Pan-European backcasting exercise, enriched with regional perspective, and including a list of short-term policy options

This deliverable reports on the results of the third and final pan-European stakeholder meeting and secondly, on the enrichment with a Pilot Area and regional perspective. The main emphasis is on backcasting as a means to arrive at long-term strategies and short-term (policy) actions

Resilience trinity: safeguarding ecosystem functioning and services across three different time horizons and decision contexts

Ensuring ecosystem resilience is an intuitive approach to safeguard the functioning of ecosystems and hence the future provisioning of ecosystem services (ES). However, resilience is a multi‐faceted concept that is difficult to operationalize. Focusing on resilience mechanisms, such as diversity, network architectures or adaptive capacity, has recently been suggested as means to operationalize resilience. Still, the focus on mechanisms is not specific enough. We suggest a conceptual framework, resilience trinity, to facilitate management based on resilience mechanisms in three distinctive decision contexts and time‐horizons: 1) reactive, when there is an imminent threat to ES resilience and a high pressure to act, 2) adjustive, when the threat is known in general but there is still time to adapt management and 3) provident, when time horizons are very long and the nature of the threats is uncertain, leading to a low willingness to act. Resilience has different interpretations and implications at these different time horizons, which also prevail in different disciplines. Social ecology, ecology and engineering are often implicitly focussing on provident, adjustive or reactive resilience, respectively, but these different notions of resilience and their corresponding social, ecological and economic tradeoffs need to be reconciled. Otherwise, we keep risking unintended consequences of reactive actions, or shying away from provident action because of uncertainties that cannot be reduced. The suggested trinity of time horizons and their decision contexts could help ensuring that longer‐term management actions are not missed while urgent threats to ES are given priority

Kohti yhteisiä tavoitteita : GAS-koulutuksen arviointihankkeen loppuraportti

Goal Attaiment Scaling eli GAS on tavoiteasetannan menetelmä, jonka avulla pyritään ottamaan asiakkaan arki kuntoutuksen lähtökohdaksi. GAS-koulutusta avokuntoutuksen ammattihenkilöille on toteutettu 15 ammattikorkeakoulussa eri puolilla Suomea vuodesta 2011 alkaen. Tämän arviointitutkimuksen tarkoituksena oli selvittää, miten koulutuksen suorittaneet ammattilaiset käyttävät GAS-menetelmää ja minkälaisena he kokevat sen käytettävyyden ja hyödynnettävyyden. Lisäksi haluttiin kartoittaa sekä koulutuksiin osallistuneiden että kouluttajien näkemyksiä GAS-menetelmästä ja -koulutuksesta ja sen kehittämistarpeista. Tutkimuksen aineisto koottiin GAS-koulutukseen osallistuneille kuntoutusammattilaisille kohdennetulla sähköisellä kyselyllä ja GAS-kouluttajien haastatteluilla. Kyselyn vastaajista (n = 178) suurin osa ilmoitti kuntoutujien osallistuvan tavoitteiden asettamiseen ja yli puolet vastaajista koki menetelmän parantaneen kuntoutujien kuntoutusmotivaatiota. Yhteistyö hoitovastuutahon kanssa GAStavoitteiden suunnittelussa ja asettamisessa on vastausten perusteella melko vähäistä. Vajaa puolet vastaajista arvioi GAS-menetelmän käyttöönoton lisänneen tai syventäneen moniammatillista yhteistyötä. Tarkasteltaessa GAS-menetelmän hallintaa havaittiin, että koulutukseen osallistuneilla näyttäisi olevan vaikeuksia lähtö- ja tavoitetason määrittelyssä, indikaattorien sanallistamisessa sekä T-scoren ymmärtämisessä. Noin kaksi kolmasosaa vastaajista arvioi GAS-koulutuksen vastanneen odotuksia, mutta kaiken kaikkiaan koulutustyytyväisyyden suhteen ammattikorkeakoulukohtaiset erot olivat suuria tilastollisesti merkitsevällä tasolla. Avoimissa vastauksissa teemoiksi nousivat moniammatillisuus ja ammattikohtaisuus koulutuksen toteutuksessa, kuntoutujiin liittyvät haasteet sekä kouluttajien GAS-osaaminen. Kouluttajien haastatteluissa esille nousivat koulutukseen osallistuneiden vastustavat ennakkoasenteet, moniammatillisen työskentelyn puute arjessa, totutuista rooleista poisoppiminen, vaikeus asettaa arkielämälähtöisiä ja tarkoituksenmukaisia tavoitteita sekä se, että kuntoutukselta puuttuu usein kokonaistavoite. Kouluttajat olivat syventäneet ja laajentaneet koulutussisältöjä ja muokanneet välitehtäviä kukin omalla tavallaan ja omien ryhmiensä tarpeista lähtien, joten GAS-koulutuksen yhdenmukaisuudesta ei voitane puhua. Raportin yhteenvetona kuvataan hyvän GAS-koulutuskäytännön elementit

