Aggerbruun6119

BACKGROUND Cys-loop receptors control neuronal excitability in the brain and their dysfunction results in numerous neurological disorders. Recently, six missense variants in GABRA2, a member of this family, have been associated with early infantile epileptic encephalopathy (EIEE). We identified a novel de novo missense variant in GABRA2 in a patient with EIEE and performed protein structural analysis of the seven variants. METHODS The novel variant was identified by trio whole-genome sequencing. We performed protein structural analysis of the seven variants, and compared them to previously reported pathogenic mutations at equivalent positions in other Cys-loop receptors. Additionally, we studied the distribution of disease-associated variants in the transmembrane helices of these proteins. RESULTS The seven variants are in the transmembrane domain, either close to the desensitization gate, the activation gate, or in inter-subunit interfaces. Six of them have pathogenic mutations at equivalent positions in other Cys-loop receptors, emphasizing the importance of these residues. Also, pathogenic mutations are more common in the pore-lining helix, consistent with this region being highly constrained for variation in control populations. CONCLUSION Our study reports a novel pathogenic variant in GABRA2, characterizes the regions where pathogenic mutations are in the transmembrane helices, and underscores the value of considering sequence, evolutionary, and structural information as a strategy for variant interpretation of novel missense mutations. © 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.BACKGROUND Prognostication is a complex clinical task that involves forming a prediction about recovery and communicating prognostic information to patients and families. In aphasia, recovery is difficult to predict and evidence-based guidance on prognosis delivery is lacking. Questions about aphasia prognosis commonly arise, but it is unknown how speech pathologists formulate and deliver information about expected recovery. An understanding of current practice in prognostication is needed to develop evidence-based guidelines for this process, and is necessary in order to ensure successful future implementation of recommended practice regarding prognosis delivery. AIMS To identify the factors speech pathologists consider important when responding to questions about aphasia prognosis; to examine how they respond in different scenarios; and to evaluate their current attitudes towards aphasia prognostication. METHODS & PROCEDURES A total of 54 speech pathologists participated in an online survey featuring hypothy, the prognostic information they deliver and the manner in which they communicate prognoses. Current approaches to aphasia prognostication are reliant on experience and professional judgement, and speech pathologists desire more support for undertaking this task. What are the potential or actual clinical implications of this work? Speech pathologists lack a consistent approach to aphasia prognostication and desire more support in this task. The present findings offer insight into clinician attitudes and practice, and provide a direction for future research to establish best-practice guidelines for this complex and demanding area of aphasia management. © 2020 Royal College of Speech and Language Therapists.BACKGROUND The Victorian Pancreas Cancer summit 2017 analysed state-wide data on management of Victorians with pancreas cancer between 2011 and 2015 to identify variations in care and outcomes. Pancreas cancer remains a formidable disease but systemic therapies are increasingly effective. Surgery remains essential but insufficient alone for cure. CDK inhibitor Understanding patterns of care and identifying variations in treatment is critical to improving outcomes. METHODS This population-based study analysed data collected prospectively by Department of Health and Human services (Victorian state government). Data were extracted from Victorian Cancer Registry (covering all Victorian cancer diagnoses), Victorian Admitted-Episodes Dataset (all inpatient data), Victorian Radiotherapy Minimum Dataset and Victorian Death Index providing demographics, tumour and treatment characteristics, age-standardized incidence, overall and median survival. RESULTS Of 3962 Victorian patients with any form of pancreatic malignancy, 82% were ductal adenocarcinoma (PDAC), of whom 67% had metastases at diagnosis. One-year overall survival for PDAC was 30% (60% non-metastatic, 15% if metastatic). Median survival with metastases increased from 2.7 to 3.9 months, and from 13.3 to 15.9 months for non-metastatic PDAC between 2011 and 2015. Thirty-one percent of non-metastatic patients underwent pancreatectomy. About 1.5% were treated with neoadjuvant chemotherapy/chemoradiation. Of patients undergoing intended curative resection, 77% proceeded to adjuvant therapy. Fifty-one percent of metastatic PDAC patients never received anti-tumour therapy. CONCLUSIONS Nearly one-fourth of surgically treated patients never received systemic therapy. More than two-thirds of non-metastatic patients never proceeded to surgery. Further consideration of neoadjuvant therapy should be given to borderline resectable patients. Most patients with PDAC still die soon after diagnosis, but median survival is increasing. © 2020 Royal Australasian College of Surgeons.BACKGROUND Event-related potentials (ERPs), which are electrophysiological neural responses time-locked to a stimulus, have become an increasingly common tool in language and communication disorders research. They can provide complementary evidence to behavioural measures as well as unique perspectives on communication disorders. ERPs have the distinct advantage of providing precise information about the timing of neural processes and can be used in cases where it is difficult to obtain responses from participants, such as infants or individuals who are minimally verbal. However, clinicians and clinician-scientists rarely receive training in how to interpret ERP research. AIMS To provide information that allows readers to better understand, interpret and evaluate research using ERPs. We focus on research related to communication sciences and disorders and the information that is most relevant to interpreting research articles. METHOD We explain what ERPs are and how ERP data are collected, referencing key texts and primary research articles.