Regional differences in willingness to pay for organic vegetables

The concern about vegetable safety, together with a booming population and the rise of the middle class has made Vietnam become a potential market for organic vegetables. This paper investigates the determinants of willingness to pay (WTP) for organic vegetables in Hanoi, Vietnam with a particular attention to regional differences and the effect of risk perception. Using Contingent Valuation Method to analyze the data from a sample of 498 consumers in Hanoi, the paper shows that the perceived use values of organic vegetables, trust in organic labels, and disposable family income increased WTP for organic vegetables in both urban and rural regions.Though risk perception of conventional vegetables was high in both regions, such heightened risk perception just translated into the WTP in the rural region. In addition, the percentage of home-grown vegetables in the total vegetable consumption of the family influenced the WTP in the rural region only. Moreover, being an organic purchaser was positively related to the WTP in the urban region but not in the rural region. The paper also discusses three policy implications for Vietnam to boost the demand for organic food.fals

The effect of hydrogen on transient flow of hydrogen natural gas mixture

Hydrogen is a high pressure gas, hence hydrogen natural gas mixture require an accurate prediction of transient flow parameter. The reduce order modelling is used in analysis of transient flow, where viscosity change is neglected thereby reducing the governing equations to Euler equation based on the assumption. The hydrogen natural gas mixture is homogenous, with pressure and velocity considered as principal dependent variable where polytrophic process is admitted. For improvement on the accurate prediction of flow parameters on the analysis of transient flow of hydrogen natural gas mixture in pipeline implicit Steger-Warming flux vector splitting method (FSM) used in the construction of efficient reduce order model. The result shows significant improvement on efficiency, accuracy and uniqueness when compared to normal conventional numerical techniques. The effect of heat transfer is observed on heat flux and internal energy of transient flow. The methods of reduced order with and without static correction show significant agreement for different gas ratio. The prediction of flow parameter along the pipeline can improvegas delivery and the analysis of transient flow behaviour at any point during the flow

Ductile bulk metallic glass by controlling structural heterogeneities

A prerequisite to utilize the full potential of structural heterogeneities for improving the room-temperature plastic deformation of bulk metallic glasses (BMGs) is to understand their interaction with the mechanism of shear band formation and propagation. This task requires the ability to artificially create heterogeneous microstructures with controlled morphology and orientation. Here, we analyze the effect of the designed heterogeneities generated by imprinting on the tensile mechanical behavior of the Zr52.5Ti5Cu18Ni14.5Al10 BMG by using experimental and computational methods. The imprinted material is elastically heterogeneous and displays anisotropic mechanical properties: strength and ductility increase with increasing the loading angle between imprints and tensile direction. This behavior occurs through shear band branching and their progressive rotation. Molecular dynamics and finite element simulations indicate that shear band branching and rotation originates at the interface between the heterogeneities, where the characteristic atomistic mechanism responsible for shear banding in a homogeneous glass is perturbed

Physiologically based modelling of tranexamic acid pharmacokinetics following intravenous, intramuscular, sub-cutaneous and oral administration in healthy volunteers

BACKGROUND: Tranexamic acid (TXA) is an antifibrinolytic drug that reduces surgical blood loss and death due to bleeding after trauma and post-partum haemorrhage. Treatment success is dependent on early intervention and rapid systemic exposure to TXA. The requirement for intravenous (IV) administration can in some situations limit accessibility to TXA therapy. Here we employ physiologically based pharmacokinetic modelling (PBPK) to evaluate if adequate TXA exposure maybe achieved when given via different routes of administration. METHODS: A commercially available PBPK software (GastroPlus®) was used to model published TXA pharmacokinetics. IV, oral and intramuscular (IM) models were developed using healthy volunteer PK data from twelve different single dose regimens (n=48 participants). The model was verified using separate IV and oral validation datasets (n=26 participants). Oral, IM and sub-cutaneous (SQ) dose finding simulations were performed. RESULTS: Across the different TXA regimens evaluated TXA plasma concentrations varied from 0.1 to 94.0 µg/mL. Estimates of the total plasma clearance of TXA ranged from 0.091 to 0.104 L/h/kg, oral bioavailability from 36 to 67 % and Tmax from 2.6 to 3.2 and 0.4 to 1.0 hours following oral and intramuscular administration respectively. Variability in the observed TXA PK could be captured through predictable demographic effects on clearance, combined with intestinal permeability and stomach transit time following oral administration and muscle blood flow and muscle/plasma partition coefficients following intra-muscular dosing. CONCLUSIONS: This study indicates that intramuscular administration is the non-intravenous route of administration with the most potential for achieving targeted TXA exposures. Plasma levels following an IM dose of 1000 mg TXA are predicted to exceed 15 mg/mL in < 15 minutes and be maintained above this level for approximately 3 hours, achieving systemic exposure (AUC0-6) of 99 to 105 µg*hr/mL after a single dose. Well-designed clinical trials to verify these predictions and confirm the utility of intramuscular TXA are recommended

