459 research outputs found
Populations of a Susceptible Amphibian Species Can Grow despite the Presence of a Pathogenic Chytrid Fungus
Disease can be an important driver of host population dynamics and epizootics can cause severe host population declines. Batrachochytrium dendrobatidis (Bd), the pathogen causing amphibian chytridiomycosis, may occur epizootically or enzootically and can harm amphibian populations in many ways. While effects of Bd epizootics are well documented, the effects of enzootic Bd have rarely been described. We used a state-space model that accounts for observation error to test whether population trends of a species highly susceptible to Bd, the midwife toad Alytes obstetricans, are negatively affected by the enzootic presence of the pathogen. Unexpectedly, Bd had no negative effect on population growth rates from 2002–2008. This suggests that negative effects of disease on individuals do not necessarily translate into negative effects at the population level. Populations of amphibian species that are susceptible to the emerging disease chytridiomycosis can persist despite the enzootic presence of the pathogen under current environmental conditions
Ecoregional Analysis of Nearshore Sea-Surface Temperature in the North Pacific
The quantification and description of sea surface temperature (SST) is critically important because it can influence the distribution, migration, and invasion of marine species; furthermore, SSTs are expected to be affected by climate change. To better understand present temperature regimes, we assembled a 29-year nearshore time series of mean monthly SSTs along the North Pacific coastline using remotely-sensed satellite data collected with the Advanced Very High Resolution Radiometer (AVHRR) instrument. We then used the dataset to describe nearshore (<20 km offshore) SST patterns of 16 North Pacific ecoregions delineated by the Marine Ecoregions of the World (MEOW) hierarchical schema. Annual mean temperature varied from 3.8°C along the Kamchatka ecoregion to 24.8°C in the Cortezian ecoregion. There are smaller annual ranges and less variability in SST in the Northeast Pacific relative to the Northwest Pacific. Within the 16 ecoregions, 31–94% of the variance in SST is explained by the annual cycle, with the annual cycle explaining the least variation in the Northern California ecoregion and the most variation in the Yellow Sea ecoregion. Clustering on mean monthly SSTs of each ecoregion showed a clear break between the ecoregions within the Warm and Cold Temperate provinces of the MEOW schema, though several of the ecoregions contained within the provinces did not show a significant difference in mean seasonal temperature patterns. Comparison of these temperature patterns shared some similarities and differences with previous biogeographic classifications and the Large Marine Ecosystems (LMEs). Finally, we provide a web link to the processed data for use by other researchers
Use of low-dose oral theophylline as an adjunct to inhaled corticosteroids in preventing exacerbations of chronic obstructive pulmonary disease: study protocol for a randomised controlled trial.
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with high morbidity, mortality, and health-care costs. An incomplete response to the anti-inflammatory effects of inhaled corticosteroids is present in COPD. Preclinical work indicates that 'low dose' theophylline improves steroid responsiveness. The Theophylline With Inhaled Corticosteroids (TWICS) trial investigates whether the addition of 'low dose' theophylline to inhaled corticosteroids has clinical and cost-effective benefits in COPD. METHOD/DESIGN: TWICS is a randomised double-blind placebo-controlled trial conducted in primary and secondary care sites in the UK. The inclusion criteria are the following: an established predominant respiratory diagnosis of COPD (post-bronchodilator forced expiratory volume in first second/forced vital capacity [FEV1/FVC] of less than 0.7), age of at least 40 years, smoking history of at least 10 pack-years, current inhaled corticosteroid use, and history of at least two exacerbations requiring treatment with antibiotics or oral corticosteroids in the previous year. A computerised randomisation system will stratify 1424 participants by region and recruitment setting (primary and secondary) and then randomly assign with equal probability to intervention or control arms. Participants will receive either 'low dose' theophylline (Uniphyllin MR 200 mg tablets) or placebo for 52 weeks. Dosing is based on pharmacokinetic modelling to achieve a steady-state serum theophylline of 1-5 mg/l. A dose of theophylline MR 200 mg once daily (or placebo once daily) will be taken by participants who do not smoke or participants who smoke but have an ideal body weight (IBW) of not more than 60 kg. A dose of theophylline MR 200 mg twice daily (or placebo twice daily) will be taken by participants who smoke and have an IBW of more than 60 kg. Participants will be reviewed at recruitment and after 6 and 12 months. The primary outcome is the total number of participant-reported COPD exacerbations requiring oral corticosteroids or antibiotics during the 52-week treatment period. DISCUSSION: The demonstration that 'low dose' theophylline increases the efficacy of inhaled corticosteroids in COPD by reducing the incidence of exacerbations is relevant not only to patients and clinicians but also to health-care providers, both in the UK and globally. TRIAL REGISTRATION: Current Controlled Trials ISRCTN27066620 was registered on Sept. 19, 2013, and the first subject was randomly assigned on Feb. 6, 2014
