Brownian motion in short range random potentials

A numerical study of Brownian motion of noninteracting particles in random potentials is presented. The dynamics are modeled by Langevin equations in the high friction limit. The random potentials are Gaussian distributed and short ranged. The simulations are performed in one and two dimensions. Different dynamical regimes are found and explained. Effective subdiffusive exponents are obtained and commented on.

Employment risk, unemployment insurance and search strategies: a disaggregated equilibrium approach with application to the Swiss labour market in the 1990-ies

The Organization of the Thesis The remainder of the thesis comprises five chapters and a conclusion. The next chapter formalizes the envisioned theory into a tractable model. Section 2.2 presents a formal description of the model economy: the individual heterogeneity, the individual objective, the UI setting, the population dynamics and the equilibrium. The welfare and efficiency criteria for qualifying various equilibrium outcomes are proposed in section 2.3. The fourth section shows how the model-generated information can be computed. Chapter 3 transposes the model from chapter 2 in conditions that enable its use in the analysis of individual labor market strategies and their implications for the labor market equilibrium. In section 3.2 the Swiss labor market data sets, stylized facts, and the UI system are presented. The third section outlines and motivates the parameterization method. In section 3.4 the model's replication ability is evaluated and some aspects of the parameter choice are discussed. Numerical solution issues can be found in the appendix. Chapter 4 examines the determinants of search-strategic behavior in the model economy and its implications for the labor market aggregates. In section 4.2, the unemployment duration distribution is examined and related to search strategies. Section 4.3 shows how the search- strategic behavior is influenced by the UI eligibility and section 4.4 how it is determined by individual heterogeneity. The composition effects generated by search strategies in labor market aggregates are examined in section 4.5. The last section evaluates the model's replication of empirical unemployment escape frequencies reported in Sheldon [67]. Chapter 5 applies the model economy to examine the effects on the labor market equilibrium of shocks to the labor market risk structure, to the deep underlying labor market structure and to the UI setting. Section 5.2 examines the effects of the labor market risk structure on the labor market equilibrium and the labor market strategic behavior. The effects of alterations in the labor market deep economic structural parameters, i.e. individual preferences and production technology, are shown in Section 5.3. Finally, the UI setting impacts on the labor market are studied in Section 5.4. This section also evaluates the role of the UI authority monitoring and the differences in the Way changes in the replacement rate and the UI benefit duration affect the labor market. In chapter 6 the model economy is applied in counterfactual experiments to assess several aspects of the Swiss labor market movements in the nineties. Section 6.2 examines the two equilibria characterizing the Swiss labor market in the nineties, the " growth" equilibrium with a "moderate" UI regime and the "recession" equilibrium with a more "generous" UI. Section 6.3 evaluates the isolated effects of the structural shocks, while the isolated effects of the UI reforms are analyzed in section 6.4. Particular dimensions of the UI reforms, the duration, replacement rate and the tax rate effects, are studied in section 6.5, while labor market equilibria without benefits are evaluated in section 6.6. In section 6.7 the structural and institutional interactions that may act as unemployment amplifiers are discussed in view of the obtained results. A welfare analysis based on individual welfare in different structural and UI settings is presented in the eighth section. Finally, the results are related to more favorable unemployment trends after 1997. The conclusion evaluates the features embodied in the model economy with respect to the resulting model dynamics to derive lessons from the model design." The thesis ends by proposing guidelines for future improvements of the model and directions for further research.

Worldwide trends in gastric cancer mortality (1980-2011), with predictions to 2015, and incidence by subtype.

Gastric cancer incidence and mortality decreased substantially over the last decades in most countries worldwide, with differences in the trends and distribution of the main topographies across regions. To monitor recent mortality trends (1980-2011) and to compute short-term predictions (2015) of gastric cancer mortality in selected countries worldwide, we analysed mortality data provided by the World Health Organization. We also analysed incidence of cardia and non-cardia cancers using data from Cancer Incidence in Five Continents (2003-2007). The joinpoint regression over the most recent calendar periods gave estimated annual percent changes (EAPC) around -3% for the European Union (EU) and major European countries, as well as in Japan and Korea, and around -2% in North America and major Latin American countries. In the United States of America (USA), EU and other major countries worldwide, the EAPC, however, were lower than in previous years. The predictions for 2015 show that a levelling off of rates is expected in the USA and a few other countries. The relative contribution of cardia and non-cardia gastric cancers to the overall number of cases varies widely, with a generally higher proportion of cardia cancers in countries with lower gastric cancer incidence and mortality rates (e.g. the USA, Canada and Denmark). Despite the favourable mortality trends worldwide, in some countries the declines are becoming less marked. There still is the need to control Helicobacter pylori infection and other risk factors, as well as to improve diagnosis and management, to further reduce the burden of gastric cancer.

