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1.
  • Zhang, G., et al. (författare)
  • Genetic Associations with Gestational Duration and Spontaneous Preterm Birth
  • 2017
  • Ingår i: New England Journal of Medicine. - 0028-4793. ; 377:12, s. 1156-1167
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND Despite evidence that genetic factors contribute to the duration of gestation and the risk of preterm birth, robust associations with genetic variants have not been identified. We used large data sets that included the gestational duration to determine possible genetic associations. We performed a genomewide association study in a discovery set of samples obtained from 43,568 women of European ancestry using gestational duration as a continuous trait and term or preterm (< 37 weeks) birth as a dichotomous outcome. We used samples from three Nordic data sets (involving a total of 8643 women) to test for replication of genomic loci that had significant genomewide association (P< 5.0x10(-8)) or an association with suggestive significance (P< 1.0x10(-6)) in the discovery set. In the discovery and replication data sets, four loci (EBF1, EEFSEC, AGTR2, and WNT4) were significantly associated with gestational duration. Functional analysis showed that an implicated variant in WNT4 alters the binding of the estrogen receptor. The association between variants in ADCY5 and RAP2C and gestational duration had suggestive significance in the discovery set and significant evidence of association in the replication sets; these variants also showed genomewide significance in a joint analysis. Common variants in EBF1, EEFSEC, and AGTR2 showed association with preterm birth with genomewide significance. An analysis of mother-infant dyads suggested that these variants act at the level of the maternal genome. In this genomewide association study, we found that variants at the EBF1, EEFSEC, AGTR2, WNT4, ADCY5, and RAP2C loci were associated with gestational duration and variants at the EBF1, EEFSEC, and AGTR2 loci with preterm birth. Previously established roles of these genes in uterine development, maternal nutrition, and vascular control support their mechanistic involvement.
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  • Solé Navais, Pol, et al. (författare)
  • Genetic effects on the timing of parturition and links to fetal birth weight.
  • 2023
  • Ingår i: Nature genetics. - 1546-1718. ; 55:4, s. 559-567
  • Tidskriftsartikel (refereegranskat)abstract
    • The timing of parturition is crucial for neonatal survival and infant health. Yet, its genetic basis remains largely unresolved. We present a maternal genome-wide meta-analysis of gestational duration (n=195,555), identifying 22 associated loci (24 independent variants) and an enrichment in genes differentially expressed during labor. A meta-analysis of preterm delivery (18,797 cases, 260,246 controls) revealed six associated loci and large genetic similarities with gestational duration. Analysis of the parental transmitted and nontransmitted alleles (n=136,833) shows that 15 of the gestational duration genetic variants act through the maternal genome, whereas 7 act both through the maternal and fetal genomes and 2 act only via the fetal genome. Finally, the maternal effects on gestational duration show signs of antagonistic pleiotropy with the fetal effects on birth weight: maternal alleles that increase gestational duration have negative fetal effects on birth weight. The present study provides insights into the genetic effects on the timing of parturition and the complex maternal-fetal relationship between gestational duration and birth weight.
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  • Chen, Jing, et al. (författare)
  • Dissecting maternal and fetal genetic effects underlying the associations between maternal phenotypes, birth outcomes, and adult phenotypes: A mendelian-randomization and haplotype-based genetic score analysis in 10,734 mother-infant pairs.
  • 2020
  • Ingår i: PLoS medicine. - : Public Library of Science (PLoS). - 1549-1676. ; 17:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Many maternal traits are associated with a neonate's gestational duration, birth weight, and birth length. These birth outcomes are subsequently associated with late-onset health conditions. The causal mechanisms and the relative contributions of maternal and fetal genetic effects behind these observed associations are unresolved.Based on 10,734 mother-infant duos of European ancestry from the UK, Northern Europe, Australia, and North America, we constructed haplotype genetic scores using single-nucleotide polymorphisms (SNPs) known to be associated with adult height, body mass index (BMI), blood pressure (BP), fasting plasma glucose (FPG), and type 2 diabetes (T2D). Using these scores as genetic instruments, we estimated the maternal and fetal genetic effects underlying the observed associations between maternal phenotypes and pregnancy outcomes. We also used infant-specific birth weight genetic scores as instrument and examined the effects of fetal growth on pregnancy outcomes, maternal BP, and glucose levels during pregnancy. The maternal nontransmitted haplotype score for height was significantly associated with gestational duration (p = 2.2 × 10-4). Both maternal and paternal transmitted height haplotype scores were highly significantly associated with birth weight and length (p < 1 × 10-17). The maternal transmitted BMI scores were associated with birth weight with a significant maternal effect (p = 1.6 × 10-4). Both maternal and paternal transmitted BP scores were negatively associated with birth weight with a significant fetal effect (p = 9.4 × 10-3), whereas BP alleles were significantly associated with gestational duration and preterm birth through maternal effects (p = 3.3 × 10-2 and p = 4.5 × 10-3, respectively). The nontransmitted haplotype score for FPG was strongly associated with birth weight (p = 4.7 × 10-6); however, the glucose-increasing alleles in the fetus were associated with reduced birth weight through a fetal effect (p = 2.2 × 10-3). The haplotype scores for T2D were associated with birth weight in a similar way but with a weaker maternal effect (p = 6.4 × 10-3) and a stronger fetal effect (p = 1.3 × 10-5). The paternal transmitted birth weight score was significantly associated with reduced gestational duration (p = 1.8 × 10-4) and increased maternal systolic BP during pregnancy (p = 2.2 × 10-2). The major limitations of the study include missing and heterogenous phenotype data in some data sets and different instrumental strength of genetic scores for different phenotypic traits.We found that both maternal height and fetal growth are important factors in shaping the duration of gestation: genetically elevated maternal height is associated with longer gestational duration, whereas alleles that increase fetal growth are associated with shorter gestational duration. Fetal growth is influenced by both maternal and fetal effects and can reciprocally influence maternal phenotypes: taller maternal stature, higher maternal BMI, and higher maternal blood glucose are associated with larger birth size through maternal effects; in the fetus, the height- and metabolic-risk-increasing alleles are associated with increased and decreased birth size, respectively; alleles raising birth weight in the fetus are associated with shorter gestational duration and higher maternal BP. These maternal and fetal genetic effects may explain the observed associations between the studied maternal phenotypes and birth outcomes, as well as the life-course associations between these birth outcomes and adult phenotypes.
