British Society of Echocardiography guideline for the transthoracic echocardiographic assessment of cardiac amyloidosis

These guidelines form an update of the BSE guideline protocol for the assessment of restrictive cardiomyopathy (Knight et al. in Echo Res Prac, 2013). Since the original recommendations were conceived in 2013, there has been an exponential rise in the diagnosis of cardiac amyloidosis fuelled by increased clinician awareness, improvements in cardiovascular imaging as well as the availability of new and effective disease modifying therapies. The initial diagnosis of cardiac amyloidosis can be challenging and is often not clear-cut on the basis of echocardiography, which for most patients presenting with heart failure symptoms remains the first-line imaging test. The role of a specialist echocardiographer will be to raise the suspicion of cardiac amyloidosis when appropriate, but the formal diagnosis of amyloid sub-type invariably requires further downstream testing. This document seeks to provide a focused review of the literature on echocardiography in cardiac amyloidosis highlighting its important role in the diagnosis, prognosis and screening of at risk individuals, before concluding with a suggested minimum data set, for use as an aide memoire when reporting

Rank Analysis of Cubic Multivariate Cryptosystems

In this work we analyze the security of cubic cryptographic constructions with respect to rank weakness. We detail how to extend the big field idea from quadratic to cubic, and show that the same rank defect occurs. We extend the min-rank problem and propose an algorithm to solve it in this setting. We show that for fixed small rank, the complexity is even lower than for the quadratic case. However, the rank of a cubic polynomial in $n$ variables can be larger than $n$, and in this case the algorithm is very inefficient. We show that the rank of the differential is not necessarily smaller, rendering this line of attack useless if the rank is large enough. Similarly, the algebraic attack is exponential in the rank, thus useless for high rank

Clinical and Genetic Evaluation of People with or at Risk of Hereditary ATTR Amyloidosis: An Expert Opinion and Consensus on Best Practice in Ireland and the UK

Hereditary transthyretin-mediated amyloidosis (hATTR) is challenging to diagnose early owing to the heterogeneity of clinical presentation, which differs according to the TTR gene variant and its penetrance in each individual. The TTR variants seen most frequently in the UK and Ireland (T80A, V142I and V50M) differ to those commonly occurring in other geographic locations and warrant a specific consideration for diagnosis and genetic testing. In addition, recent availability of treatment for this condition has reinforced the need for a more consistent approach to the management of patients, including access to specialist services, genetic testing and counselling, and clinical investigation for families living in the UK and Ireland. A multidisciplinary panel of experts from the UK and Ireland was convened to identify the current challenges, provide recommendations, and develop a consensus for the diagnosis and screening of people with, or at risk of, hATTR. Over a series of meetings, experts shared their current practices and drafted, refined and approved a consensus statement. This consensus statement provides recommendations for three different groups: (1) people with symptoms raising a possibility of hATTR amyloidosis; (2) people with biopsy-confirmed hATTR amyloidosis; and (3) people without symptoms who may have hATTR amyloidosis (i.e. relatives of people with identified TTR variants). For each group, recommendations are made for the required steps for the diagnosis and follow-up of symptomatic patients, and for guidance on the specialist support for counselling and pre-symptomatic genetic testing of at-risk individuals. This guidance is intended to be practical and based on available evidence. The aim is for regional amyloid specialist centres to provide timely diagnosis, clinical screening, and treatment for individuals and their families with hATTR amyloidosis

Strong Ultraviolet Pulse From a Newborn Type Ia Supernova

Type Ia supernovae are destructive explosions of carbon oxygen white dwarfs. Although they are used empirically to measure cosmological distances, the nature of their progenitors remains mysterious, One of the leading progenitor models, called the single degenerate channel, hypothesizes that a white dwarf accretes matter from a companion star and the resulting increase in its central pressure and temperature ignites thermonuclear explosion. Here we report observations of strong but declining ultraviolet emission from a Type Ia supernova within four days of its explosion. This emission is consistent with theoretical expectations of collision between material ejected by the supernova and a companion star, and therefore provides evidence that some Type Ia supernovae arise from the single degenerate channel.Comment: Accepted for publication on the 21 May 2015 issue of Natur

