The Driving Factors of Passenger Transport

Over the past few decades passenger transport has grown rapidly resulting in a multitude of problems including severe traffic congestion and pollution. It is expected that passenger transport will continue to grow rapidly in the future, which will worsen the situation even further. The traditional approach to deal with the problems is to expand the infrastructure. However, transport policy is a broad and versatile field. Many different types of policy measures can be observed in literature and practice. Sound transport policy-making requires knowledge on the drivers of transport demand This article is aimed at (re)structuring the many different insights in a single conceptual model, which reviews the key drivers, and how each affects the various choices that travellers make (activity type, destination, mode, time-of-day and route) and the resulting impact on overall passenger transport demand. The model was derived on the basis of a review of literature, which was supplemented by a review of thirteen exemplary urban area cases. In addition, a quantitative data analysis was carried out to assess the transport demand elasticities for various drivers. Current study has been carried out in response to the search for effective transport policy, which is discussed in the concluding section. The outcomes are of particular relevance of policy analysts and policy makers developing passenger transport policy, but are also useful for scholars and students in the field of transport

The Role of Self-Regulation in Corporate Governance

This paper assesses the effectiveness of self-regulation to promote investor interests. The Netherlands provides an excellent opportunity to gather such evidence for two reasons. First, characteristics of the Dutch corporate governance structure have made it the recent focus of attention by the European Union, the International Monetary Fund and countries (e.g., Korea) when deliberating issues of corporate governance. Second, during the period 1996-1998, a private sector initiative was undertaken to promote change in the balance of power between management and investors. Not surprisingly, the United States Securities and Exchange Commission has closely followed the Dutch "experiment" in self-regulation. We begin by identifying corporate governance characteristics that are linked to firm value. We then compare corporate governance characteristics and the relation between firm value and these characteristics before and after the private sector initiative. We find that the recommendations of the private sector initiative had no substantive effect on corporate governance characteristics or their relationship with firm value. Using event study techniques we document the market's skepticism about the successful evolution of corporate governance practices in the Netherlands through self-regulation. The one exception to this general conclusion is the market for new listings. Overall, our results confirm the importance of shareholder voting rights, and who controls these rights, when considering the design of a successful self-regulation process

On including travel time reliability of road traffic in appraisal

In many countries, decision-making on proposals for national or regional infrastructure projects in passenger and freight transport includes carrying out a cost–benefit analysis for these projects. Reductions in travel times are usually a key benefit. However, if a project also reduces the variability of travel time, travellers, freight operators and shippers will enjoy additional benefits, the ‘reliability benefits’. Until now, these benefits are usually not included in the cost–benefit analysis. To include reliability of travel or transport time in the cost–benefit analysis of infrastructure projects not only monetary values of reliability, but also reliability forecasting models are needed. As a result of an extensive feasibility study carried out for the German Federal Ministry of Transport, Building and Urban Development this paper aims to provide a literature overview and outcomes of an expert panel on how best to calculate and monetise reliability benefits, synthesised into recommendations for implementing travel time reliability into existing transport models in the short, medium, and long term. The paper focuses on road transport, which has also been the topic for most of the available literature on modelling and valuing transport time reliability

Vedolizumab for Inflammatory Bowel Disease:Two-Year Results of the Initiative on Crohn and Colitis (ICC) Registry, A Nationwide Prospective Observational Cohort Study: ICC Registry - Vedolizumab

Contains fulltext : 220028.pdf (Publisher’s version ) (Open Access)Prospective data of vedolizumab treatment for patients with inflammatory bowel disease (IBD) beyond 1 year of treatment is scarce but needed for clinical decision making. We prospectively enrolled 310 patients with IBD (191 with Crohn's disease (CD) and 119 patients with ulcerative colitis (UC)) with a follow-up period of 104 weeks (interquartile range: 103-104) in a nationwide registry. The corticosteroid-free clinical remission rate (Harvey Bradshaw Index ≤ 4, Short Clinical Colitis Activity index ≤ 2) at weeks 52 and 104 were 28% and 19% for CD and 27% and 28% for UC, respectively. Fifty-nine percent maintained corticosteroid-free clinical remission between weeks 52 and 104. Vedolizumab with concomitant immunosuppression showed comparable effectiveness outcomes compared with vedolizumab monotherapy (week 104: 21% vs. 23%; P = 0.77), whereas 8 of 13 severe infections occurred in patients treated with concomitant immunosuppression. To conclude, the clinical effect was 19% for CD and 28% for UC after 2 years of follow-up regardless of concomitant immunosuppression

The effect of induction therapy with infliximab or vedolizumab on hepcidin and iron status in patients with Inflammatory Bowel Disease

