The cost-effectiveness of an early interventional strategy in non-ST-elevation acute coronary syndrome based on the RITA 3 trial

The published version of the aritcle can be found at the link below.Background: Evidence suggests that an early interventional strategy for patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) can improve health outcomes but also increase costs when compared with a conservative strategy.Objective: The aim of this study was to assess the cost-effectiveness of an early interventional strategy in different risk groups from a UK health-service perspective.Design: Decision-analytic model based on randomised clinical trial data.Main outcome measures: Costs in UK Sterling at 2003/2004 prices and quality-adjusted life years (QALYs) combined into an incremental cost-effectiveness ratio.Methods: Data from the third Randomised Intervention Trial of unstable Angina (RITA 3) was employed to estimate rates of cardiovascular death and myocardial infarction, costs and health-related quality of life. Cost-effectiveness was estimated over patients' lifetimes within the decision-analytic model.Results: The mean incremental cost per QALY gained for an early interventional strategy was approximately £55000, £22000 and £12000 for patients at low, intermediate and high risk, respectively. The early interventional strategy is approximately 1%, 35% and 95% likely to be cost-effective for patients at low, intermediate and high risk, respectively, at a threshold of £20000 per QALY. The cost-effectiveness of early intervention in low-risk patients is sensitive to assumptions about the duration of the treatment effect.Conclusion: An early interventional strategy in patients presenting with NSTE-ACS is likely to be considered cost-effective for patients at high and intermediate risk, but this is less likely to be the case for patients at low risk

Algorithms for the self-optimisation of chemical reactions

Self-optimising chemical systems have experienced a growing momentum in recent years, with the evolution of self-optimising platforms leading to their application for reaction screening and chemical synthesis. With the desire for improved process sustainability, self-optimisation provides a cheaper, faster and greener approach to the chemical development process. The use of such platforms aims to enhance the capabilities of the researcher by removing the need for labor-intensive experimentation, allowing them to focus on more challenging tasks. The establishment of these systems have enabled opportunities for self-optimising platforms to become a key element of a laboratory’s repertoire. To enable the wider adoption of self-optimising chemical platforms, this review summarises the history of algorithmic usage in chemical reaction self-optimisation, detailing the functionality of the algorithms and their applications in a way that is accessible for chemists and highlights opportunities for the further exploitation of algorithms in chemical synthesis moving forward

A Hybridised Optimisation of an Automated Photochemical Continuous Flow Reactor

A new hybridized algorithm that combines process optimisation with response surface mapping was developed and applied in an automated continuous flow reaction. Moreover, a photochemical cascade CSTR was developed and characterised by chemical actinometry, showing photon flux density of ten times greater than previously reported in batch. The success of the algorithm was then evaluated in the aerobic oxidation of sp3 C–H bonds using benzophenone as photosensitizer in the newly developed photo reactor

Self-Optimising Reactive Extractions: Towards the Efficient Development of Multi-Step Continuous Flow Processes

Downstream purification of products and intermediates is essential for the development of continuous flow processes. Described herein, is a study on the use of a modular and reconfigurable continuous flow platform for the self-optimisation of reactive extractions and multi-step reaction-extraction processes. The selective extraction of one amine from a mixture of two similar amines was achieved with an optimum separation of 90%, and in this case, the black-box optimisation approach was superior to global polynomial modelling. Furthermore, this methodology was utilised to simultaneously optimise the continuous flow synthesis and work-up of N-benzyl-α-methylbenzylamine with respect to four variables, resulting in a significantly improved purity

Large-scale air mass characteristics observed over the remote tropical Pacific Ocean during March-April 1999: Results from PEM-Tropics B field experiment

Eighteen long-range flights over the Pacific Ocean between 38° S to 20° N and 166° E to 90° W were made by the NASA DC-8 aircraft during the NASA Pacific Exploratory Mission (PEM) Tropics B conducted from March 6 to April 18, 1999. Two lidar systems were flown on the DC-8 to remotely measure vertical profiles of ozone (O3), water vapor (H2O), aerosols, and clouds from near the surface to the upper troposphere along their flight track. In situ measurements of a wide range of gases and aerosols were made on the DC-8 for comprehensive characterization of the air and for correlation with the lidar remote measurements. The transition from northeasterly flow of Northern Hemispheric (NH) air on the northern side of the Intertropical Convergence Zone (ITCZ) to generally easterly flow of Southern Hemispheric (SH) air south of the ITCZ was accompanied by a significant decrease in O3, carbon monoxide, hydrocarbons, and aerosols and an increase in H2O. Trajectory analyses indicate that air north of the ITCZ came from Asia and/or the United States, while the air south of the ITCZ had a long residence time over the Pacific, perhaps originating over South America several weeks earlier. Air south of the South Pacific Convergence Zone (SPCZ) came rapidly from the west originating over Australia or Africa. This air had enhanced O3 and aerosols and an associated decrease in H2O. Average latitudinal and longitudinal distributions of O3 and H2O were constructed from the remote and in situ O3 and H2O data, and these distributions are compared with results from PEM-Tropics A conducted in August-October 1996. During PEM-Tropics B, low O3 air was found in the SH across the entire Pacific Basin at low latitudes. This was in strong contrast to the photochemically enhanced O3 levels found across the central and eastern Pacific low latitudes during PEM-Tropics A. Nine air mass types were identified for PEM-Tropics B based on their O3, aerosols, clouds, and potential vorticity characteristics. The data from each flight were binned by altitude according to air mass type, and these results showed the relative observational frequency of the different air masses as a function of altitude in seven regions over the Pacific. The average chemical composition of the major air mass types was determined from in situ measurements in the NH and SH, and these results provided insight into the origin, lifetime, and chemistry of the air in these regions. Copyright 2001 by the American Geophysical Union