Evaluation of the current knowledge limitations in breast cancer research: a gap analysis

BACKGROUND A gap analysis was conducted to determine which areas of breast cancer research, if targeted by researchers and funding bodies, could produce the greatest impact on patients. METHODS Fifty-six Breast Cancer Campaign grant holders and prominent UK breast cancer researchers participated in a gap analysis of current breast cancer research. Before, during and following the meeting, groups in seven key research areas participated in cycles of presentation, literature review and discussion. Summary papers were prepared by each group and collated into this position paper highlighting the research gaps, with recommendations for action. RESULTS Gaps were identified in all seven themes. General barriers to progress were lack of financial and practical resources, and poor collaboration between disciplines. Critical gaps in each theme included: (1) genetics (knowledge of genetic changes, their effects and interactions); (2) initiation of breast cancer (how developmental signalling pathways cause ductal elongation and branching at the cellular level and influence stem cell dynamics, and how their disruption initiates tumour formation); (3) progression of breast cancer (deciphering the intracellular and extracellular regulators of early progression, tumour growth, angiogenesis and metastasis); (4) therapies and targets (understanding who develops advanced disease); (5) disease markers (incorporating intelligent trial design into all studies to ensure new treatments are tested in patient groups stratified using biomarkers); (6) prevention (strategies to prevent oestrogen-receptor negative tumours and the long-term effects of chemoprevention for oestrogen-receptor positive tumours); (7) psychosocial aspects of cancer (the use of appropriate psychosocial interventions, and the personal impact of all stages of the disease among patients from a range of ethnic and demographic backgrounds). CONCLUSION Through recommendations to address these gaps with future research, the long-term benefits to patients will include: better estimation of risk in families with breast cancer and strategies to reduce risk; better prediction of drug response and patient prognosis; improved tailoring of treatments to patient subgroups and development of new therapeutic approaches; earlier initiation of treatment; more effective use of resources for screening populations; and an enhanced experience for people with or at risk of breast cancer and their families. The challenge to funding bodies and researchers in all disciplines is to focus on these gaps and to drive advances in knowledge into improvements in patient care

A Macrophage Response to Mycobacterium leprae Phenolic Glycolipid Initiates Nerve Damage in Leprosy

$\textit{Mycobacterium leprae}$ causes leprosy and is unique among mycobacterial diseases in producing peripheral neuropathy. This debilitating morbidity is attributed to axon demyelination resulting from direct interaction of the $\textit{M. leprae}$-specific phenolic glycolipid 1 (PGL-1) with myelinating glia and their subsequent infection. Here, we use transparent zebrafish larvae to visualize the earliest events of $\textit{M. leprae}$-induced nerve damage. We find that demyelination and axonal damage are not directly initiated by $\textit{M. leprae}$ but by infected macrophages that patrol axons; demyelination occurs in areas of intimate contact. PGL-1 confers this neurotoxic response on macrophages: macrophages infected with $\textit{M. marinum}$-expressing PGL-1 also damage axons. PGL-1 induces nitric oxide synthase in infected macrophages, and the resultant increase in reactive nitrogen species damages axons by injuring their mitochondria and inducing demyelination. Our findings implicate the response of innate macrophages to $\textit{M. leprae}$ PGL-1 in initiating nerve damage in leprosy.This work was supported by an A.P. Giannini Foundation Postdoctoral Fellowship, an NIH training grant (T32 AI1007411), and an NIH NRSA Postdoctoral Fellowship (AI104240) to C.A.M.; an NSF Predoctoral Fellowship and NIH training grant T32 AI55396 to C.J.C.; a UCLA Clinical Translational Science Institute grant (UL1TR001881 to K.K.S.); K08AR066545 to P.O.S.; U19AI111224 and R01AI049313 to D.B.M.; an NIH grant (R01AR064582) to A.S.; the NIH Director’s Pioneer Award, an NIH MERIT award (R37AI054503), and a Wellcome Trust Principal Research Fellowship to L.R

