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111.
Matthew J. Reed Neil R. Grubb Christopher C. Lang Rachel O’Brien Kirsty Simpson Mia Padarenga Alison Grant Sharon Tuck 《Trials》2018,19(1):711
Background
Palpitations and pre-syncope are together responsible for 300,000 annual Emergency Department (ED) attendances in the United Kingdom (UK). Diagnosis of the underlying rhythm is difficult as many patients are fully recovered on ED arrival; and examination and presenting electrocardiogram (ECG) are commonly normal. The only way to establish the underlying heart rhythm is to capture an ECG during symptoms. Recent technology advances have led to several novel ECG monitoring devices appearing on the market. This trial aims to compare the symptomatic rhythm detection rate at 90?days of one such smart phone-based event recorder (AliveCor Heart Monitor and AliveECG) with standard care for participants presenting to the ED with palpitations and pre-syncope and no obvious cause in the ED.Methods/Design
This is a multi-centre hospital ED / Acute Medical Unit (AMU) open label, randomised controlled trial. Participants will be recruited in 10 tertiary and district general hospitals in the UK. Participants aged ≥?16?years presenting with an episode of palpitations or pre-syncope with no obvious cause and whose underlying ECG rhythm during these episodes remains undiagnosed after clinical assessment will be included. Participants will be randomised to either: (1) the intervention arm, standard care plus the use of a smart phone-based event recorder; or (2) the control arm, standard care. Primary endpoint will be symptomatic rhythm detection rate at 90?days. A number of secondary clinical, process and cost-effectiveness endpoints will be collected and analysed. Analysis will be on an intention-to-treat basis.Discussion
The Investigation of Palpitations in the ED (IPED) study aims to recruit 242 participants across 10 hospital sites. It will be the first study to investigate the ability of a smart phone-based event recorder to detect symptomatic cardiac rhythms compared to standard care for ED patients with palpitations and pre-syncope with no obvious cause in the ED. This smart phone event recorder will allow ED patients who have presented with palpitations or pre-syncope to record their ECG tracing if they have a further episode and may increase the rate of underlying rhythm diagnosis.Trial registration
ClinicalTrials.gov, NCT02783898. Registered on 26 May 2016.112.
113.
Tricia L. May-Dracka Robert Arduini Andrea Bertolotti-Ciarlet Govinda Bhisetti Margot Brickelmaier Ellen Cahir-McFarland Istvan Enyedy Jason D. Fontenot Thomas Hesson Kevin Little Joe Lyssikatos Douglas Marcotte Timothy McKee Paramasivam Murugan Thomas Patterson Hairuo Peng Mia Rushe Laura Silvian Linda C. Burkly 《Bioorganic & medicinal chemistry letters》2018,28(10):1964-1971
Germinal center kinase-like kinase (GLK, also known as MAP4K3) has been hypothesized to have an effect on key cellular activities, including inflammatory responses. GLK is required for activation of protein kinase C-θ (PKCθ) in T cells. Controlling the activity of T helper cell responses could be valuable for the treatment of autoimmune diseases. This approach circumvents previous unsuccessful approaches to target PKCθ directly. The use of structure based drug design, aided by the first crystal structure of GLK, led to the discovery of several inhibitors that demonstrate potent inhibition of GLK biochemically and in relevant cell lines. 相似文献
114.
Mia Vedel Sørensen Richard Strimbeck Kristin Odden Nystuen Rozalia Erzsebet Kapas Brian J. Enquist Bente Jessen Graae 《Ecosystems》2018,21(2):316-330
Shrub communities have expanded in arctic and alpine tundra during recent decades. Changes in shrub abundance may alter ecosystem carbon (C) sequestration and storage, with potential positive or negative feedback on global C cycling. To assess potential implications of shrub expansion in different alpine plant communities, we compared C fluxes and pools in one Empetrum-dominated heath, one herb- and cryptogam-dominated meadow, and one Salix-shrub community in Central Norway. Over two growing seasons, we measured Gross Ecosystem Photosynthesis, Ecosystem Respiration (ER), and C pools for above-ground vegetation, litter, roots, and soil separated into organic and mineral horizons. Both the meadow and shrub communities had higher rates of C fixation and ER, but the total ecosystem C pool in the meadow was twice that of the shrub community because of more C in the organic soil horizon. Even though the heath community had the lowest rates of C fixation, it stored one and a half times more C than the shrub community. The results indicate that the relatively high above-ground biomass sequestering C during the growing season is not associated with high C storage in shrub-dominated communities. Instead, shrub-dominated areas may be draining the carbon-rich alpine soils because of high rates of decomposition. These processes were not shown by mid-growing season C fluxes, but were reflected by the very different distribution of C pools in the three habitats. 相似文献
115.
