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  • Hirvonen, Outi M; Leskelä, Riikka-Leena; Grönholm, Lotta; Haltia, Olli; Voltti, Samuli; Tyynelä-Korhonen, Kristiina; Rahko, Eeva K; Lehto, Juho T; Saarto, Tiina (BioMed Central, 2020)
    Abstract Background In order to avoid unnecessary use of hospital services at the end-of-life, palliative care should be initiated early enough in order to have sufficient time to initiate and carry out good quality advance care planning (ACP). This single center study assesses the impact of the PC decision and its timing on the use of hospital services at EOL and the place of death. Methods A randomly chosen cohort of 992 cancer patients treated in a tertiary hospital between Jan 2013 –Dec 2014, who were deceased by the end of 2014, were selected from the total number of 2737 identified from the hospital database. The PC decision (the decision to terminate life-prolonging anticancer treatments and focus on symptom centered palliative care) and use of PC unit services were studied in relation to emergency department (ED) visits, hospital inpatient days and place of death. Results A PC decision was defined for 82% of the patients and 37% visited a PC unit. The earlier the PC decision was made, the more often patients had an appointment at the PC unit (> 180 days prior to death 72% and < 14 days 10%). The number of ED visits and inpatient days were highest for patients with no PC decision and lowest for patients with both a PC decision and an PC unit appointment (60 days before death ED visits 1.3 vs 0.8 and inpatient days 9.9 vs 2.9 respectively, p < 0.01). Patients with no PC decision died more often in secondary/tertiary hospitals (28% vs. 19% with a PC decision, and 6% with a decision and an appointment to a PC unit). Conclusions The PC decision to initiate a palliative goal for the treatment had a distinct impact on the use of hospital services at the EOL. Contact with a PC unit further increased the likelihood of EOL care at primary care.
  • Tuomisto, Jouni T; Asikainen, Arja; Meriläinen, Päivi; Haapasaari, Päivi (BioMed Central, 2020)
    It was highlighted that the original article [1] contained a formatting error in the equations.
  • Lal, Dennis; May, Patrick; Perez-Palma, Eduardo; Samocha, Kaitlin E; Kosmicki, Jack A; Robinson, Elise B; Møller, Rikke S; Krause, Roland; Nürnberg, Peter; Weckhuysen, Sarah; De Jonghe, Peter; Guerrini, Renzo; Niestroj, Lisa M; Du, Juliana; Marini, Carla; Ware, James S; Kurki, Mitja; Gormley, Padhraig; Tang, Sha; Wu, Sitao; Biskup, Saskia; Poduri, Annapurna; Neubauer, Bernd A; Koeleman, Bobby P C; Helbig, Katherine L; Weber, Yvonne G; Helbig, Ingo; Majithia, Amit R; Palotie, Aarno; Daly, Mark J (BioMed Central, 2020)
    Abstract Background Classifying pathogenicity of missense variants represents a major challenge in clinical practice during the diagnoses of rare and genetic heterogeneous neurodevelopmental disorders (NDDs). While orthologous gene conservation is commonly employed in variant annotation, approximately 80% of known disease-associated genes belong to gene families. The use of gene family information for disease gene discovery and variant interpretation has not yet been investigated on a genome-wide scale. We empirically evaluate whether paralog-conserved or non-conserved sites in human gene families are important in NDDs. Methods Gene family information was collected from Ensembl. Paralog-conserved sites were defined based on paralog sequence alignments; 10,068 NDD patients and 2078 controls were statistically evaluated for de novo variant burden in gene families. Results We demonstrate that disease-associated missense variants are enriched at paralog-conserved sites across all disease groups and inheritance models tested. We developed a gene family de novo enrichment framework that identified 43 exome-wide enriched gene families including 98 de novo variant carrying genes in NDD patients of which 28 represent novel candidate genes for NDD which are brain expressed and under evolutionary constraint. Conclusion This study represents the first method to incorporate gene family information into a statistical framework to interpret variant data for NDDs and to discover new NDD-associated genes.