Finite-size scaling investigation of the liquid-liquid critical point in ST2 water and its stability with respect to crystallization.

The liquid-liquid critical point scenario of water hypothesizes the existence of two metastable liq- uid phases low-density liquid (LDL) and high-density liquid (HDL) deep within the supercooled region. The hypothesis originates from computer simulations of the ST2 water model, but the stabil- ity of the LDL phase with respect to the crystal is still being debated. We simulate supercooled ST2 water at constant pressure, constant temperature, and constant number of molecules N for N ≤ 729 and times up to 1 μs. We observe clear differences between the two liquids, both structural and dynamical. Using several methods, including finite-size scaling, we confirm the presence of a liquid-liquid phase transition ending in a critical point. We find that the LDL is stable with respect to the crystal in 98% of our runs (we perform 372 runs for LDL or LDL-like states), and in 100% of our runs for the two largest system sizes (N = 512 and 729, for which we perform 136 runs for LDL or LDL-like states). In all these runs, tiny crystallites grow and then melt within 1 μs. Only for N ≤ 343 we observe six events (over 236 runs for LDL or LDL-like states) of spontaneous crystal- lization after crystallites reach an estimated critical size of about 70 ± 10 molecules.

Stem cell-related "self-renewal" signature and high epidermal growth factor receptor expression associated with resistance to concomitant chemoradiotherapy in glioblastoma.

PURPOSE: Glioblastomas are notorious for resistance to therapy, which has been attributed to DNA-repair proficiency, a multitude of deregulated molecular pathways, and, more recently, to the particular biologic behavior of tumor stem-like cells. Here, we aimed to identify molecular profiles specific for treatment resistance to the current standard of care of concomitant chemoradiotherapy with the alkylating agent temozolomide. PATIENTS AND METHODS: Gene expression profiles of 80 glioblastomas were interrogated for associations with resistance to therapy. Patients were treated within clinical trials testing the addition of concomitant and adjuvant temozolomide to radiotherapy. RESULTS: An expression signature dominated by HOX genes, which comprises Prominin-1 (CD133), emerged as a predictor for poor survival in patients treated with concomitant chemoradiotherapy (n = 42; hazard ratio = 2.69; 95% CI, 1.38 to 5.26; P = .004). This association could be validated in an independent data set. Provocatively, the HOX cluster was reminiscent of a "self-renewal" signature (P = .008; Gene Set Enrichment Analysis) recently characterized in a mouse leukemia model. The HOX signature and EGFR expression were independent prognostic factors in multivariate analysis, adjusted for the O-6-methylguanine-DNA methyltransferase (MGMT) methylation status, a known predictive factor for benefit from temozolomide, and age. Better outcome was associated with gene clusters characterizing features of tumor-host interaction including tumor vascularization and cell adhesion, and innate immune response. CONCLUSION: This study provides first clinical evidence for the implication of a "glioma stem cell" or "self-renewal" phenotype in treatment resistance of glioblastoma. Biologic mechanisms identified here to be relevant for resistance will guide future targeted therapies and respective marker development for individualized treatment and patient selection.

Common variation in PHACTR1 is associated with susceptibility to cervical artery dissection.

Cervical artery dissection (CeAD), a mural hematoma in a carotid or vertebral artery, is a major cause of ischemic stroke in young adults although relatively uncommon in the general population (incidence of 2.6/100,000 per year). Minor cervical traumas, infection, migraine and hypertension are putative risk factors, and inverse associations with obesity and hypercholesterolemia are described. No confirmed genetic susceptibility factors have been identified using candidate gene approaches. We performed genome-wide association studies (GWAS) in 1,393 CeAD cases and 14,416 controls. The rs9349379[G] allele (PHACTR1) was associated with lower CeAD risk (odds ratio (OR) = 0.75, 95% confidence interval (CI) = 0.69-0.82; P = 4.46 × 10(-10)), with confirmation in independent follow-up samples (659 CeAD cases and 2,648 controls; P = 3.91 × 10(-3); combined P = 1.00 × 10(-11)). The rs9349379[G] allele was previously shown to be associated with lower risk of migraine and increased risk of myocardial infarction. Deciphering the mechanisms underlying this pleiotropy might provide important information on the biological underpinnings of these disabling conditions.

Power variation of some integral fractional processes

We consider the asymptotic behaviour of the realized power variation of processes of the form ¿t0usdBHs, where BH is a fractional Brownian motion with Hurst parameter H E(0,1), and u is a process with finite q-variation, q<1/(1¿H). We establish the stable convergence of the corresponding fluctuations. These results provide new statistical tools to study and detect the long-memory effect and the Hurst parameter.

