Identifying the science and technology dimensions of emerging public policy issues through horizon scanning

Public policy requires public support, which in turn implies a need to enable the public not just to understand policy but also to be engaged in its development. Where complex science and technology issues are involved in policy making, this takes time, so it is important to identify emerging issues of this type and prepare engagement plans. In our horizon scanning exercise, we used a modified Delphi technique [1]. A wide group of people with interests in the science and policy interface (drawn from policy makers, policy adviser, practitioners, the private sector and academics) elicited a long list of emergent policy issues in which science and technology would feature strongly and which would also necessitate public engagement as policies are developed. This was then refined to a short list of top priorities for policy makers. Thirty issues were identified within broad areas of business and technology; energy and environment; government, politics and education; health, healthcare, population and aging; information, communication, infrastructure and transport; and public safety and national security.Public policy requires public support, which in turn implies a need to enable the public not just to understand policy but also to be engaged in its development. Where complex science and technology issues are involved in policy making, this takes time, so it is important to identify emerging issues of this type and prepare engagement plans. In our horizon scanning exercise, we used a modified Delphi technique [1]. A wide group of people with interests in the science and policy interface (drawn from policy makers, policy adviser, practitioners, the private sector and academics) elicited a long list of emergent policy issues in which science and technology would feature strongly and which would also necessitate public engagement as policies are developed. This was then refined to a short list of top priorities for policy makers. Thirty issues were identified within broad areas of business and technology; energy and environment; government, politics and education; health, healthcare, population and aging; information, communication, infrastructure and transport; and public safety and national security

Minimally invasive, patient specific, beat-by-beat estimation of left ventricular time varying elastance.

peer reviewedBACKGROUND: The aim of this paper was to establish a minimally invasive method for deriving the left ventricular time varying elastance (TVE) curve beat-by-beat, the monitoring of which's inter-beat evolution could add significant new data and insight to improve diagnosis and treatment. The method developed uses the clinically available inputs of aortic pressure, heart rate and baseline end-systolic volume (via echocardiography) to determine the outputs of left ventricular pressure, volume and dead space volume, and thus the TVE curve. This approach avoids directly assuming the shape of the TVE curve, allowing more effective capture of intra- and inter-patient variability. RESULTS: The resulting TVE curve was experimentally validated against the TVE curve as derived from experimentally measured left ventricular pressure and volume in animal models, a data set encompassing 46,318 heartbeats across 5 Pietrain pigs. This simulated TVE curve was able to effectively approximate the measured TVE curve, with an overall median absolute error of 11.4% and overall median signed error of -2.5%. CONCLUSIONS: The use of clinically available inputs means there is potential for real-time implementation of the method at the patient bedside. Thus the method could be used to provide additional, patient specific information on intra- and inter-beat variation in heart function

Use of whole genome sequencing to determine genetic basis of suspected mitochondrial disorders: cohort study

Funder: University of Cambridge; FundRef: http://dx.doi.org/10.13039/501100000735Funder: Alzheimer's Society; FundRef: http://dx.doi.org/10.13039/501100000320Funder: Leverhulme Trust; FundRef: http://dx.doi.org/10.13039/501100000275Funder: National Institute for Health Research; FundRef: http://dx.doi.org/10.13039/501100000272Funder: Department of Health; FundRef: http://dx.doi.org/10.13039/501100000276Funder: Evelyn Trust; FundRef: http://dx.doi.org/10.13039/501100004282Funder: Wellcome Trust; FundRef: http://dx.doi.org/10.13039/100004440Funder: Medical Research Council; FundRef: http://dx.doi.org/10.13039/501100000265Abstract: Objective: To determine whether whole genome sequencing can be used to define the molecular basis of suspected mitochondrial disease. Design: Cohort study. Setting: National Health Service, England, including secondary and tertiary care. Participants: 345 patients with suspected mitochondrial disorders recruited to the 100 000 Genomes Project in England between 2015 and 2018. Intervention: Short read whole genome sequencing was performed. Nuclear variants were prioritised on the basis of gene panels chosen according to phenotypes, ClinVar pathogenic/likely pathogenic variants, and the top 10 prioritised variants from Exomiser. Mitochondrial DNA variants were called using an in-house pipeline and compared with a list of pathogenic variants. Copy number variants and short tandem repeats for 13 neurological disorders were also analysed. American College of Medical Genetics guidelines were followed for classification of variants. Main outcome measure: Definite or probable genetic diagnosis. Results: A definite or probable genetic diagnosis was identified in 98/319 (31%) families, with an additional 6 (2%) possible diagnoses. Fourteen of the diagnoses (4% of the 319 families) explained only part of the clinical features. A total of 95 different genes were implicated. Of 104 families given a diagnosis, 39 (38%) had a mitochondrial diagnosis and 65 (63%) had a non-mitochondrial diagnosis. Conclusion: Whole genome sequencing is a useful diagnostic test in patients with suspected mitochondrial disorders, yielding a diagnosis in a further 31% after exclusion of common causes. Most diagnoses were non-mitochondrial disorders and included developmental disorders with intellectual disability, epileptic encephalopathies, other metabolic disorders, cardiomyopathies, and leukodystrophies. These would have been missed if a targeted approach was taken, and some have specific treatments

