A scoping review of behavioural science approaches and frameworks for health protection and emergency response.

AIMS: Rapid intervention development, implementation, and evaluation are required for emergency public health contexts, such as the recent COVID-19 pandemic. A novel Agile Co-production and Evaluation (ACE) framework has been developed to assist this endeavour in future public health emergencies. This scoping review aimed to map available behavioural science resources that can be used to develop and evaluate public health guidance, messaging, and interventions in emergency contexts onto components of ACE: rapid development and implementation, co-production with patients or the public including seldom heard voices from diverse communities, and inclusion of evaluation. METHODS: A scoping review methodology was used. Searches were run on MEDLINE, EMBASE, PsycINFO, and Google, with search terms covering emergency response and behavioural science. Articles published since 2014 and which discussed a framework or guidance for using behavioural science in response to a public health emergency were included. A narrative synthesis was conducted. RESULTS: Seventeen records were included in the synthesis. The records covered a range of emergency contexts, the most frequent of which were COVID-19 (n = 7) and non-specific emergencies (n = 4). One record evaluated existing approaches, 6 proposed new approaches, and 10 described existing approaches. Commonly used approaches included the Behavioural Change Wheel; Capability, Opportunity, and Motivation Behaviour model; and social identity theory. Three records discuss co-production with the target audience and consideration of diverse populations. Four records incorporate rapid testing, evaluation, or validation methods. Six records state that their approaches are designed to be implemented rapidly. No records cover all components of ACE. CONCLUSION: We recommend that future research explores how to create guidance involving rapid implementation, co-production with patients or the public including seldom heard voices from diverse communities, and evaluation.

Low uptake of COVID-19 lateral flow testing among university students: a mixed methods evaluation.

OBJECTIVE: This study aimed to evaluate COVID-19 lateral flow testing (LFT) among asymptomatic university students. STUDY DESIGN: This study was a mixed methods evaluation of LFT among University of Bristol students. METHODS: We conducted (1) an analysis of testing uptake and exploration of demographic variations in uptake using logistic regression; (2) an online student survey about views on university testing; and (3) qualitative interviews to explore participants' experiences of testing and subsequent behaviour, analysed using a thematic approach. RESULTS: A total of 12,391 LFTs were conducted on 8025 of 36,054 (22.3%) students. Only one in 10 students had the recommended two tests. There were striking demographic disparities in uptake with those from ethnic minority groups having lower uptake (e.g. 3% of Chinese students were tested vs 30.7% of White students) and variations by level and year of study (ranging from 5.3% to 33.7%), place of residence (29.0%-35.6%) and faculty (15.2%-32.8%). Differences persisted in multivariable analyses. A total of 436 students completed the online survey, and 20 in-depth interviews were conducted. Barriers to engagement with testing included a lack of awareness, knowledge and understanding, and concerns about the accuracy and safety. Students understood the limitations of LFTs but requested further information about test accuracy. Tests were used to inform behavioural decisions, often in combination with other information, such as the potential for exposure to the virus and perceptions of vulnerability. CONCLUSIONS: The low uptake of testing brings into question the role of mass LFT in university settings. Innovative strategies may be needed to increase LFT uptake among students.

Transcriptomic variation of pharmacogenes in multiple human tissues and lymphoblastoid cell lines.

Variation in the expression level and activity of genes involved in drug disposition and action ('pharmacogenes') can affect drug response and toxicity, especially when in tissues of pharmacological importance. Previous studies have relied primarily on microarrays to understand gene expression differences, or have focused on a single tissue or small number of samples. The goal of this study was to use RNA-sequencing (RNA-seq) to determine the expression levels and alternative splicing of 389 Pharmacogenomics Research Network pharmacogenes across four tissues (liver, kidney, heart and adipose) and lymphoblastoid cell lines, which are used widely in pharmacogenomics studies. Analysis of RNA-seq data from 139 different individuals across the 5 tissues (20-45 individuals per tissue type) revealed substantial variation in both expression levels and splicing across samples and tissue types. Comparison with GTEx data yielded a consistent picture. This in-depth exploration also revealed 183 splicing events in pharmacogenes that were previously not annotated. Overall, this study serves as a rich resource for the research community to inform biomarker and drug discovery and use.

Control of carbapenemase-producing Enterobacteriaceae outbreaks in acute settings: an evidence review.

