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Technology is affecting our lives more and more. It has consequences to every human being, and we find ourselves faced with both positive and negative aspects of technology. Certainly, this has an effect on our attitudes towards technology. In this study, we tried to find out if there have been any changes in attitudes towards technology among Finnish school children during the last 30 years. The attitudes measured in 1993 were compared with the results from 2012 and 2022. The number of test participants was 267 in the first measurement, 317 in the second and 284 in the last measurement. The age of the student respondents was 11-13 years. The measurements were done with exactly the same Likert scale attitude questionnaire in all three measurements. Some positive changes were found in attitudes towards technology in girls test group. Unfortunately, boys' development between years 2012-2022 is alarming and should be of great concern The development in attitudes can be explained by the changes in technology education curriculum. From a broader point of view, the development in attitudes can be due to the changes in society as a whole.

The aim of this study was to find out if there have been any changes in technical abilities among Finnish school children during the last 30 years. Technical abilities were first measured in the affective, psychomotor, and cognitive areas in the year 1993 and these results were later compared with the results from 2012 and 2022. The number of test participants was 267 in the year 1993, 317 in 2012 and 282 in 2022. The age of the student respondents was 11-13 years. The measurements were done with exactly the same research instruments in all three years. Some positive changes were found in affective area among girls' test groups. Unfortunately, in all research groups the development was negative in the psychomotor and cognitive area. The reason for the decline could be in the reduction of craft and technology education lessons available, especially for boys. From a broader point of view, the changes can be due to the changes in society as a whole. It seems that the curriculum changes during last 30 years have not worked as they have been planned. Especially, boys underachievement is explained by the fact that, even if students work with systematic planning models and use their creativity, aesthetical design usually overshadows technological issues. It is assumed that progressive teaching and assessment favour girls and traditional methods are more congenial to boys.

The tumor microenvironments (TME) of diffuse large B-cell lymphoma (DLBCL) subgroups have remained poorly characterized. Here, we dissected the composition and spatial organization of the TME in germinal center B-cell (GCB), activated B-cell (ABC), and testicular DLBCLs (T-DLBCL) using gene expression profiling and multiplex immunohistochemistry. We found that high proportions of M2-like tumor-associated macrophages (TAMs) and cytotoxic tumor-infiltrating T cells (TILs) were characteristic of ABC DLBCL TME. Furthermore, high CD8+ TIL content translated to favorable outcomes. In contrast, GCB DLBCL TME was enriched in CD4+ TILs, regulatory TILs, and a higher M1-like/M2-like TAM ratio, and high proportions of TAMs and Granzyme B+ cells associated with worse survival. TILs and TAMs interacted more frequently with M2-like TAMs and cytotoxic TILs in the ABC DLBCLs contrary to GCB subtype, where the interactions were more abundant with other TILs and CD4+ TILs. In T-DLBCL, TME resembled that of ABC DLBCL with a higher proportion of M2-like TAMs and cytotoxic cells, except that checkpoint-positive TILs were less prominent compared to DLBCL NOS. Cytotoxic TILs also interacted more with TILs and TAMs. A high amount of CD163+ TAM interactions with distinct TILs translated to unfavorable survival both in GCB DLBCL and T-DLBCL, whereas a high number of interactions between TILs and TAMs, CD4+ TILs and TAMs, and CD4+ TILs and other TILs associated with favorable outcomes only in T-DLBCL. Together, our data demonstrate biologically and clinically relevant differences in the composition of and cellular interactions in the TME between various DLBCL entities.

Caregiver support is necessary for many long-term ill or disabled people to enable them to live at home. However, the impact of this care relationship on the caregiver is still partly unknown. This article focuses on the process of achieving personal growth in spousal caregiving. The aim of our study was to conduct an integrative literature review to describe the aspects associated with achieving personal growth as well as to analyze the relationship between the aspects involved. The thematic analysis method was used with inductive content classification to modify the themes. The analysis highlighted three main aspect categories connected with achieving personal growth: the means, coping styles, and personal or caregiving resources. In addition, the path from adversities and challenges towards personal growth and positive experiences in spousal caregiving was revealed by analyzing the relationship between the identified aspects. We found that the means, based on social support and self-care, help caregivers to adopt positive coping strategies, reframing, and resilience, which are associated with achieving personal growth. Also, personal or caregiving resources, such as meaningful caring experiences, religiosity, and spirituality, hope, positive personality characteristics, family functioning, and disease severity of the care recipient, were associated with achieving growth. Finally, our findings suggest that it is important to further study the path towards personal growth in spousal caregiving and to find the best possible ways to support caregivers in difficult moments and periods of caregiving.

