Characterization of secondary and therapy-related acute myeloid leukemia

Secondary acute myeloid leukemia (s-AML) refers to patients with either therapy-related AML (t-AML), that is, AML after treatment with chemo- and/or radiation for a prior disease, or AML progressing from an antecedent hematologic disorder (AHD-AML), typically a myelodysplastic syndrome (MDS) or a myeloproliferative neoplasm. Patients with s-AML present with higher rates of adverse cytogenetic aberrations and higher frequencies of adverse mutations and, subsequently, respond worse to therapy, and have poorer outcome compared to de novo AML. To identify clinical and molecular factors that may improve prognostication is therefore of importance to guide clinical decision-making. The general aim of this thesis was to broaden the real-world knowledge of s-AML, regarding disease properties and outcome, using population-based registries, and additionally to investigate the importance of mutations in the transformation from MDS to AML. The research papers presented herein cover mutational screening in MDS and s-AML (study I), general characteristics and outcome of s-AML (study II), the role of allogeneic hematopoietic cell transplantation (HCT) in patients with s-AML (study III), and the epidemiology and treatment outcome specifically for t-AML (study IV).In study I, high-throughput methods were used to find mutations in 22 genes in 100 MDS and 92 AML patients. The AML cohort consisted of t-AML, AHD-AML and AML with MDS-like cytogenetics. In AML, mutations were most commonly seen in oncogenes and cell signaling genes, and in MDS in splicing factor genes and epigenetic regulators. A key finding was the overrepresentation of mutated U2AF1 in cases with MDS progressing to AML. Furthermore, in addition to established risk scores, mutational status improved prognostication. In study I, high-throughput methods were used to find mutations in 22 genes in 100 MDS and 92 AML patients. The AML cohort consisted of t-AML, AHD-AML and AML with MDS-like cytogenetics. In AML, mutations were most commonly seen in oncogenes and cell signaling genes, and in MDS in splicing factor genes and epigenetic regulators. A key finding was the overrepresentation of mutated U2AF1 in cases with MDS progressing to AML. Furthermore, in addition to established risk scores, mutational status improved prognostication. In study II we used the Swedish AML registry (SAMLR) to characterize s-AML in a population-based setting. Of the 3263 AML patients included, 19% were AHD-AML and 8% t-AML. Differences between the subtypes were found in age, gender distribution and cytogenetic risk. Compared to de novo AML, complete remission rates were lower in s-AML, but early death rates were similar. In multivariable analysis, both t-AML and AHD-AML emerged as independent prognostic factors, with a more pronounced negative impact in younger age groups. HCT is a potentially curable consolidation treatment in eligible patients. In study III, data on 3337 intensively treated patients in SAMLR were combined with data from the Swedish Cancer Registry (SCR) and the Swedish transplantations centers to investigate the role of HCT in s-AML. HCT in first remission was superior to consolidation treatment with chemotherapy only. Long-term survivors with s-AML were rare without HCT. In study IV we studied 686 patients with t-AML in detail using SAMLR, SCR and the Swedish Rheumatology Quality Register. We found an increasing incidence of t-AML over time, and an increasing proportion with t-AML of AML in total. Survival was overall dismal, but comparable to de novo AML in patients with favorable cytogenetic risk and in patients with mutated NPM1 in combination with absence of FLT3-ITD. In conclusion, secondary AML is a highly heterogeneous disease with a particularly poor outcome. However, the clinical and genetic differences within the disease enable risk stratification of patients and may thus aid in treatment recommendations

Increasing synchrony of annual river-flood peaks and growing season in Europe

In a changing climate, time sensitive ecological interactions such as pollination and predation are vulnerable to temporal mismatch with direct consequences for ecosystem functioning. It is not known if synchrony and asynchrony of ecological and physical processes such as flood disturbance and plant phenology may similarly be affected by climate change. Here, by spatially merging temperature and flood peak data, we show for the first time that in Central and Eastern Europe annual river flood peaks increasingly occur within the thermal growing season. This is due to the combined effect of earlier springs and later flood peaks. Such increased physical‐phenological synchrony may especially impact river biogeomorphology and riparian floodplain ecosystem functioning through uprooting of seedlings and increased hydraulic roughness during major flood events

Gait analysis of unprovoked pig gait on clean and fouled concrete surfaces

Inadequate floor properties are considered the primary cause of the majority of claw disorders in pigs but to date no clear relationship has been found between claw disorders and floor properties such as friction and surface abrasiveness. To determine this relationship, the factors controlling pig gait must be characterised. This study examined unprovoked pig gait on a concrete floor in clean conditions and compared it with gait in fouled floor conditions. Kinematics were used to record gait parameters such as walking speed, stride length, swing and stance time, stride elevation together with limb support phases, gait symmetry, diagonality and duty factor. On clean floors, pigs had an unprovoked symmetrical gait with alternating two- and three-beat support phases and a high rate of diagonality. Stride length, swing and stance time and stride elevation showed little variation. Pigs altered their gait in accordance with floor conditions to maintain gait control by reducing walking speed, lowering diagonality and employing more three-limb support phases. Pigs also shortened their stride length and prolonged their stance time