Cost-Effectiveness of a Chemoprophylactic Intervention with Single Dose Rifampicin in Contacts of New Leprosy Patients
In 2008, 249,007 new leprosy patients were detected in the world. It therefore remains necessary to develop new and effective interventions to interrupt the transmission of M. leprae. We assessed the economic benefits of single dose rifampicin (SDR) for contacts as chemoprophylactic intervention in the control of leprosy. The study is based on a large trial including 21,711 contacts of 1,037 patients with newly diagnosed leprosy. We gave a single dose of rifampicin or placebo to contacts and followed them up for four years. The main outcome measure was the development of clinical leprosy. The cost effectiveness was expressed in US dollars per prevented leprosy case. Chemoprophylaxis with SDR for preventing leprosy among contacts of leprosy patients is cost-effective at all contact levels and thereby a cost-effective prevention strategy. In total 158 per prevented leprosy case. Implementation studies are necessary to establish whether this intervention is acceptable and feasible in other leprosy endemic areas of the world
Neonatal hearing screening: modelling cost and effectiveness of hospital- and community-based screening
BACKGROUND: Children with congenital hearing impairment benefit from early detection and management of their hearing loss. These and related considerations led to the recommendation of universal newborn hearing screening. In 2001 the first phase of a national Newborn Hearing Screening Programme (NHSP) was implemented in England. Objective of this study was to assess costs and effectiveness for hospital and community-based newborn hearing screening systems in England based on data from this first phase with regard to the effects of alterations to parameter values. METHODS: Design: Clinical effectiveness analysis using a Markov Model. Outcome measure: quality weighted detected child months (QCM). RESULTS: Both hospital and community programmes yielded 794 QCM at the age of 6 months with total costs of £3,690,000 per 100,000 screened children in hospital and £3,340,000 in community. Simulated costs would be lower in hospital in 48% of the trials. Any statistically significant difference between hospital and community in prevalence, test sensitivity, test specificity and costs would result in significant differences in cost-effectiveness between hospital and community. CONCLUSION: This modelling exercise informs decision makers by a quantitative projection of available data and the explicit and transparent statements about assumptions and the degree of uncertainty. Further evaluation of the cost-effectiveness should focus on the potential differences in test parameters and prevalence in these two settings
Cold gas accretion in galaxies
Evidence for the accretion of cold gas in galaxies has been rapidly
accumulating in the past years. HI observations of galaxies and their
environment have brought to light new facts and phenomena which are evidence of
ongoing or recent accretion:
1) A large number of galaxies are accompanied by gas-rich dwarfs or are
surrounded by HI cloud complexes, tails and filaments. It may be regarded as
direct evidence of cold gas accretion in the local universe. It is probably the
same kind of phenomenon of material infall as the stellar streams observed in
the halos of our galaxy and M31. 2) Considerable amounts of extra-planar HI
have been found in nearby spiral galaxies. While a large fraction of this gas
is produced by galactic fountains, it is likely that a part of it is of
extragalactic origin. 3) Spirals are known to have extended and warped outer
layers of HI. It is not clear how these have formed, and how and for how long
the warps can be sustained. Gas infall has been proposed as the origin. 4) The
majority of galactic disks are lopsided in their morphology as well as in their
kinematics. Also here recent accretion has been advocated as a possible cause.
In our view, accretion takes place both through the arrival and merging of
gas-rich satellites and through gas infall from the intergalactic medium (IGM).
The infall may have observable effects on the disk such as bursts of star
formation and lopsidedness. We infer a mean ``visible'' accretion rate of cold
gas in galaxies of at least 0.2 Msol/yr. In order to reach the accretion rates
needed to sustain the observed star formation (~1 Msol/yr), additional infall
of large amounts of gas from the IGM seems to be required.Comment: To appear in Astronomy & Astrophysics Reviews. 34 pages.