BackgroundA digital health check can be used to screen health behavior risks in the population, help health care professionals with standardized risk estimation for their patients, and motivate a patient to change unhealthy behaviors. Long-term unemployed individuals comprise a particular subgroup with an increased risk of lifestyle-related diseases. ObjectiveThis study aims to investigate the clinical utility of a general digital health examination, the STAR Duodecim Health Check and Coaching Program (STAR), which was developed in Finland, in the targeted screening of long-term unemployed individuals. For this purpose, we compared health challenges identified by a digital health check with those identified by a nurse during a face-to-face health check for unemployed individuals. MethodsIn this comparison study, 49 unemployed participants attending a health check were recruited from two Finnish primary health care centers. The participants used STAR and attended a nurse’s health check. Data were collected by surveys with multiple-choice and open-ended questions from the participants, nurses, and a study assistant who observed the session. The nurses were asked to name the three most significant health challenges for each participant. These health challenges were categorized into health challenges corresponding to STAR and these were compared with each other. Percentages of agreement between STAR and nurses were calculated. Sensitivity and specificity, as well as Cohen κ with P values and CIs, were computed for agreement. ResultsSTAR identified a total of 365 health challenges, an average of 7.4 (SD 2.5) health challenges per participant (n=49). The nurses named a total of 160 health challenges (n=47). In 53% (95% CI 38.1-67.9; n=25) of cases, STAR identified all categorized health challenges named by nurses. In 64% (95% CI 48.5-77.3; n=30) of cases, STAR identified at least 2/3 of the health challenges identified by nurses. Cohen κ was 0.877 (P

This paper aims to evaluate how well the increasingly popular, market-based real estate energy efficiency improvement projects support the EU’s high-level smart energy transition targets. The implications of these EU-level targets for buildings are described in the smart readiness indicator (SRI) framework. As the SRI becomes mandatory, it is important for the industry to understand whether current market practices align with the SRI framework. This study is based on a qualitative analysis of 49 energy efficiency improvement project proposal reports for properties located in Finland. We use the SRI framework to evaluate the potential impact of the various energy efficiency improvements proposed in the reports on the smart energy transition targets. Three expert interviews were also conducted to gain the interviewees’ interpretations of the industry. While energy efficiency improvement projects are obviously aimed at improving energy efficiency, the results indicate that they are beneficial for some parts of the SRI, mainly within the SRI’s main categories of heating, controlled ventilation, and monitoring and control. Some proposed actions also contribute to increased smart readiness in the categories of cooling and lighting, but the remaining four main categories are generally not being taken into consideration.

Education is recognized as crucial in addressing unsustainable practices, such as food waste. One of the aims of interdisciplinary food education in basic education is to promote sustainable food waste behavior, which can be promoted by transformative learning. This study examined how food waste is addressed in nine Finnish basic education textbooks. The content related to food waste and the pedagogical style of the texts were analyzed from home economics, biology, and geography textbooks designed for secondary level education (grades 7–9, age 13–16). The results were analysed to assess their potential to promote transformative learning. All of the textbooks approached the topic of food waste from the perspective of their own subject, and none presented it as an interdisciplinary phenomenon. Home economics textbooks focused on students' perspectives, emphasizing food waste reduction and waste sorting. Geography textbooks frequently explored the topic in the context of the food supply chain or at a global level, while biology textbooks primarily addressed the sorting of food waste. The textbooks primarily used a neutral text style focusing on information transmission. In some contexts, a persuasive style was employed to encourage critical thinking and action. The participative style, which encourages active student engagement, was utilized the least in all textbooks, and primarily for exercises. By integrating learning-supportive text styles (such as participative and persuasive), including student tasks related to food waste, and fostering an interdisciplinary understanding of food waste, textbooks have the potential to transform student learning and engagement in sustainable food practices.

Introduction: The possible beneficial effects of physical activity during doxorubicin treatment of breast cancer need further investigation as many of the existing studies have been done on non-tumor-bearing models. Therefore, in this study, we aim to assess whether short-term voluntary wheel-running exercise during doxorubicin treatment of breast cancer-bearing mice could induce beneficial cardiac effects and enhance chemotherapy efficacy.Methods: Murine breast cancer I3TC cells were inoculated subcutaneously to the flank of female FVB mice (n = 16) that were divided into exercised and non-exercised groups. Two weeks later, doxorubicin treatment was started via intraperitoneal administration (5 mg/kg weekly for 3 weeks). Organs were harvested a day after the last dose.Results: The tumor volume over time was significantly different between the groups, with the exercising group having lower tumor volumes. The exercised group had increased body weight gain, tumor apoptosis, capillaries per cardiomyocytes, and cardiac lactate dehydrogenase activity compared to the unexercised group, but tumor blood vessel density and maturation and tumor and cardiac HIF1-α and VEGF-A levels did not differ from those of the non-exercised group.Discussion: We conclude that even short-term light exercise such as voluntary wheel running exercise can decrease the subcutaneous mammary tumor growth, possibly via increased tumor apoptosis. The increase in cardiac capillaries per cardiomyocytes may also have positive effects on cancer treatment outcomes.

