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In Canada, recreational use of cannabis was legalized in October 2018. This policy change along with recent publications evaluating the efficacy of cannabis for the medical treatment of epilepsy and media awareness about its use have increased the public interest about this agent. The Canadian League Against Epilepsy Medical Therapeutics Committee, along with a multidisciplinary group of experts and Canadian Epilepsy Alliance representatives, has developed a position statement about the use of medical cannabis for epilepsy. This article addresses the current Canadian legal framework, recent publications about its efficacy and safety profile, and our understanding of the clinical issues that should be considered when contemplating cannabis use for medical purposes.
First-degree relatives of patients with psychotic disorder have higher levels of polygenic risk (PRS) for schizophrenia and higher levels of intermediate phenotypes.
We conducted, using two different samples for discovery (n = 336 controls and 649 siblings of patients with psychotic disorder) and replication (n = 1208 controls and 1106 siblings), an analysis of association between PRS on the one hand and psychopathological and cognitive intermediate phenotypes of schizophrenia on the other in a sample at average genetic risk (healthy controls) and a sample at higher than average risk (healthy siblings of patients). Two subthreshold psychosis phenotypes, as well as a standardised measure of cognitive ability, based on a short version of the WAIS-III short form, were used. In addition, a measure of jumping to conclusion bias (replication sample only) was tested for association with PRS.
In both discovery and replication sample, evidence for an association between PRS and subthreshold psychosis phenotypes was observed in the relatives of patients, whereas in the controls no association was observed. Jumping to conclusion bias was similarly only associated with PRS in the sibling group. Cognitive ability was weakly negatively and non-significantly associated with PRS in both the sibling and the control group.
The degree of endophenotypic expression of schizophrenia polygenic risk depends on having a sibling with psychotic disorder, suggestive of underlying gene–environment interaction. Cognitive biases may better index genetic risk of disorder than traditional measures of neurocognition, which instead may reflect the population distribution of cognitive ability impacting the prognosis of psychotic disorder.
Human donor milk (DM) is Holder pasteurised (62·5°C, 30 min) to ensure its microbiological safety for infant consumption. In low-resource settings, flash heating is used to pasteurise milk. Although there is considerable interest in non-thermal alternatives (high hydrostatic pressure processing (HHP) and UVC irradiation) for pasteurisation, their effect on the fatty acid composition is not well understood. Of particular interest is the effect of pasteurisation on the generation of oxylipins. DM from eight mothers containing bacteria >5 × 107 colony-forming units/l was used. In a paired design, each pool of milk underwent four pasteurisation techniques: Holder; flash heating; UVC (250 nm, 25 min) and HHP (500 MPa, 8 min). Fatty acids were quantified by GC-flame ionisation detection and oxylipins derived from arachidonic acid; 18-carbon PUFA (α-linolenic acid, linoleic acid and γ-linolenic acid) and EPA/DHA were measured by liquid chromatography-tandem MS in aliquots of raw and processed milk. There were no significant changes to the composition of fatty acids following all pasteurisation techniques compared with raw milk. The n-6:n-3 ratio remained constant ranging from 6·4 to 6·6. Several arachidonic acid-derived oxylipins were highest post-UVC and elevated post-HHP compared with raw milk. Several oxylipins derived from 18-carbon PUFA (linoleic and α-linolenic acids) were elevated in UVC-treated milk. EPA/DHA-derived oxylipins were on average, unaffected by pasteurisation. Although some PUFA-derived oxylipins were increased following UVC and HHP, no method affected the fatty acid composition of human DM. Further research is needed to determine if varying levels of oxylipins in human DM as a result of processing can potentially mediate cellular signalling; proliferation and apoptosis, especially important for preterm infant development.
