Economic evaluation of using polygenic risk score to guide risk screening and interventions for the prevention of type 2 diabetes in individuals with high overall baseline risk

Type 2 diabetes (T2D) with increasing prevalence is a significant global public health challenge. Obesity, unhealthy diet, and low physical activity are one of the major determinants of the rise in T2D prevalence. In addition, family history and genetic risk of diabetes also play a role in the process of developing T2D. Therefore, solutions for the early identification of individuals at high risk for T2D for early targeted detection of T2D, prevention, and intervention are highly preferred. Recently, novel genomic-based polygenic risk scores (PRSs) have been suggested to improve the accuracy of risk prediction supporting the targeting of preventive interventions to those at highest risk for T2D. Therefore, the aim of the present study was to assess the cost-utility of an additional PRS testing information (as a part of overall risk assessment) followed by a lifestyle intervention and an additional medical therapy when estimated 10-year overall risk for T2D exceeded 20% among Finnish individuals screened as at the high-risk category (i.e., 10%-20% 10-year overall risk of T2D) based on traditional risk factors only. For a cost-utility analysis, an individual-level state-transition model with probabilistic sensitivity analysis was constructed. A 1-year cycle length and a lifetime time horizon were applied in the base-case. A 3% discount rate was used for costs and QALYs. Cost-effectiveness acceptability curve (CEAC) and estimates for the expected value of perfect information (EVPI) were calculated to assist decision makers. The use of the targeted PRS strategy reclassified 12.4 percentage points of individuals to be very high-risk individuals who would have been originally classified as high risk using the usual strategy only. Over a lifetime horizon, the targeted PRS was a dominant strategy (i.e., less costly, more effective). One-way and scenario sensitivity analyses showed that results remained dominant in almost all simulations. However, there is uncertainty, since the probability (EVPI) of cost-effectiveness at a WTP of 0(sic)/QALY was 63.0% (243(sic)) indicating the probability that the PRS strategy is a dominant option. In conclusion, the results demonstrated that the PRS provides moderate additional value in Finnish population in risk screening leading to potential cost savings and better quality of life when compared with the current screening methods for T2D risk.Peer reviewe

Opettajan opas. Koulutus- ja tiedotusmateriaali kuljettajien ammattipätevyyskoulutukseen.

Opettajan opas pyrkii edistämään tavaraliikenteen ammattikuljettajien työterveyttä, työturvallisuutta ja työn ergonomiaa

Ammattikuljettajan työhyvinvointi - turvallinen ja ergonominen työpäivä : Opettajan opas

Opettajan opas pyrkii edistämään tavaraliikenteen ammattikuljettajien työterveyttä, työturvallisuutta ja työn ergonomiaa. Opettajan opas tuotettiin Koulutus- ja tiedotusmateriaali jakeluautonkuljettajien ammattipätevyyskoulutukseen

Glyphosate-based herbicide has soil-mediated effects on potato glycoalkaloids and oxidative status of a potato pest

Glyphosate is the most used herbicide worldwide, targeting physiological pathways in plants. Recent studies have shown that glyphosate can also cause toxic effects in animals. We investigated the glyphosate-based herbicide (GBH)-induced changes in potato (Solanum tuberosum) plant chemistry and the effects of a GBH on the survival rate and oxidative status of the Colorado potato beetle (Leptinotarsa decemlineata). The beetles were reared on potato plants grown in pots containing soil treated with a GBH (Roundup Gold, 450 g/l) or untreated soil (water control). The 2nd instar larvae were introduced to the potato plants and then collected in 2 phases: as 4th instar larvae and as adults. The main glycoalkaloids of the potato plants, α-solanine and α-chaconine, were measured twice during the experiment. The α-solanine was reduced in potato plants grown in GBH-treated soil, which can be detrimental to plant defenses against herbivores. GBH treatment had no effect on the survival rate or body mass of the larvae or the adult beetles. In the larvae, total glutathione (tGSH) concentration and the enzyme activity of catalase (CAT), superoxide dismutase, and glutathione-S-transferase were increased in the GBH treatment group. In the adult beetles, CAT activity and tGSH levels were affected by the interactive effect of GBH treatment and the body mass. To conclude, environmentally relevant concentrations of a GBH can affect the potato plant’s glycoalkaloid concentrations, but are not likely to directly affect the survival rate of the Colorado potato beetle, but instead, modify the antioxidant defense of the beetles via diet.</p