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  • Coenen, Pieter, et al. (författare)
  • Differences in heart rate reserve of similar physical activities during work and in leisure time - A study among Danish blue-collar workers
  • 2018
  • Ingår i: Physiology and Behavior. - : Elsevier BV. - 0031-9384 .- 1873-507X. ; 185, s. 45-51
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent studies suggest that while leisure-time physical activity (LTPA) promotes general health, engaging in occupational physical activity (OPA) may have negative health consequences. It has been hypothesized that the different health effects from OPA and LTPA can be explained by differences in physical activity (PA) intensity in these two domains. To assess the intensity of OPA and LTPA, we aimed to study the percentage heart rate reserve (%HRR) during similar types of OPA and LTPA during workdays. Data from the NOMAD study on Danish blue-collar workers (n=124) with objective measurements of PA (using accelerometers) and heart rate (using heart rate monitors) for 4 workdays were analysed. Activities of sitting, standing, moving, walking, and stair climbing were identified and %HRR in each of these activities was determined for work and leisure. %HRR was significantly higher during OPA than LTPA. These differences were more pronounced in men than in women. Although not statistically significant in the fully adjusted model, we found indications that these differences were more pronounced in those with low compared to high fitness. To our knowledge, this is the first study with objective measurements showing that %HRR is higher during the same gross-body postural activities when performed at work compared to leisure-time during workdays. This elevated intensity may help explaining the negative health consequences of engagement in high levels of OPA. Future guidelines should distinguish OPA from LTPA, possibly by advising workers to remain active during their leisure time, in particular when they are highly active at work.
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  • Hallman, David M., et al. (författare)
  • Effects of Heart Rate Variability Biofeedback in Subjects with Stress-Related Chronic Neck Pain : A Pilot Study
  • 2011
  • Ingår i: Applied Psychophysiology and Biofeedback. - : Springer Science and Business Media LLC. - 1090-0586 .- 1573-3270. ; 36:2, s. 71-80
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent studies focusing on autonomic nervous system (ANS) dysfunctions, together with theoretical pathophysiological models of musculoskeletal disorders, indicate the involvement of ANS regulation in development and maintenance of chronic muscle pain. Research has demonstrated the effectiveness of heart rate variability (HRV) biofeedback (BF) in increasing HRV and reducing the symptoms of different disorders characterized by ANS aberration. The study investigated the effects of resonance frequency HRV BF on autonomic regulation and perceived health, pain, stress and disability in 24 subjects with stress-related chronic neck-shoulder pain. Twelve subjects participated in 10 weekly sessions of resonant HRV BF and were compared to a control group. Subjective reports and HRV measures during relaxation and in response to a standardized stress protocol were assessed for both groups pre- and post-intervention. Group × time interactions revealed a significantly stronger increase over time in perceived health (SF-36) for the treatment group, including vitality, bodily pain and social functioning. Interactions were also seen for HRV during relaxation and reactivity to stress. The present pilot study indicates improvement in perceived health over a 10 week intervention with HRV-biofeedback in subjects with chronic neck-pain. Increased resting HRV as well as enhanced reactivity to hand grip and cold pressor tests might reflect beneficial effects on ANS regulation, and suggest that this intervention protocol is suitable for a larger controlled trial.
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  • Huusko, Johanna M, et al. (författare)
  • Integrative genetic, genomic and transcriptomic analysis of heat shock protein and nuclear hormone receptor gene associations with spontaneous preterm birth.
