156 research outputs found

    How to democratize Internet of Things devices. A participatory design research

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    The global introduction of affordable Internet of Things (IoT) devices offers an opportunity to empower a large variety of users with different needs. However, many off-the-shelf digital products are still not widely adopted by people who are hesitant technology users or by older adults, notwithstanding that the design and user-interaction of these devices is recognized to be user-friendly. In view of the potential of IoT-based devices, how can we reduce the obstacles of a cohort with low digital literacy and technology anxiety and enable them to be equal participants in the digitalized world? This article shows the method and results achieved in a community-stakeholder workshop, developed through the participatory design methodology, aiming at brainstorming problems and scenarios through a focus group and a structured survey. The research activity focused on understanding factors to increase the usability of off-the-shelf IoT devices for hesitant users and identify strategies for improving digital literacy and reducing technology anxiety. A notable result was a series of feedback items pointing to the importance of creating learning resources to support individuals with different abilities, age, gender expression, to better adopt off-the-shelf IoT-based solutions.Comment: 8 pages, 5 figure

    Evidence for an increase in cosmogenic 10Be during a geomagnetic reversal

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    Reversals in the geomagnetic field, which occur every few hundred thousand years, represent a dramatic change in the Earth's environment. Although there is no satisfactory theory for such reversals, it is generally accepted that the dipole field intensity decreases to <20% of its 'normal' value for a few thousand years during the change in direction. Because the galactic and solar cosmic rays which impinge on the Earth's atmosphere are charged, a significant fraction (about half) of them are deflected by the geomagnetic field. At the time of a reversal, this magnetic shielding is greatly reduced, and it has been suggested that the increased flux of high-energy particles could have effects on evolutionary or climatic processes. For example, the statistically significant coincidence in levels of some marine faunal extinctions and reversal boundaries in ocean sediments could be caused, directly or indirectly, by the decreased geomagnetic intensity during the reversal. We report here evidence in marine sediments for an increase in cosmogenic 10Be production in the Earth's atmosphere during the Brunhes-Matuyama reversal 730,000 yr ago. In addition to confirming an increase in cosmogenic isotope production, the results provide information on the magnitude and duration of the geomagnetic intensity decrease during such an event, and the depth at which remanent magnetism is acquired in marine sediments

    Seeking a practical definition of stable glaucoma: a Delphi consensus survey of UK glaucoma consultants

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    © 2019, The Author(s), under exclusive licence to The Royal College of Ophthalmologists. Background: To generate a practical and clinically useful consensus definition of ‘stable glaucoma’ to aid provision of glaucoma services in the UK and to provide guidance for the criteria that should be used for monitoring of glaucoma patients in primary care services. Methods: A Delphi exercise was undertaken to derive consensus through an online questionnaire. Participants were asked to score their strength of agreement for a series of clinical parameters. Results and comments from each round were used to inform subsequent rounds. A total of 3 rounds were undertaken. Results: Thirty-two glaucoma experts participated in the study with over 90% completion rate achieved over three rounds. The consensus was reached for the following parameters: IOP levels to be used for defining stability, visual field-testing techniques to define stability, the number of medication changes acceptable to define stability and the number of treatment medications allowed to define stability. No consensus was reached on the period of time over which stability was defined, however, there was considerable agreement that longer durations of follow up (36–48 months) were required. A combination of optic disc photos and ocular coherence topography (OCT) retinal nerve fibre layer (RNFL) assessment/ OCT disc structural evaluation are the preferred imaging methods for the assessment of structural stability. Oversight by a glaucoma consultant was considered important for glaucoma monitoring schemes. Conclusion: The consensus definition of glaucoma stability generated through this Delphi exercise provides guidance for allocation of patients suitable for monitoring in primary care glaucoma monitoring schemes

    Allergic lung inflammation alters neither susceptibility to Streptococcus pneumoniae infection nor inducibility of innate resistance in mice