Full-resolution version available at
http://www.astron.nl/~oosterlo/accretionRevie
The cost effectiveness of elective laparoscopic sigmoid resection for symptomatic diverticular disease: financial outcome of the randomized control Sigma trial
On the effects of the fix geometric constraint in 2D profiles on the reusability of parametric 3D CAD models
[EN] In order to be reusable, history-based feature-based parametric CAD models must reliably allow for modifications while maintaining their original design intent. In this paper, we demonstrate that relations that fix the location of geometric entities relative to the reference system produce inflexible profiles that reduce model reusability. We present the results of an experiment where novice students and expert CAD users performed a series of modifications in different versions of the same 2D profile, each defined with an increasingly higher number of fix geometric constraints. Results show that the amount of fix constraints in a 2D profile correlates with the time required to complete reusability tasks, i.e., the higher the number of fix constraints in a 2D profile, the less flexible and adaptable the profile becomes to changes. In addition, a pilot software tool to automatically track this type of constraints was developed and tested. Results suggest that the detection of fix constraint overuse may result in a new metric to assess poor quality models with low reusability. The tool provides immediate feedback for preventing high semantic level quality errors, and assistance to CAD users. Finally, suggestions are introduced on how to convert fix constraints in 2D profiles into a negative metric of 3D model quality.The authors would like to thank Raquel Plumed for her support in the statistical analysis. This work has been partially funded by Grant UJI-A02017-15 (Universitat Jaume I) and DPI201784526-R (MINECO/AEI/FEDER, UE), project CAL-MBE. The authors also wish to thank the editor and reviewers for their valuable comments and suggestions that helped us improve the quality of the paper.González-Lluch, C.; Company, P.; Contero, M.; Pérez Lopez, DC.; Camba, JD. (2019). On the effects of the fix geometric constraint in 2D profiles on the reusability of parametric 3D CAD models. International Journal of Technology and Design Education. 29(4):821-841. https://doi.org/10.1007/s10798-018-9458-zS821841294Ait-Aoudia, S., & Foufou, S. (2010). A 2D geometric constraint solver using a graph reduction method. Advances in Engineering Software, 41(10), 1187–1194. https://doi.org/10.1016/j.advengsoft.2010.07.008 .Ault, H. K. (1999). Using geometric constraints to capture design intent. Journal for Geometry and Graphics, 3(1), 39–45.Ault, H. K. (2004). Over-constrained, under-constrained or just right? Goldilocks evaluates DOF of sketched profiles. Paper presented at American Society for Engineering Education, 59th annual midyear meeting past, present and future? Williamsburg, November 21–23.Ault, H. K., Bu, L., & Liu, K. (2014). Solid modeling strategies-analyzing student choices. Paper presented at proceedings of the 121st ASEE annual conference and exposition, Indianapolis, June 15–18.Ault, H. K., & Fraser, A. (2013). A comparison of manual vs. online grading for solid models. Paper presented at 120th ASEE annual conference and exposition, Atlanta, GA, June 23–26, 2013, Paper ID #7233.Barbero, B. R., Pedrosa, C. M., & Samperio, R. Z. (2016). Learning CAD at university through summaries of the rules of design intent. International Journal of Technology and Design Education. https://doi.org/10.1007/s10798-016-9358-z .Bodein, Y., Bertrand, R., & Caillaud, E. (2014). Explicit reference modeling methodology in parametric CAD system. Computers in Industry, 65(1), 136–147. https://doi.org/10.1016/j.compind.2013.08.004 .Bouma, W., Fudos, I., Hoffmann, C., Cai, J., & Paige, R. (1995). Geometric constraint solver. Computer-Aided Design, 27(6), 487–501. https://doi.org/10.1016/0010-4485(94)00013-4 .Briggs, J. C., Hepworth, A. I., Stone, B. R., Cobum, J. Q., Jensen, C. G., & Red, E. (2015). Integrated, synchronous multi-user design and analysis. Journal of Computing and Information Science in Engineering, 15(3), 031002. https://doi.org/10.1115/1.4029801 .Buckley, J., Seery, N., & Canty, D. (2017). Heuristics and CAD modelling: An examination of student behaviour during problem solving episodes within CAD modelling activities. International Journal of Technology and Design Education. https://doi.org/10.1007/s10798-017-9423-2 .Camba, J. D., & Contero, M. (2015). Assessing the impact of