From dissemination to engagement: learning over time from a national research intermediary centre (Four Fs)

Background: There has been little applied learning from organisations engaged in making evidence useful for decision makers. More focus has been given either to the work of individuals as knowledge brokers or to theoretical frameworks on embedding evidence. More intelligence is needed on the practice of knowledge intermediation.Aims and objectives: This paper describes the evolution of approaches by one UK Centre to promote and embed evidence in health and care services. This is not a formal evaluation, given the lack of critical distance by authors who led work at the Centre, but a reflective analysis which may be helpful for other evidence intermediary bodies.Conclusions: We analyse the founding conditions and theoretical context at the start of our activity and describe four activities we developed over time. These were filter (screening research for relevance and quality); forge (engaging stakeholders in interpreting evidence); fuse (knowledge brokering with hybrid teams); and fulfil (sustained interaction with implementation partners). We reflect on the tensions between rigour and relevance in the evidence we shared and the way in which our approaches evolved from a programme of evidence outputs to greater focus on sustained engagement and deliberative activities to make sense of evidence and reach wider audiences. Over the lifetime of the Centre, we moved from linear and relational modes towards systems type approaches to embed and mobilise evidence.<br />Key messages<br /><ul><li>There is little shared learning on the practice of evidence use by knowledge intermediaries.</li><br /><li>Our account of a national evidence centre for health decision makers shows the shift towards more engaged and embedded approaches.</li><br /><li>We identify four central activities – filter, forge, fuse and fulfil – and how they evolved over time.</li><br /><li>We note the value of sustained engagement with stakeholders in shaping new evidence narratives relevant to practice.</li></ul&gt

Label-free proteomics identifies Calreticulin and GRP75/Mortalin as peripherally accessible protein biomarkers for spinal muscular atrophy

BACKGROUND: Spinal muscular atrophy (SMA) is a neuromuscular disease resulting from mutations in the survival motor neuron 1 (SMN1) gene. Recent breakthroughs in preclinical research have highlighted several potential novel therapies for SMA, increasing the need for robust and sensitive clinical trial platforms for evaluating their effectiveness in human patient cohorts. Given that most clinical trials for SMA are likely to involve young children, there is a need for validated molecular biomarkers to assist with monitoring disease progression and establishing the effectiveness of therapies being tested. Proteomics technologies have recently been highlighted as a potentially powerful tool for such biomarker discovery. METHODS: We utilized label-free proteomics to identify individual proteins in pathologically-affected skeletal muscle from SMA mice that report directly on disease status. Quantitative fluorescent western blotting was then used to assess whether protein biomarkers were robustly changed in muscle, skin and blood from another mouse model of SMA, as well as in a small cohort of human SMA patient muscle biopsies. RESULTS: By comparing the protein composition of skeletal muscle in SMA mice at a pre-symptomatic time-point with the muscle proteome at a late-symptomatic time-point we identified increased expression of both Calreticulin and GRP75/Mortalin as robust indicators of disease progression in SMA mice. We report that these protein biomarkers were consistently modified in different mouse models of SMA, as well as across multiple skeletal muscles, and were also measurable in skin biopsies. Furthermore, Calreticulin and GRP75/Mortalin were measurable in muscle biopsy samples from human SMA patients. CONCLUSIONS: We conclude that label-free proteomics technology provides a powerful platform for biomarker identification in SMA, revealing Calreticulin and GRP75/Mortalin as peripherally accessible protein biomarkers capable of reporting on disease progression in samples of muscle and skin

The third dimension: How fire-related research can advance ecology and evolutionary biology

