Development and operation of the defence COVID-19 lab as a SARS-CoV-2 diagnostic screening capability for UK military personnel.

BACKGROUND: In the face of the COVID-19 pandemic, the Defence Science and Technology Laboratory (Dstl) and Defence Pathology combined to form the Defence Clinical Lab (DCL), an accredited (ISO/IEC 17025:2017) high-throughput SARS-CoV-2 PCR screening capability for military personnel. LABORATORY STRUCTURE AND RESOURCE: The DCL was modular in organisation, with laboratory modules and supporting functions combining to provide the accredited SARS-CoV-2 (envelope (E)-gene) PCR assay. The DCL was resourced by Dstl scientists and military clinicians and biomedical scientists. LABORATORY RESULTS: Over 12 months of operation, the DCL was open on 289 days and tested over 72 000 samples. Six hundred military SARS-CoV-2-positive results were reported with a median E-gene quantitation cycle (Cq) value of 30.44. The lowest Cq value for a positive result observed was 11.20. Only 64 samples (0.09%) were voided due to assay inhibition after processing started. CONCLUSIONS: Through a sustained effort and despite various operational issues, the collaboration between Dstl scientific expertise and Defence Pathology clinical expertise provided the UK military with an accredited high-throughput SARS-CoV-2 PCR test capability at the height of the COVID-19 pandemic. The DCL helped facilitate military training and operational deployments contributing to the maintenance of UK military capability. In offering a bespoke capability, including features such as testing samples in unit batches and oversight by military consultant microbiologists, the DCL provided additional benefits to the UK Ministry of Defence that were potentially not available from other SARS-CoV-2 PCR laboratories. The links between Dstl and Defence Pathology have also been strengthened, benefitting future research activities and operational responses.

Selection of climate change scenario data for impact modelling.

Impact models investigating climate change effects on food safety often need detailed climate data. The aim of this study was to select climate change projection data for selected crop phenology and mycotoxin impact models. Using the ENSEMBLES database of climate model output, this study illustrates how the projected climate change signal of important variables as temperature, precipitation and relative humidity depends on the choice of the climate model. Using climate change projections from at least two different climate models is recommended to account for model uncertainty. To make the climate projections suitable for impact analysis at the local scale a weather generator approach was adopted. As the weather generator did not treat all the necessary variables, an ad-hoc statistical method was developed to synthesise realistic values of missing variables. The method is presented in this paper, applied to relative humidity, but it could be adopted to other variables if needed.

A human metapneumovirus outbreak at a community hospital in England, July to September 2010.

We describe an outbreak of human metapneumovirus (hMPV) which occurred in July-September 2010 at a community hospital in the East of England. Based on the medical and nursing records, cases were retrospectively defined as suspected if they had had an influenza-like illness (ILI), and probable if they had had an ILI and an epidemiological link to a laboratory-confirmed case. Of a total of 17 symptomatic inpatients, five were classified as probable cases, five were laboratory confirmed and seven were suspected. The attack rate was 29.4% for confirmed and probable cases combined. The median age of symptomatic inpatients was 85 years-old (range 68-96) and the majority (16/17) of symptomatic inpatients had an underlying medical condition. Control measures introduced appeared to restrict further exposure of susceptible patients to infection although modelling suggested that up to four of 10 confirmed and probable cases (40%) could have been prevented through more timely diagnosis and recognition of an outbreak. These findings suggest that there should be increased awareness of hMPV infection within healthcare settings, particularly when the population at risk has a high prevalence of underlying co-morbidities.

Dual sensing of oxygen and temperature using quantum dots and a ruthenium complex.

A scheme for the simultaneous determination of oxygen and temperature using quantum dots and a ruthenium complex is demonstrated. The luminescent complex [Ru(II)-tris(4,7-diphenyl-1,10-phenanthroline)]2+ is immobilized in a non-hydrolytic sol-gel matrix and used as the oxygen sensor. The temperature information is provided by the luminescent emission of core-shell CdSe-ZnS semiconductor nanocrystals immobilized in the same material. Measurements of oxygen and temperature could be performed with associated errors of +/-2% of oxygen concentration and +/-1 degrees C, respectively. In addition, it is shown that while the dye luminescence intensity is quenched both by oxygen and temperature, the nanocrystals luminescent emission responds only to temperature. Results presented demonstrate that the combined luminescence response allows the simultaneous assessment of both parameters using a single optical fiber system. In particular, it was shown that a 10% error in the measured oxygen concentration, induced by a change in the sample temperature, could be compensated using the nanocrystals temperature information and a correction function.

