Next generation of consumer aerosol valve design using inert gases

The current global consumer aerosol products such as deodorants, hairsprays, air-fresheners, polish, insecticide, disinfectant are primarily utilised unfriendly environmental propellant of liquefied petroleum gas (LPG) for over three decades. The advantages of the new innovative technology described in this paper are: (i) no butane or other liquefied hydrocarbon gas; (ii) compressed air, nitrogen or other safe gas propellant; (iii) customer acceptable spray quality and consistency during can lifetime; (iv) conventional cans and filling technology. Volatile organic compounds and greenhouse gases must be avoided but there are no flashing propellants replacements that would provide the good atomisation and spray reach. On the basis of the energy source for atomising, the only feasible source is inert gas (i.e. compressed air), which improves atomisation by gas bubbles and turbulence inside the atomiser insert of the actuator. This research concentrates on using ‘bubbly flow’ in the valve stem, with injection of compressed gas into the passing flow, thus also generating turbulence. Using a vapour phase tap in conventional aerosol valves allows the propellant gas into the liquid flow upstream of the valve. However, forcing bubbly flow through a valve is not ideal. The novel valves designed here, using compressed gas, thus achieved the following objectives when the correct combination of gas and liquid inlets to the valve, and the type and size of atomiser ‘insert’ were derived: 1. Produced a consistent flow rate and drop size of spray throughout the life of the can, compatible with the current conventional aerosols that use LPG: a new ‘constancy’ parameter is defined and used to this end. 2. Obtained a discharge flow rate suited to the product to be sprayed; typically between 0.4 g/s and 2.5 g/s. 3. Attained the spray droplets size suited to the product to be sprayed; typically between 40 mm and 120 mm

Use of attribute association error probability estimates to evaluate quality of medical record geocodes

BACKGROUND: The utility of patient attributes associated with the spatiotemporal analysis of medical records lies not just in their values but also the strength of association between them. Estimating the extent to which a hierarchy of conditional probability exists between patient attribute associations such as patient identifying fields, patient and date of diagnosis, and patient and address at diagnosis is fundamental to estimating the strength of association between patient and geocode, and patient and enumeration area. We propose a hierarchy for the attribute associations within medical records that enable spatiotemporal relationships. We also present a set of metrics that store attribute association error probability (AAEP), to estimate error probability for all attribute associations upon which certainty in a patient geocode depends. METHODS: A series of experiments were undertaken to understand how error estimation could be operationalized within health data and what levels of AAEP in real data reveal themselves using these methods. Specifically, the goals of this evaluation were to (1) assess if the concept of our error assessment techniques could be implemented by a population-based cancer registry; (2) apply the techniques to real data from a large health data agency and characterize the observed levels of AAEP; and (3) demonstrate how detected AAEP might impact spatiotemporal health research. RESULTS: We present an evaluation of AAEP metrics generated for cancer cases in a North Carolina county. We show examples of how we estimated AAEP for selected attribute associations and circumstances. We demonstrate the distribution of AAEP in our case sample across attribute associations, and demonstrate ways in which disease registry specific operations influence the prevalence of AAEP estimates for specific attribute associations. CONCLUSIONS: The effort to detect and store estimates of AAEP is worthwhile because of the increase in confidence fostered by the attribute association level approach to the assessment of uncertainty in patient geocodes, relative to existing geocoding related uncertainty metrics

Complete Remission of Unresectable Colon Cancer after Preoperative Chemotherapy Selected by Adenosine Triphosphate-Based Chemotherapy Response Assay

The adenosine triphosphate-based chemotherapy response assay (ATP-CRA) is a chemosensitivity test that offers the potential of selecting cancer treatments based on the responsiveness of individual tumors. We report a case of 47-yr-old male, presented with sigmoid colon cancer with multiple liver and peritoneal metastases, in which there was a complete response for the primary colon cancer after administration of preoperative chemotherapy selected by ATP-CRA. Oxaliplatin was the most sensitive drug based on the ATP-CRA where the specimen obtained by ultrasound-guided percutaneous liver biopsy was used. After twelve cycles of oxaliplatin-capecitabine chemotherapy, abdominopelvic computed tomography revealed marked shrinkage of the liver metastases and positron emission tomography showed no uptake of 18F-fluoro-deoxy-glucose (FDG) either in the liver or peritoneum except localized uptake in the sigmoid colon. The patient underwent an anterior resection and radiofrequency ablation of the liver metastases, which resulted in a macroscopic curative resection of the cancer cells. Histological examination revealed no residual cancer cells in the resected specimen of the sigmoid colon. This result suggested that preoperative chemotherapy chosen by ATP-CRA may be useful for treating advanced colon cancer with unresectable liver and peritoneal metastases

