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This paper studies adults' responses to children's requests by focusing on turns that account for not granting the request on the grounds of involvement in another activity, i.e., multiactivity. The data consist of everyday interactions among family members at homes and in cars. The collection – 17 request sequences – is analysed with the conversation analytic method. We show the following: first, account turns verbalise either the ongoing or the requested activity, or both; second, account turns are a practice for foregrounding and communicating "exclusive order", i.e., they indicate that two progressing activities intersect with each other and cannot be progressed simultaneously, and that one activity is prioritised over another; third, account turns are used either to suspend or abandon the course of action initiated by the request; fourth, accounts – through various sequential and turn design features – display adults' level of commitment to resuming and returning to the requested activity later; and, finally, accounts indicating high commitment negotiate the "sequential implicativenesses" of the intersecting courses of action, displaying orientation to progress initiated activities. Accounts that display partial or no commitment frame the prioritisation of an activity in terms of "incapability" or "unwillingness" to progress the request sequence and thereby construct the "limits of multiactivity" in situ. [ABSTRACT FROM AUTHOR]

In this article we examine moments in which parents or other caregivers overtly invoke rules during episodes in which they take issue with, intervene against, and try to change a child's ongoing behavior or action(s). Drawing on interactional data from four different languages (English, Finnish, German, Polish) and using Conversation Analytic methods, we first illustrate the variety of ways in which parents may use such overt rule invocations as part of their behavior modification attempts, showing them to be functionally versatile interactional objects. Their interactional flexibility notwithstanding, we find that parents typically invoke rules when, in the course of the intervention episode, they encounter trouble with achieving an acceptable compliant outcome. To get at the distinct import of rule formulations in this context, we then compare them to two sequential alternatives: parental expressions of an experienced negative affective state, and parental threats. While the former emphasize aspects of social solidarity, the latter seek to enforce compliance by foregrounding a power asymmetry between the parent and the child. Rule formulations, by contrast, are designedly impersonal and appear to be directed at what the parents construe as shortcomings in common-sense practical reasoning on the child's part. Reflexively, the child is thereby cast as not having properly applied common-sense 'practical reason' when engaging in what is treated as the problematic behavior or action. Overt rule invocations can, therefore, be understood as indexical appeals to practical reason. [ABSTRACT FROM AUTHOR]

The infant gut microbiome contains a portion of bacteria that originate from the maternal gut. In the infant gut these bacteria encounter a new metabolic environment that differs from the adult gut, consequently requiring adjustments in their activities. We used pilot community RNA sequencing data (metatranscriptomes) from ten mother-infant dyads participating in the NiPPeR Study to characterize bacterial gene expression shifts following mother-to-infant transmission. Maternally-derived bacterial strains exhibited large scale gene expression shifts following the transmission to the infant gut, with 12,564 activated and 14,844 deactivated gene families. The implicated genes were most numerous and the magnitude shifts greatest in Bacteroides spp. This pilot study demonstrates environment-dependent, strain-specific shifts in gut bacteria function and underscores the importance of metatranscriptomic analysis in microbiome studies. [ABSTRACT FROM AUTHOR]

The human ability to anticipate upcoming behavior not only enables smooth turn transitions but also makes early responses possible, as respondents use a variety of cues that provide for early projection of the type of action that is being performed. This article examines resources for projection in interaction in three unrelated languages—Finnish, Japanese, and Mandarin—in sequences where speakers make evaluative assertions on a topic. The focus is on independently agreeing responses initiated in early overlap. Our cross-linguistic analysis reveals that while projection based on the ongoing turn-constructional unit relies on language-specific grammatical constructions, projection based on the larger context seems to be less language-dependent. A crucial finding is that in the target sequences, stances taken toward the topic already during earlier talk, as well as other structural patterns, are among the resources that recipients use for projecting how and when the ongoing turn will end. [ABSTRACT FROM AUTHOR]

Nutritional supplementation is a common clinical intervention to support the growth of preterm infants. There is little information on how nutritional supplementation interacts with the developing microbiome of the small intestine, the major site for nutrient metabolism and absorption. We investigated the effect of preterm birth and nutritional supplementation on the mucosal and luminal microbiota along the gastrointestinal tract (GIT) of preterm lambs. Preterm lambs (n = 24) were enterally supplemented with branched-chain amino acids (BCAAs), carbohydrate (maltodextrin), or water for two weeks from birth. Term lambs (n = 7) received water. Mucosal scrapings and luminal samples were collected from the duodenum, jejunum, ileum (small intestine) and colon at six weeks post-term age and analysed by 16S rRNA amplicon sequencing. Anatomical site explained 54% (q = 0.0004) of the variance and differences between the term and preterm groups explained 5.7% (q = 0.024) of the variance in microbial beta-diversities. The colon was enriched with Tenericutes and Verrucomicrobia compared to the small intestine, while Actinobacteria, and superphylum Patescibacteria were present in higher abundance in the small intestine compared to the colon. Our findings highlight that early-life short-term nutritional supplementation in preterm lambs does not alter the microbial community residing in the small intestine and colon. [ABSTRACT FROM AUTHOR]

What are speakers doing when they overlap with the previous speaker and start their response at a recognition point well before the transition-relevance place? This article adds to the body of literature on overlapping talk initiated by Gail Jefferson and shows that speakers use these turn-onset points to show that they have their own reasons to agree with what the first speaker is saying. That gets on record an equal, independent commitment to the assertion that the previous speaker is making. The overlapping speaker strives for a more balanced, symmetrical relationship with the current speaker with regard to time, speakership, and agency. The data are in Finnish and Estonian with English translation. [ABSTRACT FROM AUTHOR]

