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Epilepsy is a common neurological condition that shows a marked genetic predisposition. The advent of next-generation sequencing (NGS) has transformed clinical genetic testing by allowing the rapid screen for causative variants in multiple genes. There are currently no NGS-based multigene panel diagnostic tests available for epilepsy as a licensed clinical diagnostic test in Ontario, Canada. Eligible patient samples are sent out of country for testing by commercial laboratories, which incurs significant cost to the public healthcare system.
An expert Working Group of medical geneticists, pediatric neurologists/epileptologists, biochemical geneticists, and clinical molecular geneticists from Ontario was formed by the Laboratories and Genetics Branch of the Ontario Ministry of Health and Long-Term Care to develop a programmatic approach to implementing epilepsy panel testing as a provincial service.
The Working Group made several recommendations for testing to support the clinical delivery of care in Ontario. First, an extension of community healthcare outcomes-based program should be incorporated to inform and educate ordering providers when requesting and interpreting a genetic panel test. Second, any gene panel testing must be “evidence-based” and takes into account varied clinical indications to reduce the chance of uncertain and secondary results. Finally, an ongoing evaluative process was recommended to ensure continued test improvement for the future.
This epilepsy panel testing implementation plan will be a model for genetic care directed toward a specific set of conditions in the province and serve as a prototype for genetic testing for other genetically heterogeneous diseases.
Background: Cerebellar atrophy is characterized by loss of cerebellar tissue, with evidence on brain imaging of enlarged interfolial spaces compared to the foliae. Genetic ataxias associated with cerebellar atrophy are a heterogeneous group of disorders. We investigated the prevalence in Canada and the diagnostic yield of whole exome sequencing (WES) for this group of conditions. Methods: Between 2011 and 2017, WES was performed in 91 participants with cerebellar atrophy as part of one of two national research programs, Finding of Rare Genetic Disease Genes (FORGE) or Enhanced Care for Rare Genetic Diseases in Canada (Care4Rare). Results: A genetic diagnosis was established in 58% of cases (53/91). Pathogenic variants were found in 24 known genes, providing a diagnosis for 46/53 participants (87%), and in four novel genes, accounting for 7/53 cases (13%). 38/91 cases (42%) remained unsolved. The most common diagnoses were channelopathies in 12/53 patients (23%) and mitochondrial disorders in 9/53 (17%). Inheritance was autosomal recessive in the majority of cases. Additional clinical findings provided useful clues to some of the diagnoses. Conclusions: This is the first report on the prevalence of genetic ataxias associated with cerebellar atrophy in Canada, and the utility of WES for this group of conditions.
This paper reviews progress in the application of computational models to
personality, developmental, and clinical neuroscience. We first describe the
concept of a computational phenotype, a collection of parameters derived from
computational models fit to behavioral and neural data. This approach represents
individuals as points in a continuous parameter space, complementing traditional
trait and symptom measures. One key advantage of this representation is that it
is mechanistic: The parameters have interpretations in terms of cognitive
processes, which can be translated into quantitative predictions about future
behavior and brain activity. We illustrate with several examples how this
approach has led to new scientific insights into individual differences,
developmental trajectories, and psychopathology. We then survey some of the
challenges that lay ahead.
The depth at which pitfall traps were sunk into the ground and the resulting catches of epigaeic Carabidae (Coleoptera) and Staphylinidae (Coleoptera) assemblages in subhygric to hydric ecosites with very deep organic soil layers was investigated in the upper foothills ecoregion of Alberta, Canada. Traps were installed at seven sites, with six surface traps (the pitfall trap lip <5 cm below soil surface) and six deep traps (the pitfall trap lip >20 cm below soil surface) at each site. A total of 5289 beetles representing 75 taxa were collected. There were no significant effects of trap depth on catch. Rarefaction estimates of species diversity were higher in surface pitfall traps for both taxa. The similarity of pooled catches between deep and surface traps was on average 75%, suggesting that both trap types were collecting similar faunas. We found no advantage to using deep pitfall traps in addition to surface traps to sample the epigaeic fauna of wet forest stands and peatlands.
