Contamination in complex healthcare trials:the falls in care homes (FinCH) study experience

BACKGROUND: Trials are at risk of contamination bias which can occur when participants in the control group are inadvertently exposed to the intervention. This is a particular risk in rehabilitation studies where it is easy for trial interventions to be either intentionally or inadvertently adopted in control settings. The Falls in Care Homes (FinCH) trial is used in this paper as an example of a large randomised controlled trial of a complex intervention to explore the potential risks of contamination bias. We outline the FinCH trial design, present the potential risks from contamination bias, and the strategies used in the design of the trial to minimise or mitigate against this. The FinCH trial was a multi-centre randomised controlled trial, with embedded process evaluation, which evaluated whether systematic training in the use of the Guide to Action Tool for Care Homes reduced falls in care home residents. Data were collected from a number of sources to explore contamination in the FinCH trial. Where specific procedures were adopted to reduce risk of, or mitigate against, contamination, this was recorded. Data were collected from study e-mails, meetings with clinicians, research assistant and clinician network communications, and an embedded process evaluation in six intervention care homes. During the FinCH trial, there were six new falls prevention initiatives implemented outside the study which could have contaminated our intervention and findings. Methods used to minimise contamination were: cluster randomisation at the level of care home; engagement with the clinical community to highlight the risks of early adoption; establishing local collaborators in each site familiar with the local context; signing agreements with NHS falls specialists that they would maintain confidentiality regarding details of the intervention; opening additional research sites; and by raising awareness about the importance of contamination in research among participants. CONCLUSION: Complex rehabilitation trials are at risk of contamination bias. The potential for contamination bias in studies can be minimized by strengthening collaboration and dialogue with the clinical community. Researchers should recognise that clinicians may contaminate a study through lack of research expertise

Exploration of the faecal microbiota and biomarker discovery in equine grass sickness

Equine grass sickness (EGS) is a frequently fatal disease of horses, responsible for the death of 1-2% of the UK horse population annually. The etiology of this disease is currently uncharacterized although there is evidence it is associated with Clostridium botulinum neurotoxin in the gut. Prevention is currently not possible and ileal biopsy diagnosis is invasive. The aim of this study was to characterize the fecal microbiota and biofluid metabolic profiles of EGS horses, to further understand the mechanisms underlying this disease and identify metabolic biomarkers to aid in diagnosis. Urine, plasma and feces were collected from horses with EGS, matched controls (MC), and hospital controls (HC). Sequencing the16S rRNA gene of the fecal bacterial population of the study horses found a severe dysbiosis in EGS horses, with an increase in Bacteroidetes and a decrease in Firmicutes bacteria. Metabolic profiling by 1H nuclear magnetic resonance (NMR) spectroscopy found EGS to be associated with the lower urinary excretion of hippurate and 4-cresyl sulfate and higher excretion of O-acetyl carnitine and trimethylamine-N-oxide (TMAO). The predictive ability of the complete urinary metabolic signature and using the four discriminatory urinary metabolites to classify horses by disease status was assessed using a second (test) set of horses. The urinary metabolome and a combination of the four candidate biomarkers showed promise in aiding the identification of horses with EGS. Characterization of the metabolic shifts associated with EGS offers the potential of a non-invasive test to aid pre-mortem diagnosis

The effect of relative plasma plume delay on the properties of complex oxide films grown by multi-laser multi-target combinatorial pulsed laser deposition

We report the effects of relative time delay of plasma plumes on thin garnet crystal films fabricated by dual-beam, combinatorial pulsed laser deposition. Relative plume delay was found to affect both the lattice constant and elemental composition of mixed Gd3Ga5O12 (GGG) and Gd3Sc2Ga5O12 (GSGG) films. Further analysis of the plasmas was undertaken using a Langmuir probe, which revealed that for relative plume delays shorter than ~200 µs, the second plume travels through a partial vacuum created by the first plume, leading to higher energy ion bombardment of the growing film. The resulting in-plane stresses are consistent with the transition to a higher value of lattice constant normal to the film plane that was observed around this delay value. At delays shorter than ~10 µs, plume propagation was found to overlap, leading to scattering of lighter ions from the plume and a change in stoichiometry of the resultant films

A deep-narrative analysis of energy cultures in slum rehabilitation housing of Abuja, Mumbai and Rio de Janeiro for just policy design