Background Differentiating absolute iron deficiency from functional iron restriction is challenging in active Inflammatory Bowel Disease (IBD). Hepcidin, the systemic iron regulator, could be the key in the diagnosis and management of absolute iron deficiency. In this study, we assessed hepcidin as a diagnostic iron deficiency marker and we explored the relationship between hepcidin, inflammation, hypoxia, and iron deficiency in patients receiving induction therapy with infliximab (IFX) or vedolizumab (VEDO). Methods 130 patients with IBD, who received induction therapy with IFX or VEDO for active disease, were included in this study. Clinical and biochemical data were extracted from medical records. Serum samples at baseline and week 6 of induction therapy were retrieved from the University Medical Center Groningen (UMCG) biobank and analysed for: hepcidin, inflammation (e.g., interleukins [IL] 6, 10, and Tumour Necrosis Factor-α [TNFα]), oxidative stress (free thiols), and hypoxia (e.g., erythropoietin [EPO], Macrophage Inflammatory Protein-3α [MIP3α]). For comparison, serum samples from 50 age- and gender-matched healthy controls were obtained from pre-donation biobank at the UMCG. Response to therapy was defined by either General Physician’s Assessment at week 14 of induction therapy, normalisation or at least a three-point decrease in clinical scores: Harvey-Bradshaw Index (HBI) for Crohn’s Disease, Simple Clinical Colitis Activity Index (SCCAI) for ulcerative colitis. Results Hepcidin correlated with ferritin and sTfR/log ferritin index [ρ = 0.74 and ρ = -0.79, respectively; P<0.001 for both markers], while inflammation- and hypoxia-associated markers showed only marginal correlations. Hepcidin accurately identified absolute iron deficiency: AUC(hepcidin) = 0.89 [95% CI: 0.82–0.95; P<0.001]. Induction with either IFX or VEDO decreased hepcidin [13.5 ng/mL vs. 9.5 ng/mL; P<0.001], ferritin [45.5 ug/L vs. 37.0 ug/L, P<0.05], and inflammatory markers at week 6, while transferrin increased [2.4 g/L vs. 2.5 g/L, P<0.001]. In total, 75.4% of patients responded to the induction therapy. Hepcidin and ferritin decreased, while transferrin increased (P<0.001 for all changes) in patients who responded to the therapy. In addition, hypoxia (EPO and MIP3α) and inflammatory markers such as faecal calprotectin, IL-6, IL-22, and TNFα improved significantly. In contrast, none of these improvements were observed in patients who did not respond to the therapy. Conclusion Hepcidin reflects iron deficiency in active IBD, but inflammation masks the severity of the deficiency. Induction therapy with either IFX or VEDO modulates hepcidin and iron indices, especially in patients who respond to the therapy

No Superiority of Tacrolimus Suppositories vs Beclomethasone Suppositories in a Randomized Trial of Patients With Refractory Ulcerative Proctitis

Background &amp; Aims: Ulcerative proctitis (UP) refractory to 5-aminosalicylic acid (5-ASA) suppositories is a challenge to treat, often requiring step up to immunomodulator or biological therapy. Topical tacrolimus is effective and safe in patients with refractory UP. However, it is not clear how tacrolimus suppositories fit into in the treatment algorithm of UP. Methods: We performed a randomized controlled, double-blind study at 8 hospitals in the Netherlands and Belgium from 2014 through 2017. Eighty-five patients with refractory UP (65% women) were randomly assigned to groups given once daily tacrolimus suppositories (2 mg; n = 43) or beclomethasone (3 mg; n = 42) for 4 weeks. The primary outcome was clinical response (decrease in Mayo score of 3 or more). Secondary outcomes included clinical remission, endoscopic response and remission, adverse events and quality of life. Outcomes were compared using Fisher's exact test and Mann-Whitney U test. Results: Proportions of patients with clinical responses were 63% in the tacrolimus group and 59% in the beclomethasone group (P =.812); proportions of patients in clinical remission were 46% and 38%, respectively (P =.638). Proportions of patients with an endoscopic response were 68% and 60% in the tacrolimus group and in the beclomethasone group (P =.636); proportions in endoscopic remission rates were 30% and 13%, respectively (P =.092) Median increases in the inflammatory bowel disease questionnaire score were 18.0 in the tacrolimus group and 20.5 in the beclomethasone group (P =.395). Adverse event rates did not differ significantly between groups. Conclusions: In a 4-week randomized controlled trial, tacrolimus and beclomethasone suppositories induce comparable clinical and endoscopic responses in patients with UP refractory to 5-ASA. There were no significant differences in adverse events rates. Tacrolimus and beclomethasone suppositories are therefore each safe and effective treatment options for 5-ASA refractory disease. EUDRACT 2013-001259-11; Netherlands Trial Register NL4205/NTR4416.</p

The somatostatin analog Sandostatin (SMS201-995) in treatment of DMBA-induced rat mammary tumors

The effects of treatment with a somatostatin analog (Sandostatin, SMS201-995) were investigated in female rats with dimethylbenzanthracene(DMBA)-induced rat mammary tumors. A 3-week treatment was performed using sandostatin, the LHRH-agonist buserelin alone, or buserelin in combination with sandostatin. Twice daily sandostatin treatment was performed with dosages of 0.05 μg, 0.2 μg, 1 μg, 5 μg, and 20 μg. Buserelin was used in a 2 × 5 μg/day dosage. The combined results from six different experiments show that the various dosages of sandostatin caused no tumor growth inhibition. Somatostatin receptors could not be demonstrated in these mammary tumors. Sandostatin treatment by daily injections did not suppress levels of growth hormone, prolactin, or epidermal growth factor-like activities. Estrogen (ER) and progest

