Fremtidens jernbanetrafik i Vestjylland: Et forslag til regional strategi

Atkins har for Holstebro, Herning og Ringkøbing-Skjern Kommuner udarbejdet et forslag til opgradering af regionalbanerne i Vestjylland. Baggrunden for forslaget var, at der ikke var nogen klar strategi for banerne i Midt- og Vestjylland, bortset fra at skinnelegemet skal moderniseres, og at et nyt signalsystem indføres omkring 2020-22. Disse tiltag vil i sig selv formentlig ikke medføre flere passagerer, og for at fastholde og øge passagertallet må der nødvendigvis ske en række passagervendte tiltag, der vil det gøre det mere attraktivt at rejse med toget. Tiltagene kan være flere tog, bedre stationer og ikke mindst kortere rejsetid. På kort sigt, dvs. indenfor ca. 5-10 år, foreslås mindre tilpasning af infrastruktur, etablering af nye krydsningsspor samt opgradering af hastigheden til 120 km/t, hvor dette ikke er tilfældet i dag. Trafikalt skal der sikres bedre sammenhæng mellem systemer, kortere skiftetider og omlægninger i ruter så lange skift minimeres eller undgås. Togsystemerne differentieres i regionale stoptog og hurtige regionale togsystemer med få stop (REX-tog eller IC-tog), som tilpasses i en grundkøreplan med timedrift eller 1⁄2- times drift. Dette gør det muligt at løfte kvalitet, regularitet, køretid og trafikudbud mærkbart. På længere sigt, dvs. 10 år og derover, udnyttes gevinsten af det nye signalsystem og gennemførte spormoderniseringer, således hastigheden kommer op på 140 km/t. Alle overkørsler foreslås sikret med bomanlæg, erstattet af niveaufri eller nedlagte krydsninger. På de passagertunge strækninger mellem Silkeborg-Herning og Vejle-Herning foreslås de mest kurverige strækningsafsnit udrettet og hastigheden generelt opgraderet til 180 km/t samt etablering af dobbeltspor på hovedparten af strækningerne. En helt ny dobbeltsporet bane til 180 km/t fra Århus til Silkeborg via Galten bør etableres, for at nedbringe rejsetiden mellem Vest- og Østjylland markant. Dette kan løfte banekapaciteten mærkbart og reducere køretiden så meget, at jernbanen kan komme til at konkurrere med biltrafikken på det udbyggede motorvejsnet. Der er ikke foretaget egentlig økonomiske beregninger af investeringsbehovet på kort og lang sigt, og følgelig er der ikke gennemført samfundsøkonomiske beregninger. Disse bør gennemføres, når de implicerede kommuner har aftalt de strategiske mål for jernbanerne i Vestjylland

Ulcerative colitis, Crohn's disease, and irritable bowel syndrome have different profiles of extracellular matrix turnover, which also reflects disease activity in Crohn's disease

Increased protease activity is a key pathological feature of inflammatory bowel disease (IBD). However, the differences in extracellular matrix remodelling (ECM) in Crohn's disease (CD) and ulcerative colitis (UC) are not well described. An increased understanding of the inflammatory processes may provide optimized disease monitoring and diagnostics. We investigated the tissue remodelling in IBD and IBS patients by using novel blood-based biomarkers reflecting ECM remodelling.Five ECM biomarkers (VICM, BGM, EL-NE, C5M, Pro-C5) were measured by competitive ELISAs in serum from 72 CD patients, 60 UC patients, 22 patients with irritable bowel syndrome (IBS), and 24 healthy donors. One-way analysis of variance, Mann-Whitney U-test, logistic regression models, and receiver operator characteristics (ROC) curve analysis was carried out to evaluate the diagnostic accuracy of the biomarkers.The ECM remodelling was significantly different in UC compared to CD. The best biomarker combination to differentiate UC from CD and colonic CD was BGM and VICM (AUC = 0.98, P<0.001; AUC = 0.97, P<0.001), and the best biomarker combination to differentiate IBD from IBS patients were BGM, EL-NE, and Pro-C5 (AUC = 0.8, P<0.001). When correcting for the use of immunosuppressant and elevated CRP levels (CRP>5mg/mL), correlation of Pro-C5 (r = 0.36) with CDAI was slightly improved compared to CRP (r = 0.27) corrected for the use of immunosuppressant. Furthermore, BGM and EL-NE biomarkers were highly associated with colon inflammation in CD patients.ECM fragments of tissue remodelling in IBD affect UC and CD differently, and may aid in differentiating IBD from IBS (EL-NE, BGM, Pro-C5), and UC from CD patients (BGM, VICM). Formation of type V collagen is related to the level of inflammation in CD and may reflect disease activity in CD

Evaluation of serum ARGS neoepitope as an osteoarthritis biomarker using a standardized model for exercise-induced cartilage extra cellular matrix turnover