  • 2021
  • Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Heat shock proteins are involved in the response to stress including activation of the immune response. Elevated circulating heat shock proteins are associated with spontaneous preterm birth (SPTB). Intracellular heat shock proteins act as multifunctional molecular chaperones that regulate activity of nuclear hormone receptors. Since SPTB has a significant genetic predisposition, our objective was to identify genetic and transcriptomic evidence of heat shock proteins and nuclear hormone receptors that may affect risk for SPTB. We investigated all 97 genes encoding members of the heat shock protein families and all 49 genes encoding nuclear hormone receptors for their potential role in SPTB susceptibility. We used multiple genetic and genomic datasets including genome-wide association studies (GWASs), whole-exome sequencing (WES), and placental transcriptomics to identify SPTB predisposing factors from the mother, infant, and placenta. There were multiple associations of heat shock protein and nuclear hormone receptor genes with SPTB. Several orthogonal datasets supported roles for SEC63, HSPA1L, SACS, RORA, and AR in susceptibility to SPTB. We propose that suppression of specific heat shock proteins promotes maintenance of pregnancy, whereas activation of specific heat shock protein mediated signaling may disturb maternal-fetal tolerance and promote labor.
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  • Huusko, Johanna M, et al. (författare)
  • Whole exome sequencing reveals HSPA1L as a genetic risk factor for spontaneous preterm birth.
  • 2018
  • Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 14:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Preterm birth is a leading cause of morbidity and mortality in infants. Genetic and environmental factors play a role in the susceptibility to preterm birth, but despite many investigations, the genetic basis for preterm birth remain largely unknown. Our objective was to identify rare, possibly damaging, nucleotide variants in mothers from families with recurrent spontaneous preterm births (SPTB). DNA samples from 17 Finnish mothers who delivered at least one infant preterm were subjected to whole exome sequencing. All mothers were of northern Finnish origin and were from seven multiplex families. Additional replication samples of European origin consisted of 93 Danish sister pairs (and two sister triads), all with a history of a preterm delivery. Rare exonic variants (frequency <1%) were analyzed to identify genes and pathways likely to affect SPTB susceptibility. We identified rare, possibly damaging, variants in genes that were common to multiple affected individuals. The glucocorticoid receptor signaling pathway was the most significant (p<1.7e-8) with genes containing these variants in a subgroup of ten Finnish mothers, each having had 2-4 SPTBs. This pathway was replicated among the Danish sister pairs. A gene in this pathway, heat shock protein family A (Hsp70) member 1 like (HSPA1L), contains two likely damaging missense alleles that were found in four different Finnish families. One of the variants (rs34620296) had a higher frequency in cases compared to controls (0.0025 vs. 0.0010, p = 0.002) in a large preterm birth genome-wide association study (GWAS) consisting of mothers of general European ancestry. Sister pairs in replication samples also shared rare, likely damaging HSPA1L variants. Furthermore, in silico analysis predicted an additional phosphorylation site generated by rs34620296 that could potentially affect chaperone activity or HSPA1L protein stability. Finally, in vitro functional experiment showed a link between HSPA1L activity and decidualization. In conclusion, rare, likely damaging, variants in HSPA1L were observed in multiple families with recurrent SPTB.
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  • Moberg, C, et al. (författare)
  • Selectivity and reactivity in asymmetric allylic alkylation
  • 1999
  • Ingår i: Pure and Applied Chemistry. - Royal Inst Technol, Dept Chem, SE-10044 Stockholm, Sweden. Royal Danish Sch Pharm, DK-2100 Copenhagen, Denmark. Uppsala Univ, Ctr Biomed, Dept Organ Pharmaceut Chem, SE-75123 Uppsala, Sweden. Stockholm Univ, Arrhenius Lab, Dept Struct Chem, SE-10691 Stockholm, Sweden. : Walter de Gruyter GmbH. - 0033-4545 .- 1365-3075. ; 71:8, s. 1477-1483
  • Tidskriftsartikel (refereegranskat)abstract
    • 2-(1-Hydroxyalkyl)-6-oxazolyl-and 2-(1-alkoxyalkyl)-6-oxazolylpyridines serve as versatile ligands in the palladium-catalyzed allylic substitution of rac-1,3-diphenyl-2-propenyl acetate with dimethyl malonate as nucleophile. The enantioselectivity of the reaction is dependent on the conformation of the ligands, as deduced by NMR, X-ray crystallography and DFT calculations of palladium(II) complexes of the ligands. The reactions are slow, requiring up to four days reaction time. However, with the use of microwave flash heating, reaction times are reduced to 2 min, with only minor loss in stereoselectivity.