Background: Inadequate postoperative pain control is common and is associated with negative clinical outcomes. The objective is to identify preoperative predictors of poor postoperative pain control in the adult population undergoing inpatient surgery. Methods: Meta-analysis was performed according to MOOSE guidelines. Studies were included if they evaluated postoperative pain using a validated instrument in adults undergoing inpatient surgery and reported a measure of association between poor postoperative pain control and at least one preoperative predictor. Measures of association were pooled using random effects models. Results: A total of 33 studies representing 59,259 patients were included. Significant preoperative predictors of poor postoperative pain included sleeping difficulties (OR 2.32 [95% CI 1.46-3.69]), history of depressive symptoms (OR 1.71 [95% CI 1.32-2.22]), use of preoperative analgesia (OR 1.54 [95% CI 1.18-2.03]), smoking (OR 1.33 [95% CI 1.09-1.61]), -female sex (OR 1.29 [95% CI 1.17-1.43]), presence of preoperative pain (OR 1.21 [95% CI 1.10-1.32]], history of anxiety symptoms (OR 1.22 [95% CI 1.09-1.36)], younger age (OR 1.18 [95% CI 1.05-1.32)], and higher BMI (OR 1.02 [95% CI 1.01-1.03]). Conclusions: Nine significant predictors of poor postoperative pain control were identified and these should be recognized as important factors when developing pre- and peri-operative strategies to improve pain outcomes.
A number of laser facilities coming online all over the world promise the capability of high-power laser experiments with shot repetition rates between 1 and 10 Hz. Target availability and technical issues related to the interaction environment could become a bottleneck for the exploitation of such facilities. In this paper, we report on target needs for three different classes of experiments: dynamic compression physics, electron transport and isochoric heating, and laser-driven particle and radiation sources. We also review some of the most challenging issues in target fabrication and high repetition rate operation. Finally, we discuss current target supply strategies and future perspectives to establish a sustainable target provision infrastructure for advanced laser facilities.
Background: Menkes disease is a rare, X-linked recessive disorder of the ATP7A gene, a copper transporter; resulting in systemic copper deficiency. The deficient function of copper-dependent enzymes manifests clinically with failure to thrive, seizures, hypotonia, coarse hair, connective tissue abnormalities, and neurodegeneration. Cerebral arteries are often elongated, tortuous, and fragile. Methods: This case report was prepared using the patient’s hospital chart, and a review of the literature undertaken using PubMed. Our case was subsequently compared and contrasted to known Menkes’ literature. Results: We present the case of a 2 month old male with Menkes disease who presented with new seizure onset in the setting of a Grade III intraventricular hemorrhage with hydrocephalus. He deteriorated into status epilepticus, and palliative care was instituted. On autopsy, pronounced tortuosity of his cerebral vasculature was noted, as well as a bilaterally cystic brain with an organizing hemorrhage on the ventral surface of the brainstem. Conclusions: Although Menkes disease often presents with seizures, neurologic deterioration, and abnormal cerebral vasculature; the quick demise subsequent to an intraventricular hemorrhage is somewhat unusual and discussed.
In 1975, Hoessel, Elias, Wade and Huchra commenced a near infrared survey of 80 fields in the northern Milky Way with the Palomar 1.2 m Schmidt telescope, (Hoessel et al. 1979). This has now been issued as an atlas reproduced in the form of photographic paper prints. In 1977, the SRC 1.2 m Schmidt telescope at Siding Spring was authorized to commence a complementary survey of the southern Milky Way, consisting of the 151 ESO/SRC survey fields which have centres within 10° of the galactic plane and negative declinations (see Fig. 1). A further 12 fields have subsequently been added to the survey to permit coverage of the Large and Small Magellanic Clouds.
Freshwater fishes represent among the most diverse and threatened taxa globally, accounting for more than 25% of total vertebrates (> 30,000 species described), 37% of which are threatened with extinction (Darwall et al., 2008; Chapter 1). The poor conservation status of freshwater biodiversity is directly related to the pressure that these systems experience worldwide (Vörösmarty et al., 2010). Because of their importance to human welfare and development, freshwater ecosystems and biodiversity are subject to higher pressures and threats than are adjacent terrestrial ecosystems (Nel et al., 2007). Water pollution and abstraction coupled with invasive species and habitat modification (e.g. channelling and damming) are the principal threats to the conservation of freshwater biodiversity (Strayer & Dudgeon, 2010; Vörösmarty et al., 2010). These pressures are rapidly growing due to the increase of human population worldwide and the effect of climate change (Dudgeon et al., 2006; Chapter 3).