This paper investigates the Finnish mä tiedän , ‘I know’ utterance in responsive position. The data, gathered from naturally occurring interactions, indicate that these responses occur in sequences with epistemic incongruence: the first pair part is an informing type turn, which presupposes an unknowing (or a less knowing) recipient. With the mä tiedän response, the response-speaker resists this implication and points out the epistemic incongruence there is at that moment. The mä tiedän speaker thus resists the unknowing status attributed to her/him and claims to be knowledgeable, and at the same time resists the social action being accomplished in the informing turn. The uniformity of the expression, its sequential context and interactional function suggest that this expression is rather formulaic. The verb tietää , ‘to know’ is typically described as a complement taking predicate, but the mä tiedän responses include no object argument whatsoever; the object of knowing is to be inferred from the previous turn. The form of the expression is fitted to its sequential position. The turn may also contain response particles (e.g., nii or joo ) which specify its contextual interpretation. The data suggest that the use of these Finnish utterances is different from how I know responses are used in English conversations, where the responses may signal not only knowledge but also affiliation. [ABSTRACT FROM AUTHOR]

Viruses have long been considered potential triggers of autoimmune diseases. Here we defined the intestinal virome from birth to the development of autoimmunity in children at risk for type 1 diabetes (T1D). A total of 220 virus-enriched preparations from serially collected fecal samples from 11 children (cases) who developed serum autoantibodies associated with T1D (of whom five developed clinical T1D) were compared with samples from controls. Intestinal viromes of case subjects were less diverse than those of controls. Among eukaryotic viruses, we identified significant enrichment of Circoviridae-related sequences in samples from controls in comparison with cases. Enterovirus, kobuvirus, parechovirus, parvovirus, and rotavirus sequences were frequently detected but were not associated with autoimmunity. For bacteriophages, we found higher Shannon diversity and richness in controls compared with cases and observed that changes in the intestinal virome over time differed between cases and controls. Using Random Forests analysis, we identified disease-associated viral bacteriophage contigs after subtraction of age-associated contigs. These disease-associated contigs were statistically linked to specific components of the bacterial microbiome. Thus, changes in the intestinal virome preceded autoimmunity in this cohort. Specific components of the virome were both directly and inversely associated with the development of human autoimmune disease. [ABSTRACT FROM AUTHOR]

The perinatal period represents a critical window for cognitive and immune system development, promoted by maternal and infant gut microbiomes and their metabolites. Here, we tracked the co-development of microbiomes and metabolomes from late pregnancy to 1 year of age using longitudinal multi-omics data from a cohort of 70 mother-infant dyads. We discovered large-scale mother-to-infant interspecies transfer of mobile genetic elements, frequently involving genes associated with diet-related adaptations. Infant gut metabolomes were less diverse than maternal but featured hundreds of unique metabolites and microbe-metabolite associations not detected in mothers. Metabolomes and serum cytokine signatures of infants who received regular—but not extensively hydrolyzed—formula were distinct from those of exclusively breastfed infants. Taken together, our integrative analysis expands the concept of vertical transmission of the gut microbiome and provides original insights into the development of maternal and infant microbiomes and metabolomes during late pregnancy and early life. [Display omitted] • Mobile genetic elements from maternal bacteria shape offspring gut microbiomes • Microbiome and metabolome shifts in pregnancy may impact maternal metabolic health • The infant gut harbors unique metabolites and species-metabolite relationships • Diet modulates metabolomic profiles and immune system maturation in infants Maternal gut bacteria that fail to engraft in infants instead influence the assembly and metabolic potential of the infant gut microbiome through horizontal gene transfer. [ABSTRACT FROM AUTHOR]

Summary According to the hygiene hypothesis, the increasing incidence of autoimmune diseases in western countries may be explained by changes in early microbial exposure, leading to altered immune maturation. We followed gut microbiome development from birth until age three in 222 infants in Northern Europe, where early-onset autoimmune diseases are common in Finland and Estonia but are less prevalent in Russia. We found that Bacteroides species are lowly abundant in Russians but dominate in Finnish and Estonian infants. Therefore, their lipopolysaccharide (LPS) exposures arose primarily from Bacteroides rather than from Escherichia coli , which is a potent innate immune activator. We show that Bacteroides LPS is structurally distinct from E. coli LPS and inhibits innate immune signaling and endotoxin tolerance; furthermore, unlike LPS from E. coli , B. dorei LPS does not decrease incidence of autoimmune diabetes in non-obese diabetic mice. Early colonization by immunologically silencing microbiota may thus preclude aspects of immune education. [ABSTRACT FROM AUTHOR]

The gut microbiome has an important role in infant health and development. We characterized the fecal microbiome and metabolome of 222 young children in Dhaka, Bangladesh during the first two years of life. A distinct Bifidobacterium longum clade expanded with introduction of solid foods and harbored enzymes for utilizing both breast milk and solid food substrates. The clade was highly prevalent in Bangladesh, present globally (at lower prevalence), and correlated with many other gut taxa and metabolites, indicating an important role in gut ecology. We also found that the B. longum clades and associated metabolites were implicated in childhood diarrhea and early growth, including positive associations between growth measures and B. longum subsp. infantis , indolelactate and N-acetylglutamate. Our data demonstrate geographic, cultural, seasonal, and ecological heterogeneity that should be accounted for when identifying microbiome factors implicated in and potentially benefiting infant development. [Display omitted] • Gut microbiomes of infants from Bangladesh harbored three Bifidobacterium longum clades • Transitional B. longum clade carried enzymes to utilize breast milk and food substrates in weaning • B. longum clades and associated metabolites were implicated in diarrhea and growth Transitional B. longum , a clade prevalent in Bangladeshi children during weaning, harbors enzymes for utilizing both breast milk and solid food substrates. [ABSTRACT FROM AUTHOR]

