Bus travel time reliability analysis: A case study

The travel time reliability of buses has become increasingly important for public transit companies. In this study, a novel approach is proposed to evaluate and analyse the travel time reliability of bus services provided by TransLink in Queensland, Australia. In view of their stochastic features, the two components of travel time-dwell time and driving time-are represented by discrete distributed and normally distributed random variables respectively. Accordingly, the travel time could be described by Gaussian mixture models. Based on the proposed model, impact analysis shows that bus line reliability would increase by around 15% if onboard top-up for 'go cards' (electronic tickets) was not offered by TransLink. It was found that not providing this top-up method would not significantly harm the benefit of go card users, but it would substantially increase the total social benefit thanks to improved bus line reliability

Application of human mesenchymal and pluripotent stem cell microcarrier cultures in cellular therapy: Achievements and future direction

AbstractMesenchymal stem cells (MSCs) have recently made significant progress with multiple clinical trials targeting modulation of immune responses, regeneration of bone, cartilage, myocardia, and diseases like Metachromatic leukodystrophy and Hurler syndrome. On the other hand, the use of human embryonic and induced pluripotent stem cells (hPSCs) in clinical trials is rather limited mainly due to safety issues. Only two clinical trials, retinal pigment epithelial transplantation and treatment of spinal cord injury were reported. Cell doses per treatment can range between 50,000 and 6billion cells. The current 2-dimensional tissue culture platform can be used when low cell doses are needed and it becomes impractical when doses above 50million are needed. This demand for future cell therapy has reinvigorated interests in the use of the microcarrier platform for generating stem cells in a scalable 3-dimensional manner.Microcarriers developed for culturing adherent cell lines in suspension have been used mainly in vaccine production and research purposes. Since MSCs grow as monolayers similar to conventional adherent cell lines, adapting MSCs to a microcarrier based expansion platform has been progressing rapidly. On the other hand, establishing a robust microcarrier platform for hPSCs is more challenging as these cells grow in multilayer colonies on extracellular matrices and are more susceptible to shear stress.This review describes properties of commercially available microcarriers developed for cultivation of anchorage dependent cells and present current achievements for expansion and differentiation of stem cells. Key issues such as microcarrier properties and coatings, cell seeding conditions, medium development and improved bioprocess parameters needed for optimal stem cell systems are discussed

Micronutrient losses during renal replacement therapy for acute kidney injury

Malnutrition is common in acute kidney injury (AKI) patients, particularly on the ICU, where they often receive renal replacement therapy (RRT). RRT may exacerbate loss of water-soluble micronutrients (e.g. trace elements, amino acids and B-vitamins). No clinical study has quantified these losses and contrasted between types of RRT that use different methods to remove solutes i.e. by diffusion (intermittent haemodialysis, IHD) by convection (continuous veno-venous haemofiltration, CVVH) or by a combination of both (sustained low-efficiency diafiltration, SLEDf). Using a prospective, observational design patients (n=24 per modality) were consented before their first treatment session. Blood and RRT effluent (dialysate or filtrate) were sampled at baseline (pre-RRT), mid and end-RRT. Amino acids were measured by HPLC, trace elements by ICP-MS and B-vitamins (B1, B3, B6, B9, B12) by LC-MS. Plasma concentrations were corrected for dialysis dose using the urea reduction ratio (for IHD & SLEDf, but not CVVH). Micronutrient losses (mass-corrected) were calculated as concentration × RRT effluent volume, corrected for plasma concentration and RRT dose (i.e. solute removal index). Data were analysed by restricted maximum likelihood estimating equations (Genstat v16, VSNi Ltd, UK). Patients receiving CVVH had significantly higher plasma amino acids, but not plasma trace elements, at baseline (amino acids: CVVH, 3762 ± 357; IHD, 2039 ± 337; SLEDf, 2505 ± 423 µmol/L; trace elements: IHD, 4156 ± 465; SLEDf 3732 ± 521; CVVH 3982 ± 465 µg/L). At RRT end, plasma amino acids and trace elements had significantly reduced (429 ± 223 µmol/L; 600 ± 400 µg/L, respectively). No trace element was lost to a greater extent between types of RRT, but many (>10) individual amino acids declined to a much greater extent with SLEDf vs. HD or CVVH (e.g. effect size for lysine was -64 ± 23 µmol/L). Two significant sources of micronutrient loss were noted: to effluent and through dialyser adsorption. The latter contributed <1g amino acids but in effluent recorded losses of up to 25g were noted with CVVH (5-10g for IHD and SLEDf, respectively). Effluent losses of trace elements varied significantly, but in all cases were greater for CVVH (e.g. effect size for copper was +850 ± 475 µg vs. HD or SLED-F). B-vitamins were not detectable in effluent. Significant loss of micronutrients during RRT, particularly for patients in ICU, is a possible aggravating factor for patients known to be at high risk of malnutrition. The type of RRT used influences the pattern of loss but not consistently for all nutrients. Adsorption of amino acids to dialysers adds a small, but cumulative loss that may become important if further treatment sessions are indicated

