Tracking an invasion front with environmental DNA.

Data from environmental DNA (eDNA) may revolutionize environmental monitoring and management, providing increased detection sensitivity at reduced cost and survey effort. However, eDNA data are rarely used in decision-making contexts, mainly due to uncertainty around (1) data interpretation and (2) whether and how molecular tools dovetail with existing management efforts. We address these challenges by jointly modeling eDNA detection via qPCR and traditional trap data to estimate the density of invasive European green crab (Carcinus maenas), a species for which, historically, baited traps have been used for both detection and control. Our analytical framework simultaneously quantifies uncertainty in both detection methods and provides a robust way of integrating different data streams into management processes. Moreover, the joint model makes clear the marginal information benefit of adding eDNA (or any other) additional data type to an existing monitoring program, offering a path to optimizing sampling efforts for species of management interest. Here, we document green crab eDNA beyond the previously known invasion front and find that the value of eDNA data dramatically increases with low population densities and low traditional sampling effort, as is often the case at leading-edge locations. We also highlight the detection limits of the molecular assay used in this study, as well as scenarios under which eDNA sampling is unlikely to improve existing management efforts.

GABAB Receptor Chemistry and Pharmacology: Agonists, Antagonists, and Allosteric Modulators.

The GABAB receptors are metabotropic G protein-coupled receptors (GPCRs) that mediate the actions of the primary inhibitory neurotransmitter, γ-aminobutyric acid (GABA). In the CNS, GABA plays an important role in behavior, learning and memory, cognition, and stress. GABA is also located throughout the gastrointestinal (GI) tract and is involved in the autonomic control of the intestine and esophageal reflex. Consequently, dysregulated GABAB receptor signaling is associated with neurological, mental health, and gastrointestinal disorders; hence, these receptors have been identified as key therapeutic targets and are the focus of multiple drug discovery efforts for indications such as muscle spasticity disorders, schizophrenia, pain, addiction, and gastroesophageal reflex disease (GERD). Numerous agonists, antagonists, and allosteric modulators of the GABAB receptor have been described; however, Lioresal® (Baclofen; ß-(4-chlorophenyl)-γ-aminobutyric acid) is the only FDA-approved drug that selectively targets GABAB receptors in clinical use; undesirable side effects, such as sedation, muscle weakness, fatigue, cognitive deficits, seizures, tolerance and potential for abuse, limit their therapeutic use. Here, we review GABAB receptor chemistry and pharmacology, presenting orthosteric agonists, antagonists, and positive and negative allosteric modulators, and highlight the therapeutic potential of targeting GABAB receptor modulation for the treatment of various CNS and peripheral disorders.

Quantitative determination of neuronal size and density using flow cytometry.

BACKGROUND: Recent anthropomorphic disturbances are occurring at an increasing rate leading to organisms facing a variety of challenges. This change is testing the information processing capacity (IPC) of all animals. Brain function is widely accepted to be influenced by a variety of factors, including relative size, number of neurons and neuronal densities. Therefore, in order to understand what drives an animals IPC, a methodological approach to analyze these factors must be established. NEW METHOD: Here we created a protocol that allowed for high-throughput, non-biased quantification of neuronal density and size across six regions of the brain. We used the Isotropic Fractionator method in combination with flow cytometry to identify neuronal and non-neuronal cells in the brains of adult rats. COMPARISON WITH EXISTING METHODS: The results obtained were comparable to those identified using stereological counting methods. RESULTS: By employing this new method, the number of nuclei in a specific brain region can be compared between replicate animals within an experiment. By calibrating the forward scatter channel of the flow cytometer with size standard beads, neuronal and non-neuronal nuclear sizes can be estimated simultaneously with nuclei enumeration. These techniques for nuclear counting and size estimation are technically and biologically reproducible. CONCLUSION: Use of flow cytometry provides a methodological approach that allows for consistency in research, so that information on brain morphology, and subsequent function, will become comparable across taxa.