Best food - good life

Visio tulevaisuuden ruokajärjestelmästä vastaa niin globaaleihin kuin paikallisiinkin haasteisiin, jotka johtuvat ilmastonmuutoksesta, ekosysteemipalvelujen heikkenemisestä, resurssien niukkenemisesta, ruoan ja energian lisääntyvästä tarpeesta, nopeasta sosiaalisesta eriarvoistumisesta, maahanmuutosta ja kansalaisten etääntymisestä ruoan alkuperästä. Visio ottaa kantaa ruoan huoltovarmuuteen kansallisesti ja ruokaan globaalina ihmisoikeutena. Visiossa hahmotellaan tulevaisuuden ruokajärjestelmä ja keinot sen toteuttamiseksi viiden seuraavan kokonaisuuden avulla. 1. Tavoitteena ruokaturva Kotimainen ruokaturva perustuu kannattavaan ja ympäristöystävälliseen, paikalliseen ja verkottuneeseen tuotantojärjestelmään, joka on tärkeimpien tuotannontekijöitten suhteen kansallisesti omavarainen. Järjestelmän perusominaisuuksiin kuuluu kierrätys ja vähäiset hävikit. Ruokajärjestelmä pystyy takaamaan kansalaisille kaikissa olosuhteissa ravitsemuksellisesti riittävän ruoan, samalla kun se tuottaa muita biotuotannon raaka-aineita ja energiaa. Ruokajärjestelmälle on annettu yhteisöjä vahvistava tehtävä, ja sen sosiaalipoliittinen merkitys on huomattu. 2. Kuluttamisesta osallistumiseen Osallistava ruokajärjestelmä kytkee jokaisen ihmisen ruoantuotantoon ja lisää näin tietoisuutta sekä arvostusta ruoan tuottamisesta ja ympäristöstä. Ruokakansalainen on tietoinen ruoan laadun eri ulottuvuuksista. Osallistuminen mm. lähiruokayhteisöihin luo merkityksellisyyttä ja hyvinvointia. 3. Ihmisten yhteisöjä ja luonnon resursseja vaalien Tehokkain ekologisin menetelmin viljelty maa tuottaa ravitsemuksellisesti korkeita ja varmoja satoja. Viljelymaat sitovat hiiltä maaperään ja hidastavat ilmastonmuutosta. Tasapainoinen tuotantorakenne on mahdollistanut kierrätysmaatalouden: rehu- ja ravinnevirrat ovat paikallisia. Maatalousmaan väheneminen on estetty maankäytön kokonaisvaltaisella suunnittelulla, ja maanvuokrausta on kehitetty pitkäjänteiseksi mahdollistamaan investoinnit maan laatuun. Maatalouden ja elintarvikejalostuksen paikalliset, integroidut järjestelmät ovat tuoneet ruoan huoltovarmuuden kannalta merkityksellistä sitkeyttä ja vakautta, ne mahdollistavat tehokkaan uusiutuvan energian tuotannon sekä ravinteiden kierrätyksen. Maaseudun yhteisöt ovat vahvistuneet ja niiden yhteydet kaupunkialueisiin konkretisoituneet. Maaseutu on jälleen paikka työskennellä, harrastaa, asua ja elää. 4. Ruoantuotanto turvaa ja tuottaa ekosysteemipalveluja Uudet tuotantotavat nojaavat ekosysteemipalveluihin. Ruoka ymmärretään ekosysteemipalveluna, ja viljely-ympäristöjen monimuotoinen eliöstö ymmärretään ekosysteemipalvelujen perustaksi. Ekosysteeminen ajattelu huomioidaan läpäisevästi niin perus- ja ammattiopetuksessa kuin maankäytön suunnittelussakin. Ruoan lisäksi viljelijät luonnon- ja maisemanhoitajina ansaitsevat muiden ekosysteemipalvelujen tuottamisesta sekä monimuotoisuuden vaalimisesta. 5. Maatalouspolitiikasta ruokapolitiikkaan Uusi ruokapolitiikka vähentää maataloustuotannon tukiriippuvuutta ja kannustaa ekologisesti tehokkaaseen korkeatuottoiseen, korkea-arvoisen ruoan tuotantoon. Politiikkatoimin on ohjattu ruokajärjestelmä toteuttamaan paitsi ravitsemuksellisia ja terveydellisiä, myös ympäristöllisiä, sosiaalisia ja taloudellisia tavoitteita. Ruokaturva, oikeus hyvään ravitsemukseen on nostettu ruokapolitiikan perustaksi, ja Suomi edistää tätä näkemystä kansainvälisesti

