Using Rasch analysis to form plausible health states amenable to valuation: the development of CORE-6D from CORE-OM in order to elicit preferences for common mental health problems

Purpose: To describe a new approach for deriving a preference-based index from a condition specific measure that uses Rasch analysis to develop health states. Methods: CORE-OM is a 34-item instrument monitoring clinical outcomes of people with common mental health problems. CORE-OM is characterised by high correlation across its domains. Rasch analysis was used to reduce the number of items and response levels in order to produce a set of unidimensionally-behaving items, and to generate a credible set of health states corresponding to different levels of symptom severity using the Rasch item threshold map. Results: The proposed methodology resulted in the development of CORE-6D, a 2-dimensional health state description system consisting of a unidimensionally-behaving 5-item emotional component and a physical symptom item. Inspection of the Rasch item threshold map of the emotional component helped identify a set of 11 plausible health states, which, combined with the physical symptom item levels, will be used for the valuation of the instrument, resulting in the development of a preference-based index. Conclusions: This is a useful new approach to develop preference-based measures where the domains of a measure are characterised by high correlation. The CORE-6D preference-based index will enable calculation of quality adjusted life years in people with common mental health problems.Rasch analysis; health-related quality of life; condition-specific measure; preference-based health; health states; CORE-6D; CORE-OM; mental health; quality-adjusted life years

Coastal landform management in Massachusetts : proceedings of a workshop held at the Woods Hole Oceanographic Institution, Woods Hole, MA USA, October 9-10, 1997

The primary objective of this publication is to share with a wider audience the information and ideas that were shared by those attending the first workshop on Coastal Landform Management in Massachusetts that was held at the Woods Hole Oceanographic Institution on October 9 and 10, 1997. The workshop was designed to benefit resource management decision-makers through interactive exercises and discussions of coastal problems ranging from those that arise everyday to those of unusual complexity. The immediate objective of the workshop was to improve familarity with existing management methodologies. The long-term objective was to improve the methodologies themselves. The workshop was divided into four sessions, each beginning with a presentation followed by discussion. The discussions took place in four separate "breakout groups"-each led by a facilitator-that looked critically at the presentation and prepared a response. The entire group then reconvened for a panel discussion led by the facilitators and the presenter. The first presentation (J. O'Connell) discussed the diverse landforms of the Massachusetts coast, the processes that produce and maintain them, and the problems associated with selecting the most appropriate management techniques. The second (S. Macfarlane) focused on difficulties of managing inner shores using the Nauset and Pleasant Bay estuaries as examples. The third (J. Tanski) discussed management of altered shores using as an example Westhampton Beach on the south shore of Long Island. The final presentation (M. Reynolds and G. Giese) concerned the monitoring of changes in coastal landform sustainability and described checklists prepared to help managers monitor such changes.Sponsored by the Sea Grant Program of the Woods Hole Oceanographic Institution and co-sponsored by Massachusetts Coastal Zone Management, Cape Cod Commission and Massachusetts Institute of Technology Sea Grant College Program

Electromagnetic Actuated stirring in Microbioreactors enabling easier multiplexing & flexible device design

This paper was presented at the 4th Micro and Nano Flows Conference (MNF2014), which was held at University College, London, UK. The conference was organised by Brunel University and supported by the Italian Union of Thermofluiddynamics, IPEM, the Process Intensification Network, the Institution of Mechanical Engineers, the Heat Transfer Society, HEXAG - the Heat Exchange Action Group, and the Energy Institute, ASME Press, LCN London Centre for Nanotechnology, UCL University College London, UCL Engineering, the International NanoScience Community, www.nanopaprika.eu.The development of a novel electromagnetically (EM) actuated stirring method, for use in microbioreactors, is reported. Mixing in microbioreactors is critical to ensure even distribution of nutrients to microorganisms and cells. Magnetically driven stirrer bars or peristaltic mixing are the most commonly utilised mixing methods employed in completely liquid-filled microbioreactors. However the circular reactor shape required for mixing with a stirrer bar and frequently used for peristaltically mixed microbioreactors presents difficulties for bubble-free priming in a microfluidic bioreactor. Moreover the circular shape and the hardware required for both types of mixing reduces the potential packing density of multiplexed reactors. We present a new method of mixing, displaying design flexibility by demonstrating mixing in circular and diamond-shaped reactors and a duplex diamond reactor and fermentation of the gram-positive bacteria S. carnosus in a diamond-shaped microbioreactor system. The results of the optimisation of this mixing method for performing fermentations alongside both batch and continuous culture fermentations are presented

