Cracks in turnout sleepers -- Conclusions from a questionnaire to the UIC Track Expert Group

To investigate the occurrence of cracks in turnout sleepers, how these were assessed and handled, a questionnaire was sent out to 15 members of the UIC Track expert group in December 2020. By February 20, 2021, eleven responses have been received. The responses are summarised and commented below

Överlevnad, höjd och skador i odlingstester och proveniensförsök med douglasgran i södra Sverige

Den pågående klimatförändringen påverkar odlingsförutsättningarna för såväl inhemska som icke inhemska arter. Douglasgran (Pseudotsuga menziesii [Mirb.] Franco) är ett av de trädslag som anses kunna växa bra i ett förändrat klimat och skulle kunna bli ett komplement till t.ex. granen i något större omfattning än vad som är fallet idag. En av de faktorer som hämmar en sådan ökad etablering är kunskap om och tillgång till lämpliga provenienser. Med utgångspunkt i befintliga svenska proveniensförsök införskaffade Södra skog och SkogForsk 2007 ett fröparti från British Columbia, Kanada, bestående av sju provenienser av douglasgran. Fyra av dessa var kustnära, latitud 48–52°N, och de övriga tre härstammar från det inlandet, latitud 50°N. Plantor från dessa frön odlades upp och under 2009 och 2010 anlades odlingstester där provenienserna ingick. I odlingstesterna ingår 12 lokaler och på dessa har inventeringar genomförts efter en, tre och sex växtsäsonger. På fem av dessa lokaler gjordes en radvis inblandning av hybridlärk (Larix × marschlinsii Coaz) och på två lokaler planterades förutom douglasgran även vanlig gran gran (Picea abies [L.] Karst.). Ett proveniensförsök anlades 2010 i Tönnersjöhedens försökspark där de sju provenienserna ingår och detta försök har inventerats på samma sätt som odlingstesterna. Under våren 2013 drabbades många föryngringar av vinterfrosttorka och då gjordes en särskild uppföljning av odlingstesterna och proveniensförsöket. Det fanns inga signifikanta skillnader i överlevnad mellan de olika provenienserna, varken efter en eller tre tillväxtsäsonger i odlingstesterna. Inlandsprovenienserna Larch Hills och Three Valley hade signifikant högre överlevnad (76 och 71 %) än kustprovenienserna Caycuse River och Bowser Heaman (50 och 48 %), efter sex växtsäsonger. Bowser Heaman-plantorna var signifikant högre (2,09 m) än Three Valley-plantorna (1,67 m), efter sex växtsäsonger. I övrigt fanns inga signifikanta höjdskillnader mellan provenienserna i något av experimenten vid någon tidpunkt. Medelhöjden för de 10 högsta träden tenderade att vara svagt positivt korrelerad med högre temperatursumma för provenienser från kusten, medan detta samband inte kunde ses för inlandsprovenienserna. Resultaten visar att det är hög risk för avgångar i stora delar av Götaland om man inte använder tillräckligt härdiga provenienser för vårt klimat. De härdigare inlandsprovenienserna är därför troligen att föredra, med undantag för gynnsamma klimatzoner i sydligaste Sverige och vissa kustnära områden. När många plantor i Småland fick skador av vinterfrosttorka i april 2013, drabbades kustprovenienserna av douglasgran hårdare än de från inlandet. Orsaken kan vara att kustproveniensernas senare invintring kan medföra skador på hösten. De var då redan försvagade eller kanske till och med döda våren därpå. Detta ger ytterligare fog för en rekommendation att använda de härdigare inlandsprovenienserna, med tidigare invintring, i stora delar av Götaland

Novel subgroups of adult-onset diabetes and their association with outcomes : a data-driven cluster analysis of six variables