BACKGROUND: In recent years, infections with carbapenemase-producing Enterobacteriaceae (CPE) have been increasing globally and present a major public health challenge. AIM: To review the international literature: (i) to describe CPE outbreaks in acute hospital settings globally; and (ii) to identify the control measures used during these outbreaks and report on their effectiveness. METHODS: A systematic search of MEDLINE and EMBASE databases, abstract lists for key conferences and reference lists of key reviews was undertaken, and information on unpublished outbreaks was sought for 2000-2015. Where relevant, risk of bias was assessed using the Newcastle-Ottawa scale. A narrative synthesis of the evidence was conducted. FINDINGS: Ninety-eight outbreaks were eligible. These occurred worldwide, with 53 reports from Europe. The number of cases (CPE infection or colonization) involved in outbreaks varied widely, from two to 803. In the vast majority of outbreaks, multi-component infection control measures were used, commonly including: patient screening; contact precautions (e.g. gowns, gloves); handwashing interventions; staff education or monitoring; enhanced environmental cleaning/decontamination; cohorting of patients and/or staff; and patient isolation. Seven studies were identified as providing the best-available evidence on the effectiveness of control measures. These demonstrated that CPE outbreaks can be controlled successfully using a range of appropriate, commonly used, infection control measures. However, risk of bias was considered relatively high for these studies. CONCLUSION: The findings indicate that CPE outbreaks can be controlled using combinations of existing measures. However, the quality of the evidence base is weak and further high-quality research is needed, particularly on the effectiveness of individual infection control measures.

Citrobacter freundii as a test platform for recombinant cellulose degradation systems.

Cellulosic biomass represents a huge reservoir of renewable carbon, but converting it into useful products is challenging. Attempts to transfer cellulose degradation capability to industrially useful micro-organisms have met with limited success, possibly due to poorly understood synergy between multiple cellulases. This is best studied by co-expression of many combinations of cellulases and associated proteins. Here, we describe the development of a test platform based on Citrobacter freundii, a cellobiose-assimilating organism closely related to Escherichia coli. Standard E. coli cloning vectors worked well in Cit. freundii. Expression of cellulases CenA and Cex of Cellulomonas fimi in Cit. freundii gave recombinant strains which were able to grow at the expense of cellulosic filter paper or microcrystalline cellulose (Avicel) in a mineral medium supplemented with a small amount of yeast extract. Periodic physical agitation of the cultures was highly beneficial for growth at the expense of filter paper. This provides a test platform for the expression of combinations of genes encoding biomass-degrading enzymes to develop effective genetic cassettes for degradation of different biomass streams. SIGNIFICANCE AND IMPACT OF THE STUDY: Biofuels have been shown to be the best sustainable and alternative source of fuel to replace fossil fuels. Of the different types of feedstocks used for producing biofuels, lignocellulosic biomass is the most abundant. Converting this biomass to useful products has met with little success. Different approaches are being used and microbial platforms are the most promising and sustainable method. This study shows that Citrobacter freundii is a better test platform than Escherichia coli for testing various combinations of cellulases for the development of microbial systems for biomass conversion.

Presentation for care and antenatal management of HIV in the UK, 2009-2014.

OBJECTIVES: Despite very low rates of vertical transmission of HIV in the UK overall, rates are higher among women starting antenatal antiretroviral therapy (ART) late. We investigated the timing of key elements of the care of HIV-positive pregnant women [antenatal care booking, HIV laboratory assessment (CD4 count and HIV viral load) and antenatal ART initiation], to assess whether clinical practice is changing in line with recommendations, and to investigate factors associated with delayed care. METHODS: We used the UK's National Study of HIV in Pregnancy and Childhood for 2009-2014. Data were analysed by fitting logistic regression and Cox proportional hazards models. RESULTS: A total of 5693 births were reported; 79.5% were in women diagnosed with HIV prior to that pregnancy. Median gestation at antenatal booking was 12.1 weeks [interquartile range (IQR) 10.0-15.6 weeks] and booking was significantly earlier during 2012-2014 vs. 2009-2011 (P < 0.001), although only in previously diagnosed women. Overall, 42.2% of pregnancies were booked late (≥ 13 gestational weeks). Among women not already on treatment, antenatal ART commenced at a median of 21.4 (IQR18.1-24.5) weeks and started significantly earlier in the most recent time period (P < 0.001). Compared with previously diagnosed women, those newly diagnosed during the current pregnancy booked later for antenatal care and started antenatal ART later (both P < 0.001). Multivariable analyses revealed demographic variations in access to or uptake of care, with groups including migrants and parous women initiating care later. CONCLUSIONS: Although women are accessing antenatal and HIV care earlier in pregnancy, some continue to face barriers to timely initiation of antenatal care and ART.

