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Background: This study was designed to review the obstetrical outcome of a consecutive series of cerebral venous thrombosis (CVT) affecting fertile women over a long period of time. Methods: From a computerized database of four hospitals of a French region (Poitou-Charentes), we selected patients admitted to hospital for CVT between January 1995 and February 2012. All the case notes were re-examined by two neurologists to confirm the initial diagnosis of CVT. The criterion of inclusion in our study was the occurrence of CVT in a woman ≤40 years of age. All the patients were recontacted by telephone in September 2012 and could be seen in an outpatient clinic. The data of interest were: occurrence of subsequent pregnancies, outcome of these pregnancies, their possible complications, their management with respect to preventive medication, details on the birth and the neonate. Results: Out of 190 consecutive patients hospitalized for CVT, 62 women aged ≤40 years were included (mean age 27.2 ± 6.7 years at the time of their cerebrovascular event). The mean duration of follow-up was 89.5 ± 60.6 months (median: 76 months). There were 45 pregnancies in 24 of the women. Among these 45 pregnancies, 1 was in progress, 24 were completed resulting in normal children, whereas 20 were terminated (5 voluntary abortions, 14 miscarriages and 1 medical abortion). During the pregnancies recorded, there was one recurrence of CVT and no extra-CVT. Various management strategies were adopted, depending on the identified cause(s) for CVT and the medical history of the patient. Conclusions: Our study confirms that the occurrence of a CVT in young women is not a contraindication for subsequent pregnancy. However, it points to a high incidence of miscarriage. Apart from this fact, there is no increase in materno-fetal complications during pregnancy and childbirth, and the neonates are healthy. The risk of recurrence of a CVT or extra-CVT during subsequent pregnancy is low but most of patients were on preventive antithrombotic medication.

Tangier disease is characterized by low serum high density lipoproteins and a biochemical defect in the cellular efflux of lipids to high density lipoproteins. ABC1, a member of the ATP-binding cassette family, recently has been identified as the defective gene in Tangier disease. We report here the organization of the human ABC1 gene and the identification of a mutation in the ABC1 gene from the original Tangier disease kindred. The organization of the human ABC1 gene is similar to that of the mouse ABC1 gene and other related ABC genes. The ABC1 gene contains 49 exons that range in size from 33 to 249 bp and is over 70 kb in length. Sequence analysis of the ABC1 gene revealed that the proband for Tangier disease was homozygous for a deletion of nucleotides 3283 and 3284 (TC) in exon 22. The deletion results in a frameshift mutation and a premature stop codon starting at nucleotide 3375. The product is predicted to encode a nonfunctional protein of 1,084 aa, which is approximately half the size of the full-length ABC1 protein. The loss of a Mn/1 restriction site, which results from the deletion, was used to establish the genotype of the rest of the kindred. In summary, we report on the genomic organization of the human ABC1 gene and identify a frameshift mutation in the ABC1 gene of the index case of Tangier disease. These results will be useful in the future characterization of the structure and function of the ABC1 gene and the analysis of additional ABC1 mutations in patients with Tangier disease.

The ABCA1 gene, a member of the ATP-binding cassette A (ABCA1) transporter superfamily, encodes a membrane protein that facilitates the cellular efflux of cholesterol and phospholipids. Mutations in ABCA1 lead to familial high density lipoprotein deficiency and Tangier disease. We report the complete human ABCA1 gene sequence, including 1,453 bp of the promoter, 146,581 bp of introns and exons, and 1 kb of the 3′flanking region. The ABCA1 gene spans 149 kb and comprises 50 exons. Sixty-two repetitive Alu sequences were identified in introns 1-49. The transcription start site is 315 bp upstream of a newly identified initiation methionine codon and encodes an ORF of 6,783 bp. Thus, the ABCA1 protein is comprised of 2,261 aa. Analysis of the 1,453 bp 5′upstream of the transcriptional start site reveals multiple binding sites for transcription factors with roles in lipid metabolism. Comparative analysis of the mouse and human ABCA1 promoter sequences identified specific regulatory elements, which are evolutionarily conserved. The human ABCA1 promoter fragment -200 to -80 bp that contains binding motifs for SP1, SP3, E-box, and AP1 modulates cellular cholesterol and cAMP regulation of ABCA1 gene expression. These combined findings provide insights into ABCA1-mediated regulation of cellular cholesterol metabolism and will facilitate the identification of new pharmacologic agents for the treatment of atherosclerosis in humans.