Although freshwater ecosystems and biodiversity are in urgent need of protection, there has been little emphasis on declaring protected areas for the primary purpose of conserving freshwater biodiversity (although see attempts in South Africa since the early 1970s (Roux & Nel, 2013 for a brief history) or the USA (Moyle & Yoshiyama, 1994)). Instead, uninformed opportunism has reigned, whereby the conservation of freshwater ecosystems has remained peripheral to conservation goals developed for terrestrial ecosystems, unless considered important for terrestrial biodiversity (Nel et al., 2007; Olden et al., 2010). The implementation of conservation is constrained by limited budgets and potential conflicts with other human uses. For this reason, it is unfeasible to protect all the areas that contribute to the persistence of biodiversity (Margules et al., 2002), and adequate planning is required. Conservation planning is a discipline that tries to deal with these issues to inform stakeholders and decision-makers on how to best invest limited resources available for conservation. The development of a conservation plan typically draws on knowledge spanning several scientific disciplines, increasingly also from the social sciences.
To be effective for freshwater conservation in general and fish in particular, protected areas must consider some particularities of freshwater ecosystems from the early planning stages (e.g. when deciding where to implement conservation) to the daily management. Freshwater ecosystems pose some unique challenges to the implementation of effective conservation (Abell, 2002), such as the importance of connectivity at maintaining natural processes and facilitating the propagation of threats (Linke et al., 2011).
Migratory fishes are natural wonders. For many people, the term migratory fish evokes images of salmon audaciously jumping at waterfalls as they return to their own riverine birthplace to spawn after years of growth in the ocean, but freshwater fishes actually show a broad spectrum of migration strategies. Migratory fishes include small species – three-spined sticklebacks that spawn in coastal streams around the northern Pacific and gobies that move from the ocean into tropical island streams by climbing waterfalls (McDowall, 1988) – as well as some of the largest freshwater fishes in the world, such as the Mekong dog-eating catfish and the Chinese paddlefish (Stone, 2007). Aside from migratory habits, these species have few shared characteristics; they encompass numerous evolutionary lineages, enormous differences in life history, and every possible direction and distance of migration. Biologists treat migratory freshwater fishes as a functional group because their life-history strategy revolves around long-distance movement between ecosystems in a perilous quest to take advantage of both high-quality breeding sites and bountiful feeding areas. As humans have physically blocked fish migrations, degraded breeding and feeding grounds and relentlessly harvested migrants for their flesh and roe, many populations have declined or been extirpated. This chapter will provide an overview of fundamental and applied research that is helping to guide efforts to conserve migratory freshwater fishes.
For practical purposes, we define migratory behaviour as the synchronized movement of a substantial proportion of a population between distinct habitats, which is repeated through time within or across generations. Modern definitions of fish migrations typically recognise both the adaptive benefits of migrating and individual variation in executing the general strategy (see McDowall, 1988; Lucas & Baras, 2001). Not every individual must move, the timing may vary somewhat from year to year, and the motive for migrating may include seeking refuge from harsh conditions in addition to breeding and feeding. Nonetheless, in most cases, migration is critical to individual fitness and population persistence because it enables specialised use of different habitats for growth and reproduction. Where their migration routes are blocked or key habitats are lost, migratory fishes often suffer rapid and catastrophic losses.
Human appropriation and degradation of the Earth's freshwater ecosystems (Vörösmarty et al., 2010; Carpenter et al., 2011) have transformed this reliance on multiple habitats into a detriment for many migratory fishes.
Cricopharyngeal dysfunction following head and neck cancer treatment may lead to a significant reduction in oral intake. Carbon dioxide laser is an established procedure for the treatment of non-malignant cricopharyngeal disorders. We report our experience of laser cricopharyngeal myotomy with objective swallowing outcome measures, before and after treatment.