Criteria for hitting probabilities with applications to systems of stochastic wave equations

We develop several results on hitting probabilities of random fields which highlight the role of the dimension of the parameter space. This yields upper and lower bounds in terms of Hausdorff measure and Bessel-Riesz capacity, respectively. We apply these results to a system of stochastic wave equations in spatial dimension k >- 1 driven by a d-dimensional spatially homogeneous additive Gaussian noise that is white in time and colored in space.

Acute mesenteric vein thrombosis: factors associated with evolution to chronic mesenteric vein thrombosis

OBJECTIVE. Acute mesenteric venous thrombosis signs at MDCT are well described, but the literature lacks studies assessing their evolution. We aimed to describe the radiologic evolution of isolated acute mesenteric venous thrombosis and associated prognostic factors. MATERIALS AND METHODS. Patients with isolated acute mesenteric venous thrombosis with follow-up for a minimum of 1 month with MDCT were selected. Images at the acute phase and on follow-up were reviewed in consensus reading. For acute mesenteric venous thrombosis, we searched for low-attenuated intraluminal filling defect. For chronic mesenteric venous thrombosis, we searched for vessel stenosis or occlusion associated with collateral mesenteric veins. Treatment, thrombosis risk factor, symptoms, location, and length and diameter of mesenteric venous thrombosis were reported and correlated with evolution over time. RESULTS. Twenty patients (nine women and 11 men; mean age, 52 years) were selected. Four patients recovered without radiologic sequelae, and 16 developed chronic mesenteric venous thrombosis signs. Anticoagulation did not influence recovery (p = 1). Patients with recovery compared with patients with chronic mesenteric venous thrombosis showed more frequent central lesions (p = 0.03). At diagnosis, the thrombosed segment was shorter and larger in the complete radiologic recovery group compared with the chronic mesenteric venous thrombosis signs group: mean length (± SD) 6.25 ± 3.21 cm and 12.81 ± 5.96 cm, respectively (p = 0.01); mean transverse diameter 1.82 ± 0.42 cm and 1.12 ± 0.34 cm, respectively (p = 0.01). Mesenteric fat infiltration at diagnosis was more frequent in the chronic mesenteric venous thrombosis signs group than in the complete recovery group (p = 0.03). CONCLUSION. Most cases of acute mesenteric venous thrombosis evolve toward the chronic form with vein stenosis or occlusion and development of collateral veins. Location, length of mesenteric venous thrombosis, transverse diameter of the vein, and mesenteric fat infiltration at diagnosis are determinant factors for mesenteric venous thrombosis evolution.

Canakinumab (Acz885) Relieves Pain And Controls Inflammation Rapidly In Patients With Difficult-To-Treat Gouty Arthritis : Comparison With Triamcinolone Acetonide

Background : Monosodium urate (MSU) crystals stimulate the productionof interleukin-1b (IL-1b), a potent inflammatory cytokine. Targeted IL-1b blockade with canakinumab, a fully human monoclonal anti-IL-1b antibody, is a novel treatment for gouty arthritis. Its effects on pain and inflammation in acute gouty arthritis flares were compared with triamcinolone acetonide (TA). TA has been shown to be effective in the treatment of acute gouty arthritis flares.Methods : This was an 8-week, dose-ranging, multicenter, blinded, active-controlled trial. Patients _18 to _80 years with an acute gouty arthritis flare, refractory to or contraindicated to NSAIDs and/or colchicine were randomized to one subcutaneous dose of canakinumab (10, 25, 50, 90, or 150 mg; n¼143) or one intramuscular dose of TA (40 mg; n¼57). Primary outcome was pain intensity at 72 hours post dose on VAS scale (0-100 mm). Secondary outcomes included Creactive protein (CRP), serum amyloid A (SAA), and physician's assessment of tenderness, swelling and erythema of target joint at 72 hours, 7 days, 4 and 8-weeks post dose.Results : 191/200 patients completed the study. Canakinumab showed a statistically significant dose response at 72 hours. The 150mg dose group reached superior pain relief compared to TA group starting from 24 hours as previously reported. At 72 hours post dose, 78% of canakinumab 150mg treated patients achieved _75% and 96% achieved _50% reduction in pain from baseline. In contrast, 45% and 61% of patients treated with TA achieved _75% and _50% pain reduction, respectively. Median CRP/SAA levels were normalized by Day 7 for all canakinumab doses above 10mg and remained below the upper limit of normal [(ULN): CRP 3.0 mg/L; SAA 6.7 mg/L)] for rest of the study. In TA group, median CRP levels remained above the ULN throughout the study while median SAA levels decreased below ULN only 28 days after first dose. At 72 hours post dose, canakinumab 150mg group was 3.2 (95% CI, 1.27-7.89) times more likely to have less joint tenderness and 2.7 (95% CI, 1.09-6.5) times more likely to have less joint swelling than TA group (p<0.05). At 72 hours post dose, erythema disappeared in 74.1% of patients receiving canakinumab150mg and 69.6% of patients receiving TA. At 7 days post dose, erythema was absent in 96.3% of canakinumab 150mg treated patients vs. 83.9% of patients receiving TA. The overall incidence of AEs was similar for canakinumab (41%) and triamcinolone acetonide (42%). Serious AEs (canakinumab treatment groups n¼4, TA n¼1) were not considered treatment-related by investigators. No discontinuationsdue to AEs occurred.Conclusions : Canakinumab 150mg provided superior pain relief compared to TA for acute flares in difficult-to-treat gouty arthritis patients. Canakinumab provided rapid normalization of markers of inflammation accompanied by reduction of clinical signs and symptoms of inflammation.Disclosure statement : U.A., V.M., D.R. and P.S. are shareholders and employees of Novartis Pharma AG. A.P. has received research support from Novartis Pharma AG. N.S. has received research support from and acts as a consultant for Novartis Pharmaceuticals Corporation, has served on advisory boards for Novartis, Takeda, Savient, URL Pharma and Enzyme Rx, and is/has been a member of a speakers' bureau for Takeda. A.S. has received consultancy fees from Novartis Pharma AG, Abbott, Wyeth, UCB, Roche, MSD, Pfizer, Essex and Bristol-Myers Squibb. All other authors have declared no conflicts of interest.

