Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)

Accuracy of LightCycler(R) SeptiFast for the detection and identification of pathogens in the blood of patients with suspected sepsis : a systematic review protocol

Background There is growing interest in the potential utility of molecular diagnostics in improving the detection of life-threatening infection (sepsis). LightCycler® SeptiFast is a multipathogen probe-based real-time PCR system targeting DNA sequences of bacteria and fungi present in blood samples within a few hours. We report here the protocol of the first systematic review of published clinical diagnostic accuracy studies of this technology when compared with blood culture in the setting of suspected sepsis. Methods/design Data sources: the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects (DARE), the Health Technology Assessment Database (HTA), the NHS Economic Evaluation Database (NHSEED), The Cochrane Library, MEDLINE, EMBASE, ISI Web of Science, BIOSIS Previews, MEDION and the Aggressive Research Intelligence Facility Database (ARIF). Study selection: diagnostic accuracy studies that compare the real-time PCR technology with standard culture results performed on a patient's blood sample during the management of sepsis. Data extraction: three reviewers, working independently, will determine the level of evidence, methodological quality and a standard data set relating to demographics and diagnostic accuracy metrics for each study. Statistical analysis/data synthesis: heterogeneity of studies will be investigated using a coupled forest plot of sensitivity and specificity and a scatter plot in Receiver Operator Characteristic (ROC) space. Bivariate model method will be used to estimate summary sensitivity and specificity. The authors will investigate reporting biases using funnel plots based on effective sample size and regression tests of asymmetry. Subgroup analyses are planned for adults, children and infection setting (hospital vs community) if sufficient data are uncovered. Dissemination Recommendations will be made to the Department of Health (as part of an open-access HTA report) as to whether the real-time PCR technology has sufficient clinical diagnostic accuracy potential to move forward to efficacy testing during the provision of routine clinical care

Decolorization of textile dyestuffs by a mixed bacterial consortium

A mixed anaerobic bacterial culture decolorized Drimaren Orange K-GL, Everzol Red RBN and Everdirect Supra Yellow PG dyestuffs at 200 mg dyestuff l(-1) over 24 h. Improved performance with complete decolorization within 24 h was achieved by incubation with 5 g yeast extract l(-1) compared to glucose, lactose and sucrose though 50 mg yeast extract l(-1) supplemented with 5 g lactose l(-1) or 5 g sucrose l(-1) also resulted in complete decolorization within 24 h

Effect of environmental conditions on biological decolorization of textile dyestuff by C. versicolor

Effects of environmental conditions such as pH, media composition, Carbon and nitrogen sources, TOC/N ratio, and dyestuff concentrations on decolorization of reactive phytalocyanin type textile dyestuff Everzol Turquoise Blue G by white rot fungi, Coriolus versicolor MUCL were investigated. pH = 4.5 and the media III were found to be the most suitable ones among the others tested. Compared to the other carbon and nitrogen sources tested, glucose and urea resulted in better decolorization performances. High TOC/N ratio (TOC/N > 20) or low nitrogen concentration was essential for effective decolorization of the dyestuff. Dyestuff concentration should be lower than 500 mg/l for complete decolorization. Only partial decolorization was observed for dyestuff concentrations above 500 mg/l. Adsorption of the dyestuff on surfaces of the fungi was insignificant ( < 20%). Published by Elsevier Science Inc

Effect of environmental conditions on biological decolorization of textile dyestuff by C. versicolor

Identified regulatory sites containing somatic mutations. (XLSX 2006 kb

Audit of the use of antimicrobial prophylaxis in nasal surgery at a speciali

Background: In 2002&minus;03 a retrospective audit of the use of surgical antimicrobial prophylaxis (AMP) for elective nasal surgery was undertaken at the Royal Victorian Eye and Ear Hospital (RVEEH). The RVEEH is a publicly funded teaching hospital that provides specialist eye, nose and throat medicine in Victoria, Australia. The aim of the audit was to determine the extent to which the use of antimicrobial prophylaxis in the hospital was consistent with Australian and international evidence-based guidelines and if there was a need for the hospital to develop internal guidelines for the use of AMP.Methods: The histories of 500 consecutive patients who had undergone nasal surgery within the study period of August 2001 and July 2002 were examined. The data collected from these histories included information such as the patients\u27 age, gender, diagnosis, surgical procedure performed, antimicrobial agents used, and the length of follow up and a range of factors shown in previous studies to increase the risk of surgical site infection.Results: A total of 306 (72.86%) patients were found to have received antimicrobial agents either prior to admission, during admission or on discharge. Only 24 patients (5.71%) were administered antimicrobials immediately prior to surgery and at no other time.Conclusions: The findings of this study support the need for further research to examine the appropriateness of the use of AMP at the RVEEH and the need for internal guidelines for its use.<br /