Arterial stiffness and vascular complications in patients with type 1 diabetes: The finnish diabetic nephropathy (FinnDiane) study

While patients with type 1 diabetes (T1D) are known to suffer from early cardiovascular disease (CVD), we examined associations between arterial stiffness and diabetic complications in a large patient group with T1D.This study included 807 subjects (622 T1D and 185 healthy volunteers (age 40.6 ± 0.7 versus 41.6 ± 1.2 years; P = NS)). Arterial stiffness was measured by pulse wave analysis from each participant. Furthermore, information on diabetic retinopathy, nephropathy, and CVD was collected. The renal status was verified from at least two out of three urine collections.Patients with T1D without signs of diabetic nephropathy had stiffer arteries measured as the augmentation index (AIx) than age-matched control subjects (17.3% ± 0.6% versus 10.0% ± 1.2%; P0.001). Moreover, AIx (OR 1.08; 95% CI 1.03-1.13; P = 0.002) was associated with diabetic laser-treated retinopathy in patients with normoalbuminuria in a multivariate logistic regression analysis. The same was true for AIx and diabetic nephropathy (1.04 (1.01-1.08); P = 0.004) as well as AIx and CVD (1.06 (1.00-1.12); P = 0.01) in patients with T1D.Arterial stiffness was associated with microvascular and macrovascular complications in patients with T1D

Continuation of fluoropyrimidine treatment with S-1 after cardiotoxicity on capecitabine- or 5-fluorouracil-based therapy in patients with solid tumours : a multicentre retrospective observational cohort study

Publisher Copyright: © 2022 The Author(s)Background: Capecitabine- or 5-fluorouracil (5-FU)-based chemotherapy is widely used in many solid tumours, but is associated with cardiotoxicity. S-1 is a fluoropyrimidine with low rates of cardiotoxicity, but evidence regarding the safety of switching to S-1 after 5-FU- or capecitabine-associated cardiotoxicity is scarce. Patients and methods: This retrospective study (NCT04260269) was conducted at 13 centres in 6 countries. The primary endpoint was recurrence of cardiotoxicity after switch to S-1-based treatment due to 5-FU- or capecitabine-related cardiotoxicity: clinically meaningful if the upper boundary of the 95% confidence interval (CI; by competing risk) is not including 15%. Secondary endpoints included cardiac risk factors, diagnostic work-up, treatments, outcomes, and timelines of cardiotoxicity. Results: Per protocol, 200 patients, treated between 2011 and 2020 [median age 66 years (range 19-86); 118 (59%) males], were included. Treatment intent was curative in 145 (73%). Initial cardiotoxicity was due to capecitabine (n = 170), continuous infusion 5-FU (n = 22), or bolus 5-FU (n = 8), which was administered in combination with other chemotherapy, targeted agents, or radiotherapy in 133 patients. Previous cardiovascular comorbidities were present in 99 (50%) patients. Cardiotoxic events (n = 228/200) included chest pain (n = 125), coronary syndrome/infarction (n = 69), arrhythmia (n = 22), heart failure/cardiomyopathy (n = 7), cardiac arrest (n = 4), and malignant hypertension (n = 1). Cardiotoxicity was severe or life-threatening in 112 (56%) patients and led to permanent capecitabine/5-FU discontinuation in 192 (96%). After switch to S-1, recurrent cardiotoxicity was observed in eight (4%) patients (95% CI 2.02-7.89, primary endpoint met). Events were limited to grade 1-2 and occurred at a median of 16 days (interquartile range 7-67) from therapy switch. Baseline ischemic heart disease was a risk factor for recurrent cardiotoxicity (odds ratio 6.18, 95% CI 1.36-28.11). Conclusion: Switching to S-1-based therapy is safe and feasible after development of cardiotoxicity on 5-FU- or capecitabine-based therapy and allows patients to continue their pivotal fluoropyrimidine-based treatment.Peer reviewe

Modelling the impacts of agricultural management practices on river water quality in Eastern England

