Cerebral Venous Thrombosis in the Mediterranean Area in Children

Cerebral Venous Sinus (sinovenous) Thrombosis (CSVT) is a serious and rare disorder, increasingly recognized and diagnosed in pediatric patients. The etiology and pathophisiology has not yet been completely clarified, and unlike adults with CSVT, management in children and neonates remains controversial. However, morbidity and mortality are significant, highlighting the continued need for high-quality studies within this field. The following review will highlight aspects of CSVT in the mediteranian area in children

Strategies for Health Research: Lessons from 3 Mobile Intervention Studies

The capacity of Mobile Health (mHealth) technologies to propel healthcare forward is directly linked to the quality of mobile interventions developed through careful mHealth research. mHealth research entails several unique characteristics, including collaboration with technologists at all phases of a project, reliance on regional telecommunication infrastructure and commercial mobile service providers, and deployment and evaluation of interventions in the wild , with participants using mobile tools in uncontrolled environments. In the current paper, we summarize the lessons our multi-institutional/multi-disciplinary team has learned conducting a range of mHealth projects using mobile phones with diverse clinical populations. First, we describe three ongoing projects that we draw from to illustrate throughout the paper. We then provide an example for multidisciplinary teamwork and conceptual mHealth intervention development that we found to be particularly useful. Finally, we discuss mHealth research challenges (i.e. evolving technology, mobile phone selection, user characteristics, the deployment environment, and mHealth system bugs and glitches ), and provide recommendations for identifying and resolving barriers, or preventing their occurrence altogether

FoldIndex©: a simple tool to predict whether a given protein sequence is intrinsically unfolded

Summary: An easy-to-use, versatile and freely available graphic web server, FoldIndex© is described: it predicts if a given protein sequence is intrinsically unfolded implementing the algorithm of Uversky and co-workers, which is based on the average residue hydrophobicity and net charge of the sequence. FoldIndex© has an error rate comparable to that of more sophisticated fold prediction methods. Sliding windows permit identification of large regions within a protein that possess folding propensities different from those of the whole protein. Availability: FoldIndex© can be accessed at http://bioportal.weizmann.ac.il/fldbin/findex Contact: [email protected] Supplementary information: http://www.weizmann.ac.il/sb/faculty_pages/Sussman/papers/suppl/Prilusky_200

CrossCheck:toward passive sensing and detection of mental health changes in people with schizophrenia

Early detection of mental health changes in individuals with serious mental illness is critical for effective intervention. CrossCheck is the first step towards the passive monitoring of mental health indicators in patients with schizophrenia and paves the way towards relapse prediction and early intervention. In this paper, we present initial results from an ongoing randomized control trial, where passive smartphone sensor data is collected from 21 outpatients with schizophrenia recently discharged from hospital over a period ranging from 2-8.5 months. Our results indicate that there are statistically significant associations between automatically tracked behavioral features related to sleep, mobility, conversations, smartphone usage and self-reported indicators of mental health in schizophrenia. Using these features we build inference models capable of accurately predicting aggregated scores of mental health indicators in schizophrenia with a mean error of 7.6% of the score range. Finally, we discuss results on the level of personalization that is needed to account for the known variations within people. We show that by leveraging knowledge from a population with schizophrenia, it is possible to train accurate personalized models that require fewer individual-specific data to quickly adapt to new user

Estimating the incidence of rotavirus infection in children from India and Malawi from serial anti-rotavirus IgA titres.

Accurate estimates of rotavirus incidence in infants are crucial given disparities in rotavirus vaccine effectiveness from low-income settings. Sero-surveys are a pragmatic means of estimating incidence however serological data is prone to misclassification. This study used mixture models to estimate incidence of rotavirus infection from anti-rotavirus immunoglobulin A (IgA) titres in infants from Vellore, India, and Karonga, Malawi. IgA titres were measured using serum samples collected at 6 month intervals for 36 months from 373 infants from Vellore and 12 months from 66 infants from Karonga. Mixture models (two component Gaussian mixture distributions) were fit to the difference in titres between time points to estimate risk of sero-positivity and derive incidence estimates. A peak incidence of 1.05(95% confidence interval [CI]: 0.64, 1.64) infections per child-year was observed in the first 6 months of life in Vellore. This declined incrementally with each subsequent time interval. Contrastingly in Karonga incidence was greatest in the second 6 months of life (1.41 infections per child year [95% CI: 0.79, 2.29]). This study demonstrates that infants from Vellore experience peak rotavirus incidence earlier than those from Karonga. Identifying such differences in transmission patterns is important in informing vaccine strategy, particularly where vaccine effectiveness is modest

Estimating the incidence of rotavirus infection in children from India and Malawi from serial anti-rotavirus IgA titres.