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  • Tsao, K., et al. (författare)
  • Effects of regional differences and demography in modelling foot-and-mouth disease in cattle at the national scale
  • 2020
  • Ingår i: Interface Focus. - : Royal Society Publishing. - 2042-8898 .- 2042-8901. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Foot-and-mouth disease (FMD) is a fast-spreading viral infection that can produce large and costly outbreaks in livestock populations. Transmission occurs at multiple spatial scales, as can the actions used to control outbreaks. The US cattle industry is spatially expansive, with heterogeneous distributions of animals and infrastructure. We have developed a model that incorporates the effects of scale for both disease transmission and control actions, applied here in simulating FMD outbreaks in US cattle. We simulated infection initiating in each of the 3049 counties in the contiguous US, 100 times per county. When initial infection was located in specific regions, large outbreaks were more likely to occur, driven by infrastructure and other demographic attributes such as premises clustering and number of cattle on premises. Sensitivity analyses suggest these attributes had more impact on outbreak metrics than the ranges of estimated disease parameter values. Additionally, although shipping accounted for a small percentage of overall transmission, areas receiving the most animal shipments tended to have other attributes that increase the probability of large outbreaks. The importance of including spatial and demographic heterogeneity in modelling outbreak trajectories and control actions is illustrated by specific regions consistently producing larger outbreaks than others. © 2019 The Author(s) Published by the Royal Society. All rights reserved.
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  • Aludden, H. C., et al. (författare)
  • Lateral ridge augmentation with Bio-Oss alone or Bio-Oss mixed with particulate autogenous bone graft: a systematic review
  • 2017
  • Ingår i: International Journal of Oral and Maxillofacial Surgery. - : Elsevier BV. - 0901-5027. ; 46:8, s. 1030-1038
  • Tidskriftsartikel (refereegranskat)abstract
    • The objective of this systematic review was to test the hypothesis of no difference in implant treatment outcomes when using Bio-Oss alone or Bio-Oss mixed with particulate autogenous bone grafts for lateral ridge augmentation. A search of the MEDLINE, Cochrane Library, and Embase databases in combination with a hand-search of relevant journals was conducted. Human studies published in English from 1 January 1990 to 1 May 2016 were included. The search provided 337 titles and six studies fulfilled the inclusion criteria. Considerable variation prevented a meta-analysis from being performed. The two treatment modalities have never been compared within the same study. Non-comparative studies demonstrated a 3-year implant survival of 96% with 50% Bio-Oss mixed with 50% autogenous bone graft. Moreover, Bio-Oss alone or Bio-Oss mixed with autogenous bone graft seems to increase the amount of newly formed bone as well as the width of the alveolar process. Within the limitations of this systematic review, lateral ridge augmentation with Bio-Oss alone or in combination with autogenous bone graft seems to induce newly formed bone and increase the width of the alveolar process, with high short-term implant survival. However, long-term studies comparing the two treatment modalities are needed before final conclusions can be drawn.
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  • Gilbertson, Kendra, et al. (författare)
  • The Importance of Livestock Demography and Infrastructure in Driving Foot and Mouth Disease Dynamics
  • 2022
  • Ingår i: Life. - : MDPI. - 2075-1729. ; 12:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Transboundary animal diseases, such as foot and mouth disease (FMD) pose a significant and ongoing threat to global food security. Such diseases can produce large, spatially complex outbreaks. Mathematical models are often used to understand the spatio-temporal dynamics and create response plans for possible disease introductions. Model assumptions regarding transmission behavior of premises and movement patterns of livestock directly impact our understanding of the ecological drivers of outbreaks and how to best control them. Here, we investigate the impact that these assumptions have on model predictions of FMD outbreaks in the U.S. using models of livestock shipment networks and disease spread. We explore the impact of changing assumptions about premises transmission behavior, both by including within-herd dynamics, and by accounting for premises type and increasing the accuracy of shipment predictions. We find that the impact these assumptions have on outbreak predictions is less than the impact of the underlying livestock demography, but that they are important for investigating some response objectives, such as the impact on trade. These results suggest that demography is a key ecological driver of outbreaks and is critical for making robust predictions but that understanding management objectives is also important when making choices about model assumptions.
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  • Hallman, David M., 1979-, et al. (författare)
  • Long-term monitoring of physical behavior reveals different cardiac responses to physical activity among subjects with and without chronic neck pain
  • 2015
  • Ingår i: BioMed Research International. - : Hindawi Limited. - 2314-6133 .- 2314-6141. ; 2015
  • Tidskriftsartikel (refereegranskat)abstract
    • Background We determined the extent to which heart rate variability (HRV) responses to daily physical activity differ between subjects with and without chronic neck pain. Method Twenty-nine subjects (13 women) with chronic neck pain and 27 age- and gender-matched healthy controls participated. Physical activity (accelerometry), HRV (heart rate monitor) and spatial location (Global Positioning System (GPS)) were recorded for 74 hours. GPS data were combined with a diary to identify periods of work, and of leisure at home and elsewhere. Time- and frequency-domain HRV indices were calculated, and stratified by period and activity type (lying/sitting, standing, or walking). ANCOVAs with multiple adjustments were used to disclose possible group differences in HRV. Results The pain group showed a reduced HRV response to physical activity compared with controls (p=.001), according to the sympathetic-baroreceptor HRV index (LF/HF, ratio between low and high frequency power), even after adjustment for leisure time physical activity, work stress, sleep quality, mental health, and aerobic capacity (p=.02). The parasympathetic response to physical activity did not differ between groups.Conclusions Relying on long-term monitoring of physical behavior and heart rate variability, we found an aberrant sympathetic-baroreceptor response to daily physical activity among subjects with chronic neck pain.
