Marfan syndrome and pregnancy: maternal and neonatal outcomes

Objective To report outcomes in a recent series of pregnancies in women with Marfan syndrome (MFS). Design Retrospective case note review. Setting Tertiary referral unit (Chelsea and Westminster and Royal Brompton Hospitals). Sample Twenty-nine pregnancies in 21 women with MFS between 1995 and 2010. Methods Multidisciplinary review of case records. Main outcome measures Maternal and neonatal mortality and morbidity of patients with MFS and healthy controls. Results There were no maternal deaths. Significant cardiac complications occurred in five pregnancies (17%): one woman experienced a type–A aortic dissection; two women required cardiac surgery within 6 months of delivery; and a further two women developed impaired left ventricular function during the pregnancy. Women with MFS were also more likely to have obstetric complications (OR 3.29, 95% CI 1.30–8.34), the most frequent of which was postpartum haemorrhage (OR 8.46, 95% CI 2.52–28.38). There were no perinatal deaths, although babies born to mothers with MFS were delivered significantly earlier than those born to the control group (median 39 versus 40 weeks of gestation, Mann–Whitney U–test, P = 0.04). These babies were also significantly more likely to be small for gestational age (24% in the MFS group versus 6% in the controls; OR 4.95, 95% CI 1.58–15.55). Conclusions Pregnancy in women with MFS continues to be associated with significant rates of maternal, fetal, and neonatal complications. Effective pre-pregnancy counselling and meticulous surveillance during pregnancy, delivery, and the puerperium by an experienced multidisciplinary team are warranted for women with MFS

Search for cardiac calcium cycling gene mutations in familial ventricular arrhythmias resembling catecholaminergic polymorphic ventricular tachycardia

<p>Abstract</p> <p>Background</p> <p>Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a severe inherited cardiac disorder caused by mutations predominantly in the ryanodine receptor (<it>RyR2</it>) gene. We sought to identify mutations in genes affecting cardiac calcium cycling in patients with CPVT and in less typical familial exercise-related ventricular arrhythmias.</p> <p>Methods and Results</p> <p>We recruited 33 consecutive patients with frequent ventricular premature complexes (VPCs) without structural heart disease and often history of syncope or sudden death in family. Sixteen of the patients featured a phenotype typical of CPVT. In 17 patients, VPCs emerged also at rest. Exercise stress test and echocardiography were performed to each patient and 232 family members. Familial background was evident in 42% of cases (n = 14). We sequenced all the coding exons of the <it>RyR2</it>, <it>FKBP1B</it>, <it>ATP2A2 </it>and <it>SLC8A1 </it>genes from the index patients. Single channel recordings of a mutant RyR2 were performed in planar lipid bilayers. Two novel <it>RyR2 </it>missense mutations (R1051P and S616L) and two <it>RyR2 </it>exon 3 deletions were identified, explaining 25% of the CPVT phenotypes. A rare variant (N3308S) with open probabilities similar to the wild type channels <it>in vitro</it>, was evident in a patient with resting VPCs. No disease-causing variants were detectable in the <it>FKBP1B</it>, <it>ATP2A2 </it>or <it>SLC8A1 </it>genes.</p> <p>Conclusion</p> <p>We report two novel CPVT-causing <it>RyR2 </it>mutations and a novel <it>RyR2 </it>variant of uncertain clinical significance in a patient with abundant resting VPCs. Our data also strengthen the previous assumption that exon 3 deletions of <it>RyR2 </it>should screened for in CPVT and related phenotypes.</p

Ways to teach modelling—a 50 year study

This article describes a sequence of design research projects, some exploratory others more formal, on the teaching of modelling and the analysis of modelling skills. The initial motivation was the author’s observation that the teaching of applied mathematics in UK high schools and universities involved no active modelling by students, but was entirely focused on their learning standards models of a restricted range of phenomena, largely from Newtonian mechanics. This did not develop the numeracy/mathematical literacy that was so clearly important for future citizens. Early explorations started with modelling workshops with high school teachers and mathematics undergraduates, observed and analysed—in some case using video. The theoretical basis of this work has been essentially heuristic, though the Shell Centre studies included, for example, a detailed analysis of formulation processes that has not, as so often, been directly replicated. Recent work has focused on developing a formative assessment approach to teaching modelling that has proved both successful and popular. Finally, the system-level challenges in trying to establish modelling as an integral part of mathematics curricula are briefly discussed

Species-level functional profiling of metagenomes and metatranscriptomes.