Treatment-related late toxicities after pediatric allogeneic hematopoietic SCT (allo-HSCT) are increasingly important as long-term survival has become an expected outcome for many transplanted children and adolescents. In a retrospective cohort study, we assessed long-term health outcomes in 204 allo-HSCT survivors transplanted in childhood or adolescence (<20 years) between 1978 through 2000 after a median follow-up time of 12 (range 4-28) years. Data on conditioning regimen, adverse health events (AE) and growth and hormonal substitutions (hormone replacement therapies (HRTs)) were obtained from medical records. AEs were graded retrospectively according to Common Terminology Criteria for Adverse Events v3.0. Late deaths (⩾48 months after allo-HSCT) were evaluated separately. Multivariate analysis demonstrated that chronic GVHD (P<0.000) and longer follow-up time (P<0.05) correlated with AEs, whereas CY-based conditioning was inversely correlated (P<0.002). TBI and longer follow-up duration predicted more severe AEs (P<0.001 and P<0.001, respectively). HRTs were more frequent after TBI. Diabetes type II, dyslipidemia and hypertension were detected in 9, 7 and 7% of the survivors, respectively. Late deaths (n=22) were most frequently due to pulmonary failure (n=7), followed by secondary malignancy (n=5). The occurrence of AEs after pediatric allo-HSCT is high and likely to increase during extended follow-up, particularly in patients who have received TBI. [ABSTRACT FROM AUTHOR]

The article aims to show how local industry life cycles impact the development of Finnish resource-based rural towns. This study reveals five long-term and overlapping industry cycles which were based on natural resources, assembly industries and service production. In general, the cycles have shortened over time. Transitions from cycle to cycle were enabled by the phases of resilience, which were highly dependent on political and economic processes at different scales. However, the political interventions of the last decades were unable to compensate for the disadvantages in competitiveness of this remote area and lay sustainable foundations for new industries. In the long run, the only exception has been the forest-related processing industry which has a capacity to renew its own operations and adapt to changing market situations. The results demonstrate the high significance of absolute advantage in rural development [ABSTRACT FROM AUTHOR]

In this paper, we study fundamental properties of the Self-Organizing Map (SOM) and the Generative Topographic Mapping (GTM), ramifications of the initialization of the algorithms and properties of the algorithms in the presence of missing data. We show that the commonly used principal component analysis (PCA) initialization of the GTM does not guarantee good learning results with high-dimensional data. Initializing the GTM with the SOM is shown to yield improvements in self-organization with three high-dimensional data sets: commonly used MNIST and ISOLET data sets and epigenomic ENCODE data set. We also propose a revision of handling missing data to the batch SOM algorithm called the Imputation SOM and show that the new algorithm is more robust in the presence of missing data. We benchmark the performance of the topographic mappings in the missing value imputation task and conclude that there are better methods for this particular task. Finally, we announce a revised version of the SOM Toolbox for Matlab with added GTM functionality. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study was to evaluate long-term ovarian function after allogeneic hematopoietic stem cell transplantation (HSCT) in childhood and adolescence. Subjects and methods: Predictive factors for ovarian function were evaluated among 92 adult or pubertal female survivors transplanted at Huddinge and Helsinki University Hospital during 1978-2000, at a mean age of 9±4.3 years (range 1-19). At the time of the study a meanGS.D. of 13±5.5 years (range 6-27) had elapsed since the HSCT and the mean age of the participants was 22±6.3 years (range 9-41). Results: Spontaneous puberty based on breast development occurred in 40 and menarche in 30 of the 70 girls who were prepubertal at transplantation. Six out of 20 girls who received HSCTafter initiation of pubertal development recovered their ovarian function. Younger age at HSCT, conditioning without total body irradiation (TBI), and a non-leukemia diagnosis predicted the spontaneous menarche. The incidence of menarche was higher after fractioned vs single fraction TBI (P<0.05), cyclophosphamide (Cy) vs busulfan (Bu)-based conditioning (P<0.05), and among leukemia patients transplanted at first remission vs later remissions (P<0.01) and with no cranial irradiation (cranial radiotherapy, CRT) vs given CRT (14-24 Gy) (P<0.01). The majority of recipients conditioned with only Cy vs TBI (P<0.001) or vs Bu-based regimens (P<0.01) showed preserved ovarian function and required no estrogen replacement at their latest follow-up visit at a mean age of 23±6.3 years (range 15-41). Ten women became pregnant. Conclusions: Patients conditioned with TBI or Bu-based regimes are at high risk of ovarian failure. Intensive antileukemia therapy before HSCT including CRT especially among relapsed patients may further decrease the possibility of spontaneous menarche. [ABSTRACT FROM AUTHOR]

Background. Collimation of irregularly shaped clinical electron beams is currently based on electron inserts made of low melting point alloys. The present investigation compares a conventional electron applicator with insert and add-on eMLC-based dose distributions in the postoperative chest wall irradiation of left-sided breast cancer. Material and methods. Voxel Monte Carlo++ (VMC++) calculated dose distributions related to electron fields were compared with 10 left-sided breast cancer patients after radical mastectomy. The prescription dose was 50 Gy at a build-up maximum. The same dose was prescribed for the ipsilateral axillary, parasternal and supraclavicular lymph nodes that were treated with photons and calculated with a pencil beam algorithm. The insert beams were shaped with 1.5 cm thick Wood's metal electron inserts in an electron applicator of a Varian 2100 C/D linac. Doses for the eMLC-shaped beams were calculated for an eMLC prototype with 2 cm thick and 5 mm wide steel leaves. The same collimator-to-surface distance (CSD) of 5.8 cm was used for both collimators. Results. The mean PTV dose was slightly higher for the eMLC plans (50.7 vs 49.5 Gy, p<0.001, respectively). The maximum doses assessed by D5% for the eMLC and insert were 60.9 and 59.1 Gy (p<0.001). The difference was due to the slightly higher doses near the field edges for the eMLC. The left lung V20 volumes were 34.5% and 34.0% (p<0.001). There was only a marginal difference in heart doses. Discussion: Despite a slight increase of maximum dose in PTV the add-on electron MLC for chest wall irradiation results in practically no differences in dose distributions compared with the present insert-based collimation. [ABSTRACT FROM AUTHOR]