Limited added value of laboratory monitoring in thiopurine maintenance monotherapy in inflammatory bowel disease patients

Background: To timely detect myelotoxicity and hepatotoxicity, laboratory monitoring at 3-month intervals is advised throughout thiopurine maintenance treatment for IBD. However, reported incidence rates of myelotoxicity and hepatotoxicity in maintenance treatment are low. Aim: To assess incidence rates and clinical consequences of myelotoxicity and hepatotoxicity in thiopurine maintenance therapy after at least 1 year of thiopurine treatment. Methods: Retrospective analysis of therapy adjustment for laboratory toxicity in adult IBD patients after 12 consecutive months of azathioprine (AZA) or mercaptopurine monotherapy (ie baseline) between 2000 and 2016. Incidence rates of laboratory toxicity (ie myelotoxicity [leucocyte count <4.0 × 10e9/L, and/or platelet count <150 × 10e9/L] and/or hepatotoxicity (gamma-glutamyltransferase [GGT], alkaline phosphatase [AP], ALT and/or AST above ULN, excluding isolated increased AST/AP]) and associated diagnostic procedures and complications were assessed. Results: In total, 12.391 laboratory assessments were performed on 1132 patients (56% female, AZA 74%) during 3.3 years of median follow-up. Median monitoring frequency was 3.1 assessments/treatment year. Only 83/12.391 (0.7%) assessments resulted in therapy adjustment, dose reduction in 46 patients, cessation in 28 and allopurinol initiation in nine; risk of therapy adjustment was 1.9% per treatment year. Incidence rates of myelotoxicity were 7.1% (5.1% mild/1.8% moderate/0.1% severe) and hepatotoxicity 5.1% (3.8% mild/1.1% moderate/0.2% severe) per treatment year. Treatment-related complications with concurrent laboratory toxicity occurred in 12 patients (1.1%) and would not have been prevented by monitoring. Conclusion: Severe laboratory toxicity is uncommon after 1 year of thiopurine monotherapy at 4-month monitoring intervals. Therapy adjustments are rare after detection of laboratory toxicity. After 1 year of thiopurine monotherapy, laboratory monitoring may be lowered to less than a 4-month interval

Prognostic Value of the Modified Rutgeerts Score for Long-Term Outcomes After Primary Ileocecal Resection in Crohn’s Disease

IntroductionThe prognostic value of the modified Rutgeerts score (mRS) in patients with Crohn's disease (CD) needs to be further elucidated. This study assessed the prognostic value of the mRS for long-term outcomes after primary ileocecal resection in patients with CD.METHODS: Patients with CD after primary ileocecal resection with an available mRS at first postoperative ileocolonoscopy (index mRS) were retrospectively included. The primary outcome was surgical recurrence. Secondary outcomes were clinical recurrence and progression to severe endoscopic recurrence (‡i3). Cox proportional hazard models were used to assess the association between index mRS and outcomes. RESULTS: Six hundred fifty-two patients were included (mean follow-up: 6.4 years, SD: 4.6). Surgical recurrence rates were 7.7%, 5.3%, 12.9%, 19.1%, 28.8%, 47.8% for index mRS i0, i1, i2a, i2b, i3, and i4, respectively. Clinical recurrence occurred in 42.2% (i0), 53.7% (i1), 58.5% (i2a), 80.2% (i2b), 79.4% (i3), and 95.3% (i4) of patients. Progression to severe endoscopic recurrence occurred in 21.1% (i0), 33.9% (i1), 26.8% (i2a), and 33.3% (i2b) of patients. An index mRS of i2b (adjusted hazard ratio [aHR] 3.0; 1.5–5.6), i3 (aHR 4.0; 2.0–7.9) and i4 (aHR 8.0; 4.0–16.0) were associated with surgical recurrence. An index mRS of i1 (aHR 1.7; 1.2–2.4), i2a (aHR 1.7; 1.2–2.4), i2b (aHR 4.4; 3.2–6.0), i3 (aHR 3.6; 2.5–5.2), and i4 (aHR 7.3; 4.8–10.9) were associated with clinical recurrence. An index mRS of i1 (aHR 2.0; 1.1–3.7) or i2b (aHR 2.5; 1.4–4.6) was associated with progression to severe endoscopic recurrence.DISCUSSION: The increasing mRS corresponds closely with the risk of surgical and clinical recurrence. An index mRS ‡ i2b is associated with surgical recurrence, an index mRS ‡ i1 is associated with clinical recurrence, and i1 or i2b with progression to severe endoscopic recurrence. These results support tight monitoring of disease activity and treatment optimization in patients with ileal lesions and a more conservative management in patients with anastomotic lesions.</p