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Abstract Background Production of relatively low value, bulk commodity chemicals and fuels by microbial species requires a step-change in approach to decrease the capital and operational costs associated with scaled fermentation. The utilisation of the robust and halophilic industrial host organisms of the genus Halomonas could dramatically decrease biomanufacturing costs owing to their ability to grow in seawater, using waste biogenic feedstocks, under non-sterile conditions. Results We describe the isolation of Halomonas rowanensis, a novel facultative chemoautotrophic species of Halomonas from a natural brine spring. We investigated the ability of this species to produce ectoine, a compound of considerable industrial interest, under heterotrophic conditions. Fixation of radiolabelled NaH14CO3 by H. rowanensis was confirmed in mineral medium supplied with thiosulfate as an energy source. Genome sequencing suggested carbon fixation proceeds via a reductive tricarboxylic acid cycle, and not the Calvin–Bensen–Bassham cycle. The mechanism of energy generation to support chemoautotrophy is unknown owing to the absence of an annotated SOX-based thiosulfate-mediated energy conversion system. We investigated further the biotechnological potential of the isolated H. rowanensis by demonstrating production of the gaseous hydrocarbon (bio-propane), bioplastics (poly-3-hydroxybutyrate) and osmolytes (ectoine) under heterotrophic and autotrophic CO2 fixation growth conditions. Conclusions This proof-of-concept study illustrates the value of recruiting environmental isolates as industrial hosts for chemicals biomanufacturing, where CO2 utilisation could replace, or augment, the use of biogenic feedstocks in non-sterile, industrialised bioreactors.

Cytochrome P450 monooxygenases are useful biocatalysts for C–H activation, and there is a need to expand the range of these enzymes beyond what is naturally available. A panel of 93 variants of active self-sufficient P450cam[Tyr96Phe]-RhFRed fusion enzymes with a broad diversity in active site amino acids was developed by screening a large mutant library of 16,500 clones using a simple, highly sensitive colony-based colorimetric screen against indole. These mutants showed distinct fingerprints of activity not only when screened in oxidations of substituted indoles but also for unrelated oxidations such as benzylic hydroxylations.

The ability of Rhodococcus rhodochrous (NCIMB 9703) to catalyse the regio- and stereoselective hydroxylation of a range of benzyloxy-substituted heterocycles has been investigated. Incubation of 2-benzyloxytetrahydropyrans with resting cell suspensions of the organism yielded predominantly a mixture of 5-hydroxylated isomers in combined yields of up to 40%. Exposure of the corresponding 2-benzyloxytetrahydrofuran derivatives to the cell suspensions gave predominantly the 4-hydroxylated isomers in yields of up to 26%. Most interestingly, 2-(4-nitrobenzyloxy)tetrahydrofuran and 2-(4-nitrobenzyloxy)tetrahydropyran were transformed in high yields to the 4-hydroxylated and 5-hydroxylated products, respectively.

A high-throughput screening protocol for evaluating chimeric, self-sufficient P450 biocatalysts and their mutants against a panel of substrates was developed, leading to the identification of a number of novel biooxidation activities.

Abstract Background Usutu virus (USUV), which is closely related to West Nile virus (WNV), sharing a similar ecology and transmission cycle, was first reported in the UK in the southeast of England in 2020. Both USUV and WNV are emerging zoonotic viruses hosted by wild birds. The 2020 finding of USUV in England raised awareness of this virus and highlighted the importance of understanding the seasonality of Culex pipiens sensu lato (Cx. pipiens s.l.), the main enzootic vector of these viruses. Zoos are prime locations for trapping mosquitoes because of their infrastructure, security, and range of vertebrate hosts and aquatic habitats. Methods Three independent zoo-based case studies at four locations that cover the seasonality of Cx. pipiens s.l. in England were undertaken: (i) London Zoo (Zoological Society London [ZSL]) and surrounding areas, London; (ii) Chester Zoo (Cheshire); (ii) Twycross Zoo (Leicestershire); and (iv) Flamingo Land (zoo; North Yorkshire). Various adult mosquito traps were used to catch adult Cx. pipiens s.l. across seasons. Results High yields of Cx. pipiens s.l./Culex torrentium were observed in Biogents-Mosquitaire and Center for Disease Control and Prevention Gravid traps in all studies where these traps were used. Mosquito counts varied between sites and between years. Observations of adult Cx. pipiens s.l./Cx. torrentium abundance and modelling studies demonstrated peak adult abundance between late July and early August, with active adult female Cx. pipiens s.l./Cx. torrentium populations between May and September. Conclusions The information collated in this study illustrates the value of multiple mosquito monitoring approaches in zoos to describe the seasonality of this UK vector across multiple sites in England and provides a framework that can be used for ongoing and future surveillance programmes and disease risk management strategies. Graphical Abstract

Objective: The impact of adjunctive manual thrombus aspiration (TA) in patients with stent thrombosis (ST) treated with percutaneous intervention has not been evaluated in the current era of potent P2Y12 agents and new-generation drug-eluting stents. We sought to assess the effect of TA using data from a large contemporary registry. Methods: The study population was derived from the Essex ST Investigation Registry (ESTHIR), which contains all consecutive cases of angiographically determined definite ST undergoing interventional treatment in a tertiary cardiac centre between November 2015 and June 2018. Propensity score matching was performed to match patients who underwent TA (TA group) to those who did not (n-TA group). The study endpoints were final TIMI flow and survival free of cardiovascular death (CD) or target lesion revascularisation (TLR). Results: A total of 128 ST patients were included in the present analysis. The mean age was 65 ± 11 years, and 84% were male. About 90% of the patients presented with STEMI, and 85% had very late ST. Seventy-two patients (56%) underwent TA. After propensity score matching, 30 patients were included in each study group. A higher rate of final TIMI III flow was observed in the TA group (TA vs n-TA group, 100% vs 83%), but this difference did not reach statistical significance (p = 0.052). At 1000 days of follow-up, survival free of CD or TLR was not different between the two groups (p = 0.8). Conclusion: In a propensity-matched population of ST patients undergoing PCI in a contemporary setting, TA was not associated with improved final TIMI flow or long-term cardiovascular outcomes.