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    <p>Abstract</p> <p>Background</p> <p>Protective host responses to respiratory pathogens are typically characterized by inflammation. However, lung inflammation is not always protective and it may even become deleterious to the host. We have recently reported substantial protection against <it>Streptococcus pneumoniae </it>(pneumococcal) pneumonia by induction of a robust inflammatory innate immune response to an inhaled bacterial lysate. Conversely, the allergic inflammation associated with asthma has been proposed to promote susceptibility to pneumococcal disease. This study sought to determine whether preexisting allergic lung inflammation influences the progression of pneumococcal pneumonia or reduces the inducibilty of protective innate immunity against bacteria.</p> <p>Methods</p> <p>To compare the effect of different inflammatory and secretory stimuli on defense against pneumonia, intraperitoneally ovalbumin-sensitized mice were challenged with inhaled pneumococci following exposure to various inhaled combinations of ovalbumin, ATP, and/or a bacterial lysate. Thus, allergic inflammation, mucin degranulation and/or stimulated innate resistance were induced prior to the infectious challenge. Pathogen killing was evaluated by assessing bacterial CFUs of lung homogenates immediately after infection, the inflammatory response to the different conditions was evaluated by measurement of cell counts of bronchoalveolar lavage fluid 18 hours after challenge, and mouse survival was assessed after seven days.</p> <p>Results</p> <p>We found no differences in survival of mice with and without allergic inflammation, nor did the induction of mucin degranulation alter survival. As we have found previously, mice treated with the bacterial lysate demonstrated substantially increased survival at seven days, and this was not altered by the presence of allergic inflammation or mucin degranulation. Allergic inflammation was associated with predominantly eosinophilic infiltration, whereas the lysate-induced response was primarily neutrophilic. The presence of allergic inflammation did not significantly alter the neutrophilic response to the lysate, and did not affect the induced bacterial killing within the lungs.</p> <p>Conclusion</p> <p>These results suggest that allergic airway inflammation neither promotes nor inhibits progression of pneumococcal lung infection in mice, nor does it influence the successful induction of stimulated innate resistance to bacteria.</p

    Genome wide association study identifies KCNMA1 contributing to human obesity

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    <p>Abstract</p> <p>Background</p> <p>Recent genome-wide association (GWA) analyses have identified common single nucleotide polymorphisms (SNPs) that are associated with obesity. However, the reported genetic variation in obesity explains only a minor fraction of the total genetic variation expected to be present in the population. Thus many genetic variants controlling obesity remain to be identified. The aim of this study was to use GWA followed by multiple stepwise validations to identify additional genes associated with obesity.</p> <p>Methods</p> <p>We performed a GWA analysis in 164 morbidly obese subjects (BMI:body mass index > 40 kg/m<sup>2</sup>) and 163 Swedish subjects (> 45 years) who had always been lean. The 700 SNPs displaying the strongest association with obesity in the GWA were analyzed in a second cohort comprising 460 morbidly obese subjects and 247 consistently lean Swedish adults. 23 SNPs remained significantly associated with obesity (nominal <it>P</it>< 0.05) and were in a step-wise manner followed up in five additional cohorts from Sweden, France, and Germany together comprising 4214 obese and 5417 lean or population-based control individuals. Three samples, n = 4133, were used to investigate the population-based associations with BMI. Gene expression in abdominal subcutaneous adipose tissue in relation to obesity was investigated for14 adults.</p> <p>Results</p> <p>Potassium channel, calcium activated, large conductance, subfamily M, alpha member <it>(KCNMA1) </it>rs2116830*G and <it>BDNF </it>rs988712*G were associated with obesity in five of six investigated case-control cohorts. In meta-analysis of 4838 obese and 5827 control subjects we obtained genome-wide significant allelic association with obesity for <it>KCNMA1 </it>rs2116830*G with <it>P </it>= 2.82 × 10<sup>-10 </sup>and an odds ratio (OR) based on cases vs controls of 1.26 [95% C.I. 1.12-1.41] and for <it>BDNF </it>rs988712*G with <it>P </it>= 5.2 × 10<sup>-17</sup>and an OR of 1.36 [95% C.I. 1.20-1.55]. <it>KCNMA1 </it>rs2116830*G was not associated with BMI in the population-based samples. Adipose tissue (<it>P </it>= 0.0001) and fat cell (<it>P </it>= 0.04) expression of <it>KCNMA1 </it>was increased in obesity.</p> <p>Conclusions</p> <p>We have identified <it>KCNMA1 </it>as a new susceptibility locus for obesity, and confirmed the association of the <it>BDNF </it>locus at the genome-wide significant level.</p

