Glycerophospholipid oxidation and production of aldehydes in oesophageal adenocarcinoma

Oesophageal adenocarcinoma (OAC) has an unmet clinical need, with five year survival in the UK remaining at 15%. There has been little improvement with advances in surgical practice or systemic chemotherapeutic regimens. Early diagnosis holds the key to radical treatment, the clinical utility of breath testing has highlighted aldehydes as a potential early marker of cancer. The emerging field of lipidomics has identified variations in lipid composition between cancer and benign tissue. These observed changes have highlighted phospholipids as particularly important class responsible for structural membrane stability, cell signalling and replication. In this research, multiple mass spectrometry techniques were implemented to identify and correlate lipid abundance with increased aldehyde quantitation. Desorption Electrospray Ionisation- Mass Spectrometry (DESI-MS) was utilised for lipid profiling in oesophageal adenocarcinoma tissue to reveal a prevalence of Phosphatidic acids (PA) and Phosphatidylglycerol (PG) species. Comprehensive bioinformatics analysis highlighted the PG pathway with significantly dysregulation and positive phenotype to PG production. The investigation of aldehydes was performed in vivo by lipid oxidation and corroborated in OAC tissue by a targeted Liquid Chromatography mass spectrometry (LC-MS) method. This identified medium and long chain aldehydes (Pentanal, Nonanal, Un-decanal) at particularly increased concentration. To investigate the lipid product correlation, the chemistry of lipid oxidation was defined and characterised. To explored the origin of the increased PA and PG a targeted LC-MS method was created and patient tissue and surface mucus samples were collected at paired sites. The analysis confirmed a relative increase of PAs and PGs in OAC tissue and mucus of representative intensities suggesting a correlation between mucus sampling and cell phospholipid concentration. These data highlight the Phospholipid products of a genetically dysregulated pathway in OAC, which may contribute to the production of unstable polyunsaturated lipids which are prone to oxidation and formation of aldehydes.Open Acces

Direct Digital Synthesis: A Flexible Architecture for Advanced Signals Research for Future Satellite Navigation Payloads

In legacy Global Positioning System (GPS) Satellite Navigation (SatNav) payloads, the architecture does not provide the flexibility to adapt to changing circumstances and environments. GPS SatNav payloads have largely remained unchanged since the system became fully operational in April 1995. Since then, the use of GPS has become ubiquitous in our day-to-day lives. GPS availability is now a basic assumption for distributed infrastructure; it has become inextricably tied to our national power grids, cellular networks, and global financial systems. Emerging advancements of easy to use radio technologies, such as software-defined radios (SDRs), have greatly lowered the difficulty of discovery and exploitation of vulnerabilities to these systems. The promise of a Direct Digital Synthesis (DDS) architecture provides the flexibility of incorporating countermeasures to emerging threats while maintaining backward capability with existing GPS signals. The objective of the proposed research is to determine if DDS architecture is a viable replacement for legacy GPS SatNav payloads. The overall performance of several architectures is analyzed and evaluated. The architecture with the best performance is chosen and implemented onto a programmable logic device, and GPS signals are generated. The advantages and disadvantages of using the DDS model are discussed and an end-to-end numerical and mathematical models are developed. The end-to-end mathematical model analyzes the quantization effects of the DDS architecture, and it predicts the location and power levels of the desired signal and spurious content present in the spectrum. The spurious content may potentially cause intermodulation distortion to the desired signal. The appropriate DDS architecture and resources are selected by the information gained from the mathematical model

THE ROLE OF PRINT ADVERTISING DURING PRODUCT RECALL CRISIS

A product recall is a request to return to the maker a batch or an entire production run of a product, usually due to the discovery of safety issues. The recall is an effort to limit liability for corporate negligence (which can cause costly legal penalties) and to improve or avoid damage to publicity. Recalls are costly to a company because they often entail replacing the recalled product or paying for damage caused by use, although possibly less costly than consequential costs caused by damage to brand name and reduced trust in the manufacturer. Product recalls are pervasive economic phenomenon, which occur frequently and can have devastating consequences for the recalling firm. This paper documents the significance of product recalls, and of advertising as a means of recall communication. This paper presents taxonomy of the major modes of advertising encountered in product recall campaigns. Additionally, certain prescriptive admonitions are suggested for each of the three dominant print modes; direct mail, display ads, and point-of-sales messages. Finally, a series of basic generalizations about recall print advertising are advanced.Â

Health expenditure comparison of extended-release metoprolol succinate and immediate-release metoprolol tartarate