Abstract Following the first detection in the United Kingdom of Usutu virus (USUV) in wild birds in 2020, we undertook a multidisciplinary investigation that combined screening host and vector populations with interrogation of national citizen science monitoring datasets to assess the potential for population impacts on avian hosts. Pathological findings from six USUV-positive wild passerines were non-specific, highlighting the need for molecular and immunohistochemical examinations to confirm infection. Mosquito surveillance at the index site identified USUV RNA in Culex pipiens s.l. following the outbreak. Although the Eurasian blackbird (Turdus merula) is most frequently impacted by USUV in Europe, national syndromic surveillance failed to detect any increase in occurrence of clinical signs consistent with USUV infection in this species. Furthermore, there was no increase in recoveries of dead blackbirds marked by the national ringing scheme. However, there was regional clustering of blackbird disease incident reports centred near the index site in 2020 and a contemporaneous marked reduction in the frequency with which blackbirds were recorded in gardens in this area, consistent with a hypothesis of disease-mediated population decline. Combining results from multidisciplinary schemes, as we have done, in real-time offers a model for the detection and impact assessment of future disease emergence events.

Abstract Background Timely restoration of bloodflow acute ST-segment elevation myocardial infarction (STEMI) reduces myocardial damage and improves prognosis. The objective of this study was describe the association of demographic factors with hospitalisation rates for STEMI and time to angiography, Percutaneous Coronary Intervention (PCI) and Coronary Artery Bypass Graft (CABG) in New South Wales (NSW) and the Australian Capital Territory (ACT), Australia. Methods This was an observational cohort study using linked population health data. We used linked records of NSW and the ACT hospitalisations and the Australian Government Medicare Benefits Schedule (MBS) for persons aged 35 and over hospitalised with STEMI in the period 1 July 2010 to 30 June 2014. Survival analysis was used to determine the time between STEMI admission and angiography, PCI and CABG, with a competing risk of death without cardiac procedure. Results Of 13,117 STEMI hospitalisations, 71% were among males; 55% were 65-plus years; 64% lived in major cities, and 2.6% were Aboriginal people. STEMI hospitalisation occurred at a younger age in males than females. Angiography and PCI rates decreased with age: angiography 69% vs 42% and PCI 60% vs 34% on day 0 for ages 35-44 and 75-plus respectively. Lower angiography and PCI rates and higher CABG rates were observed outside major cities. Aboriginal people with STEMI were younger and more likely to live outside a major city. Angiography, PCI and CABG rates were similar for Aboriginal and non-Aboriginal people of the same age and remoteness area. Conclusions There is a need to improve access to definitive revascularisation for STEMI among appropriately selected older patients and in regional areas. Aboriginal people with STEMI, as a population, are disproportionately affected by access to definitive revascularisation outside major cities. Improving access to timely definitive revascularisation in regional areas may assist in closing the gap in cardiovascular outcomes between Aboriginal and non-Aboriginal people.

Abstract Background Culicoides biting midges are biological vectors of arboviruses including bluetongue virus (BTV), Schmallenberg virus (SBV) and African horse sickness virus (AHSV). Zoos are home to a wide range of ‘at risk’ exotic and native species of animals. These animals have a high value both in monetary terms, conservation significance and breeding potential. To understand the risk these viruses pose to zoo animals, it is necessary to characterise the Culicoides fauna at zoos and determine which potential vector species are feeding on which hosts. Methods Light-suction traps were used at two UK zoos: the Zoological Society of London (ZSL) London Zoo (LZ) and ZSL Whipsnade Zoo (WZ). Traps were run one night each week from June 2014 to June 2015. Culicoides were morphologically identified to the species level and any blood-fed Culicoides were processed for blood-meal analysis. DNA from blood meals was extracted and amplified using previously published primers. Sequencing was then carried out to determine the host species. Results A total of 11,648 Culicoides were trapped and identified (n = 5880 from ZSL WZ; n = 5768 from ZSL LZ), constituting 25 different species. The six putative vectors of BTV, SBV and AHSV in northern Europe were found at both zoos and made up the majority of the total catch (n = 10,701). A total of 31 host sequences were obtained from blood-fed Culicoides. Culicoides obsoletus/C. scoticus, Culicoides dewulfi, Culicoides parroti and Culicoides punctatus were found to be biting a wide range of mammals including Bactrian camels, Indian rhinoceros, Asian elephants and humans, with Culicoides obsoletus/C. scoticus also biting Darwin’s rhea. The bird-biting species, Culicoides achrayi, was found to be feeding on blackbirds, blue tits, magpies and carrion crows. Conclusions To our knowledge, this is the first study to directly confirm blood-feeding of Culicoides on exotic zoo animals in the UK and shows that they are able to utilise a wide range of exotic as well as native host species. Due to the susceptibility of some zoo animals to Culicoides-borne arboviruses, this study demonstrates that in the event of an outbreak of one of these viruses in the UK, preventative and mitigating measures would need to be taken.