    Alternative Splicing and Nonsense-Mediated RNA Decay Contribute to the Regulation of SHOX Expression

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    The human SHOX gene is composed of seven exons and encodes a paired-related homeodomain transcription factor. SHOX mutations or deletions have been associated with different short stature syndromes implying a role in growth and bone formation. During development, SHOX is expressed in a highly specific spatiotemporal expression pattern, the underlying regulatory mechanisms of which remain largely unknown. We have analysed SHOX expression in diverse embryonic, fetal and adult human tissues and detected expression in many tissues that were not known to express SHOX before, e.g. distinct brain regions. By using RT-PCR and comparing the results with RNA-Seq data, we have identified four novel exons (exon 2a, 7-1, 7-2 and 7-3) contributing to different SHOX isoforms, and also established an expression profile for the emerging new SHOX isoforms. Interestingly, we found the exon 7 variants to be exclusively expressed in fetal neural tissues, which could argue for a specific role of these variants during brain development. A bioinformatical analysis of the three novel 3′UTR exons yielded insights into the putative role of the different 3′UTRs as targets for miRNA binding. Functional analysis revealed that inclusion of exon 2a leads to nonsense-mediated RNA decay altering SHOX expression in a tissue and time specific manner. In conclusion, SHOX expression is regulated by different mechanisms and alternative splicing coupled with nonsense-mediated RNA decay constitutes a further component that can be used to fine tune the SHOX expression level

    Complex evolutionary history of the Mexican stoneroller Campostoma ornatum Girard, 1856 (Actinopterygii: Cyprinidae)

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    <p>Abstract</p> <p>Background</p> <p>Studies of the phylogeography of Mexican species are steadily revealing genetic patterns shared by different species, which will help to unravel the complex biogeographic history of the region. <it>Campostoma ornatum </it>is a freshwater fish endemic to montane and semiarid regions in northwest Mexico and southern Arizona. Its wide range of distribution and the previously observed morphological differentiation between populations in different watersheds make this species a useful model to investigate the biogeographic role of the Sierra Madre Occidental and to disentangle the actions of Pliocene tecto-volcanic processes <it>vs </it>Quaternary climatic change. Our phylogeographic study was based on DNA sequences from one mitochondrial gene (<it>cytb</it>, 1110 bp, n = 285) and two nuclear gene regions (S7 and RAG1, 1822 bp in total, n = 56 and 43, respectively) obtained from 18 to 29 localities, in addition to a morphological survey covering the entire distribution area. Such a dataset allowed us to assess whether any of the populations/lineages sampled deserve to be categorised as an evolutionarily significant unit.</p> <p>Results</p> <p>We found two morphologically and genetically well-differentiated groups within <it>C. ornatum</it>. One is located in the northern river drainages (Yaqui, Mayo, Fuerte, Sonora, Casas Grandes, Santa Clara and Conchos) and another one is found in the southern drainages (Nazas, Aguanaval and Piaxtla). The split between these two lineages took place about 3.9 Mya (CI = 2.1-5.9). Within the northern lineage, there was strong and significant inter-basin genetic differentiation and also several secondary dispersal episodes whit gene homogenization between drainages. Interestingly, three divergent mitochondrial lineages were found in sympatry in two northern localities from the Yaqui river basin.</p> <p>Conclusions</p> <p>Our results indicate that there was isolation between the northern and southern phylogroups since the Pliocene, which was related to the formation of the ancient Nazas River paleosystem, where the southern group originated. Within groups, a complex reticulate biogeographic history for <it>C. ornatum </it>populations emerges, following the taxon pulse theory and mainly related with Pliocene tecto-volcanic processes. In the northern group, several events of vicariance promoted by river or drainage isolation episodes were found, but within both groups, the phylogeographic patterns suggest the occurrence of several events of river capture and fauna interchange. The Yaqui River supports the most diverse populations of <it>C. ornatum</it>, with several events of dispersal and isolation within the basin. Based on our genetic results, we defined three ESUs within <it>C. ornatum </it>as a first attempt to promote the conservation of the evolutionary processes determining the genetic diversity of this species. They will likely be revealed as a valuable tool for freshwater conservation policies in northwest Mexico, where many environmental problems concerning the use of water have rapidly arisen in recent decades.</p
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