CR1 Knops blood group alleles are not associated with severe malaria in the Gambia

The Knops blood group antigen erythrocyte polymorphisms have been associated with reduced falciparum malaria-based in vitro rosette formation (putative malaria virulence factor). Having previously identified single-nucleotide polymorphisms (SNPs) in the human complement receptor 1 (CR1/CD35) gene underlying the Knops antithetical antigens Sl1/Sl2 and McC(a)/McC(b), we have now performed genotype comparisons to test associations between these two molecular variants and severe malaria in West African children living in the Gambia. While SNPs associated with Sl:2 and McC(b+) were equally distributed among malaria-infected children with severe malaria and control children not infected with malaria parasites, high allele frequencies for Sl 2 (0.800, 1,365/1,706) and McC(b) (0.385, 658/1706) were observed. Further, when compared to the Sl 1/McC(a) allele observed in all populations, the African Sl 2/McC(b) allele appears to have evolved as a result of positive selection (modified Nei-Gojobori test Ka-Ks/s.e.=1.77, P-value <0.05). Given the role of CR1 in host defense, our findings suggest that Sl 2 and McC(b) have arisen to confer a selective advantage against infectious disease that, in view of these case-control study data, was not solely Plasmodium falciparum malaria. Factors underlying the lack of association between Sl 2 and McC(b) with severe malaria may involve variation in CR1 expression levels

Hyperglycemia regulates thioredoxin-ROS activity through induction of thioredoxin-interacting protein (TXNIP) in metastatic breast cancer-derived cells MDA-MB-231

<p>Abstract</p> <p>Background</p> <p>We studied the RNA expression of the genes in response to glucose from 5 mM (condition of normoglycemia) to 20 mM (condition of hyperglycemia/diabetes) by microarray analysis in breast cancer derived cell line MDA-MB-231. We identified the thioredoxin-interacting protein (TXNIP), whose RNA level increased as a gene product particularly sensitive to the variation of the level of glucose in culture media. We investigated the kinesis of the TXNIP RNA and protein in response to glucose and the relationship between this protein and the related thioredoxin (TRX) in regulating the level of reactive oxygen species (ROS) in MDA-MB-231 cells.</p> <p>Methods</p> <p>MDA-MB-231 cells were grown either in 5 or 20 mM glucose chronically prior to plating. For glucose shift (5/20), cells were plated in 5 mM glucose and shifted to 20 mM at time 0. Cells were analyzed with Affymetrix Human U133A microarray chip and gene expression profile was obtained. Semi-quantitative RT-PCR and Western blot was used to validate the expression of TXNIP RNA and protein in response to glucose, respectively. ROS were detected by CM-H2DCFDA (5–6-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate) and measured for mean fluorescence intensity with flow cytometry. TRX activity was assayed by the insulin disulfide reducing assay.</p> <p>Results</p> <p>We found that the regulation of TXNIP gene expression by glucose in MDA-MB-231 cells occurs rapidly within 6 h of its increased level (20 mM glucose) and persists through the duration of the conditions of hyperglycemia. The increased level of TXNIP RNA is followed by increased level of protein that is associated with increasing levels of ROS and reduced TRX activity. The inhibition of the glucose transporter GLUT1 by phloretin notably reduces TXNIP RNA level and the inhibition of the p38 MAP kinase activity by SB203580 reverses the effects of TXNIP on ROS-TRX activity.</p> <p>Conclusion</p> <p>In this study we show that TXNIP is an oxidative stress responsive gene and its expression is exquisitely regulated by glucose level in highly metastatic MDA-MB-231 cells.</p

Mathematical modelling of polyamine metabolism in bloodstream-form trypanosoma brucei: An application to drug target identification

