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The highway construction industry has been increasingly using design-build (D-B) project delivery because of its documented benefits. Only limited studies, if any, have compared D-B and traditional...

Modeling risk management systems in construction projects is a complex process because of various internal and external factors and their interrelationships. Fuzzy system dynamics (FSD) have been commonly employed to model and analyze construction risk management systems. To run FSD simulation models, all hard (objective) and soft (subjective) causal relationships between variables must be quantified. However, a research gap exists regarding structured methods for constructing soft causal relationships in FSD models. This paper proposes an adaptive hybrid model consisting of fuzzy analytical hierarchy process, weighted principle of justifiable granularity, and fuzzy aggregation operators to determine crisp values of causality degree for soft (subjective) causal relationships in FSD modeling of construction risk analysis. The proposed model is implemented in analyzing construction risks of a windfarm project to illustrate its applicability. The proposed model generates two results: (1) optimized membership functions for linguistic terms representing the causality degree of soft relationships and (2) the crisp value for the causality degree of soft relationships. The contribution of study is to propose a structured model to improve efficiency and effectiveness of developing FSD quantitative modeling by addressing soft causal relationships between different variables in FSD models and considering multiple risk expertise of heterogeneous experts in construction risk assessment.

IL-17-producing CD8 (Tc17) T cells have been shown to play an important role in infection and chronic inflammation, however their implications in hepatocellular carcinoma (HCC) remain elusive. In this study, we performed cytometry by time-of-flight (CyTOF) and revealed the distinctive immunological phenotypes of two IFNγ

Although construction owners have long utilized Best-Value (BV) procurement within alternative delivery, they have historically been less willing to do so when selecting contractor teams in traditi...

Hypoxia is one of the central players in shaping the immune context of the tumor microenvironment (TME). However, the complex interplay between immune cell infiltrates within the hypoxic TME of HCC remains to be elucidated.We analyzed the immune landscapes of hypoxia-low and hypoxia-high tumor regions using cytometry by time of light, immunohistochemistry, and transcriptomic analyses. The mechanisms of immunosuppression in immune subsets of interest were further explored using in vitro hypoxia assays. Regulatory T cells (Tregs) and a number of immunosuppressive myeloid subsets, including M2 macrophages and human leukocyte antigen-DR isotype (HLA-DRWe uncovered the unique immunosuppressive landscapes and identified key immune subsets enriched in hypoxic HCC. In particular, we identified a potential Treg-mediated immunosuppression through interaction with a cDC2 subset in HCC that could be exploited for immunotherapies.

Design-build (DB) project delivery is often used to overcome limitations of the traditional design-bid-build delivery method. Identification of project performance influencing factors is im...

In the recent years, owners and construction management companies have shown an increasingly more interest in adopting approaches that result in enhanced quality and less risks, conflicts, and wastes on their projects despite potentially higher initial cost. Implementing advanced technology trends and incorporating more integrated methods of delivering projects have proven to be highly value-adding and forward-thinking approaches. The objective of this research was to evaluate the effectiveness of and the synergy between three of such trending concepts in the construction industry, namely, integrated project delivery (IPD), lean principles, and building information modeling (BIM) in terms of cost and schedule performance measures. Data analysis was conducted on 72 vertical projects through interviews and study of the published articles, reports, and case studies. Qualitative analysis was performed through grounded theory while quantitative analysis was implemented using univariate and multivariate analysis of variance tests on schedule performance and cost performance. Results of the grounded theory analysis summarize six crucial characteristics required for an effective coordination between IPD, lean construction, and BIM. Statistical analysis on different combination of these three components revealed considerable effectiveness in terms of schedule performance while the effect on cost performance was not as much significant. This study contributes to the body of knowledge and practice in the field of construction by demonstrating the cost and schedule benefits realized through the use of IPD, lean construction, and BIM and identifying their collective conceptual advantages.

The best-value (BV) procurement method has been increasingly used by owners in the context of design–bid–build (DBB) project delivery. The objective of this study was to determine whether a...

