Large historical growth in global terrestrial gross primary production.

Growth in terrestrial gross primary production (GPP)-the amount of carbon dioxide that is 'fixed' into organic material through the photosynthesis of land plants-may provide a negative feedback for climate change. It remains uncertain, however, to what extent biogeochemical processes can suppress global GPP growth. As a consequence, modelling estimates of terrestrial carbon storage, and of feedbacks between the carbon cycle and climate, remain poorly constrained. Here we present a global, measurement-based estimate of GPP growth during the twentieth century that is based on long-term atmospheric carbonyl sulfide (COS) records, derived from ice-core, firn and ambient air samples. We interpret these records using a model that simulates changes in COS concentration according to changes in its sources and sinks-including a large sink that is related to GPP. We find that the observation-based COS record is most consistent with simulations of climate and the carbon cycle that assume large GPP growth during the twentieth century (31% ± 5% growth; mean ± 95% confidence interval). Although this COS analysis does not directly constrain models of future GPP growth, it does provide a global-scale benchmark for historical carbon-cycle simulations.

An audit of dementia education and training in UK health and social care: a comparison with national benchmark standards.

BACKGROUND: Despite people living with dementia representing a significant proportion of health and social care users, until recently in the United Kingdom (UK) there were no prescribed standards for dementia education and training. This audit sought to review the extent and nature of dementia education and training offered to health and social care staff in the UK against the standards described in the 2015 Dementia Training Standards Framework, which describes the knowledge and skills required of the UK dementia workforce. METHODS: This audit presents national data concerning the design, delivery, target audience, length, level, content, format of training, number of staff trained and frequency of delivery within existing dementia training programmes offered to health and social care staff. The Dementia Training Standards Framework was used as a reference for respondents to describe the subjects and learning outcomes associated with their training. RESULTS: The findings are presented from 614 respondents offering 386 training packages, which indicated variations in the extent and quality of training. Many training packages addressed the subjects of 'person-centred care', 'communication', 'interaction and behaviour in dementia care', and 'dementia awareness'. Few training packages addressed subjects concerning 'pharmacological interventions in dementia care', 'leadership' and 'end of life care'. Fewer than 40% of The Dementia Training Standards Framework learning outcomes targeted to staff with regular contact with people with dementia or in leadership roles were covered by the reported packages. However, for training targeted at increasing dementia awareness more than 70% of the learning outcomes identified in The Dementia Training Standards Framework were addressed. Many training packages are not of sufficient duration to derive impact; although the majority employed delivery methods likely to be effective. CONCLUSIONS: The development of new and existing training and education should take account of subjects that are currently underrepresented and ensure that training reflects the Training Standard Framework and evidence regarding best practice for delivery. Lessons regarding the limitations of training in the UK serve as a useful illustration of the challenge of implementing national dementia training standards; particularly for countries who are developing or have recently implemented national dementia strategies.

Optimization of Time- and Code-Division-Multiplexed Readout for Athena X-IFU.

Readout of a large, spacecraft-based array of superconducting transition-edge sensors (TESs) requires careful management of the layout area and power dissipation of the cryogenic-circuit components. We present three optimizations of our time- (TDM) and code-division-multiplexing (CDM) systems for the X-ray Integral Field Unit (X-IFU), a several-thousand-pixel-TES array for the planned Athena-satellite mission. The first optimization is a new readout scheme that is a hybrid of CDM and TDM. This C/TDM architecture balances CDM's noise advantage with TDM's layout compactness. The second is a redesign of a component: the shunt resistor that provides a dc-voltage bias to the TESs. A new layout and a thicker Pd-Au resistive layer combine to reduce this resistor's area by more than a factor of 5. Third, we have studied the power dissipated by the first-stage SQUIDs (superconducting quantum-interference devices) and the readout noise versus the critical current of the first-stage SqUIDs. As a result, the X-IFU TDM and C/TDM SQUIDs will have a specified junction critical current of 5 µA. Based on these design optimizations and TDM experiments described by Durkin, et al. (these proceedings), TDM meets all requirements to be X-IFU's backup-readout option. Hybrid C/TDM is another viable option that could save spacecraft resources.