Abstract Background Systems science methods such as dynamic simulation modelling are well suited to address questions about public health policy as they consider the complexity, context and dynamic nature of system-wide behaviours. Advances in technology have led to increased accessibility and interest in systems methods to address complex health policy issues. However, the involvement of policy decision makers in health-related simulation model development has been lacking. Where end-users have been included, there has been limited examination of their experience of the participatory modelling process and their views about the utility of the findings. This paper reports the experience of end-user decision makers, including senior public health policy makers and health service providers, who participated in three participatory simulation modelling for health policy case studies (alcohol related harm, childhood obesity prevention, diabetes in pregnancy), and their perceptions of the value and efficacy of this method in an applied health sector context. Methods Semi-structured interviews were conducted with end-user participants from three participatory simulation modelling case studies in Australian real-world policy settings. Interviewees were employees of government agencies with jurisdiction over policy and program decisions and were purposively selected to include perspectives at different stages of model development. Results The ‘co-production’ aspect of the participatory approach was highly valued. It was reported as an essential component of building understanding of the modelling process, and thus trust in the model and its outputs as a decision-support tool. The unique benefits of simulation modelling included its capacity to explore interactions of risk factors and combined interventions, and the impact of scaling up interventions. Participants also valued simulating new interventions prior to implementation in the real world, and the comprehensive mapping of evidence and its gaps to prioritise future research. The participatory aspect of simulation modelling was time and resource intensive and therefore most suited to high priority complex topics with contested options for intervening. Conclusion These findings highlight the value of a participatory approach to dynamic simulation modelling to support its utility in applied health policy settings.

Bluetongue virus (BTV) and African horse sickness virus (AHSV) cause economically important diseases that are currently exotic to the United Kingdom (UK), but have significant potential for introduction and onward transmission. Given the susceptibility of animals kept in zoo collections to vector-borne diseases, a qualitative risk assessment for the introduction of BTV and AHSV to ZSL London Zoo was performed. Risk pathways for each virus were identified and assessed using published literature, animal import data and outputs from epidemiological models. Direct imports of infected animals, as well as wind-borne infected Culicoides, were considered as routes of incursion. The proximity of ongoing disease events in mainland Europe and proven capability of transmission to the UK places ZSL London Zoo at higher risk of BTV release and exposure (estimated as low to medium) than AHSV (estimated as very low to low). The recent long-range expansion of AHSV into Thailand from southern Africa highlights the need for vector competence studies of Palearctic Culicoides for AHSV to assess the risk of transmission in this region.

Introduction Hyperglycemia in pregnancy (HIP, including gestational diabetes and pre-existing type 1 and type 2 diabetes) is increasing, with associated risks to the health of women and their babies. Strategies to manage and prevent this condition are contested. Dynamic simulation models (DSM) can test policy and program scenarios before implementation in the real world. This paper reports the development and use of an advanced DSM exploring the impact of maternal weight status interventions on incidence of HIP.Methods A consortium of experts collaboratively developed a hybrid DSM of HIP, comprising system dynamics, agent-based and discrete event model components. The structure and parameterization drew on a range of evidence and data sources. Scenarios comparing population-level and targeted prevention interventions were simulated from 2018 to identify the intervention combination that would deliver the greatest impact.Results Population interventions promoting weight loss in early adulthood were found to be effective, reducing the population incidence of HIP by 17.3% by 2030 (baseline (‘business as usual’ scenario)=16.1%, 95% CI 15.8 to 16.4; population intervention=13.3%, 95% CI 13.0 to 13.6), more than targeted prepregnancy (5.2% reduction; incidence=15.3%, 95% CI 15.0 to 15.6) and interpregnancy (4.2% reduction; incidence=15.5%, 95% CI 15.2 to 15.8) interventions. Combining targeted interventions for high-risk groups with population interventions promoting healthy weight was most effective in reducing HIP incidence (28.8% reduction by 2030; incidence=11.5, 95% CI 11.2 to 11.8). Scenarios exploring the effect of childhood weight status on entry to adulthood demonstrated significant impact in the selected outcome measure for glycemic regulation, insulin sensitivity in the short term and HIP in the long term.Discussion Population-level weight reduction interventions will be necessary to ‘turn the tide’ on HIP. Weight reduction interventions targeting high-risk individuals, while beneficial for those individuals, did not significantly impact forecasted HIP incidence rates. The importance of maintaining interventions promoting healthy weight in childhood was demonstrated.

Background This study aimed to investigate longitudinal physiological changes in the recanalized coronary chronic total occlusion (CTO) vessel and its dependent myocardium after successful percutaneous coronary intervention (PCI). Methods and Results In this pilot study, 25 patients scheduled for elective CTO PCI with viable myocardium and angiographically visible collaterals were included. Absolute coronary blood flow and absolute microvascular resistance were measured invasively using continuous thermodilution. Measurements were performed immediately after successful CTO PCI and at short‐term follow‐up. In a subgroup of patients, physiological measurements were performed at the predominant donor vessel before CTO PCI, immediately afterwards, and at follow‐up. Absolute coronary blood flow in the recanalized CTO artery increased from 148±53 mL/min immediately after PCI to 221±77 mL/min at follow‐up (P