Introduction: Use of the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) during chemotherapy is associated with decreased hospitalization rates, improved quality of life, and longer survival. Limited data exist on the benefit of this symptom assessment tool for monitoring immune-related adverse events (irAEs). Methods: We incorporated irAE-related items from the National Cancer Institute’s (NCI) PRO-CTCAE in a trial evaluating ipilimumab in combination with androgen deprivation therapy in 16 patients with hormone-sensitive prostate cancer. For comparison, NCI’s CTCAE version 4.0 was used by clinicians. Results: IrAE-related PRO-CTCAE surveys and matched CTCAEs (184 pairs) reporting abdominal pain, diarrhea, fatigue, anorexia, nausea, vomiting, rash, and pruritus were collected at each treatment administration and during follow-up. Fatigue, diarrhea, rash, and pruritus were the symptoms most frequently reported by both patients and clinicians. Agreement was lowest for pruritus (κ = 0.10) and highest for rash (κ = 0.64). IrAEs were more commonly reported and of higher grade with PRO-CTCAE scores compared with CTCAE grades. Conclusion: PRO-CTCAEs focused on irAEs capture the patient’s immunotherapy experience while complementing the clinician’s toxicity assessment measures. Further study is needed to assess PRO-CTCAE’s utility in identifying and managing irAEs.

Abstract Introduction Mental disorders are one of the most common and disabling health conditions worldwide. There is however no consensus on the best practice of system level mental health services (MHS) provision, in order to prevent e.g. mood disorder disability pensions (DPs). We analyzed the MHS provision between Finland’s three largest hospital districts Helsinki and Uusimaa (HUS), Southwest Finland and Pirkanmaa, with known differences in mood disorder DP risk but presumably equal rates of mood disorder prevalence. Methods We used public MHS data analyzed with the standardized DEscription and Evaluation of Services and DirectoriEs for Long Term Care (DESDE-LTC) mapping tool, focusing on all MHS, outpatient care provision, local services without and with gatekeeping, and centralized services. We also collected demographic data based on the European Socio-Demographic Schedule (ESDS). As a novel approach, the Gini-Simpson Diversity Index (GSDI) was calculated for the districts. Results Evident differences were observed regarding the districts’ MHS factors. As the hospital district with lower DP risk, HUS was characterized by the highest level of regional socioeconomic prosperity as well as high service richness and diversity. With a nationally average DP risk, Southwest Finland had the highest number of MHS personnel in full-time equivalents (FTE) per 100 000 inhabitants. Pirkanmaa, with a higher DP risk, had overall the lowest service richness and the lowest FTE of the three districts in all MHS, outpatient care and local services with gatekeeping. Conclusions Our findings indicate that greater richness and diversity of MHS, especially in outpatient and community-based settings, may serve as indicators of a balanced, high-quality service system that is more effective in preventing mood disorder DP and meeting the different needs of the population. In addition, the need for sufficient resourcing in all MHS and outpatient services is indicated. We suggest using diversity indices to complement the measuring and reporting of regional service variation.

It is vital to consider acoustic scattering when using geometrical acoustic simulation techniques, such as ray tracing. However, there are few methods for modelling scattering, and most rely on strong assumptions of uniformity on the distribution of scattered energy. In this paper, a model for directional scattering in ray tracers is presented. The model is based on an idealized model of a 1D scatterer, which is then used to extend the most commonly used scattering algorithm in ray tracers today. The developed algorithm is implemented in a ray tracer and tested to evaluate its performance compared to existing methods. It is found that the directional scattering algorithm can be used to replicate measured effects on room acoustic parameters caused by changes in the orientation of 1D scatterers.

The research is based on a comparative study of craft and technology education curriculums and students' attitudes towards craft and technology in Finland, Slovenia, Estonia and Iceland. The study was undertaken by the Helsinki University, University of Ljubljana, University of Tallinn and University of Iceland. A literature review was completed, in order to examine and compare the curriculums of technology education in Finland, Slovenia, Estonia and Iceland. In addition, a quantitative survey was subsequently distributed to 864 school students in Finland, Slovenia, Estonia and Iceland. It consisted of 14 questions, which aimed to ascertain students? attitudes towards craft and technology. The survey showed substantial differences in students? attitudes towards technology education in the four countries: these differences may be explained by differences in the national curriculums, the different pedagogical traditions and cultural differences in the field of technology. In addition, the study tried to examine the structure of students? attitudes towards technology. The factors can be interpreted as matching with the affective, cognitive and behavioral components. However, no far-reaching generalizations were allowed regarding the structure or properties of the attitudes towards technology as the questionnaire consisted of only 14 items.