Developing performance indicators that reflect an expanded view of health: findings from the use of an innovative methodology.

BACKGROUND: The increasing presence of managed health care in the United States has been accompanied by the widespread use of performance indicators to assess health plans along various dimensions of quality. Current performance indicator sets virtually ignore psychosocial and behavioral factors in the prevention and management of illness, especially chronic illness, in spite of documented evidence in the medical literature of the importance of these factors. Instead, current indicator sets focus primarily on biomedical interventions to prevent, treat, and manage illness. METHODOLOGY: In a novel method for developing performance indicators--the use of a storytelling methodology--eight interdisciplinary panels, composed of health care experts at the community, state, and national levels, each completed two stories about patients with chronic illnesses. The first story described experiences a patient might have in the health care system as it is today; the second story retold the events that might transpire if attention to psychosocial and behavioral factors were integrated into the health care system. FINDINGS: Differences between the two sets of stories developed by the panels revealed common themes and specific areas where indicator development might prove fruitful. Performance indicators were identified from these themes, and work is underway to operationalize them; to identify barriers and opportunities for their inclusion in indicator sets; and to further document their potential health and cost-effectiveness. DISCUSSION: Although not scientifically rigorous, the storytelling method was found to provide consistent results and may be applied to many aspects of the health care planning process, health education, and quality improvement efforts.

An optical biosensor for real-time chromatography monitoring: breakthrough determination.

The use of an optical biosensor for immunorecognition of protein products during affinity chromatography is discussed to provide rapid data describing the loading and subsequent breakthrough, followed by elution and fraction collection. The optical biosensor works by following in real-time the interaction of soluble ligate with an appropriate ligand attached to the optically active surface. The initial rate of interaction between soluble ligate and immobilized ligand has been shown to correlate well with ligate concentration. This method of analysis has also been shown to agree well with ELISA, the traditionally employed technique for immunoassay of protein products lacking, for example, catalytic activity. Forward prediction, using models of the breakthrough fitted to the real-time data, has enabled the column saturation point to be determined before it has been reached, thus enabling appropriate action to ensure minimal loss of protein product while improving column utilization efficiency. The biosensor, operated within a flow injection analysis regime, has been demonstrated to provide concentration data within 10 s, with a total assay turnaround of 30 s.

Bioprocess monitoring: an optical biosensor for rapid bioproduct analysis.

The use of an optical biosensor for rapid bioproduct analysis is described. The biosensor, which is sensitive to changes in the concentration of bioproduct at its biologically active surface, has been shown to provide concentration data within 10 s of sample addition to the device. This has been achieved through the use of linear regression analysis to extract information from the early part of the biosensor interaction profiles. The system has been used to monitor both the production and purification of antibody fragments expressed during batch fermentation of recombinant Escherichia coli. Data obtained using the biosensor have been used to provide real-time profiles describing the location of antibody fragments during bioprocessing. Biosensor data have also been compared with those obtained from ELISA, the traditional method of retrospective analyses of samples collected during bioprocessing.

Second-order kinetic analysis of IAsys biosensor data: its use and applicability.

The kinetic analysis of IAsys biosensor association data usually relies upon the assumption of constant ligate concentration. In certain circumstances this assumption may no longer be valid. In a similar vein, the analysis of the dissociation phase assumes the concentration of ligate to be negligible in the liquid phase-an assumption that may not be sustainable for high-affinity interactions. In this paper we derive analytical solutions of the second-order differential kinetic equations for the association and dissociation phases, together with a binding isotherm that also allows for changes in concentration of both the ligand and the ligate. Using these equations it is possible to determine the conditions under which the pseudo-first-order assumption ceases to be valid. It is found that the effect of ligate depletion on the association rate constant becomes significant only when binding low ligate concentrations to ligand on surfaces with high binding capacities or high affinities. Similarly, the rebinding in the dissociation phase is dependent upon the affinity and the ligand capacity together with the starting dissociation response compared to the capacity. Finally, depletion also affects the form of the binding isotherm, particularly in situations involving high matrix capacities for ligate and high-affinity interactions.

A review of Ontario's revised drug cost programs.

Ontario's PARCOST program was introduced in 1970. This paper examines the changes wrought in the program since its inception and the economic and political reasons for those changes. It describes the components of the pharmacist's claim, the nature of price controls, and the problems with formulary decisions. The authors suggest that the driving force behind budget restraints is cost containment through lower drug prices with little emphasis on therapeutic considerations.