geometric design intent annotations on parametric model alteration activities. Computers in Industry, 71, 35–45. https://doi.org/10.1016/j.compind.2015.03.006 .Camba, J. D., Contero, M., & Company, P. (2016). Parametric CAD modeling: An analysis of strategies for design reusability. Computer-Aided Design, 74, 18–31. https://doi.org/10.1016/j.cad.2016.01.003 .Camba, J. D., Contero, M., & Company, P. (2017). CAD reusability and the role of modeling information in the MBE context. Model-based enterprise summit 2017. National Institute of Standards and Technology (NIST), Gaithersburg, MD, April 3–7. MBE17-020. https://www.nist.gov/file/361581 .Cheng, Z., & Ma, Y. (2017). A functional feature modeling method. Advanced Engineering Informatics, 33, 1–15. https://doi.org/10.1016/j.aei.2017.04.003 .Cheng, Z., Xie, Y., & Ma, Y. (2018). Graph centrality analysis of feature dependencies to unveil modeling intents. Computer-Aided Design and Applications. https://doi.org/10.1080/16864360.2018.1441236 .Chester, I. (2007). Teaching for CAD expertise. International Journal of Technology and Design Education, 17, 23–35. https://doi.org/10.1007/s10798-006-9015-z .Company, P., Contero, M., Otey, J., & Plumed, R. (2015). Approach for developing coordinated rubrics to convey quality criteria in CAD training. Computer-Aided Design, 63, 101–117. https://doi.org/10.1016/j.cad.2014.10.00 .Company, P., & González-Lluch, C. (2013). CAD 3D con SolidWorks ® Tomo I: Diseño básico. Publicacions de la Universitat Jaume I. (Colección Sapientia, Núm. 86). http://cad3dconsolidworks.uji.es .Contero, M., Company, P., Vila, C., & Aleixos, N. (2002). Product data quality and collaborative engineering. IEEE Computer Graphics Applications, 22(3), 32–42. https://doi.org/10.1109/MCG.2002.999786 .Dixon, B. M., & Dannenhoffer, J. F., III. (2014). Geometric sketch constraint solving with user feedback. Journal of Aerospace Information Systems, 11(5), 316–325. https://doi.org/10.2514/1.I010110 .Fudos, I., & Hoffmann, C. M. (1997). A graph-constructive approach to solving systems of geometric constraints. ACM Transactions on Graphics, 16(2), 179–216. https://doi.org/10.1145/248210.248223 .Ge, J. X., Chou, S. C., & Gao, X. S. (1999). Geometric constraint satisfaction using optimization methods. Computer-Aided Design, 31(14), 867–879. https://doi.org/10.1016/S0010-4485(99)00074-3 .González-Lluch, C., Company, P., Contero, M., Camba, J. D., & Colom, J. (2017a). A case study on the use of model quality testing tools for the assessment of MCAD models and drawings. International Journal of Engineering Education, 33(5), 1643–1653.González-Lluch, C., Company, P., Contero, M., Camba, J. D., & Plumed, R. (2017b). A survey on 3D CAD model quality assurance and testing tools. Computer-Aided Design, 83, 64–79. https://doi.org/10.1016/j.cad.2016.10.003 .Hamade, R. F. (2009). Profiling the desirable CAD trainee: Technical background, personality attributes, and learning preferences. Journal of Mechanical Design, 131(12), 121009–121019. https://doi.org/10.1115/1.4000455 .Hekman, K. A., & Gordon, M. T. (2013). Automated grading of first year student CAD work. Paper presented at the 120th ASEE annual conference and exposition 2013, Atlanta, GA, June 23–26. Paper ID #6379.Hepworth, A., Tew, K., Trent, M., Ricks, R., Jensen, C. G., & Red, E. R. (2014). Model consistency and conflict resolution with data preservation in multi-user computer aided design. Journal of Computing and Information Science in Engineering, 14(2), 021008. https://doi.org/10.1115/1.4026553 .Jackson, C., & Buxton, M. (2007). The design reuse benchmark report: Seizing the opportunity to shorten product development. Boston: Aberdeen Group.Joan-Arinyo, R., Soto-Riera, A., Vila-Marta, S., & Vilaplana-Pastó, J. (2003). Transforming an under-constrained geometric constraint problem into a well-constrained one. Paper presented at proceedings of ACM SM03, Seatle, June 16–20.Kirstukas, S. J. (2016). Development and evaluation of a computer program to assess student CAD models. Paper presented at ASEE annual conference and exposition, New Orleans, June 26.Kramer, G. (1991). Using degrees of freedom analysis to solve geometric constraint systems. Paper presented at proceedings of the first ACM symposium on solid modeling foundations and CAD/CAM applications 1991, Austin, June 05–07.Kwon, S., Kim, B. C., Mun, D., & Han, S. (2015). Graph-based simplification of feature-based three-dimensional computer-aided design models for preserving connectivity. Journal of Computing and Information Science in Engineering, 15(3), 