Abstract Background 3D culture is increasingly used in cancer research, as it allows the growth of cells in an environment that mimics in vivo conditions. Metastases are the primary cause of morbidity and mortality in cancer patients, and solid tumour metastases are mostly located in lymph nodes. Currently, there are no techniques that model the pre-metastatic lymph node microenvironment in vitro. In this study, we prepared a novel extracellular matrix, Lymphogel, which is derived from lymph nodes, mimicking the tumour microenvironment (TME) of metastatic carcinoma cells. We tested the suitability of the new matrix in various functional experiments and compared the results with those obtained using existing matrices. Methods We used both commercial and patient-derived primary and metastatic oral tongue squamous cell carcinoma (OTSCC) cell lines. We characterized the functional differences of these cells using three different matrices (human uterine leiomyoma-derived Myogel, human pre-metastatic neck lymph node-derived Lymphogel (h-LG), porcine normal neck lymph node-derived Lymphogel (p-LG) in proliferation, adhesion, migration and invasion assays. We also performed proteomic analyses to compare the different matrices in relation to their functional properties. Results OTSCC cells exhibited different adhesion and invasion patterns depending on the matrix. Metastatic cell lines showed improved ability to adhere to h-LG, but the effects of the matrices on cell invasion fluctuated non-significantly between the cell lines. Proteomic analyses showed that the protein composition between matrices was highly variable; Myogel contained 618, p-LG 1823 and h-LG 1520 different proteins. The comparison of all three matrices revealed only 120 common proteins. Analysis of cellular pathways and processes associated with proteomes of each matrix revealed similarities of Myogel with h-LG but less with p-LG. Similarly, p-LG contained the least adhesion-related proteins compared with Myogel and h-LG. The highest number of unique adhesion-related proteins was present in h-LG. Conclusions We demonstrated that human pre-metastatic neck lymph node-derived matrix is suitable for studying metastatic OTSCC cells. As a whole-protein extract, h-LG provides new opportunities for in vitro carcinoma cell culture experiments.

Purpose Various complications are associated with percutaneous endoscopic gastrostomy (PEG) procedures in children. The push technique is being increasingly used, but its complications are insufficiently characterized. We aimed to assess all complications related to PEG procedures and compare the safety of the pull and push techniques.Methods Retrospective review of consecutive pediatric patients who underwent PEG between 2002 and 2020.Results In total, 216 children underwent 217 PEG procedures. The push technique was used in 138 (64%) cases, and the pull technique in 79 (36%) cases. The median follow-up time was 6.1 (0.1–18.3) years. The complication rate was high (57%) and patients experienced complications years after the procedure. Overall, 51% and 67% of patients experienced complications in the push and pull groups, respectively. The rates of minor and major complications were higher in the pull group than in the push group (63% vs 48%, p=0.028; and 11% vs 6%, p=0.140, respectively). Reoperation was also more common in the pull group (17% vs 7%, p=0.020).Conclusions The overall complication rate of PEG procedures is high. Fortunately, most complications are mild and do not require reoperations. The increasing push technique appears to be safer than the traditional pull technique. Significant long-term morbidity is related to gastrostomies in children.

Selection of the target site is an inherent question for any project aiming for directed transgene integration. Genomic safe harbour (GSH) loci have been proposed as safe sites in the human genome for transgene integration. Although several sites have been characterised for transgene integration in the literature, most of these do not meet criteria set out for a GSH and the limited set that do have not been characterised extensively. Here, we conducted a computational analysis using publicly available data to identify 25 unique putative GSH loci that reside in active chromosomal compartments. We validated stable transgene expression and minimal disruption of the native transcriptome in three GSH sites in vitro using human embryonic stem cells (hESCs) and their differentiated progeny. Furthermore, for easy targeted transgene expression, we have engineered constitutive landing pad expression constructs into the three validated GSH in hESCs.

Abstract Background Cryptosporidiosis has increased in recent years in Finland. We aimed to identify risk factors for human cryptosporidiosis and to determine the significance of Cryptosporidium parvum as a causative agent. Based on notifications to the Finnish Infectious Disease Register (FIDR), we conducted a case-control study and genotyped Cryptosporidium species from patient samples from July to December 2019. We also retrieved the occupational cryptosporidiosis cases from 2011 to 2019 from the Finnish Register of Occupational Diseases (FROD). Results Of 272 patient samples analyzed, 76% were C. parvum and 3% C. hominis. In the multivariable logistic regression analysis of 82 C. parvum cases and 218 controls, cryptosporidiosis was associated with cattle contact (OR 81, 95% confidence interval (CI) 26–251), having a family member with gastroenteritis (OR 34, 95% CI 6.2–186), and spending time at one’s own vacation home (OR 15, 95% CI 4.2–54). Of the cases, 65% had regular cattle contact. The most common gp60 subtypes identified were IIaA15G2R1 and IIaA13G2R1. In FROD, 68 recognized occupational cryptosporidiosis cases were registered in 2011–2019. Conclusions C. parvum is the most common Cryptosporidium species found in humans in Finland and poses a moderate to high risk of occupational infection for people working with cattle. The number of occupational notifications of cryptosporidiosis increased between 2011 and 2019. Cryptosporidiosis should be recognized as an important occupational disease among persons working with livestock in Finland, criteria to identify occupational cryptosporidiosis need to be created, and occupational safety in cattle-related work should be improved.