Self-induced ultrafast electron-hole plasma temperature oscillations in nanowire lasers

Nanowire lasers can be monolithically and site-selectively integrated onto silicon photonic circuits. To assess their full potential for ultrafast opto-electronic devices, a detailed understanding of their lasing dynamics is crucial. However, the roles played by their resonator geometry and the microscopic processes that mediate energy exchange between the photonic, electronic, and phononic subsystems are largely unexplored. Here, we study the dynamics of GaAs-AlGaAs core-shell nanowire lasers at cryogenic temperatures using a combined experimental and theoretical approach. Our results indicate that these NW lasers exhibit sustained intensity oscillations with frequencies ranging from 160 GHz to 260 GHz. As the underlying physical mechanism, we identified self-induced electron-hole plasma temperature oscillations resulting from a dynamic competition between photoinduced carrier heating and cooling via phonon scattering. These dynamics are intimately linked to the strong interaction between the lasing mode and the gain material, which arises from the wavelength-scale dimensions of these lasers. We anticipate that our results could lead to new approaches for ultrafast intensity and phase modulation of chip-integrated nanoscale semiconductor lasers.Comment: Revised manuscrip

Predicting major adverse cardiovascular events for secondary prevention: protocol for a systematic review and meta-analysis of risk prediction models

INTRODUCTION: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality globally. With advances in early diagnosis and treatment of CVD and increasing life expectancy, more people are surviving initial CVD events. However, models for stratifying disease severity risk in patients with established CVD for effective secondary prevention strategies are inadequate. Multivariable prognostic models to stratify CVD risk may allow personalised treatment interventions. This review aims to systematically review the existing multivariable prognostic models for the recurrence of CVD or major adverse cardiovascular events in adults with established CVD diagnosis. METHODS AND ANALYSIS: Bibliographic databases (Ovid MEDLINE, EMBASE, PsycINFO and Web of Science) will be searched, from database inception to April 2020, using terms relating to the clinical area and prognosis. A hand search of the reference lists of included studies will also be done to identify additional published studies. No restrictions on language of publications will be applied. Eligible studies present multivariable models (derived or validated) of adults (aged 16 years and over) with an established diagnosis of CVD, reporting at least one of the components of the primary outcome of major adverse cardiovascular events (defined as either coronary heart disease, stroke, peripheral artery disease, heart failure or CVD-related mortality). Reviewing will be done by two reviewers independently using the pre-defined criteria. Data will be extracted for included full-text articles. Risk of bias will be assessed using the Prediction model study Risk Of Bias ASsessment Tool (PROBAST). Prognostic models will be summarised narratively. If a model is tested in multiple validation studies, the predictive performance will be summarised using a random-effects meta-analysis model to account for any between-study heterogeneity. ETHICS AND DISSEMINATION: Ethics approval is not required. The results of this study will be submitted to relevant conferences for presentation and a peer-reviewed journal for publication. PROSPERO REGISTRATION NUMBER: CRD42019149111

Remote effects of acute kidney injury in a porcine model

Background: Acute Kidney Injury (AKI) is a common and serious disease with no specific treatment. An episode of AKI may affect organs distant to the kidney, further increasing the morbidity associated with AKI. The mechanism of organ cross-talk after AKI is unclear. The renal and immune systems of pigs and humans are alike. Using a preclinical animal (porcine) model, we test the hypothesis that early effects of AKI on distant organs is by immune cell infiltration leading to inflammatory cytokine production, extravasation and edema. Study Design: In 29 pigs exposed to either sham-surgery or renal ischemia-reperfusion (control, n=12; AKI, n=17) we assessed remote organ (liver, lung, brain) effects in the short-(from 2 to 48h reperfusion) and longer-term (5 weeks later) using immunofluorescence (for leucocyte infiltration, apoptosis), a cytokine array, tissue elemental analysis (electrolytes), blood hematology and chemistry (e.g. liver enzymes) and PCR (for inflammatory markers). Results: AKI elicited significant, short-term (~24h) increments in enzymes indicative of acute liver damage (e.g. AST:ALT ratio; P=0.02) and influenced tissue biochemistry in some remote organs (e.g. lung tissue [Ca++] increased; P=0.04). These effects largely resolved after 48h and no further histopathology, edema, apoptosis or immune cell infiltration was noted in liver, lung or hippocampus in the short- and longer-term. Conclusions: AKI has subtle biochemical effects on remote organs in the short-term including a transient increment in markers of acute liver damage. These effects resolved by 48h and no further remote organ histopathology, apoptosis, edema or immune cell infiltration was noted