Energy calibration of high-resolution X-Ray TES microcalorimeters with 3 eV optical photons.

With the improving energy resolution of transitionedge sensor (TES) based microcalorimeters, performance verification and calibration of these detectors has become increasingly challenging, especially in the energy range below 1 keV where fluorescent atomic X-ray lines have linewidths that are wider than the detector energy resolution and require impractically high statistics to determine the gain and deconvolve the instrumental profile. Better behaved calibration sources such as grating monochromators are too cumbersome for space missions and are difficult to use in the lab. As an alternative, we are exploring the use of pulses of 3 eV optical photons delivered by an optical fiber to generate combs of known energies with known arrival times. Here, we discuss initial results of this technique obtained with 2 eV and 0.7 eV resolution X-ray microcalorimeters. With the 2 eV detector, we have achieved photon number resolution for pulses with mean photon number up to 133 (corresponding to 0.4 keV).

Demonstration of Athena X-IFU Compatible 40-Row Time-Division-Multiplexed Readout.

Time-division multiplexing (TDM) is the backup readout technology for the X-ray Integral Field Unit (X-IFU), a 3,168-pixel X-ray transition-edge sensor (TES) array that will provide imaging spectroscopy for ESA's Athena satellite mission. X-0IFU design studies are considering readout with a multiplexing factor of up to 40. We present data showing 40-row TDM readout (32 TES rows + 8 repeats of the last row) of TESs that are of the same type as those being planned for X-IFU, using measurement and analysis parameters within the ranges specified for X-IFU. Singlecolumn TDM measurements have best-fit energy resolution of (1.91 ± 0.01) eV for the Al Kα complex (1.5 keV), (2.10 ± 0.02) eV for Ti Kα (4.5 keV), (2.23 ± 0.02) eV for Mn Kα (5.9 keV), (2.40 ± 0.02) eV for Co Kα (6.9 keV), and (3.44 ± 0.04) eV for Br Kα (11.9 keV). Three-column measurements have best-fit resolution of (2.03 ± 0.01) eV for Ti Kα and (2.40 ± 0.01) eV for Co Kα. The degradation due to the multiplexed readout ranges from 0.1 eV at the lower end of the energy range to 0.5 eV at the higher end. The demonstrated performance meets X-IFU's energy-resolution and energy-range requirements. True 40-row TDM readout, without repeated rows, of kilopixel scale arrays of X-IFU-like TESs is now under development.

Fabrication of X-ray Microcalorimeter Focal Planes Composed of Two Distinct Pixel Types.

We are developing superconducting transition-edge sensor (TES) microcalorimeter focal planes for versatility in meeting specifications of X-ray imaging spectrometers including high count-rate, high energy resolution, and large field-of-view. In particular, a focal plane composed of two sub-arrays: one of fine-pitch, high count-rate devices and the other of slower, larger pixels with similar energy resolution, offers promise for the next generation of astrophysics instruments, such as the X-ray Integral Field Unit (X-IFU) instrument on the European Space Agency's Athena mission. We have based the sub-arrays of our current design on successful pixel designs that have been demonstrated separately. Pixels with an all gold X-ray absorber on 50 and 75 micron scales where the Mo/Au TES sits atop a thick metal heatsinking layer have shown high resolution and can accommodate high count-rates. The demonstrated larger pixels use a silicon nitride membrane for thermal isolation, thinner Au and an added bismuth layer in a 250 micron square absorber. To tune the parameters of each sub-array requires merging the fabrication processes of the two detector types. We present the fabrication process for dual production of different X-ray absorbers on the same substrate, thick Au on the small pixels and thinner Au with a Bi capping layer on the larger pixels to tune their heat capacities. The process requires multiple electroplating and etching steps, but the absorbers are defined in a single ion milling step. We demonstrate methods for integrating heatsinking of the two types of pixel into the same focal plane consistent with the requirements for each sub-array, including the limiting of thermal crosstalk. We also discuss fabrication process modifications for tuning the intrinsic transition temperature (Tc) of the bilayers for the different device types through variation of the bilayer thicknesses. The latest results on these "hybrid" arrays will be presented.