Abstract Background Fasciolosis is a parasitic infection caused by the liver fluke Fasciola hepatica that can have a major economic impact on livestock industry. The prevalence of the disease has recently been increasing in many North European countries. The objective of this study was to determine the prevalence of antibody against F. hepatica in Finnish cattle herds and sheep flocks during 2019 by using a commercial enzyme-linked immunosorbent assay (ELISA). Randomly selected bulk tank milk samples were obtained from 660 dairy herds. Blood samples were collected at slaughterhouses from 1944 suckler cows from 309 herds and from 1120 sheep from 95 flocks. Results Antibodies against F. hepatica were found in 0.45% (95% confidence interval (CI): 0.15–1.33) of the dairy herds and 0.97% (95% CI: 0.33–2.82) of the suckler cow herds. The seropositive herds were located in eastern and central Finland. None of the sampled sheep flocks tested had antibodies against F. hepatica (95% CI: 0–3.89). The results of the assays were compared with meat inspection data received from the slaughterhouses. All positive herds also had liver condemnations due to F. hepatica based on the meat inspection reports. Conclusions Compared to other North European countries, the prevalence of fasciolosis in Finland can be considered low, and according to meat inspection reports, there are no indications of the prevalence increasing in Finland.

Abstract Background Revascularization of an occluded artery by either thrombolysis or mechanical thrombectomy is a time-critical intervention in ischaemic stroke. Each link in the stroke chain of survival should minimize the delay to definitive treatment in every possible way. In this study, we investigated the effect of routine dispatch of a first response unit (FRU) on prehospital on-scene time (OST) on stroke missions. Methods Medical dispatch of FRU together with an emergency medical service (EMS) ambulance was a routine strategy in the Tampere University Hospital area before 3 October 2018, after which the FRU has only been dispatched to medical emergencies on the decision of an EMS field commander. This study presents a retrospective before–after analysis of 2,228 paramedic-suspected strokes transported by EMSs to Tampere University Hospital. We collected data from EMS medical records from April 2016 to March 2021, and used statistical tests and binary logistic regression to detect the associations between the variables and the shorter and longer half of OSTs. Results The median OST of stroke missions was 19 min, IQR [14–25] min. The OST decreased when the routine use of the FRU was discontinued (19 [14–26] min vs. 18 [13–24] min, p

Background Treatment options for pancreatic ductal adenocarcinoma (PDAC) are limited and checkpoint blockade inhibitors have been disappointing in this disease. Pegilodecakin has demonstrated single agent anti-tumor activity in immune-sensitive tumors. Phase 1 and preclinical data indicate synergy of pegilodecakin with 5-FU and platins. We assessed the safety and activity of pegilodecakin+FOLFOX in patients with PDAC. Methods IVY (NCT02009449) was an open-label phase 1b trial in the United States. Here we report on all enrolled patients from cohort C. Heavily pretreated patients were treated with pegilodecakin (self-administered subcutaneously daily at 2.5, 5, or 10 μg/kg) + 5-flurouracil/leucovorin/oxaliplatin (FOLFOX), dosed per manufacturers prescribing information, until tumor progression. Eligible patients had measurable disease per immune-related response criteria (irRC), were ≥ 18 years of age, and had ECOG performance status of 0 or 1. Patients were evaluated for primary(safety) and secondary (tumor response per irRC) endpoints. Results From 5 August 2014-12 July 2016, 39 patients enrolled in cohort C. All patients were evaluable for safety. In this advanced population, regimen had manageable toxicities with no immune-related adverse events (irAEs) greater than grade 1. The most common grade 3/4/5 TEAEs were thrombocytopenia (21[53.8%] of 39) and anemia (17[43.6%] of 39). In evaluable PDAC patients, the best overall response of pegilodecakin+FOLFOX was 3(14%) with CRs in 2(9%) patients. Conclusions Pegilodecakin+FOLFOX had an acceptable tolerability profile in PDAC, with no substantial irAEs seen, and promising efficacy with the combination yielding a 2-year OS of 24% (95% CI 10-42). These data led to the phase 3 study with pegilodecakin+FOLFOX as second-line therapy of PDAC (SEQUOIA).

