Managing the national road network maintenance in Spain

The Spanish Ministry of Public Works manages the National Road Network, which consists in 27,000 km. In 1992, the average age of pavements was 7.2 years, whereas at present it has increased to 9 years. The great heterogeneity of pavements, the constant increase in the network length and its gradual aging demand important budgets but also agile technical, economic and administrative management models. The Subdirectorate of Maintenance and Operation is responsible of management systems for this network, now helped by the engineering consultancy GETINSA. This communication shows the actual state of the pavement management that consists in an Integrated Database System comprising many parameters both about technical values and administrative follow-up of actions. It is connected to various pavement evolution models that allow managers to predict the future state of the roads, then to establish a maintenance policy. Finally, the Management System calculates a maintenance plan, detailing actions to be done in each section in a multi-year scenario, so that the investment and the road quality are optimised. The Management System software combines analytical formula with geographical information, used for representing results as well as part of the forecast and optimisation models, using the modern technology of “dynamic segments”. Attention has been paid to conciliate the operational organisation of maintenance works with the fact that optimal needs are detailed for each road section in too short distances to be executed separately. The communication starts analysing other existing Pavement Management Systems, then describes the Spanish situation and justifies which Pavement Management System is needed. The body of the text covers the description of the functionalities and design assumptions of the new System. Finally, the conclusions present some future evolutions for the Spanish Management Systems and the possibility to generalise its use to other road networks, either for pavement or other assets.

Tylose Formation and Changes in Phenolic Compounds of Grape Roots Infected with «Phaeomoniella chlamydospora» and «Phaeoacremonium» Species

The role of phenolic compounds in strengthening resistance of grapevine to young grapevine decline was analysed. The formation of tyloses has also been associated with this disease. A microscopic study showed that tyloses originated in parenchyma cells associated with the xylem and from there invaded the xylem lumen. As tyloses formed, there were changes in the cell wall, associated with the accumulation of crystalline structures. The cells surrounding the blocked xylem contained more polyphenolic compounds than the cells of intact xylem. Changes in the level and composition of polyphenolic compounds occurred in relation to the severity of infection. Tannin concentrations also increased with increasing numbers of xylem vessels containing tyloses. Root extracts added to fungal culture media inhibited mycelial growth of Phaeomoniella chlamydospora, Phaeoacremonium aleophilum and Pm. inflatipes. Inhibition was greater with extracts from roots with tyloses, and was also correlated with polyphenol content. Extracts of the leaves, stems and berries of vines treated with Brotomax, which increases the biosynthesis of phenolic compounds, inhibited mycelial growth of the fungi compared to untreated control plants

Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

Background Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. Methods In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH,non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2–F3, or F1 with at least oneaccompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpointsfor the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2–F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. Findings Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1–F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2–F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1–F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). Interpretation Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes

An upper limit to the photon fraction in cosmic rays above 10^19 eV from the Pierre Auger Observatory

An upper limit of 16% (at 95% c.l.) is derived for the photon fraction in cosmic rays with energies above 10^19 eV, based on observations of the depth of shower maximum performed with the hybrid detector of the Pierre Auger Observatory. This is the first such limit on photons obtained by observing the fluorescence light profile of air showers. This upper limit confirms and improves on previous results from the Haverah Park and AGASA surface arrays. Additional data recorded with the Auger surface detectors for a subset of the event sample, support the conclusion that a photon origin of the observed events is not favoured

The effect of the geomagnetic field on cosmic ray energy estimates and large scale anisotropy searches on data from the Pierre Auger Observatory

We present a comprehensive study of the influence of the geomagnetic field on the energy estimation of extensive air showers with a zenith angle smaller than $60^\circ$, detected at the Pierre Auger Observatory. The geomagnetic field induces an azimuthal modulation of the estimated energy of cosmic rays up to the ~2% level at large zenith angles. We present a method to account for this modulation of the reconstructed energy. We analyse the effect of the modulation on large scale anisotropy searches in the arrival direction distributions of cosmic rays. At a given energy, the geomagnetic effect is shown to induce a pseudo-dipolar pattern at the percent level in the declination distribution that needs to be accounted for.Comment: 20 pages, 14 figure

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

BACKGROUND Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. METHODS In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH, non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2-F3, or F1 with at least one accompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpoints for the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2-F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. FINDINGS Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1-F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2-F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1-F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). INTERPRETATION Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes. FUNDING Intercept Pharmaceuticals

La formacion en gestion de proyectos

Currently, Project management can be found as a subject in many engineer training programs at the graduate level and is the exclusive subject of many post-graduate programs; It is interesting to look at some varieties among this broad catalogue.En la actualidad, la gestion de proyectos se encuentra como asignatura en muchos programas de formacion de ingeniero a nivel de grado y tambien es objeto de atencion unico en numerosos postgrados. Es interesante apreciar algunas variedades entre este amplio catalogo