Rapid assessment of management options for promoting stock rebuilding in data-poor species under climate change.

The development of species recovery plans requires considering likely outcomes of different management interventions, but the complicating effects of climate change are rarely evaluated. We examined how qualitative network models (QNMs) can be deployed to support decision making when data, time, and funding limitations restrict use of more demanding quantitative methods. We used QNMs to evaluate management interventions intended to promote the rebuilding of a collapsed stock of blue king crab (Paralithodes platypus) (BKC) around the Pribilof Islands (eastern Bering Sea) to determine how their potential efficacy may change under climate change. Based on stakeholder input and a literature review, we constructed a QNM that described the life cycle of BKC, key ecological interactions, potential climate-change impacts, relative interaction strengths, and uncertainty in terms of interaction strengths and link presence. We performed sensitivity analyses to identify key sources of prediction uncertainty. Under a scenario of no climate change, predicted increases in BKC were reliable only when stock enhancement was implemented in a BKC hatchery-program scenario. However, when climate change was accounted for, the intervention could not counteract its adverse impacts, which had an overall negative effect on BKC. The remaining management scenarios related to changes in fishing effort on BKC predators. For those scenarios, BKC outcomes were unreliable, but climate change further decreased the probability of observing recovery. Including information on relative interaction strengths increased the likelihood of predicting positive outcomes for BKC approximately 5-50% under the management scenarios. The largest gains in prediction precision will be made by reducing uncertainty associated with ecological interactions between adult BKC and red king crab (Paralithodes camtschaticus). Qualitative network models are useful options when data are limited, but they remain underutilized in conservation.

Evaluación Rápida de las Opciones de Manejo para la Promoción de la Recuperación de Especies con Deficiencia de Datos bajo el Cambio Climático Resumen El desarrollo de los planes de recuperación de especies requiere de la consideración de los resultados probables de las diferentes intervenciones de manejo, pero los efectos agravantes del cambio climático rara vez están incluidos en esta evaluación. Examinamos cómo los modelos cualitativos de redes (QNMs) pueden implementarse para apoyar la toma de decisiones cuando los datos, el tiempo y el financiamiento sufren limitaciones que restringen el uso de métodos cuantitativos más demandantes. Usamos los QNMs para evaluar las intervenciones de manejo con la intención de promover el repoblamiento del colapsado cangrejo rey azul (Paralithodes platypus) (BKC) alrededor de las islas Pribilof (oriente del Mar de Bering) y así determinar cómo su eficiencia potencial puede modificarse bajo el cambio climático. Con base en aportaciones de los grupos de interés y una revisión bibliográfica construimos una QNM que describía el ciclo de vida del BKC, sus interacciones ecológicas importantes, impactos potenciales del cambio climático, fortalezas relativas de interacción, y la incertidumbre en relación con las fortalezas de interacción y la presencia de vínculos. Realizamos análisis de sensibilidad para identificar las fuentes clave de incertidumbre en la predicción. Bajo un escenario de ausencia de cambio climático, los incrementos pronosticados en la población de BKC fueron confiables solamente cuando el reforzamiento de la población se realizó en un escenario de programa de cultivo de BKC. Sin embargo, cuando se incluyó el cambio climático, la intervención de conservación no pudo contrarrestar los impactos adversos del cambio climático, lo cual tuvo un efecto negativo generalizado sobre los BKC. Los escenarios de manejo restantes estuvieron relacionados con los cambios en los esfuerzos de pesca sobre los depredadores del BKC. Para los estos últimos escenarios, los resultados de la población de BKC no fueron confiables, pero el cambio climático disminuyó todavía más la probabilidad de observar una recuperación. La inclusión de información sobre las fortalezas relativas de interacción incrementó la posibilidad de predecir los resultados de la población de BKC en ∼ 5 - 50% bajo los escenarios de manejo. Las mayores ganancias en la precisión de la predicción se lograrán reduciendo la incertidumbre asociada con las interacciones ecológicas entre los BKC adultos y el cangrejo rey rojo (Paralithodes camtschaticus). Los modelos cualitativos de redes son opciones útiles cuando los datos son limitados, pero permanecen subutilizados en la conservación.

