101 research outputs found

    Spontaneous pneumothorax can be associated with TGFBR2 mutation.

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    TGFBR2 mutations that cause Loeys-Dietz Syndrome can present as pneumothorax. In vitro kinase assays can help confirm pathogenicity of novel variants.SJM is an MRC Senior Clinical FellowThis is the author accepted manuscript. The final version is available from the European Respiratory Society via http://dx.doi.org/10.1183/13993003.00952-201

    Adaptive time-lapse optimized survey design for electrical resistivity tomography monitoring

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    Adaptive optimal experimental design methods use previous data and results to guide the choice and design of future experiments. This paper describes the formulation of an adaptive survey design technique to produce optimal resistivity imaging surveys for time-lapse geoelectrical monitoring experiments. These survey designs are time-dependent and, compared to dipole–dipole or static optimized surveys that do not change over time, focus a greater degree of the image resolution on regions of the subsurface that are actively changing. The adaptive optimization method is validated using a controlled laboratory monitoring experiment comprising a well-defined cylindrical target moving along a trajectory that changes its depth and lateral position. The algorithm is implemented on a standard PC in conjunction with a modified automated multichannel resistivity imaging system. Data acquisition using the adaptive survey designs requires no more time or power than with comparable standard surveys, and the algorithm processing takes place while the system batteries recharge. The results show that adaptively designed optimal surveys yield a quantitative increase in image quality over and above that produced by using standard dipole–dipole or static (time–independent) optimized surveys

    Adaptive time-lapse optimized survey design for electrical resistivity tomography monitoring

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    Adaptive optimal experimental design methods use previous data and results to guide the choice and design of future experiments. This paper describes the formulation of an adaptive survey design technique to produce optimal resistivity imaging surveys for time-lapse geoelectrical monitoring experiments. These survey designs are time-dependent and, compared to dipole-dipole or static optimized surveys that do not change over time, focus a greater degree of the image resolution on regions of the subsurface that are actively changing. The adaptive optimization method is validated using a controlled laboratory monitoring experiment comprising a well-defined cylindrical target moving along a trajectory that changes its depth and lateral position. The algorithm is implemented on a standard PC in conjunction with a modified automated multichannel resistivity imaging system. Data acquisition using the adaptive survey designs requires no more time or power than with comparable standard surveys, and the algorithm processing takes place while the system batteries recharge. The results show that adaptively designed optimal surveys yield a quantitative increase in image quality over and above that produced by using standard dipole-dipole or static (time-independent) optimized survey

    Actin dynamics tune the integrated stress response by regulating eukaryotic initiation factor 2α dephosphorylation.

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    Four stress-sensing kinases phosphorylate the alpha subunit of eukaryotic translation initiation factor 2 (eIF2α) to activate the integrated stress response (ISR). In animals, the ISR is antagonised by selective eIF2α phosphatases comprising a catalytic protein phosphatase 1 (PP1) subunit in complex with a PPP1R15-type regulatory subunit. An unbiased search for additional conserved components of the PPP1R15-PP1 phosphatase identified monomeric G-actin. Like PP1, G-actin associated with the functional core of PPP1R15 family members and G-actin depletion, by the marine toxin jasplakinolide, destabilised the endogenous PPP1R15A-PP1 complex. The abundance of the ternary PPP1R15-PP1-G-actin complex was responsive to global changes in the polymeric status of actin, as was its eIF2α-directed phosphatase activity, while localised G-actin depletion at sites enriched for PPP1R15 enhanced eIF2α phosphorylation and the downstream ISR. G-actin's role as a stabilizer of the PPP1R15-containing holophosphatase provides a mechanism for integrating signals regulating actin dynamics with stresses that trigger the ISR.This work was funded by the Medical Research Council (UK) (MRC Ref G1002610) and a Wellcome Trust Strategic Award for core facilities to the Cambridge Institute for Medical Research (CIMR, Wellcome 100140). SJM holds a Senior Clinical Research Fellowship from the Medical Research Council (MRC Ref G1002610). DR is a Wellcome Trust Principal Research Fellow (Wellcome 084812/Z/08/Z). The June Hancock Mesothelioma Research Fund funded LED (JH09-2); the British Lung Foundation funded HJC (APHD11-4); CD is a member of the CIMR PhD programme funded by the Wellcome Trust; and VP holds a Diabetes UK Arthur and Sadie Pethybridge PhD Studentship.This is the final published version. It first appeared at http://elifesciences.org/content/4/e04872

    Inactivation of Ppp1r15a minimises weight gain and insulin resistance during caloric excess in female mice.

