Empirical perspective on activity durations for project-management simulation studies

Simulation has played an important role in project-management studies of the last decades, but in order for them to produce practical results, a realistic distribution model for activity durations is indispensable. The construction industry often has needed historical records of project executions, to serve as inputs to the distribution models, but a clearly outlined calibration procedure is not always readily available, nor are their results readily interpretable. This study seeks to illustrate how data from the construction industry can be used to derive realistic input distributions. Therefore, the Parkinson simulation model with a lognormal core is applied to a large empirical dataset from the literature and the results are described. From a discussion of these results, an empirical classification of project executions is presented. Three possible uses are presented for the calibration procedure and the classification in project management simulation studies. These were validated using a case study of a construction company

Setting tolerance limits for statistical project control using earned value management

Project control has been a research topic since decades that attracts both academics and practitioners. Project control systems indicate the direction of change in preliminary planning variables compared with actual performance. In case their current project performance deviates from the planned performance, a warning is indicated by the system in order to take corrective actions. Earned value management/earned schedule (EVM/ES) systems have played a central role in project control, and provide straightforward key performance metrics that measure the deviations between planned and actual performance in terms of time and cost. In this paper, a new statistical project control procedure sets tolerance limits to improve the discriminative power between progress situations that are either statistically likely or less likely to occur under the project baseline schedule. In this research, the tolerance limits are derived from subjective estimates for the activity durations of the project. Using the existing and commonly known EVM/ES metrics, the resulting project control charts will have an improved ability to trigger actions when variation in a project׳s progress exceeds certain predefined thresholds A computational experiment has been set up to test the ability of these statistical project control charts to discriminate between variations that are either acceptable or unacceptable in the duration of the individual activities. The computational experiments compare the use of statistical tolerance limits with traditional earned value management thresholds and validate their power to report warning signals when projects tend to deviate significantly from the baseline schedule

Myosin IIA-mediated forces regulate multicellular integrity during vascular sprouting

Angiogenic sprouting is a critical process involved in vascular network formation within tissues. During sprouting, tip cells and ensuing stalk cells migrate collectively into the extracellular matrix while preserving cell-cell junctions, forming patent structures that support blood flow. Although several signaling pathways have been identified as controlling sprouting, it remains unclear to what extent this process is mechanoregulated. To address this question, we investigated the role of cellular contractility in sprout morphogenesis, using a biomimetic model of angiogenesis. Three-dimensional maps of mechanical deformations generated by sprouts revealed that mainly leader cells, not stalk cells, exert contractile forces on the surrounding matrix. Surprisingly, inhibiting cellular contractility with blebbistatin did not affect the extent of cellular invasion but resulted in cell-cell dissociation primarily between tip and stalk cells. Closer examination of cell-cell junctions revealed that blebbistatin impaired adherens-junction organization, particularly between tip and stalk cells. Using CRISPR/Cas9-mediated gene editing, we further identified NMIIA as the major isoform responsible for regulating multicellularity and cell contractility during sprouting. Together, these studies reveal a critical role for NMIIA-mediated contractile forces in maintaining multicellularity during sprouting and highlight the central role of forces in regulating cell-cell adhesions during collective motility.R01 EB000262 - NIBIB NIH HHS; R01 HL115553 - NHLBI NIH HHSPublished versio

Private Shareholder Engagements on Material ESG Issues

We study private shareholder engagements with 2,465 listed firms about environmental, social, and governance (ESG) issues from 2007 to 2020. We examine the extent to which private engagements address financially material ESG issues and contribute to firm performance. We find that material engagements succeed more often than immaterial engagements and that the targets of successful material engagements significantly outperform their peers by 2.5% over the next 14 months. Further, we find that material engagements are more often associated with improvements in profitability and cost ratios than immaterial engagements. Finally, our evidence indicates that a decrease in CO2e emission intensity accompanies environmental engagements

Pharmacodynamic mechanism-based interaction model for the haemodynamic effects of remifentanil and propofol in healthy volunteers

