A 2018 Horizon Scan of Emerging Issues for Global Conservation and Biological Diversity.

This is our ninth annual horizon scan to identify emerging issues that we believe could affect global biological diversity, natural capital and ecosystem services, and conservation efforts. Our diverse and international team, with expertise in horizon scanning, science communication, as well as conservation science, practice, and policy, reviewed 117 potential issues. We identified the 15 that may have the greatest positive or negative effects but are not yet well recognised by the global conservation community. Themes among these topics include new mechanisms driving the emergence and geographic expansion of diseases, innovative biotechnologies, reassessments of global change, and the development of strategic infrastructure to facilitate global economic priorities

Human and mouse essentiality screens as a resource for disease gene discovery

The identification of causal variants in sequencing studies remains a considerable challenge that can be partially addressed by new gene-specific knowledge. Here, we integrate measures of how essential a gene is to supporting life, as inferred from viability and phenotyping screens performed on knockout mice by the International Mouse Phenotyping Consortium and essentiality screens carried out on human cell lines. We propose a cross-species gene classification across the Full Spectrum of Intolerance to Loss-of-function (FUSIL) and demonstrate that genes in five mutually exclusive FUSIL categories have differing biological properties. Most notably, Mendelian disease genes, particularly those associated with developmental disorders, are highly overrepresented among genes non-essential for cell survival but required for organism development. After screening developmental disorder cases from three independent disease sequencing consortia, we identify potentially pathogenic variants in genes not previously associated with rare diseases. We therefore propose FUSIL as an efficient approach for disease gene discovery. Discovery of causal variants for monogenic disorders has been facilitated by whole exome and genome sequencing, but does not provide a diagnosis for all patients. Here, the authors propose a Full Spectrum of Intolerance to Loss-of-Function (FUSIL) categorization that integrates gene essentiality information to aid disease gene discovery

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

A reduced global Alfven eigenmodes model for Mirnov array data on the H-1NF heliac

We extend a reduced-dimension stellarator ideal-MHD normal-mode model to include a vacuum region, and describe magnetic fluctuations in the H-1 heliac. We apply the reduced model to a magnetic field configuration with high density and compute the two lowest frequency global Alfvén eigenmodes (GAEs): (m, n) = (4, 5) and (7, 9). The poloidal mode number, predicted frequency and radial attenuation profile are then compared with measurements from a poloidal Mirnov array. Of the two candidates, the (7, 9) mode has a closer match in frequency and radial attenuation profile, and its narrower radial eigenfunction is a better match to recent optical-emission measurements [18]. Measurements of the temporal evolution of the mode are also consistent with the inferred Alfven frequency scaling at the radial localization of the (7, 9) mode. Combined, these observations suggest the measured fluctuation is a (7, 9) GAE. A wider benefit of our work includes the potential of a reduced-dimension normal-mode MHD model, with negligible computational needs, to characterize and identify mode activity in real time based on frequency, phase information, internal measurements and vacuum region attenuation. Such a model, which is likely to improve in accuracy for devices with simpler configuration such as a tokamak, may be useful as a tool for real time MHD spectroscopy, and to predict and control global eigenmodes associated with fast ion loss in burning plasmas

A research synthesis of therapeutic interventions for whiplash-associated disorder (WAD): Part 4 – noninvasive interventions for chronic WAD

Whiplash-associated disorder (WAD) represents a significant public health problem, resulting in substantial social and economic costs throughout the industrialized world. While many treatments have been advocated for patients with WAD, scientific evidence supporting their effectiveness is often lacking. A systematic review was conducted to evaluate the strength of evidence for various WAD therapies. Multiple databases (including Web of Science, EMBASE and PubMed) were searched to identify all studies published from January 1980 through March 2009 that evaluated the effectiveness of any clearly defined treatment for acute (less than two weeks), subacute (two to 12 weeks) or chronic (longer than 12 weeks) WAD. The present article, the fourth in a five-part series, evaluates the evidence for noninvasive interventions initiated during the chronic phase of WAD. Twenty-two studies that met the inclusion criteria were identified, 12 of which were randomized controlled trials with ‘good’ overall methodological quality (median Physiotherapy Evidence Database score of 6). For the treatment of chronic WAD, there is evidence to suggest that exercise programs are effective in relieving whiplash-related pain, at least over the short term. While the majority of a subset of nine studies supported the effectiveness of interdisciplinary interventions, the two randomized controlled trials provided conflicting results. Finally, there was limited evidence, consisting of one supportive case series each, that both manual joint manipulation and myofeedback training may provide some benefit. Based on the available research, exercise programs were the most effective noninvasive treatment for patients with chronic WAD, although many questions remain regarding the relative effectiveness of various exercise regimens

A Research Synthesis of Therapeutic Interventions for Whiplash-Associated Disorder: Part 1 – Overview and Summary