Cryptosporidiosis outbreak in visitors of a UK industry-compliant petting farm caused by a rare Cryptosporidium parvum subtype: a case-control study.

A case-control study was conducted to investigate an outbreak of 46 cases of cryptosporidiosis in visitors to a petting farm in England. Details of exposures on the farm were collected for 38 cases and 39 controls, recruited through snowball sampling. Multivariable logistic regression identified that cases were 5·5 times more likely than controls to have eaten without washing their hands [95% confidence interval (CI) 1·51-19·9, P = 0·01] and 10 times less likely to report being informed of risk of infection on arrival (odds ratio 0·10, 95% CI 0·01-0·71, P = 0·02). An uncommon Cryptosporidium parvum gp60 subtype (IIaA19G1R1) was identified in a lamb faecal sample and all subtyped cases (n = 22). We conclude that lack of verbal advice and non-compliance with hand washing are significantly associated with a risk of cryptosporidiosis on open farms. These findings highlight the public health importance of effectively communicating risk to petting farm visitors in order to prevent future outbreaks of zoonotic infections.

Increased cortical synaptic activation of TrkB and downstream signaling markers in a mouse model of Down Syndrome.

Down Syndrome (DS), trisomy 21, is characterized by synaptic abnormalities and cognitive deficits throughout the lifespan and with development of Alzheimer's disease (AD) neuropathology and progressive cognitive decline in adults. Synaptic abnormalities are also present in the Ts65Dn mouse model of DS, but which synapses are affected and the mechanisms underlying synaptic dysfunction are unknown. Here we show marked increases in the levels and activation status of TrkB and associated signaling proteins in cortical synapses in Ts65Dn mice. Proteomic analysis at the single synapse level of resolution using array tomography (AT) uncovered increased colocalization of activated TrkB with signaling endosome related proteins, and demonstrated increased TrkB signaling. The extent of increases in TrkB signaling differed in each of the cortical layers examined and with respect to the type of synapse, with the most marked increases seen in inhibitory synapses. These findings are evidence of markedly abnormal TrkB-mediated signaling in synapses. They raise the possibility that dysregulated TrkB signaling contributes to synaptic dysfunction and cognitive deficits in DS.

Obesity resistance and multiple mechanisms of triglyceride synthesis in mice lacking Dgat.

Triglycerides (or triacylglycerols) represent the major form of stored energy in eukaryotes. Triglyceride synthesis has been assumed to occur primarily through acyl CoA:diacylglycerol transferase (Dgat), a microsomal enzyme that catalyses the final and only committed step in the glycerol phosphate pathway. Therefore, Dgat has been considered necessary for adipose tissue formation and essential for survival. Here we show that Dgat-deficient (Dgat-/-) mice are viable and can still synthesize triglycerides. Moreover, these mice are lean and resistant to diet-induced obesity. The obesity resistance involves increased energy expenditure and increased activity. Dgat deficiency also alters triglyceride metabolism in other tissues, including the mammary gland, where lactation is defective in Dgat-/- females. Our findings indicate that multiple mechanisms exist for triglyceride synthesis and suggest that the selective inhibition of Dgat-mediated triglyceride synthesis may be useful for treating obesity.

Cognitive performance of military men and women during prolonged load carriage.