Creating spatially continuous maps of past land cover from point estimates: A new statistical approach applied to pollen data

International audienceReliable estimates of past land cover are critical for assessing potential effects of anthropogenic land-cover changes on past earth surface-climate feedbacks and landscape complexity. Fossil pollen records from lakes and bogs have provided important information on past natural and human-induced vegetation cover. However, those records provide only point estimates of past land cover, and not the spatially continuous maps at regional and sub-continental scales needed for climate modelling. We propose a set of statistical models that create spatially continuous maps of past land cover by combining two data sets: 1) pollen-based point estimates of past land cover (from the REVEALS model) and 2) spatially continuous estimates of past land cover, obtained by combining simulated potential vegetation (from LPJ-GUESS) with an anthropogenic land-cover change scenario (KK10). The proposed models rely on statistical methodology for compositional data and use Gaussian Markov Random Fields to model spatial dependencies in the data. Land-cover reconstructions are presented for three time windows in Europe: 0.05, 0.2, and 6 ka years before present (BP). The models are evaluated through cross-validation, deviance information criteria and by comparing the reconstruction of the 0.05 ka time window to the present-day land-cover data compiled by the European Forest Institute (EFI). For 0.05 ka, the proposed models provide reconstructions that are closer to the EFI data than either the REVEALS-or LPJ-GUESS/KK10-based estimates; thus the statistical combination of the two estimates improves the reconstruction. The reconstruction by the proposed models for 0.2 ka is also good. For 6 ka, however, the large differences between the REVEALS-and LPJ-GUESS/KK10-based estimates reduce the reliability of the proposed models. Possible reasons for the increased differences between REVEALS and LPJ-GUESS/KK10 for older time periods and further improvement of the proposed models are discussed

A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape

Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways

Rare and low-frequency coding variants alter human adult height

Height is a highly heritable, classic polygenic trait with ~700 common associated variants identified so far through genome - wide association studies . Here , we report 83 height - associated coding variants with lower minor allele frequenc ies ( range of 0.1 - 4.8% ) and effects of up to 2 16 cm /allele ( e.g. in IHH , STC2 , AR and CRISPLD2 ) , >10 times the average effect of common variants . In functional follow - up studies, rare height - increasing alleles of STC2 (+1 - 2 cm/allele) compromise d proteolytic inhibition of PAPP - A and increased cleavage of IGFBP - 4 in vitro , resulting in higher bioavailability of insulin - like growth factors . The se 83 height - associated variants overlap genes mutated in monogenic growth disorders and highlight new biological candidates ( e.g. ADAMTS3, IL11RA, NOX4 ) and pathways ( e.g . proteoglycan/ glycosaminoglycan synthesis ) involved in growth . Our results demonstrate that sufficiently large sample sizes can uncover rare and low - frequency variants of moderate to large effect associated with polygenic human phenotypes , and that these variants implicate relevant genes and pathways

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