Functional profiles of microbial communities are typically generated using comprehensive metagenomic or metatranscriptomic sequence read searches, which are time-consuming, prone to spurious mapping, and often limited to community-level quantification. We developed HUMAnN2, a tiered search strategy that enables fast, accurate, and species-resolved functional profiling of host-associated and environmental communities. HUMAnN2 identifies a community's known species, aligns reads to their pangenomes, performs translated search on unclassified reads, and finally quantifies gene families and pathways. Relative to pure translated search, HUMAnN2 is faster and produces more accurate gene family profiles. We applied HUMAnN2 to study clinal variation in marine metabolism, ecological contribution patterns among human microbiome pathways, variation in species' genomic versus transcriptional contributions, and strain profiling. Further, we introduce 'contributional diversity' to explain patterns of ecological assembly across different microbial community types

Implementing health research through academic and clinical partnerships : a realistic evaluation of the Collaborations for Leadership in Applied Health Research and Care (CLAHRC)

Background: The English National Health Service has made a major investment in nine partnerships between higher education institutions and local health services called Collaborations for Leadership in Applied Health Research and Care (CLAHRC). They have been funded to increase capacity and capability to produce and implement research through sustained interactions between academics and health services. CLAHRCs provide a natural ‘test bed’ for exploring questions about research implementation within a partnership model of delivery. This protocol describes an externally funded evaluation that focuses on implementation mechanisms and processes within three CLAHRCs. It seeks to uncover what works, for whom, how, and in what circumstances. Design and methods: This study is a longitudinal three-phase, multi-method realistic evaluation, which deliberately aims to explore the boundaries around knowledge use in context. The evaluation funder wishes to see it conducted for the process of learning, not for judging performance. The study is underpinned by a conceptual framework that combines the Promoting Action on Research Implementation in Health Services and Knowledge to Action frameworks to reflect the complexities of implementation. Three participating CLARHCS will provide indepth comparative case studies of research implementation using multiple data collection methods including interviews, observation, documents, and publicly available data to test and refine hypotheses over four rounds of data collection. We will test the wider applicability of emerging findings with a wider community using an interpretative forum. Discussion: The idea that collaboration between academics and services might lead to more applicable health research that is actually used in practice is theoretically and intuitively appealing; however the evidence for it is limited. Our evaluation is designed to capture the processes and impacts of collaborative approaches for implementing research, and therefore should contribute to the evidence base about an increasingly popular (e.g., Mode two, integrated knowledge transfer, interactive research), but poorly understood approach to knowledge translation. Additionally we hope to develop approaches for evaluating implementation processes and impacts particularly with respect to integrated stakeholder involvement

Analyse multidimensionnelle interactive de résultats de simulation (aide à la décision dans le domaine de l'agroécologie)

Dans cette thèse, nous nous sommes intéressés à l'analyse des données de simulation issues du modèle agro-hydrologique TNT. Les objectifs consistaient à élaborer des méthodes d'analyse des résultats de simulation qui replacent l'utilisateur au coeur du processus décisionnel, et qui permettent d'analyser et d'interpréter de gros volumes de données de manière efficace. La démarche développée consiste à utiliser des méthodes d'analyse multidimensionnelle interactive. Tout d'abord, nous avons proposé une méthode d'archivage des résultats de simulation dans une base de données décisionnelle (i.e. entrepôt de données), adaptée au caractère spatio-temporel des données de simulation produites. Ensuite, nous avons suggéré d'analyser ces données de simulations avec des méthodes d'analyse en ligne (OLAP) afin de fournir aux acteurs des informations stratégiques pour améliorer le processus d'aide à la prise de décision. Enfin, nous avons proposé deux méthodes d'extraction de skyline dans le contexte des entrepôts de données afin de permettre aux acteurs de formuler de nouvelles questions en combinant des critères environnementaux contradictoires, et de trouver les solutions compromis associées à leurs attentes, puis d'exploiter les préférences des acteurs pour détecter et faire ressortir les données susceptibles de les intéresser. La première méthode EC2Sky, permet un calcul incrémental et efficace des skyline en présence de préférences utilisateurs dynamiques, et ce malgré de gros volumes de données. La deuxième méthode HSky, étend la recherche des points skyline aux dimensions hiérarchiques. Elle permet aux utilisateurs de naviguer le long des axes des dimensions hiérarchiques (i.e. spécialisation / généralisation) tout en assurant un calcul en ligne des points skyline correspondants. Ces contributions ont été motivées et expérimentées par l'application de gestion des pratiques agricoles pour l'amélioration de la qualité des eaux des bassins versants agricoles, et nous avons proposé un couplage entre le modèle d'entrepôt de données agro-hydrologiques construit et les méthodes d'extraction de skyline proposées.This thesis concerns the analysis of simulation data generated by the agrohydrological model TNT. Our objective is to develop analytical methods for massive simulation results. We want to place the user at the heart of the decision-making process, while letting him handle and analyze large amounts of data in a very efficient way. Our first contribution is an original approach N-Catch, relying on interactive multidimensional analysis methods for archiving simulation results in a decisional database (i.e. data warehouse) adapted to the spatio-temporal nature of the simulation data. In addition, we suggest to analyze the simulation data with online analytical methods (OLAP) to provide strategic information for stakeholders to improve the decision making process. Our second contribution concern two methods for computing skyline queries in the context of data warehouses. These methods enable stakeholders to formulate new questions by combining conflicting environmental criteria, to find compromise solutions associated with their expectations, and to exploit the stakeholder preferences to identify and highlight the data of potential interest. The first method EC2Sky, focuses on how to answer efficiently and progressively skyline queries in the presence of several dynamic user preferences despite of large volume of data. The second method HSky, extends the skyline computation to hierarchical dimensions. It allows the user to navigate along the dimensions hierarchies (i.e. specialize / generalize) while ensuring the online computation of associated skylines. Finally, we present the application of our proposals for managing agricultural practices to improve water quality in agricultural watersheds. We propose a coupling between the agro-hydrological data warehouse model N-Catch and the proposed skyline computation methods.RENNES1-Bibl. électronique (352382106) / SudocSudocFranceF