A pH-based biosensor for detection of arsenic in drinking water.

Arsenic contaminated groundwater is estimated to affect over 100 million people worldwide, with Bangladesh and West Bengal being among the worst affected regions. A simple, cheap, accurate and disposable device is required for arsenic field testing. We have previously described a novel biosensor for arsenic in which the output is a change in pH, which can be detected visually as a colour change by the use of a pH indicator. Here, we present an improved formulation allowing sensitive and accurate detection of less than 10 ppb arsenate with static overnight incubation. Furthermore, we describe a cheap and simple high-throughput system for simultaneous monitoring of pH in multiple assays over time. Up to 50 samples can be monitored continuously over the desired time period. Cells can be stored and distributed in either air-dried or freeze-dried form. This system was successfully tested on arsenic-contaminated groundwater samples from the South East region of Hungary. We hope to continue to develop this sensor to produce a device suitable for field trials.

The impact of immigration on tuberculosis rates in the United Kingdom compared with other European countries.

OBJECTIVE: To investigate whether trends in tuberculosis (TB) rates across Europe are linked to patterns of migration. DESIGN: Descriptive analysis of Organisation for Economic Co-operation and Development population statistics and EuroTB data for 21 European countries for 1996-2005. RESULTS: TB notification rates increased in only three of the 21 countries: the United Kingdom, Norway and Sweden. In all three countries, approximately three quarters of cases were foreign-born. The UK had the third highest number of foreign nationals overall, but the highest number from a country with a TB incidence > or =250 cases/100000 (219000, 13%). European countries with declining TB rates had varying patterns of migration, but did not generally receive migrants from very high-incidence countries and/or had a smaller proportion of their total TB cases in their migrant population. CONCLUSIONS: The increase in the rate of TB in the UK, which contrasts with most other European countries, may, at least in part, be due to the fact that a high proportion of UK cases occur in the foreign-born, coupled with a comparatively large number of foreign nationals from countries with a very high incidence of TB.

The influence of socio-economic deprivation on tuberculosis treatment delays in England, 2000-2005.

This study investigates the association between socio-economic deprivation and tuberculosis (TB) treatment delays in England, 2000-2005. Patients reported to the Enhanced TB Surveillance system were assigned a deprivation score based on residential postcode, and categorized into deprivation quartiles. Data were analysed using Cox regression. The median interval from symptom onset to treatment initiation was 67 days (inter-quartile range 30-131). The effect of deprivation on this interval was modified by ethnic group and place of birth/time since entry into the United Kingdom. Longer intervals were experienced by the most deprived black Africans, Indians/Pakistanis/Bangladeshis and recent entrants to the United Kingdom, compared to the least deprived. In contrast, among white and UK-born patients, longer intervals were experienced by the least deprived. In conclusion, the effect of deprivation on TB treatment delays varies in different population groups. Efforts are needed to reduce delays including improving awareness of TB and increasing the index of clinical suspicion.

Epidemiology and treatment outcome of childhood tuberculosis in England and Wales: 1999-2006.

OBJECTIVE: To describe the recent trends in demographic, clinical and microbiological characteristics and outcome of treatment in paediatric cases of tuberculosis. DESIGN: National surveillance study. SETTING: England and Wales. PATIENTS: All children under the age of 16 years reported with tuberculosis to the national enhanced surveillance system between 1999 and 2006 were included. MAIN OUTCOME MEASURES: Proportions, and rates of disease, by demographic characteristics, site of disease, diagnostic delay, culture confirmation, species, drug susceptibility and treatment outcome. RESULTS: 3563 cases of tuberculosis in children were reported between 1999 and 2006. The incidence rate remained stable at around 4.3 per 100,000 (95% CI 4.1 to 4.4). Patients born outside the UK had a tuberculosis rate higher than children born in the UK (37 per 100,000 vs 2.5 per 100,000) and this rate increased over the period. Rates in the black African ethnic group were highest at 88 per 100,000. 60% of children had pulmonary disease, the commonest presentation, but only 948 (27%) had culture confirmed tuberculosis. The median time to diagnosis from onset of symptoms was 37 days (interquartile range 12-89). The proportions of cases with rifampicin, isoniazid and multi-drug resistant isolates were 2.4%, 9.3% and 2.3%, respectively. 88% of children completed treatment and less than 1% died. CONCLUSIONS: Overall rates of tuberculosis in children have remained stable, with the majority completing treatment. Rates are, however, highest in children not born in the UK, particularly among certain ethnic minority groups. Levels of drug resistance are also high.