BACKGROUND: This study evaluated cognitive workload in soldiers undertaking a long duration march wearing different loads. METHODS: Military participants (n=12 men and n=10 women) performed four 3-hour loaded marches (12.25 km at 4.9 km/hour) wearing either 21 kg, 26 kg, 33 kg or 43 kg. During the march, accuracy and response time were measured using the verbal working memory n-back test (0, 1, 2 and 3) and two bespoke Go/No Go tests (visual/auditory) to assess inhibition of a pre-potent response. RESULTS: The physical demands of the march increased with load and march duration but remained at moderate intensity. N-back test accuracy ranged from 74% to 98% in men and 62% to 98% in women. Reduced accuracy was observed as load and time increased. Accuracy during the visual Go/No Go test also reduced with load, accuracy ranged from 69% to 89% in men and 65% to 90% in women. No differences due to load or time were observed during completion of the auditory Go/No Go task; accuracy ranged from 93% to 97% in men and 77% to 95% in women. A number of participants were unable to complete the march due to discomfort. Reports of discomfort were more frequent in women, which may have contributed to the greater reductions in accuracy observed. CONCLUSION: These data provide further evidence that cognitive performance of military personnel can be affected during long duration loaded marching. Women reported discomfort from equipment more frequently than men, which may make them more susceptible to declines in cognitive performance. These findings highlight important considerations for equipment procurement.

To know or not to know? Dilemmas for women receiving unknown oocyte donation.

BACKGROUND: This study aims to provide insight into the reasons for choosing an unknown oocyte donor and to explore recipients' feelings and wishes regarding donor information. METHODS: In-depth interviews were carried out with 11 women at different stages of treatment. Seven were on a waiting list and four have given birth to donor oocyte babies. The interviews were analysed using interpretative phenomenological analysis. RESULTS: The choice of unknown donor route was motivated by a wish to feel secure in the role of mother as well as to avoid possible intrusions into family relationships. The information that is available about unknown donors is often very limited. In the preconception phase of treatment, some participants wanted more information about the donor but others adopted a not-knowing stance that protected them from the emotional impact of needing a donor. In the absence of information that might normalize her, there was a tendency to imagine the donor in polarised simplistic terms, so she may be idealized or feared. Curiosity about the donor intensified once a real baby existed, and the task of telling a child was more daunting when very little was known about the donor. A strong wish for same-donor siblings was expressed by all of the participants who had given birth. CONCLUSIONS: This qualitative study throws light on the factors that influence the choice of unknown donation. It also highlights the scope for attitudes to donor information to undergo change over the course of treatment and after giving birth. The findings have implications for pretreatment counselling and raise a number of issues that merit further exploration.

Temperature increase of 21st century mitigation scenarios.

Estimates of 21st Century global-mean surface temperature increase have generally been based on scenarios that do not include climate policies. Newly developed multigas mitigation scenarios, based on a wide range of modeling approaches and socioeconomic assumptions, now allow the assessment of possible impacts of climate policies on projected warming ranges. This article assesses the atmospheric CO(2) concentrations, radiative forcing, and temperature increase for these new scenarios using two reduced-complexity climate models. These scenarios result in temperature increase of 0.5-4.4 degrees C over 1990 levels or 0.3-3.4 degrees C less than the no-policy cases. The range results from differences in the assumed stringency of climate policy and uncertainty in our understanding of the climate system. Notably, an average minimum warming of approximately 1.4 degrees C (with a full range of 0.5-2.8 degrees C) remains for even the most stringent stabilization scenarios analyzed here. This value is substantially above previously estimated committed warming based on climate system inertia alone. The results show that, although ambitious mitigation efforts can significantly reduce global warming, adaptation measures will be needed in addition to mitigation to reduce the impact of the residual warming.

Cross-sectional associations of schoolchildren's fruit and vegetable consumption, and meal choices, with their mental well-being: a cross-sectional study.