Summary: Objective: To propose a standardized model for exercise-induced cartilage turnover and investigate residual levels and dynamics of biomarker serum ARGS (sARGS) in primary osteoarthritis (OA) patients and a supportive group of young healthy subjects. Method: The trial is a randomized, cross-over, exploratory study with interventions of exercise and inactivity. 20 subjects with knee OA, as well as 20 young healthy subjects (mean age 25.7 years (range; 19–30), 50% male), underwent cycling, running and resting interventions on separate days one week apart. Blood samples were taken at baseline, immediately, 1, 2, 3 and 24 h after activity start. sARGS was measured by sandwich ELISA. Results: Intraclass correlation between visits were 0.97 and 0.77 for the OA and healthy group, respectively. An acute drop in sARGS in response to high-intensity exercise was observed in both groups. Minute acute sARGS increase was observed in OA subjects in response to moderate intensity running and cycling, which normalized within 24 h. In healthy subjects an acute drop in sARGS was seen immediately after running, but not cycling, and no other changes were observed. A negative correlation between baseline Kellgren-Lawrence (KL) grade and baseline sARGS (r = −0.69, p = 0.002) in OA was found. A negative correlation between age and sARGS was found in healthy subjects (r = −0.67, p = <0.002). Conclusion: sARGS sensitivity to physical activity is considered low and sARGS is a reproducible and stable marker. Minute acute increases in sARGS were observed in the hours following moderate intensity exercise

Suppression of MMP activity in bovine cartilage explants cultures has little if any effect on the release of aggrecanase-derived aggrecan fragments

<p>Abstract</p> <p>Background</p> <p>Progressive loss of articular cartilage is a central hallmark in many joint disease, however, the relative importance of individual proteolytic pathways leading to cartilage erosion is at present unknown. We therefore investigated the time-dependant release <it>ex vivo </it>of MMP- and aggrecanase-derived fragments of aggrecan and type II collagen into the supernatant of bovine cartilage explants cultures using neo-epitope specific immunoassays, and to associate the release of these fragments with the activity of proteolytic enzymes using inhibitors.</p> <p>Findings</p> <p>Bovine cartilage explants were cultured in the presence or absence of the catabolic cytokines oncostatin M (OSM) and tumor necrosis factor alpha (TNFα). In parallel, explants were co-cultured with protease inhibitors such as GM6001, TIMP1, TIMP2 and TIMP3. Fragments released into the supernatant were determined using a range of neo-epitope specific immunoassays; (1) sandwich ³⁴²FFGVG-G2 ELISA, (2) competition NITEGE³⁷³ELISA (3) sandwich G1-NITEGE³⁷³ELISA (4) competition ³⁷⁴ARGSV ELISA, and (5) sandwich ³⁷⁴ARGSV-G2 ELISA all detecting aggrecan fragments, and (6) sandwich CTX-II ELISA, detecting C-telopeptides of type II collagen. We found that (1) aggrecanase-derived aggrecan fragments are released in the early (day 2-7) and mid phase (day 9-14) into the supernatant from bovine explants cultures stimulated with catabolic cytokines, (2) the release of NITEGE³⁷³neo-epitopes are delayed compared to the corresponding ³⁷⁴ARGSV fragments, (3) the MMP inhibitor GM6001 did not reduce the release of aggrecanase-derived fragment, but induced a further delay in the release of these fragments, and finally (4) the MMP-derived aggrecan and type II collagen fragments were released in the late phase (day 16-21) only.</p> <p>Conclusion</p> <p>Our data support the model, that aggrecanases and MMPs act independently in the processing of the aggrecan molecules, and furthermore that suppression of MMP-activity had little if any effect on the quantity of aggrecanase-derived fragments released from explants cultures.</p

The Citrullinated and MMP-degraded Vimentin Biomarker (VICM) Predicts Early Response to Anti-TNF alpha Treatment in Crohn's Disease

Background: In Crohn's disease (CD), 10% to 40% of patients do not respond to anti-tumor necrosis factor- (TNF) treatment. Currently, there are no biomarkers with adequate sensitivity to separate responders from nonresponders at an early stage. Aim: The aim of this study was to investigated whether early changes in the VICM (citrullinated and matrix metalloproteinase-degraded vimentin) biomarker were associated with response to anti-TNF treatment in patients with CD. Methods: Serum VICM levels were measured by ELISA in 2 independent cohorts of CD patients (n=42) treated with anti-TNF (infliximab or adalimumab). Response was determined by achieving clinical remission (Harvey Bradshaw Index<5). Results: Compared with baseline, VICM serum levels were reduced by anti-TNF in the infliximab cohort (week 6 and 14) and in the adalimumab cohort (week 8). VICM was lower in the responders compared with the nonresponders [infliximab: Week 6, P<0.05; area under the curve (AUC)=0.90; adalimumab: Week 1, P<0.01 (AUC=0.91), and week 8, P<0.05 (AUC=0.86)], and were able to predict response to treatment after 1 week of treatment with an odds ratio of 42.5. Conclusions: The VICM biomarker was time dependently reduced in CD patients responding to anti-TNF treatment. We suggest that VICM may be used as a marker for monitoring early response to anti-TNF in patients with CD