Trilemma of Nordic–Baltic Forestry—How to Implement UN Sustainable Development Goals

Forests are the dominant land cover in Nordic–Baltic countries, and forestry, the management of forests for improved ecosystem-service (ES) delivery, is an important contributor to sustainability. Forests and forestry support multiple United Nations Sustainability Goals (UN SDGs) and a number of EU policies, and can address conflicting environmental goals. Forests provide multiple ecosystem services and natural solutions, including wood and fibre production, food, clear and clean water and air, animal and plant habitats, soil formation, aesthetics, and cultural and social services. Carbon sequestered by growing trees is a key factor in the envisaged transition from a fossil-based to a biobased economy. Here, we highlight the possibilities of forest-based solutions to mitigate current and emerging societal challenges. We discuss forestry effects on forest ecosystems,focusing on the optimisation of ES delivery and the fulfilment of UN SDGs while counteracting unwanted effects. In particular, we highlight the trilemma of (i) increasing wood production to substitute raw fossil materials, (ii) increasing forest carbon storage capacity, and (iii) improving forest biodiversity and other ES delivery

A new prediction model for ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy

Aims Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) is characterized by ventricular arrhythmias (VAs) and sudden cardiac death (SCD). We aimed to develop a model for individualized prediction of incident VA/SCD in ARVC patients.Methods and results Five hundred and twenty-eight patients with a definite diagnosis and no history of sustained VAs/SCD at baseline, aged 38.2 +/- 15.5 years, 44.7% male, were enrolled from five registries in North America and Europe. Over 4.83 (interquartile range 2.44-9.33) years of follow-up, 146 (27.7%) experienced sustained VA, defined as SCD, aborted SCD, sustained ventricular tachycardia, or appropriate implantable cardioverter-defibrillator (ICD) therapy. A prediction model estimating annual VA risk was developed using Cox regression with internal validation. Eight potential predictors were pre-specified: age, sex, cardiac syncope in the prior 6 months, non-sustained ventricular tachycardia, number of premature ventricular complexes in 24 h, number of leads with T-wave inversion, and right and left ventricular ejection fractions (LVEFs). All except LVEF were retained in the final model. The model accurately distinguished patients with and without events, with an optimism-corrected C-index of 0.77 [95% confidence interval (CI) 0.73-0.81] and minimal over-optimism [calibration slope of 0.93 (95% CI 0.92-0.95)]. By decision curve analysis, the clinical benefit of the model was superior to a current consensus-based ICD placement algorithm with a 20.6% reduction of ICD placements with the same proportion of protected patients (P &lt;0.001).Conclusion Using the largest cohort of patients with ARVC and no prior VA, a prediction model using readily available clinical parameters was devised to estimate VA risk and guide decisions regarding primary prevention ICDs (www.arvcrisk.com).</p

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

Sudden Cardiac Death Prediction in Arrhythmogenic Right Ventricular Cardiomyopathy: A Multinational Collaboration

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with ventricular arrhythmias (VA) and sudden cardiac death (SCD). A model was recently developed to predict incident sustained VA in patients with ARVC. However, since this outcome may overestimate the risk for SCD, we aimed to specifically predict life-threatening VA (LTVA) as a closer surrogate for SCD. METHODS: We assembled a retrospective cohort of definite ARVC cases from 15 centers in North America and Europe. Association of 8 prespecified clinical predictors with LTVA (SCD, aborted SCD, sustained, or implantable cardioverter-defibrillator treated ventricular tachycardia >250 beats per minute) in follow-up was assessed by Cox regression with backward selection. Candidate variables included age, sex, prior sustained VA (≥30s, hemodynamically unstable, or implantable cardioverter-defibrillator treated ventricular tachycardia; or aborted SCD), syncope, 24-hour premature ventricular complexes count, the number of anterior and inferior leads with T-wave inversion, left and right ventricular ejection fraction. The resulting model was internally validated using bootstrapping. RESULTS: A total of 864 patients with definite ARVC (40±16 years; 53% male) were included. Over 5.75 years (interquartile range, 2.77-10.58) of follow-up, 93 (10.8%) patients experienced LTVA including 15 with SCD/aborted SCD (1.7%). Of the 8 prespecified clinical predictors, only 4 (younger age, male sex, premature ventricular complex count, and number of leads with T-wave inversion) were associated with LTVA. Notably, prior sustained VA did not predict subsequent LTVA (P=0.850). A model including only these 4 predictors had an optimism-corrected C-index of 0.74 (95% CI, 0.69-0.80) and calibration slope of 0.95 (95% CI, 0.94-0.98) indicating minimal over-optimism. CONCLUSIO

A new prediction model for ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy

AIMS: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) is characterized by ventricular arrhythmias (VAs) and sudden cardiac death (SCD). We aimed to develop a model for individualized prediction of incident VA/SCD in ARVC patients. METHODS AND RESULTS: Five hundred and twenty-eight patients with a definite diagnosis and no history of sustained VAs/SCD at baseline, aged 38.2 ± 15.5 years, 44.7% male, were enrolled from five registries in North America and Europe. Over 4.83 (interquartile range 2.44-9.33) years of follow-up, 146 (27.7%) experienced sustained VA, defined as SCD, aborted SCD, sustained ventricular tachycardia, or appropriate implantable cardioverter-defibrillator (ICD) therapy. A prediction model estimating annual VA risk was developed using Cox regression with internal validation. Eight potential predictors were pre-specified: age, sex, cardiac syncope in the prior 6 months, non-sustained ventricular tachycardia, number of premature ventricular complexes in 24 h, number of leads with T-wave inversion, and right and left ventricular ejection fractions (LVEFs). All except LVEF were retained in the final model. The model accurately distinguished patients with and without events, with an optimism-corrected C-index of 0.77 [95% confidence interval (CI) 0.73-0.81] and minimal over-optimism [calibration slope of 0.93 (95% CI 0.92-0.95)]. By decision curve analysis, the clinical benefit of the model was superior to a current consensus-based ICD placement algorithm with a 20.6% reduction of ICD placements with the same proportion of protected patients (P < 0.001). CONCLUSION: Using the largest cohort of patients with ARVC and no prior VA, a prediction model using readily available clinical parameters was devised to estimate VA risk and guide decisions regarding primary prevention ICDs (www.arvcrisk.com)

Arrhythmogenic Right Ventricular Cardiomyopathy : Genetic and Electrocardiographic Aspects on Risk of Ventricular Arrhythmia and Diagnosis