Background Diabetes is presently classified into two main forms, type 1 and type 2 diabetes, but type 2 diabetes in particular is highly heterogeneous. A refined classification could provide a powerful tool to individualise treatment regimens and identify individuals with increased risk of complications at diagnosis. Methods We did data-driven cluster analysis (k-means and hierarchical clustering) in patients with newly diagnosed diabetes (n=8980) from the Swedish All New Diabetics in Scania cohort. Clusters were based on six variables (glutamate decarboxylase antibodies, age at diagnosis, BMI, HbA(1c), and homoeostatic model assessment 2 estimates of beta-cell function and insulin resistance), and were related to prospective data from patient records on development of complications and prescription of medication. Replication was done in three independent cohorts: the Scania Diabetes Registry (n=1466), All New Diabetics in Uppsala (n=844), and Diabetes Registry Vaasa (n=3485). Cox regression and logistic regression were used to compare time to medication, time to reaching the treatment goal, and risk of diabetic complications and genetic associations. Findings We identified five replicable clusters of patients with diabetes, which had significantly different patient characteristics and risk of diabetic complications. In particular, individuals in cluster 3 (most resistant to insulin) had significantly higher risk of diabetic kidney disease than individuals in clusters 4 and 5, but had been prescribed similar diabetes treatment. Cluster 2 (insulin deficient) had the highest risk of retinopathy. In support of the clustering, genetic associations in the clusters differed from those seen in traditional type 2 diabetes. Interpretation We stratified patients into five subgroups with differing disease progression and risk of diabetic complications. This new substratification might eventually help to tailor and target early treatment to patients who would benefit most, thereby representing a first step towards precision medicine in diabetes.Peer reviewe

BIG3 - Undersökning

BIG3 is a Scanian research project in which the name BIG3 is aiming at three major diseases: chronic obstructive pulmonary disease (COPD), cardiovascular diseases and lung cancer. The overall goal of BIG3 is to understand the mechanisms underlying these diseases in order to develop new treatments that can lead to earlier, better and more accurate diagnosis for better and more individualized treatment. BIG3 is an open prospective longitudinal cohort study in Sweden. As a first step, around 100 000 people in Scania between 45 and 75 years have the opportunity to answer a questionnaire about lifestyle, living environment and tobacco habits. Then about 10 000 individuals from the respondents will be summoned to undergo examinations. These include ECG, CT scan of the heart and lungs, pulmonary function tests and blood tests. The blood samples will be analyzed both directly for a number of markers and also stored in a biobank for later analysis. The goal is to try to get about 50% of smokers in the cohort. Ultimately, the study aims to find out which individuals that are at greater risk of developing one or more of the three diseases and why some individuals seem to be protected. Purpose: BIG3 aims to increase understanding and to reduce morbidity / mortality in chronic diseases such as COPD, lung cancer and cardiovascular diseases, and to improve the care and quality of life for individuals with these disorders. In the second stage, approximately 10 000 individuals of those submitted the questionnaire, are randomly invited to an examination at Skåne University Hospital. Until September 2014, approximately 1000 individuals completed an examination.BIG3 är ett skånskt forskningsprojekt där namnet BIG3 syftar på tre av våra folksjukdomar: kroniskt obstruktiv lungsjukdom (KOL), kardiovaskulära sjukdomar och lungcancer. Det övergripande målet med BIG3 är att förstå mekanismerna bakom dessa sjukdomar för att kunna ta fram nya behandlingsmetoder som kan leda till tidigare, bättre och säkrare diagnostik för bättre och en mer individualiserad behandling. BIG3 är en öppen prospektiv longitudinell kohortstudie i Skåne. Som ett första steg kommer ungefär 100 000 skåningar mellan 45 och 75 år att få möjlighet att besvara en enkät med frågor om livsstil, boendemiljö och tobaksvanor. Sedan kommer ca 10 000 individer från de som besvarat enkäten att kallas till att genomgå undersökningar. Dessa innefattar bland annat EKG, skiktröntgen av hjärta och lungor, lungfunktionsundersökningar och blodprover. Blodproverna analyseras dels direkt med avseende på ett antal markörer och lagras även i en biobank för senare analys. Målet är att försöka få ca 50% rökare i kohorten. I slutändan vill man veta vilka individer som löper en större risk att utveckla en eller flera av de tre sjukdomarna och varför en del verkar ha ett skydd. Syfte: Målet med BIG3 är att öka förståelsen och minska sjukligheten / dödligheten i kroniska sjukdomar som KOL, lungcancer och hjärt-kärlsjukdomar, och förbättra vården och livskvaliteten för personer med dessa sjukdomar. I det andra steget kommer ca 10 000 individer, av dem som skickat in enkäten, slumpmässigt att bjudas in till undersökning på Skånes universitetssjukhus. Fram till och med september 2014 var det ca 1000 individer som genomgått undersökning