Considerations about quality in model-driven engineering

The final publication is available at Springer via http://dx.doi.org/10.1007/s11219-016-9350-6The virtue of quality is not itself a subject; it depends on a subject. In the software engineering field, quality means good software products that meet customer expectations, constraints, and requirements. Despite the numerous approaches, methods, descriptive models, and tools, that have been developed, a level of consensus has been reached by software practitioners. However, in the model-driven engineering (MDE) field, which has emerged from software engineering paradigms, quality continues to be a great challenge since the subject is not fully defined. The use of models alone is not enough to manage all of the quality issues at the modeling language level. In this work, we present the current state and some relevant considerations regarding quality in MDE, by identifying current categories in quality conception and by highlighting quality issues in real applications of the model-driven initiatives. We identified 16 categories in the definition of quality in MDE. From this identification, by applying an adaptive sampling approach, we discovered the five most influential authors for the works that propose definitions of quality. These include (in order): the OMG standards (e.g., MDA, UML, MOF, OCL, SysML), the ISO standards for software quality models (e.g., 9126 and 25,000), Krogstie, Lindland, and Moody. We also discovered families of works about quality, i.e., works that belong to the same author or topic. Seventy-three works were found with evidence of the mismatch between the academic/research field of quality evaluation of modeling languages and actual MDE practice in industry. We demonstrate that this field does not currently solve quality issues reported in industrial scenarios. The evidence of the mismatch was grouped in eight categories, four for academic/research evidence and four for industrial reports. These categories were detected based on the scope proposed in each one of the academic/research works and from the questions and issues raised by real practitioners. We then proposed a scenario to illustrate quality issues in a real information system project in which multiple modeling languages were used. For the evaluation of the quality of this MDE scenario, we chose one of the most cited and influential quality frameworks; it was detected from the information obtained in the identification of the categories about quality definition for MDE. We demonstrated that the selected framework falls short in addressing the quality issues. Finally, based on the findings, we derive eight challenges for quality evaluation in MDE projects that current quality initiatives do not address sufficiently.F.G, would like to thank COLCIENCIAS (Colombia) for funding this work through the Colciencias Grant call 512-2010. This work has been supported by the Gene-ralitat Valenciana Project IDEO (PROMETEOII/2014/039), the European Commission FP7 Project CaaS (611351), and ERDF structural funds.Giraldo-Velásquez, FD.; España Cubillo, S.; Pastor López, O.; Giraldo, WJ. (2016). Considerations about quality in model-driven engineering. Software Quality Journal. 1-66. https://doi.org/10.1007/s11219-016-9350-6S166(1985). Iso information processing—documentation symbols and conventions for data, program and system flowcharts, program network charts and system resources charts. ISO 5807:1985(E) (pp. 1–25).(2011). Iso/iec/ieee systems and software engineering – architecture description. 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Model-driven engineering: a survey supported by the unified conceptual model. Computer Languages Systems and Structures, 43, 139–155.Da Silva Teixeira, D.G.M., Quirino, G.K., Gailly, F., De Almeida Falbo, R., Guizzardi, G., & Perini Barcellos, M. (2016). PoN-S: a Systematic Approach for Applying the Physics of Notation (PoN), (pp. 432–447). Cham: Springer International Publishing.Davies, I., Green, P., Rosemann, M., Indulska, M., & Gallo, S. (2006). How do practitioners use conceptual modeling in practice? Data and Knowledge Engineering, 58(3), 358 – 380. Including the special issue : {ER} 2004ER 2004.Davies, J., Milward, D., Wang, C.