BACKGROUND: Poor mental well-being is a major issue for young people and is likely to have long-term negative consequences. The contribution of nutrition is underexplored. We, therefore, investigated the association between dietary choices and mental well-being among schoolchildren. METHODS: Data from 7570 secondary school and 1253 primary school children in the Norfolk Children and Young People Health and Well-being Survey, open to all Norfolk schools during October 2017, were analysed. Multivariable linear regression was used to measure the association between nutritional factors and mental well-being assessed by the Warwick-Edinburgh Mental Well-being Scale for secondary school pupils, or the Stirling Children's Well-being Scale for primary school pupils. We adjusted all analyses for important covariates including demographic, health variables, living/home situation and adverse experience variables. RESULTS: In secondary school analyses, a strong association between nutritional variables and well-being scores was apparent. Higher combined fruit and vegetable consumption was significantly associated with higher well-being: well-being scores were 3.73 (95% CI 2.94 to 4.53) units higher in those consuming five or more fruits and vegetables (p<0.001; n=1905) compared with none (n=739). The type of breakfast or lunch consumed was also associated with significant differences in well-being score. Compared with children consuming a conventional type of breakfast (n=5288), those not eating any breakfast had mean well-being scores 2.73 (95% CI 2.11 to 3.35) units lower (p<0.001; n=1129) and those consuming only an energy drink had well-being scores 3.14 (95% CI 1.20 to 5.09) units lower (p=0.002; n=91). Likewise, children not eating any lunch had well-being scores 2.95 (95% CI 2.22 to 3.68) units lower (p<0.001; 860) than those consuming a packed lunch (n=3744). In primary school analyses, the type of breakfast or lunch was associated with significant differences in well-being scores in a similar way to those seen in secondary school data, although no significant association with fruit and vegetable intake was evident. CONCLUSION: These findings suggest that public health strategies to optimise the mental well-being of children should include promotion of good nutrition.

Reduced Complexity Model Intercomparison Project Phase 2: Synthesizing Earth System Knowledge for Probabilistic Climate Projections.

Over the last decades, climate science has evolved rapidly across multiple expert domains. Our best tools to capture state-of-the-art knowledge in an internally self-consistent modeling framework are the increasingly complex fully coupled Earth System Models (ESMs). However, computational limitations and the structural rigidity of ESMs mean that the full range of uncertainties across multiple domains are difficult to capture with ESMs alone. The tools of choice are instead more computationally efficient reduced complexity models (RCMs), which are structurally flexible and can span the response dynamics across a range of domain-specific models and ESM experiments. Here we present Phase 2 of the Reduced Complexity Model Intercomparison Project (RCMIP Phase 2), the first comprehensive intercomparison of RCMs that are probabilistically calibrated with key benchmark ranges from specialized research communities. Unsurprisingly, but crucially, we find that models which have been constrained to reflect the key benchmarks better reflect the key benchmarks. Under the low-emissions SSP1-1.9 scenario, across the RCMs, median peak warming projections range from 1.3 to 1.7°C (relative to 1850-1900, using an observationally based historical warming estimate of 0.8°C between 1850-1900 and 1995-2014). Further developing methodologies to constrain these projection uncertainties seems paramount given the international community's goal to contain warming to below 1.5°C above preindustrial in the long-term. Our findings suggest that users of RCMs should carefully evaluate their RCM, specifically its skill against key benchmarks and consider the need to include projections benchmarks either from ESM results or other assessments to reduce divergence in future projections.

Large-scale sequencing of SARS-CoV-2 genomes from one region allows detailed epidemiology and enables local outbreak management.