  • Husu, Henrik L; Kuronen, Jouni A; Leppäniemi, Ari K; Mentula, Panu J (BioMed Central, 2020)
    Abstract Background Multiple organ failure and early surgery are associated with high morbimortality after open necrosectomy. Data are mostly derived from historical cohorts with early necrosectomy bereft of step-up treatment algorithm implementation. Thus, mostly circumstantial evidence suggests a better clinical course following mini-invasive surgical and endoscopic necrosectomy. We studied the results of open necrosectomy in a contemporary cohort of patients with complicated pancreatic necrosis treated at a tertiary center. Methods A retrospective cohort study from a university teaching hospital. Results of 109 consecutive patients treated with open necrosectomy during a 12-year period are reported. Results The overall 90-day mortality rate was 22.9%. The 90-day mortality rate was 10.6% if necrosectomy could be delayed until 4 weeks from symptom onset and the necrosis had become walled off on preoperative imaging. The risk factors for 90-day mortality were age over 60 years (OR 19.4), pre-existing co-morbidities (OR 16.9), necrosectomy within 4 weeks (OR 6.5), multiple organ failure (OR 12.2), white blood cell count over 23 × 109 (OR 21.4), and deterioration or prolonged organ failure as an indication for necrosectomy (OR 10.4). None or one of these risk factors was present in 52 patients (47.7% of all patients), and these patients had no mortality. Conclusion Late open necrosectomy for walled-off necrosis has a low mortality risk. Open necrosectomy can be done without mortality in the absence of multiple risk factors for surgery.
  • Steene-Johannessen, Jostein; Hansen, Bjørge H; Dalene, Knut E; Kolle, Elin; Northstone, Kate; Møller, Niels C; Grøntved, Anders; Wedderkopp, Niels; Kriemler, Susi; Page, Angie S; Puder, Jardena J; Reilly, John J; Sardinha, Luis B; van Sluijs, Esther M F; Andersen, Lars B; van der Ploeg, Hidde; Ahrens, Wolfgang; Flexeder, Claudia; Standl, Marie; Shculz, Holger; Moreno, Luis A; De Henauw, Stefaan; Michels, Nathalie; Cardon, Greet; Ortega, Francisco B; Ruiz, Jonatan; Aznar, Susana; Fogelholm, Mikael; Decelis, Andrew; Olesen, Line G; Hjorth, Mads F; Santos, Rute; Vale, Susana; Christiansen, Lars B; Jago, Russ; Basterfield, Laura; Owen, Christopher G; Nightingale, Claire M; Eiben, Gabriele; Polito, Angela; Lauria, Fabio; Vanhelst, Jeremy; Hadjigeorgiou, Charalambos; Konstabel, Kenn; Molnár, Dénes; Sprengeler, Ole; Manios, Yannis; Harro, Jaanus; Kafatos, Anthony; Anderssen, Sigmund A; Ekelund, Ulf (BioMed Central, 2020)
    Abstract Background Levels of physical activity and variation in physical activity and sedentary time by place and person in European children and adolescents are largely unknown. The objective of the study was to assess the variations in objectively measured physical activity and sedentary time in children and adolescents across Europe. Methods Six databases were systematically searched to identify pan-European and national data sets on physical activity and sedentary time assessed by the same accelerometer in children (2 to 9.9 years) and adolescents (≥10 to 18 years). We harmonized individual-level data by reprocessing hip-worn raw accelerometer data files from 30 different studies conducted between 1997 and 2014, representing 47,497 individuals (2–18 years) from 18 different European countries. Results Overall, a maximum of 29% (95% CI: 25, 33) of children and 29% (95% CI: 25, 32) of adolescents were categorized as sufficiently physically active. We observed substantial country- and region-specific differences in physical activity and sedentary time, with lower physical activity levels and prevalence estimates in Southern European countries. Boys were more active and less sedentary in all age-categories. The onset of age-related lowering or leveling-off of physical activity and increase in sedentary time seems to become apparent at around 6 to 7 years of age. Conclusions Two third of European children and adolescents are not sufficiently active. Our findings suggest substantial gender-, country- and region-specific differences in physical activity. These results should encourage policymakers, governments, and local and national stakeholders to take action to facilitate an increase in the physical activity levels of young people across Europe.
  • Seikkula, Heikki; Boström, Peter J; Seppä, Karri; Pitkäniemi, Janne; Malila, Nea; Kaipia, Antti (BioMed Central, 2020)
    Abstract Background Androgen deprivation therapy (ADT) remains a primary treatment for localized prostate cancer (PCa) even though there is no evidence that its use is beneficial in the absence of curative treatment. Methods Men aged ≥70 years (n = 16,534) diagnosed with localized PCa from 1985 to 2014 and managed either with primary observation or ADT in the absence of curative treatment were included. The cases were identified from the population-based Finnish Cancer Registry. We estimated the standardized mortality ratios (SMR) for overall mortality by treatment group. We determined the relative risk (RR) of PCa-specific mortality (PCSM) and other-cause mortality between the two treatment groups. Survival was determined using the life table method. Two age groups (70–79 years and ≥ 80 years) and three calendar time cohorts (1985–1994, 1995–2004, and 2005–2014) were compared following adjustment of propensity score matching between the treatment groups with four covariates (age, year of diagnosis, educational level, and hospital district). Follow-up continued until death or until December 31, 2015. Results Patients in the observation group had lower overall SMRs than those in the ADT group in both age cohorts over the entire study period. PCSM was higher in men aged 70–79 years undergoing primary ADT compared to those managed by observation only (RR: 1.70, 95% confidence interval [CI]: 1.29–2.23 [1985–1994]; RR 1.55, 95% CI: 1.35–1.84 [1995–2004]; and RR 2.71, 95% CI: 2.08–3.53 [2005–2014]); p = 0.005 for periodic trend. A similar trend over time was also observed in men aged > 80 years; (p for age–period interaction = 0.237). Overall survival was also higher among men in their 70’s managed by observation compared to those undergoing ADT. Conclusions Primary ADT within four months period from diagnosis is not associated with improved long-term overall survival or decreased PCSM compared to primary conservative management for men with localized PCa. However, this observational study’s conclusions should be weighted with confounding factors related to cancer aggressiveness and comorbidities.