Slum rehabilitation housing (SRH) are critical transitional spaces in urban informality that has deep-rooted implications on poverty alleviation efforts. However, current literature reports systemic injustices in SRH on access to essential services, including energy injustices. This study investigated distributive injustices in the SRH across three cities, Abuja, Mumbai and Rio de Janeiro, developing ‘energy cultures’ narratives. It employed a computational social science methodology that used textual analysis, followed by a constructivist grounded theoretic approach to inform just policy design. The analysis was performed at two scales to identify and contrast injustices in the study areas. The result at an aggregated scale showed commonalities were around the poor design of the built environment, administrative lags of the utilities and high electricity bills. Case study-specific results showed that poverty penalties were linked with the energy cultures of each SRHs. In the Mumbai case, poverty penalties were associated with the aspirational purchase of household appliances due to move from slums to SRH. The Abuja case showed low power quality and load shedding frequently damaged appliances that increase the maintenance costs for the occupants. The Rio de Janeiro SRH case had injustices embedded through the adoption of inefficient appliances received as charity from higher-income households. Fuel stacking was also observed in the SRH that illustrated cultural identities associated with cooking energy. The conclusion was drawn to support just policy design by considering the socio-cultural context of the built environment, improving utility governance and promoting cleaner fuel mix at the household level

Fe(III) (oxyhydr)oxide reduction by the thermophilic iron-reducing bacterium Desulfovulcanus ferrireducens

Some thermophilic bacteria from deep-sea hydrothermal vents grow by dissimilatory iron reduction, but our understanding of their biogenic mineral transformations is nascent. Mineral transformations catalyzed by the thermophilic iron-reducing bacterium Desulfovulcanus ferrireducens during growth at 55°C were examined using synthetic nanophase ferrihydrite, akaganeite, and lepidocrocite separately as terminal electron acceptors. Spectral analyses using visible-near infrared (VNIR), Fourier-transform infrared attenuated total reflectance (FTIR-ATR), and Mössbauer spectroscopies were complemented with x-ray diffraction (XRD) and transmission electron microscopy (TEM) using selected area electron diffraction (SAED) and energy dispersive X-ray (EDX) analyses. The most extensive biogenic mineral transformation occurred with ferrihydrite, which produced a magnetic, visibly dark mineral with spectral features matching cation-deficient magnetite. Desulfovulcanus ferrireducens also grew on akaganeite and lepidocrocite and produced non-magnetic, visibly dark minerals that were poorly soluble in the oxalate solution. Bioreduced mineral products from akaganeite and lepidocrocite reduction were almost entirely absorbed in the VNIR spectroscopy in contrast to both parent minerals and the abiotic controls. However, FTIR-ATR and Mössbauer spectra and XRD analyses of both biogenic minerals were almost identical to the parent and control minerals. The TEM of these biogenic minerals showed the presence of poorly crystalline iron nanospheres (50–200 nm in diameter) of unknown mineralogy that were likely coating the larger parent minerals and were absent from the controls. The study demonstrated that thermophilic bacteria transform different types of Fe(III) (oxyhydr)oxide minerals for growth with varying mineral products. These mineral products are likely formed through dissolution-reprecipitation reactions but are not easily predictable through chemical equilibrium reactions alone

Cryptic diversity within the major trypanosomiasis vector Glossina fuscipes revealed by molecular markers

Background: The tsetse fly Glossina fuscipes s.l. is responsible for the transmission of approximately 90% of cases of human African trypanosomiasis (HAT) or sleeping sickness. Three G. fuscipes subspecies have been described, primarily based upon subtle differences in the morphology of their genitalia. Here we describe a study conducted across the range of this important vector to determine whether molecular evidence generated from nuclear DNA (microsatellites and gene sequence information), mitochondrial DNA and symbiont DNA support the existence of these taxa as discrete taxonomic units. Principal Findings: The nuclear ribosomal Internal transcribed spacer 1 (ITS1) provided support for the three subspecies. However nuclear and mitochondrial sequence data did not support the monophyly of the morphological subspecies G. f.fuscipes or G. f. quanzensis. Instead, the most strongly supported monophyletic group was comprised of flies sampled fromEthiopia. Maternally inherited loci (mtDNA and symbiont) also suggested monophyly of a group from Lake Victoria basin and Tanzania, but this group was not supported by nuclear loci, suggesting different histories of these markers. Microsatellite data confirmed strong structuring across the range of G. fuscipes s.l., and was useful for deriving the interrelationship of closely related populations. Conclusion/Significance: We propose that the morphological classification alone is not used to classify populations of G. fuscipes for control purposes. The Ethiopian population, which is scheduled to be the target of a sterile insect release (SIT) programme, was notably discrete. From a programmatic perspective this may be both positive, given that it may reflect limited migration into the area or negative if the high levels of differentiation are also reflected in reproductive isolation between this population and the flies to be used in the release programme

