8,228 research outputs found
Does a monetary incentive improve the response to a postal questionnaire in a randomised controlled trial? : the MINT incentive study
Background: Sending a monetary incentive with postal questionnaires has been found to improve
the proportion of responders, in research in non-healthcare settings. However, there is little
research on use of incentives to improve follow-up rates in clinical trials, and existing studies are
inconclusive. We conducted a randomised trial among participants in the Managing Injuries of the
Neck Trial (MINT) to investigate the effects on the proportion of questionnaires returned and
overall non-response of sending a £5 gift voucher with a follow-up questionnaire.
Methods: Participants in MINT were randomised to receive either: (a) a £5 gift voucher (incentive
group) or (b) no gift voucher (no incentive group), with their 4 month or 8 month follow-up
questionnaire. We recorded, for each group, the number of questionnaires returned, the number
returned without any chasing from the study office, the overall number of non-responders (after
all chasing efforts by the study office), and the costs of following up each group.
Results: 2144 participants were randomised, 1070 to the incentive group and 1074 to the no
incentive group. The proportion of questionnaires returned (RR 1.10 (95% CI 1.05, 1.16)) and the
proportion returned without chasing (RR 1.14 (95% CI 1.05, 1.24) were higher in the incentive
group, and the overall non-response rate was lower (RR 0.68 (95% CI 0.53, 0.87)). Adjustment for
injury severity and hospital of recruitment to MINT made no difference to these results, and there
were no differences in results between the 4-month and 8-month follow up questionnaires.
Analysis of costs suggested a cost of £67.29 per additional questionnaire returned.
Conclusion: Monetary incentives may be an effective way to increase the proportion of postal
questionnaires returned and minimise loss to follow-up in clinical trials
Tasmanian reserve geoconservation inventory assessment using Geographic Information Technology (GIT)
Geoconservation is, at its foundation, a grass-roots movement with geoheritage represented by geosites containing the most scientifically significant and valuable geodiversity elements. Problems arise in the assessment and communication of inventory due in part to inconsistent and traditionally time-consuming, ‘snapshot’ assessments that are difficult to spatially monitor.The case study of kunanyi/Mount Wellington and the encompassing IUCN Category II Wellington Park Reserve (18,250 ha) (42°53′24″ S 147°13′48″ E, Tasmania, Australia) was chosen to explore the complexities of geosite and geodiversity site assessment, detection and communication. Using digital tools, we revised a 25-year-old snapshot inventory, configuring the ESRI ‘Collector for ArcGIS’ app for in-field data collection. Putative geosite and geodiversity site attributes were assessed for scientific value, potential touristic use, and potential educational use, using theBrilha (2016) method. Additional digital tools supported spatially accurate, engaging and interactive online inventory.Our findings suggested that many of the putative geosites in the park had low or moderate scientific values, but higher additional educational or touristic use values, especially in the urban-facing park zones. Though site degradation risk was low-moderate, sites in closer proximity to City of Hobart might experience additional impacts from visitation.The Wellington Park is a significant protected area that aims to tell an important story about the evolution of the periglaciated terrain and the endemic fauna and flora that depend upon it. In this sense, the possibility that not all putative geosites have high scientific value (and instead, might be better classed as geodiversity sites) is of limited concern, because the myriad geodiversity elements and additional value rankings (including 50% being highly ‘representative’ elements) provide an opportunity for all who visit the park to observe a coherent story about Tasmania in an easily accessible location. The opportunities realised in the creation of the digital inventory and assessment process remedy many issues that currently hamper practical Geoconservation, improving cost, consistency and standardisation of the inventory assessment and the quality of geotouristic and educational products. This digital approach could assist protected area managers and geoconservationists to monitor, protect and communicate inventory over the long-term
Leukemia-associated Rho guanine-nucleotide exchange factor is not critical for RhoA regulation, yet is important for platelet activation and thrombosis in mice.
BACKGROUND: RhoA is an important regulator of platelet responses downstream of Gα13 , yet we still know little about its regulation in platelets. Leukemia-associated Rho guanine-nucleotide exchange factor (GEF [LARG]), a RhoA GEF, is highly expressed in platelets and may constitute a major upstream activator of RhoA. To this end, it is important to determine the role of LARG in platelet function and thrombosis. METHODS AND RESULTS: Using a platelet-specific gene knockout, we show that the absence of LARG results in a marked reduction in aggregation and dense-granule secretion in response to the thromboxane mimetic U46619 and proteinase-activated receptor 4-activating peptide, AYPGKF, but not to adenosine diphosphate. In a ferric chloride thrombosis model in vivo, this translated into a defect, under mild injury conditions. Importantly, agonist-induced RhoA activation was not affected by the absence of LARG, although basal activity was reduced, suggesting that LARG may play a housekeeper role in regulating constitutive RhoA activity. CONCLUSIONS: LARG plays an important role in platelet function and thrombosis in vivo. However, although LARG may have a role in regulating the resting activation state of RhoA, its role in regulating platelet function may principally be through RhoA-independent pathways, possibly through other Rho family members
CARMA1 is a novel regulator of T-ALL disease and leukemic cell migration to the CNS
No abstract available
Cdc7 is a potent anti-cancer target in pancreatic cancer due to abrogation of the DNA origin activation checkpoint.