Dosimetric verification of a new Monte Carlo beam model for multi-leaf collimated electrons was performed using experimental data from an add-on electron multi-leaf collimator (eMLC) prototype. The measurements were compared against calculations using an electron phase space sampled from a parameterized electron beam model and the voxel Monte Carlo++ (VMC++) code for in-phantom energy deposition. Verification of the calculations was performed in a water phantom with the developed eMLC attached to a Varian 2100 C/D radiotherapy accelerator with nominal energies 6 MeV, 9 MeV, 12 MeV, 16 MeV and 20 MeV. The eMLC prototype consisting of 2 cm thick and 5 mm wide steel leaves is fixed under the 20 × 20 cm2 electron applicator with a source-to-leaf distance 97.2 cm. The eMLC prototype has non-motorized leaves with straight leaf edges and a maximum field size of 20 × 20 cm2 at SSD 100 cm. The beam model is a coupled multi-source model with parameters derived from detailed beam characterization measurements and a kernel model for the indirect leaf-scattered electrons. Typical calculation times with a 2% mean statistical uncertainty was under 5 min. In extensive set of in-water measurements 88% of the voxels were within 2%/2 mm acceptance criterion. Although at SSD 100 cm the dose near the phantom surface is slightly pronounced due to the short collimator-to-surface distance, the new beam model was suitable for dose calculation of the add-on type eMLC. [ABSTRACT FROM AUTHOR]

Ten years in the EU (European Union) have passed and structural changes have taken place in the food sector, but it is a common opinion that as far as production is concerned the food sector has managed better than expected. In this paper, we study structural changes in the Finnish food industry in 1989-2002, with the focus on the use of domestic and imported inputs and value-added formation before and after joining the EU. An input-output (I-O) analysis output approach will be applied, as this enables to trace the multiplier effects of an industry's total output. The results confirm an increase in imported inputs as well as in demand of the domestic service industries; and conversely, a decrease in the food industry's (own) value added. It is concluded that outsourcing, labour reduction and increased imports have improved the efficiency of the Finnish food industry and contributed to its stable development after accession to the EU. [ABSTRACT FROM AUTHOR]

Wearing of the ladle slag line is the biggest refractory material problem with ladles. The purpose of this work was to study the wearing mechanism of refractory materials in a steel ladle slag line. The studied refractory materials were MgO-C bricks, doloma brick, corundum castable and spinel castable. Rotating-furnace and sessile-drop tests were conducted with converter and ladle slags. The corrosion index, infiltration zone and refractory/slag mineralogical reactions were studled. The wear mechanisms of refractory materials were studled using SEM, XRF and XRD analysing techniques. The driving force behind chemical wearing is the chemical poten- tial differences of the components between lining and slag. In general, the main principles of chemical wearing depend on the structure and mineralogical character of the refractory material. [ABSTRACT FROM AUTHOR]

The melanocortin peptides have an important role in regulating body weight and appetite. Mice that lack the desacetyl-α-MSH and α-MSH peptides (Pomctm1/tm1) develop obesity. This effect is exacerbated by a high fat diet (HFD). However, development of obesity in female Pomctm1/tm1 mice during chronic HFD conditions is not fully accounted for by the increased energy intake. We hypothesized that the protection against chronic HFD-induced obesity imparted by MSH peptides in females is mediated by sex-specific alterations in the gut structure and gut microbiota. We determined that female WT mice had reduced jejunum villus length and increased crypt depth in response to chronic HFD. WT males and Pomctm1/tm1 mice lacked this adaptation to a chronic HFD. Both Pomctm1/tm1 genotype and chronic HFD were significantly associated with gut microbiota composition. Sex-specific associations between Pomctm1/tm1 genotype and gut microbiota were observed in the presence of a chronic HFD. Pomctm1/tm1 females had significantly reduced fecal acetate and propionate concentrations when compared to WT females. We conclude that MSH peptides influence jejunum villus length, crypt depth and the structure of the gut microbiota. These effects favor reduced nutrient absorption and occur in addition to the recognized roles of desacetyl-α-MSH and α-MSH peptides in appetite control. [ABSTRACT FROM AUTHOR]

The novel life cycle assessment (LCA)-based carbon handprint indicator represents a potential carbon footprint reduction that producers/products create for customers who use the(ir) product instead of a baseline product. The research question is how to consider a situation in which multiple customers use a product for different purposes to provide a carbon handprint quantification and the associated communication. The study further provides new insight into the greenhouse gas (GHG) emissions reduction potential within the mobile telecommunications and energy sectors. The carbon handprint of a novel Finnish liquid-cooled base station technology is quantified. The liquid-cooled base station provides a telecommunications service and waste heat that is recoverable through the cooling liquid for heating purposes. The baseline solutions are an air-cooled base station, and district and electrical heating. The liquid-cooled base station creates a carbon handprint, both through energy savings in telecommunications and additional waste heat reuse, replacing other energy production methods. A large-scale climate change mitigation potential through a liquid-cooled base station expansion could be significant. Different supply chain operators' contributions to the total carbon handprint could be terminologically distinguished in communications to emphasize their roles in a shared handprint. The handprint should be transparently communicated for each customer and function. [ABSTRACT FROM AUTHOR]

In this paper, we address the larger notion of cooperation in interaction and its underlying dimensions as defined in Conversation Analysis: alignment and affiliation. Focusing on three cases from three different languages (Danish, Estonian and Finnish) we investigate a specific practice, that of anticipatory completions, in a particular context, that of storytelling, and show that the practice of completing another speaker's turn in an anticipatory manner is not de facto definable as either an aligning or non-aligning action, nor can it be said to be either affiliating or non-affiliating. Through our analyses, we aim to distinguish and illustrate the manifold layers of and perspectives to alignment and affiliation and argue for their relevance for studies of interactional phenomena. We conclude that the notion of cooperation and its implementation through affiliating and/or aligning actions is a multi-layered and complex issue, the intricacies of which are best understood and captured through detailed sequential analyses. [ABSTRACT FROM AUTHOR]