The association between HIV and antituberculosis drug resistance.

In the UK, HIV is considered to be a risk factor for antituberculosis drug resistance. Evidence of the association is, however, inconclusive and there are few population-level data. The present study investigated the association in England and Wales during the period 1999-2005. National tuberculosis surveillance data for adults were matched to HIV/AIDS reports. Unmatched cases were assumed to be HIV-negative. Separate analyses were conducted on new tuberculosis cases and those with a previous diagnosis. Logistic regression was used for univariable and multivariable analyses. There were 1,657 previously diagnosed cases (80 HIV-positive) and 18,130 new cases (1,156 HIV-positive). Isoniazid resistance was found in 8.1% of previously diagnosed cases and 6.6% of new cases, and multidrug resistance in 2.8% and 0.7%, respectively. There was no evidence of an association between HIV and antituberculosis drug resistance among previously diagnosed cases. Among new cases, there was no overall association between HIV and isoniazid or multidrug resistance after adjusting for confounding factors. White HIV-positive patients were more likely to have multidrug resistance, but numbers were small. In contrast to some previous studies, this large, up-to-date study provides little evidence that HIV co-infected tuberculosis patients in England and Wales are at increased risk of firstline antituberculosis drug resistance.

Tuberculosis in non-UK-born persons, England and Wales, 2001-2003.

SETTING: England and Wales, 2001-2003. OBJECTIVES: To describe demographic and clinical characteristics of tuberculosis (TB) in non-UK-born persons and compare with UK-born cases to inform public health action and health service provision. DESIGN: Analysis of surveillance data. RESULTS: Among the 67% of cases who were non-UK-born, TB incidence was 88/100000 compared to 4/100000 among the UK-born. UK-born minority ethnic groups were also at increased risk of TB. Although the highest TB incidence occurred in recent entrants to the UK, nearly half the cases had been resident for >or=5 years. The majority of non-UK-born cases originated from South Asia (48%) and sub-Saharan Africa (35%). The demographic characteristics of non-UK-born and UK-born cases differed. In addition, non-UK-born cases were less likely to have pulmonary TB than the UK-born (52% vs. 73%, chi(2) P<0.001), but were more likely to have isoniazid-resistant disease (8% vs. 6%, chi(2) P=0.002), depending on region of birth. CONCLUSIONS: During 2001-2003, most TB cases were non-UK-born. TB services need to take the characteristics of TB in this group into account. Furthermore, awareness of the risk of disease is required among the non-UK-born for many years after arrival into the UK, and among UK-born minority ethnic groups.

Phytodetoxification of TNT by transgenic plants expressing a bacterial nitroreductase.

There is major international concern over the wide-scale contamination of soil and associated ground water by persistent explosives residues. 2,4,6-Trinitrotoluene (TNT) is one of the most recalcitrant and toxic of all the military explosives. The lack of affordable and effective cleanup technologies for explosives contamination requires the development of better processes. Significant effort has recently been directed toward the use of plants to extract and detoxify TNT. To explore the possibility of overcoming the high phytotoxic effects of TNT, we expressed bacterial nitroreductase in tobacco plants. Nitroreductase catalyzes the reduction of TNT to hydroxyaminodinitrotoluene (HADNT), which is subsequently reduced to aminodinitrotoluene derivatives (ADNTs). Transgenic plants expressing nitroreductase show a striking increase in ability to tolerate, take up, and detoxify TNT. Our work suggests that expression of nitroreductase (NR) in plants suitable for phytoremediation could facilitate the effective cleanup of sites contaminated with high levels of explosives.

Cofactor regeneration by a soluble pyridine nucleotide transhydrogenase for biological production of hydromorphone.

