Developing a spatially explicit modelling and evaluation framework for integrated carbon sequestration and biodiversity conservation: application in southern Finland

The challenges posed by climate change and biodiversity loss are deeply interconnected. Successful co-managing of these tangled drivers requires innovative methods that can prioritize and target management actions against multiple criteria, while also enabling cost-effective land use planning and impact scenario assessment. This paper synthesises the development and application of an integrated multidisciplinary modelling and evaluation framework for carbon and biodiversity in forest systems. By analysing and spatio-temporally modelling carbon processes and biodiversity elements, we determine an optimal solution for their co-management in the study landscape. We also describe how advanced Earth Observation measurements can be used to enhance mapping and monitoring of biodiversity and ecosystem processes. The scenarios used for the dynamic models were based on official Finnish policy goals for forest management and climate change mitigation. The development and testing of the system were executed in a large region in southern Finland (Kokemäenjoki basin, 27 024 km2) containing highly instrumented LTER (Long-Term Ecosystem Research) stations; these LTER data sources were complemented by fieldwork, remote sensing and national data bases. In the study area, estimated total net emissions were currently 4.2 TgCO2eq a-1, but modelling of forestry measures and anthropogenic emission reductions demonstrated that it would be possible to achieve the stated policy goal of carbon neutrality by low forest harvest intensity. We show how this policy-relevant information can be further utilised for optimal allocation of set-aside forest areas for nature conservation, which would significantly contribute to preserving both biodiversity and carbon values in the region. Biodiversity gain in the area could be increased without a loss of carbon-related benefits.The challenges posed by climate change and biodiversity loss are deeply interconnected. Successful co-managing of these tangled drivers requires innovative methods that can prioritize and target management actions against multiple criteria, while also enabling cost-effective land use planning and impact scenario assessment. This paper synthesises the development and application of an integrated multidisciplinary modelling and evaluation framework for carbon and biodiversity in forest systems. By analysing and spatio-temporally modelling carbon processes and biodiversity elements, we determine an optimal solution for their co-management in the study landscape. We also describe how advanced Earth Observation measurements can be used to enhance mapping and monitoring of biodiversity and ecosystem processes. The scenarios used for the dynamic models were based on official Finnish policy goals for forest management and climate change mitigation. The development and testing of the system were executed in a large region in southern Finland (Kokemäenjoki basin, 27,024 km2) containing highly instrumented LTER (Long-Term Ecosystem Research) stations; these LTER data sources were complemented by fieldwork, remote sensing and national data bases. In the study area, estimated total net emissions were currently 4.2 TgCO2eq a−1, but modelling of forestry measures and anthropogenic emission reductions demonstrated that it would be possible to achieve the stated policy goal of carbon neutrality by low forest harvest intensity. We show how this policy-relevant information can be further utilized for optimal allocation of set-aside forest areas for nature conservation, which would significantly contribute to preserving both biodiversity and carbon values in the region. Biodiversity gain in the area could be increased without a loss of carbon-related benefits.Peer reviewe

Ustekinumab for Crohn’s disease: a nationwide real-life cohort study from Finland (FINUSTE)

Background: Ustekinumab (UST), a human anti-IL12/23p40 monoclonal antibody, has been approved for treatment of Crohn?s Disease (CD) since the end of 2016. This nationwide noninterventional, retrospective chart review explored real-life data in patients receiving UST to provide guidance in UST treatment in the era of increasing prevalence of CD.Methods: The study assessed UST treatment patterns such as dosing frequency, concomitant medication and persistence in 48?CD patients commencing UST therapy in 12 Finnish hospitals during 2017. Clinical remission and response rates were explored using a modified Harvey?Bradshaw index (mHBI) and endoscopic response via the simple endoscopic score for Crohn?s disease (SES-CD) as proportions of patients at week 16 and at the end of follow-up.Results: Forty patients (83%) continued UST-treatment at the end of follow-up. At week 16, clinical response and endoscopic healing was observed, where data were available; mHBI decreased from 9 to 3 (p?=?.0001) and SES-CD from 12 to 3 (p?=?.009). Clinical benefit was achieved by 83% (19/23) at week 16 and by 76% (16/21) at the end of follow-up. The proportion of patients using corticosteroids decreased from 48% to 25% at week 16 and to 13% at the end of the follow-up.Conclusion: UST showed to be effective and persistent, inducing short-term clinical benefit and endoscopic response in this real-life nationwide study of CD patients. Significant corticosteroid tapering in patients with highly treatment refractory and long-standing CD was observed.Peer reviewe

Ustekinumab for Crohn's disease: a nationwide real-life cohort study from Finland (FINUSTE)

Background: Ustekinumab (UST), a human anti-IL12/23p40 monoclonal antibody, has been approved for treatment of Crohn's Disease (CD) since the end of 2016. This nationwide noninterventional, retrospective chart review explored real-life data in patients receiving UST to provide guidance in UST treatment in the era of increasing prevalence of CD. Methods: The study assessed UST treatment patterns such as dosing frequency, concomitant medication and persistence in 48 CD patients commencing UST therapy in 12 Finnish hospitals during 2017. Clinical remission and response rates were explored using a modified Harvey-Bradshaw index (mHBI) and endoscopic response via the simple endoscopic score for Crohn's disease (SES-CD) as proportions of patients at week 16 and at the end of follow-up. Results: Forty patients (83%) continued UST-treatment at the end of follow-up. At week 16, clinical response and endoscopic healing was observed, where data were available; mHBI decreased from 9 to 3 (p = .0001) and SES-CD from 12 to 3 (p = .009). Clinical benefit was achieved by 83% (19/23) at week 16 and by 76% (16/21) at the end of follow-up. The proportion of patients using corticosteroids decreased from 48% to 25% at week 16 and to 13% at the end of the follow-up. Conclusion: UST showed to be effective and persistent, inducing short-term clinical benefit and endoscopic response in this real-life nationwide study of CD patients. Significant corticosteroid tapering in patients with highly treatment refractory and long-standing CD was observed

Contribution of rare and common variants to intellectual disability in a sub-isolate of Northern Finland

The contribution of de novo variants in severe intellectual disability (ID) has been extensively studied whereas the genetics of mild ID has been less characterized. To elucidate the genetics of milder ID we studied 442 ID patients enriched for mild ID (>50%) from a population isolate of Finland. Using exome sequencing, we show that rare damaging variants in known ID genes are observed significantly more often in severe (27%) than in mild ID (13%) patients. We further observe a significant enrichment of functional variants in genes not yet associated with ID (OR: 2.1). We show that a common variant polygenic risk significantly contributes to ID. The heritability explained by polygenic risk score is the highest for educational attainment (EDU) in mild ID (2.2%) but lower for more severe ID (0.6%). Finally, we identify a Finland enriched homozygote variant in the CRADD ID associated gene.Peer reviewe

The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals

To dissect the genetic architecture of blood pressure and assess effects on target-organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure loci, of which 17 were novel and 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target-organ damage in multiple tissues, with minor effects in the kidney. Our findings expand current knowledge of blood pressure pathways and highlight tissues beyond the classic renal system in blood pressure regulation

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Evidence for the additivity of rare and common variant burden throughout the spectrum of intellectual disability

Peer reviewe