Cardiogene: an innovative multidisciplinary consultation for genetic arrhythmias

Introduction: Over the past decade clinically relevant progress has been made regarding the genetic origin of sudden cardiac death due to arrhythmic syndromes such as congenital long QT syndrome (LQTS), Brugada syndrome (BrS), catecholinergic polymorphic ventricular tachycardia (CPVT) and short QT (SQTS). An increased number of patients are diagnosed and their offspring sent for screening. In order to optimize care of these families we have set up a multidisciplinary consultation, "Cardiogene", consisting of a pediatric and an adult cardiologist and a clinical geneticist. All families are seen at a common consult in order to take the family history, genetic background and to explain the disease to patients and their families. Appropriate cardiac investigations and genetic testing are then performed and the families seen again in a multidisciplinary fashion for the results. We have reviewed all our cases over the past 5 years. Methods: retrospective review of all cases seen at Cardiogene Clinic for suspicion of arrhythmic syndromes since 2007. Results: 23 families were seen at the Cardiogene Clinic with a total of 41 children. The suspected arrhythmic syndrome was LQTS in 14 families (26 children), BrS in 7 families (14 children), SQTS in1 family (2 children) and CPVT in 1 family (3 children). Of the 41 children 17 were genetically positive for an arrhythmic syndrome: 14 were for LQTS, 3 for BrS. 24 children were genetically negative however 4 of those were phenotypically positive: 2 LQTS, 1 BrS and 1 CPVT. In 3 families the diagnosis was initially made in a child and then found in the parent. In 2 families the diagnosis was made after a sudden death of one of their children, 1 LQTS (3 week old child), 1 BrS (20 year old). Discussion: Genetic testing is an essential part of diagnosis and permits an improved targeting of patients needing follow-up and treatment. In our series, a mutation has been found in most families with LQTS. In all other genetic arrhythmias, the yield of genetic testing is less but nevertheless helpful for medical care of these pts. Conclusion: A multidisciplinary approach to genetic arrhythmias permits a better and more efficient screening and therapy in affected families. It helps families to better understand their disease and improves follow-up in the affected individuals.

Robust Estimates of the Negative Binomial Model

We consider robust parametric procedures for univariate discrete distributions, focusing on the negative binomial model. The procedures are based on three steps: ?First, a very robust, but possibly inefficient, estimate of the model parameters is computed. ?Second, this initial model is used to identify outliers, which are then removed from the sample. ?Third, a corrected maximum likelihood estimator is computed with the remaining observations. The final estimate inherits the breakdown point (bdp) of the initial one and its efficiency can be significantly higher. Analogous procedures were proposed in [1], [2], [5] for the continuous case. A comparison of the asymptotic bias of various estimates under point contamination points out the minimum Neyman's chi-squared disparity estimate as a good choice for the initial step. Various minimum disparity estimators were explored by Lindsay [4], who showed that the minimum Neyman's chi-squared estimate has a 50% bdp under point contamination; in addition, it is asymptotically fully efficient at the model. However, the finite sample efficiency of this estimate under the uncontaminated negative binomial model is usually much lower than 100% and the bias can be strong. We show that its performance can then be greatly improved using the three step procedure outlined above. In addition, we compare the final estimate with the procedure described in

Multidisciplinary approach of lumbo-sacral chordoma: From oncological treatment to reconstructive surgery.

Lumbo-sacral chordoma is a rare, slow-growing tumor, arising from embryonic nothocordal remnants. Wide en bloc excision with clear margins remains mandatory to achieve satisfactory recurrence rates and disease-free survival. No chemotherapy has been demonstrated to be effective and radiotherapy is only marginally effective. Tyrosine kinase receptor inhibitors have showed encouraging results in locally advanced and metastatic chordoma. Reconstructive surgery may become very complex. Multidisciplinary approach in tertiary hospitals is always necessary. J. Surg. Oncol. 2015; 112:544-554. © 2015 Wiley Periodicals, Inc.

On the robust measurement of inflectional diversity

Lexical diversity measures are notoriously sensitive to variations of sample size and recent approaches to this issue typically involve the computation of the average variety of lexical units in random subsamples of fixed size. This methodology has been further extended to measures of inflectional diversity such as the average number of wordforms per lexeme, also known as the mean size of paradigm (MSP) index. In this contribution we argue that, while random sampling can indeed be used to increase the robustness of inflectional diversity measures, using a fixed subsample size is only justified under the hypothesis that the corpora that we compare have the same degree of lexematic diversity. In the more general case where they may have differing degrees of lexematic diversity, a more sophisticated strategy can and should be adopted. A novel approach to the measurement of inflectional diversity is proposed, aiming to cope not only with variations of sample size, but also with variations of lexematic diversity. The robustness of this new method is empirically assessed and the results show that while there is still room for improvement, the proposed methodology considerably attenuates the impact of lexematic diversity discrepancies on the measurement of inflectional diversity.