The sense and nonsense of direct-to-consumer genetic testing for cardiovascular disease

Expectations are high that increasing knowledge of the genetic basis of cardiovascular disease will eventually lead to personalised medicine—to preventive and therapeutic interventions that are targeted to at-risk individuals on the basis of their genetic profiles. Most cardiovascular diseases are caused by a complex interplay of many genetic variants interacting with many non-genetic risk factors such as diet, exercise, smoking and alcohol consumption. Since several years, genetic susceptibility testing for cardiovascular diseases is being offered via the internet directly to consumers. We discuss five reasons why these tests are not useful, namely: (1) the predictive ability is still limited; (2) the risk models used by the companies are based on assumptions that have not been verified; (3) the predicted risks keep changing when new variants are discovered and added to the test; (4) the tests do not consider non-genetic factors in the prediction of cardiovascular disease risk; and (5) the test results will not change recommendations of preventive interventions. Predictive genetic testing for multifactorial forms of cardiovascular disease clearly lacks benefits for the public. Prevention of disease should therefore remain focused on family history and on non-genetic risk factors as diet and physical activity that can have the strongest impact on disease risk, regardless of genetic susceptibility

Efficient Finite Groups Arising in the Study of Relative Asphericity

We study a class of two-generator two-relator groups, denoted Jn(m, k), that arise in the study of relative asphericity as groups satisfying a transitional curvature condition. Particular instances of these groups occur in the literature as finite groups of intriguing orders. Here we find infinite families of non-elementary virtually free groups and of finite metabelian non-nilpotent groups, for which we determine the orders. All Mersenne primes arise as factors of the orders of the non-metacyclic groups in the class, as do all primes from other conjecturally infinite families of primes. We classify the finite groups up to isomorphism and show that our class overlaps and extends a class of groups Fa,b,c with trivalent Cayley graphs that was introduced by C.M.Campbell, H.S.M.Coxeter, and E.F.Robertson. The theory of cyclically presented groups informs our methods and we extend part of this theory (namely, on connections with polynomial resultants) to ?bicyclically presented groups? that arise naturally in our analysis. As a corollary to our main results we obtain new infinite families of finite metacyclic generalized Fibonacci groups

Assessment in the service of learning: challenges and opportunities or Plus ça Change, Plus c’est la même Chose

This paper begins with a brief overview of literature indicating that, although there have been significant advances in the field’s capacity to conduct both formative and summative assessments over the past decades, those advances have not been matched by comparable impact. The bulk of the paper is devoted to a series of examples from the Mathematics Assessment Project that illustrate issues of methods, and the unrealized potential for advances

A microcosting study of microsurgery, LINAC radiosurgery, and gamma knife radiosurgery in meningioma patients

The aim of the present study is to determine and compare initial treatment costs of microsurgery, linear accelerator (LINAC) radiosurgery, and gamma knife radiosurgery in meningioma patients. Additionally, the follow-up costs in the first year after initial treatment were assessed. Cost analyses were performed at two neurosurgical departments in The Netherlands from the healthcare providers’ perspective. A total of 59 patients were included, of whom 18 underwent microsurgery, 15 underwent LINAC radiosurgery, and 26 underwent gamma knife radiosurgery. A standardized microcosting methodology was employed to ensure that the identified cost differences would reflect only actual cost differences. Initial treatment costs, using equipment costs per fraction, were €12,288 for microsurgery, €1,547 for LINAC radiosurgery, and €2,412 for gamma knife radiosurgery. Higher initial treatment costs for microsurgery were predominantly due to inpatient stay (€5,321) and indirect costs (€4,350). LINAC and gamma knife radiosurgery were equally expensive when equipment was valued per treatment (€2,198 and €2,412, respectively). Follow-up costs were slightly, but not significantly, higher for microsurgery compared with LINAC and gamma knife radiosurgery. Even though initial treatment costs were over five times higher for microsurgery compared with both radiosurgical treatments, our study gives indications that the relative cost difference may decrease when follow-up costs occurring during the first year after initial treatment are incorporated. This reinforces the need to consider follow-up costs after initial treatment when examining the relative costs of alternative treatments