Abstract Objective: The Australian Capital Territory ‘It's Your Move!’ (ACT‐IYM) was a three‐year (2012–2014) systems intervention to prevent obesity among adolescents. Methods: The ACT‐IYM project involved three intervention schools and three comparison schools and targeted secondary students aged 12–16 years. The intervention consisted of multiple initiatives at individual, community, and school policy level to support healthier nutrition and physical activity. Intervention school‐specific objectives related to increasing active transport, increasing time spent physically active at school, and supporting mental wellbeing. Data were collected in 2012 and 2014 from 656 students. Anthropometric data were objectively measured and behavioural data self‐reported. Results: Proportions of overweight or obesity were similar over time within the intervention (24.5% baseline and 22.8% follow‐up) and comparison groups (31.8% baseline and 30.6% follow‐up). Within schools, two of three the intervention schools showed a significant decrease in the prevalence of overweight and obesity (p

Sleep disorders: More assessments, shorter waits with community sleep service A community-based service for common sleep disorders can provide rapid and easily accessed sleep assessment and treatment. A team led by Michael Hlavac and Michael Epton from Christchurch Hospital describe the creation of a sleep assessment service within the Canterbury district of New Zealand, in which initial assessments are conducted throughout the community by general practice teams under guidance and advice from sleep specialists at the region’s largest hospital. Before the service, there were around 300 sleep assessments per year in all of Canterbury, a region with a population of around 510,000. Now, that number has more than tripled, with shorter waiting times for treatment, especially for people with severe sleep apnoea. The authors conclude that most patients can be assessed for a suspected sleep disorder without needing to visit a hospital’s sleep unit.

Purpose: We examine the performance of pure model-based iterative reconstruction with reduced-dose CT in follow-up of patients with early-stage testicular cancer. Methods: Sixteen patients (mean age 35.6 ± 7.4 years) with stage I or II testicular cancer underwent conventional dose (CD) and low-dose (LD) CT acquisition during CT surveillance. LD data was reconstructed with model-based iterative reconstruction (LD–MBIR). Datasets were objectively and subjectively analysed at 8 anatomical levels. Two blinded clinical reads were compared to gold-standard assessment for diagnostic accuracy. Results: Mean radiation dose reduction of 67.1% was recorded. Mean dose measurements for LD–MBIR were: thorax – 66 ± 11 mGy cm (DLP), 1.0 ± 0.2 mSv (ED), 2.0 ± 0.4 mGy (SSDE); abdominopelvic – 128 ± 38 mGy cm (DLP), 1.9 ± 0.6 mSv (ED), 3.0 ± 0.6 mGy (SSDE). Objective noise and signal-to-noise ratio values were comparable between the CD and LD–MBIR images. LD–MBIR images were superior (p

The Australian Capital Territory (ACT) is a small Australian jurisdiction with a single tier of government and a population of approximately 400,000 people. Despite enjoying comparatively high levels of income, education, physical amenity, and access to nutritious food, overweight and obesity is the most prevalent risk factor for chronic disease in the ACT. From 2011, the ACT Government Health Directorate (ACT Health) led the development of a whole of Government plan (the Action Plan) to address obesity. A political imperative to take such action and recent administrative reform assisted the development of a plan with specific actions to be undertaken by different government agencies. Obesity is a “wicked problem” with a diversity of opinion about its causes and potential solutions. These opinions remained influential even when an official course of action had been decided upon. Strong decision making and accountability processes were therefore necessary to support the development of the Action Plan. A lack of understanding beyond the health sector in relation to the evidence for effective, population level interventions to address obesity and a tendency to try and address population health risks by scaling up client-centered models of Government services also proved problematic. This experience highlights the critical importance of designing obesity policy within a robust governance framework in order to ensure progress is made in a highly contested environment. Whilst the observations included here are strongly influenced by local contextual factors, there are important lessons which can be applied elsewhere.

Introduction. Systemic absorption of oral vancomycin is poor due to the size of the molecule and its pharmacokinetics. It has an elimination half life of 5–11 hours in patients with normal renal function. We present a rare case of ototoxicity after oral vancomycin administration and detectable serum vancomycin levels 24 hours after cessation of vancomycin. Case Presentation. A 42-year-old woman with a history of hypertension, diabetes mellitus, and previously treated Clostridium difficile colitis presented with abdominal pain and diarrhea for two weeks. Clostridium difficile infection was confirmed by PCR, and at the time of diagnosis and initiation of therapy, the patient had normal renal function. Vancomycin was initiated at a dose of 125 mg po q6h. After the third dose of oral vancomycin, the patient reported new symptoms of lightheadedness, sensations of “buzzing” and whistling of bilateral ears, and decreased perception of hearing described as “clogged ears.” The patient reported to the emergency department the next day due to worsening of these symptoms, and vancomycin dosing was reduced to every 8 hours; however, the patient reported the auditory symptoms persisted. On day three, vancomycin was discontinued with gradual resolution of symptoms over the next 12 hours. On day four, a serum random vancomycin level obtained 24 hours after the last dose was detectable at 2 mcg/dl. Temporal association of the patient’s symptoms and improvement with cessation of therapy along with a detectable vancomycin level indicates systemic absorption of oral vancomycin with subsequent ototoxicity. Discussion. The potential for absorption of oral vancomycin is not well described and is attributed to compromised intestinal epithelium allowing for increased drug absorption. Few studies suggested that oral vancomycin may result in therapeutic or even potentially toxic levels of serum vancomycin in patients with impaired renal function. Ototoxicity may be a transient or permanent side effect of vancomycin therapy and is related to high serum levels. Symptoms usually resolve after decreasing the dose or cessation of vancomycin. No detectable serum vancomycin levels were found in 98% of the patients treated with oral vancomycin in a prospective study. The described case is unusual because despite normal renal function, the patient still developed ototoxicity, and systemic absorption of the drug was confirmed with a measurable vancomycin level approximately 24 hours after the drug was stopped. Additionally, the only other medication prescribed to the patient at the time of vancomycin administration was metformin at a dose of 500 mg po bid which has no known idiosyncratic interactions potentiating adverse side effects to vancomycin. This case reflects that some patients may be more susceptible to increased systemic absorption via the oral route, and the possibility for ototoxicity should be considered and discussed with patients while prescribing oral vancomycin.