Influence of 100% and 40% oxygen on penumbral blood flow, oxygen level, and T2*-weighted MRI in a rat stroke model

Accurate imaging of the ischemic penumbra is a prerequisite for acute clinical stroke research. T2* magnetic resonance imaging (MRI) combined with an oxygen challenge (OC) is being developed to detect penumbra based on changes in blood deoxyhemoglobin. However, inducing OC with 100% O2 induces sinus artefacts on human scans and influences cerebral blood flow (CBF), which can affect T2* signal. Therefore, we investigated replacing 100% O2 OC with 40% O2 OC (5 minutes 40% O2 versus 100% O2) and determined the effects on blood pressure (BP), CBF, tissue pO2, and T2* signal change in presumed penumbra in a rat stroke model. Probes implanted into penumbra and contralateral cortex simultaneously recorded pO2 and CBF during 40% O2 (n=6) or 100% O2 (n=8) OC. In a separate MRI study, T2* signal change to 40% O2 (n=6) and 100% O2 (n=5) OC was compared. Oxygen challenge (40% and 100% O2) increased BP by 8.2% and 18.1%, penumbra CBF by 5% and 15%, and penumbra pO2 levels by 80% and 144%, respectively. T2* signal significantly increased by 4.56%±1.61% and 8.65%±3.66% in penumbra compared with 2.98%±1.56% and 2.79%±0.66% in contralateral cortex and 1.09%±0.82% and −0.32%±0.67% in ischemic core, respectively. For diagnostic imaging, 40% O2 OC could provide sufficient T2* signal change to detect penumbra with limited influence in BP and CBF

Exploring New Molecular Targets in Advanced Ovarian Cancer: The Aryl Hydrocarbon Receptor (AhR) and Antitumor Benzothiazole Ligands as Potential Therapeutic Candidates

Antitumor benzothiazoles, including 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole (5F 203; NSC 703786), non-fluorinated parent compound DF 203 (NSC 674495), and Phortress (NSC 710305), the lysyl amide prodrug of 5F 203, are experimental anticancer agents with activity in ovarian and breast cancer models in vitro and in vivo. These compounds require (and induce their own) metabolism by cytochrome P450 (CYP) enzymes (e.g., CYP1A1) for antitumor action. The aryl hydrocarbon receptor (AhR) is the main transcriptional regulator of CYP1A1, and we have previously demonstrated that DF 203 and 5F 203 are potent AhR ligands and trigger activation of AhR signaling in sensitive breast and ovarian cancer cells, causing nuclear translocation of AhR. We propose that AhR may represent a new molecular target in the treatment of ovarian tumors, and 5F 203 may exemplify a potential novel treatment. Furthermore, putative biomarkers of sensitivity to this agent have been identified

Net and Acoustic Examination of Bathypelagic Nekton on the Mid-Atlantic Ridge

Spatial distributions of organisms play a key role in facilitating trophic interactions, which influence pelagic ecosystem structure and function. This study combines discrete net trawl sampling with continuous acoustic measurements to investigate the distribution of bathypelagic (1000- 3000 m depth) nekton biomass along the Mid-Atlantic Ridge from Iceland to the Azores. Two, previously unknown, acoustic scattering layers (ASLs) were observed using 18 kHz echosounder data. The first extended approximately 200 m from 2000 m depth and was ubiquitous wherever bottom depth allowed. The second, found within the 1500-2000 m depth stratum, only occurred south of the Sub-Polar Front. Backscatter from the 2000 m ASL was attributed to fish from a suite of bathypelagic species observed throughout the study area, rather than any specific group. No general increase in backscatter, as a proxy for pelagic nekton biomass, was observed in close proximity to the bottom (≤ 200 m), but previously unreported localized concentrations of backscatter were observed when bottom topography was steep. Together these observations demonstrate higher complexity in the spatial structuring of bathypelagic ecosystems than has been previously reported and is likely to affect local ecosystem function