A national need is to prepare for and respond to accidental or intentional disasters categorized as chemical, biological, radiological, nuclear, or explosive (CBRNE). These incidents require specific subject-matter expertise, yet have commonalities. We identify 7 core elements comprising CBRNE science that require integration for effective preparedness planning and public health and medical response and recovery. These core elements are (1) basic and clinical sciences, (2) modeling and systems management, (3) planning, (4) response and incident management, (5) recovery and resilience, (6) lessons learned, and (7) continuous improvement. A key feature is the ability of relevant subject matter experts to integrate information into response operations. We propose the CBRNE medical operations science support expert as a professional who (1) understands that CBRNE incidents require an integrated systems approach, (2) understands the key functions and contributions of CBRNE science practitioners, (3) helps direct strategic and tactical CBRNE planning and responses through first-hand experience, and (4) provides advice to senior decision-makers managing response activities. Recognition of both CBRNE science as a distinct competency and the establishment of the CBRNE medical operations science support expert informs the public of the enormous progress made, broadcasts opportunities for new talent, and enhances the sophistication and analytic expertise of senior managers planning for and responding to CBRNE incidents.
Starting in 2016, we initiated a pilot tele-antibiotic stewardship program at 2 rural Veterans Affairs medical centers (VAMCs). Antibiotic days of therapy decreased significantly (P < .05) in the acute and long-term care units at both intervention sites, suggesting that tele-stewardship can effectively support antibiotic stewardship practices in rural VAMCs.
A 2018 workshop on the White Mountain Apache Tribe lands in Arizona examined ways to enhance investigations into cultural property crime (CPC) through applications of rapidly evolving methods from archaeological science. CPC (also looting, graverobbing) refers to unauthorized damage, removal, or trafficking in materials possessing blends of communal, aesthetic, and scientific values. The Fort Apache workshop integrated four generally partitioned domains of CPC expertise: (1) theories of perpetrators’ motivations and methods; (2) recommended practice in sustaining public and community opposition to CPC; (3) tactics and strategies for documenting, investigating, and prosecuting CPC; and (4) forensic sedimentology—uses of biophysical sciences to link sediments from implicated persons and objects to crime scenes. Forensic sedimentology served as the touchstone for dialogues among experts in criminology, archaeological sciences, law enforcement, and heritage stewardship. Field visits to CPC crime scenes and workshop deliberations identified pathways toward integrating CPC theory and practice with forensic sedimentology’s potent battery of analytic methods.
Cougar Mountain Cave is located in Oregon's Fort Rock Basin. In 1958, avocationalist John Cowles excavated most of the cave's deposits and recovered abundant fiber, lithic, wood, and osseous artifacts. A crew from the University of California, Davis returned to the site in 1966 to evaluate the potential for further research, collecting additional lithic and fiber artifacts from disturbed deposits and in situ charcoal from apparently undisturbed deposits. Because Cowles took few notes or photographs, the Cougar Mountain Cave collection—most of which is housed at the Favell Museum in Klamath Falls, Oregon—has largely gone unstudied even though it contains diagnostic artifacts spanning the Holocene and, potentially, the terminal Pleistocene. We recently submitted charcoal and basketry from the site for radiocarbon dating, providing the first reliable sense of when Cougar Mountain Cave was first occupied. Our results indicate at least a Younger Dryas age for initial occupation. The directly dated basketry has provided new information about the age ranges and spatial distributions of diagnostic textile types in the northwestern Great Basin.
Determining infectious cross-transmission events in healthcare settings involves manual surveillance of case clusters by infection control personnel, followed by strain typing of clinical/environmental isolates suspected in said clusters. Recent advances in genomic sequencing and cloud computing now allow for the rapid molecular typing of infecting isolates.
To facilitate rapid recognition of transmission clusters, we aimed to assess infection control surveillance using whole-genome sequencing (WGS) of microbial pathogens to identify cross-transmission events for epidemiologic review.
Clinical isolates of Staphylococcus aureus, Enterococcus faecium, Pseudomonas aeruginosa, and Klebsiella pneumoniae were obtained prospectively at an academic medical center, from September 1, 2016, to September 30, 2017. Isolate genomes were sequenced, followed by single-nucleotide variant analysis; a cloud-computing platform was used for whole-genome sequence analysis and cluster identification.