Ductile bulk metallic glass by controlling structural heterogeneities

A prerequisite to utilize the full potential of structural heterogeneities for improving the room-temperature plastic deformation of bulk metallic glasses (BMGs) is to understand their interaction with the mechanism of shear band formation and propagation. This task requires the ability to artificially create heterogeneous microstructures with controlled morphology and orientation. Here, we analyze the effect of the designed heterogeneities generated by imprinting on the tensile mechanical behavior of the ZrTiCuNiAl BMG by using experimental and computational methods. The imprinted material is elastically heterogeneous and displays anisotropic mechanical properties: strength and ductility increase with increasing the loading angle between imprints and tensile direction. This behavior occurs through shear band branching and their progressive rotation. Molecular dynamics and finite element simulations indicate that shear band branching and rotation originates at the interface between the heterogeneities, where the characteristic atomistic mechanism responsible for shear banding in a homogeneous glass is perturbed

Artificial membrane-binding proteins stimulate oxygenation of stem cells during engineering of large cartilage tissue

Restricted oxygen diffusion can result in central cell necrosis in engineered tissue, a problem that is exacerbated when engineering large tissue constructs for clinical application. Here we show that pre-treating human mesenchymal stem cells (hMSCs) with synthetic membrane-active myoglobin-polymer–surfactant complexes can provide a reservoir of oxygen capable of alleviating necrosis at the centre of hyaline cartilage. This is achieved through the development of a new cell functionalization methodology based on polymer–surfactant conjugation, which allows the delivery of functional proteins to the hMSC membrane. This new approach circumvents the need for cell surface engineering using protein chimerization or genetic transfection, and we demonstrate that the surface-modified hMSCs retain their ability to proliferate and to undergo multilineage differentiation. The functionalization technology is facile, versatile and non-disruptive, and in addition to tissue oxygenation, it should have far-reaching application in a host of tissue engineering and cell-based therapies

The effectiveness and safety of antifibrinolytics in patients with acute intracranial haemorrhage: statistical analysis plan for an individual patient data meta-analysis

Introduction: The Antifibrinolytic Trialists Collaboration aims to increase knowledge about the effectiveness and safety of antifibrinolytic treatment by conducting individual patient data (IPD) meta-analyses of randomised trials. This article presents the statistical analysis plan for an IPD meta-analysis of the effects of antifibrinolytics for acute intracranial haemorrhage. Methods: The protocol for the IPD meta-analysis has been registered with PROSPERO (CRD42016052155). We will conduct an individual patient data meta-analysis of randomised controlled trials with 1000 patients or more assessing the effects of antifibrinolytics in acute intracranial haemorrhage. We will assess the effect on two co-primary outcomes: 1) death in hospital at end of trial follow-up, and 2) death in hospital or dependency at end of trial follow-up. The co-primary outcomes will be limited to patients treated within three hours of injury or stroke onset. We will report treatment effects using odds ratios and 95% confidence intervals. We use logistic regression models to examine how the effect of antifibrinolytics vary by time to treatment, severity of intracranial bleeding, and age. We will also examine the effect of antifibrinolytics on secondary outcomes including death, dependency, vascular occlusive events, seizures, and neurological outcomes. Secondary outcomes will be assessed in all patients irrespective of time of treatment. All analyses will be conducted on an intention-to-treat basis. Conclusions: This IPD meta-analysis will examine important clinical questions about the effects of antifibrinolytic treatment in patients with intracranial haemorrhage that cannot be answered using aggregate data. With IPD we can examine how effects vary by time to treatment, bleeding severity, and age, to gain better understanding of the balance of benefit and harms on which to base recommendations for practice

The WOMAN trial: clinical and contextual factors surrounding the deaths of 483 women following post-partum haemorrhage in developing countries.