  • Wikström, Miia; Anttila, Heidi; Savinainen, Minna; Kouvonen, Anne; Joensuu, Matti (BioMed Central, 2020)
    Abstract Background The unemployed have lower work ability and poorer health than the employed. This situation deteriorates when unemployment continues. The long-term unemployed often have co-morbidities and face many other challenges. This increases the need for a multidimensional assessment of work ability and functioning in different service settings. In this study, we describe the development and analyse the content validity of the Abilitator, a self-report questionnaire on work ability and functioning for those in a weak labour market position. Methods The Abilitator was developed in 2014–2017. Its construct was assessed by members of academic expert panels (n = 30), practical expert panels of professionals (n = 700) and target group clients (n = 28). The structure and the content of the questionnaire was co-developed in 29 workshops and adjusted twice based on the expert panels’ feedback. The Abilitator was also implemented among target group clients (n = 3360) in different services and projects. During its development the Abilitator was linked to the International Classification of Functioning, Disability and Health (ICF). The content validation process followed the guidelines recommended by the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) panel. Results The construct of the Abilitator combines the multidimensional and biopsychosocial models of work ability and functioning. It also includes aspects of social inclusion and employability. It evaluates social, psychological, cognitive and physical functioning, and the ability to cope with everyday life. The content of these concepts was validated by the academic and practical expert panels. The Abilitator’s 79 ICF codes covered 57% of the Generic, 77% of the Brief Vocational Rehabilitation, and 8% of the Minimal Environmental ICF Core Sets. When compared with the Work Ability Index (WAI) and the World Health Organization Disability Assessment Schedule (WHODAS 2.0), the direct equivalences of the ICF codes were 36 and 44%, respectively. Conclusion The Abilitator sufficiently comprehensively covers the relevant aspects to enable the assessment of the overall work ability and functioning of the population in a weak labour market position.
  • Aaltonen, Niina; Singha, Prosanta K; Jakupović, Hermina; Wirth, Thomas; Samaranayake, Haritha; Pasonen-Seppänen, Sanna; Rilla, Kirsi; Varjosalo, Markku; Edgington-Mitchell, Laura E; Kasperkiewicz, Paulina; Drag, Marcin; Kälvälä, Sara; Moisio, Eemeli; Savinainen, Juha R; Laitinen, Jarmo T (BioMed Central, 2020)
    Abstract Background Serine hydrolases (SHs) are a functionally diverse family of enzymes playing pivotal roles in health and disease and have emerged as important therapeutic targets in many clinical conditions. Activity-based protein profiling (ABPP) using fluorophosphonate (FP) probes has been a powerful chemoproteomic approach in studies unveiling roles of SHs in various biological systems. ABPP utilizes cell/tissue proteomes and features the FP-warhead, linked to a fluorescent reporter for in-gel fluorescence imaging or a biotin tag for streptavidin enrichment and LC-MS/MS-based target identification. Existing ABPP approaches characterize global SH activity based on mobility in gel or MS-based target identification and cannot reveal the identity of the cell-type responsible for an individual SH activity originating from complex proteomes. Results Here, by using an activity probe with broad reactivity towards the SH family, we advance the ABPP methodology to glioma brain cryosections, enabling for the first time high-resolution confocal fluorescence imaging of global SH activity in the tumor microenvironment. Tumor-associated cell types were identified by extensive immunohistochemistry on activity probe-labeled sections. Tissue-ABPP indicated heightened SH activity in glioma vs. normal brain and unveiled activity hotspots originating from tumor-associated neutrophils (TANs), rather than tumor-associated macrophages (TAMs). Thorough optimization and validation was provided by parallel gel-based ABPP combined with LC-MS/MS-based target verification. Conclusions Our study advances the ABPP methodology to tissue sections, enabling high-resolution confocal fluorescence imaging of global SH activity in anatomically preserved complex native cellular environment. To achieve global portrait of SH activity throughout the section, a probe with broad reactivity towards the SH family members was employed. As ABPP requires no a priori knowledge of the identity of the target, we envisage no imaginable reason why the presently described approach would not work for sections regardless of species and tissue source.