Most strains of the 4 studied pathogens were unrelated, and 34 potential transmission clusters were present. The characteristics of the potential clusters were complex and likely not identifiable by traditional surveillance alone. Notably, only 1 cluster had been suspected by routine manual surveillance.
Our work supports the assertion that integration of genomic and clinical epidemiologic data can augment infection control surveillance for both the identification of cross-transmission events and the inclusion of missed and exclusion of misidentified outbreaks (ie, false alarms). The integration of clinical data is essential to prioritize suspect clusters for investigation, and for existing infections, a timely review of both the clinical and WGS results can hold promise to reduce HAIs. A richer understanding of cross-transmission events within healthcare settings will require the expansion of current surveillance approaches.
The x-ray energy emitted from laser-produced plasmas has been measured under various experimental conditions. Two Nd-glass lasers were used in separate experiments to focus pulsed laser light on planar targets. X-ray fluences were measured with newly developed silicon detector calorimeters. Results for various experimental conditions are reported in terms of the efficiency with which the laser light was converted to x-ray energy by plasma production.
We present a new approach to model coastal waves in the shoaling and surf zones. The model can be described as a depth-averaged large-eddy simulation model with a cutoff in the inertial subrange. The large-scale turbulence is explicitly resolved through an extra variable called enstrophy while the small-scale turbulence is modelled with a turbulent-viscosity hypothesis. The equations are derived by averaging the mass, momentum and kinetic energy equations assuming a shallow-water flow, a negligible bottom shear stress and a weakly turbulent flow assumption which is not restrictive in practice. The model is fully nonlinear and has the same dispersive properties as the Green–Naghdi equations. It is validated by numerical tests and by comparison with experimental results of the literature on the propagation of a one-dimensional solitary wave over a mild sloping beach. The wave breaking is characterized by a sudden increase of the enstrophy which allows us to propose a breaking criterion based on the new concept of virtual enstrophy. The model features three empirical parameters. The first one governs the turbulent dissipation and was found to be a constant. The eddy viscosity is determined by a turbulent Reynolds number depending only on the bottom slope. The third parameter defines the breaking criterion and depends only on the wave initial nonlinearity. These dependences give a predictive character to the model which is suitable for further developments.
A point-prevalence study of antimicrobial use among inpatients at 5 public hospitals in Sri Lanka revealed that 54.6% were receiving antimicrobials: 43.1% in medical wards, 68.0% in surgical wards, and 97.6% in intensive care wards. Amoxicillin-clavulanate was most commonly used for major indications. Among patients receiving antimicrobials, 31.0% received potentially inappropriate therapy.
Objectives: Prior research has identified numerous genetic (including sex), education, health, and lifestyle factors that predict cognitive decline. Traditional model selection approaches (e.g., backward or stepwise selection) attempt to find one model that best fits the observed data, risking interpretations that only the selected predictors are important. In reality, several predictor combinations may fit similarly well but result in different conclusions (e.g., about size and significance of parameter estimates). In this study, we describe an alternative method, Information-Theoretic (IT) model averaging, and apply it to characterize a set of complex interactions in a longitudinal study on cognitive decline. Methods: Here, we used longitudinal cognitive data from 1256 late–middle aged adults from the Wisconsin Registry for Alzheimer’s Prevention study to examine the effects of sex, apolipoprotein E (APOE) ɛ4 allele (non-modifiable factors), and literacy achievement (modifiable) on cognitive decline. For each outcome, we applied IT model averaging to a set of models with different combinations of interactions among sex, APOE, literacy, and age. Results: For a list-learning test, model-averaged results showed better performance for women versus men, with faster decline among men; increased literacy was associated with better performance, particularly among men. APOE had less of an association with cognitive performance in this age range (∼40–70 years). Conclusions: These results illustrate the utility of the IT approach and point to literacy as a potential modifier of cognitive decline. Whether the protective effect of literacy is due to educational attainment or intrinsic verbal intellectual ability is the topic of ongoing work. (JINS, 2019, 25, 119–133)