The COVID-19 pandemic has spread rapidly throughout the world. In the UK, the initial peak was in April 2020; in the county of Norfolk (UK) and surrounding areas, which has a stable, low-density population, over 3200 cases were reported between March and August 2020. As part of the activities of the national COVID-19 Genomics Consortium (COG-UK) we undertook whole genome sequencing of the SARS-CoV-2 genomes present in positive clinical samples from the Norfolk region. These samples were collected by four major hospitals, multiple minor hospitals, care facilities and community organizations within Norfolk and surrounding areas. We combined clinical metadata with the sequencing data from regional SARS-CoV-2 genomes to understand the origins, genetic variation, transmission and expansion (spread) of the virus within the region and provide context nationally. Data were fed back into the national effort for pandemic management, whilst simultaneously being used to assist local outbreak analyses. Overall, 1565 positive samples (172 per 100 000 population) from 1376 cases were evaluated; for 140 cases between two and six samples were available providing longitudinal data. This represented 42.6 % of all positive samples identified by hospital testing in the region and encompassed those with clinical need, and health and care workers and their families. In total, 1035 cases had genome sequences of sufficient quality to provide phylogenetic lineages. These genomes belonged to 26 distinct global lineages, indicating that there were multiple separate introductions into the region. Furthermore, 100 genetically distinct UK lineages were detected demonstrating local evolution, at a rate of ~2 SNPs per month, and multiple co-occurring lineages as the pandemic progressed. Our analysis: identified a discrete sublineage associated with six care facilities; found no evidence of reinfection in longitudinal samples; ruled out a nosocomial outbreak; identified 16 lineages in key workers which were not in patients, indicating infection control measures were effective; and found the D614G spike protein mutation which is linked to increased transmissibility dominates the samples and rapidly confirmed relatedness of cases in an outbreak at a food processing facility. The large-scale genome sequencing of SARS-CoV-2-positive samples has provided valuable additional data for public health epidemiology in the Norfolk region, and will continue to help identify and untangle hidden transmission chains as the pandemic evolves.

Premature mortality in refractory partial epilepsy: does surgical treatment make a difference?

BACKGROUND: Epilepsy carries an increased risk of premature death. For some people with intractable focal epilepsy, surgery offers hope for a seizure-free life. The authors aimed to see whether epilepsy surgery influenced mortality in people with intractable epilepsy. METHODS: The authors audited survival status in two cohorts (those who had surgery and those who had presurgical assessment but did not have surgery). RESULTS: There were 40 known deaths in the non-surgical group (3365 person years of follow-up) and 19 in the surgical group (3905 person-years of follow-up). Non-operated patients were 2.4 times (95% CI 1.4 to 4.2) as likely to die as those who had surgery. They were 4.5 times (95% CI 1.9 to 10.9) as likely to die a probable epilepsy-related death. In the surgical group, those with ongoing seizures 1 year after surgery were 4.0 (95% CI 1.2 to 13.7) times as likely to die as those who were seizure-free or who had only simple partial seizures. Time-dependent Cox analysis showed that the yearly outcome group did not significantly affect mortality (HR 1.3, 95% CI 0.9 to 1.8). CONCLUSION: Successful epilepsy surgery was associated with a reduced risk of premature mortality, compared with those with refractory focal epilepsy who did not have surgical treatment. To some extent, the reduced mortality is likely to be conferred by inducing freedom from seizures. It is not certain whether better survival is attributable only to surgery, as treatment decisions were not randomised, and there may be inherent differences between the groups.

Pre-oxygenation in healthy volunteers: a comparison of the supine and 45° seated positions*.

Pre-oxygenation in the seated (sitting) position has been associated with better oxygenation. This randomised, cross over study compared oxygenation in the supine position with that in the 45° seated position in 40 young, healthy volunteers. Oxygen was administered through a circle system and tight fitting facemask. Transcutaneous P(O)2 levels were recorded at 10-s intervals from two measurement points during 4 min of oxygenation in the two positions. The mean (SD) values of 12 measurements taken between the third and fourth minute were recorded. There was no difference in the increase in tissue oxygenation when comparing the supine and seated positions (32.7 (7.3) vs 32.6 (6.7) kPa, respectively). We conclude that there is no evidence that pre-oxygenation in the 45° seated position improves tissue oxygenation in young healthy volunteers compared with the supine position.

Outcome and long-term follow-up of 20 horses undergoing surgery for caecal impaction: a retrospective study (2000-2008).