-W., & Welch, J. (2015). Formal model-driven engineering of critical information systems. Science of Computer Programming, 103(0), 88 – 113. Selected papers from the First International Workshop on Formal Techniques for Safety-Critical Systems (FTSCS 2012).De Oca, I.M.-M., Snoeck, M., Reijers, H.A., & Rodríguez-Morffi, A. (2015). A systematic literature review of studies on business process modeling quality. Information and Software Technology, 58, 187–205.DenHaan, J. (2009). 8 reasons why model driven development is dangerous @ONLINE.DenHaan, J. (2010). Model driven engineering vs the commando pattern @ONLINE.DenHaan, J. (2011a). Why aren’t we all doing model driven development yet @ONLINE.DenHaan, J. (2011b). Why there is no future model driven development @ONLINE.Di Ruscio, D., Iovino, L., & Pierantonio, A. (2013). Managing the coupled evolution of metamodels and textual concrete syntax specifications. cited By (since 1996)0.Dijkman, R.M., Dumas, M., & Ouyang, C. (2008). Semantics and analysis of business process models in {BPMN}. Information and Software Technology, 50(12), 1281–1294.Domínguez-Mayo, F.J., Escalona, M.J., Mejías, M., Ramos, I., & Fernández, L. (2011). A framework for the quality evaluation of mdwe methodologies and information technology infrastructures. International Journal of Human Capital and Information Technology Professionals, 2(4), 11–22.Domínguez-Mayo, F.J., Escalona, M.J., Mejías, M., & Torres, A.H. (2010). A quality model in a quality evaluation framework for mdwe methodologies. pages 495–506. Affiliation: Departamento de Lenguajes y Sistemas Informíticos, University of Seville, Seville, Spain., Cited By (since 1996):1.Dubray, J.-J. (2011). Why did mde miss the boat?.Escalona, M.J., Gutiérrez, J.J., Pérez-Pérez, M., Molina, A., Domínguez-Mayo, E., & Domínguez-Mayo, F.J. (2011). Measuring the Quality of Model-Driven Projects with NDT-Quality, (pp. 307–317). New York: Springer.Espinilla, M., Domínguez-Mayo, F.J., Escalona, M.J., Mejías, M., Ross, M., & Staples, G. (2011). A Method Based on AHP to Define the Quality Model of QuEF (Vol. 123, pp. 685–694). Berlin, Heidelberg: Springer.Fabra, J., Castro, V.D., Álvarez, P., & Marcos, E. (2012). 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Uml support for designing software product lines: the package merge mechanism, 16(17), 2313–2332.Lange, C. (2007a). Model size matters. Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics), 4364 LNCS:211–216. cited By (since 1996)1.Lange, C., & Chaudron, M. (2005). Managing Model Quality in UML-Based Software Development. In 13th IEEE International Workshop on Technology and Engineering Practice, 2005 (pp. 7–16).Lange, C., Chaudron, M.R.V., Muskens, J., Somers, L.J., & Dortmans, H.M. (2003). An empirical investigation in quantifying inconsistency and incompleteness of uml designs. In Incompleteness of UML Designs, Proceedings Workshop on Consistency Problems in UML-based Software Development, 6th International Conference on Unified Modeling Language, UML, 2003.Lange, C., DuBois, B., Chaudron, M., & Demeyer, S. (2006). An experimental investigation of uml modeling conventions. 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Chameleon radiation by oceanic dispersal

Historical biogeography is dominated by vicariance methods that search for a congruent pattern of fragmentation of ancestral distributions produced by shared Earth history(1-3). A focus of vicariant studies has been austral area relationships and the break-up of the supercontinent Gondwana(3-5). Chameleons are one of the few extant terrestrial vertebrates thought to have biogeographic patterns that are congruent with the Gondwanan break-up of Madagascar and Africa(6,7). Here we show, using molecular and morphological evidence for 52 chameleon taxa, support for a phylogeny and area cladogram that does not fit a simple vicariant history. Oceanic dispersal-not Gondwanan breakup-facilitated species radiation, and the most parsimonious biogeographic hypothesis supports a Madagascan origin for chameleons, with multiple 'out-of-Madagascar' dispersal events to Africa, the Seychelles, the Comoros archipelago, and possibly Reunion Island. Although dispersal is evident in other Indian Ocean terrestrial animal groups(8-16), our study finds substantial out-of-Madagascar species radiation, and further highlights the importance of oceanic dispersal as a potential precursor for speciation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62614/1/415784a.pd