031010. https://doi.org/10.1115/1.4030748 .Leea, J. Y., & Kimb, K. (1998). A 2-D geometric constraint solver using DOF-based graph reduction. Computer-Aided Design, 30(11), 883–896. https://doi.org/10.1016/S0010-4485(98)00045-1 .Mata Burgarolas, N. (1997). Solving incidence and tangency constraints in 2D. Technical report LSI-97-3R, Departament LiSI, Universitat Politècnica de Catalunya.Petrina, S. (2003). Two cultures of technical courses and discourses: The case of computer aided design. International Journal of Technology and Design Education, 13, 47–73.Race, P. (2001). The lecturers toolkit—A practical guide to learning, teaching and assessment. Great Britain: Glasgow.Red, E., French, D., Jensen, G., Walker, S. S., & Madsen, P. (2013). Emerging design methods and tools in collaborative product development. Journal of Computing and Information Science in Engineering, 13(3), 031001. https://doi.org/10.1115/1.4023917 .Robertson, B. F., Walther, J., & Radcliffe, D. (2007). Creativity and the use of CAD tools: Lessons for engineering design education from industry. Journal of Mechanical Design, 129(7), 753–760. https://doi.org/10.1115/1.2722329 .Stone, B., Salmon, J., Eves, K., Killian, M., Wright, L., Oldroyd, J., et al. (2017). A multi-user computer-aided design competition: Experimental findings and analysis of team-member dynamics. Journal of Computing and Information Science in Engineering, 17(3), 031003. https://doi.org/10.1115/1.4035674 .Summers, J. D., & Shah, J. J. (2010). Mechanical engineering design complexity metrics: Size, coupling, and solvability. Journal of Mechanical Design, 132(2), 21004–21015. https://doi.org/10.1115/1.4000759 .Szewczyk, J. (2003). Difficulties with the novices’ comprehension of the computer-aided design (CAD) interface: Understanding visual representations of CAD tools. Journal of Engineering Design, 14(2), 169–185. https://doi.org/10.1080/0954482031000091491
Within- and Among-Population Variation in Chytridiomycosis-Induced Mortality in the Toad Alytes obstetricans
Background
Chytridiomycosis is a fungal disease linked to local and global extinctions of amphibians. Susceptibility to chytridiomycosis varies greatly between amphibian species, but little is known about between- and within-population variability. However, this kind of variability is the basis for the evolution of tolerance and resistance evolution to disease.
Methodology/Principal Findings
In a common garden experiment, we measured mortality after metamorphosis of Alytes obstetricans naturally infected with Batrachochytrium dendrobatidis. Mortality rates differed significantly among populations and ranged from 27 to 90%. Within populations, mortality strongly depended on mass at and time through metamorphosis.
Conclusions/Significance
Although we cannot rule out that the differences observed resulted from differences in skin microbiota, different pathogen strains or environmental effects experienced by the host or the pathogen prior to the start of the experiment, we argue that genetic differences between populations are a likely source of at least part of this variation. To our knowledge, this is the first study showing differences in survival between and within populations under constant laboratory conditions. Assuming that some of this intraspecific variation has a genetic basis, this may suggest that there is the potential for the evolution of resistance or tolerance, which might allow population persistence
Cryo-EM structure of lysenin pore elucidates membrane insertion by an aerolysin family protein
Lysenin from the coelomic fluid of the earthworm Eisenia fetida belongs to the aerolysin family of small β-pore-forming toxins (β-PFTs), some members of which are pathogenic to humans and animals. Despite efforts, a high-resolution structure of a channel for this family of proteins has been elusive and therefore the mechanism of activation and membrane insertion remains unclear. Here we determine the pore structure of lysenin by single particle cryo-EM, to 3.1 Å resolution. The nonameric assembly reveals a long β-barrel channel spanning the length of the complex that, unexpectedly, includes the two pre-insertion strands flanking the hypothetical membrane-insertion loop. Examination of other members of the aerolysin family reveals high structural preservation in this region, indicating that the membrane-insertion pathway in this family is conserved. For some toxins, proteolytic activation and pro-peptide removal will facilitate unfolding of the pre-insertion strands, allowing them to form the β-barrel of the channel
- …