Risk factors for cerebrospinal fluid shunt infections during an outbreak: a case-control study.

BACKGROUND: There are few published reports of cerebrospinal fluid (CSF) shunt infection outbreaks. In 2017-2018, British Columbia Children's Hospital (BCCH) experienced an increase in CSF shunt infections co-incident with a move to new operating rooms and a change in shunt catheters used. AIMS: To describe how an outbreak was detected, investigations were undertaken to determine the cause, risk factors associated with CSF shunt infection during the outbreak, and changes implemented to attempt to control the outbreak. METHODS: Retrospective case-control study. Population included patients who underwent new shunt insertion or revision. Univariate logistic regression models were fitted for each of the variables. Associations with P-values <0.2 were considered of potential interest for further investigation. FINDINGS: There were six cases of CSF shunt infection and 19 controls. The causative organism was different in each case. The only risk factors that met the criteria for further investigation were being a neonate at the time of surgery [odds ratio (OR) 9.0, 95% confidence interval (CI) 0.7-125.3, P=0.10] and the presence of gastrointestinal disease (OR 3.8, 95% CI 0.5-26.2, P=0.18). No association was found with the operating room used or the surgical staff. In response to the outbreak, human traffic through the operating rooms was limited, rigid adherence to the wearing of surgical masks was enforced, and return to the previous CSF shunt catheters used was implemented. CONCLUSION: No modifiable risk factors were associated with CSF shunt infection. After implementation of surgical protocol changes, no further cases of CSF shunt infection linked to the outbreak were identified.

Metrics of progress in the understanding and management of threats to Australian birds.

Although evidence-based approaches have become commonplace for determining the success of conservation measures for the management of threatened taxa, there are no standard metrics for assessing progress in research or management. We developed 5 metrics to meet this need for threatened taxa and to quantify the need for further action and effective alleviation of threats. These metrics (research need, research achievement, management need, management achievement, and percent threat reduction) can be aggregated to examine trends for an individual taxon or for threats across multiple taxa. We tested the utility of these metrics by applying them to Australian threatened birds, which appears to be the first time that progress in research and management of threats has been assessed for all threatened taxa in a faunal group at a continental scale. Some research has been conducted on nearly three-quarters of known threats to taxa, and there is a clear understanding of how to alleviate nearly half of the threats with the highest impact. Some management has been attempted on nearly half the threats. Management outcomes ranged from successful trials to complete mitigation of the threat, including for one-third of high-impact threats. Progress in both research and management tended to be greater for taxa that were monitored or occurred on oceanic islands. Predation by cats had the highest potential threat score. However, there has been some success reducing the impact of cat predation, so climate change (particularly drought), now poses the greatest threat to Australian threatened birds. Our results demonstrate the potential for the proposed metrics to encapsulate the major trends in research and management of both threats and threatened taxa and provide a basis for international comparisons of evidence-based conservation science.