Lee B. Jacoby Deborah Jones Kevin Davis David Kronn M. Priscilla Short James Gusella Mia MacCollin 《American journal of human genetics》1997,61(6):1293-1302
Patients with multiple schwannomas without vestibular schwannomas have been postulated to compose a distinct subclass of neurofibromatosis (NF), termed "schwannomatosis." To compare the molecular-genetic basis of schwannomatosis with NF2, we examined the NF2 locus in 20 unrelated schwannomatosis patients and their affected relatives. Tumors from these patients frequently harbored typical truncating mutations of the NF2 gene and loss of heterozygosity of the surrounding region of chromosome 22. Surprisingly, unlike patients with NF2, no heterozygous NF2-gene changes were seen in normal tissues. Examination of multiple tumors from the same patient revealed that some schwannomatosis patients are somatic mosaics for NF2-gene changes. By contrast, other individuals, particularly those with a positive family history, appear to have an inherited predisposition to formation of tumors that carry somatic alterations of the NF2 gene. Further work is needed to define the pathogenetics of this unusual disease mechanism. 相似文献
116.
117.
The MMS22L–TONSL heterodimer directly promotes RAD51‐dependent recombination upon replication stress 下载免费PDF全文
Wojciech Piwko Karun Mutreja Lepakshi Ranjha Diana Stafa Alexander Smirnov Mia ML Brodersen Ralph Zellweger Andreas Sturzenegger Pavel Janscak Massimo Lopes Matthias Peter Petr Cejka 《The EMBO journal》2016,35(23):2584-2601
Homologous recombination (HR) is a key pathway that repairs DNA double‐strand breaks (DSBs) and helps to restart stalled or collapsed replication forks. How HR supports replication upon genotoxic stress is not understood. Using in vivo and in vitro approaches, we show that the MMS22L–TONSL heterodimer localizes to replication forks under unperturbed conditions and its recruitment is increased during replication stress in human cells. MMS22L–TONSL associates with replication protein A (RPA)‐coated ssDNA, and the MMS22L subunit directly interacts with the strand exchange protein RAD51. MMS22L is required for proper RAD51 assembly at DNA damage sites in vivo, and HR‐mediated repair of stalled forks is abrogated in cells expressing a MMS22L mutant deficient in RAD51 interaction. Similar to the recombination mediator BRCA2, recombinant MMS22L–TONSL limits the assembly of RAD51 on dsDNA, which stimulates RAD51‐ssDNA nucleoprotein filament formation and RAD51‐dependent strand exchange activity in vitro. Thus, by specifically regulating RAD51 activity at uncoupled replication forks, MMS22L–TONSL stabilizes perturbed replication forks by promoting replication fork reversal and stimulating their HR‐mediated restart in vivo. 相似文献
118.
Adriaan J. Reinecke Mia van Wyk Sophie A. Reinecke 《Soil & Sediment Contamination》2016,25(8):868-881
For landfarming of oil refinery waste to be sustainable, it is crucial to know the toxicity and chemical composition of the waste. We determined the chemical composition of waste known as American Petroleum Institute sludge and tested its toxicity in two different soils using the earthworm Eisenia andrei (Oligochaeta) in standardized bioassays. We compared the chemical composition of the sludge with available chemical profiles of the landfarming site where sludge of the same origin had been landfarmed for several years. The concentrations of Al, Mn, Pb, S and Zn and diesel range organics were higher in the landfarmed soil than in the sludge, indicating possible accumulation in the soil over time. Although no traces of volatile organic compounds were previously found in the landfarming site soil, we found high levels in the American Petroleum Institute sludge, indicating that these volatiles may not pose a long-term problem in the soil. Polycyclic aromatic hydrocarbons and gasoline range organics were present in the sludge at higher concentrations than in the site soil, indicating that their remediation through landfarming may have had some degree of success.Earthworm biomass and reproduction were detrimentally affected at low sludge concentrations, which could have population level effects over time in a landfarming site. 相似文献
119.
120.
Ronald?PetieEmail author Michael?R.?Hall Mia?Hyldahl Anders?Garm 《Coral reefs (Online)》2016,35(4):1139-1150
Photoreception in echinoderms has been known for over 200 years, but their visual capabilities remain poorly understood. As has been reported for some asteroids, the crown-of-thorns starfish (Acanthaster planci) possess a seemingly advanced eye at the tip of each of its 7–23 arms. With such an array of eyes, the starfish can integrate a wide field of view of its surroundings. We hypothesise that, at close range, orientation and directional movements of the crown-of-thorns starfish are visually guided. In this study, the eyes and vision of A. planci were examined by means of light microscopy, electron microscopy, underwater goniometry, electroretinograms and behavioural experiments in the animals’ natural habitat. We found that only animals with intact vision could orient to a nearby coral reef, whereas blinded animals, with olfaction intact, walked in random directions. The eye had peak sensitivity in the blue part (470 nm) of the visual spectrum and a narrow, horizontal visual field of approximately 100° wide and 30° high. With approximately 250 ommatidia in each adult compound eye and average interommatidial angles of 8°, crown-of-thorns starfish have the highest spatial resolution of any starfish studied to date. In addition, they have the slowest vision of all animals examined thus far, with a flicker fusion frequency of only 0.6–0.7 Hz. This may be adaptive as fast vision is not required for the detection of stationary objects such as reefs. In short, the eyes seem optimised for detecting large, dark, stationary objects contrasted against an ocean blue background. Our results show that the visual sense of the crown-of-thorns starfish is much more elaborate than has been thus far appreciated and is essential for orientation and localisation of suitable habitats. 相似文献