Impact of etanercept-methotrexate therapy on patient-reported outcomes in rheumatoid arthritis patients with up to 12 months of symptoms.

Background/Purpose: Patient-reported outcomes (PROs) in patients with rheumatoid arthritis (RA) are critical in evaluating RA treatment effects on function and health-related quality of life (HR-QoL). Significant improvement in PROs has been reported in RA studies of biologic agents, including etanercept (ETN), but most studies have been conducted in patients with established disease. In addition to assessing treatment effects in early RA, there is interest in therapeutic strategies that allow dose reduction or withdrawal of biologic therapy (biologic-free) after induction of response. The PRIZE trial is an ongoing, 3-period study to evaluate the efficacy of combined ETN and methotrexate (MTX) therapy in patients with early, moderate-to-severe RA and to assess whether efficacy (remission) can be maintained with ETN dose reduction or biologic-free (Period 2) or drug-free (Period 3). Herein we report PROs associated with ETN 50 mg QW plus MTX (ETN50/MTX) therapy administered for 52 wks in Period 1 (induction) of the PRIZE trial. Methods: In Period 1, MTX- and biologic-naı‥ve patients with early, active RA (symptom onset 12 mo from enrollment; DAS28 _3.2) received open-label ETN50/MTX for 52 wks. The starting dose of MTX was 10 mg QW; at the discretion of the investigator, titration was permitted up to a maximum of 25 mg QW to achieve remission. Corticosteroid boosts were administered to patients not achieving low disease state at wks 13 and 26, unless contraindicated or not tolerated. PROs were assessed using the Health Assessment Questionnaire (HAQ) total score; Patient Acceptable Symptom State (PASS); EuroQol-5 Dimensions (EQ-5D) total index; Short Form Health Survey (SF-36); Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue; Work Instability Scale for Rheumatoid Arthritis (RAWIS); and Work Productivity and Activity Impairment Questionnaire: Rheumatoid Arthritis (WPAI:RA). Results: A total of 306 patients received treatment in Period 1 (mITT population); 222 (73%) patients completed the period. The majority of patients were female (70%), with a mean age of 50 y, mean DAS28 of 6.0 (median, 6.0), and duration of disease symptoms from onset of 6.5 months (median, 6.3 mo). Significant and clinically meaningful improvements in PROs, including in HAQ, EQ-5D, SF-36, and FACIT-Fatigue, were demonstrated with ETN50/MTX therapy from baseline to the final on therapy visit (Table; P_0.0001). Similar improvements were observed in all dimensions of RA-WIS and WPAI:RA (Table; P_0.0001). Conclusion: Combination therapy with ETN50/MTX for 52 wks in patients with _12 mo of symptomatic, active RA resulted in significant, clinically important improvements in measures of physical function, including normal HAQ (66.6% of patients), HR-QoL, fatigue, and work productivity. These outcomes are consistent with those reported in prior studies in patients with more established disease.

Yield formation of spring rye at high latitudes with reference to seeding rate and plant growth regulation

Selostus: Kylvötiheyden ja kasvunsääteiden vaikutus kevätrukiin satoon