BACKGROUND: Post-partum haemorrhage (PPH) is a leading cause of maternal death worldwide. The WOMAN trial assessed the effects of tranexamic acid (TXA) on death and surgical morbidity in women with PPH. The trial recorded 483 maternal deaths. We report the circumstances of the women who died. METHODS: The WOMAN trial recruited 20,060 women with a clinical diagnosis of PPH after a vaginal birth or caesarean section. We randomly allocated women to receive TXA or placebo. When a woman died, we asked participating clinicians to report the cause of death and to provide a short narrative of the events surrounding the death. We collated and edited for clarity the narrative data. RESULTS: Case fatality rates were 3.0% in Africa and 1.7% in Asia. Nearly three quarters of deaths were within 3 h of delivery and 91% of these deaths were from bleeding. Women who delivered outside a participating hospital (12%) were three times more likely to die (OR = 3.12, 95%CI 2.55-3.81) than those who delivered in hospital. Blood was often unavailable due to shortages or because relatives could not afford to buy it. Clinicians highlighted late presentation, maternal anaemia and poor infrastructure as key contributory factors. CONCLUSIONS: Although TXA use reduces bleeding deaths by almost one third, mortality rates similar to those in high income countries will not be achieved without tackling late presentation, maternal anaemia, availability of blood for transfusion and poor infrastructure

Pharmacokinetics of intramuscular tranexamic acid in bleeding trauma patients: a clinical trial.

BACKGROUND: Intravenous tranexamic acid (TXA) reduces bleeding deaths after injury and childbirth. It is most effective when given early. In many countries, pre-hospital care is provided by people who cannot give i.v. injections. We examined the pharmacokinetics of intramuscular TXA in bleeding trauma patients. METHODS: We conducted an open-label pharmacokinetic study in two UK hospitals. Thirty bleeding trauma patients received a loading dose of TXA 1 g i.v., as per guidelines. The second TXA dose was given as two 5 ml (0·5 g each) i.m. injections. We collected blood at intervals and monitored injection sites. We measured TXA concentrations using liquid chromatography coupled to mass spectrometry. We assessed the concentration time course using non-linear mixed-effect models with age, sex, ethnicity, body weight, type of injury, signs of shock, and glomerular filtration rate as possible covariates. RESULTS: Intramuscular TXA was well tolerated with only mild injection site reactions. A two-compartment open model with first-order absorption and elimination best described the data. For a 70-kg patient, aged 44 yr without signs of shock, the population estimates were 1.94 h-1 for i.m. absorption constant, 0.77 for i.m. bioavailability, 7.1 L h-1 for elimination clearance, 11.7 L h-1 for inter-compartmental clearance, 16.1 L volume of central compartment, and 9.4 L volume of the peripheral compartment. The time to reach therapeutic concentrations (5 or 10 mg L-1) after a single intramuscular TXA 1 g injection are 4 or 11 min, with the time above these concentrations being 10 or 5.6 h, respectively. CONCLUSIONS: In bleeding trauma patients, intramuscular TXA is well tolerated and rapidly absorbed. CLINICAL TRIAL REGISTRATION: 2019-000898-23 (EudraCT); NCT03875937 (ClinicalTrials.gov)

Managing clinical trials

Managing clinical trials, of whatever size and complexity, requires efficient trial management. Trials fail because tried and tested systems handed down through apprenticeships have not been documented, evaluated or published to guide new trialists starting out in this important field. For the past three decades, trialists have invented and reinvented the trial management wheel. We suggest that to improve the successful, timely delivery of important clinical trials for patient benefit, it is time to produce standard trial management guidelines and develop robust methods of evaluation