BackgroundLoyalty card data automatically collected by retailers provide an excellent source for evaluating health-related purchase behavior of customers. The data comprise information on every grocery purchase, including expenditures on product groups and the time of purchase for each customer. Such data where customers have an expenditure value for every product group for each time can be formulated as 3D tensorial data. ObjectiveThis study aimed to use the modern tensorial principal component analysis (PCA) method to uncover the characteristics of health-related purchase patterns from loyalty card data. Another aim was to identify card holders with distinct purchase patterns. We also considered the interpretation, advantages, and challenges of tensorial PCA compared with standard PCA. MethodsLoyalty card program members from the largest retailer in Finland were invited to participate in this study. Our LoCard data consist of the purchases of 7251 card holders who consented to the use of their data from the year 2016. The purchases were reclassified into 55 product groups and aggregated across 52 weeks. The data were then analyzed using tensorial PCA, allowing us to effectively reduce the time and product group-wise dimensions simultaneously. The augmentation method was used for selecting the suitable number of principal components for the analysis. ResultsUsing tensorial PCA, we were able to systematically search for typical food purchasing patterns across time and product groups as well as detect different purchasing behaviors across groups of card holders. For example, we identified customers who purchased large amounts of meat products and separated them further into groups based on time profiles, that is, customers whose purchases of meat remained stable, increased, or decreased throughout the year or varied between seasons of the year. ConclusionsUsing tensorial PCA, we can effectively examine customers’ purchasing behavior in more detail than with traditional methods because it can handle time and product group dimensions simultaneously. When interpreting the results, both time and product dimensions must be considered. In further analyses, these time and product groups can be directly associated with additional consumer characteristics such as socioeconomic and demographic predictors of dietary patterns. In addition, they can be linked to external factors that impact grocery purchases such as inflation and unexpected pandemics. This enables us to identify what types of people have specific purchasing patterns, which can help in the development of ways in which consumers can be steered toward making healthier food choices.

Human endogenous retroviruses (HERVs) are remnants of ancient retroviral infections in the human genome. RNA expression of individual HERVs has frequently been observed in various pathologic conditions, but some activity can also be seen in healthy individuals, e.g. in the blood. To quantitate the basal expression levels of HERVs in the brain, we now used high-throughput sequencing-based metagenomic analysis to characterize the expression profiles of the HERV-K (HML-2) family proviruses in different brain regions of healthy brain tissue. To this end, RNA-seq data from the Genotype-Tissue Expression (GTEx) project was used. The GTEx project is a public resource to study tissue-specific gene expression and regulation, consisting of a large selection of sequenced samples from different tissues. The GTEx data used in this study consisted of 378 samples taken from 13 brain regions from 55 individuals. The data demonstrated that out of 99 intact proviruses in the family 58 were expressed, but the expression profiles were highly divergent and there were no significant differences in the expression profiles between the various anatomic regions of the brain. It is known that the brain contains a variety of infiltrating immune cells, which are probably of great importance both in the normal defense mechanisms as well as in the various pathogenic processes. Digital cytometry (CIBERSORTx) was used to quantify the proportions of the infiltrating immune cells in the same brain samples. Six most abundant (>5 % of the total population) cell types were observed to be CD4 memory resting T cells, M0 macrophages, plasma cells, CD8 T cells, CD4 memory activated T cells, and monocytes. Analysis of the correlations between the individual HERVs and infiltrating cell types indicated that a cluster of 6 HERVs had a notable correlation signature between T cell type infiltrating cell proportions and HERV RNA expression intensity. The correlations between inflammatory type infiltrating cells were negative or weak. Taken together, these data indicate that the expression of HERVs is associated with a T cell type immunity.

Ray tracing is a frequently used method for acoustic simulations, valued for its calculation speed and ease of use. Although it is fast, there are no fully ray tracing-based real-time simulation methods or engines. Under real-time restrictions, ray tracing simulations lose precision and the variance inherent in the random simulation method has too much impact on the outcome. In this paper, an algorithm called iterative ray tracing is presented that reduces the negative effects of real-time restrictions by iteratively improving the initial calculation and increasing the precision over time. In addition, new estimates of the expected value and variance of ray tracing simulations are presented and used to show the iteration steps in the new algorithm reduce variance, while maintaining the expected value. Simulations using iterative ray tracing are compared to measurements and simulations using the classical ray tracing method, and it is shown that iterative ray tracing can be used to improve precision over time. Although more testing is needed, iterative ray tracing can be used to extend most ray tracing algorithms, in order to decrease the adverse effects of real-time restrictions.

Abstract Mitochondrial fatty acid synthesis (mtFAS) is essential for respiratory function. MtFAS generates the octanoic acid precursor for lipoic acid synthesis, but the role of longer fatty acid products has remained unclear. The structurally well-characterized component of mtFAS, human 2E-enoyl-ACP reductase (MECR) rescues respiratory growth and lipoylation defects of a Saccharomyces cerevisiae Δetr1 strain lacking native mtFAS enoyl reductase. To address the role of longer products of mtFAS, we employed in silico molecular simulations to design a MECR variant with a shortened substrate binding cavity. Our in vitro and in vivo analyses indicate that the MECR G165Q variant allows synthesis of octanoyl groups but not long chain fatty acids, confirming the validity of our computational approach to engineer substrate length specificity. Furthermore, our data imply that restoring lipoylation in mtFAS deficient yeast strains is not sufficient to support respiration and that long chain acyl-ACPs generated by mtFAS are required for mitochondrial function.