Beta decay of 71,73Co; probing single particle states approaching doubly magic 78Ni

Low-energy excited states in 71,73Ni populated via the {\beta} decay of 71,73Co were investigated in an experiment performed at the National Superconducting Cyclotron Laboratory (NSCL) at Michigan State University (MSU). Detailed analysis led to the construction of level schemes of 71,73Ni, which are interpreted using systematics and analyzed using shell model calculations. The 5/2- states attributed to the the f5/2 orbital and positive parity 5/2+ and 7/2+ states from the g9/2 orbital have been identified in both 71,73Ni. In 71Ni the location of a 1/2- {\beta}-decaying isomer is proposed and limits are suggested as to the location of the isomer in 73Ni. The location of positive parity cluster states are also identified in 71,73Ni. Beta-delayed neutron branching ratios obtained from this data are given for both 71,73Co.Comment: Accepted for publication in PR

Is current management of the Antarctic krill fishery in the Atlantic sector of the Southern Ocean precautionary?

This paper explains the management of the Antarctic krill (Euphausia superba) fishery in the Atlantic sector of the Southern Ocean, and current knowledge about the state of the regional krill stock. In this region, krill fishing is permitted in an area of approximately 3.5 million km2 which is divided into four subareas (labelled Subareas 48.1 to 48.4) for management and reporting purposes. The effective regional catch limit (or ‘trigger level’), established in 1991, is 0.62 million tonnes year–1, equivalent to ~1% of the regional biomass estimated in 2000. Each subarea has also had its own catch limit, between 0.093 and 0.279 million tonnes year–1, since 2009. There is some evidence for a decline in the abundance of krill in the 1980s, but no evidence of a further decline in recent decades. Local-scale monitoring programs have been established in three of the subareas to monitor krill biomass in survey grids covering between 10 000 and 125 000 km2. Cautious extrapolation from these local monitoring programs provides conservative estimates of the regional biomass in recent years. This suggests that fishing at the trigger level would be equivalent to a long-term exploitation rate (annual catch divided by biomass) of <7%, which is below the 9.3% level considered appropriate to maintain the krill stock and support krill predators. Subarea catch limits exceed 9.3% of conservatively estimated subarea biomass in up to 20% of years due to high variability in krill biomass indices. The actual exploitation rate in each subarea has remained <3% because annual catches have been <50% of the trigger level since 1991. Comparison with the 9.3% reference exploitation rate suggests that current management is precautionary at the regional scale. The subarea catch limits help prevent excessive concentration of catch at the subarea scale. Finer-scale management might be necessary to manage the risk of adverse impacts which might occur as a result of concentrated fishing in sensitive areas or climate change. Frequent assessment of the krill stock will enhance CCAMLR’s ability to manage these risks. Continuing the local monitoring programs will provide valuable information on krill variability, but more information is required on how the monitored biomass relates to biomass at the subarea and regional scales

Mean-risk models using two risk measures: A multi-objective approach

This paper proposes a model for portfolio optimisation, in which distributions are characterised and compared on the basis of three statistics: the expected value, the variance and the CVaR at a specified confidence level. The problem is multi-objective and transformed into a single objective problem in which variance is minimised while constraints are imposed on the expected value and CVaR. In the case of discrete random variables, the problem is a quadratic program. The mean-variance (mean-CVaR) efficient solutions that are not dominated with respect to CVaR (variance) are particular efficient solutions of the proposed model. In addition, the model has efficient solutions that are discarded by both mean-variance and mean-CVaR models, although they may improve the return distribution. The model is tested on real data drawn from the FTSE 100 index. An analysis of the return distribution of the chosen portfolios is presented