This paper explores the topic of children having restricted rights to engage in conversation with adults in multiparty interactions. Drawing on the principles of conversation analysis, and 7 h of video-recorded Finnish and English naturally occurring in-car family interactions, our focus is on moments when a child summons the driver while the driver is driving and having a conversation with another passenger. We suggest that the composition and position of the child's summons relative to other ongoing conversations play a crucial role in whether the child receives a response, or whether the summons will be ignored or suspended by the driver. Positioning and designing summonses in different ways is a resource for the child to exert agency and mobilize a response from the driver to different degrees, which affects the child's likelihood of entering in interaction with the driver at that moment. The analysis suggests that children cannot be a priori determined to have (or not to have) certain kinds of speaking rights; instead, the "right" to engage in a conversation is contingent and situated, (re)negotiated and accomplished in situ. Finally, summons-answer sequences provide adults a resource for socializing children into the regularities of turn allocation and turn distribution. • This paper studies children's summonses to their parents or caretakers in cars. • The position and composition of the summons contribute to response-pressure. • With their ways of summoning, children exert interactional agency. • Children's rights to engage are contingent and accomplished in situ. • Adults' responses socialize children into the systematics of social interaction. [ABSTRACT FROM AUTHOR]

We examine how other-repetitions in Finnish are used for repairing interactional problems in hearing and understanding and for registering what another has just said, describing how prosody and grammar interact in accomplishing these goals. In the repair-initiating repetitions, the pitch contours build a continuum of different degrees of falling pitch from moderate to steep, the latter being associated with some type of an affective stance. In the registering repetitions, the pitch fall is generally narrower than in the repair-initiations, the pitch span of the repetition turn typically matching that of the original turn. A notable feature of other-repetitions in Finnish is the use of particles (mostly ai and vai), which deal specifically with the informational aspects of other-repetitions, thus contributing to the design of both repair-initiating and registering repetitions. The article illustrates the complex layering of actions that Finnish as a 'particle language' affords. (Conversation analysis, other-repetition, prosody, grammar, Finnish, repair, registering, affectivity, response particle) [ABSTRACT FROM AUTHOR]

In a very high-dimensional vector space, two randomly-chosen vectors are almost orthogonal with high probability. Starting from this observation, we develop a statistical factor model, the random factor model, in which factors are chosen stochastically based on the random projection method. Randomness of factors has the consequence that correlation and covariance matrices are well preserved in a linear factor representation. It also enables derivation of probabilistic bounds for the accuracy of the random factor representation of time-series, their cross-correlations and covariances. As an application, we analyze reproduction of time-series and their cross-correlation coefficients in the well-diversified Russell 3,000 equity index. [ABSTRACT FROM AUTHOR]

There is growing evidence suggesting that chemical exposure alters gut microbiota composition. However, not much is known about the impact of per- and polyfluoroalkyl substances (PFAS) on the gut microbial community. Here, in a mother-infant study, we set out to identify the gut bacterial species that associate with chemical exposure before (maternal) and after (maternal, infant) birth. Paired serum and stool samples were collected from mother-infant dyads (n = 30) in a longitudinal setting. PFAS were quantified in maternal serum to examine their associations with the microbial compositions (determined by shotgun metagenomic sequencing) in mothers and infants. High maternal exposure to PFAS was consistently associated with increased abundance of Methanobrevibacter smithii in maternal stool. Among individual PFAS compounds, PFOS and PFHpS showed the strongest association with M. smithii. However, maternal total PFAS exposure associated only weakly with the infant microbiome. Our findings suggest that PFAS exposure affects the composition of the adult gut microbiome. [ABSTRACT FROM AUTHOR]

The article presents a study which examines the local economic impacts of the national park tourism in Finland through Nordic method and input-output method.

Background Left ventricular mass ( LVM) and synchrony have prognostic value for many cardiovascular disease states. We report the agreement and repeatability of LVM estimation by three-dimensional (3 D) versus M-mode and repeatability of 3 D estimation of systolic dyssynchrony. Methods 3 DLVM was computed by subtraction of endocardial from epicardial volume X1.05 both at end-diastole and end-systole. M-mode measurements were made at end-diastole. This prospective study comprised 40 subjects, 20 patients with chronic kidney disease or treated neuroblastoma and 20 healthy individuals. The median age was 17 (range 6-29 years). Results Intra- and inter-observer intraclass correlation was excellent for 3 D systolic LVM (0.99, 0.87), 3 D diastolic LVM (0.99, 0.93), M-mode LVM (0.88, 0.93), moderate for 16-segment SDI (0.77, 062), moderate to low for 12-segment SDI (0.48, 0.73), and 6-segment SDI (0.37, 0.69). The median (range) LVM measurement for 3 D diastolic LVM was 125 g (50-253), 3 D systolic LVM 109 g (40-195), and M-mode LVM 115 g (range 40-207). There was a significant bias for diastolic 3 DLVM to be higher than systolic 3 D or M-mode. Limits of agreement between methods were wide. The median (range) systolic dyssynchrony measurements were 2.0 (0.4-7.0), 1.5 (0.3-4.3), and 1.4 (0.3-4.5) for 16-segment, 12-segment, and 6-segment models, respectively. Conclusion 3 D and M-mode measurement of LVM are highly repeatable. Measurement bias and wide limits of agreement mean that the same echocardiographic technique should be used during follow-up. Measurement of 3 D systolic dyssynchrony is most repeatable using a 16-segment model. [ABSTRACT FROM AUTHOR]

In order to theorize the phenomenon of urban shrinkage, the paper draws from resilience theories that focus on the ability of communities to react to abrupt as well as slowly occurring disturbances. Mechanisms for resilience are defined and identified. The empirical case study is a peripherally located small city in Finland. It is a specific feature for shrinking cities in Finland that many of them, now facing the challenge of population decline, have grown to be economically dependent on the utilization and processing of natural resources, most importantly timber and minerals. Recent transformations in the global division of labour have caused employment opportunities to decline, resulting in out-migration and ageing. Due to lack of a general regional policy dealing with this issue, these cities and settlements now have to find individual strategies to adapt to these wider-scale transformations. Nevertheless, these communities have faced such situations previously and, therefore, it is possible to learn from their former adaptation strategies. The conditions under which the case city has been able to adapt to change in the past are analysed as well as the preconditions for future adaptation, thereby making it possible to refine theories of resilience and adaptability from the perspective of industrialized Northern Europe. [ABSTRACT FROM PUBLISHER]