© 2013 Gu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedThis article has been made available through the Brunel Open Access Publishing Fund.We present the first computational kinetic model of polyamine metabolism in bloodstream-form Trypanosoma brucei, the causative agent of human African trypanosomiasis. We systematically extracted the polyamine pathway from the complete metabolic network while still maintaining the predictive capability of the pathway. The kinetic model is constructed on the basis of information gleaned from the experimental biology literature and defined as a set of ordinary differential equations. We applied Michaelis-Menten kinetics featuring regulatory factors to describe enzymatic activities that are well defined. Uncharacterised enzyme kinetics were approximated and justified with available physiological properties of the system. Optimisation-based dynamic simulations were performed to train the model with experimental data and inconsistent predictions prompted an iterative procedure of model refinement. Good agreement between simulation results and measured data reported in various experimental conditions shows that the model has good applicability in spite of there being gaps in the required data. With this kinetic model, the relative importance of the individual pathway enzymes was assessed. We observed that, at low-to-moderate levels of inhibition, enzymes catalysing reactions of de novo AdoMet (MAT) and ornithine production (OrnPt) have more efficient inhibitory effect on total trypanothione content in comparison to other enzymes in the pathway. In our model, prozyme and TSHSyn (the production catalyst of total trypanothione) were also found to exhibit potent control on total trypanothione content but only when they were strongly inhibited. Different chemotherapeutic strategies against T. brucei were investigated using this model and interruption of polyamine synthesis via joint inhibition of MAT or OrnPt together with other polyamine enzymes was identified as an optimal therapeutic strategy.The work was carried out under a PhD programme partly funded by Prof. Ray Welland, School of Computing Science, University of Glasgo

Targeted hepatitis C antibody testing interventions: a systematic review and meta-analysis

Testing for hepatitis C virus (HCV) infection may reduce the risk of liver-related morbidity, by facilitating earlier access to treatment and care. This review investigated the effectiveness of targeted testing interventions on HCV case detection, treatment uptake, and prevention of liver-related morbidity. A literature search identified studies published up to 2013 that compared a targeted HCV testing intervention (targeting individuals or groups at increased risk of HCV) with no targeted intervention, and results were synthesised using meta-analysis. Exposure to a targeted testing intervention, compared to no targeted intervention, was associated with increased cases detected [number of studies (n) = 14; pooled relative risk (RR) 1.7, 95 % CI 1.3, 2.2] and patients commencing therapy (n = 4; RR 3.3, 95 % CI 1.1, 10.0). Practitioner-based interventions increased test uptake and cases detected (n = 12; RR 3.5, 95 % CI 2.5, 4.8; and n = 10; RR 2.2, 95 % CI 1.4, 3.5, respectively), whereas media/information-based interventions were less effective (n = 4; RR 1.5, 95 % CI 0.7, 3.0; and n = 4; RR 1.3, 95 % CI 1.0, 1.6, respectively). This meta-analysis provides for the first time a quantitative assessment of targeted HCV testing interventions, demonstrating that these strategies were effective in diagnosing cases and increasing treatment uptake. Strategies involving practitioner-based interventions yielded the most favourable outcomes. It is recommended that testing should be targeted at and offered to individuals who are part of a population with high HCV prevalence, or who have a history of HCV risk behaviour

Cost-effectiveness of HBV and HCV screening strategies:a systematic review of existing modelling techniques

Introduction: Studies evaluating the cost-effectiveness of screening for Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) are generally heterogeneous in terms of risk groups, settings, screening intervention, outcomes and the economic modelling framework. It is therefore difficult to compare cost-effectiveness results between studies. This systematic review aims to summarise and critically assess existing economic models for HBV and HCV in order to identify the main methodological differences in modelling approaches. Methods: A structured search strategy was developed and a systematic review carried out. A critical assessment of the decision-analytic models was carried out according to the guidelines and framework developed for assessment of decision-analytic models in Health Technology Assessment of health care interventions. Results: The overall approach to analysing the cost-effectiveness of screening strategies was found to be broadly consistent for HBV and HCV. However, modelling parameters and related structure differed between models, producing different results. More recent publications performed better against a performance matrix, evaluating model components and methodology. Conclusion: When assessing screening strategies for HBV and HCV infection, the focus should be on more recent studies, which applied the latest treatment regimes, test methods and had better and more complete data on which to base their models. In addition to parameter selection and associated assumptions, careful consideration of dynamic versus static modelling is recommended. Future research may want to focus on these methodological issues. In addition, the ability to evaluate screening strategies for multiple infectious diseases, (HCV and HIV at the same time) might prove important for decision makers

Twenty Years of SUGRA

A brief review is given of the developments of mSUGRA and its extensions since the formulation of these models in 1982. Future directions and prospects are also discussed.Comment: Invited talk at the International Conference BEYOND-2003, Schloss Ringberg, Germany, June 10-14, 2003; 21 pages, Late