaque brain, including spatial minimal preprocessing of structural, functional MRI (fMRI), and diffusion MRI (dMRI). The coil provides the necessary high signal-to-noise ratio and high efficiency in data acquisition, allowing four- and five-fold accelerations for dMRI and fMRI. Automated FreeSurfer segmentation of cortex, reconstruction of cortical surface, removal of artefacts and nuisance signals in fMRI, and distortion correction of dMRI all performed well, and the overall quality of basic neurobiological measures was comparable with those for the HCP. Analyses of functional connectivity in fMRI revealed high sensitivity as compared with those from publicly shared datasets. Tractography-based connectivity estimates correlated with tracer connectivity similarly to that achieved using ex-vivo dMRI. The resulting HCP-style in vivo macaque MRI data show considerable promise for analyzing cortical architecture and functional and structural connectivity using advanced methods that have previously only been available in studies of the human brain.

Tumor microenvironment (TME) and limited immune surveillance play important roles in lymphoma pathogenesis. Here, we aimed to characterize immunological profiles of diffuse large B-cell lymphoma (DLBCL), and predict the outcome in response to immunochemotherapy. We profiled the expression of 730 immune-related genes in tumor tissues of 81 patients with DLBCL utilizing the Nanostring platform, and used multiplex immunohistochemistry to characterize T-cell phenotypes, including cytotoxic T-cells (CD8, Granzyme B, OX40, Ki67), T-cell immune checkpoint (CD3, CD4, CD8, PD1, TIM3, LAG3), as well as regulatory T-cells and Th1 effector cells (CD3, CD4, FOXP3, TBET) in 188 patients. We observed a high degree of heterogeneity at the transcriptome level. Correlation matrix analysis identified gene expression signatures with highly correlating genes - the main cluster containing genes for cytolytic factors, immune checkpoint molecules, T-cells and macrophages, together entitled as a TME immune cell signature. Immunophenotyping of the distinct cell subsets revealed that a high proportion of immune checkpoint positive T-cells translated to unfavorable survival. Together, our results demonstrate that the immunological profile of DLBCL TME is heterogeneous and clinically meaningful. This highlights the potential impact of T-cell immune checkpoint in regulating survival and resistance to immunochemotherapy.

Summary: How are closely related lineages, including liver, pancreas, and intestines, diversified from a common endodermal origin? Here, we apply principles learned from developmental biology to rapidly reconstitute liver progenitors from human pluripotent stem cells (hPSCs). Mapping the formation of multiple endodermal lineages revealed how alternate endodermal fates (e.g., pancreas and intestines) are restricted during liver commitment. Human liver fate was encoded by combinations of inductive and repressive extracellular signals at different doses. However, these signaling combinations were temporally re-interpreted: cellular competence to respond to retinoid, WNT, TGF-β, and other signals sharply changed within 24 hr. Consequently, temporally dynamic manipulation of extracellular signals was imperative to suppress the production of unwanted cell fates across six consecutive developmental junctures. This efficiently generated 94.1% ± 7.35% TBX3+HNF4A+ human liver bud progenitors and 81.5% ± 3.2% FAH+ hepatocyte-like cells by days 6 and 18 of hPSC differentiation, respectively; the latter improved short-term survival in the Fah−/−Rag2−/−Il2rg−/− mouse model of liver failure.