Studying personality in captive animals may enable the development of individual-based management decisions, which may improve animal welfare. Asiatic lions at London Zoo represent an opportunity to research an understudied species’ response to new environments since they have experienced social and physical changes, such as new enclosures and increased social interaction with humans. This project aimed to investigate the role of personality in behavioral responses to these changes. Lion personality questionnaires completed by keepers and direct focal animal observations were used to create personality profiles. Time budgets and enclosure use were determined and compared between control nights and event nights and between the lions’ previous enclosure and their new one. The results showed a lack of difference in time budget and enclosure use between control and social event nights, and the spread of participation index values revealed that the lions use their enclosures unevenly. Personality profiles identified various traits that could assist with individual-based management decisions. As the first study to assess Asiatic lions personality, this research contributes to the creation of consistent and valid methodology for evaluating captive animal personality that may improve husbandry and welfare protocols for individual lions, leading to the improved health and success of the species.

Background: Currently, little is known about the types of evidence used by policy makers. This study aimed to investigate how policy makers in the health domain use and evaluate evidence and how this differs from academic epidemiologists. By having a better understanding of how policy makers select, evaluate and use evidence, academics can tailor the way in which that evidence is produced, potentially leading to more effective knowledge translation.Methods: An exploratory mixed-methods study design was used. Quantitative measures were collected via an anonymous online survey (n= 28), with sampling from three health-related government and non-government organisations. Semi-structured interviews with policy makers (n=20) and epidemiologists (n=6) were conducted to gather qualitative data. Results: Policy makers indicated systematic reviews were the preferred research resource (19%), followed closely by qualitative research (16%). Neither policy makers nor epidemiologists used grading instruments to evaluate evidence. In the web survey policy makers reported that consistency and strength of evidence (93%), the quality of data (93%), bias in the evidence (79%) and recency of evidence (79%) were the most important factors taken into consideration when evaluating the available evidence. The same results were found in the qualitative interviews. Epidemiologists focused on the methodology used in the study. The most cited barriers to using robust evidence, according to policy makers, were political considerations (60%), time limitations (55%), funding (50%) and research not being applicable to current policies (50%). Conclusion: The policy makers investigated did not report a systematic approach to evaluating evidence. Although there was some overlap between what policy makers and epidemiologists identified as high quality evidence, there was also some important differences. This suggests that the best scientific evidence may not routinely be used in the development of policy. In essence the policy making process relied on other jurisdictions’ policies and the opinions of internal staff members as primary evidence sources to inform policy decisions. Findings of this study suggest that efforts should be directed towards making scientific information more systematically available to policy makers.

ObjectiveTo illuminate the key components of multi-sector reform to address the obesogenic environment in New York City during the administration of Mayor Michael Bloomberg from 2002 to 2013, we conducted a case study consisting of interviews with and a critical analysis of the experiences of leading decision makers and implementers.MethodKey informant interviews (N=41) conducted in 2014 were recorded, transcribed, coded and thematically analyzed. Participants included officials from the Health Department and other New York City Government agencies, academics, civil society members and private sector executives. ResultsParticipants described Mayor Bloomberg as a data-driven politician who wanted to improve the lives of New Yorkers. He appointed talented Commissioners and encouraged them and their staff to be bold, innovative and collaborative. Multiple programs spanning multiple sectors, with varied approaches and targets were supported. This study found that much of the work relied on loose coalitions across City Government, with single agencies responsible for their own agendas, some with health co-benefits. Many policies were implemented through non-legislative mechanisms such as executive orders and the Health Code. Despite support from academic and some civil society groups, strong lobbying from industry and an unfavorable media led to some reforms being modified, legally challenged or blocked completely, particularly food environment modifiers. In contrast, reforms of the physical environment were described as highly consultative across and outside government and resulted in slower but more sustained reform.ConclusionsThe Bloomberg administration was a window of opportunity with the imprimatur of the executive to progress a long-term, multi-faceted obesity prevention strategy which has successfully reversed childhood trends. Through the involvement of external researchers and the extensive use of empirical data from a wide range of participants, this study offers a distinctive insight into the ways in which this was achieved. Whilst some of the aspects of the reforms in New York City are unique to that setting at that time, there are important lessons that are transferable to other urban settings. These include: strong and consistent leadership; a commitment to innovative approaches and cross-sectoral collaboration and; and a context to support and encourage this approach.