Återvunnen mineralullsisolering som lösull i lantbrukets ekonomibyggnader

Återvinningsföretaget Sydskånes avfallsaktiebolag (Sysav AB) har konstaterat att allt mindre mängder avfall deponeras och att mineralullsisolering har blivit en allt större andel av deponerade material. Producenterna av glasull och stenull tycks inte vara intresserade av att återvinna isoleringsmaterialet. Detta projekt har syftat till att studera teknik och ekonomi för återvunnen mineralullsisolering som lösull i lantbrukets ekonomibyggnader. I projektet har man praktiskt utvärderat hur det går att tillverka lösfyllnadsisolering av återvunnen isolering samt testat metodiken för att tillföra återvunnen lösull till ett vindsbjälklag. I projektet har även möjligheterna att bygga upp en marknad för avsättning av återvunnen mineralullsisolering analyserats. Projektet har visat att konceptet med att återvinna mineralull som lösullsisolering i lantbrukets ekonomibyggnader har en viss potential ur produktionsteknisk synpunkt. Marknaden för denna isolerprodukt i lantbrukets ekonomibyggnader är emellertid relativt begränsad men den kan eventuellt bli en nischprodukt för gör-det-självare inom lantbruket

Knäpparlarver knäpparlarvskador

Knäpparna tillhör skalbaggarna. Den fullbildade insekten kan, om den vänds på rygg, slunga sig upp i luften och komma nerpå rätt köl. Härvid hörs ett svagt knäppande ljud, något som givit gruppen dess namn. Av de ca 80svenska arterna är endast ett fåtal skadegörare och till dem hör arter inom bl. a. släktet Ag riotes

Session A3: Think Big: Adding Large Structures To Improve Ecosystem Health

Abstract: The Vindel River is one of the few freeflowing its entire catchment are part of the Natura 2000 network. The river was exploited for timber floating between 1850–1976; rapids in the main channel and tributaries below the alpine tree line were channelized to increase timber transport capacity. Side channels were cut off and the flow was concentrated to a single channel from which boulders and large wood were removed. Hence, previously heterogeneous environments were replaced by more homogeneous systems with limited habitat for riverine species. The Vindel River LIFE project (LIFE08 NAT/S/000266) works with the restoration of 25 tributaries in the Vindel River system. The project strives to alleviate the effects of fragmentation and channelization in affected rapids, to improve the quality of water and riparian habitats. The work has included the construction of over 1000 spawning grounds for brown trout, removal of 17 splash dams, the relocation of rocks into the channels, and the strategic placement of large boulders and dead wood in over 50 km of river. Follow up studies have been done in the channels that have been restored with “demonstration methods,” where previously best-practice restored reaches have been re-restored by adding large boulders and large wood (i.e., entire trees, including root wads) from adjacent upland to the channel. The demonstration restoration has generated wider and more complex streams, which in turn has led to more variable water flow and higher water levels. This will decrease the risk of erosion during high flow and reduce the risk of losing spawning areas. However, fish population data collected by electrofishing before and after restoration show very inconsistent results among tributaries. This highlights the need for considering potential catchment scale degradation and not only concentrating on reach scale problems in order to re-establish ecosystem health

Regeneration failure of Scots pine changes the species composition of young forests

How seedling mortality and browsing affects species composition of regenerating forests has been mostly studied on a small scale. Yet, large-scale analyses based on extensive data are essential for robust prediction of species composition in young forests. In this study, we used a dataset from a national inventory of young forests (1-4 metres in height) to investigate the species composition of young forests across Sweden. We found that most of the regenerated forest area (almost 90%) was planted with Norway spruce (southern Sweden) and Scots pine (northern Sweden). Regeneration of Norway spruce was generally relatively successful but as a consequence of seedling mortality and browsing, almost 40% of the area regenerated with Scots pine will probably not develop into pine-dominated stands. Thus, low survival of Scots pine seedlings and trees can profoundly change the trajectory of species composition of the young forest from what was originally intended, and a large proportion of the young stands may develop into mixtures of conifers and broadleaves. While such mixtures may benefit certain biodiversity and ecosystem services, a loss of Scots pine dominated stands may also have adverse impacts on the economic returns as well as pine-dependent biodiversity and recreational values

Session A5: Dam Removal: Enhancing or Degrading Ecological Integrity?