Tumor-derived exosomes confer antigen-specific immunosuppression in a murine delayed-type hypersensitivity model

Exosomes are endosome-derived small membrane vesicles that are secreted by most cell types including tumor cells. Tumor-derived exosomes usually contain tumor antigens and have been used as a source of tumor antigens to stimulate anti-tumor immune responses. However, many reports also suggest that tumor-derived exosomes can facilitate tumor immune evasion through different mechanisms, most of which are antigen-independent. In the present study we used a mouse model of delayed-type hypersensitivity (DTH) and demonstrated that local administration of tumor-derived exosomes carrying the model antigen chicken ovalbumin (OVA) resulted in the suppression of DTH response in an antigen-specific manner. Analysis of exosome trafficking demonstrated that following local injection, tumor-derived exosomes were internalized by CD11c+ cells and transported to the draining LN. Exosome-mediated DTH suppression is associated with increased mRNA levels of TGF-β1 and IL-4 in the draining LN. The tumor-derived exosomes examined were also found to inhibit DC maturation. Taken together, our results suggest a role for tumor-derived exosomes in inducing tumor antigen-specific immunosuppression, possibly by modulating the function of APCs. © 2011 Yang et al

Automated Self-Optimisation of Multi-Step Reaction and Separation Processes Using Machine Learning

There has been an increasing interest in the use of automated self-optimising continuous flow platforms for the development and manufacture in synthesis in recent years. Such processes include multiple reactive and work-up steps, which need to be efficiently optimised. Here, we report the combination of multi-objective optimisation based on machine learning methods (TSEMO algorithm) with self-optimising platforms for the optimisation of multi-step continuous reaction processes. This is demonstrated for a pharmaceutically relevant Sonogashira reaction. We demonstrate how optimum reaction conditions are re-evaluated with the changing downstream work-up specifications in the active learning process. Furthermore, a Claisen-Schmidt condensation reaction with subsequent liquid-liquid separation was optimised with respect to three-objectives. This approach provides the ability to simultaneously optimise multi-step processes with respect to multiple objectives, and thus has the potential to make substantial savings in time and resources

The Age of the Galactic Disk

I review different methods devised to derive the age of the Galactic Disk, namely the Radio-active Decay (RD), the Cool White Dwarf Luminosity Function (CWDLF), old opne clusters (OOC) and the Color Magnitude Diagram (CMD) of the stars in the solar vicinity. I argue that the disk is likely to be 8-10 Gyr old. Since the bulk of globulars has an age around 13 Gyr, the possibility emerges that the Galaxy experienced a minimum of Star Formation at the end of the halo/bulge formation. This minimum might reflect the time at which the Galaxy started to acquire material to form the disk inside-out.Comment: 10 pages, 4 figure, invited review, in "The chemical evolution of the Milky Way : Stars vs Clusters, Vulcano (Italy), 20-24 September 199

How a bird is an island

Replicate adaptive radiations occur when lineages repeatedly radiate and fill new but similar niches and converge phenotypically. While this is commonly seen in traditional island systems, it may also be present in host-parasite relationships, where hosts serve as islands. In a recent article in BMC Biology, Johnson and colleagues have produced the most extensive phylogeny of the avian lice (Ischnocera) to date, and find evidence for this pattern. This study opens the door to exploring adaptive radiations from a novel host-parasite perspective

Post-exercise skimmed milk, but not a sucrose beverage decreases energy intake at the next meal compared to a placebo beverage in active males

This study compared the appetite and energy intake effects of three post-exercise beverages at a subsequent post-exercise meal. On three occasions, ten active males: (mean ± sd) age 21.3 ± 1.2 y, V̇ O2peak 58 ± 5 mL/kg/min) performed 30-min cycling at ∼60% V̇ O2peak and five 4-min intervals at 85% V̇ O2peak. Post-exercise, placebo (PLA: 57 kJ), skimmed milk (MILK: 1002 kJ) or sucrose (CHO: 1000 kJ) beverages (615 mL) were consumed. Sixty min post-beverage, subjects consumed an ad-libitum pasta lunch in a 30 min eating period. Subjective appetite and plasma acylated ghrelin and plasma glucose were determined pre-exercise, post-exercise and pre-meal, with sensory characteristics of beverages rated. Ad-libitum energy intake in MILK (6746 ± 2035) kJ) was lower than CHO (7762 ± 1921) kJ) (P = 0.038; dz = 0.98; large effect) and tended to be lower than PLA (7672 (2005) kJ) (P = 0.078; dz = 0.76; medium effect). Including energy consumed in beverages, energy intake was greater in CHO than PLA (P = 0.010; dz = 1.24; large effect) or MILK (P = 0.026; dz = 0.98; large effect), with PLA and MILK not different (P = 0.960; dz = 0.02; trial effect). Plasma ghrelin, plasma glucose and appetite were not different between trials. MILK was perceived thicker than CHO (P = 0.020; dz = 1.11; large effect) and creamier than PLA (P = 0.026; dz = 1.06; large effect). These results suggest that when energy balance is important for an exerciser, post-exercise skimmed milk ingestion reduces energy intake compared to a sucrose beverage and might therefore help facilitate recovery/adaptation without affecting energy balance