Objectives: A major challenge in cognitive aging is differentiating preclinical disease-related cognitive decline from changes associated with normal aging. Neuropsychological test authors typically publish single time-point norms, referred to here as unconditional reference values. However, detecting significant change requires longitudinal, or conditional reference values, created by modeling cognition as a function of prior performance. Our objectives were to create, depict, and examine preliminary validity of unconditional and conditional reference values for ages 40–75 years on neuropsychological tests. Method: We used quantile regression to create growth-curve–like models of performance on tests of memory and executive function using participants from the Wisconsin Registry for Alzheimer’s Prevention. Unconditional and conditional models accounted for age, sex, education, and verbal ability/literacy; conditional models also included past performance on and number of prior exposures to the test. Models were then used to estimate individuals’ unconditional and conditional percentile ranks for each test. We examined how low performance on each test (operationalized as <7th percentile) related to consensus-conference–determined cognitive statuses and subjective impairment. Results: Participants with low performance were more likely to receive an abnormal cognitive diagnosis at the current visit (but not later visits). Low performance was also linked to subjective and informant reports of worsening memory function. Conclusions: The percentile-based methods and single-test results described here show potential for detecting troublesome within-person cognitive change. Development of reference values for additional cognitive measures, investigation of alternative thresholds for abnormality (including multi-test criteria), and validation in samples with more clinical endpoints are needed. (JINS, 2019, 25, 1–14)
Examination gloves have been previously noted as a possible barrier to hand hygiene. We performed a prospective quantitative and qualitative study to investigate. Glove usage was found to be a potential barrier to hand hygiene; this was driven by desire for personal safety and potentially learned during professional training.
The current study examined trajectories of maternal and paternal depression in the year following the birth of an infant sibling, and relations with family risk factors and firstborn children's internalizing and externalizing behavior problems. Latent class growth analysis was conducted on 231 families in a longitudinal investigation (prebirth and 1, 4, 8, and 12 months postbirth) and revealed four classes of families: both mother and father low in depressive symptoms (40.7%); mother high–father low (25.1%); father high–mother low (24.7%), and both mother and father high (9.5%). Families with both mothers and fathers high on depressive symptoms were higher on marital negativity, parenting stress, and children's internalizing and externalizing problems, and lower on marital positivity and parental efficacy than other classes. Children, parents, and marital relationships were more problematic in families with fathers higher on depressive symptoms than in families in which mothers were higher, indicating the significant role of paternal support for firstborn children undergoing the transition to siblinghood. Maternal and paternal depression covaried with an accumulation of family risks over time, no doubt increasing the likelihood of children's problematic adjustment after the birth of their infant sibling.
The family physician is key to facilitating access to psychiatric treatment for young people with first-episode psychosis, and this involvement can reduce aversive events in pathways to care. Those who seek help from primary care tend to have longer intervals to psychiatric care, and some people receive ongoing psychiatric treatment from the family physician.
Our objective is to understand the role of the family physician in help-seeking, recognition and ongoing management of first-episode psychosis.
We will use a mixed-methods approach, incorporating health administrative data, electronic medical records (EMRs) and qualitative methodologies to study the role of the family physician at three points on the pathway to care. First, help-seeking: we will use health administrative data to examine access to a family physician and patterns of primary care use preceding the first diagnosis of psychosis; second, recognition: we will identify first-onset cases of psychosis in health administrative data, and look back at linked EMRs from primary care to define a risk profile for undetected cases; and third, management: we will examine service provision to identified patients through EMR data, including patterns of contacts, prescriptions and referrals to specialised care. We will then conduct qualitative interviews and focus groups with key stakeholders to better understand the trends observed in the quantitative data.
These findings will provide an in-depth description of first-episode psychosis in primary care, informing strategies to build linkages between family physicians and psychiatric services to improve transitions of care during the crucial early stages of psychosis.