Introduction: ARVC (Arrhythmogenic Right Ventricular Cardiomyopathy) is a heritable rare disease of the heart muscle, primarily affecting the right ventricle, that may cause arrhythmias and heart failure. Aim: The overall aim of this thesis was to study various aspects of genetic information and electrocardiography (ECG), for their use in diagnosis and risk evaluation in ARVC. Material and methods: Paper I: The genotype-phenotype correlations in four unrelated families with a plakophilin 2 gene variant (PKP2 c.2146-1C&gt;G) were studied, to determine 1) to what extent family members fulfil diagnostic criteria and 2) to assess whether these gene carriers had any specific clinical characteristics in common. Paper II: Patients with definite ARVC but one group with and one without diagnostic ECG criteria were compared to each other and a healthy control group. Vectorcardiographic parameters were assessed alongside QRS duration, corrected QT interval and an angle measuring the upslope and downslope of the S wave (S-wave angle). Paper III: Combined Annotation Dependent Depletion (CADD, a bioinformatic tool) scores were calculated for all pathogenic and likely pathogenic variants in PKP2 found in patients from two ARVC Registries, and the scores association with arrhythmic events and age at definite ARVC diagnosis were assessed. Paper IV: Digital ECGs (n=6871) from 353 patients with definite ARVC were analysed using Glasgow algorithm to describe the longitudinal development of different ECG characteristics, but also to assess the relationship between the ECG parameters and 1) structural abnormalities and 2) sustained ventricular tachycardia (VT) during a 10-year follow-up. Results: Paper I: In 41 family members evaluated, 23 were mutation carriers, and seven of them fulfilled diagnostic criteria. The clinical presentation was variable, and no specific genotype-phenotype correlation was found. Paper II: The vectorcardiographic parameters significantly differentiated the ARVC patients with normal ECGs from controls (p&gt;0.004 to p&lt;0.001). Paper III: In total, 33 unique genetic variants were reported in 179 patients. CADD score was neither associated with age at cardiac events (HR 1.002, 95% CI: 0.953-1.054, p=0.933) nor with age at definite ARVC diagnosis (HR 0.992, 95% CI: 0.947-1.039, p=0.731). Paper IV: Progressive changes in depolarisation and repolarisation parameters before as well as after the diagnosis was established confirming the progressive nature of ARVC developing over the course of decades, possibly in parallel with structural changes in the ventricles. The presence of T wave inversion in leads V3 or aVF at first ECG was significantly associated with ventricular tachycardia during 10 years follow-up (for lead V3 [HRadj 2.11, 95%CI 1.28-3.49, p=0.003], lead aVF [HRadj 1.68, 95%CI 1.02-2.77, p=.041] both adjusted for age, sex and proband status). Conclusions: Our studies confirms previous results that, with our current knowledge, genetic variants in desmosomal genes are useful for diagnosis and cascade screening in family members but not for detailed risk stratification or prediction of diagnosis. Progressive changes in depolarisation and repolarisation ECG parameters before as well as after the diagnosis were established, confirming the progressive nature of ARVC developing over the course of decades, possibly in parallel with structural changes in the ventricles. Novel vectorcardiographic markers may aid in early detection of disease progression, possibly with biggest potential in cascade screening.ARVC (Arrhythmogenic Right Ventricular Cardiomyopathy) är en relativt sällsynt och ärftlig hjärtmuskelsjukdom, som i sin klassiska form drabbar främst höger hjärtkammare (right ventricle). Det uppstår mikroskopiska skador i hjärtmuskeln, och dessa läker genom inlagring av ärrvävnad och fettceller. Med tiden påverkar denna process både hjärtmuskulaturens elektriska ledningsförmåga och dess förmåga att effektivt dra sig samman, vilket kan ge upphov till såväl rytmrubbningar (arytmier) som hjärtsvikt. I de mest dramatiska fallen kan kammarrytmrubbningarna leda till plötslig hjärtdöd, som kan vara det första symtomet. Det är därför av stor vikt att hitta individer som har sjukdomen och/eller bär på ett genetiskt anlag för sjukdomen tidigt, och värdera deras risk för arytmier. En svårighet i sammanhanget är att även om en individ bär på ett anlag för sjukdomen är det inte säkert att vederbörande någonsin får symtom eller hjärtmuskelförändringar, anlagen har mycket varierande grad av genomslag (penetrans). Det finns idag ingen specifik behandling för ARVC, men om symptom på hjärtsvikt eller hjärtrytmrubbningar uppträder behandlas dessa. Om risken för allvarlig hjärtrytmrubbning bedöms hög kan en ICD (Implantable Cardioverter Defibrillator, en så kallad hjärtstartare) opereras in. Syftet med avhandlingen var att studera om och hur olika aspekter av genetisk information och EKG (elektrokardiografi) kan användas för diagnostik och riskvärdering. I det första delarbetet studerade vi fyra familjer med en sjukdomsorsakande variant (tidigare kallad mutation) i den gen som kodar för proteinet plakofilin 2, för att se om det fanns något symtom eller sjukdomstecken som kan hjälpa oss att identifiera individer med genomslag av genen. Bland de 23 individerna som bar på genvarianten varierade graden av fynd och symtom påtagligt, och något gemensamt sjukdomstecken återfanns inte. I det andra delarbetet använde vi oss av så kallad vektorkardiografi, som är ett sätt att beskriva hjärtats elektriska aktivitet i tre dimensioner, till skillnad från standard-EKG som tittar i två dimensioner. Målet var att se om vektorkardiografiska avläsningar, delvis på ett nytt sätt jämfört tidigare studier, kunde identifiera patienter med ARVC där klassiska sjukdomstecken på EKG saknades. Studien visar att det går att påvisa förändringar tidigare med tredimensionellt än med tvådimensionellt EKG. Metoden skulle kunna adderas i befintliga uppföljningsprogram för att identifiera patienter tidigt i sjukdomsförloppet. Delarbete tre handlade åter om hjärtmuskelproteinet plakofilin 2, som tidigare beskrivits som i hög grad associerat med hjärtrytmstörningar. Ett poängberäkningssystem, CADD-score, har hittills använts för bedömning av genetiska avvikelsers svårighetsgrad och en värdering huruvida de är sjukdomsorsakande. En hög poäng innebär att proteinet bedöms påverkat i hög grad, och vi studerade om det innebar att individer med högre poäng på CADD-score fick mer rytmrubbningar eller diagnosen tidigare i livet än individer med låga poäng. Någon sådan koppling kunde inte ses, och slutsatsen blev att vi inte kan använda CADD-score för riskvärdering i det enskilda fallet. Fjärde delarbetet kartlägger en stor grupp ARVC-patienters EKG-förändringar över tid. Vi beskriver hur olika delar av EKG-bilden förändras i relation till ålder men också i relation till tiden för diagnos, och kan visa att flera parametrar ändras signifikant med tiden. Vissa EKG-parametrars förändringar sammanfaller i tid med att avvikelser även ses vid undersökning med hjärtultraljud. Vi undersöker också om det finns någon enskild EKGförändring som, om den ses på det första EKG som tas på patienten, förutsäger en ökad risk för farliga hjärtrytmrubbningar under de kommande 10 åren. Två av EKG-förändringarna visade en sådan ökad risk, och vi diskuterar att dessa parametrar kanske framgent kan inkluderas i riskmodeller. Sammanfattningsvis visar våra studier att genetiska analyser, som används för att hitta sjukdomsorsakande genetiska varianter hos patienter med ARVC för att i nästa steg identifiera riskindivider i familjen, med dagens kunskap inte kan hjälpa oss att avgöra en individs risk för allvarlig sjukdom och/eller hjärtrytmrubbning. EKG, både två- som tredimensionellt, bidrar till såväl diagnostik som riskvärdering, och vår studie ger en unik bild av sjukdomens påverkan på olika EKG-parametrar över tid