BIG3 - Enkätundersökning

BIG3 is a Scanian research project in which the name BIG3 is aiming at three major diseases: chronic obstructive pulmonary disease (COPD), cardiovascular diseases and lung cancer. The overall goal of BIG3 is to understand the mechanisms underlying these diseases in order to develop new treatments that can lead to earlier, better and more accurate diagnosis for better and more individualized treatment. BIG3 is an open prospective longitudinal cohort study in Sweden. As a first step, around 100 000 people in Scania between 45 and 75 years have the opportunity to answer a questionnaire about lifestyle, living environment and tobacco habits. Then about 10 000 individuals from the respondents will be summoned to undergo examinations. These include ECG, CT scan of the heart and lungs, pulmonary function tests and blood tests. The blood samples will be analyzed both directly for a number of markers and also stored in a biobank for later analysis. The goal is to try to get about 50% of smokers in the cohort. Ultimately, the study aims to find out which individuals that are at greater risk of developing one or more of the three diseases and why some individuals seem to be protected. Purpose: BIG3 aims to increase understanding and to reduce morbidity / mortality in chronic diseases such as COPD, lung cancer and cardiovascular diseases, and to improve the care and quality of life for individuals with these disorders. As a first step, around 100,000 individuals between 45 and 75 years and living in Scania have the opportunity to answer a questionnaire about lifestyle and health. Until September 2014, the number of respondents to the questionnaire was about 3000.BIG3 är ett skånskt forskningsprojekt där namnet BIG3 syftar på tre av våra folksjukdomar: kroniskt obstruktiv lungsjukdom (KOL), kardiovaskulära sjukdomar och lungcancer. Det övergripande målet med BIG3 är att förstå mekanismerna bakom dessa sjukdomar för att kunna ta fram nya behandlingsmetoder som kan leda till tidigare, bättre och säkrare diagnostik för bättre och en mer individualiserad behandling. BIG3 är en öppen prospektiv longitudinell kohortstudie i Skåne. Som ett första steg kommer ungefär 100 000 skåningar mellan 45 och 75 år att få möjlighet att besvara en enkät med frågor om livsstil, boendemiljö och tobaksvanor. Sedan kommer ca 10 000 individer från de som besvarat enkäten att kallas till att genomgå undersökningar. Dessa innefattar bland annat EKG, skiktröntgen av hjärta och lungor, lungfunktionsundersökningar och blodprover. Blodproverna analyseras dels direkt med avseende på ett antal markörer och lagras även i en biobank för senare analys. Målet är att försöka få ca 50% rökare i kohorten. I slutändan vill man veta vilka individer som löper en större risk att utveckla en eller flera av de tre sjukdomarna och varför en del verkar ha ett skydd. Syfte: Målet med BIG3 är att öka förståelsen och minska sjukligheten / dödligheten i kroniska sjukdomar som KOL, lungcancer och hjärt-kärlsjukdomar, och förbättra vården och livskvaliteten för personer med dessa sjukdomar. I det första steget kommer ca 100 000 skåningar mellan 45 och 75 år få möjlighet att svara på en enkät om bland annat livsstil och hälsa. Fram till och med september 2014 var antalet individer som svarat på enkäten har ca 3000

Effects of long-term portal hypertension on structure, active force and content of contractile and structural proteins in smooth muscle of the rat portal vein

