Investigation of Ion Concentration Polarization in original Micro-Nanofluidic devices

AbstractIon perm-selectivity is one of the major proprieties of nanofluidic devices. Within the influence of an electric field through an ion-selective nanochannel, a phenomenon called ICP “Ion Concentration Polarization” appears and creates near the micro-nanojunction an ion depletion/concentration zone at the anodic/cathodic side, respectively. Recent works have shown that the anodic depletion can be used as a powerfull preconcentration tool for detection of molecules (DNA, proteins…). Here, we present an original micro-nanofluidic device realized by standard silicon technology which exhibits circular micro-nanojuction. The ICP phenomenon was demonstrated on fluorescent molecules (fluorescein). The radial configuration of the nanochannels may bring different advantages compared to the classical “Bypass” device mostly reported in literature

The Generalized Problematic Internet Use Scale-2 in a French sample: psychometric evaluation of the theoretical model

Objectives: The Generalized Problematic Internet Use Scale-2 (GPIUS-2) is a short self-report questionnaire assessing Internet addiction based on a cognitive behavioral model. Our main goal was to evaluate the psychometric properties of its French version among a sample of students and to appraise the relevance of the generalized problematic Internet use model. Methods: A sample of 563 university students aged between 18 and 35 years (M = 20.8; SD = 2.7) completed several online self-report questionnaires including the GPIUS-2, the Internet Addiction Test (IAT) and the Center for Epidemiologic Study-Depression scale (CES-D). Results: Confirmatory Factorial Analyses revealed a poor but acceptable overall fit for the original five-factor model and the original four-factor model. Path analyses, testing Structural Equation Modeling provided showed a poor fit to the data, suggesting insufficient construct validity. Convergent and concurrent validities analyzed through correlational analyses revealed significant relationships between the GPIUS-2, its factors, the IAT, time spent online and the CES-D. Conclusions: This research highlights the insufficient psychometric properties of the GPIUS-2 in a French sample, similar to previous results. However, this French version appears to be a useful multidimensional tool for assessing problematic Internet use among students, and reveals promise for future research and clinical applications of the measure, given its solid theoretical basis and despite the results of this psychometric study

Curtailment and Stochastic Curtailment to Shorten the CES-D

The Center for Epidemiologic Studies-Depression (CES-D) scale is a well-known self-report instrument that is used to measure depressive symptomatology. Respondents who take the full-length version of the CES-D are administered a total of 20 items. This article investigates the use of curtailment and stochastic curtailment (SC), two sequential analysis methods that have recently been proposed for health questionnaires, to reduce the respondent burden associated with taking the CES-D. A post hoc simulation based on 1,392 adolescents' responses to the CES-D was used to compare these methods with a previously proposed computerized adaptive testing (CAT) approach. Curtailment lowered average test lengths by as much as 22% while always matching the classification decision of the full-length CES-D. SC and CAT achieved further reductions in average test length, with SC's classifications exhibiting more concordance with the full-length CES-D than do CAT's. Advantages and disadvantages of each method are discussed. © The Author(s) 2012

Creatine and guanidinoacetate reference values in a French population

Creatine and guanidinoacetate are biomarkers of creatine metabolism. Their assays in body fluids may be used for detecting patients with primary creatine deficiency disorders (PCDD), a class of inherited diseases. Their laboratory values in blood and urine may vary with age, requiring that reference normal values are given within the age range. Despite the long known role of creatine for muscle physiology, muscle signs are not necessarily the major complaint expressed by PCDD patients. These disorders drastically affect brain function inducing, in patients, intellectual disability, autistic behavior and other neurological signs (delays in speech and language, epilepsy, ataxia, dystonia and choreoathetosis), being a common feature the drop in brain creatine content. For this reason, screening of PCDD patients has been repeatedly carried out in populations with neurological signs. This report is aimed at providing reference laboratory values and related age ranges found for a large scale population of patients with neurological signs (more than 6 thousand patients) previously serving as a background population for screening French patients with PCDD. These reference laboratory values and age ranges compare rather favorably with literature values for healthy populations. Some differences are also observed, and female participants are discriminated from male participants as regards to urine but not blood values including creatine on creatinine ratio and guanidinoacetate on creatinine ratio values. Such gender differences were previously observed in healthy populations; they might be explained by literature differential effects of testosterone and estrogen in adolescents and adults, and by estrogen effects in prepubertal age on SLC6A8 function. Finally, though they were acquired on a population with neurological signs, the present data might reasonably serve as reference laboratory values in any future medical study exploring abnormalities of creatine metabolism and transport

Ataluren delays loss of ambulation and respiratory decline in nonsense mutation Duchenne muscular dystrophy patients

Aim: We investigated the effect of ataluren plus standard of care (SoC) on age at loss of ambulation (LoA) and respiratory decline in patients with nonsense mutation Duchenne muscular dystrophy (nmDMD) versus patients with DMD on SoC alone. / Patients & methods: Study 019 was a long-term Phase III study of ataluren safety in nmDMD patients with a history of ataluren exposure. Propensity score matching identified Study 019 and CINRG DNHS patients similar in disease progression predictors. / Results & conclusion: Ataluren plus SoC was associated with a 2.2-year delay in age at LoA (p = 0.0006), and a 3.0-year delay in decline of predicted forced vital capacity to <60% in nonambulatory patients (p = 0.0004), versus SoC. Ataluren plus SoC delays disease progression and benefits ambulatory and nonambulatory patients with nmDMD. / ClinicalTrials.gov: NCT01557400

The Edinburgh Postnatal Depression Scale (EPDS): translation and validation study of the Iranian version