Background: Decreased exposure to microbial agents in industrialized countries and urban living areas is considered as a risk factor of developing immune‐mediated diseases, such as allergies and asthma. Epithelial surfaces in the gastrointestinal and respiratory tracts and in the skin constitute the primary areas in contact with the environmental microbial load. Methods: We analyzed the levels of 30 cytokines and growth factors in serum or plasma as markers of the immune maturation in the participants in the DIABIMMUNE study from Russian Karelia (n = 60), Estonia (n = 83) and Finland (n = 89), three neighboring countries with remarkable differences in the incidences of allergies, asthma and autoimmune diseases. Results: We observed an upregulation of T helper cell signature cytokines during the first 12 months of life, reflecting natural development of adaptive immune responses. During the first years of life, circulating concentrations of epidermal growth factor (EGF) were significantly higher, especially in Russian children compared with Finnish children. The children who developed IgE sensitization showed lower levels of EGF than those without such responses. Conclusion: Our results suggest that low circulating EGF levels associate with the risk of allergies possibly via the effects on the epithelial integrity and mucosal homeostasis. [ABSTRACT FROM AUTHOR]

Objective: To estimate the prevalence of dementia with Lewy bodies (DLB) according to the consensus criteria in a general population aged 75 years or older.Methods: The "Kuopio 75+ study" is a population based health survey focused on the clinical epidemiology of dementia and functional capacity among elderly subjects aged 75 years or older. On 1 January 1998, a random sample of 700 subjects was drawn from a total population born before 1 January 1923, living in the city of Kuopio, northeast Finland (n = 4518). The study subjects underwent a structured interview and clinical examination.Results: 601 elderly subjects (86% of the random sample) were examined. A dementia disorder was diagnosed in 137-a prevalence of 22.8% (95% confidence interval 19.4% to 26.2%). The prevalence of DLB was 5.0% (3.2% to 6.7%), comprising 22% of all demented subjects. Probable DLB was diagnosed in 20 subjects (3.3% (1.9% to 4.8%)), and possible DLB in 10 (1.7% (0.6% to 2.7%)). The prevalence of Alzheimer's disease was 10.6% (47% of all demented subjects), of vascular dementia, 5.3% (23%), and of other types of dementing disorders, 1.8% (8%).Conclusions: In a general population aged 75 years and older, the prevalence of a disorder fulfilling the diagnostic criteria of DLB is half that of Alzheimer's disease and the same as for vascular dementia. [ABSTRACT FROM AUTHOR]

The carbon handprint is an approach to showcase the positive environmental impact—that is, greenhouse gas (GHG) emissions reduction—a product or service has compared to a baseline offer. Companies whose product or service is performing comparably well in terms of GHG emissions can use the carbon handprint to communicate their sustainable performance and positive environmental value of their solution to stakeholders. To better understand the uses, benefits, and challenges of the carbon handprint, we interviewed informants from seven large companies with some years of experience using the approach. The objective was to determine how the early adopters use the carbon handprint and create value from it. The results indicate that the early adopters have found valuable applications for the approach, particularly because it accounts for the positive impact of the company's business. At the same time, the users communicated that since the approach is not yet widely known in all stakeholder groups, there is potential to increase the value derived from the handprint approach, especially if it gains more international acceptance, awareness, and recognition. • The approach is not yet established, but the interest in it appears to be increasing. • The handprint appears to create value for users in multiple ways. • To further increase the handprint's value, the users call for its standardization. [ABSTRACT FROM AUTHOR]

Abstract The capacity to calculate and communicate the beneficial environmental impact of products and services is lacking in scientific guidelines. To fill this gap, this article presents a new approach for calculating the carbon handprint of products. The core of the suggested approach involves comparing the carbon footprint of an improved product with the carbon footprint of the baseline product, and subsequently calculating the reduction in greenhouse gas emission that can be achieved by utilizing the improved product. The proposed approach is founded on the standardized life cycle assessment methodology for footprints until the use stage, and it provides a framework to recognize the effects of the remaining life cycle stages in the actual operational environment. This calculation is meant to be used by manufacturers that wish to show potential customers the positive climate impacts offered by the manufacturer's product. The carbon handprint approach complements the existing methodologies by introducing new definitions and consistent guidelines for comparing the baseline product and the improved product. This article presents the developed calculation approach and demonstrates the approach with one case study about renewable diesel. Results of the diesel handprint calculation indicate that a driver can reduce greenhouse gas emissions by choosing renewable diesel over baseline fuel. Thus, the producer of the renewable diesel will create a handprint. Organizations can use carbon handprints for quantifying the greenhouse gas reductions their customers can achieve by utilizing the product. Thus, the carbon handprint can be a powerful tool in communications and marketing. By conducting carbon handprint assessments, a company can also find out how their product qualifies in comparison to baseline products. Therefore, carbon handprints can also support decision-making and lifelong product design. Highlights • Guidelines for calculating the positive climate impacts of products are created. • Carbon handprint refers to customer's greenhouse gas reductions the product enables. • The reduction is calculated against the determined baseline. • Carbon handprint can be used for decision-making, as well as for communication. [ABSTRACT FROM AUTHOR]