  • Smits, Dins; Brigis, Girts; Pavare, Jana; Urtane, Inga; Kovalovs, Sandis; Barengo, Noël C (BioMed Central, 2020)
    Abstract Background The problem of nonadherence to therapy is a key reason of insufficient asthma control. Evaluating the beliefs about asthma medication, cognitive and emotional perceptions may help to identify patients with poor adherence to treatment in clinical practice which need additional attention in order to increase the likelihood of them taking their asthma medication according to the prescribed treatment protocol. The purpose of this study is to assess whether beliefs about asthma medication, cognitive and emotional factors are related to poor treatment adherence of asthma medication in a sample of asthma patients in Latvia. Methods Study subjects were asthma patients attending outpatient pulmonologist consultations in Latvia during September 2013 to December 2015. Beliefs about asthma medicine, cognitive and emotional factors related to asthma were determined in a cross-sectional, self-administered survey. The validated Beliefs about Medicines Questionnaire (BMQ) and the Brief Illness Perception Questionnaire (brief IPQ) were used. Treatment adherence was assessed using 5-item version of the Medication Adherence Reporting Scale (MARS). The total sample size was 352 patients. Logistic regression models were used to predict poor adherence to asthma treatment. The validity of each logistic regression model was assessed by the Hosmer/Lemeshow test. The main outcome measure was self-reported adherence to treatment. Results The more the patients agreed with the statement “My future health depends on my asthma medication” the lower the possibility of poor adherence to asthma treatment (OR 0.42; 95% CI 0.24–0.74). The more concerned the patients were in regard to long-term effects of their medication (OR 2; 95% CI 1.22–3.27), the higher the probability of poor treatment adherence. Conclusions Screening asthma patients using the BMQ may help to identify those to benefit from interventions targeting their concerns and medication beliefs in order to improve adherence to asthma medication.
  • Merid, Simon K; Novoloaca, Alexei; Sharp, Gemma C; Küpers, Leanne K; Kho, Alvin T; Roy, Ritu; Gao, Lu; Annesi-Maesano, Isabella; Jain, Pooja; Plusquin, Michelle; Kogevinas, Manolis; Allard, Catherine; Vehmeijer, Florianne O; Kazmi, Nabila; Salas, Lucas A; Rezwan, Faisal I; Zhang, Hongmei; Sebert, Sylvain; Czamara, Darina; Rifas-Shiman, Sheryl L; Melton, Phillip E; Lawlor, Debbie A; Pershagen, Göran; Breton, Carrie V; Huen, Karen; Baiz, Nour; Gagliardi, Luigi; Nawrot, Tim S; Corpeleijn, Eva; Perron, Patrice; Duijts, Liesbeth; Nohr, Ellen A; Bustamante, Mariona; Ewart, Susan L; Karmaus, Wilfried; Zhao, Shanshan; Page, Christian M; Herceg, Zdenko; Jarvelin, Marjo-Riitta; Lahti, Jari; Baccarelli, Andrea A; Anderson, Denise; Kachroo, Priyadarshini; Relton, Caroline L; Bergström, Anna; Eskenazi, Brenda; Soomro, Munawar H; Vineis, Paolo; Snieder, Harold; Bouchard, Luigi; Jaddoe, Vincent W; Sørensen, Thorkild I A; Vrijheid, Martine; Arshad, S. H; Holloway, John W; Håberg, Siri E; Magnus, Per; Dwyer, Terence; Binder, Elisabeth B; DeMeo, Dawn L; Vonk, Judith M; Newnham, John; Tantisira, Kelan G; Kull, Inger; Wiemels, Joseph L; Heude, Barbara; Sunyer, Jordi; Nystad, Wenche; Munthe-Kaas, Monica C; Räikkönen, Katri; Oken, Emily; Huang, Rae-Chi; Weiss, Scott T; Antó, Josep M; Bousquet, Jean; Kumar, Ashish; Söderhäll, Cilla; Almqvist, Catarina; Cardenas, Andres; Gruzieva, Olena; Xu, Cheng-Jian; Reese, Sarah E; Kere, Juha; Brodin, Petter; Solomon, Olivia; Wielscher, Matthias; Holland, Nina; Ghantous, Akram; Hivert, Marie-France; Felix, Janine F; Koppelman, Gerard H; London, Stephanie J; Melén, Erik (BioMed Central, 2020)
    Abstract Background Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children. Methods We performed meta-analysis of Illumina’s HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4–18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung. Results We identified 8899 CpGs in cord blood that were associated with gestational age (range 27–42 weeks), at Bonferroni significance, P < 1.06 × 10− 7, of which 3343 were novel. These were annotated to 4966 genes. After restricting findings to at least three significant adjacent CpGs, we identified 1276 CpGs annotated to 325 genes. Results were generally consistent when analyses were restricted to term births. Cord blood findings tended not to persist into childhood and adolescence. Pathway analyses identified enrichment for biological processes critical to embryonic development. Follow-up of identified genes showed correlations between gestational age and DNA methylation levels in fetal brain and lung tissue, as well as correlation with expression levels. Conclusions We identified numerous CpGs differentially methylated in relation to gestational age at birth that appear to reflect fetal developmental processes across tissues. These findings may contribute to understanding mechanisms linking gestational age to health effects.