This study was designed to assess the return to work, the poststroke depression and the quality of life after a cerebral infarction in young adults and was conducted on 71 consecutive young patients (aged 15–45 years) affected by a cerebral infarct who were hospitalized for the first time and discharged at least 1 year before the study. Data about risk factors, etiology, side and territory of stroke, social characteristics of the patient (age, sex, profession, educational level, family situation), poststroke seizures, recurrent stroke, other vascular events, and deaths were collected. Neurological deficits were graded with the National Institutes of Health (NIH) Stroke Scale. Poststroke depression (PSD) was quantified using the DSM-IIIR criteria and the Montgomery Asberg Depression Rating Scale. Outcomes were rated with the Ranking Scale, the Barthel Index and the Glasgow Outcome Scale. Quality of life was assessed with the Sickness Impact Profile. Follow-up information was obtained by interview and neurological examination. Follow-up information was obtained in 65 patients at a mean of 31.7 ± 13.0 (range 12–59) months, as 2 patients died and 4 were lost to follow-up and were thus excluded from this study. Poststroke seizures occurred in 7 patients (10.8%) and recurrent strokes in 4 patients (6.2%), but none were fatal. The outcome after stroke among survivors was usually good, since more than two-thirds of the patients (69.8%) reported no problem, 11.1% moderate handicap and one-fifth major handicap. Forty-six patients (73%) returned to work; the time period ranging from several days after stroke to 40 months, with a mean of 8 months. However, adjustments in their occupation were necessary for 12 patients (26.1%). PSD was common, since 48.3% of the patients were classified as depressed. PSD was associated with the localization of the infarct (carotid territory), a severe disability, a bad general outcome, and an absence of return to work. Their opinion about their quality of life was negative among approximately 30% of the patients, especially in emotional and alertness behaviors, social interaction, recreation and pastimes.The general outcome after cerebral infarct in young adults is usually good. However, the risk of a PSD is high, and only half of the patients had returned to their previous work. A remaining psychosocial handicap and depression of sexual activity impaired the quality of life. In multivariate analysis, a low NIH score at admission is a significant predictor for return to work, the absence of PSD, and a good quality of life.

Marie Rosier gives suggestions on the next stage of your search for the right school.

Marie Rosier, Registrar and Marketing Director for Mentone Grammar, uses her experience to make recommendations for families in search of the right school.