Interpreting the Spatial Distribution of Bathypelagic Nekton Along the Mid-Atlantic Ridge

The spatial distribution of organisms plays a key role in facilitating biological processes, such as trophic interactions, which govern ecosystem structure and function. Attempts to understand bathypelagic (1000-4000 m depth) ecosystem dynamics have been hampered by the coarse temporal-spatial resolution and static nature of most sampling strategies. This study combines a traditional approach, based on discrete net trawls sampling small volumes, with the continuous full water column coverage provided by fisheries acoustics to investigate the distribution of biomass along the Mid-Atlantic Ridge (MAR). The limited trawl samples have been interpreted as showing a positive relationship between the presence of the MAR in the bathypelagic depth zone and biomass of bathypelagic fish species. Using 18 kHz echosounder data we explored this apparent association, and used comparisons of trawl data with the acoustic backscatter distribution to provide insights into how the distribution of biomass may influence trophic interactions in the bathypelagos. As such, this research provides a valuable case study of the potential contribution of acoustics to ecosystem studies, both within fisheries management and in a wider biological context

Design of a high efficiency cyclone for collection of rare and low concentration airborne pathogens

Recent serious outbreaks of pathogens such as Chalara Fraxinea, (Ash Dieback) demonstrate the vulnerability of UK’s forests, woods, and trees. Early detection of threats is critical in the fight against such tree pests and pathogens. This requires a process for collecting and analysing the spores which is robust, flexible and can be deployed rapidly, but which also has sufficient sensitivity to detect the earliest precursors. The work presented here describes a newly-developed high-efficiency detection apparatus and is part of an ongoing BBRSC project to improve the UK’s biosecurity. Our automatic spore system is capable of collecting and analysing Chalara Fraxinea using a novel cyclonic pathogen collector. Cyclones are an effective way to separate small particles (spores) from large quantities of surrounding air and store them for analysis. Our system incorporates a purpose-designed high efficiency cyclone directly integrated with a low power custom impeller to maximise volumetric air sampling while minimising the power requirement. 3D printing was used extensively to validate theoretical models and the particle collection and retention capability of this series of prototypes was evaluated experimentally within our Aerosol test chamber. We found that we could collect greater than 90% of particulate in the target size range, thus providing a front-end to a detection platform. Our system is capable of operating autonomously and at low power, with a high sensitivity to ambient particles. The final system design incorporates the use of multiple cyclone storage vessels ensuring complete isolation of each sample, eradicating cross-contamination, and facilitating automated handling of the sample inside the same apparatus. COTS – commercial off the shelf components were incorporated into the cyclone to make a series of cost effective collection vessels. Early collection and detection of pathogens in-situ represents a considerable advance in surveillance and monitoring of pathogens strengthening UK biosecurity for the future

Development of an automated smart trap for wheat pathogens

National surveys show fungicide use on wheat continues to increase despite fluctuations in disease pressure, reaching a 30 year high in 2012 (Defra). Septoria tritici is the most significant foliar disease in UK wheat causing between £43M to £53M in yield losses annually; Yellow and brown rust are more sporadic but have caused significant losses during high disease years. In all cases control is by fungicide application costing £82M annually (GFK Kynetec 2013). Effective disease management relies on either prophylactic pesticide use or significant manual intervention and time consuming assessment of crop disease indicators by farmers and agronomists. Furthermore indications are that current levels of pesticide use could lead to increased risk of pesticide resistance, if this should occur it is estimated that wheat yields could reduce by up to 20%. To address this we have developed a prototype integrated and automated spore detection system, designed for unattended field application, to monitor and identify the presence of Septoria, brown and yellow rust. The prototype system incorporates novel cyclonic pathogen collection, on-board sample processing and isothermal DNA amplification chemistry (LAMP). We present the engineering design, optimisation and evaluation of our prototype system reporting on successfully completed laboratory testing and initial field trial results. This prototype will be the basis for the development of a commercially available system which, in addition to inoculum detection, will be capable of providing growers/agronomists with real-time information on inoculum moving into a crop enabling more effective timing and selection of fungicide application, and thus better control, increased yield, and improved environmental stewardship