  • Stahlmann, Katharina; Hebestreit, Antje; DeHenauw, Stefaan; Hunsberger, Monica; Kaprio, Jaakko; Lissner, Lauren; Molnár, Dénes; Ayala-Marín, Alelí M; Reisch, Lucia A; Russo, Paola; Tornaritis, Michael; Veidebaum, Toomas; Pohlabeln, Hermann; Bogl, Leonie H (BioMed Central, 2020)
    Abstract Background There has been an increase in children growing up in non-traditional families, such as single-parent and blended families. Children from such families have a higher prevalence of obesity and poorer health outcomes, but research on the relationship with obesogenic behaviours is limited. Objectives Therefore, the aim of this study was to investigate whether there are associations between family structures and obesogenic behaviours and related family rules in European children and adolescents. Methods The sample included 7664 children (mean age ± SD: 10.9 ± 2.9) from 4923 families who were participants of the multi-centre I.Family study (2013/2014) conducted in 8 European countries. Family structure was assessed by a detailed interview on kinship and household. Obesogenic behaviours (screen time, sleep duration, consumption of sugar-sweetened beverages (SSBs)) and family rules (rules for computer and television, bedtime routine, availability of SSBs during meals) were determined by standardized questionnaires. Multilevel mixed-effects linear and logistic regression models were used to model the associations of family structure with obesogenic behaviours and family rules. Sex, age, parental education level, number of children and adults in the household and BMI z-score were covariates in the models. Two-parent biological families were set as the reference category. Results Children from single-parent families were less likely to have family rules regarding screen time (OR: 0.62, 95% CI: 0.40–0.94, p = 0.026) with higher reported hours of screen time per week (β = 2.70 h/week, 95% CI: 1.39–4.00, p < 0.001). The frequency of weekly SSB consumption differed by family structure in a sex-specific manner: girls from single-parent (β = 3.19 frequency/week, 95% CI: 0.91–5.47, p = 0.006) and boys from blended/adoptive families (β = 3.01 frequency/week, 95% CI: 0.99–5.03, p = 0.004) consumed more SSBs. Sleep duration, bedtime routines and availability of SSBs during meals did not differ between children from these family structures. Parental education did not modify any of these associations. Conclusions Parents in non-traditional family structures appear to experience more difficulties in restricting screen time and the intake of SSBs in their children than parents in traditional two-parent family structures. Our findings therefore suggest that additional support and effective strategies for parents in non-traditional families may help to reduce obesogenic behaviours in children from such family types.
  • Swindell, Nils; Rees, Paul; Fogelholm, Mikael; Drummen, Mathijs; MacDonald, Ian; Martinez, J. A; Navas-Carretero, Santiago; Handjieva-Darlenska, Teodora; Boyadjieva, Nadka; Bogdanov, Georgi; Poppitt, Sally D; Gant, Nicholas; Silvestre, Marta P; Brand-Miller, Jennie; Schlicht, Wolfgang; Muirhead, Roslyn; Brodie, Shannon; Tikkanen, Heikki; Jalo, Elli; Westerterp-Plantenga, Margriet; Adam, Tanja; Vestentoft, Pia S; Larsen, Thomas M; Raben, Anne; Stratton, Gareth (BioMed Central, 2020)
    Abstract Background Physical activity, sedentary time and sleep have been shown to be associated with cardio-metabolic health. However, these associations are typically studied in isolation or without accounting for the effect of all movement behaviours and the constrained nature of data that comprise a finite whole such as a 24 h day. The aim of this study was to examine the associations between the composition of daily movement behaviours (including sleep, sedentary time (ST), light intensity physical activity (LIPA) and moderate-to-vigorous activity (MVPA)) and cardio-metabolic health, in a cross-sectional analysis of adults with pre-diabetes. Further, we quantified the predicted differences following reallocation of time between behaviours. Methods Accelerometers were used to quantify daily movement behaviours in 1462 adults from eight countries with a body mass index (BMI) ≥25 kg·m− 2, impaired fasting glucose (IFG; 5.6–6.9 mmol·l− 1) and/or impaired glucose tolerance (IGT; 7.8–11.0 mmol•l− 1 2 h following oral glucose tolerance test, OGTT). Compositional isotemporal substitution was used to estimate the association of reallocating time between behaviours. Results Replacing MVPA with any other behaviour around the mean composition was associated with a poorer cardio-metabolic risk profile. Conversely, when MVPA was increased, the relationships with cardiometabolic risk markers was favourable but with smaller predicted changes than when MVPA was replaced. Further, substituting ST with LIPA predicted improvements in cardio-metabolic risk markers, most notably insulin and HOMA-IR. Conclusions This is the first study to use compositional analysis of the 24 h movement composition in adults with overweight/obesity and pre-diabetes. These findings build on previous literature that suggest replacing ST with LIPA may produce metabolic benefits that contribute to the prevention and management of type 2 diabetes. Furthermore, the asymmetry in the predicted change in risk markers following the reallocation of time to/from MVPA highlights the importance of maintaining existing levels of MVPA. Trial registration ClinicalTrials.gov (NCT01777893).