Growth of the smooth muscle cells in the rat portal vein was induced by a partial ligation of the vessel. The ligation caused an increase in the transmural pressure and segments of the portal vein were investigated 6 weeks after the ligation. The spontaneous contractile activity of the ligated veins was similar to that of the control veins. In the ligated vessels the active force at optimal length for force development was doubled, 22.8 +/- 1.3 compared with 12.5 +/- 1.4 mN for the controls. The cross-sectional area of the media in the ligated veins, determined on transverse sections, increased from the control value of 0.10 +/- 0.01 to 0.19 +/- 0.01 mm2. Electron microscopy revealed that the mean cross-sectional area of the smooth muscle cells in the ligated portal vein was doubled (controls: 6.4 +/- 0.6, hypertrophic: 13.6 +/- 1.8 microns2). This suggests hypertrophy of the smooth muscle cells in the vessel wall as the cause for the increase in cross-sectional area of the ligated veins. An increase in the number of intermediate filaments was observed in the hypertrophied smooth muscle. The relative contents of contractile (myosin and actin) and structural (desmin and vimentin) proteins were determined with SDS-polyacrylamide gel electrophoresis. The actin/myosin and vimentin/actin ratios were unaltered by hypertrophy. The hypertrophied veins showed an increase in the desmin/actin ratio (control: 0.20 +/- 0.01, hypertrophied: 0.27 +/- 0.03). The increased amounts of desmin correlates with the increased number of intermediate filaments observed by electron microscopy.(ABSTRACT TRUNCATED AT 250 WORDS

Correlation between isoform composition of the 17 kDa myosin light chain and maximal shortening velocity in smooth muscle

The relation between the isoform distribution of the myosin 17 kDa essential light chain (LC17) and the mechanical properties of smooth muscle was investigated. The relative content of the basic (LC17b) and acidic (LC17a) isoelectric variants of the 17 kDa myosin light chain was determined in different mammalian smooth muscle tissues. The relative content of LC17b varied between muscles: rabbit rectococcygeus 0%, rabbit trachea 5%, guinea-pig taenia coli 21%, rat uterus 38%, rabbit aorta 56% and rat aorta 60%. The rate of tension development was determined following photolysis of caged-adenosine triphosphate (ATP) in skinned fibres activated with thiophosphorylation of the regulatory light chains. The half-time for force development was 0.67 s in rabbit rectococcygeus, 1.6 s in rabbit trachea, 1.13 s in guinea-pig taenia coli and 1.38 s in rabbit aorta. The maximal shortening velocity (Vmax) was determined with the isotonic quick release technique in skinned fibre preparations activated with thiophosphorylation. Vmax was 0.25 muscle lengths per second (ML/s) in rabbit rectococcygeus, 0.24 ML/s in rabbit trachea, 0.17 ML/s in guinea-pig taenia coli, 0.11 ML/s in rat uterus and 0.03 ML/s in rabbit aorta. The range of variation in Vmax between muscles was larger than in the half-time for force development. The inverse relationship between Vmax and the relative content of LC17b in the investigated muscles suggests that the type of essential myosin light chain influences the Vmax in smooth muscle

Regulation of force and shortening velocity by calcium and myosin phosphorylation in chemically skinned smooth muscle

The phosphatase inhibitor okadaic acid (OA) was used to study the relationship between [Ca2+], rates of phosphorylation/dephosphorylation and the mechanical properties of smooth muscle fibres. Force/velocity relationships were determined with the isotonic quick release technique in chemically skinned guinea-pig taenia coli muscles at 22 degrees C. In the maximally thiophosphorylated muscle neither OA (10 microM) nor Ca2+ (increase from pCa 9.0 to pCa 4.5) influenced the force-velocity relationship. When the degree of activation was altered by varying [Ca2+] in the presence of 0.5 microM calmodulin, both force and the maximal shortening velocity (Vmax) were altered. At pCa 5.75, at which force was about 35% of the maximal at pCa 4.5, Vmax was 55% of the maximal value. When OA was introduced into fibres at pCa 6.0, force was increased from less than 5% to 100% of the maximal force obtained in pCa 4.5. The relationship between the degree of myosin light chain phosphorylation and force was similar in the two types of activation; varied [OA] at constant [Ca2+] and at varied [Ca2+]. The relation between force and Vmax when the degree of activation was altered with OA was almost identical to that obtained with varied [Ca2+]. The results show that Ca2+ and OA do not influence force or Vmax in the maximally phosphorylated state and suggest that the level of myosin light chain phosphorylation is the major factor determining Vmax. The finding that the relationship between force and Vmax was similar when activation was altered with OA and Ca2+ suggests, however, that alterations in the absolute rates of phosphorylation and dephosphorylation at a constant phosphorylation level do not influence the mechanical properties of the skinned smooth muscle fibres