PROBLEM: The World Health Organization (WHO) developed a guideline with 10 control measures to reduce transmission of A(H5N1) avian influenza virus in markets in low-resource settings. The practical aspects of guide implementation have never been described. APPROACH: WHO's guideline was implemented in two Indonesian markets in the city of Makassar to try to reduce transmission of the A(H5N1) virus. The guideline was operationalized using a participatory approach to introduce a combination of infrastructural and behavioural changes. LOCAL SETTING: Avian influenza is endemic in birds in Makassar. Two of the city's 22 dilapidated, poorly-run bird markets were chosen for the study. Before the intervention, neither market was following any of WHO's 10 recommended control measures except for batch processing. RELEVANT CHANGES: Market stakeholders' knowledge about the avian influenza A(H5N1) virus improved after the interventions. WHO guideline recommendations for visual inspection, cleaning and poultry-holding practices, as well as infrastructural requirements for zoning and for water supply and utilities, began to conform to the WHO guideline. Low-maintenance solutions such as installation of wastewater treatment systems and economic incentives such as composting were well received and appropriate for the low-resource setting. LESSONS LEARNT: Combining infrastructural changes with behaviour change interventions was critical to guideline implementation. Despite initial resistance to behaviour change, the participatory approach involving monthly consultations and educational sessions facilitated the adoption of safe food-handling practices and sanitation. Market authorities assumed important leadership roles during the interventions and this helped shift attitudes towards regulation and market maintenance needs. This shift may enhance the sustainability of the interventions.

Understanding the dynamics of influenza transmission on international flights is necessary for prioritizing public health response to pandemic incursions. A retrospective cohort study to ascertain in-flight transmission of pandemic (H1N1) 2009 and influenza-like illness (ILI) was undertaken for 2 long-haul flights entering Australia during May 2009. Combined results, including survey responses from 319 (43%) of 738 passengers, showed that 13 (2%) had an ILI in flight and an ILI developed in 32 (5%) passengers during the first week post arrival. Passengers were at 3.6% increased risk of contracting pandemic (H1N1) 2009 if they sat in the same row as or within 2 rows of persons who were symptomatic preflight. A closer exposed zone (2 seats in front, 2 seats behind, and 2 seats either side) increased the risk for postflight disease to 7.7%. Efficiency of contact tracing without compromising the effectiveness of the public health intervention might be improved by limiting the exposed zone.

To identify environmental sites commonly contaminated by avian influenza virus A (H5N1) in live-bird markets in Indonesia, we investigated 83 markets in 3 provinces in Indonesia. At each market, samples were collected from up to 27 poultry-related sites to assess the extent of contamination. Samples were tested by using real-time reverse transcription–PCR and virus isolation. A questionnaire was used to ascertain types of birds in the market, general infrastructure, and work practices. Thirty-nine (47%) markets showed contamination with avian influenza virus in >1 of the sites sampled. Risk factors were slaughtering birds in the market and being located in West Java province. Protective factors included daily removal of waste and zoning that segregated poultry-related work flow areas. These results can aid in the design of evidence-based programs concerning environmental sanitation, food safety, and surveillance to reduce the risk for avian influenza virus A (H5N1) transmission in live-bird markets.

Encephalitis is a clinical syndrome commonly caused by emerging pathogens, which are not under surveillance in Australia. We reviewed rates of hospitalization for patients with encephalitis in Australia’s most populous state, New South Wales, from January 1990 through December 2007. Encephalitis was the primary discharge diagnosis for 5,926 hospital admissions; average annual hospitalization rate was 5.2/100,000 population. The most commonly identified pathogen was herpes simplex virus (n = 763, 12.9%). Toxoplasma encephalitis and subacute sclerosing panencephalitis showed notable declines. The average annual encephalitis case-fatality rate (4.6%) and the proportion of patients hospitalized with encephalitis with no identified pathogen (69.8%, range 61.5%–78.7%) were stable during the study period. The nonnotifiable status of encephalitis in Australia and the high proportion of this disease with no known etiology may conceal emergence of novel pathogens. Unexplained encephalitis should be investigated, and encephalitis hospitalizations should be subject to statutory notification in Australia.

The evidence-based policy (EBP) movement has received significant attention in the scientific literature, however, there is still very little empirical research to provide insight into how policy decisions are made and how evidence is used. The lack of research on this topic in low and middle-income countries is of particular note. We examine the maternity waiting home policy in Timor-Leste to understand the role of context, policy characteristics, individual actors and how evidence is used to influence the policy agenda. The research tracked the maternity waiting home policy from 2005 to 2009 and is based on in-depth interviews with 31 senior policy-makers, department managers, non-government organisation (NGO) representatives and United Nations (UN) advisors. It is also informed by direct observation, attendance at meetings and workshops and analysis of policy documents. The findings from this case study demonstrate the importance of political context, policy characteristics and the power of senior Ministry of Health officials rather than donors in setting the policy agenda. Maternity waiting homes were appealing because they were a visible, non-controversial and logical solution to the problem of accessing maternal health services. Evidence was used in a variety of ways, from supporting pre-determined agendas to informing new policy directions. In the pursuit of EBP, we conclude that the power of research to inform policy lies in its timeliness and relevance, and is facilitated by the connection between researchers and policy-makers.

BackgroundVitamin D (vitD) and L-arginine have important antimycobacterial effects in humans. Adjunctive therapy with these agents has the potential to improve outcomes in active tuberculosis (TB).MethodsIn a 4-arm randomised, double-blind, placebo-controlled factorial trial in adults with smear-positive pulmonary tuberculosis (PTB) in Timika, Indonesia, we tested the effect of oral adjunctive vitD 50,000 IU 4-weekly or matching placebo, and L-arginine 6.0 g daily or matching placebo, for 8 weeks, on proportions of participants with negative 4-week sputum culture, and on an 8-week clinical score (weight, FEV1, cough, sputum, haemoptysis). All participants with available endpoints were included in analyses according to the study arm to which they were originally assigned. Adults with new smear-positive PTB were eligible. The trial was registered at ClinicalTrials.gov NCT00677339.Results200 participants were enrolled, less than the intended sample size: 50 received L-arginine + active vitD, 49 received L-arginine + placebo vit D, 51 received placebo L-arginine + active vitD and 50 received placebo L-arginine + placebo vitD. According to the factorial model, 99 people received arginine, 101 placebo arginine, 101 vitamin D, 99 placebo vitamin D. Results for the primary endpoints were available in 155 (4-week culture) and 167 (clinical score) participants. Sputum culture conversion was achieved by week 4 in 48/76 (63%) participants in the active L-arginine versus 48/79 (61%) in placebo L-arginine arms (risk difference -3%, 95% CI -19 to 13%), and in 44/75 (59%) in the active vitD versus 52/80 (65%) in the placebo vitD arms (risk difference 7%, 95% CI -9 to 22%). The mean clinical outcome score also did not differ between study arms. There were no effects of the interventions on adverse event rates including hypercalcaemia, or other secondary outcomes.ConclusionNeither vitD nor L-arginine supplementation, at the doses administered and with the power attained, affected TB outcomes.RegistryClinicalTrials.gov. Registry number: NCT00677339.