REASONS FOR PERFORMING STUDY: If untreated, caecal impaction may progress to rupture of the caecum and reports of long-term outcome for horses undergoing surgery for caecal impaction are required. OBJECTIVES: To describe short- and long-term complication rates for horses undergoing surgery for caecal impaction in an otherwise life-threatening gastrointestinal condition. METHODS: Case records were reviewed for horses undergoing surgery for caecal impaction. Horses were included in the study if an abnormally large, fluid-distended or feed-impacted caecum was the primary diagnosis at surgery and excluded if the caecum had already ruptured upon opening the abdomen, necessitating euthanasia. Short-term follow-up data were obtained from clinical records; and included complications, repeat celiotomy and survival to discharge. Long-term survival was defined as survival for >1 year post operatively. Long-term follow-up data were obtained through telephone interviews with owners and referring veterinary surgeons. Survival, occurrence of post operative colic and subsequent use of the horse were recorded. RESULTS: Twenty horses underwent surgery for caecal impaction: 16 horses underwent caecal bypass (typhlotomy and removal of caecal contents, ileal transection followed by ileocolostomy); 3 underwent typhlotomy alone; and one horse underwent typhlotomy followed by a second procedure where caecal bypass was performed. Five horses (25%) were admitted for colic evaluation with primary caecal impactions, in 10/20 (50%) of cases the impaction was secondary to previous orthopaedic surgery and in 5/20 (25%) caecal impaction was identified at repeat celiotomy following a previous colic surgery. Sixty-five percent (13/20) of horses survived to discharge; 11/13 (85%) of horses discharged survived long term; 100% (3/3) horses that received typhlotomy alone were discharged and survived long term. CONCLUSIONS: The prognosis following caecal impaction surgery is fair, if the horse survives to discharge then prognosis for long-term survival is good. POTENTIAL RELEVANCE: Surgery for caecal impaction carries a fair prognosis for a potentially life threatening disease, in particular where caecal dysfunction is suspected.

Do current clinical trials in cystic fibrosis match the priorities of patients and clinicans? A systematic review.

There are many uncertainties regarding Cystic Fibrosis (CF) treatment. Recently, the first James Lind Alliance (JLA) Priority Setting Partnership (PSP) in CF was completed, bringing clinicians, patients and carers together to identify the Top 10 research priorities. Here we investigate how well the current clinical trials landscape reflects these priorities. Trials in CF were identified through searches of research databases (Pubmed, ANZCTR, EU clinical trials register, ClinicalTrials.gov and ISRCTN). Trials meeting inclusion criteria of registered intervention studies in CF published between 01.012016 and 11.09.2017 were matched to the Top 10 priorities. We identified 259 trials, with 193 fulfilling the inclusion criteria. Only 63 (33%) of these matched one or more of the JLA priorities showing that current clinical trials poorly reflect the JLA Top 10. By increasing awareness of the Top 10 priorities, it is hoped that this will fuel future research in areas important to the CF community.

Can exercise replace airway clearance techniques in cystic fibrosis? A survey of patients and healthcare professionals.

Airway clearance techniques (ACTs) are recommended in cystic fibrosis (CF) to prevent accumulation of secretions and lung infection. "Can exercise replace chest physiotherapy for people with CF?" is one of the CF community's top 10 research questions. We conducted an online survey of the CF community to gather data on current ACT use, recommendations, reported adherence levels and exercise strategies used. There were 488 respondents: 194 (40%) people with CF (pwCF), 141 (29%) family and 153 (31%) healthcare professionals (HCPs) (mostly physiotherapists). Only 10/285 (4%) of pwCF do no exercise at present and 163/303 (54%) already incorporate exercise into ACTs. ACTs were omitted by 128/267 (48%) of pwCF when they exercised. Nearly all (110/129, 93%) of HCPs currently recommend exercise to support ACTs. A trial replacing some or all ACTs with exercise, was supported by 80/110 (73%) of HCPs, with an additional 9/110 (8%) willing to consider in selected patients.