Introduction and hypothesisThis article from Chapter 1 of the International Urogynecology Consultation (IUC) on Pelvic Organ Prolapse (POP) establishes the prevalence of lower urinary tract disorders, bowel symptoms, vulvo-vaginal/lower abdominal/back pain and sexual dysfunction in women with POP.MethodsAn international group of nine urogynecologists/urologists and one medical student performed a search of the literature using pre-specified search terms in Ovid, MEDLINE, Embase and CINAHL from January 2000 to March 2019. Publications were eliminated if not relevant or they did not include clear definitions of POP or the symptoms associated with POP. Definitions of POP needed to include both a physical examination finding using a validated examination technique and the complaint of a bothersome vaginal bulge. Symptoms were categorized into symptom groups for ease of evaluation. The Specialist Unit for Review Evidence (SURE) was used to evaluate for quality of the included articles. The resulting list of articles was used to determine the prevalence of various symptoms in women with POP. Cohort studies were used to evaluate for possible causation of POP as either causing or worsening the symptom category.ResultsThe original search yielded over 12,000 references, of which 50 were used. More than 50% of women with POP report lower urinary tract symptoms. Cohort studies suggest that women with POP have more obstructive lower urinary tract symptoms than women without POP. Pain described in various ways is frequently reported in women with POP, with low back pain being the most common pain symptom reported in 45% of women with POP. In cohort studies those with POP had more pain complaints than those without POP. Sexual dysfunction is reported by over half of women with POP and obstructed intercourse in 37–100% of women with POP. Approximately 40% of women have complaints of bowel symptoms. There was no difference in the median prevalence of bowel symptoms in those with and without POP in cohort studies.ConclusionsThe prevalence of lower urinary tract disorders, bowel symptoms, vulvo-vaginal/lower abdominal/back pain and sexual dysfunction in women with POP are common but inconsistently reported. There are few data on incidence of associated symptoms with POP, and cohort studies evaluating causality are rare or inconsistent. Obstructive voiding, lower abdominal and pelvic pain, and sexual dysfunction are most frequently associated with POP.

This article focuses on the practical issue of a recent theoretical method proposed for trend estimation in high dimensional time series. This method falls within the scope of the low-rank matrix factorization methods in which the temporal structure is taken into account. It consists of minimizing a penalized criterion, theoretically efficient but which depends on two constants to be chosen in practice. We propose a two-step strategy to solve this question based on two different known heuristics. The performance and a comparison of the strategies are studied through an important simulation study in various scenarios. In order to make the estimation method with the best strategy available to the community, we implemented the method in an R package TrendTM which is presented and used here. Finally, we give a geometric interpretation of the results by linking it to PCA and use the results to solve a high-dimensional curve clustering problem. The package is available on CRAN.

This article focuses on the practical issue of a recent theoretical method proposed for trend estimation in high dimensional time series. This method falls within the scope of the low-rank matrix factorization methods in which the temporal structure is taken into account. It consists of minimizing a penalized criterion, theoretically efficient but which depends on two constants to be chosen in practice. We propose a two-step strategy to solve this question based on two different known heuristics. The performance and a comparison of the strategies are studied through an important simulation study in various scenarios. In order to make the estimation method with the best strategy available to the community, we implemented the method in an R package TrendTM which is presented and used here. Finally, we give a geometric interpretation of the results by linking it to PCA and use the results to solve a high-dimensional curve clustering problem. The package is available on CRAN.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a strong genetic component whose knowledge evolves quickly. Next-generation sequencing is the only effective technology to deal with the high genetic heterogeneity of ASD in a clinical setting. However, rigorous criteria to classify rare genetic variants conferring ASD susceptibility are currently lacking. We have performed whole-exome sequencing to identify both nucleotide variants and copy number variants (CNVs) in 253 ASD patients, including 68 patients with intellectual disability (ID) and 90 diagnosed as Asperger syndrome. Using explicit criteria to classify both susceptibility genes and susceptibility variants we prioritized 217 genes belonging to the following categories: syndromic genes, genes with an excess of de novo protein truncating variants and genes targeted by rare CNVs. We obtained a susceptibility variant detection rate of 19.7% (95% CI: [15–25.2%]). The rate for CNVs was 7.1% (95% CI: [4.3–11%]) and 12.6% (95% CI: [8.8–17.4%]) for nucleotide variants. The highest rate (30.1%, 95% CI: [20.2–43.2%]) was obtained in the ASD + ID subgroup. A strong contributor for at risk nucleotide variants was the recently identified set of genes ( n  = 81) harboring an excess of de novo protein truncating variants. Since there is currently no evidence that the genes targeted here are necessary and sufficient to cause ASD, we recommend to avoid the term “causative of ASD” when delivering the information about a variant to a family and to use instead the term “genetic susceptibility factor contributing to ASD”.