Trouvez ma clinique!

The \u201cFind my clinic!\u201d Google Maps-based application allows users to locate clinics that are open at a specific time of the day within an area around a given postal code . A proof of concept for this application is currently functional for a subset of walk-in clinics in Moncton, New Brunswick and could be easily expanded to cover all major cities in the province and in Atlantic Canada.L\u2019application \u201cTrouvez ma clinique!\u201d bas\ue9e sur la technologie Google Maps permet aux utilizateurs de localiser des cliniques qui sont ouvertes \ue0 un moment pr\ue9cis de la journ\ue9e dans une region autour d\u2019un code postal donn\ue9e. Une prevue de concept pour cette application est actuellement fonctionelle pour un sous-ensemble des cliniques sans rendez-vous dans Moncton, au Nouveau-Brunswick et pourrait \ueatre facilement \ue9tendue pour couvrir toutes les grandes villes de la province et du Canada Atlantique.Peer reviewed: NoNRC publication: Ye

Collapsing cristobalitelike structures in silica analogues at high pressure

The cristobalitelike forms of the ternary silica analogues BPO4 and BAsO4 were investigated at high pressure by x-ray diffraction and theoretical methods. The behavior of these compounds represents an extreme case in which the tilt angle of the constituent tetrahedra increases in a spectacular way at high pressure resulting in a major change in topology from a cristobalitelike framework towards a \ufffdcollapsed cristobalite\ufffd structure. These compounds provide the first examples of the collapse of a framework structure to a close-packed form in a continuous manner without an intervening phase transition.NRC publication: Ye

PP2A-Bgamma subunit and KCNQ2 K(+) channels in bipolar disorder

Many bipolar affective disorder (BD) susceptibility loci have been identified but the molecular mechanisms responsible for the disease remain to be elucidated. In the locus 4p16, several candidate genes were identified but none of them was definitively shown to be associated with BD. In this region, the PPP2R2C gene encodes the Bgamma-regulatory subunit of the protein phosphatase 2A (PP2A-Bgamma). First, we identified, in two different populations, single nucleotide polymorphisms and risk haplotypes for this gene that are associated to BD. Then, we used the Bgamma subunit as bait to screen a human brain cDNA library with the yeast two-hybrid technique. This led us to two new splice variants of KCNQ2 channels and to the KCNQ2 channel itself. This unusual K+ channel has particularly interesting functional properties and belongs to a channel family that is already known to be implicated in several other monogenic diseases. In one of the BD populations, we also found a genetic association between the KCNQ2 gene and BD. We show that KCNQ2 splice variants differ from native channels by their shortened C-terminal sequences and are unique as they are active and exert a dominant-negative effect on KCNQ2 wild-type (wt) channel activity. We also show that the PP2A-Bgamma subunit significantly increases the current generated by KCNQ2wt, a channel normally inhibited by phosphorylation. The kinase glycogen synthase kinase 3 beta (GSK3beta) is considered as an interesting target of lithium, the classical drug used in BD. GSK3beta phosphorylates the KCNQ2 channel and this phosphorylation is decreased by Li+

Randomised controlled trial of methotrexate for chronic inflammatory demyelinating polyradiculoneuropathy (RMC trial): a pilot, multicentre study

BACKGROUND: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) responds to treatment with corticosteroids, intravenous immunoglobulin, and plasma exchange. We aimed to test whether the standard immunosuppressive drug methotrexate was of use in treatment of CIDP. METHODS: In a pilot, multicentre, randomised, double-blind, controlled trial we compared oral methotrexate 7.5 mg weekly for 4 weeks, then 10 mg weekly for 4 weeks, and finally 15 mg weekly for 32 weeks (40 weeks' total treatment) with placebo in patients with CIDP requiring intravenous immunoglobulin or corticosteroids. After about 16 weeks, the dose of corticosteroids or intravenous immunoglobulin was decreased by 20% every 4 weeks if participants did not deteriorate. Primary outcome was a greater than 20% reduction in mean weekly dose in the last 4 weeks of the trial compared with the first 4 weeks. Secondary outcomes analysed separately at the mid-trial and final visits measured activity limitations and strength. Analyses were done by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN73774524. FINDINGS: 59 of the 60 enrolled participants completed the trial. 14 (52%) of 27 taking methotrexate and 14 (44%) of 32 taking placebo had a greater than 20% reduction in mean weekly dose of corticosteroids or intravenous immunoglobulin (adjusted odds ratio 1.21, 95% CI 0.40-3.70). There were no clinically and statistically significant differences in secondary outcomes. The one serious adverse event in the placebo group and the three in the methotrexate group were not thought to be related to treatment. INTERPRETATION: Oral methotrexate 15 mg weekly showed no significant benefit, but limitations in the trial design and the high rate of response in the placebo group meant that a treatment effect could not be excluded. This study can inform design of future trials in CIDP. FUNDING: The GBS/CIDP Foundation International