Immune evasion is key to cancer initiation and later at metastasis, but its dynamics at intermediate stages, where potential therapeutic interventions could be applied, is undefined. Here we show, using multi-dimensional analyses of resected tumours, their adjacent non-tumour tissues and peripheral blood, that extensive immune remodelling takes place in patients with stage I to III hepatocellular carcinoma (HCC). We demonstrate the depletion of anti-tumoural immune subsets and accumulation of immunosuppressive or exhausted subsets along with reduced tumour infiltration of CD8 T cells peaking at stage II tumours. Corresponding transcriptomic modification occur in the genes related to antigen presentation, immune responses, and chemotaxis. The progressive immune evasion is validated in a murine model of HCC. Our results show evidence of ongoing tumour-immune co-evolution during HCC progression and offer insights into potential interventions to reverse, prevent or limit the progression of the disease.

Intravesical Bacillus Calmette-Guerin (BCG) is an effective immunotherapy for non-muscle invasive bladder cancer (NMIBC). However, recurrence and progression remain frequent warranting deeper insights into its mechanism. We herein comprehensively profiled blood and tissues obtained from NMIBC patients before, during and after BCG treatment using cytometry by time-of-flight (CyTOF) and RNA sequencing to identify the key immune subsets crucial for anti-tumor activity. We observed the temporal changes of peripheral immune subsets including NKT cells, central memory CD4+ T cells, CD8+ T cells and regulatory T cells (Treg) during the course of BCG. Gene expression analysis revealed enriched immune pathways involving in T cell activation and chemotaxis, as well as a more diversified T cell receptor repertoire in post-BCG tissues. Moreover, tissue multiplexed-immunofluorescence (mIF) showed baseline densities of non-Treg and CD8+PD-1+ T cells were predictive of response and better recurrence-free survival after BCG. Remarkably, post-BCG tissues from responders were found to be infiltrated with more active CD8+PD-1- T cells and non-Treg CD4+FOXP3- T cells; but increased exhausted CD8+PD-1+ T cells were found in non-responders. Taken together, we identified predictive biomarkers for response and uncovered the post-treatment expansion of exhausted PD-1+CD8+ T cells as key to BCG resistance, which could potentially be restored by combining with anti-PD-1 immunotherapy.

Manual material handling tasks have the potential to be highly unsafe from an ergonomic viewpoint. Safety inspections to monitor body postures can help mitigate ergonomic risks of material handling. However, the real effect of awkward muscle movements, strains, and excessive forces that may result in an injury may not be identified by external cues. This paper evaluates the ability of surface electromyogram (EMG)-based systems together with machine learning algorithms to automatically detect body movements that may harm muscles in material handling. The analysis utilized a lifting equation developed by the U.S. National Institute for Occupational Safety and Health (NIOSH). This equation determines a Recommended Weight Limit, which suggests the maximum acceptable weight that a healthy worker can lift and carry, as well as a Lifting Index value to assess the risk extent. Four different machine learning models, namely Decision Tree, Support Vector Machine, K-Nearest Neighbor, and Random Forest are developed to classify the risk assessments calculated based on the NIOSH lifting equation. The sensitivity of the models to various parameters is also evaluated to find the best performance using each algorithm. Results indicate that Decision Tree models have the potential to predict the risk level with close to 99.35% accuracy.

Selection of a project delivery method in highway construction is a challenging task because of the many decision criteria involved. In addition to quantitative project attributes, the proj...

The clinical relevance of immune landscape intratumoural heterogeneity (immune-ITH) and its role in tumour evolution remain largely unexplored. Here, we uncover significant spatial and phenotypic immune-ITH from multiple tumour sectors and decipher its relationship with tumour evolution and disease progression in hepatocellular carcinomas (HCC). Immune-ITH is associated with tumour transcriptomic-ITH, mutational burden and distinct immune microenvironments. Tumours with low immune-ITH experience higher immunoselective pressure and escape via loss of heterozygosity in human leukocyte antigens and immunoediting. Instead, the tumours with high immune-ITH evolve to a more immunosuppressive/exhausted microenvironment. This gradient of immune pressure along with immune-ITH represents a hallmark of tumour evolution, which is closely linked to the transcriptome-immune networks contributing to disease progression and immune inactivation. Remarkably, high immune-ITH and its transcriptomic signature are predictive for worse clinical outcome in HCC patients. This in-depth investigation of ITH provides evidence on tumour-immune co-evolution along HCC progression., Intratumoural heterogeneity is a feature of liver cancer. Here, the authors demonstrate that heterogeneity exists at the immune cell level in liver cancer and show that tumours with high intratumoural immune heterogeneity demonstrated an immune suppressive microenvironment, which was associated with tumour evolution and a poor prognosis.