Abstract: Removal of dams is increasingly being used to restore fragmented rivers and streams. The incentive is often to give migrating fish access to upstream spawning habitats, but dam removal may also bring other benefits, such as recovery of riparian vegetation and a more heterogeneous environment for aquatic invertebrates. Dam removal may also act as a disturbance on the system, releasing trapped sediments to downstream reaches. Depending on the amount of sediments in the former reservoir this disturbance may be transient or act over a longer time period. Whether dam removal is beneficial or not to the ecosystem may therefore depend on the type of organism. We have studied the effect of dam removal on riparian vegetation and benthic invertebrates in two Swedish streams over a period of 3 and 5 years respectively, and found that riparian vegetation generally benefitted from removal. Species richness increased, and species composition became more similar to a reference situation within a three year period. In contrast, benthic invertebrates seemed to be negatively affected by dam removal. While we saw no effects on community composition of benthic invertebrates, taxon richness decreased continuously over a five year period and total densities decreased initially but showed weak signs of recovery over the five year period. Our results also indicate that the response varies between invertebrate taxa

Comparison of plant establishment after different intensities of regeneration in the region of Svealand

I Sverige tillämpar vi skogsbruk på en stor del av vår skogsmark, vilket oftast skapar en serie av skötselåtgärder, däribland föryngring av skogsmark. Det finns ett urval av metoder för föryngring, varav ett fåtal är mer beprövade och tillämpade än andra. Skogsvårdslagen ställer krav på antalet etablerade plantor vid en viss tidpunkt efter avverkning, vilket kan påverka val av föryngringsmetod. Den vanligaste föryngringsmetoden är plantering, oftast föregånget av maskinell markberedning. Det finns även alternativet att inte göra någon åtgärd alls efter avverkning utan lita till naturens egen förmåga att föryngra. Denna metod är relativt outforskad och därför anlades på 80-talet ett försök med olika skötselintensiteter vid beståndsanläggning. Försöket skulle representera olika ambitionsnivåer i skogsbruket och visa på hur de olika bestånden utvecklade sig. Vår studie bygger på inventeringsdata från tre lokaler där granplantering efter markberedning normalt skulle vara standard. På varje lokal jämfördes ett för tiden intensivt föryngringsarbete med normen för vad som klassades som normalt föryngringsarbete. En tredje jämförelse gjordes mot ytor lämnade utan vidare åtgärder i föryngringsarbetet. Syftet var att undersöka hur föryngringsintensiteten påverkat plantetableringen/plantuppslag i form av antal etablerade plantor, och vidare om de olika intensiteterna påverkade höjdutvecklingen från respektive beståndsanläggning till dess första inventering 1991. En statistisk analys kunde inte påvisa att skötselintensiteten påverkade plantetableringen men om man visuellt jämför medelvärden för antal plant hos intensiteterna ser vi att intensiv har flest plantor och extensiv lägst antal plantor. Dock fanns ett visst statistiskt samband mellan plantetablering och blockvariabeln, dvs. var i landet blocken var placerade. Blocket med torvmark hade lägst plantetablering i alla intensiteter. Vad gäller plantornas höjdtillväxt påvisade ingen enskild skötselintensitet ett högre medelvärde för plantorns höjdtillväxt kontra de andra.Våra resultat kommer från ett fåtal platser med till viss del olika mark och är därför inte representativt i ett större perspektiv.In Sweden most of the forest land is being managed according to existing silviculture practice, which includes forest regeneration. There is a number of regeneration methods to choose among, some of which are more proven and practiced than others. According to the Forestry Act there has to be a certain number of established plants at a certain point after the felling, which could affect the choice of regeneration method. The most common regeneration method is planting, often preceded by soil scarification. Alternatives to planting could be natural regeneration, shelter trees or sowing. There is also the option of doing nothing and trust nature’s ability to regenerate itself. This method is relatively uncharted; hence an experiment initiated in the 80s with different management intensities when establishing new stands. The experiment would represent different degrees of ambition in silviculture and show how the different stands developed. For the following study, values from three blocks in said experiment have been used. For those blocks, planting of spruce after soil scarification would be the normal procedure. On each site a high intensity regeneration method was compared to what at the time was considered a normal intensity for regeneration. A third comparison was made to test areas who had been left untouched after the final felling of the previous stand. The aim of this study was to analyze how the regeneration intensity affected plant establishment/number of plants and furthermore how the intensity affected height growth during the time from final felling to the first inventory in 1991. A statistical analysis did not indicate that the management intensity had any effect on plant establishment. However, a visual overview of the mean values of number of plants shows that the intense regeneration method had the highest number of plants and the low intensity had the lowest number of plants. There was however a connection between plant establishment and the block variable, i.e. where the experiment site was situated. The block situated on peat land had the lowest number of plants in all intensities. Regarding the height of the plants, no plants regularly showed a different development than the others, when comparing the different management intensities. Our results originate from only a few experiment sites, with partially different soils and are therefore not very representative in a bigger perspective