Ultra-high Field (7 T) MRI and a Novel Robust Segmentation of Thalamic Nuclei on DWI for Gamma Knife Surgery Purposes: The Targeting of the Ventrointermediate Nucleus

Introduction: Gamma Knife surgery (GKS) is a noninvasive neurosurgical stereotactic procedure, increasingly used as an alternative to open functional procedures. This includes the targeting of the ventrointermediate nucleus of the thalamus (e.g., Vim) for tremor. Objective: To enhance anatomic imaging for Vim GKS using high-field (7 T) MRI and Diffusion Weighted Imaging (DWI). Methods: Five young healthy subjects and two patients were scanned both on 3 and 7 T MRI. The protocol was the same in all cases, and included: T1-weighted (T1w) and DWI at 3T; susceptibility weighted images (SWI) at 7T for the visualization of thalamic subparts. SWI was further integrated into the Gamma Plan Software® (LGP, Elekta Instruments, AB, Sweden) and co-registered with 3T images. A simulation of targeting of the Vim was done using the quadrilatere of Guyot. Furthermore, a correlation with the position of the found target on SWI and also on DWI (after clustering of the different thalamic nuclei) was performed. Results: For the 5 healthy subjects, there was a good correlation between the position of the Vim on SWI, DWI and the GKS targeting. For the patients, on the pretherapeutic acquisitions, SWI helped in positioning the target. For posttherapeutic sequences, SWI supposed position of the Vim matched the corresponding contrast enhancement seen at follow-up MRI. Additionally, on the patient's follow-up T1w images, we could observe a small area of contrast-enhancement corresponding to the target used in GKS (e.g., Vim), which belongs to the Ventral-Lateral-Ventral (VLV) nuclei group. Our clustering method resulted in seven thalamic groups. Conclusion: The use of SWI provided us with a superior resolution and an improved image contrast within the central gray matter, enabling us to directly visualize the Vim. We additionally propose a novel robust method for segmenting the thalamus in seven anatomical groups based on DWI. The localization of the GKS target on the follow-up T1w images, as well as the position of the Vim on 7 T, have been used as a gold standard for the validation of VLV cluster's emplacement. The contrast enhancement corresponding to the targeted area was always localized inside the expected cluster, providing strong evidence of the VLV segmentation accuracy. The anatomical correlation between the direct visualization on 7T and the current targeting methods on 3T (e.g., quadrilatere of Guyot, histological atlases, DWI) seems to show a very good anatomical matching.

Robust DNA Methylation in the Clonal Raider Ant Brain.

Social insects are promising model systems for epigenetics due to their immense morphological and behavioral plasticity. Reports that DNA methylation differs between the queen and worker castes in social insects [1-4] have implied a role for DNA methylation in regulating division of labor. To better understand the function of DNA methylation in social insects, we performed whole-genome bisulfite sequencing on brains of the clonal raider ant Cerapachys biroi, whose colonies alternate between reproductive (queen-like) and brood care (worker-like) phases [5]. Many cytosines were methylated in all replicates (on average 29.5% of the methylated cytosines in a given replicate), indicating that a large proportion of the C. biroi brain methylome is robust. Robust DNA methylation occurred preferentially in exonic CpGs of highly and stably expressed genes involved in core functions. Our analyses did not detect any differences in DNA methylation between the queen-like and worker-like phases, suggesting that DNA methylation is not associated with changes in reproduction and behavior in C. biroi. Finally, many cytosines were methylated in one sample only, due to either biological or experimental variation. By applying the statistical methods used in previous studies [1-4, 6] to our data, we show that such sample-specific DNA methylation may underlie the previous findings of queen- and worker-specific methylation. We argue that there is currently no evidence that genome-wide variation in DNA methylation is associated with the queen and worker castes in social insects, and we call for a more careful interpretation of the available data.

Consultation pluridisciplinaire "Souffrance au travail": une expérience romande [Multidisciplinary consultation "Suffering at work": an experience in western Switzerland].

Les problèmes de santé mentale au travail constituent un défi à la fois clinique, professionnel, économique et de santé publique. Les coûts totaux qu'ils génèrent en Suisse équivalent à 3,2 % du produit intérieur brut (PIB) suisse et ils aboutissent très souvent à un licenciement. La grande majorité des personnes sont soignées par un médecin de premier recours. L'Institut de Santé au Travail propose une consultation spécialisée dans les questions de souffrance au travail, offrant aux soignants de première ligne un avis ou un soutien pluridisciplinaire, dans une perspective collaborative des soins. Son action, adaptée aux besoins de chaque situation, va d'un avis à une orientation vers des spécialistes pouvant étoffer durablement le réseau (suivi psychiatrique, programme de soutien à l'emploi, avis juridique ou social). Mental health problems at work constitute a challenge in the clinical feld, as well in the professional, the economic and the public health perspective. The total costs they generate in Switzerland are equivalent to 3.2% of the Swiss gross domestic product and they very often lead to dismissal. The vast majority of people are treated by their primary care physician. The Institute for Work and Health features a specialized consultation on the topic of suffering at work, offering the primary care physicians a pluridisciplinary advice or support, in a collaborative care prospect. Its action, adapted to each situation's needs, goes from an advice to a referral to specialists that can strengthen the network on a long-term basis (mental health follow-up, supported employment program, legal or social advice).