  • Sandelin, Atte; Härtel, Heidi; Seppä-Lassila, Leena; Kaartinen, Liisa; Rautala, Helena; Soveri, Timo; Simojoki, Heli (BioMed Central, 2020)
    Abstract Background Bovine respiratory disease (BRD) continues to be great challenge in calf rearing units. The urgent need to decrease the use of antibiotics and increase animal welfare in beef production has forced us to introduce new preventive methods. Vaccinations could contribute to the solution, but the high incidence of BRD already at an early age has made it difficult to introduce suitable vaccination programs. Challenge studies have shown promising results in 3–14 day old calves vaccinated with intranasal BRD vaccine, but very few field trials are available to assess the efficacy of the intranasal vaccines in field conditions. We evaluated the effect of one dose of commercial intranasal vaccination on calf mortality, daily gain, and treatment incidence for BRD in one calf rearing unit. In total, 497 calves (mean age 19 days) were included in our study, 247 of which were vaccinated at the time of arrival to the unit and 250 served as negative controls (unvaccinated). Vaccinated and unvaccinated calves were situated in separate compartments until weaning. Daily gain, treatment incidence, and mortality were recorded until the calves were transported to the finishing unit, which averaged 154.5 days from arrival. Results Average daily gain over the complete study period was 1151.9 g/day (SD 137.9) for the vaccinated calves and 1139.5 g/day (SD 135.9) for the unvaccinated calves. Intranasal vaccination combined with older arrival age (17 days or older) resulted in a higher daily gain (47.8 g/day) compared with unvaccinated calves (coef. 0.0478, p = 0.003). This association was not recorded in calves that were younger than 17 days upon arrival. Intranasal vaccination was not significantly associated either with mortality (OR 0.976, p = 0.968) or treatment incidence for BRD (OR 1.341, p = 0.120). In total, six vaccinated calves (2.43%) and six unvaccinated calves (2.40%) died during the study period. Conclusions Vaccinating arriving calves with intranasal vaccine in the calf rearing unit did not decrease the mortality or treatment incidence for BRD, but it significantly improved the weight gain in calves transported to the unit at the age of 17 days or older.
  • Matschoss, Kaisa; Pietilä, Maria; Rask, Mikko; Suni, Tanja (Springer Berlin Heidelberg, 2020)
    Abstract Co-creation principles have become prominent in the scientific disciplines that aim to respond to global sustainability challenges especially in the global south. This paper analyses a co-creation pilot of global change research in the novel context of a Nordic country, Finland. The pilot was organised to learn how to create a future agenda for a complex and transdisciplinary research field of global change. This paper analyses its conceptualisation in Finland, how did the series of engagement events increase the capacities of participants and how did the process contribute to a change towards a new, societally responsible way of co-creating global change research. The study found that co-creation suits well for the translation of important societal questions into global research agendas and for networking actors to co-creation activities. Based on the study, we argue that co-creation offers a socially acceptable approach to address socially critical topics to design transdisciplinary social and sustainability research.