We have applied the soluble pyridine nucleotide transhydrogenase of Pseudomonas fluorescens to a cell-free system for the regeneration of the nicotinamide cofactors NAD and NADP in the biological production of the important semisynthetic opiate drug hydromorphone. The original recombinant whole-cell system suffered from cofactor depletion resulting from the action of an NADP(+)-dependent morphine dehydrogenase and an NADH-dependent morphinone reductase. By applying a soluble pyridine nucleotide transhydrogenase, which can transfer reducing equivalents between NAD and NADP, we demonstrate with a cell-free system that efficient cofactor cycling in the presence of catalytic amounts of cofactors occurs, resulting in high yields of hydromorphone. The ratio of morphine dehydrogenase, morphinone reductase, and soluble pyridine nucleotide transhydrogenase is critical for diminishing the production of the unwanted by-product dihydromorphine and for optimum hydromorphone yields. Application of the soluble pyridine nucleotide transhydrogenase to the whole-cell system resulted in an improved biocatalyst with an extended lifetime. These results demonstrate the usefulness of the soluble pyridine nucleotide transhydrogenase and its wider application as a tool in metabolic engineering and biocatalysis.

Cloning of the sth gene from Azotobacter vinelandii and construction of chimeric soluble pyridine nucleotide transhydrogenases.

The gene encoding the soluble pyridine nucleotide transhydrogenase (STH) of Azotobacter vinelandii was cloned and sequenced. This is the third sth gene identified and further defines a new subfamily within the flavoprotein disulfide oxidoreductases. The three STHs identified all lack one of the redox active cysteines that are characteristic for this large family of enzymes, and instead they contain a conserved threonine residue at this position. The recombinant A. vinelandii enzyme was purified to homogeneity and shown to form filamentous structures different from those of Pseudomonas fluorescens and Escherichia coli STH. Chimeric STHs were constructed which showed that the C-terminal region is important for polymer formation. The A. vinelandii STH containing the C-terminal region of P. fluorescens or E. coli STH showed structures resembling those of the STH contributing the C-terminal portion of the protein.

Mechanistic studies of morphine dehydrogenase and stabilization against covalent inactivation.

Morphine dehydrogenase (MDH) of Pseudomonas putida M10 catalyses the NADP(+)-dependent oxidation of morphine and codeine to morphinone and codeinone. This enzyme forms the basis of a sensitive detection and assay method for heroin metabolites and a biotransformation process for production of hydromorphone and hydrocodone. To improve these processes we have undertaken a thorough examination of the kinetic mechanism of MDH. Sequence comparisons indicated that MDH belongs within the aldose reductase enzyme family. MDH was shown to be specific for the pro-R hydrogen of NADPH. In steady-state kinetic studies, product inhibition patterns suggested that MDH follows a Theorell-Chance mechanism for codeinone reduction at pH 7, and a non-Theorell-Chance sequential ordered mechanism for codeine oxidation at pH 9.5. Residues corresponding to the catalytically important Tyr-48, Lys-77 and Asp-43 of aldose reductase were modified by site-directed mutagenesis, resulting in substantial loss of activity consistent with a catalytic role for these residues. Loss of activity of MDH in the presence of the reaction product morphinone was found to be due to the formation of a covalent adduct with Cys-80; alteration of Cys-80 to serine resulted in an enzyme with greatly enhanced stability.

Biodegradation of explosives by transgenic plants expressing pentaerythritol tetranitrate reductase.

Plants offer many advantages over bacteria as agents for bioremediation; however, they typically lack the degradative capabilities of specially selected bacterial strains. Transgenic plants expressing microbial degradative enzymes could combine the advantages of both systems. To investigate this possibility in the context of bioremediation of explosive residues, we generated transgenic tobacco plants expressing pentaerythritol tetranitrate reductase, an enzyme derived from an explosive-degrading bacterium that enables degradation of nitrate ester and nitroaromatic explosives. Seeds from transgenic plants were able to germinate and grow in the presence of 1 mM glycerol trinitrate (GTN) or 0.05 mM trinitrotoluene, at concentrations that inhibited germination and growth of wild-type seeds. Transgenic seedlings grown in liquid medium with 1 mM GTN showed more rapid and complete denitration of GTN than wild-type seedlings. This example suggests that transgenic plants expressing microbial degradative genes may provide a generally applicable strategy for bioremediation of organic pollutants in soil.

The udhA gene of Escherichia coli encodes a soluble pyridine nucleotide transhydrogenase.

The udhA gene of Escherichia coli was cloned and expressed in E. coli and found to encode an enzyme with soluble pyridine nucleotide transhydrogenase activity. The N-terminal end of the enzyme contains the fingerprint motif of a dinucleotide binding domain, not present in published E. coli genome sequences due to a sequencing error. E. coli is hereby the first organism reported to possess both a soluble and a membrane-bound pyridine nucleotide transhydrogenase.