The increasing prevalence of infections caused by antibiotic-resistant bacteria is a global healthcare crisis. Understanding the spread of resistance is predicated on the surveillance of antibiotic resistance genes within an environment. Bioinformatics and artificial intelligence (AI) methods applied to metagenomic sequencing data offer the capacity to detect known and infer yet-unknown resistance mechanisms, and predict future outbreaks of antibiotic-resistant infections. Machine learning methods, in particular, could revive the waning antibiotic discovery pipeline by helping to predict the molecular structure and function of antibiotic resistance compounds, and optimising their interactions with target proteins. Consequently, AI has the capacity to play a central role in guiding antibiotic stewardship and future clinical decision-making around antibiotic resistance. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract that is associated with changes in the gut microbiome. Here, we sought to identify strain-specific functional correlates with IBD outcomes. Methods: We performed metagenomic sequencing of monthly stool samples from 20 IBD patients and 12 controls (266 total samples). These were taxonomically profiled with MetaPhlAn2 and functionally profiled using HUMAnN2. Differentially abundant species were identified using MaAsLin and strain-specific pangenome haplotypes were analyzed using PanPhlAn. Results: We found a significantly higher abundance in patients of facultative anaerobes that can tolerate the increased oxidative stress of the IBD gut. We also detected dramatic, yet transient, blooms of Ruminococcus gnavus in IBD patients, often co-occurring with increased disease activity. We identified two distinct clades of R. gnavus strains, one of which is enriched in IBD patients. To study functional differences between these two clades, we augmented the R. gnavus pangenome by sequencing nine isolates from IBD patients. We identified 199 IBD-specific, strain-specific genes involved in oxidative stress responses, adhesion, iron-acquisition, and mucus utilization, potentially conferring an adaptive advantage for this R. gnavus clade in the IBD gut. Conclusions: This study adds further evidence to the hypothesis that increased oxidative stress may be a major factor shaping the dysbiosis of the microbiome observed in IBD and suggests that R. gnavus may be an important member of the altered gut community in IBD. [ABSTRACT FROM AUTHOR]

The association between HLA genotypes and type 1 diabetes is well known. We set out to examine incidence rates and ratios of type 1 diabetes depending on the risk afflicted by HLA genotype. Children with the high-risk genotype have a 45-fold disease risk compared to peers with neutral or protective genotypes. [ABSTRACT FROM AUTHOR]

Background: Gut microbiome dysbiosis has been demonstrated in subjects with newly diagnosed and chronic inflammatory bowel disease (IBD). In this study we sought to explore longitudinal changes in dysbiosis and ascertain associations between dysbiosis and markers of disease activity and treatment outcome. Methods: We performed a prospective cohort study of 19 treatment-naïve pediatric IBD subjects and 10 healthy controls, measuring fecal calprotectin and assessing the gut microbiome via repeated stool samples. Associations between clinical characteristics and the microbiome were tested using generalized estimating equations. Random forest classification was used to predict ultimate treatment response (presence of mucosal healing at follow-up colonoscopy) or non-response using patients' pretreatment samples. Results: Patients with Crohn's disease had increased markers of inflammation and dysbiosis compared to controls. Patients with ulcerative colitis had even higher inflammation and dysbiosis compared to those with Crohn's disease. For all cases, the gut microbial dysbiosis index associated significantly with clinical and biological measures of disease severity, but did not associate with treatment response. We found differences in specific gut microbiome genera between cases/controls and responders/non-responders including Akkermansia, Coprococcus, Fusobacterium, Veillonella, Faecalibacterium, and Adlercreutzia. Using pretreatment microbiome data in a weighted random forest classifier, we were able to obtain 76.5 % accuracy for prediction of responder status. Conclusions: Patient dysbiosis improved over time but persisted even among those who responded to treatment and achieved mucosal healing. Although dysbiosis index was not significantly different between responders and non-responders, we found specific genus-level differences. We found that pretreatment microbiome signatures are a promising avenue for prediction of remission and response to treatment. [ABSTRACT FROM AUTHOR]

Deep sequencing of the gut microbiomes of 1135 participants from a Dutch population-based cohort shows relations between the microbiome and 126 exogenous and intrinsic host factors, including 31 intrinsic factors, 12 diseases, 19 drug groups, 4 smoking categories, and 60 dietary factors. These factors collectively explain 18.7% of the variation seen in the interindividual distance of microbial composition. We could associate 110 factors to 125 species and observed that fecal chromogranin A (CgA), a protein secreted by enteroendocrine cells, was exclusively associated with 61 microbial species whose abundance collectively accounted for 53% of microbial composition. Low CgA concentrations were seen in individuals with a more diverse microbiome. These results are an important step toward a better understanding of environment-diet-microbe-host interactions. [ABSTRACT FROM AUTHOR]

Background: A gluten-free diet (GFD) is the most commonly adopted special diet worldwide. It is an effective treatment for coeliac disease and is also often followed by individuals to alleviate gastrointestinal complaints. It is known there is an important link between diet and the gut microbiome, but it is largely unknown how a switch to a GFD affects the human gut microbiome. Methods: We studied changes in the gut microbiomes of 21 healthy volunteers who followed a GFD for four weeks. We collected nine stool samples from each participant: one at baseline, four during the GFD period, and four when they returned to their habitual diet (HD), making a total of 189 samples. We determined microbiome profiles using 16S rRNA sequencing and then processed the samples for taxonomic and imputed functional composition. Additionally, in all 189 samples, six gut health-related biomarkers were measured. Results: Inter-individual variation in the gut microbiota remained stable during this short-term GFD intervention. A number of taxon-specific differences were seen during the GFD: the most striking shift was seen for the family Veillonellaceae (class Clostridia), which was significantly reduced during the intervention (p = 2.81 x 10-05). Seven other taxa also showed significant changes; the majority of them are known to play a role in starch metabolism. We saw stronger differences in pathway activities: 21 predicted pathway activity scores showed significant association to the change in diet. We observed strong relations between the predicted activity of pathways and biomarker measurements. Conclusions: A GFD changes the gut microbiome composition and alters the activity of microbial pathways. [ABSTRACT FROM AUTHOR]