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  • Hallman, David M., et al. (författare)
  • Objectively measured physical activity and 12-month trajectories of neck-shoulder pain in workers : a prospective study in DPHACTO
  • 2017
  • Ingår i: Scandinavian Journal of Public Health. - : SAGE Publications. - 1403-4948 .- 1651-1905. ; 45:3, s. 288-298
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: This study aimed to investigate the association between objectively measured physical activity at work and leisure and the intensity (mean level and time course) of neck–shoulder pain (NSP) over 12 months among male and female blue collar workers. Methods: Data were obtained from 625 blue collar workers from the Danish cohort DPHACTO. Physical activity was measured objectively at baseline using accelerometers. The percentage of time spent in physical activity (walking, climbing stairs, running and cycling) was calculated for both work and leisure time. Longitudinal data on the intensity of NSP (numerical rating scale 0–10) were collected using text messages every fourth week over 12 months. Linear mixed models were used to investigate the associations between occupational physical activity (OPA) and leisure time physical activity (LTPA) and the trajectories of the intensity of NSP, adjusted for individual, biomechanical and psychosocial factors, and baseline pain. Results: OPA was not associated with the mean intensity of NSP over 12 months. LTPA was negatively associated with the mean intensity of NSP both among men (B=−0.71, 95% CI −1.31 to −0.11) and women (B=−0.85, 95% CI −1.57 to −0.13). Sex interactions on the 12-month trajectories of NSP showed that higher physical activity was associated with a slower reduction in NSP among men for OPA only (B=0.03, 95% CI 0.01-0.05) and women for LTPA only (B=0.05, 95% CI 0.00-0.09). Conclusions: We found that more time in LTPA was associated with a lower overall intensity of NSP over 12 months among blue collar workers. However, depending on sex and domain, high physical activity had an unfavourable effect on the course of NSP over 12 months.
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  • Hallman, David M., et al. (författare)
  • Temporal patterns of sitting at work are associated with neck-shoulder pain in blue-collar workers : a cross-sectional analysis of accelerometer data in the DPHACTO study
  • 2016
  • Ingår i: International Archives of Occupational and Environmental Health. - : Springer Science and Business Media LLC. - 0340-0131 .- 1432-1246. ; 89:5, s. 823-833
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundOur aim was to examine the extent to which temporal patterns of sitting during occupational work and during leisure-time, assessed using accelerometry, are associated with intense neck–shoulder pain (NSP) in blue-collar workers.MethodsThe population consisted of 659 Danish blue-collar workers. Accelerometers were attached to the thigh, hip, trunk and upper dominant arm to measure sitting time and physical activity across four consecutive days. Temporal sitting patterns were expressed separately for work and leisure by the proportion of total time spent sitting in brief bursts (0–5 min), moderate (>5–20 min) and prolonged (>20 min) periods. The peak NSP intensity during the previous 3 months was assessed using a numerical rating scale (range 0–10) and dichotomized into a lower (≤4) and higher (>4) NSP score. Logistic regression analyses with multiple adjustments for individual and occupational factors were performed to determine the association between brief, moderate and prolonged sitting periods, and NSP intensity.ResultsTime in brief bursts of occupational sitting was negatively associated with NSP intensity (adjusted OR 0.68, 95 % CI 0.48–0.98), while time in moderate periods of occupational sitting showed a positive association with NSP (adjusted OR 1.32, 95 % CI 1.04–1.69). Time in prolonged periods of occupational sitting was not associated with NSP (adjusted OR 0.78, 95 % CI 0.78–1.09). We found no significant association between brief, moderate or prolonged sitting periods during leisure, and NSP.ConclusionOur findings indicate that the association between occupational sitting time and intense NSP among blue-collar workers is sensitive to the temporal pattern of sitting.
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  • Hallman, David M., et al. (författare)
  • Time course of neck-shoulder pain among workers : A longitudinal latent class growth analysis.
