Incorporating the effect of weather in construction scheduling and management with sine wave curves: application in the United Kingdom

The impact of (adverse) weather is a common cause of delays, legal claims and economic losses in construction projects. Research has recently been carried out aimed at incorporating the effect of weather in project planning; but these studies have focussed on either a narrow set of weather variables, or a very limited range of construction activities or projects. A method for processing a country’s historical weather data into a set of weather delay maps for some representative standard construction activities is proposed. Namely, sine curves are used to associate daily combinations of weather variables to delay and provide coefficients for expected productivity losses. A complete case study comprising the construction of these maps and the associated sine waves for the UK is presented along with an example of their use in building construction planning. Findings of this study indicate that UK weather extends project durations by an average of 21%. However, using climatological data derived from weather observations when planning could lead to average reductions in project durations of 16%, with proportional reductions in indirect and overhead costs

Improving Existing Delay Analysis Techniques for the Establishment of Delay Liabilities

Delay analysis and schedule compression are normally treated as separate, independent, aspects of the study of delays and their effects on the completion of construction projects. This paper examines the feasibility of integrating the delay analysis and schedule compression functions into a broad-scoped two-stage process. The main issue is shown to be the kind of delay analysis required for each stage of the process and seven existing techniques are illustrated for use in conjunction with schedule compression. Some necessary modifications to these techniques are identified together with a typology for categorising each technique

Systems Pharmacology Modeling Predicts Delayed Presentation and Species Differences in Bile Acid–Mediated Troglitazone Hepatotoxicity

Troglitazone (TGZ) caused delayed, life-threatening drug-induced liver injury (DILI) in some patients, but was not hepatotoxic in rats. This study investigated altered bile acid (BA) homeostasis as a mechanism of TGZ hepatotoxicity using a systems pharmacology model incorporating drug/metabolite disposition, BA physiology/pathophysiology, hepatocyte life cycle, and liver injury biomarkers. In the simulated human population, TGZ (200–600mg/day×6months) resulted in delayed increases in serum ALT>3× ULN in 0.3–5.1% of the population with concomitant bilirubin elevations>2× ULN in 0.3–3.6%. In contrast, pioglitazone (15–45mg/day×6months) did not elicit hepatotoxicity, consistent with clinical data. TGZ was not hepatotoxic in the simulated rat population. In summary, mechanistic modeling based only on BA effects accurately predicted the incidence, delayed presentation, and species differences in TGZ hepatotoxicity, and the relative liver safety of pioglitazone. Systems pharmacology models integrating physiology and experimental data can evaluate DILI mechanisms and may be useful to predict hepatotoxic potential of drug candidates

Patient Age, Sex, and Inflammatory Bowel Disease Phenotype Associate With Course of Primary Sclerosing Cholangitis

Background & Aims Primary sclerosing cholangitis (PSC) is an orphan hepatobiliary disorder associated with inflammatory bowel disease (IBD). We aimed to estimate the risk of disease progression based on distinct clinical phenotypes in a large international cohort of patients with PSC. Methods We performed a retrospective outcome analysis of patients diagnosed with PSC from 1980 through 2010 at 37 centers in Europe, North America, and Australia. For each patient, we collected data on sex, clinician-reported age at and date of PSC and IBD diagnoses, phenotypes of IBD and PSC, and date and indication of IBD-related surgeries. The primary and secondary endpoints were liver transplantation or death (LTD) and hepatopancreatobiliary malignancy, respectively. Cox proportional hazards models were applied to determine the effects of individual covariates on rates of clinical events, with time-to-event analysis ascertained through Kaplan-Meier estimates. Results Of the 7121 patients in the cohort, 2616 met the primary endpoint (median time to event of 14.5 years) and 721 developed hepatopancreatobiliary malignancy. The most common malignancy was cholangiocarcinoma (n = 594); patients of advanced age at diagnosis had an increased incidence compared with younger patients (incidence rate: 1.2 per 100 patient-years for patients younger than 20 years old, 6.0 per 100 patient-years for patients 21–30 years old, 9.0 per 100 patient-years for patients 31–40 years old, 14.0 per 100 patient-years for patients 41–50 years old, 15.2 per 100 patient-years for patients 51–60 years old, and 21.0 per 100 patient-years for patients older than 60 years). Of all patients with PSC studied, 65.5% were men, 89.8% had classical or large-duct disease, and 70.0% developed IBD at some point. Assessing the development of IBD as a time-dependent covariate, Crohn's disease and no IBD (both vs ulcerative colitis) were associated with a lower risk of LTD (unadjusted hazard ratio [HR], 0.62; P <.001 and HR, 0.90; P =.03, respectively) and malignancy (HR, 0.68; P =.008 and HR, 0.77; P =.004, respectively). Small-duct PSC was associated with a lower risk of LTD or malignancy compared with classic PSC (HR, 0.30 and HR, 0.15, respectively; both P <.001). Female sex was also associated with a lower risk of LTD or malignancy (HR, 0.88; P =.002 and HR, 0.68; P <.001, respectively). In multivariable analyses assessing the primary endpoint, small-duct PSC characterized a low-risk phenotype in both sexes (adjusted HR for men, 0.23; P <.001 and adjusted HR for women, 0.48; P =.003). Conversely, patients with ulcerative colitis had an increased risk of liver disease progression compared with patients with Crohn's disease (HR, 1.56; P <.001) or no IBD (HR, 1.15; P =.002). Conclusions In an analysis of data from individual patients with PSC worldwide, we found significant variation in clinical course associated with age at diagnosis, sex, and ductal and IBD subtypes. The survival estimates provided might be used to estimate risk levels for patients with PSC and select patients for clinical trials. © 2017 AGA Institut