We identified 11 patients who had undergone carbon dioxide laser cricopharyngeal myotomy for dysphagia following radiotherapy, with or without chemotheraphy between January 2006 and July 2011. We analysed the swallowing outcomes following carbon dioxide laser cricopharyngeal myotomy by retrospective grading of pre- and post-procedure videofluoroscopic swallowing study of liquids, using the validated Modified Barium Swallow Impairment Profile.
The median Modified Barium Swallow Impairment Profile score was 13 pre-myotomy and 10 post-myotomy. This difference between scores was non-significant (p = 0.41). The median, cricopharyngeal-specific Modified Barium Swallow Impairment Profile variables (14 and 17) improved from 3 to 2, but were similarly non-significant (p = 0.16). We observed the improved Modified Barium Swallow Impairment Profile scores post-procedure in the majority of patients.
Endoscopic carbon dioxide laser cricopharyngeal myotomy remains a viable option in treatment-related cricopharyngeal dysfunction; its targeted role requires further prospective study. Objective analysis of the technique can be reported using the validated Modified Barium Swallow Impairment Profile.
High Speed Sintering (HSS) is a novel additive manufacturing technology which currently uses Nylon 12 as the standard feedstock material. To expand the number of processable materials, the preferred characteristics of polymeric powder as a feedstock powder are presented, appropriate materials identified, parts made, and mechanical properties measured. Two commercially available laser sintering (LS) grade powders previously untested for HSS were selected, DuraForm® HST10 and ALM TPE 210-S. Tensile test specimens were manufactured using each material and mechanical properties analyzed and compared to the manufacturers' specification for LS. Tensile test specimens built using DuraForm® PA show higher tensile strength and elongation at break than LS whereas DuraForm® HST10 shows somewhat reduced tensile strength but slightly increased elongation at break. ALM TPE 210-S shows elongation at break of more than double that of LS demonstrating the capability of HSS to process viscous materials. The results indicate that HSS is capable of processing LS grade polymeric powders and may extend beyond.
It is unrealistic to achieve high-resolution biodiversity inventories required to support local conservation strategies over large areas; however, benchmark associations between arthropods and ecosystem classification can support landscape scale biomonitoring. We investigated habitat associations of ground-dwelling spiders (Araneae), staphylinid beetles (Coleoptera: Staphylinidae), and carabid beetles (Coleoptera: Carabidae) in three forest ecosystems in northwestern Alberta, Canada and also studied the effect of variation in depth of pitfall trap installation on catch. Composition and diversity of all three taxa were correlated with the ecosystem classification map, and 20 species were strong indicators of particular habitats. The black spruce (Picea mariana (Miller) Britton, Sterns, and Poggenburg; Pinaceae) bog supported fewer species and individuals of beetles but this trend was not observed for spiders because of natural history traits associated with their performance in this environment. Pitfall trapping biases were constant among habitats enabling proper comparison of ground-dwelling invertebrate assemblages. Three species of beetles (Agonum retractum LeConte (Coleoptera: Carabidae), Pterostichus brevicornis (Kirby) (Coleoptera: Carabidae), and Quedius velox Smetana (Coleoptera: Staphylinidae)) were disproportionally active beneath the soil surface, as catches were greater in pitfall traps with the lip situated 15–25 cm below the soil surface. Thus, even highly standardised trap placement will influence the concept of biodiversity achieved through pitfall trapping, because some target organisms are disproportionately active in subterranean zones.
Oral mucositis is common for patients undergoing chemoradiotherapy for squamous cell carcinoma of the head and neck (SCCHN). Despite the significant detrimental sequelae associated, there is no consensus on the optimum mouth care regimen. This prospective audit aims to record mucositis and dysphagia toxicity and the level of analgesia prescribed when recent products: MuGard™, Caphosol® and Episil® are compared with our standard departmental mouth care regimen.
Patients undergoing concurrent chemoradiotherapy for locally advanced SCCHN at University Hospital Birmingham, UK were prospectively audited weekly for 8 consecutive weeks starting from week 1 of chemoradiotherapy from June 2009 until January 2011. Patients received either standard oral care regimen of aspirin, glycerin and sucralfate, or, MuGard™, Caphosol® or Episil®. Grade of mucositis, dysphagia and analgesia score were prospectively recorded using the common toxicity criteria v3·0.