Abstract Immune cells infiltrating the central nervous system (CNS) are involved in the defense against invading microbes as well as in the pathogenesis of neuroinflammatory diseases. In these conditions, the presence of several types of immune and inflammatory cells have been demonstrated. However, some studies have also reported low amounts of immune cells that have been detected in the CNS of healthy individuals, but the cell types present have not been systematically analyzed. To do this, we now used brain samples from The Genotype- Tissue Expression (GTEx) project to analyze the relative abundance of 22 infiltrating leukocyte types using a digital cytometry tool (CIBERSORTx). To characterize cell proportions in different parts of the CNS, samples from 13 different anatomic brain regions were used. The data obtained demonstrated that several leukocyte types were present in the CNS. Six leukocyte types (CD4 memory resting T cells, M0 macrophages, plasma cells, CD8 T cells, CD4 memory activated T cells, and monocytes) were present with a proportion higher than 0.05, i.e. 5%. These six cell types were present in most brain regions with only insignificant variation. A consistent association with age was seen with monocytes, CD8 T cells, and follicular helper T cells. Taken together, these data show that several infiltrating immune cell types are present in the non-diseased CNS tissue and that the proportions of infiltrating cells are affected by age in a manner that is consistent with literature on immunosenecence and inflammaging.

The main idea of this research was to find out if there is a relationship between students' undertakings within Craft and Technology education and their ability to understand technological concepts. Study participants' technological knowledge and reasoning was measured with a questionnaire regarding mechanical systems connected with simple physical phenomena. The research was undertaken in Finnish and Estonian schools during the years 2014-2016. The research model was quantitative survey and the data was collected using a questionnaire distributed to 303 students in Estonia and 317 in Finland. The age of study participants was eleven and thirteen. The results highlighted general lack of technological knowledge and reasoning, which could be due to old-fashioned pedagogical methods in teaching technology. The total average of right answers to 28 questions was in Estonia 15.4 and in Finland 15.0. Main difference was found between Finnish and Estonian 11-year-old students while the Estonian figure was 14.9 and 14.1 in Finland. For 13-year-old students, the difference was almost diminished while the average in Estonia was 15.8 and 15.7 in Finland. This is explained by curriculum differences. In Finnish technology education both Technical craft and Textile craft are compulsory for both boys and girls. In Estonia, students can choose the subject based on their wishes and interests. This allows students to study in greater detail the subject that they are really interested in. In addition, boys' and girls' different interests and earlier experiences obviously have an impact on motivation for learning about technology.

Food packaging has an essential function in the contemporary food supply chain, but it is also a key source of municipal solid waste. The ability to package foods has changed eating habits as takeaway coffees, bottled water, and fast food have become more commonplace. Although the task of recycling packaging materials falls on the consumer who is guided to sort the waste and ensure it is taken to a recycling bin, the consumer perspectives of the mutually constitutive market device–consumer relationship are not yet well-known. This paper studies how food shoppers are constructing their relationship with packaging in their everyday lives, and especially how their moral considerations construct the relationship with sustainability and materiality of packaging. Based on the analysis of consumer interviews, the study argues that consumers' perspective on packaging use is renegotiated during their continuous relationship with packaging. Food packaging acts as a political market device that evokes morally charged consumer perspectives throughout different stages of consumption processes beyond the supermarket. In the first stage, the consumer is mainly focused on finding the products that have already become a part of their daily routine and the materiality of packaging oftentimes remains unseen. Tensions arise as packaging is both a source of frustration, and a necessary element of managing food consumption. After eating the food product, the packaging turns into waste and the consumer “becomes aware” of the packaging materials and several negative interpretations arise. Finally, packaging waste becomes morally charged: it invites consumers to partake in recycling work and evokes environmental anxieties. The results indicate that consumers often have an uneasy, cyclical relationship with packaging use.

In this study, we conducted a comprehensive geophysical survey near Kuusamo (Finland) to assess the potential of electrical resistivity methods in delineating mineral deposits at depths greater than 1 km. Preliminary investigations, including magnetic and gravity methods as well as drilling, revealed significant anomalous structures in the survey area. We employed multiple electrical and electromagnetic methods at the site, comprising controlled-source electromagnetic (CSEM), magnetotelluric (MT), electrical resistivity tomography (ERT), and induced polarization (IP). To obtain the geophysical data in very large-scale area, we used a total of 25 transmitter dipoles with 1km long using three distinct transmitter systems and recorded data at 119 receiver stations. In this paper, we present the acquisition and preliminary results from ERT-IP. Analysis of the resistivity and IP responses revealed notable IP signals at depths exceeding 1.5 km. Meanwhile, the resistivity data indicated generally very high values, around 10,000 ohm-m, with complex variations observed near the surface.