  • 2018
  • Ingår i: Scandinavian Journal of Work, Environment and Health. - : Scandinavian Journal of Work, Environment and Health. - 0355-3140 .- 1795-990X. ; 44:1, s. 47-57
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectivesThe aims of this study were to (i) identify trajectories of neck-shoulder pain (NSP) over one year in an occupational population and (ii) determine whether these trajectories are predicted by NSP characteristics as well as personal and occupational factors at baseline.MethodsThis longitudinal study was conducted among Danish workers (N=748) from 2012-2014. Text messages were used to collect frequent data on NSP over one year (14 waves in total). Peak NSP intensity in the past month was rated on a 0-10 numeric scale. A baseline questionnaire covered NSP characteristics (pain intensity, duration, comorbidity, pain medication, and pain interference) as well as personal (age, gender, body mass index) and occupational (seniority, work type, physical strain at work) factors. Latent class growth analysis was used to distinguish trajectories of NSP. Multivariate regression models with odds ratios (OR) were constructed to predict trajectories of NSP.ResultsSix distinct trajectories of NSP were identified (asymptomatic 11%, very low NSP 10%, low recovering NSP 18%, moderate recovering NSP 28%, strong fluctuating NSP 24% and severe persistent NSP 9% of the workers). Female gender, age, physical strain at work, NSP intensity and duration, pain medication, and pain interference in daily work at baseline were positively associated with severe persistent NSP and strong fluctuating NSP (all P<0.05). Altogether, personal and occupational factors accounted for 14% of the variance, while NSP characteristics accounted for 54%.ConclusionsIn an occupational sample, six distinct trajectories of NSP were identified. Physical strain at work appears to be a pertinent occupational factor predicting strong fluctuating and severe persistent NSP.
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  • Hallman, M, et al. (författare)
  • Histologic analysis of clinical biopsies taken 6 months and 3 years after maxillary sinus floor augmentation with 80% bovine hydroxyapatite and 20% autogenous bone mixed with fibrin glue.
  • 2001
  • Ingår i: Clinical Implant Dentistry and Related Research. - 1523-0899 .- 1708-8208. ; 3:2, s. 87-96
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Bovine hydroxyapatite (Bio-Oss, Geistlich Pharmaceutical, Wollhausen, Switzerland) has been suggested to be used in maxillary sinus floor augmentation procedures prior to or in conjunction with implant placement. However, the long-term histologic fate of this material is not well understood. PURPOSE: The aim with this study was to histologically evaluate the tissue response in patients to a mixture of bovine hydroxyapatite (BH), autogenous bone, and fibrin glue 6 months and 3 years after a maxillary sinus floor augmentation procedure. MATERIALS AND METHOD: Biopsies were taken from a group of 20 consecutive patients 6 months (n = 16) and 3 years (n = 12) after maxillary sinus floor augmentation with a mixture of BH (80%), autogenous bone (20%), and fibrin glue and prepared for histologic analysis. RESULTS: Light microscopy and morphometry from biopsies taken after 6 months showed various amounts of mineralized bone tissue. The specimen area was occupied by 54.1 +/- 12.6% nonmineralized tissue, followed by 21.2 +/- 24.5% lamellar bone, 14.5 +/- 10.3% BH particles, and 10.2 +/- 13.4% woven bone. The nonmineralized tissue seen in bone-forming areas consisted of a loose connective tissue, rich with vessels and cells. There were no signs of resorption of the BH particles. The lamellar bone appeared to have originated from the recipient site and was seldom in contact with the BH particles. After 3 years, the nonmineralized tissue area had decreased to 36.0 +/- 19.0% (p < .05) and consisted mainly of bone marrow tissue. The surface area of lamellar bone had increased to 50.7 +/- 22.8% (p < .05), and there was almost no immature bone. The mean specimen area occupied by BH particles, was 12.4 +/- 8.7% and had not changed from 6 months (not significant). Moreover, the sizes of the particles were similar after 6 months and 3 years. The degree of BH particle-bone contact had increased from 28.8% +/- 19.9% after 6 months to 54.5 +/- 28.8% after 3 years (p < .05). CONCLUSION: Histology of specimens from maxillary sinuses augmented with 80% BH particles, 20% autogenous bone, and fibrin glue showed a positive bone tissue response after 6 months and 3 years after augmentation of the maxillary sinus floor prior to implant placement in a group fo 20 patients. The bone surrounding and in contact with the BH particles after 6 months was mainly immature woven bone, which with time was replaced by mature lamellar bone filling the interparticle space as observed in the 3-year specimens. Moreover, bone-integrated BH particles seem to be resistant to resorption. The results indicate that the procedure may be considered when only small amounts of intraoral autogenous bone graft are available.
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  • Hiltunen, Anniina E., et al. (författare)
  • Variant in NHLRC2 leads to increased hnRNP C2 in developing neurons and the hippocampus of a mouse model of FINCA disease
  • 2020
  • Ingår i: Molecular Medicine. - : SPRINGER. - 1076-1551 .- 1528-3658. ; 26:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundFINCA disease is a pediatric cerebropulmonary disease caused by variants in the NHL repeat-containing 2 (NHLRC2) gene. Neurological symptoms are among the first manifestations of FINCA disease, but the consequences of NHLRC2 deficiency in the central nervous system are currently unexplored.MethodsThe orthologous mouse gene is essential for development, and its complete loss leads to early embryonic lethality. In the current study, we used CRISPR/Cas9 to generate an Nhlrc2 knockin (KI) mouse line, harboring the FINCA patient missense mutation (c.442G>T, p.Asp148Tyr). A FINCA mouse model, resembling the compound heterozygote genotype of FINCA patients, was obtained by crossing the KI and Nhlrc2 knockout mouse lines. To reveal NHLRC2-interacting proteins in developing neurons, we compared cortical neuronal precursor cells of E13.5 FINCA and wild-type mouse embryos by two-dimensional difference gel electrophoresis.ResultsDespite the significant decrease in NHLRC2, the mice did not develop severe early onset multiorgan disease in either sex. We discovered 19 altered proteins in FINCA neuronal precursor cells; several of which are involved in vesicular transport pathways and actin dynamics which have been previously reported in other cell types including human to have an association with dysfunctional NHLRC2. Interestingly, isoform C2 of hnRNP C1/C2 was significantly increased in both developing neurons and the hippocampus of adult female FINCA mice, connecting NHLRC2 dysfunction with accumulation of RNA binding protein.ConclusionsWe describe here the first NHLRC2-deficient mouse model to overcome embryonic lethality, enabling further studies on predisposing and causative mechanisms behind FINCA disease. Our novel findings suggest that disrupted RNA metabolism may contribute to the neurodegeneration observed in FINCA patients.