Prehospital transdermal glyceryl trinitrate in patients with ultra-acute presumed stroke (RIGHT-2): an ambulance-based, randomised, sham-controlled, blinded, phase 3 trial

Background High blood pressure is common in acute stroke and is a predictor of poor outcome; however, large trials of lowering blood pressure have given variable results, and the management of high blood pressure in ultra-acute stroke remains unclear. We investigated whether transdermal glyceryl trinitrate (GTN; also known as nitroglycerin), a nitric oxide donor, might improve outcome when administered very early after stroke onset. Methods We did a multicentre, paramedic-delivered, ambulance-based, prospective, randomised, sham-controlled, blinded-endpoint, phase 3 trial in adults with presumed stroke within 4 h of onset, face-arm-speech-time score of 2 or 3, and systolic blood pressure 120 mm Hg or higher. Participants were randomly assigned (1:1) to receive transdermal GTN (5 mg once daily for 4 days; the GTN group) or a similar sham dressing (the sham group) in UK based ambulances by paramedics, with treatment continued in hospital. Paramedics were unmasked to treatment, whereas participants were masked. The primary outcome was the 7-level modified Rankin Scale (mRS; a measure of functional outcome) at 90 days, assessed by central telephone follow-up with masking to treatment. Analysis was hierarchical, first in participants with a confirmed stroke or transient ischaemic attack (cohort 1), and then in all participants who were randomly assigned (intention to treat, cohort 2) according to the statistical analysis plan. This trial is registered with ISRCTN, number ISRCTN26986053. Findings Between Oct 22, 2015, and May 23, 2018, 516 paramedics from eight UK ambulance services recruited 1149 participants (n=568 in the GTN group, n=581 in the sham group). The median time to randomisation was 71 min (IQR 45–116). 597 (52%) patients had ischaemic stroke, 145 (13%) had intracerebral haemorrhage, 109 (9%) had transient ischaemic attack, and 297 (26%) had a non-stroke mimic at the final diagnosis of the index event. In the GTN group, participants’ systolic blood pressure was lowered by 5·8 mm Hg compared with the sham group (p<0·0001), and diastolic blood pressure was lowered by 2·6 mm Hg (p=0·0026) at hospital admission. We found no difference in mRS between the groups in participants with a final diagnosis of stroke or transient ischaemic stroke (cohort 1): 3 (IQR 2–5; n=420) in the GTN group versus 3 (2–5; n=408) in the sham group, adjusted common odds ratio for poor outcome 1·25 (95% CI 0·97–1·60; p=0·083); we also found no difference in mRS between all patients (cohort 2: 3 [2–5]; n=544, in the GTN group vs 3 [2–5]; n=558, in the sham group; 1·04 [0·84–1·29]; p=0·69). We found no difference in secondary outcomes, death (treatment-related deaths: 36 in the GTN group vs 23 in the sham group [p=0·091]), or serious adverse events (188 in the GTN group vs 170 in the sham group [p=0·16]) between treatment groups. Interpretation Prehospital treatment with transdermal GTN does not seem to improve functional outcome in patients with presumed stroke. It is feasible for UK paramedics to obtain consent and treat patients with stroke in the ultraacute prehospital setting. Funding British Heart Foundation

GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5–2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements as contributing mechanisms to ICP susceptibility

Proof of concept non-invasive estimation of peripheral venous oxygen saturation

Abstract Background Pulse oximeters continuously monitor arterial oxygen saturation. Continuous monitoring of venous oxygen saturation (SvO2) would enable real-time assessment of tissue oxygen extraction (O2E) and perfusion changes leading to improved diagnosis of clinical conditions, such as sepsis. Methods This study presents the proof of concept of a novel pulse oximeter method that utilises the compliance difference between arteries and veins to induce artificial respiration-like modulations to the peripheral vasculature. These modulations make the venous blood pulsatile, which are then detected by a pulse oximeter sensor. The resulting photoplethysmograph (PPG) signals from the pulse oximeter are processed and analysed to develop a calibration model to estimate regional venous oxygen saturation (SpvO2), in parallel to arterial oxygen saturation estimation (SpaO2). A clinical study with healthy adult volunteers (n = 8) was conducted to assess peripheral SvO2 using this pulse oximeter method. A range of physiologically realistic SvO2 values were induced using arm lift and vascular occlusion tests. Gold standard, arterial and venous blood gas measurements were used as reference measurements. Modulation ratios related to arterial and venous systems were determined using a frequency domain analysis of the PPG signals. Results A strong, linear correlation (r 2  = 0.95) was found between estimated venous modulation ratio (RVen) and measured SvO2, providing a calibration curve relating measured RVen to venous oxygen saturation. There is a significant difference in gradient between the SpvO2 estimation model (SpvO2 = 111 − 40.6*R) and the empirical SpaO2 estimation model (SpaO2 = 110 − 25*R), which yields the expected arterial-venous differences. Median venous and arterial oxygen saturation accuracies of paired measurements between pulse oximeter estimated and gold standard measurements were 0.29 and 0.65%, respectively, showing good accuracy of the pulse oximeter system. Conclusions The main outcome of this study is the proof of concept validation of a novel pulse oximeter sensor and calibration model to assess peripheral SvO2, and thus O2E, using the method used in this study. Further validation, improvement, and application of this model can aid in clinical diagnosis of microcirculation failures due to alterations in oxygen extraction