Immunisation programs are designed to reduce serious morbidity and mortality from influenza, but most evidence supporting the effectiveness of this intervention has focused on disease in the community or in primary care settings. We aimed to examine the effectiveness of influenza vaccination against hospitalisation with confirmed influenza. We compared influenza vaccination status in patients hospitalised with PCR-confirmed influenza with patients hospitalised with influenza-negative respiratory infections in an Australian sentinel surveillance system. Vaccine effectiveness was estimated from the odds ratio of vaccination in cases and controls. We performed both simple multivariate regression and a stratified analysis based on propensity score of vaccination. Vaccination status was ascertained in 333 of 598 patients with confirmed influenza and 785 of 1384 test-negative patients. Overall estimated crude vaccine effectiveness was 57% (41%, 68%). After adjusting for age, chronic comorbidities and pregnancy status, the estimated vaccine effectiveness was 37% (95% CI: 12%, 55%). In an analysis accounting for a propensity score for vaccination, the estimated vaccine effectiveness was 48.3% (95% CI: 30.0, 61.8%). Influenza vaccination was moderately protective against hospitalisation with influenza in the 2010 and 2011 seasons.

Weight gain achieved during pulmonary tuberculosis (PTB) treatment is associated with the likelihood of bacteriological treatment success. It is recognised that weight and body mass index (BMI) characteristics differ between ethnic groups in health and illness states. However there has been no prior investigation of how ethnic differences in BMI might influence tuberculosis treatment outcome. Our aim was to investigate predictors of microbiological response to PTB treatment at the Tuberculosis Clinic in Timika, Papua Province, Indonesia and specifically, to determine the contribution of ethnicity. The population comprises two distinct ethnic groups - Asian (Non-Papuan) and Melanesian (Papuan). We conducted a prospective study of adults with smear-positive PTB. Treatment outcomes were 1- and 2-month sputum culture and time to microscopy conversion. Clinical measures included weight, BMI, chest radiograph, pulmonary function including forced expiratory volume in 1 second (FEV1) and haemoglobin. One hundred eighty six participants (83 Papuan, 103 non-Papuan Indonesians) were enrolled. At baseline, Papuans had higher mean weight and BMI than non-Papuans (50.0 kg versus 46.9 kg, p = 0.006 and 20.0 kg/m2 versus 18.7 kg/m2, p = 0.001 respectively). This was despite having lower mean haemoglobin (11.3 vs 13.1 g/dL, p

Given current extinction trends, the number of species requiring conservation breeding programs (CBPs) is likely to increase dramatically. To inform CBP policies for threatened terrestrial vertebrates, we evaluated the number and representation of threatened vertebrate species on the IUCN Red List held in the ISIS zoo network and estimated the complexity of their management as metapopulations. Our results show that 695 of the 3,955 (23%) terrestrial vertebrate species in ISIS zoos are threatened. Only two of the 59 taxonomic orders show a higher proportion of threatened species in ISIS zoos than would be expected if species were selected at random. In addition, for most taxa, the management of a zoo metapopulation of more than 250 individuals will require the coordination of a cluster of 11 to 24 ISIS zoos within a radius of 2,000 km. Thus, in the zoo network, the representation of species that may require CBPs is currently low and the spatial distribution of these zoo populations makes management difficult. Although the zoo community may have the will and the logistical potential to contribute to conservation actions, including CBPs, to do so will require greater collaboration between zoos and other institutions, alongside the development of international agreements that facilitate cross-border movement of zoo animals. To maximize the effectiveness of integrated conservation actions that include CBPs, it is fundamental that the non-zoo conservation community acknowledges and integrates the expertise and facilities of zoos where it can be helpful.

In pulmonary tuberculosis (PTB), morbidity during treatment and residual pulmonary disability can be under-estimated.Among adults with smear-positive PTB at an outpatient clinic in Papua, Indonesia, we assessed morbidity at baseline and during treatment, and 6-month residual disability, by measuring functional capacity (six-minute walk test [6MWT] and pulmonary function), quality of life (St George's Respiratory Questionnaire [SGRQ]) and Adverse Events ([AE]: new symptoms not present at outset). Results were compared with findings in locally-recruited volunteers.200 PTB patients and 40 volunteers were enrolled. 6WMT was 497m (interquartile range 460-529) in controls versus 408m (IQR 346-450) in PTB patients at baseline (p