PURPOSE: Cdc7 is a serine/threonine kinase which is responsible for the 'firing' of replication origins leading to initiation of DNA replication. Inhibition or depletion of Cdc7 in normal cells triggers a DNA origin activation checkpoint causing a reversible G1 arrest. Here we investigate Cdc7 as a novel therapeutic target in pancreatic cancer. EXPERIMENTAL DESIGN: Cdc7 target validation was performed by immunoexpression profiling in a cohort of 73 patients with pancreatic adenocarcinoma including 24 controls. Secondly Cdc7 kinase was targeted in Capan-1 and PANC-1 pancreatic cancer cell line models using either an siRNA against Cdc7 or alternatively a small molecule inhibitor (SMI) of Cdc7 (PHA-767491). RESULTS: Cdc7 was significantly overexpressed in pancreatic adenocarcinoma compared to benign pancreatic tissue (median LI 34.3% vs. 1.3%; P<0.0001). Cdc7 knockdown using siRNA in Capan-1 and PANC-1 cells resulted in marked apoptotic cell death when compared with control cells. A prominent sub-G1 peak was seen on flow cytometry (sub-G1 51% vs. 3% and 45% vs. 0.7% in Capan-1 and PANC-1 cells, respectively). Annexin V labelling confirmed apoptosis in 64% vs. 11% and 75% vs. 8%, respectively. Western blotting showed cleavage of PARP-1 and caspase-3 and presence of γH2A.X. TUNEL assay showed strong staining in treated cells. These results were mirrored following Cdc7 kinase inhibition with PHA-767491. CONCLUSIONS: Our findings show that Cdc7 is a potent anti-cancer target in pancreatic adenocarcinoma and that Cdc7 immunoexpression levels might be used as a companion diagnostic to predict response to therapeutic siRNAs or SMIs directed against this kinase
β1-Integrin-Mediated Uptake of Chondrocyte Extracellular Vesicles Regulates Chondrocyte Homeostasis.
Osteoarthritis (OA) is the most prevalent age-related degenerative disorder, which severely reduces the quality of life of those affected. Whilst management strategies exist, no cures are currently available. Virtually all joint resident cells generate extracellular vesicles (EVs), and alterations in chondrocyte EVs during OA have previously been reported. Herein, we investigated factors influencing chondrocyte EV release and the functional role that these EVs exhibit. Both 2D and 3D models of culturing C28I/2 chondrocytes were used for generating chondrocyte EVs. We assessed the effect of these EVs on chondrogenic gene expression as well as their uptake by chondrocytes. Collectively, the data demonstrated that chondrocyte EVs are sequestered within the cartilage ECM and that a bi-directional relationship exists between chondrocyte EV release and changes in chondrogenic differentiation. Finally, we demonstrated that the uptake of chondrocyte EVs is at least partially dependent on β1-integrin. These results indicate that chondrocyte EVs have an autocrine homeostatic role that maintains chondrocyte phenotype. How this role is perturbed under OA conditions remains the subject of future work
Genes Suggest Ancestral Colour Polymorphisms Are Shared across Morphologically Cryptic Species in Arctic Bumblebees
email Suzanne orcd idCopyright: © 2015 Williams et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
On the Computational Complexity of MapReduce
In this paper we study MapReduce computations from a complexity-theoretic
perspective. First, we formulate a uniform version of the MRC model of Karloff
et al. (2010). We then show that the class of regular languages, and moreover
all of sublogarithmic space, lies in constant round MRC. This result also
applies to the MPC model of Andoni et al. (2014). In addition, we prove that,
conditioned on a variant of the Exponential Time Hypothesis, there are strict
hierarchies within MRC so that increasing the number of rounds or the amount of
time per processor increases the power of MRC. To the best of our knowledge we
are the first to approach the MapReduce model with complexity-theoretic
techniques, and our work lays the foundation for further analysis relating
MapReduce to established complexity classes
- …