Measuring lung mechanics of expiratory tidal breathing with non-invasive breath occlusion

BACKGROUND AND OBJECTIVE: Lung mechanics measurements provide clinically useful information about disease progression and lung health. Currently, there are no commonly practiced methods to non-invasively measure both resistive and elastic lung mechanics during tidal breathing, preventing the important information provided by lung mechanics from being utilised. This study presents a novel method to easily assess lung mechanics of spontaneously breathing subjects using a dynamic elastance, single-compartment lung model. METHODS: A spirometer with a built-in shutter was used to occlude expiration during tidal breathing, creating exponentially decaying flow when the shutter re-opened. The lung mechanics measured were respiratory system elastance and resistance, separated from the exponentially decaying flow, and interrupter resistance calculated at shutter closure. Progressively increasing resistance was added to the spirometer mouthpiece to simulate upper airway obstruction. The lung mechanics of 17 healthy subjects were successfully measured through spirometry. RESULTS: N = 17 (8 female, 9 male) healthy subjects were recruited. Measured decay rates ranged from 5 to 42/s, subjects with large variation of decay rates showed higher muscular breathing effort. Lung elastance measurements ranged from 3.9 to 21.2 cmH[Formula: see text]O/L, with no clear trend between change in elastance and added resistance. Resistance calculated from decay rate and elastance ranged from 0.15 to 1.95 cmH[Formula: see text]Os/L. These very small resistance values are due to the airflow measured originating from low-resistance areas in the centre of airways. Occlusion resistance measurements were as expected for healthy subjects, and increased as expected as resistance was added. CONCLUSIONS: This test was able to identify reasonable dynamic lung elastance and occlusion resistance values, providing new insight into expiratory breathing effort. Clinically, this lung function test could impact current practice. It does not require high levels of cooperation from the subject, allowing a wider cohort of patients to be assessed more easily. Additionally, this test can be simply implemented in a small standalone device, or with standard lung function testing equipment

Future novel threats and opportunities facing UK biodiversity identified by horizon scanning.

1. Horizon scanning is an essential tool for environmental scientists if they are to contribute to the evidence base for Government, its agencies and other decision makers to devise and implement environmental policies. The implication of not foreseeing issues that are foreseeable is illustrated by the contentious responses to genetically modified herbicide-tolerant crops in the UK, and by challenges surrounding biofuels, foot and mouth disease, avian influenza and climate change. 2. A total of 35 representatives from organizations involved in environmental policy, academia, scientific journalism and horizon scanning were asked to use wide consultation to identify the future novel or step changes in threats to, and opportunities for, biodiversity that might arise in the UK up to 2050, but that had not been important in the recent past. At least 452 people were consulted. 3. Cases for 195 submitted issues were distributed to all participants for comments and additions. All issues were scored (probability, hazard, novelty and overall score) prior to a 2-day workshop. Shortlisting to 41 issues and then the final 25 issues, together with refinement of these issues, took place at the workshop during another two rounds of discussion and scoring. 4. We provide summaries of the 25 shortlisted issues and outline the research needs. 5. We suggest that horizon scanning incorporating wide consultation with providers and users of environmental science is used by environmental policy makers and researchers. This can be used to identify gaps in knowledge and policy, and to identify future key issues for biodiversity, including those arising from outside the domains of ecology and biodiversity. 6. Synthesis and applications. Horizon scanning can be used by environmental policy makers and researchers to identify gaps in knowledge and policy. Drawing on the experience, expertise and research of policy advisors, academics and journalists, this exercise helps set the agenda for policy, practice and research

Sustainability Policy Research: A Review and Synthesis

This paper reviews theoretical and empirical approaches drawn from influential journal articles and books on sustainability policy published over the last 10 years (2007 through 2017). Due to the widespread application of sustainability as a concept and space limitations, the paper more narrowly focuses on sustainability research in three critical policy areas: climate change, urban development, and agroecology and food systems. Drawing from information provided primarily by citation indexes, the study identifies and analyzes the research literature related to sustainability in these three fields. Future theoretical and empirical research approaches that can better integrate and connect the current diffuse and incongruent literature on sustainability are discussed in the paper. The findings of the literature review generate a number of possible future research directions that are discussed in the study