PTEN controls glandular morphogenesis through a juxtamembrane β-Arrestin1/ARHGAP21 scaffolding complex

PTEN controls three-dimensional (3D) glandular morphogenesis by coupling juxtamembrane signalling to mitotic spindle machinery. While molecular mechanisms remain unclear, PTEN interacts through its C2 membrane-binding domain with the scaffold protein β-Arrestin1. Because β-Arrestin1 binds and suppresses the Cdc42 GTPase-activating protein ARHGAP21, we hypothesize that PTEN controls Cdc42-dependent morphogenic processes through a β-Arrestin1-ARHGAP21 complex. Here we show that PTEN knockdown (KD) impairs β-Arrestin1 membrane localization, β-Arrestin1-ARHGAP21 interactions, Cdc42 activation, mitotic spindle orientation and 3D glandular morphogenesis. Effects of PTEN-deficiency were phenocopied by β-Arrestin1 KD or inhibition of β-Arrestin1-ARHGAP21 interactions. Conversely, silencing of ARHGAP21 enhanced Cdc42 activation and rescued aberrant morphogenic processes of PTEN-deficient cultures. Expression of the PTEN C2 domain mimicked effects of full-length PTEN but a membrane-binding defective mutant of the C2 domain abrogated these properties. Our results show that PTEN controls multicellular assembly through a membrane-associated regulatory protein complex composed of β-Arrestin1, ARHGAP21 and Cdc42

Self-induced ultrafast electron-hole-plasma temperature oscillations in nanowire lasers

Nanowire lasers can be monolithically and site-selectively integrated onto silicon photonic circuits. To assess their full potential for ultrafast optoelectronic devices, a detailed understanding of their lasing dynamics is crucial. However, the roles played by their resonator geometry and the microscopic processes that mediate energy exchange between the photonic, electronic, and phononic subsystems are largely unexplored. Here, we study the dynamics of GaAs-AlGaAs core-shell nanowire lasers at cryogenic tem- peratures using a combined experimental and theoretical approach. Our results indicate that these NW lasers exhibit sustained intensity oscillations with frequencies ranging from 160 GHz to 260 GHz. As the underlying physical mechanism, we have identified self-induced electron-hole plasma temperature oscilla- tions resulting from a dynamic competition between photoinduced carrier heating and cooling via phonon scattering. These dynamics are intimately linked to the strong interaction between the lasing mode and the gain material, which arises from the wavelength-scale dimensions of these lasers. We anticipate that our results could lead to optimised approaches for ultrafast intensity and phase modulation of chip-integrated semiconductor lasers at the nanoscale

Micronutrient and amino acid losses during renal replacement therapy for acute kidney injury

© 2019 International Society of Nephrology Introduction: Malnutrition is common in patients with acute kidney injury (AKI), particularly in those requiring renal replacement therapy (RRT). Use of RRT removes metabolic waste products and toxins, but it will inevitably also remove useful molecules such as micronutrients, which might aggravate malnutrition. The RRT modalities vary in mechanism of solute removal; for example, intermittent hemodialysis (IHD) uses diffusion, continuous veno-venous hemofiltration (CVVH) uses convection, and sustained low-efficiency diafiltration (SLEDf) uses a combination of these. Methods: We assessed micronutrient and amino acid losses in 3 different RRT modalities in patients with AKI (IHD, n = 27; SLEDf, n = 12; CVVH, n = 21) after correction for dialysis dose and plasma concentrations. Results: Total losses were affected by modality; generally CVVH >> SLEDf > IHD (e.g., amino acid loss was 18.69 ± 3.04, 8.21 ± 4.07, and 5.13 ± 3.1 g, respectively; P < 0.001). Loss of specific trace elements (e.g., copper and zinc) during RRT was marked, with considerable heterogeneity between RRT types (e.g., +849 and +2325 μg/l lost during SLEDf vs. IHD, respectively), whereas effluent losses of copper and zinc decreased during CVVH (effect size relative to IHD, −3167 and −1442 μg/l, respectively). B vitamins were undetectable in effluent, but experimental modeling estimated 40% to 60% loss within the first 15 minutes of RRT. Conclusion: Micronutrient and amino acid losses are marked during RRT in patients with AKI, with variation between RRT modalities and micronutrients