Varun Vaidya, Pranav PatelCollege of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH, USABackground: Metoprolol, a selective beta-1 blocker, is available in two different salt forms in the market – metoprolol succinate (MS) and metoprolol tartarate (MT). Both the formulations are Food and Drug Administration approved for the treatment of hypertension. Several studies have shown similar efficacies between the two salts; however, they differ in their pharmacokinetic properties and are therefore priced differently. The primary objective of this study was to compare the overall health care expenditures of hypertensive patients on MT and MS to see if the price difference in the two preparations is offset by savings in overall expenditure.Methods: Two cohorts of patients using MT and MS were selected from the 2008 Medical Expenditure Panel Survey. Propensity score matching technique was used to balance the cohorts on various parameters such as demographic information, insurance status, and comorbidity score. Patients using MT were matched to patients using MS on the logit of propensity score using calipers of width equal to 0.2 of the standard deviation of the logit of the propensity score. Multiple regression analysis was carried out to examine the association between health expenditure and type of metoprolol salt, adjusting for other covariates.Results: A total of 742 patients were found to use metoprolol (MT-388, MS-354). After propensity score matching, a total of 582 patients were left in the sample for final analysis (291 patients in each cohort). The average annual health care expenditure was slightly higher in the MT cohort; however, after adjusting for covariates in a multivariate analysis, the difference was found to be statistically insignificant (P = 0.23).Conclusion: Both the products of metoprolol were found to have similar average annual total health care expenditure; however, MS once a day has higher out-of-pocket cost.Keywords: hypertension, cost, propensity scor

End-to-End Direct Digital Synthesis Simulation and Mathematical Model to Minimize Quantization Effects of Digital Signal Generation

Direct digital synthesis (DDS) architectures are becoming more prevalent as modern digital-to-analog converter (DAC) and programmable logic devices evolve to support higher bandwidths. The DDS architecture provides the benefit of digital control but at a cost of generating spurious content in the spectrum. The generated spurious content may cause intermodulation distortion preventing proper demodulation of the received signal. The distortion may also interfere with the neighboring frequency bands. This article presents the various DDS architectures and explores the DDS architecture which provides the most digital reconfigurability with the lowest spurious content. End-to-end analytical equations, numerical and mathematical models are developed to determine the location and power levels of spurs. Afterwards, the analytical equations, numerical and mathematical models are shown to be consistent with the experimental data. A developer can use the information to design a DDS architecture that meets their minimum requirements

ESTIMATION OF CELECOXIB IN HUMAN PLASMA BY RAPID AND SELECTIVE LC-MS/MS METHOD FOR A BIOEQUIVALENCE STUDY

Objective: A selective, sensitive and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay has been developed for the determination of celecoxib (CXB) in negative ionization mode.Methods: Celecoxib and celecoxib-D7 (CXB-D7) as internal standard (IS) were extracted from 300 µl human plasma by solid-phase extraction using strata-X SPE cartridges. Chromatographic separation was achieved on ACE C8-300 (50 × 4.0 mm, 3.0 μm) column using methanol-1.0 mmol ammonium acetate solution in 80:20 (v/v) ratio. The protonated precursor to product ion transitions studied for CXB and CXB-D7 were m/z 380.0 → 315.9 and 387.0 → 323.0, respectively.Results: The limit of detection (LOD) and lower limit of quantitation of the method were 2.50 and 10.0 ng/ml respectively with a linear dynamic range of 10.0-4000 ng/ml for CXB. The intra-batch and inter-batch precision (% CV) and mean relative recovery across quality control levels is<7.2 % and 85.5 % respectively. Matrix effect in human plasma, expressed as IS-normalized matrix factor ranged from 0.99-1.03.Conclusion: The method was successfully applied in healthy subjects using a single dose of 400 mg celecoxib capsules under fasting and fed conditions. The reproducibility in the measurement of study data is demonstrated by incurred sample reanalysis

Static & Thermal Analysis of Piston for Single Cylinder Diesel Engine by Ansys : A Review

The main objective of this present research work is to investigate and analyze the stresses which are acting on the piston. The parameter which is used for analysis is temperature, operating pressure and properties of materials. Piston in internal combustion engine play most important role because it transfers the force which is produced during the combustion of fuel to crankshaft due to which it converts the pressure energy into mechanical energy. Piston fails due to thermal and mechanical stresses which are produced under the running condition of engine. The boundary conditions are applied for static and thermal analysis which includes pressure on piston head during working period and uneven temperature distributions occurs from head of piston to skirt of piston. The 3D-model will be created using SOLIDWORKS2018.the 3D model will be imported in the Ansys software for geometry and meshing purposes then the FEM Analysis will be done on ANSYS software. Analysis will help to change the existing design for reduce the weight. Finite Element Analysis is the best method for analyzing the stresses in piston

Quantitation of nitrofurantoin in human plasma by liquid chromatography tandem mass spectrometry

A reliable, selective and sensitive LC-MS/MS assay has been proposed for the determination of nitrofurantoin in human plasma. The analyte and nitrofurazone were extracted from 100 µL of human plasma via SPE on Strata-X 33 µm extraction cartridges. Chromatography was done on a BDS Hypersil C18 (100 mm × 4.6 mm, 5 µm) column under isocratic conditions. Quantitation was done using the multiple reaction monitoring (MRM) mode for deprotonated precursor to product ion transitions of nitrofurantoin (m/z 237.0 → 151.8) and nitrofurazone (m/z 197.0 →123.9). The limit of detection and the lowest limit of quantitation of the method were 0.25 ng mL–1 and 5.00 ng mL–1, respectively, with a linear dynamic range of 5.00–1500 ng mL–1 for nitrofurantoin. The intra-batch and inter-batch precision (RSD, %) was ≤ 5.8 %, while the mean extraction recovery was > 92 %. The method was successfully applied to a bioequivalence study of a 100 mg nitrofurantoin capsule formulation in 36 healthy subjects