BACKGROUND: Disease transmission patterns are needed to inform public health interventions, but remain largely unknown for avian influenza H5N1 virus infections. A recent study on the 139 outbreaks detected in Indonesia between 2005 and 2009 found that the type of exposure to sources of H5N1 virus for both the index case and their household members impacted the risk of additional cases in the household. This study describes the disease transmission patterns in those outbreak households. METHODOLOGY/PRINCIPAL FINDINGS: We compared cases (n = 177) and contacts (n = 496) in the 113 sporadic and 26 cluster outbreaks detected between July 2005 and July 2009 to estimate attack rates and disease intervals. We used final size household models to fit transmission parameters to data on household size, cases and blood-related household contacts to assess the relative contribution of zoonotic and human-to-human transmission of the virus, as well as the reproduction number for human virus transmission. The overall household attack rate was 18.3% and secondary attack rate was 5.5%. Secondary attack rate remained stable as household size increased. The mean interval between onset of subsequent cases in outbreaks was 5.6 days. The transmission model found that human transmission was very rare, with a reproduction number between 0.1 and 0.25, and the upper confidence bounds below 0.4. Transmission model fit was best when the denominator population was restricted to blood-related household contacts of index cases. CONCLUSIONS/SIGNIFICANCE: The study only found strong support for human transmission of the virus when a single large cluster was included in the transmission model. The reproduction number was well below the threshold for sustained transmission. This study provides baseline information on the transmission dynamics for the current zoonotic virus and can be used to detect and define signatures of a virus with increasing capacity for human-to-human transmission.

BACKGROUND: Digital pathology provides a digital environment for the management and interpretation of pathological images and associated data. It is becoming increasing popular to use modern computer based tools and applications in pathological education, tissue based research and clinical diagnosis. Uptake of this new technology is stymied by its single user orientation and its prerequisite and cumbersome combination of mouse and keyboard for navigation and annotation. METHODOLOGY: In this study we developed SurfaceSlide, a dedicated viewing platform which enables the navigation and annotation of gigapixel digitised pathological images using fingertip touch. SurfaceSlide was developed using the Microsoft Surface, a 30 inch multitouch tabletop computing platform. SurfaceSlide users can perform direct panning and zooming operations on digitised slide images. These images are downloaded onto the Microsoft Surface platform from a remote server on-demand. Users can also draw annotations and key in texts using an on-screen virtual keyboard. We also developed a smart caching protocol which caches the surrounding regions of a field of view in multi-resolutions thus providing a smooth and vivid user experience and reducing the delay for image downloading from the internet. We compared the usability of SurfaceSlide against Aperio ImageScope and PathXL online viewer. CONCLUSION: SurfaceSlide is intuitive, fast and easy to use. SurfaceSlide represents the most direct, effective and intimate human-digital slide interaction experience. It is expected that SurfaceSlide will significantly enhance digital pathology tools and applications in education and clinical practice.

Background Pandemic influenza H1N1/09 emerged in April 2009 and spread widely in Australia and New Zealand. Although an unprecedented number of cases required intensive care, comparative community-based studies with seasonal influenza strains have not shown any significant differences in clinical symptoms or severity.Methods The authors performed active surveillance on confirmed influenza-related admissions and compared the clinical profile of patients with pandemic H1N1/09 influenza and patients with seasonal influenza at eight hospitals in Australia and one hospital in New Zealand.Results During the 1 July and 30 November 2009, 560 patients with confirmed influenza were admitted, of which 478 had H1N1/09, and 82 had other seasonal strains. Patients with H1N1/09 influenza were younger, were more likely to have fever and were more likely to be pregnant but less likely to have chronic obstructive pulmonary disease and ischaemic heart disease than patients with seasonal strains. Other clinical features and comorbidities were reported in similar proportions. Admission to intensive care was required in 22% of patients with H1N1/09 influenza and 12% in patients with other strains. Hospital mortality was 5% in patients with H1N1 influenza.Conclusions The clinical features of H1N1/09 influenza and seasonal strains were similar in hospitalised patients. A higher proportion of patients had comorbidities than had been reported in community-based studies. Although the overall mortality was similar, the authors found evidence that H1N1/09 caused severe disease in a higher proportion of hospitalised patients.

IntroductionInfluenza infections present with wide-ranging clinical features. We aim to compare the differences in presentation between influenza and non-influenza cases among those with febrile respiratory illness (FRI) to determine predictors of influenza infection.MethodsPersonnel with FRI (defined as fever ≥ 37.5 °C, with cough or sore throat) were recruited from the sentinel surveillance system in the Singapore military. Nasal washes were collected, and tested using the Resplex II and additional PCR assays for etiological determination. Interviewer-administered questionnaires collected information on patient demographics and clinical features. Univariate comparison of the various parameters was conducted, with statistically significant parameters entered into a multivariate logistic regression model. The final multivariate model for influenza versus non-influenza cases was used to build a predictive probability clinical diagnostic model.Results821 out of 2858 subjects recruited from 11 May 2009 to 25 Jun 2010 had influenza, of which 434 (52.9%) had 2009 influenza A (H1N1), 58 (7.1%) seasonal influenza A (H3N2) and 269 (32.8%) influenza B. Influenza-positive cases were significantly more likely to present with running nose, chills and rigors, ocular symptoms and higher temperature, and less likely with sore throat, photophobia, injected pharynx, and nausea/vomiting. Our clinical diagnostic model had a sensitivity of 65% (95% CI: 58%, 72%), specificity of 69% (95% CI: 62%, 75%), and overall accuracy of 68% (95% CI: 64%, 71%), performing significantly better than conventional influenza-like illness (ILI) criteria.ConclusionsUse of a clinical diagnostic model may help predict influenza better than the conventional ILI definition among young adults with FRI.