Aims The loss of nuclear factor E2-related factor 2 (Nrf2) has been shown to protect against atherogenesis in apoE-deficient mice. The mechanism by which Nrf2 deficiency affords atheroprotection in this model is currently unknown, but combined systemic and local vascular effects on lesion macrophages have been proposed. We investigated the effect of bone marrow-specific loss of Nrf2 on early atherogenesis in low-density lipoprotein (LDL) receptor-deficient (LDLR−/−) mice, and assessed the effect of Nrf2 on cellular accumulation of modified LDLs and the expression of inflammatory markers in macrophages. Methods and results The effect of bone marrow-specific loss of Nrf2 on atherogenesis was studied using bone marrow transplantation of wild-type (WT) or Nrf2−/− bone marrow to LDLR−/− mice. Mice transplanted with Nrf2−/− bone marrow and fed a high-fat diet for 6 weeks exhibited significantly larger atherosclerotic lesions than WT bone marrow transplanted mice. Moreover, in thioglycollate-elicited Nrf2−/− macrophages, the uptake of acetylated and malondialdehyde-modified LDLs was increased in comparison with WT controls, with the concomitant increase in the expression of scavenger receptor A and toll-like receptor 4. In addition, the expression of pro-inflammatory monocyte chemoattractant protein-1 and interleukin-6 were increased in Nrf2−/− vs. WT macrophages. Conclusion Nrf2 deficiency specific to bone marrow-derived cells aggravates atherosclerosis in LDLR−/− mice. Furthermore, the loss of Nrf2 in macrophages enhances foam cell formation and promotes the pro-inflammatory phenotype. [ABSTRACT FROM PUBLISHER]

Controversy between alternative uses of forests in Finnish Upper Lapland has been going on for decades, and in recent years it has been escalated to a serious conflict. The core of the conflict is the adverse impacts of forestry on old forests which are important grazing areas for reindeer and which are regarded as intact nature and wilderness areas. This paper describes the experiences of applying multi-criteria decision analysis interview approach on this conflict. The approach provides tools for structuring the problem and preferences of the stakeholders as well as for analyzing the effects of different alternatives in a common framework. We focus on the practical experiences gained from the application of this approach in this context. Multi-criteria decision analysis was found to be a useful approach to evaluate the economic, ecological and cultural aspects of this intense conflict. The obtained experiences also support the view that the approach works best when tightly integrated into the planning process. [Copyright &y& Elsevier]

The role of microglia recruited from bone marrow (BM) into the CNS during the progression of Alzheimer's disease (AD) is poorly understood. To investigate whether β-amyloid (Aβ) associated microglia are derived from blood monocytes, we transplanted BM cells from enhanced green fluorescent protein expressing mice into young or old transgenic AD mice and determined the engraftment of BM-derived cells into the brain and their relative distribution near Aβ deposits. When young transgenic mice were transplanted before the onset of AD-like pathology and the brains analyzed 6.5 months later, the number of engrafted cells was significantly higher than in age-matched wild type mice. Moreover, the number of BM-derived cells associated with Aβ was significantly higher than in old transgenic mice transplanted after the establishment of AD-like pathology. Local inflammation caused by intrahippocampal lipopolysaccharide injection significantly increased the engraftment of BM-derived cells in old AD mice and decreased the hippocampal Aβ burden. These results suggest that infiltration of BM-derived monocytic cells into the brain contributes to the development of microglial reaction in AD. [ABSTRACT FROM AUTHOR]

Decarbonization of metal production is currently a unique challenge for the industry. To gain insights, environmental impacts of ferrochrome smelting technologies were estimated using simulation-based life cycle assessment. Two leading technologies: (1) Steel Belt Sintering-Submerged Electric Arc Furnace (SBS-SAF), and (2) Rotary Kiln-Submerged Electric Arc Furnace (RK-SAF) were investigated. Four environmental impact categories: climate change, acidification, particulate matter, and resource use (minerals and metals), were considered. Results showed that GHG emissions for producing high carbon ferrochrome vary to a greater extent depending on location of processing plant because of differences in electricity emission factors. For example, South African energy grid generates more GHG emission than Finnish energy grid. Furthermore, though prereduction reduced SAF energy consumption, it did not necessarily result in reduced net GHG emissions due to high coal consumption of RK. Acidification and particulate matter were higher when using RK-SAF technology. Ferrochrome production generally had low impact on resource use. [Display omitted] • Simulation based life cycle assessment of ferrochrome production demonstrated. • Estimation of greenhouse gas emissions for two ferrochrome smelting technologies done. • Technology using rotary kiln has higher emissions at 3.72 tCO 2 /ton ferrochrome. • Prereduction reduces smelting energy consumption but not net greenhouse gas emissions. • Carbon neutral electricity and biocarbon use recommended for low greenhouse emissions. [ABSTRACT FROM AUTHOR]

Metabolic diseases are increasing among adolescents with obesity. Although the reported prevalence of metabolic syndrome is approximately 30% worldwide, its prevalence is largely unknown among New Zealand adolescents. Therefore, we assessed the health of adolescents with obesity (BMI ≥ 30 kg/m2) enrolled in a randomised clinical trial (Gut Bugs Trial), to identify the prevalence of undiagnosed comorbidities. Assessments included anthropometry, 24-h ambulatory blood pressure monitoring, and insulin sensitivity. We report on baseline data (pre-randomisation) on 87 participants (14–18 years; 59% females), with mean BMI 36.9 ± 5.3 kg/m2 (BMI SDS 3.33 ± 0.79). Approximately 40% of participants had undiagnosed metabolic syndrome, which was twice as common among males. Half (53%) had pre-diabetes and 92% a reduction in insulin sensitivity. Moreover, 31% had pre-hypertension/hypertension, 69% dyslipidaemia, and 25% abnormal liver function. Participants with class III obesity had a greater risk of metabolic syndrome than those with classes I/II [relative risk 1.99 (95% CI 1.19, 3.34)]. Risks for pre-hypertension/hypertension and inflammation were also greater among those with class III obesity. We identified a high prevalence of undiagnosed comorbidities among adolescents with obesity in New Zealand. As adolescent obesity tracks into adulthood, early interventions are needed to prevent progression to overt cardiometabolic diseases. [ABSTRACT FROM AUTHOR]

An abstract of the article "Inhibition of Apolipoprotein B-100 Expression by Lentivirus Mediated RNA Interference in Mice after Stem Cell Transduction and Transplantation," by Mikko P. Turunen, Petri I. Makinen and Seppo Yla-Herttuala is presented.