Contractile properties during development of hypertrophy of the smooth muscle in the rat portal vein

Structural and mechanical alterations during hypertrophy of the rat portal vein were investigated. Growth of the vessel was induced by a partial ligature of the vessel causing an increased transmural pressure. Vessel segments from animals kept with ligature for 1, 3, 5 and 7 days, were compared with vessels from sham-operated animals. Maximal active force and vessel cross-sectional area increased with time in the ligated group. On day 7, force and cross-sectional area at the optimal length, were markedly increased in the ligated group (21.1 +/- 1.0 mN, 0.55 +/- 0.04 mm2, n = 9) compared with the control vessels (11.7 +/- 1.0 mN, 0.30 +/- 0.02 mm2, n = 7). Light and electron microscopy of preparations fixed at optimal length showed that the amount of smooth muscle and the cross-sectional area of cell profiles were almost doubled in the ligated group on day 7, consistent with hypertrophy of the smooth muscle. The force per smooth muscle cell area was similar in the two groups (ligated: 132 +/- 15; control: 145 +/- 16 mN mm-2, n = 4-5). The maximal shortening velocity was significantly lower in the hypertrophied group (ligated: 0.28 +/- 0.02; control: 0.41 +/- 0.01 optimal length s-1, n = 6). In chemically skinned preparations, activated by maximal thiophosphorylation of the myosin light chains, force was higher in the ligated group compared to the controls but no difference in maximal shortening velocity was observed. In conclusion, the increased transmural pressure is associated with a rapid increase in the amount of smooth muscle in the portal vein. The mechanical data show that after 7 days the force generating ability of the contractile system has increased in proportion to the smooth muscle cell mass. The unaltered maximal shortening velocity in the skinned hypertrophied preparations suggests that the kinetic properties of the maximally activated contractile system are unaltered. The decreased maximal shortening velocity in the intact hypertrophied preparations may reflect alterations in the excitation-contraction coupling

Cross-bridge cycling in smooth muscle: a short review

This review is focused on the cross-bridge interaction of the organized contractile system of smooth muscle fibres. By using chemically skinned preparations the different enzymatic reactions of actin-myosin interaction have been associated with mechanical events. A rigor state has been identified in smooth muscle and the binding of ATP causes dissociation of rigor cross-bridges at rates slightly slower than those in skeletal muscle, but fast enough not to be rate-limiting for cross-bridge turn over in the muscle fibre. The release of inorganic phosphate (Pi) is associated with force generation, and this process is not rate-limiting for maximal shortening velocity (Vmax) in the fully activated muscle. The binding of ADP to myosin is strong in the smooth muscle contractile system, a property that might be associated with the generally slow cross-bridge turn over. Both force and Vmax are modulated by the extent of myosin light chain phosphorylation. Low levels of activation are considered to be associated with the recruitment of slowly cycling dephosphorylated cross-bridges which reduces shortening velocity. The attachment of these cross-bridge states in skinned smooth muscles can be regulated by cooperative mechanisms and thin filament associated systems. Smooth muscles exhibit a large diversity in their Vmax and the individual smooth muscle tissue can alter its Vmax under physiological conditions. The diversity and the long-term modulation of phenotype are associated with changes in myosin heavy and light chain isoform expression