  • Vlasov, Hanna; Juvonen, Tatu; Hiippala, Seppo; Suojaranta, Raili; Peltonen, Markku; Schramko, Alexey; Arvonen, Kaapo; Salminen, Ulla-Stina; Kleine Budde, Ilona; Eränen, Tiina; Mazanikov, Maxim; Meinberg, Mihkel; Vähäsilta, Tommi; Wilkman, Erika; Pettilä, Ville; Pesonen, Eero (BioMed Central, 2020)
    Abstract Background In cardiac surgery with cardiopulmonary bypass (CPB), large amounts of fluids are administered. CPB priming with crystalloid solution causes marked hemodilution and fluid extravasation. Colloid solutions may reduce fluid overload because they have a better volume expansion effect than crystalloids. The European Medicines Agency does not recommend the use of hydroxyethyl starch solutions (HES) due to harmful renal effects. Albumin solution does not impair blood coagulation but the findings on kidney function are conflicting. On the other hand, albumin may reduce endothelial glycocalyx destruction and decrease platelet count during CPB. No large randomized, double-blind, clinical trials have compared albumin solution to crystalloid solution in cardiac surgery. Methods/design In this single-center, double-blind, randomized controlled trial comprising 1386 adult cardiac surgery patients, 4% albumin solution will be compared to Ringer’s acetate solution in CPB priming and volume replacement up to 3200 mL during surgery and the first 24 h of intensive care unit stay. The primary efficacy outcome is the number of patients with at least one major adverse event (MAE) during 90 postoperative days (all-cause death, acute myocardial injury, acute heart failure or low output syndrome, resternotomy, stroke, major arrhythmia, major bleeding, infection compromising post-procedural rehabilitation, acute kidney injury). Secondary outcomes are total number of MAEs, incidence of major adverse cardiac events (MACE; cardiac death, acute myocardial injury, acute heart failure, arrhythmia), amount of each type of blood product transfused (red blood cells, fresh frozen plasma, platelets), total fluid balance at the end of the intervention period, total measured blood loss, development of acute kidney injury, days alive without mechanical ventilation in 90 days, days alive outside intensive care unit at 90 days, days alive at home at 90 days, and 90-day mortality. Discussion The findings of this study will provide new evidence regarding efficacy and safety of albumin solution in adult patients undergoing cardiac surgery with CPB. Trial registration EudraCT (clinicaltrialsregister.eu) 2015–002556-27 Registered 11 Nov 2016 and ClinicalTrials.gov NCT02560519. Registered 25 Sept 2015.
  • Mattila, Hans K; Mäkinen, Mari; Lundell, Taina (BioMed Central, 2020)
    Abstract Background Fungal decomposition of wood is considered as a strictly aerobic process. However, recent findings on wood-decaying fungi to produce ethanol from various lignocelluloses under oxygen-depleted conditions lead us to question this. We designed gene expression study of the white rot fungus Phlebia radiata (isolate FBCC0043) by adopting comparative transcriptomics and functional genomics on solid lignocellulose substrates under varying cultivation atmospheric conditions. Results Switch to fermentative conditions was a major regulator for intracellular metabolism and extracellular enzymatic degradation of wood polysaccharides. Changes in the expression profiles of CAZy (carbohydrate-active enzyme) encoding genes upon oxygen depletion, lead into an alternative wood decomposition strategy. Surprisingly, we noticed higher cellulolytic activity under fermentative conditions in comparison to aerobic cultivation. In addition, our results manifest how oxygen depletion affects over 200 genes of fungal primary metabolism including several transcription factors. We present new functions for acetate generating phosphoketolase pathway and its potential regulator, Adr1 transcription factor, in carbon catabolism under oxygen depletion. Conclusions Physiologically resilient wood-decomposing Basidiomycota species P. radiata is capable of thriving under respirative and fermentative conditions utilizing only untreated lignocellulose as carbon source. Hypoxia-response mechanism in the fungus is, however, divergent from the regulation described for Ascomycota fermenting yeasts or animal-pathogenic species of Basidiomycota.
  • Laitila, Jenni M; McNamara, Elyshia L; Wingate, Catherine D; Goullee, Hayley; Ross, Jacob A; Taylor, Rhonda L; van der Pijl, Robbert; Griffiths, Lisa M; Harries, Rachel; Ravenscroft, Gianina; Clayton, Joshua S; Sewry, Caroline; Lawlor, Michael W; Ottenheijm, Coen A C; Bakker, Anthony J; Ochala, Julien; Laing, Nigel G; Wallgren-Pettersson, Carina; Pelin, Katarina; Nowak, Kristen J (BioMed Central, 2020)
    Abstract Nemaline myopathy (NM) caused by mutations in the gene encoding nebulin (NEB) accounts for at least 50% of all NM cases worldwide, representing a significant disease burden. Most NEB-NM patients have autosomal recessive disease due to a compound heterozygous genotype. Of the few murine models developed for NEB-NM, most are Neb knockout models rather than harbouring Neb mutations. Additionally, some models have a very severe phenotype that limits their application for evaluating disease progression and potential therapies. No existing murine models possess compound heterozygous Neb mutations that reflect the genotype and resulting phenotype present in most patients. We aimed to develop a murine model that more closely matched the underlying genetics of NEB-NM, which could assist elucidation of the pathogenetic mechanisms underlying the disease. Here, we have characterised a mouse strain with compound heterozygous Neb mutations; one missense (p.Tyr2303His), affecting a conserved actin-binding site and one nonsense mutation (p.Tyr935*), introducing a premature stop codon early in the protein. Our studies reveal that this compound heterozygous model, NebY2303H, Y935X, has striking skeletal muscle pathology including nemaline bodies. In vitro whole muscle and single myofibre physiology studies also demonstrate functional perturbations. However, no reduction in lifespan was noted. Therefore, NebY2303H,Y935X mice recapitulate human NEB-NM and are a much needed addition to the NEB-NM mouse model collection. The moderate phenotype also makes this an appropriate model for studying NEB-NM pathogenesis, and could potentially be suitable for testing therapeutic applications.