Patient Age, Sex, and Inflammatory Bowel Disease Phenotype Associate With Course of Primary Sclerosing Cholangitis

Background & Aims Primary sclerosing cholangitis (PSC) is an orphan hepatobiliary disorder associated with inflammatory bowel disease (IBD). We aimed to estimate the risk of disease progression based on distinct clinical phenotypes in a large international cohort of patients with PSC. Methods We performed a retrospective outcome analysis of patients diagnosed with PSC from 1980 through 2010 at 37 centers in Europe, North America, and Australia. For each patient, we collected data on sex, clinician-reported age at and date of PSC and IBD diagnoses, phenotypes of IBD and PSC, and date and indication of IBD-related surgeries. The primary and secondary endpoints were liver transplantation or death (LTD) and hepatopancreatobiliary malignancy, respectively. Cox proportional hazards models were applied to determine the effects of individual covariates on rates of clinical events, with time-to-event analysis ascertained through Kaplan-Meier estimates. Results Of the 7121 patients in the cohort, 2616 met the primary endpoint (median time to event of 14.5 years) and 721 developed hepatopancreatobiliary malignancy. The most common malignancy was cholangiocarcinoma (n = 594); patients of advanced age at diagnosis had an increased incidence compared with younger patients (incidence rate: 1.2 per 100 patient-years for patients younger than 20 years old, 6.0 per 100 patient-years for patients 21–30 years old, 9.0 per 100 patient-years for patients 31–40 years old, 14.0 per 100 patient-years for patients 41–50 years old, 15.2 per 100 patient-years for patients 51–60 years old, and 21.0 per 100 patient-years for patients older than 60 years). Of all patients with PSC studied, 65.5% were men, 89.8% had classical or large-duct disease, and 70.0% developed IBD at some point. Assessing the development of IBD as a time-dependent covariate, Crohn's disease and no IBD (both vs ulcerative colitis) were associated with a lower risk of LTD (unadjusted hazard ratio [HR], 0.62; P <.001 and HR, 0.90; P =.03, respectively) and malignancy (HR, 0.68; P =.008 and HR, 0.77; P =.004, respectively). Small-duct PSC was associated with a lower risk of LTD or malignancy compared with classic PSC (HR, 0.30 and HR, 0.15, respectively; both P <.001). Female sex was also associated with a lower risk of LTD or malignancy (HR, 0.88; P =.002 and HR, 0.68; P <.001, respectively). In multivariable analyses assessing the primary endpoint, small-duct PSC characterized a low-risk phenotype in both sexes (adjusted HR for men, 0.23; P <.001 and adjusted HR for women, 0.48; P =.003). Conversely, patients with ulcerative colitis had an increased risk of liver disease progression compared with patients with Crohn's disease (HR, 1.56; P <.001) or no IBD (HR, 1.15; P =.002). Conclusions In an analysis of data from individual patients with PSC worldwide, we found significant variation in clinical course associated with age at diagnosis, sex, and ductal and IBD subtypes. The survival estimates provided might be used to estimate risk levels for patients with PSC and select patients for clinical trials

Search for resonances in the dijet mass spectrum from 7 TeV pp collisions at CMS

A search for narrow resonances with a mass of at least 1 TeV in the dijet mass spectrum is performed using pp collisions at sqrt(s)=7 TeV corresponding to an integrated luminosity of 1 inverse femtobarn, collected by the CMS experiment at the LHC. No resonances are observed. Upper limits at the 95% confidence level are presented on the product of the resonance cross section, branching fraction into dijets, and acceptance, separately for decays into quark-quark, quark-gluon, and gluon-gluon pairs. The data exclude new particles predicted in the following models at the 95% confidence level: string resonances with mass less than 4.00 TeV, E6 diquarks with mass less than 3.52 TeV, excited quarks with mass less than 2.49 TeV, axigluons and colorons with mass less than 2.47 TeV, and W' bosons with mass less than 1.51 TeV

Performance of τ\tau-lepton reconstruction and identification in CMS

The performance of tau-lepton reconstruction and identification algorithms is studied using a data sample of proton-proton collisions at sqrt(s)=7 TeV, corresponding to an integrated luminosity of 36 inverse picobarns collected with the CMS detector at the LHC. The tau leptons that decay into one or three charged hadrons, zero or more short-lived neutral hadrons, and a neutrino are identified using final-state particles reconstructed in the CMS tracker and electromagnetic calorimeter. The reconstruction efficiency of the algorithms is measured using tau leptons produced in Z-boson decays. The tau-lepton misidentification rates for jets and electrons are determined