Agricultural diffuse water pollution remains a notable global pressure on water quality, posing risks to aquatic ecosystems, human health and water resources and as a result legislation has been introduced in many parts of the world to protect water bodies. Due to their efficiency and cost-effectiveness, water quality models have been increasingly applied to catchments as Decision Support Tools (DSTs) to identify mitigation options that can be introduced to reduce agricultural diffuse water pollution and improve water quality. In this study, the Soil and Water Assessment Tool (SWAT) was applied to the River Wensum catchment in eastern England with the aim of quantifying the long-term impacts of potential changes to agricultural management practices on river water quality. Calibration and validation were successfully performed at a daily time-step against observations of discharge, nitrate and total phosphorus obtained from high-frequency water quality monitoring within the Blackwater sub-catchment, covering an area of 19.6 km2. A variety of mitigation options were identified and modelled, both singly and in combination, and their long-term effects on nitrate and total phosphorus losses were quantified together with the 95% uncertainty range of model predictions. Results showed that introducing a red clover cover crop to the crop rotation scheme applied within the catchment reduced nitrate losses by 19.6%. Buffer strips of 2 m and 6 m width represented the most effective options to reduce total phosphorus losses, achieving reductions of 12.2% and 16.9%, respectively. This is one of the first studies to quantify the impacts of agricultural mitigation options on long-term water quality for nitrate and total phosphorus at a daily resolution, in addition to providing an estimate of the uncertainties of those impacts. The results highlighted the need to consider multiple pollutants, the degree of uncertainty associated with model predictions and the risk of unintended pollutant impacts when evaluating the effectiveness of mitigation options, and showed that high-frequency water quality datasets can be applied to robustly calibrate water quality models, creating DSTs that are more effective and reliable

Frequent and intensive physical activity reduces risk of cardiovascular events in type 1 diabetes

Aims/hypothesis Cardiovascular disease (CVD) is the most common cause of premature death and disability among patients with type 1 diabetes. Diabetic nephropathy accounts for the increased cardiovascular morbidity and mortality of these patients. We recently showed that the intensity of exercise predicts the incidence and progression of diabetic nephropathy in patients with type 1 diabetes. Little is known about the relationship between physical activity and CVD. Therefore, we studied how physical activity affects the risk of CVD events in patients with type 1 diabetes. Methods A 10 year follow-up study including 2180 type 1 diabetes patients from the nationwide multicentre Finnish Diabetic Nephropathy Study (FinnDiane). Leisure time physical activity (LTPA) was assessed by a previously validated self-report questionnaire. A CVD event was defined as a verified myocardial infarction, coronary procedure or stroke. Patients were analysed separately for the risk of developing a first ever CVD event and for the risk of a recurrent CVD event following a baseline event. Results A total of 206 patients had an incident CVD event during follow-up. A higher total LTPA and higher intensity, frequency and duration of activity were associated with a lower risk of incident CVD events. The observed association between exercise frequency and incident CVD remained significant when adjusted for classic risk factors. Exercise intensity also had a borderline effect on the recurrence-free time in patients with a major CVD event at baseline. Conclusion/interprelation This study suggests that exercise, particularly high frequency and high intensity exercise, may reduce the risk of CVD events in patients with type 1 diabetes.Peer reviewe

Association Testing of Previously Reported Variants in a Large Case-Control Meta-analysis of Diabetic Nephropathy

We formed the GEnetics of Nephropathy–an International Effort (GENIE) consortium to examine previously reported genetic associations with diabetic nephropathy (DN) in type 1 diabetes. GENIE consists of 6,366 similarly ascertained participants of European ancestry with type 1 diabetes, with and without DN, from the All Ireland-Warren 3-Genetics of Kidneys in Diabetes U.K. and Republic of Ireland (U.K.-R.O.I.) collection and the Finnish Diabetic Nephropathy Study (FinnDiane), combined with reanalyzed data from the Genetics of Kidneys in Diabetes U.S. Study (U.S. GoKinD). We found little evidence for the association of the EPO promoter polymorphism, rs161740, with the combined phenotype of proliferative retinopathy and end-stage renal disease in U.K.-R.O.I. (odds ratio [OR] 1.14, P = 0.19) or FinnDiane (OR 1.06, P = 0.60). However, a fixed-effects meta-analysis that included the previously reported cohorts retained a genome-wide significant association with that phenotype (OR 1.31, P = 2 × 10−9). An expanded investigation of the ELMO1 locus and genetic regions reported to be associated with DN in the U.S. GoKinD yielded only nominal statistical significance for these loci. Finally, top candidates identified in a recent meta-analysis failed to reach genome-wide significance. In conclusion, we were unable to replicate most of the previously reported genetic associations for DN, and significance for the EPO promoter association was attenuated