Type I Tobit Bayesian Additive Regression Trees for censored outcome regression

Censoring occurs when an outcome is unobserved beyond some threshold value. Methods that do not account for censoring produce biased predictions of the unobserved outcome. This paper introduces Type I Tobit Bayesian Additive Regression Tree (TOBART-1) models for censored outcomes. Simulation results and real data applications demonstrate that TOBART-1 produces accurate predictions of censored outcomes. TOBART-1 provides posterior intervals for the conditional expectation and other quantities of interest. The error term distribution can have a large impact on the expectation of the censored outcome. Therefore, the error is flexibly modeled as a Dirichlet process mixture of normal distributions. An R package is available at https://github.com/EoghanONeill/TobitBART.</p

Type I Tobit Bayesian Additive Regression Trees for censored outcome regression

Censoring occurs when an outcome is unobserved beyond some threshold value. Methods that do not account for censoring produce biased predictions of the unobserved outcome. This paper introduces Type I Tobit Bayesian Additive Regression Tree (TOBART-1) models for censored outcomes. Simulation results and real data applications demonstrate that TOBART-1 produces accurate predictions of censored outcomes. TOBART-1 provides posterior intervals for the conditional expectation and other quantities of interest. The error term distribution can have a large impact on the expectation of the censored outcome. Therefore, the error is flexibly modeled as a Dirichlet process mixture of normal distributions. An R package is available at https://github.com/EoghanONeill/TobitBART.</p

5-Hydroxyethyl-3-tetradecanoyltetramic acid represents a novel treatment for intravascular catheter infections due to Staphylococcus aureus

Objectives: Biofilm infections of intravascular catheters caused by Staphylococcus aureus may be treated with catheter lock solutions (CLSs). Here we investigated the antibacterial activity, cytotoxicity and CLS potential of 5-hydroxyethyl-3-tetradecanoyltetramic acid (5HE-C14-TMA) compared with the related compounds 3-tetradecanoyltetronic (C14-TOA) and 3-tetradecanoylthiotetronic (C14-TTA), which are variants of quorum sensing signalling molecules produced by Pseudomonas aeruginosa. Methods: Antibacterial activity and mechanism of action of 5HE-C14-TMA, C14-TOA and C14-TTA were determined via MIC, bacterial killing, membrane potential and permeability assays. Susceptibility of S. aureus biofilms formed in the presence of plasma in vitro was investigated, MTT cytotoxicity testing was undertaken and cytokine release in human blood upon exposure to 5HE-C14-TMA and/or S. aureus biofilms was quantified. The effectiveness of 5HE-C14-TMA as CLS therapy in vivo was assessed using a rat intravascular catheter biofilm infection model. Results: MICs of 5HE-C14-TMA, C14-TOA and C14-TTA ranged from 2 to 4 mg/L. 5HE-C14-TMA and C14-TTA were bactericidal; all three compounds perturbed the staphylococcal membrane by increasing membrane permeability, depolarized the transmembrane potential and caused ATP leakage. Cytotoxicity and haemolytic activity were compound and target cell type-dependent. 5HE-C14-TMA reduced S. aureus biofilm viability in a dose-dependent manner in vitro and in vivo and did not trigger release of cytokines in human blood, but inhibited the high levels of IL-8 and TNF-α induced by S. aureus biofilms. Conclusions: 5HE-C14-TMA, C14-TOA and C14-TTA are membrane-active agents. 5HE-C14-TMA was the most potent, eradicating S. aureus biofilms at 512–1024 mg/L both in vitro and in vivo as a CLS

Eradication of Staphylococcus aureus Biofilm Infections Using Synthetic Antimicrobial Peptides

Here, we demonstrate that antimicrobial peptides (AMPs) are an effective antibiofilm treatment when applied as catheter lock solutions (CLSs) against S. aureus biofilm infections. The activity of synthetic AMPs (Bac8c, HB43, P18, Omiganan, WMR, Ranalexin, and Polyphemusin) was measured against early and mature biofilms produced by methicillin-resistant S. aureus and methicillin-susceptible S. aureus isolates from patients with device-related infections grown under in vivo-relevant biofilm conditions. The cytotoxic and hemolytic activities of the AMPs against human cells and their immunomodulatory potential in human blood were also characterized. The D-Bac8c2,5Leu variant emerged as the most effective AMP during in vitro studies and was also highly effective in eradicating S. aureus biofilm infection when used in a CLS rat central venous catheter infection model. These data support the potential use of D-Bac8c2,5Leu, alone or in combination with other AMPs, in the treatment of S. aureus intravenous catheter infections

Hydrodynamic modelling approaches to assess mechanisms affecting the structural performance and maintenance of vortex drops shaft structures