BACKGROUND: Propofol and remifentanil are frequently combined for the induction and maintenance of general anaesthesia. Both propofol and remifentanil cause vasodilation and potentially reduce arterial BP. We aimed to develop a mechanism-based model that characterises the haemodynamic interactions between remifentanil and propofol.METHODS: Data from two clinical trials in healthy volunteers were analysed using remifentanil-alone, propofol-alone, and combination groups. We evaluated remifentanil effects on haemodynamics using a previously developed mechanism-based haemodynamic model of propofol. The interaction between propofol and remifentanil was explored using the principles of the general pharmacodynamic interaction (GPDI) model.RESULTS: Remifentanil alone increased the dissipation rate of total peripheral resistance by 50% at 3.0 ng ml-1. Additionally, the dissipation rates of HR and stroke volume were attenuated by 4.8% and 4.9% per 1 ng ml-1 increase in remifentanil concentration, respectively. The maximal effect of propofol alone in decreasing the production rate of total peripheral resistance was 78%, which decreased to 32% when combined with remifentanil 4 ng ml-1. The effects of remifentanil on HR and stroke volume were attenuated by propofol with maximum decreases of 11.9% and 21.2%, respectively. Goodness-of-fit plots and prediction-corrected visual predictive check plots showed good predictive performance of the models.CONCLUSIONS: The structure of the previous mechanism-based haemodynamic model for propofol was able to describe the effects of remifentanil alone on haemodynamic variables. The GPDI model provided a good framework for characterising the pharmacodynamic interaction between remifentanil and propofol on haemodynamic properties.CLINICAL TRIAL REGISTRATION: NCT02043938; NCT03143972.</p

Implications of the new MRI-based rectum definition according to the sigmoid take-off:multicentre cohort study

Background: The introduction of the sigmoid take-off definition might lead to a shift from rectal cancers to sigmoid cancers. The aim of this retrospective cohort study was to determine the clinical impact of the new definition. Methods: In this multicentre retrospective cohort study, patients were included if they underwent an elective, curative total mesorectal excision for non-metastasized rectal cancer between January 2015 and December 2017, were registered in the Dutch Colorectal Audit as having a rectal cancer according to the previous definition, and if MRI was available. All selected rectal cancer cases were reassessed using the sigmoid take-off definition. The primary outcome was the number of patients reassessed with a sigmoid cancer. Secondary outcomes included differences between the newly defined rectal and sigmoid cancer patients in treatment, perioperative results, and 3-year oncological outcomes (overall and disease-free survivals, and local and systemic recurrences). Results: Out of 1742 eligible patients, 1302 rectal cancer patients were included. Of these, 170 (13.1 per cent) were reclassified as having sigmoid cancer. Among these, 93 patients (54.7 per cent) would have been offered another adjuvant or neoadjuvant treatment according to the Dutch guideline. Patients with a sigmoid tumour after reassessment had a lower 30-day postoperative complication rate (33.5 versus 48.3 per cent, P &lt; 0.001), lower reintervention rate (8.8 versus 17.4 per cent, P &lt; 0.007), and a shorter length of stay (a median of 5 days (i.q.r. 4-7) versus a median of 6 days (i.q.r. 5-9), P &lt; 0.001). Three-year oncological outcomes were comparable. Conclusion: Using the anatomical landmark of the sigmoid take-off, 13.1 per cent of the previously classified patients with rectal cancer had sigmoid cancer, and 54.7 per cent of these patients would have been treated differently with regard to neoadjuvant therapy or adjuvant therapy.</p

Implications of the new MRI-based rectum definition according to the sigmoid take-off:multicentre cohort study

Background: The introduction of the sigmoid take-off definition might lead to a shift from rectal cancers to sigmoid cancers. The aim of this retrospective cohort study was to determine the clinical impact of the new definition. Methods: In this multicentre retrospective cohort study, patients were included if they underwent an elective, curative total mesorectal excision for non-metastasized rectal cancer between January 2015 and December 2017, were registered in the Dutch Colorectal Audit as having a rectal cancer according to the previous definition, and if MRI was available. All selected rectal cancer cases were reassessed using the sigmoid take-off definition. The primary outcome was the number of patients reassessed with a sigmoid cancer. Secondary outcomes included differences between the newly defined rectal and sigmoid cancer patients in treatment, perioperative results, and 3-year oncological outcomes (overall and disease-free survivals, and local and systemic recurrences). Results: Out of 1742 eligible patients, 1302 rectal cancer patients were included. Of these, 170 (13.1 per cent) were reclassified as having sigmoid cancer. Among these, 93 patients (54.7 per cent) would have been offered another adjuvant or neoadjuvant treatment according to the Dutch guideline. Patients with a sigmoid tumour after reassessment had a lower 30-day postoperative complication rate (33.5 versus 48.3 per cent, P &lt; 0.001), lower reintervention rate (8.8 versus 17.4 per cent, P &lt; 0.007), and a shorter length of stay (a median of 5 days (i.q.r. 4-7) versus a median of 6 days (i.q.r. 5-9), P &lt; 0.001). Three-year oncological outcomes were comparable. Conclusion: Using the anatomical landmark of the sigmoid take-off, 13.1 per cent of the previously classified patients with rectal cancer had sigmoid cancer, and 54.7 per cent of these patients would have been treated differently with regard to neoadjuvant therapy or adjuvant therapy.</p