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    Phosphorylation of the translation initiation factor eIF2α within the mediobasal hypothalamus is known to suppress food intake, but the role of the eIF2α phosphatases in regulating body weight is poorly understood. Mice deficient in active PPP1R15A, a stress-inducible eIF2α phosphatase, are healthy and more resistant to endoplasmic reticulum stress than wild type controls. We report that when female Ppp1r15a mutant mice are fed a high fat diet they gain less weight than wild type littermates owing to reduced food intake. This results in healthy leaner Ppp1r15a mutant animals with reduced hepatic steatosis and improved insulin sensitivity, albeit with a possible modest defect in insulin secretion. By contrast, no weight differences are observed between wild type and Ppp1r15a deficient mice fed a standard diet. We conclude that female mice lacking the C-terminal PP1-binding domain of PPP1R15A show reduced dietary intake and preserved glucose tolerance. Our data indicate that this results in reduced weight gain and protection from diet-induced obesity.The work was also supported by Diabetes UK and the MRC [G1002610]. VP held an Arthur and Sadie Pethybridge PhD Studentship from Diabetes UK. The CIMR microscopy core facility is supported by a Wellcome Trust Strategic Award [100140] and a Wellcome Trust equipment grant [093026]

    Ten-Year Analysis of Bacterial Colonisation and Outcomes of Major Burn Patients with a Focus on Pseudomonas aeruginosa

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    A retrospective descriptive study included patients admitted with severe burns over the course of 10 years (2008–2018). Across all patients, there were 39 different species of bacteria, with 23 species being Gram-negative and 16 being Gram-positive bacteria, with also five different species of fungi cultured. Pseudomonas aeruginosa was the most commonly isolated organism, with 57.45% of patients having a positive culture. There was a significant difference in the number of P. aeruginosa isolated from patients that acquired their burns at work, in a garden, inside a vehicle, in a garage or in a public place. In patients that were positive for P. aeruginosa, the number of operations was higher (2.4) and the length of stay was significantly increased (80.1 days). Patients that suffered from substance abuse demonstrated significantly higher numbers of isolated P. aeruginosa (14.8%). Patients that suffered from both mental health illness and substance abuse demonstrated significantly higher numbers of P. aeruginosa isolated (18.5%). In the P. aeruginosa-negative group, there were significantly fewer patients that had been involved in a clothing fire. Furthermore, in the P. aeruginosa-negative patient cohort, the mortality rate was significantly higher (p = 0.002). Since the incidence of P. aeruginosa was also associated with a decreased mortality rate, it may be that patients admitted to hospital for shorter periods of time were less likely to be colonised with P. aeruginosa. This study demonstrates novel factors that may increase the incidence of P. aeruginosa isolated from burn patients

    The effects of changes in the order of verbal labels and numerical values on children's scores on attitude and rating scales

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    Research with adults has shown that variations in verbal labels and numerical scale values on rating scales can affect the responses given. However, few studies have been conducted with children. The study aimed to examine potential differences in children’s responses to Likert-type rating scales according to their anchor points and scale direction, and to see whether or not such differences were stable over time. 130 British children, aged 9 to 11, completed six sets of Likert-type rating scales, presented in four different ways varying the position of positive labels and numerical values. The results showed, both initially and 8-12 weeks later, that presenting a positive label or a high score on the left of a scale led to significantly higher mean scores than did the other variations. These findings indicate that different arrangements of rating scales can produce different results which has clear implications for the administration of scales with children

    Seasonal trends of Amazonian rainforest phenology, net primary productivity, and carbon allocation.:Seasonal trends of Amazonian forests.

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    The seasonality of solar irradiance and precipitation may regulate seasonal variations in tropical forests carbon cycling. Controversy remains over their importance as drivers of seasonal dynamics of net primary productivity in tropical forests. We use ground data from nine lowland Amazonian forest plots collected over 3 years to quantify the monthly primary productivity (NPP) of leaves, reproductive material, woody material, and fine roots over an annual cycle. We distinguish between forests that do not experience substantial seasonal moisture stress (“humid sites”) and forests that experience a stronger dry season (“dry sites”). We find that forests from both precipitation regimes maximize leaf NPP over the drier season, with a peak in production in August at both humid (mean 0.39 ± 0.03 Mg C ha−1 month−1 in July, n = 4) and dry sites (mean 0.49 ± 0.03 Mg C ha−1 month−1 in September, n = 8). We identify two distinct seasonal carbon allocation patterns (the allocation of NPP to a specific organ such as wood leaves or fine roots divided by total NPP). The forests monitored in the present study show evidence of either (i) constant allocation to roots and a seasonal trade-off between leaf and woody material or (ii) constant allocation to wood and a seasonal trade-off between roots and leaves. Finally, we find strong evidence of synchronized flowering at the end of the dry season in both precipitation regimes. Flower production reaches a maximum of 0.047 ± 0.013 and 0.031 ± 0.004 Mg C ha−1 month−1 in November, in humid and dry sites, respectively. Fruitfall production was staggered throughout the year, probably reflecting the high variation in varying times to development and loss of fruit among species
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