Most of the Earth’s vegetated surface is fireprone but the relevance of fire in understanding how nature works is not always recognized. We aim to show that, by adding the fire dimension to observations on biological phenomena, interpretations can be im-proved; how fire-related research can be used to answer ‘fundamental’ questions in ecology; and how theories/models developed for fireprone ecosystems can be applied to advancing disturbance ecology, biogeography and evolutionary biology more generally. We compiled lists from the world-wide web of the most highly cited papers in fire ecology, and examined papers that had been approached from multiple viewpoints, including fire. We show that great advances over the last 20 years have been made in our understanding of the pivotal role of fire as a driver of many ecological processes and a powerful selective agent/evolutionary trigger among biota. We document 21 sets of observations originally interpreted in the context of the two traditional dimensions, prevailing environment and biotic interactions, but can also be shown to have a strong, if not dominant, historical link to fire. We note that fire-related research is able to address 55 of the 100 questions considered ‘fundamental’ in ecology and that many have already received some attention in fireprone ecosystems. We show how theories/ models that had their origins in fireprone systems can be applied to other disturbance-prone systems and thus have wide application in ecology and evolutionary biology. Fire and other disturbances should be included as variables in research about possible critical environmental and biotic constraints controlling ecosystem function in general. Adding this third dimension to research endeavours greatly enriches our understanding of how nature works at the global scale in an era where ecosystems are changing rapidly and novel species-environmental interactions are emerging

Variations in Remotely-Sensed Phytoplankton Size Structure of a Cyclonic Eddy in the Southwest Indian Ocean

Phytoplankton size classes were derived from weekly-averaged MODIS Aqua chlorophyll a data over the southwest Indian Ocean in order to assess changes in surface phytoplankton community structure within a cyclonic eddy as it propagated across the Mozambique Basin in 2013. Satellite altimetry was used to identify and track the southwesterly movement of the eddy from its origin off Madagascar in mid-June until mid-October, when it eventually merged with the Agulhas Current along the east coast of South Africa. Nano- and picophytoplankton comprised most of the community in the early phase of the eddy development in June, but nanophytoplankton then dominated in austral winter (July and August). Microphytoplankton was entrained into the eddy by horizontal advection from the southern Madagascar shelf, increasing the proportion of microphytoplankton to 23% when the chlorophyll a levels reached a peak of 0.36 mg·m−3 in the third week of July. Chlorophyll a levels declined to 50% of the population. As far as is known, this is the first study to investigate temporal changes in chlorophyll a and community structure in a cyclonic eddy propagating across an ocean basin in the southwest Indian Ocean

Seasonal variation in remotely-sensed phytoplankton size structure around Southern Africa

The three-component model of Brewin et al. (2010) computes fractional contributions of three phytoplankton size classes (micro- (> 20μm), nano- (2–20μm), picophytoplankton ( 1 mgm−3 was limited to shelf regions along the coasts of Southern Africa and Madagascar, while values 50% of the total Chla in these regions with little change throughout the year. The AR shelf differed, with picophytoplankton dominating in summer, and micro- and nanophytoplankton the rest of the year. In the open ocean domains of the NB, SB, and AB regions, nanophytoplankton dominated for most of the year, with picophytoplankton being more prevalent during summer and autumn. In contrast, in the AR open ocean, nanophytoplankton were dominant only during winter and early spring, whereas picophytoplankton dominated throughout the year in the MC open ocean. The refined model characterised previously unknown spatial and temporal changes in size structure in various ecosystems around Southern Africa

Pre-Gondwanan-breakup origin of Beauprea (Proteaceae) explains its historical presence in New Caledonia and New Zealand

New Caledonia and New Zealand belong to the now largely submerged continent Zealandia. Their high levels of endemism and species richness are usually considered the result of transoceanic dispersal events followed by diversification after they re-emerged from the Pacific Ocean in the mid-Cenozoic. We explore the origin and evolutionary history of Beauprea (Proteaceae), which is now endemic to New Caledonia but was once spread throughout eastern Gondwana, including New Zealand. We review the extensive Beauprea-type pollen data in the fossil records and analyze the relationship of these fossil taxa to extant genera within Proteaceae. We further reconstruct the phylogenetic relations among nine extant species of Beauprea and estimate the age of the Beauprea clade. By incorporating extinct taxa into the Beauprea phylogenetic tree, we reconstruct the ancient distribution of this genus. Our analysis shows that Beauprea originated c. 88 Ma (million years ago) in Antarctica–Southeastern Australia and spread throughout Gondwana before its complete breakup. We propose that Beauprea, already existing as two lineages, was carried with Zealandia when it separated from the rest of Gondwana c. 82 Ma, thus supporting an autochthonous origin for Beauprea species now in New Caledonia and historically in New Zealand up to 1 Ma. We show that the presence of Beauprea through transoceanic dispersal is implausible. This means that neither New Caledonia nor New Zealand has been entirely submerged since the Upper Cretaceous; thus, possible vicariance and allopatry must be taken into account when considering the high levels of endemism and species richness of these island groups