Whiplash-associated disorder (WAD) represents a significant public health problem, resulting in a substantial socioeconomic burden throughout the industrialized world, wherever costs are documented. While many treatments have been advocated for patients with WAD, scientific evidence of their effectiveness is often lacking. A systematic review was conducted to evaluate the strength of evidence supporting various WAD therapies. Multiple databases (including Web of Science, EMBASE and PubMed) were searched to identify all studies published from January 1980 through March 2009 that evaluated the effectiveness of any clearly defined treatment for acute (less than two weeks), subacute (two to 12 weeks) or chronic (longer than 12 weeks) WAD. The present article, the first in a five-part series, provides an overview of the review methodology as well as a summary and discussion of the review’s main findings. Eighty-three studies met the inclusion criteria, 40 of which were randomized controlled trials. The majority of studies (n=47) evaluated treatments initiated in the chronic stage of the disorder, while 23 evaluated treatments for acute WAD and 13 assessed therapies for subacute WAD. Exercise and mobilization programs for acute and chronic WAD had the strongest supporting evidence, although many questions remain regarding the relative effectiveness of various protocols. At present, there is insufficient evidence to support any treatment for subacute WAD. For patients with chronic WAD who do not respond to conventional treatments, it appears that radiofrequency neurotomy may be the most effective treatment option. The present review found a relatively weak but growing research base on which one could make recommendations for patients at any stage of the WAD continuum. Further research is needed to determine which treatments are most effective at reducing the disabling symptoms associated with WAD

A research synthesis of therapeutic interventions for whiplash-associated disorder (WAD): Part 3 – interventions for subacute WAD

Whiplash-associated disorder (WAD) represents a significant public health problem, resulting in substantial social and economic costs throughout the industrialized world. While many treatments have been advocated for patients with WAD, scientific evidence supporting their effectiveness is often lacking. A systematic review was conducted to evaluate the strength of evidence associated with various WAD therapies. Multiple databases (including Web of Science, EMBASE and PubMed) were searched to identify all studies published from January 1980 through March 2009 that evaluated the effectiveness of any clearly defined treatment for acute (less than two weeks), subacute (two to 12 weeks) or chronic (longer than 12 weeks) WAD. The present article, the third in a five-part series, evaluates the evidence for interventions initiated during the subacute phase of WAD. Thirteen studies that met the inclusion criteria were identified, six of which were randomized controlled trials with ‘good’ overall methodology (median Physiotherapy Evidence Database score of 6). Although some evidence was identified to support the use of interdisciplinary interventions and chiropractic manipulation, the evidence was not strong for any of the evaluated treatments. There is a clear need for further research to evaluate interventions aimed at treating patients with subacute WAD because there are currently no interventions satisfactorily supported by the research literature

A research synthesis of therapeutic interventions for whiplash-associated disorder (WAD): Part 2 – interventions for acute WAD

Whiplash-associated disorder (WAD) represents a significant public health problem, resulting in substantial social and economic costs throughout the industrialized world. While many treatments have been advocated for patients with WAD, scientific evidence supporting their effectiveness is often lacking. A systematic review was conducted to evaluate the strength of evidence associated with various WAD therapies. Multiple databases (including Web of Science, EMBASE and PubMed) were searched to identify all studies published from January 1980 through March 2009 that evaluated the effectiveness of any clearly defined treatment for acute (less than two weeks), subacute (two to 12 weeks) or chronic (more than 12 weeks) WAD. The present article, the second in a five-part series, evaluates the evidence for interventions initiated during the acute phase of WAD. Twenty-three studies that met the inclusion criteria were identified, 16 of which were randomized controlled trials with ‘fair’ overall methodological quality (median Physiotherapy Evidence Database score of 5.5). For the treatment of acute WAD, there was strong evidence to suggest that not only is immobilization with a soft collar ineffective, but it may actually impede recovery. Conversely, although exercise programs, active mobilization and advice to act as usual all appeared to improve recovery, it is not clear which of these interventions was the most effective. While there was also evidence supporting the use of pulsed electromagnetic field therapy and methylprednisolone infusion, the evidence was insufficient to establish the effectiveness of either of these treatments. Based on current evidence, activation-based therapy is recommended for the treatment of acute WAD; however, additional research is required to determine the relative effectiveness of various exercise/mobilization programs

The effect of green exercise on blood pressure, heart rate and mood state in primary school children

The aim of this study was exploratory and sought to examine the effect on blood pressure (BP), heart rate (HR) and mood state responses in primary school children of moderate intensity cycling whilst viewing a green environment compared to exercise alone. Following ethics approval and parental informed consent, 14 children (seven boys, seven girls, Mean age ± SD = 10 ± 1 years) undertook two, 15 min bouts of cycling at a moderate exercise intensity in a counterbalanced order. In one bout they cycled whilst viewing a film of cycling in a forest setting. In the other condition participants cycled with no visual stimulus. Pre-, immediately post-exercise and 15 min post-exercise, BP, HR and Mood state were assessed. Analysis of variance, indicated significant condition X time interaction for SBP (p = 0.04). Bonferroni post-hoc pairwise comparisons indicated that systolic blood pressure (SBP) 15 min post exercise was significantly lower following green exercise compared to the control condition (p = 0.01). There were no significant differences in diastolic blood pressure (DBP) (all p > 0.05). HR immediately post exercise was significantly higher than HR pre exercise irrespective of green exercise or control condition (p = 0.001). Mood scores for fatigue were significantly higher and scores for vigor lower 15 min post exercise irrespective of green exercise or control condition (both p = 0.0001). Gender was not significant in any analyses (p > 0.05). Thus, the present study identifies an augmented post exercise hypotensive effect for children following green exercise compared to exercise alone