Vortex drop shafts, a key hydraulic structure within modern day deep sewer conveyance systems, must be designed structurally to sustain performance and longevity of operating life under very energetic loading conditions. This has significant cost implications but to date little research has been undertaken to investigate the loading conditions with a view to optimising the shaft designs and thus lowering costs. In this study, several modelling methods were adopted to simulate hydrodynamic conditions within a vortex drop shaft to assess hydrodynamic mechanisms that impact a drop shaft liners structural performance and maintenance. A 1/10 scaled physical hydraulic model of a tangential inlet vortex drop shaft structure is tested and used to validate a three-dimensional multiphase numerical model. Collectively, the study presents methods on identifying hydrodynamic phenomena such as pressures, velocities, erosion and abrasion mechanisms, debris impact locations and blocking mechanisms. The study highlighted that the hydrodynamic forces that threaten structural integrity reside in the vortex generator and a short length of the drop shaft downstream. This is shown through a new model developed by the authors to predict centrifugal forces along the length of the drop. Through these methods, the study proposes that drop shaft liners can be designed more efficiently.The authors of this work would like to thank Ward and Burke Construction Ltd for their support when compiling this article. The authors would further like to express gratitude to Edward Kilcullen and Dermot Mc Dermott for their assistance during physical modelling investigations.peer-reviewed2020-07-2

When Will First-Price Work Well? The Impact of Anti-Corruption Rules on Photovoltaic Power Generation Procurement Auctions

Along with the prevalence of photovoltaic (PV) procurement contracts, the corruption between auctioneers and potential electricity suppliers has attracted the attention of energy regulators. This study considers a corruption-proof environment wherein corruption is strictly suppressed. It elaborates a mechanism to explore the impact of corruption-proof measures on PV procurement auctions. It adopts incentive compatible constraints based on revelation principle to reflect PV firms’ optimal utilities. It employs first-price and first-score auctions and uses the Bayesian Nash equilibrium to provide a description of market outcomes. The results show that several strategies have different impacts on social welfare, PV firms’ utility, and the benefits of corruption. First, a first-price auction cannot act as a suitable policy because it may encourage corruption. Second, the first-score choice is desirable for social welfare to fit the forthcoming high-quality and low-price surroundings. Third, the first-score strategy maximizes PV firms’ utility and total income. The implications suggest that regulators ought not to employ first-price auctions in the future PV market from the perspective of social welfare. Another disadvantage of the first-price approach is that it enables the PV firm to maintain the utmost benefit from corruption

Hydrodynamic modelling approaches to assess mechanisms affecting the structural performance and maintenance of vortex drops shaft structures

Vortex drop shafts, a key hydraulic structure within modern day deep sewer conveyance systems, must be designed structurally to sustain performance and longevity of operating life under very energetic loading conditions. This has significant cost implications but to date little research has been undertaken to investigate the loading conditions with a view to optimising the shaft designs and thus lowering costs. In this study, several modelling methods were adopted to simulate hydrodynamic conditions within a vortex drop shaft to assess hydrodynamic mechanisms that impact a drop shaft liners structural performance and maintenance. A 1/10 scaled physical hydraulic model of a tangential inlet vortex drop shaft structure is tested and used to validate a three-dimensional multiphase numerical model. Collectively, the study presents methods on identifying hydrodynamic phenomena such as pressures, velocities, erosion and abrasion mechanisms, debris impact locations and blocking mechanisms. The study highlighted that the hydrodynamic forces that threaten structural integrity reside in the vortex generator and a short length of the drop shaft downstream. This is shown through a new model developed by the authors to predict centrifugal forces along the length of the drop. Through these methods, the study proposes that drop shaft liners can be designed more efficiently.The authors of this work would like to thank Ward and Burke Construction Ltd for their support when compiling this article. The authors would further like to express gratitude to Edward Kilcullen and Dermot Mc Dermott for their assistance during physical modelling investigations.2020-07-2

Major mechanisms of biofilm expressed by <i>S</i>. <i>aureus</i>.

<p>(A) Polysaccharide-type biofilm is dependent of expression of PIA/PNAG by intracellular adhesion operon (<i>icaADBC</i>)-carrying strains and is common in methicillin-sensitive <i>S</i>. <i>aureus</i> isolates. (B) Surface proteins such as BAP, the FnBPs, and SasG/Aap mediate direct cell-to-cell contact during biofilm accumulation. Cytoplasmic proteins and eDNA released following cell lysis can also act as components of the biofilm matrix. (C) Coagulase-mediated conversion of fibrinogen (Fg) into fibrin, which is recruited into a biofilm scaffold that can be dispersed by plasmin produced following staphylokinase-mediated activation of plasminogen. (D) Phenol-soluble modules have surfactant qualities that can promote biofilm dispersal but can also accumulate as amyloid aggregates that promote biofilm accumulation.</p

Eradication of staphylococcus aureus biofilm infections using synthetic antimicrobial peptides

Here, we demonstrate that antimicrobial peptides (AMPs) are an effective antibiofilm treatment when applied as catheter lock solutions (CLSs) against S. aureus biofilm infections. The activity of synthetic AMPs (Bac8c, HB43, P18, Omiganan, WMR, Ranalexin, and Polyphemusin) was measured against early and mature biofilms produced by methicillin-resistant S. aureus and methicillin-susceptible S. aureus isolates from patients with device-related infections grown under in vivo-relevant biofilm conditions. The cytotoxic and hemolytic activities of the AMPs against human cells and their immunomodulatory potential in human blood were also characterized. The D-Bac8c2,5Leu variant emerged as the most effective AMP during in vitro studies and was also highly effective in eradicating S. aureus biofilm infection when used in a CLS rat central venous catheter infection model. These data support the potential use of D-Bac8c2,5Leu, alone or in combination with other AMPs, in the treatment of S. aureus intravenous catheter infections