Accurate estimates of rotavirus incidence in infants are crucial given disparities in rotavirus vaccine effectiveness from low-income settings. Sero-surveys are a pragmatic means of estimating incidence however serological data is prone to misclassification. This study used mixture models to estimate incidence of rotavirus infection from anti-rotavirus immunoglobulin A (IgA) titres in infants from Vellore, India, and Karonga, Malawi. IgA titres were measured using serum samples collected at 6 month intervals for 36 months from 373 infants from Vellore and 12 months from 66 infants from Karonga. Mixture models (two component Gaussian mixture distributions) were fit to the difference in titres between time points to estimate risk of sero-positivity and derive incidence estimates. A peak incidence of 1.05(95% confidence interval [CI]: 0.64, 1.64) infections per child-year was observed in the first 6 months of life in Vellore. This declined incrementally with each subsequent time interval. Contrastingly in Karonga incidence was greatest in the second 6 months of life (1.41 infections per child year [95% CI: 0.79, 2.29]). This study demonstrates that infants from Vellore experience peak rotavirus incidence earlier than those from Karonga. Identifying such differences in transmission patterns is important in informing vaccine strategy, particularly where vaccine effectiveness is modest

Novel mutations in the CDKL5 gene, predicted effects and associated phenotypes

It has been found that CDKL5 gene mutations are responsible for early-onset epilepsy and drug resistance. We screened a population of 92 patients with classic/atypical Rett syndrome, 17 Angelman/Angelman-like patients and six idiopathic autistic patients for CDKL5 mutations and exon deletions and identified seven novel mutations: six in the Rett subset and one in an Angelman patient. This last, an insertion in exon 11, c.903_904 dupGA, p.Leu302Aspfx49X, is associated with a relatively mild clinical presentation as the patient is the only one capable of sitting and walking alone. Of the six mutations, two are de novo missense changes affecting highly conserved aminoacid residues, c.215 T > C p.Ile72Thr and c.380A > G p.His127Arg (present in a mosaic condition) found in two girls with the most severe clinical presentation, while the remaining are the splicing c.145 + 2 T > C and c.2376 + 5G > A, the c.1648C > T p.Arg550X and the MPLA-identified c.162_99del261 mutation. RNA characterisation of four mutations revealed the aberrant transcript of the missense allele (case 2) and not the stop mutation (case 3), but also allowed the splicing mutation (case 1) and the c.-162_99del261 (case 4) to be ategorised as truncating. The obtained data reinforce the view that a more severe phenotype is due more to an altered protein than haploinsufficiency. Furthermore, the mutational repertoire of the CDKL5 gene is shown to be expanded by testing patients with phenotypical overlap to Rett syndrome and applying multiplex ligation-dependent probe amplification

The phenotype associated with a large deletion on MECP2

Multiplex ligation-dependent Probe Amplification (MLPA) has become available for the detection of a large deletion on the MECP2 gene allowing genetic confirmation of previously unconfirmed cases of clinical Rett syndrome. This study describes the phenotype of those with a large deletion and compares with those with other pathogenic MECP2 mutations. Individuals were ascertained from the Australian Rett Syndrome and InterRett databases with data sourced from family and clinician questionnaires, and two case studies were constructed from the longitudinal Australian data. Regression and survival analysis were used to compare severity and age of onset of symptoms in those with and without a large deletion. Data were available for 974 individuals including 51 with a large deletion and ages ranged from 1 year 4 months to 49 years (median 9 years). Those with a large deletion were more severely affected than those with other mutation types. Specifically, individuals with large deletions were less likely to have learned to walk (OR 0.42, 95% CI: 0.22–0.79, P=0.007) and to be currently walking (OR 0.53, 95% CI: 0.26–1.10, P=0.089), and were at higher odds of being in the most severe category of gross motor function (OR 1.84, 95% CI: 0.98–3.48, P=0.057) and epilepsy (OR 2.72, 95% CI: 1.38–5.37, P=0.004). They also developed epilepsy, scoliosis, hand stereotypies and abnormal breathing patterns at an earlier age. We have described the disorder profile associated with a large deletion from the largest sample to date and have found that the phenotype is severe with motor skills particularly affected

FoldIndex: a simple tool to predict whether a given protein sequence is intrinsically unfolded

An easy-to-use, versatile and freely available graphic web server, FoldIndex is described: it predicts if a given protein sequence is intrinsically unfolded implementing the algorithm of Uversky and co-workers, which is based on the average residue hydrophobicity and net charge of the sequence. FoldIndex has an error rate comparable to that of more sophisticated fold prediction methods. Sliding windows permit identification of large regions within a protein that possess folding propensities different from those of the whole protein