One hundred and four patients were included. There was no difference in the grade and duration of mucositis (p = 0·82), dysphagia (p = 0·99) or analgesia score (p = 0·61) for either MuGard™, Caphosol® or Episil® compared with standard oral care.
There is no evidence from this audit that Mugard™, Caphosol® or Episil® improves mucositis and dysphagia toxicity or the level of analgesia prescribed compared with our standard departmental mouth care regimen. Randomised trials comparing these approaches are required to detect any meaningful clinical benefit.
Background: Recent research has highlighted the importance of psychological interventions such as cognitive behavioural therapy (CBT) in improving outcomes and promoting recovery for people with experience of psychosis, although a lack of trained therapists means that availability of face-to-face CBT is low. Alternative modes of delivering CBT are being explored, such as telephone and self-help methods, although research to date on whether they can be implemented effectively is limited. Aims: The aims of the present study were to describe and evaluate a new therapy fidelity scale (ROSTA; Recovery Oriented Self-help and Telephone therapy Adherence). This scale was developed to assess fidelity to cognitive behaviour therapy for psychosis (CBTp) focused on improving recovery, with optional subscales for delivery over the telephone and alongside a self-help guide. Method: Experienced CBT therapists rated recorded therapy sessions using the ROSTA scale. The scores were used to assess internal consistency and inter-rater reliability, before being compared to scores from an independent expert rater using an alternative fidelity scale for cognitive therapy in psychosis (the CTS-Psy), to investigate concurrent validity. Results: The ROSTA scale demonstrated excellent internal consistency, inter-rater reliability and validity when evaluated as a whole, although findings were mixed in terms of the individual subscales and items. Conclusions: The ROSTA scale is, on the whole, a reliable and valid tool, which may be useful in training and supervision, a utility that would be further emphasized if the therapeutic intervention it assesses is deemed to be efficacious based on future work.
Using the 22-m ‘Mopra’ antenna (near Coonabarabran, NSW) of the Australia Telescope National Facility (ATNF), we have observed emission from the 115-GHz J = 1−0 transition of CO towards the centre of each of the 1101 clouds listed in the Catalogue of Southern Dark Clouds (SDC) of Hartley et al. (1986). The velocity range covered was −96 to +70 km s−1, with a velocity resolution of 0· 120 km s−1. CO was detected at 1049 of the positions, with 367 spectra showing emission at more than one radial velocity. Here we present the most comprehensive general survey of the SDC catalogue, with the intensity, velocity and half-width of the CO detection and a code describing the profile shape. The presence of blue- or red-shifted wings in many observations can provide a starting point in searches for star-forming regions.
Treatment options for large subglottic haemangioma include steroids, laser ablation, open excision, tracheostomy and, more recently, propranolol. This article aims to present the Great Ormond Street Hospital guidelines for using propranolol to treat infantile isolated subglottic haemangioma by ENT surgeons.
The vascular malformations multidisciplinary team at Great Ormond Street Hospital has developed guidelines for treating infantile haemangioma with propranolol.
The Great Ormond Street Hospital guidelines for propranolol treatment for infantile subglottic haemangioma include investigation, treatment and follow up. Propranolol is started at 1 mg/kg/day divided into three doses, increasing to 2 mg/kg/day one week later. On starting propranolol and when increasing the dose, the pulse rate and blood pressure must be checked every 30 minutes for the first 2 hours. Lesion response to treatment is assessed via serial endoscopy.
Recent reports of dramatic responses to oral propranolol in children with haemangioma and acute airway obstruction have led to increased use. We advocate caution, and have developed guidelines (including pre-treatment investigation and monitoring) to improve treatment safety. Propranolol may in time prove to be the best medical treatment for subglottic haemangioma, but at present is considered to be still under evaluation.
The current study examined the use of biographical data to predict errors, tardiness, policy violations, overall job performance, and turnover among nurses. The results of the study indicate that biodata measures are valid selection devices for nurses and effective at predicting nurse errors, tardiness, policy violations, and overall job performance, but the instrument was not an effective predictor of turnover, voluntary or involuntary. Additionally, examination of group differences revealed that White subjects scored significantly higher on the biodata instrument compared to Black subjects but produced group differences considerably smaller than typically found with measures of cognitive ability. Future research directions and implications for practice are discussed.