Pr\ue9faces d\u2019antiromans: la contrefa\ue7on pr\ue9facielle chez l\u2019abb\ue9 Laurent Bordelon

Il contributo intende dimostrare come le prefazioni degli "antiromanzi" dell'abate Lorent Bordelon mantengano il loro statuto testuale a dispetto dei procedimenti metafinzionali che vengono messi in atto dall'autore

European Society for Paediatric Endocrinology consensus guidelines on screening, diagnosis, and management of congenital hypothyroidism.

OBJECTIVE: The aim was to formulate practice guidelines for the diagnosis and management of congenital hypothyroidism (CH). EVIDENCE: A systematic literature search was conducted to identify key articles relating to the screening, diagnosis, and management of CH. The evidence-based guidelines were developed with the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system, describing both the strength of recommendations and the quality of evidence. In the absence of sufficient evidence, conclusions were based on expert opinion. CONSENSUS PROCESS: Thirty-two participants drawn from the European Society for Paediatric Endocrinology and five other major scientific societies in the field of pediatric endocrinology were allocated to working groups with assigned topics and specific questions. Each group searched the literature, evaluated the evidence, and developed a draft document. These papers were debated and finalized by each group before presentation to the full assembly for further discussion and agreement. RECOMMENDATIONS: The recommendations include: worldwide neonatal screening, approaches to assess the cause (including genotyping) and the severity of the disorder, the immediate initiation of appropriate L-T4 supplementation and frequent monitoring to ensure dose adjustments to keep thyroid hormone levels in the target ranges, a trial of treatment in patients suspected of transient CH, regular assessments of developmental and neurosensory functions, consulting health professionals as appropriate, and education about CH. The harmonization of diagnosis, management, and routine health surveillance would not only optimize patient outcomes, but should also facilitate epidemiological studies of the disorder. Individuals with CH require monitoring throughout their lives, particularly during early childhood and pregnancyObjective: The aim was to formulate practice guidelines for the diagnosis and management of congenital hypothyroidism (CH). Evidence: A systematic literature search was conducted to identify key articles relating to the screening, diagnosis, andmanagementof CH. The evidence-based guidelines were developed with the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system, describing both the strength of recommendations and the quality of evidence. In the absence of sufficient evidence, conclusions were based on expert opinion. Consensus Process: Thirty-two participants drawn from the European Society for Paediatric Endocrinology and five other major scientific societies in the field of pediatric endocrinology were allocated to working groups with assigned topics and specific questions. Each group searched the literature, evaluated the evidence, and developed a draft document. These papers were debated and finalized by each group before presentation to the full assembly for further discussion and agreement. Recommendations: The recommendations include: worldwide neonatal screening, approaches to assess the cause (including genotyping) and the severity of the disorder, the immediate initiation of appropriate L-T4 supplementation and frequent monitoring to ensure dose adjustments to keep thyroid hormone levels in the target ranges, a trial of treatment in patients suspected of transient CH, regular assessments of developmental and neurosensory functions, consulting health professionals as appropriate, and education about CH. The harmonization of diagnosis, management, and routine health surveillance would not only optimize patient outcomes, but should also facilitate epidemiological studies of the disorder. Individuals with CH require monitoring throughout their lives, particularly during early childhood and pregnancy