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38.
  • Kleberg, Johan L., et al. (författare)
  • No transfer of arousal from other’s eyes in Williams syndrome
  • 2023
  • Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Typically developing humans automatically synchronize their arousal levels, resulting in pupillary contagion, or spontaneous adaptation of pupil size to that of others. This phenomenon emerges in infancy and is believed to facilitate social interaction. Williams syndrome (WS) is a genetic condition characterized by a hyper-social personality and social interaction challenges. Pupillary contagion was examined in individuals with WS (n = 44), age-parallel-matched typically developing children and adults (n = 65), and infants (n = 79). Bayesian statistics were used. As a group, people with WS did not show pupillary contagion (Bayes factors supporting the null: 25–50) whereas control groups did. This suggests a very early emerging atypical developmental trajectory. In WS, higher pupillary contagion was associated with lower autistic symptoms of social communication. Diminished synchronization of arousal may explain why individuals with WS have social challenges, whereas synchronization of arousal is not a necessary correlate of high social motivation.
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44.
  • Pasanen, Anu, et al. (författare)
  • Meta-analysis of genome-wide association studies of gestational duration and spontaneous preterm birth identifies new maternal risk loci.
  • 2023
  • Ingår i: PLoS genetics. - 1553-7404. ; 19:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Preterm birth (<37 weeks of gestation) is a major cause of neonatal death and morbidity. Up to 40% of the variation in timing of birth results from genetic factors, mostly due to the maternal genome.We conducted a genome-wide meta-analysis of gestational duration and spontaneous preterm birth in 68,732 and 98,370 European mothers, respectively.The meta-analysis detected 15 loci associated with gestational duration, and four loci associated with preterm birth. Seven of the associated loci were novel. The loci mapped to several biologically plausible genes, for example HAND2 whose expression was previously shown to decrease during gestation, associated with gestational duration, and GC (Vitamin D-binding protein), associated with preterm birth. Downstream in silico-analysis suggested regulatory roles as underlying mechanisms for the associated loci. LD score regression found birth weight measures as the most strongly correlated traits, highlighting the unique nature of spontaneous preterm birth phenotype. Tissue expression and colocalization analysis revealed reproductive tissues and immune cell types as the most relevant sites of action.We report novel genetic risk loci that associate with preterm birth or gestational duration, and reproduce findings from previous genome-wide association studies. Altogether, our findings provide new insight into the genetic background of preterm birth. Better characterization of the causal genetic mechanisms will be important to public health as it could suggest new strategies to treat and prevent preterm birth.
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45.
  • Sellman, Stefan, et al. (författare)
  • Modeling nation-wide US swine movement networks at the resolution of the individual premises
  • 2022
  • Ingår i: Epidemics. - : Elsevier. - 1755-4365 .- 1878-0067. ; 41
  • Tidskriftsartikel (refereegranskat)abstract
    • The spread of infectious livestock diseases is a major cause for concern in modern agricultural systems. In the dynamics of the transmission of such diseases, movements of livestock between herds play an important role. When constructing mathematical models used for activities such as forecasting epidemic development, evaluating mitigation strategies, or determining important targets for disease surveillance, including between -premises shipments is often a necessity. In the United States (U.S.), livestock shipment data is not routinely collected, and when it is, it is not readily available and mostly concerned with between-state shipments. To bridge this gap in knowledge and provide insight into the complete livestock shipment network structure, we have developed the U.S. Animal Movement Model (USAMM). Previously, USAMM has only existed for cattle shipments, but here we present a version for domestic swine. This new version of USAMM consists of a Bayesian model fit to premises demography, county-level livestock industry variables, and two limited data sets of between-state swine movements. The model scales up the data to simulate nation-wide networks of both within-and between-state shipments at the level of individual premises. Here we describe this shipment model in detail and subsequently explore its usefulness with a rudimentary predictive model of the prevalence of porcine epidemic diarrhea virus (PEDv) across the U.S. Additionally, in order to promote further research on livestock disease and other topics involving the movements of swine in the U.S., we also make 250 synthetic premises-level swine shipment networks with complete coverage of the entire conterminous U.S. freely available to the research community as a useful surrogate for the absent shipment data.