BACKGROUND: The Edinburgh Postnatal Depression Scale (EPDS) is a widely used instrument to measure postnatal depression. This study aimed to translate and to test the reliability and validity of the EPDS in Iran. METHODS: The English language version of the EPDS was translated into Persian (Iranian language) and was used in this study. The questionnaire was administered to a consecutive sample of 100 women with normal (n = 50) and caesarean section (n = 50) deliveries at two points in time: 6 to 8 weeks and 12 to 14 weeks after delivery. Statistical analysis was performed to test the reliability and validity of the EPDS. RESULTS: Overall 22% of women at time 1 and 18% at time 2 reported experiencing postpartum depression. In general, the Iranian version of the EPDS was found to be acceptable to almost all women. Cronbach's alpha coefficient (to test reliability) was found to be 0.77 at time 1 and 0.86 at time 2. In addition, test-rest reliability was performed and the intraclass correlation coefficient was found to be 0.80. Validity as performed using known groups comparison showed satisfactory results. The questionnaire discriminated well between sub-groups of women differing in mode of delivery in the expected direction. The factor analysis indicated a three-factor structure that jointly accounted for 58% of the variance. CONCLUSION: This preliminary validation study of the Iranian version of the EPDS proved that it is an acceptable, reliable and valid measure of postnatal depression. It seems that the EPDS not only measures postpartum depression but also may be measuring something more

Truncating and missense mutations in IGHMBP2 cause Charcot-Marie Tooth disease type 2.

Using a combination of exome sequencing and linkage analysis, we investigated an English family with two affected siblings in their 40s with recessive Charcot-Marie Tooth disease type 2 (CMT2). Compound heterozygous mutations in the immunoglobulin-helicase-μ-binding protein 2 (IGHMBP2) gene were identified. Further sequencing revealed a total of 11 CMT2 families with recessively inherited IGHMBP2 gene mutations. IGHMBP2 mutations usually lead to spinal muscular atrophy with respiratory distress type 1 (SMARD1), where most infants die before 1 year of age. The individuals with CMT2 described here, have slowly progressive weakness, wasting and sensory loss, with an axonal neuropathy typical of CMT2, but no significant respiratory compromise. Segregating IGHMBP2 mutations in CMT2 were mainly loss-of-function nonsense in the 5' region of the gene in combination with a truncating frameshift, missense, or homozygous frameshift mutations in the last exon. Mutations in CMT2 were predicted to be less aggressive as compared to those in SMARD1, and fibroblast and lymphoblast studies indicate that the IGHMBP2 protein levels are significantly higher in CMT2 than SMARD1, but lower than controls, suggesting that the clinical phenotype differences are related to the IGHMBP2 protein levels

Brain activity underlying negative self- and other-perception in adolescents: The role of attachment-derived self-representations

One of teenagers' key developmental tasks is to engage in new and meaningful relationships with peers and adults outside the family context. Attachment-derived expectations about the self and others in terms of internal attachment working models have the potential to shape such social reorientation processes critically and thereby influence adolescents' social-emotional development and social integration. Because the neural underpinnings of this developmental task remain largely unknown, we sought to investigate them by functional magnetic resonance imaging. We asked n = 44 adolescents (ages 12.01-18.84 years) to evaluate positive and negative adjectives regarding either themselves or a close other during an adapted version of the well-established self-other trait-evaluation task. As measures of attachment, we obtained scores reflecting participants' positive versus negative attachment-derived self- and other-models by means of the Relationship Questionnaire. We controlled for possible confounding factors by also obtaining scores reflecting internalizing/externalizing problems, schizotypy, and borderline symptomatology. Our results revealed that participants with a more negative attachment-derived self-model showed increased brain activity during positive and negative adjective evaluation regarding the self, but decreased brain activity during negative adjective evaluation regarding a close other, in bilateral amygdala/parahippocampus, bilateral anterior temporal pole/anterior superior temporal gyrus, and left dorsolateral prefrontal cortex. These findings suggest that a low positivity of the self-concept characteristic for the attachment anxiety dimension may influence neural information processing, but in opposite directions when it comes to self- versus (close) other-representations. We discuss our results in the framework of attachment theory and regarding their implications especially for adolescent social-emotional development and social integration

Meta-analyses of ataluren randomized controlled trials in nonsense mutation Duchenne muscular dystrophy.

Aim: Assess the totality of efficacy evidence for ataluren in patients with nonsense mutation Duchenne muscular dystrophy (nmDMD). Materials & methods: Data from the two completed randomized controlled trials (ClinicalTrials.gov: NCT00592553; NCT01826487) of ataluren in nmDMD were combined to examine the intent-to-treat (ITT) populations and two patient subgroups (baseline 6-min walk distance [6MWD] \u3e= 300-\u3c400 or \u3c400 m). Meta-analyses examined 6MWD change from baseline to week 48.Results:Statistically significant differences in 6MWD change with ataluren versus placebo were observed across all three meta-analyses. Least-squares mean difference (95% CI): ITT (n = 342), +17.2 (0.2-34.1) m, p = 0.0473; \u3e= 300-\u3c400 m (n = 143), +43.9 (18.2-69.6) m, p = 0.0008; \u3c400 m (n = 216), +27.7 (6.4-49.0) m, p = 0.0109. Conclusion: These meta-analyses support previous evidence for ataluren in slowing disease progression versus placebo in patients with nmDMD over 48 weeks. Treatment benefit was most evident in patients with a baseline 6MWD \u3e= 300-\u3c400 m (the ambulatory transition phase), thereby informing future trial design