  • Kilpi, Jorma; Norros, Ilkka; Kuusela, Pirkko; Malin, Fanny; Räty, Tomi (Springer International Publishing, 2020)
    Abstract We study the problem of making algorithmic statistical inferences about the dynamics of city traffic. Our data is based on loop detector counts of observed vehicles in various roads in the city of Tampere, Finland. We show that meaningful correlations can be found between traffic asymmetries at different measurement locations. The traffic asymmetry is the difference of the traffic counts of the opposite directions of a road. The correlations can be further quantified by estimating how much they effect on the average values of the traffic asymmetries at the neighbouring locations. Conditional expectations, both sample and binormal model-based versions are useful tools for quantifying this effect. The uncertainty bounds of conditional expectations of the binormal model distribution are extremely useful for outlier detection. Furthermore, conditional expectations of the multinormal distribution model can be used to recover missing data with bounds to uncertainty.
  • Sinclair-Waters, Marion; Ødegård, Jørgen; Korsvoll, Sven A; Moen, Thomas; Lien, Sigbjørn; Primmer, Craig R; Barson, Nicola J (BioMed Central, 2020)
    Abstract Background Understanding genetic architecture is essential for determining how traits will change in response to evolutionary processes such as selection, genetic drift and/or gene flow. In Atlantic salmon, age at maturity is an important life history trait that affects factors such as survival, reproductive success, and growth. Furthermore, age at maturity can seriously impact aquaculture production. Therefore, characterizing the genetic architecture that underlies variation in age at maturity is of key interest. Results Here, we refine our understanding of the genetic architecture for age at maturity of male Atlantic salmon using a genome-wide association study of 11,166 males from a single aquaculture strain, using imputed genotypes at 512,397 single nucleotide polymorphisms (SNPs). All individuals were genotyped with a 50K SNP array and imputed to higher density using parents genotyped with a 930K SNP array and pedigree information. We found significant association signals on 28 of 29 chromosomes (P-values: 8.7 × 10−133–9.8 × 10−8), including two very strong signals spanning the six6 and vgll3 gene regions on chromosomes 9 and 25, respectively. Furthermore, we identified 116 independent signals that tagged 120 candidate genes with varying effect sizes. Five of the candidate genes found here were previously associated with age at maturity in other vertebrates, including humans. Discussion These results reveal a mixed architecture of large-effect loci and a polygenic component that consists of multiple smaller-effect loci, suggesting a more complex genetic architecture of Atlantic salmon age at maturity than previously thought. This more complex architecture will have implications for selection on this key trait in aquaculture and for management of wild salmon populations.
  • Alanko, Jarno; Bannai, Hideo; Cazaux, Bastien; Peterlongo, Pierre; Stoye, Jens (BioMed Central, 2020)
    Abstract Recent large-scale community sequencing efforts allow at an unprecedented level of detail the identification of genomic regions that show signatures of natural selection. Traditional methods for identifying such regions from individuals’ haplotype data, however, require excessive computing times and therefore are not applicable to current datasets. In 2019, Cunha et al. (Advances in bioinformatics and computational biology: 11th Brazilian symposium on bioinformatics, BSB 2018, Niterói, Brazil, October 30 - November 1, 2018, Proceedings, 2018. https://doi.org/10.1007/978-3-030-01722-4_3) suggested the maximal perfect haplotype block as a very simple combinatorial pattern, forming the basis of a new method to perform rapid genome-wide selection scans. The algorithm they presented for identifying these blocks, however, had a worst-case running time quadratic in the genome length. It was posed as an open problem whether an optimal, linear-time algorithm exists. In this paper we give two algorithms that achieve this time bound, one conceptually very simple one using suffix trees and a second one using the positional Burrows–Wheeler Transform, that is very efficient also in practice.

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