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46.
  • Sellman, Stefan, et al. (författare)
  • Modeling US cattle movements until the cows come home: Who ships to whom and how many?
  • 2022
  • Ingår i: Computers and Electronics in Agriculture. - : ELSEVIER SCI LTD. - 0168-1699 .- 1872-7107. ; 203
  • Tidskriftsartikel (refereegranskat)abstract
    • Livestock movements between agricultural premises is an important pathway for the spread of infectious disease. Data providing details about the origin and destination of shipments, as well as information about the shipment size is an important component of computer models used to formulate mitigation strategies and design surveillance programs. The United States (U.S.) currently lacks a comprehensive database of farm animal shipments, which hinders such efforts. With the U.S. Animal Movement Model (USAMM), earlier work has successfully scaled up from limited data based on interstate certificates of veterinary inspection (CVI) to comprehensive county-level shipment networks at the national scale. In this work, we present three major improvements to earlier versions of USAMM: (1) increased resolution of the model and simulated networks to the level of individual premises; (2) predictions of shipment sizes; (3) taking into account the types and herd sizes of the premises. We fitted parameters in a Bayesian framework to two sets of CVI data consisting of sub-samples of one years between-state beef and dairy shipments. Through posterior predictive simulation, we then created 1,000 synthetic beef and dairy networks, which we make publicly available to support livestock disease modeling. The simulated networks were validated against summary statistics of the training data as well as out-of-sample CVI data from subsequent years. This new development opens up the possibility of using USAMM in a broader spectrum of applications where information about shipment size and premises identity is necessary and gives novel insights into the U.S. cattle shipment network.
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47.
  • Srinivasan, Divya, et al. (författare)
  • Effects of concurrent physical and cognitive demands on muscle activity and heart rate variability in a repetitive upper-extremity precision task
  • 2016
  • Ingår i: European Journal of Applied Physiology. - : Springer. - 1439-6319 .- 1439-6327. ; 116:1, s. 227-239
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose Most previous studies of concurrent physical and cognitive demands have addressed tasks of limited relevance to occupational work, and with dissociated physical and cognitive task components. This study investigated effects on muscle activity and heart rate variability of executing a repetitive occupational task with an added cognitive demand integral to correct task performance.Methods Thirty-five healthy females performed 7.5 min of standardized repetitive pipetting work in a baseline condition and a concurrent cognitive condition involving a complex instruction for correct performance. Average levels and variabilities of electromyographic activities in the upper trapezius and extensor carpi radialis (ECR) muscles were compared between these two conditions. Heart rate and heart rate variability were also assessed to measure autonomic nervous system activation. Subjects also rated perceived fatigue in the neck–shoulder region, as well as exertion.Results Concurrent cognitive demands increased trapezius muscle activity from 8.2 % of maximum voluntary exertion (MVE) in baseline to 9.0 % MVE (p = 0.0005), but did not significantly affect ECR muscle activity, heart rate, heart rate variability, perceived fatigue or exertion.Conclusion Trapezius muscle activity increased by about 10 %, without any accompanying cardiovascular response to indicate increased sympathetic activation. We suggest this slight increase in trapezius muscle activity to be due to changed muscle activation patterns within or among shoulder muscles. The results suggest that it may be possible to introduce modest cognitive demands necessary for correct performance in repetitive precision work without any major physiological effects, at least in the short term.
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50.
  • Wijk, Katarina, et al. (författare)
  • Sense of Coherence, Health, Well-Being, and Work Satisfaction before and after Implementing Activity-Based Workplaces
  • 2020
  • Ingår i: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 17:14
  • Tidskriftsartikel (refereegranskat)abstract
    • Activity-based workplaces (ABWs) are implemented with possible implications for health, well-being, and work satisfaction in the workplace. Drawing on the theoretical framework, i.e., sense of coherence (SOC), the aim was to investigate how indicators pf SOC-meaningfulness, manageability and comprehensibility-are associated with, or function as barriers or facilitators for, health, well-being and work satisfaction during relocation to an ABW. We followed the implementation of ABWs at the Swedish Transport Administration (2018-2019). Questionnaires were administered before (n= 536), 3 months (n= 409) and 9 months (n= 373) after relocation. Focus group interviews (15) were conducted before and after. Data were analyzed using repeated measures ANOVA and content analysis. Relocation to an ABW was associated with a reduced work satisfaction (physicalp< 0.001; psychosocialp< 0.001), and minor changes in health and occupational well-being during relocation (p> 0.001). The reduction in work satisfaction was smaller among employees with high meaningfulness in the relocation process (p< 0.001). All SOC indicators were positively associated with overall health, well-being and work satisfaction (p< 0.001). Interviews suggested that meaningfulness was facilitated by participation in the presented activities and that communication before relocation was crucial. The results indicate that organizations implementing ABWs should promote perceived meaningfulness in the process to mitigate possible declines in satisfaction with the physical and psychosocial work environment.
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