Selecting an appropriate delivery method for highway projects is a complex decision process. Delivery decisions typically involve evaluating both quantitative (e.g., cost, schedule) and qua...

Construction engineering and management (CEM) becomes more complex with increasing project size and complexity. Various fuzzy hybrid techniques have been implemented to handle subjective uncertainty and vagueness in CEM problems. The objective of this paper is to investigate applications of fuzzy hybrid techniques across different CEM applications (e.g., prediction, decision making, optimization) through a systematic review of 255 journal articles published from 2004 to 2021. A checklist of selection criteria for choosing an appropriate fuzzy hybrid technique to solve a specific CEM problem was also established. This study contributes to the body of knowledge by providing a state-of-the-art review of existing fuzzy hybrid techniques utilized in CEM to (1) demonstrate their capabilities to overcome limitations of some standard techniques in solving complex construction problems, (2) determine selection criteria for their applications, and (3) examine the applicability of each fuzzy hybrid technique’s category to given practical construction problems.

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-21556-y.

Optimum design of the sand control devices in oil sand reservoirs plays a vital role in minimizing the sand production and increasing the reservoir productivity in Steam-Assisted Gravity Drainage (SAGD) operations. Various sand control testing facilities have been developed to evaluate the performance of sand control screens, such as the pre-packed Sand Retention Test (SRT). Current testing apparatuses are based on the linear flow regime. However, fluid flow around SAGD production wells is radial flow, not linear. This study introduces a Full-scale Completion Test (FCT) facility to emulate the radial-flow condition in SAGD wells. Instead of using a disk-shaped screen coupon, this facility utilizes a cylindrical-shaped screen. A couple of tests were carried out to determine the flow uniformity inside the cell and identify the test repeatability. Test results show that flow is distributed uniformly inside the cell, and experiments are repeatable in terms of differential pressures, fines production, and sanding levels. Therefore, this innovative FCT experimental setup and procedure allows a more realistic evaluation of the liner performance by emulating the real SAGD flow regime around the liner. Testing results obtained from the FCT can be used to complement and validate the current testing procedures. These tools can be adopted for an objective custom-design and selection of standalone screens in SAGD.

The solvation of propylene oxide (PO) in water has been studied using vibrational circular dichroism (VCD) spectroscopy, optical rotation dispersion (ORD) spectroscopy, molecular dynamics simulations, and ab initio calculations. VCD and ORD measurements were carried out for PO as neat liquid, in CCl4, and in water solutions. The classical molecular dynamics simulations were carried out for the PO + water binary mixtures at different concentrations, and the solvation information was derived from the radial distribution functions obtained in the simulations. The total number of water molecules within the closest vicinity of PO was predicted to be about 3. The geometry optimizations, vibrational frequencies, and VCD intensities were evaluated for the PO monomer and the PO-(H2O)n clusters with n = 1-3 , using density functional theory calculations at the B3LYP/aug-cc-pVTZ level of theory. The chirality transfer VCD feature, which is a direct result of the explicit H-bonding between water and the chiral PO solute, was detected experimentally at the water bending band region. This feature exhibits high sensitivity to the solvation structure around PO. Comparison of the calculated and experimental chirality transfer features leads to the conclusion that the PO-water binary complex is the dominating species in aqueous solution at room temperature and the anti conformation, where water is on the opposite side of the oxirane ring of the PO methyl group, is preferred over the syn one. This conclusion is also supported by the complementary ORD studies. Possible contributions from the ternary and quaternary PO-water complexes are also discussed.