A Cretaceous origin for fire adaptations in the Cape flora

Fire has had a profound effect on the evolution of worldwide biotas. The Cape Floristic Region is one of the world’s most species-rich regions, yet it is highly prone to recurrent fires and fire-adapted species contribute strongly to the overall flora. It is hypothesized that the current fire regimes in the Cape could be as old as 6–8 million years (My), while indirect evidence indicates that the onset of fire could have reached 18 million years ago (Ma). Here, we trace the origin of fire-dependent traits in two monocot families that are significant elements in the fire-prone Cape flora. Our analysis shows that fire-stimulated flowering originated in the Cape Haemodoraceae 81 Ma, while fire-stimulated germination arose in the African Restionaceae at least 70 Ma, implying that wildfires have been a significant force in the evolution of the Cape flora at least 60 My earlier than previous estimates. Our results provide strong evidence for the presence of fire adaptations in the Cape from the Cretaceous, leading to the extraordinary persistence of a fire-adapted flora in this biodiversity hotspot, and giving support to the hypothesis that Cretaceous fire was a global phenomenon that shaped the evolution of terrestrial floras

Baseline LHC machine parameters and configuration of the 2015 proton run

This paper shows the baseline LHC machine parameters for the 2015 start-up. Many systems have been upgraded during LS1 and in 2015 the LHC will operate at a higher energy than before and with a tighter filling scheme. Therefore, the 2015 commissioning phase risks to be less smooth than in 2012. The proposed starting configuration puts the focus on feasibility rather than peak performance and includes margins for operational uncertainties. Instead, once beam experience and a better machine knowledge has been obtained, a push in $\beta^*$ and performance can be envisaged. In this paper, the focus is on collimation settings and reach in $\beta^*$---other parameters are covered in greater depth by other papers in these proceedings.Comment: submitted for publication in a CERN yellow report (Proceedings of the LHC Performance Workshop - Chamonix 2014

Factors that affect the uptake of community-based health insurance in low-income and middle-income countries : a systematic protocol

Many people residing in low-income and middle-income countries (LMICs) are regularly exposed to catastrophic healthcare expenditure. It is therefore pertinent that LMICs should finance their health systems in ways that ensure that their citizens can use needed healthcare services and are protected from potential impoverishment arising from having to pay for services. Ways of financing health systems include government funding, health insurance schemes and out-of-pocket payment. A health insurance scheme refers to pooling of prepaid funds in a way that allows for risks to be shared. The health insurance scheme particularly suitable for the rural poor and the informal sector in LMICs is community-based health insurance (CBHI), that is, insurance schemes operated by organisations other than governments or private for-profit companies. We plan to search for and summarise currently available evidence on factors associated with the uptake of CBHI, as we are not aware of previous systematic reviews that have looked at this important topic

A photoelectron diffraction investigation of vanadyl phthalocyanine on Au(1 1 1)

Scanned-energy mode photoelectron diffraction using the O 1s and V 2p emission perpendicular to the surface has been used to investigate the orientation and internal conformation of vanadyl phthalocyanine (VOPc) adsorbed on Au(1 1 1). The results confirm earlier indications from scanning tunnelling microscopy that the Vdouble bond; length as m-dashO vanadyl bond points out of, and not into, the surface. The Vdouble bond; length as m-dashO bondlength is 1.60 ± 0.04 Å, not significantly different from its value in bulk crystalline VOPc. However, the V atom in the adsorbed molecule is almost coplanar with the surrounding N atoms and is thus pulled down into the approximately planar region defined by the N and C atoms by 0.52 (+0.14/−0.10) Å, relative to its location in crystalline VOPc. This change must be attributed to the bonding interaction between the molecule and the underlying metal surface