Currently, the consumption of liquid milk in Western European countries and the US is declining. At the same time, the consumption of other dairy products, including cheese and sour-milk products, is increasing. Dairy production, along with meat production, is one of the main food sources of greenhouse gases, which cause climate change. Thus, the transition toward more sustainable diets requires a reduction in the consumption of both meat and dairy products. Consumers who do not use milk (e.g., vegans) have received more scholarly attention compared to those who are reducing milk consumption. Our study focuses on Finnish consumers who have reduced the use of cow's milk but have not abandoned dairy entirely. Through qualitative data, we analyze how consumers on the one hand narrate their detachment from using milk and on the other hand justify their ongoing use of dairy products. The results show that consumers began their dietary change by first reducing meat eating, followed by milk. For the consumers, cheese eating was a source of enjoyment that was difficult to resist and to replace with plant-based alternatives, even though they were aware of the animal suffering caused by milk production. Consumers recognized the interdependence between meat and milk production and consumption, yet, at the level of everyday practices, giving up milk proved to be more challenging than giving up meat. We argue that the declining use of fluid milk contributes to the de-dairyfication of eating habits, but obstacles remain in reducing the consumption of other dairy products.

BackgroundIL-10 has anti-inflammatory and CD8+ T-cell stimulating activities. Pegilodecakin (pegylated IL-10) is a first-in-class, long-acting IL-10 receptor agonist that induces oligoclonal T-cell expansion and has single-agent activity in advanced solid tumours. We assessed the safety and activity of pegilodecakin with anti-PD-1 monoclonal antibody inhibitors in patients with advanced solid tumours.MethodsWe did a multicentre, multicohort, open-label, phase 1b trial (IVY) at 12 cancer research centres in the USA. Patients were assigned sequentially into cohorts. Here, we report on all enrolled patients from two cohorts treated with pegilodecakin combined with anti-PD-1 inhibitors. Eligible patients were aged at least 18 years with histologically or cytologically confirmed advanced malignant solid tumours refractory to previous therapies, and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients with uncontrolled infectious diseases were excluded. Pegilodecakin was provided in single-use 3 mL vials and was self-administered subcutaneously by injection at home at 10 μg/kg or 20 μg/kg once per day in combination with pembrolizumab (2 mg/kg every 3 weeks or 200 mg every 3 weeks) or nivolumab (3 mg/kg every 2 weeks or 240 mg every 2 weeks or 480 mg every 4 weeks at the approved dosing), both of which were given intravenously at the study site. Patients received pembrolizumab or nivolumab with pegilodecakin until disease progression, toxicity necessitating treatment discontinuation, patient withdrawal of consent, or study end. The primary endpoints were safety and tolerability, assessed in all patients enrolled in the study who received any amount of study medication including at least one dose of pegilodecakin, and pharmacokinetics (previously published). Secondary endpoints included objective response by immune-related response criteria in all patients who were treated and had evaluable measurements. The study is active but no longer recruiting, and is registered with ClinicalTrials.gov, NCT02009449.FindingsBetween Feb 13, 2015, and Sept 12, 2017, 111 patients were enrolled in the two cohorts. 53 received pegilodecakin plus pembrolizumab, and 58 received pegilodecakin plus nivolumab. 34 (31%) of 111 patients had non-small-cell lung cancer, 37 (33%) had melanoma, and 38 (34%) had renal cell carcinoma; one (

Transformation to squamous cell carcinoma (SCC) after initial treatment of a primary prostate adenocarcinoma is rare and typically results in rapid treatment-refractory disease progression and death. Here, we present a case of a 70-year-old man who was initially treated with prostatectomy and radiotherapy, and later developed bone metastases. After commencing systemic therapy with androgen deprivation therapy (ADT) and apalutamide, his prostate-specific antigen (PSA) declined to undetectable levels, yet short-interval imaging demonstrated oligo-progression at T4, with biopsy specimen demonstrating pure SCC. Molecular profiling of both the primary prostate tumor and T4 demonstrated alterations in TMPRSS2-ERG, TP53, and FOXA1 confirming site of origin, with loss of RNF43 in the squamous metastasis. He was treated with stereotactic body radiation therapy to the SCC metastasis and continued on ADT and apalutamide with stable disease for a year post-radiation. This case highlights the importance of imaging to detect non– PSA-producing metastatic disease, the utility of radiation therapy in oligo-progression, and use of molecular profiling to provide insights into the pathogenesis of histologic transformation.