Sufficiently strong electric fields in plasmas can accelerate charged particles to relativistic energies. In this paper we describe the dynamics of positrons accelerated in such electric fields, and calculate the fraction of created positrons that become runaway accelerated, along with the amount of radiation that they emit. We derive an analytical formula that shows the relative importance of the different positron production processes, and show that, above a certain threshold electric field, the pair production by photons is lower than that by collisions. We furthermore present analytical and numerical solutions to the positron kinetic equation; these are applied to calculate the fraction of positrons that become accelerated or thermalized, which enters into rate equations that describe the evolution of the density of the slow and fast positron populations. Finally, to indicate operational parameters required for positron detection during runaway in tokamak discharges, we give expressions for the parameter dependencies of detected annihilation radiation compared to bremsstrahlung detected at an angle perpendicular to the direction of runaway acceleration. Using the full leading-order pair-production cross-section, we demonstrate that previous related work has overestimated the collisional pair production by at least a factor of four.
The value of the nosological distinction between non-affective and affective psychosis has frequently been challenged. We aimed to investigate the transdiagnostic dimensional structure and associated characteristics of psychopathology at First Episode Psychosis (FEP). Regardless of diagnostic categories, we expected that positive symptoms occurred more frequently in ethnic minority groups and in more densely populated environments, and that negative symptoms were associated with indices of neurodevelopmental impairment.
This study included 2182 FEP individuals recruited across six countries, as part of the EUropean network of national schizophrenia networks studying Gene–Environment Interactions (EU-GEI) study. Symptom ratings were analysed using multidimensional item response modelling in Mplus to estimate five theory-based models of psychosis. We used multiple regression models to examine demographic and context factors associated with symptom dimensions.
A bifactor model, composed of one general factor and five specific dimensions of positive, negative, disorganization, manic and depressive symptoms, best-represented associations among ratings of psychotic symptoms. Positive symptoms were more common in ethnic minority groups. Urbanicity was associated with a higher score on the general factor. Men presented with more negative and less depressive symptoms than women. Early age-at-first-contact with psychiatric services was associated with higher scores on negative, disorganized, and manic symptom dimensions.
Our results suggest that the bifactor model of psychopathology holds across diagnostic categories of non-affective and affective psychosis at FEP, and demographic and context determinants map onto general and specific symptom dimensions. These findings have implications for tailoring symptom-specific treatments and inform research into the mood-psychosis spectrum.
To test the feasibility of using telehealth to support antimicrobial stewardship at Veterans Affairs medical centers (VAMCs) that have limited access to infectious disease-trained specialists.
A prospective quasi-experimental pilot study.
Two rural VAMCs with acute-care and long-term care units.
At each intervention site, medical providers, pharmacists, infection preventionists, staff nurses, and off-site infectious disease physicians formed a videoconference antimicrobial stewardship team (VAST) that met weekly to discuss cases and antimicrobial stewardship-related education.
Descriptive measures included fidelity of implementation, number of cases discussed, infectious syndromes, types of recommendations, and acceptance rate of recommendations made by the VAST. Qualitative results stemmed from semi-structured interviews with VAST participants at the intervention sites.
Each site adapted the VAST to suit their local needs. On average, sites A and B discussed 3.5 and 3.1 cases per session, respectively. At site A, 98 of 140 cases (70%) were from the acute-care units; at site B, 59 of 119 cases (50%) were from the acute-care units. The most common clinical syndrome discussed was pneumonia or respiratory syndrome (41% and 35% for sites A and B, respectively). Providers implemented most VAST recommendations, with an acceptance rate of 73% (186 of 256 recommendations) and 65% (99 of 153 recommendations) at sites A and B, respectively. Qualitative results based on 24 interviews revealed that participants valued the multidisciplinary aspects of the VAST sessions and felt that it improved their antimicrobial stewardship efforts and patient care.
This pilot study has successfully demonstrated the feasibility of using telehealth to support antimicrobial stewardship at rural VAMCs with limited access to local infectious disease expertise.