Medidas de Progreso en el Entendimiento y el Manejo de las Amenazas que Enfrentan las Aves Australianas Resumen Aunque los métodos basados en evidencias se han vuelto muy comunes para la determinación del éxito de las medidas de conservación del manejo de los taxones amenazados, hoy en día no existen medidas estandarizadas para la evaluación del progreso de la investigación o el manejo. Desarrollamos cinco medidas para cumplir con esta necesidad que tienen los taxones amenazados y para cuantificar la necesidad de una mayor acción y un alivio efectivo de las amenazas. Estas medidas (falta de investigación, éxito de la investigación, falta de manejo, éxito del manejo y porcentaje de reducción de amenazas) pueden agregarse para examinar las tendencias de un taxón individual o las tendencias de las amenazas para múltiples taxones. Probamos la utilidad de estas medidas por medio de su aplicación en aves australianas amenazadas, que parece ser la primera vez que se evalúa el progreso en la investigación y en el manejo de amenazas para el caso de varios taxones amenazados dentro de un grupo faunístico a escala continental. Se ha realizado algún tipo de investigación sobre casi tres cuartas partes de las amenazas conocidas para los taxones, y hay un claro entendimiento de cómo aliviar casi la mitad de las amenazas con el impacto más alto. Se ha intentado algún tipo de manejo con casi la mitad de las amenazas. Los resultados del manejo variaron desde ensayos exitosos hasta la mitigación completa de la amenaza, incluso para un tercio de las amenazas de alto impacto. Tanto el progreso en la investigación como en el manejo tendió a ser mayor para los taxones que estaban siendo monitoreados, o que ocurrían en islas oceánicas. La depredación por gatos tuvo el puntaje más como amenaza potencial. Sin embargo, ha habido poco de éxito en la reducción del impacto de la depredación por gatos, así que ahora el cambio climático (particularmente la sequía) es la mayor amenaza para las aves amenazadas en Australia. Nuestros resultados demuestran el potencial que tienen las medidas propuestas de encapsular las tendencias más importantes en la investigación y en el manejo tanto de las amenazas como de los taxones amenazados y de proporcionar una base para comparaciones internacionales de la ciencia de la conservación basada en evidencias.

Implementation of Medical Assistance in Dying: A Scoping Review of Health Care Providers' Perspectives.

RESEARCH AIMS: With the growing interest in Medical Assistance in Dying (MAiD), understanding health care professionals' roles and experiences in handling requests is necessary to evaluate the quality, consistency, and efficacy of current practices. This scoping review sought to map the existing literature on health care providers' perspectives of their involvement in MAiD. METHODS: A scoping review was conducted to address the following: 1) What are the roles of diverse health care professionals in the provision of MAiD? and 2) What professional challenges arise when confronted with MAiD requests? A literature search in electronic databases and gray literature sources was performed. Articles were screened, and a thematic content analysis synthesized key findings. RESULTS: After evaluating 1715 citations and 148 full-text papers, 33 articles were included. Perspectives of nurses (n = 10), physicians (n = 7), mental health providers (n = 7), pharmacists (n = 4), social workers (n = 3), and medical examiners (n = 1) were explored. Professional roles included consulting/supporting patients and/or other staff members with requests, assessing eligibility, administering/dispensing the lethal drugs, providing aftercare to bereaved relatives, and regulatory oversight. Challenges included lack of clear guidelines/protocols, role ambiguity, evaluating capacity/consent, conscientious objection, and lack of interprofessional collaboration. CONCLUSION: Evidence from various jurisdictions highlighted a need for clear guidelines and protocols that define each profession's role, scope of practice, and legal boundaries for MAiD. Comprehensive models of care that incorporate multidisciplinary teams alongside improved clinician education may be effective to support MAiD implementation. Little is known about health care providers' perspectives in handling requests, especially outside physician practice and nursing.

Active elimination of radio frequency interference for improved signal-to-noise ratio for in-situ NMR experiments in strong magnetic field gradients.

Improvement in the signal-to-noise ratio of Nuclear Magnetic Resonance (NMR) systems may be achieved either by increasing the signal amplitude or by decreasing the noise. The noise has multiple origins - not all of which are strictly "noise": incoherent thermal noise originating in the probe and pre-amplifiers, probe ring down or acoustic noise and coherent externally broadcast radio frequency transmissions. The last cannot always be shielded in open access experiments. In this paper, we show that pulsed, low radio-frequency data communications are a significant source of broadcast interference. We explore two signal processing methods of de-noising short T2∗ NMR experiments corrupted by these communications: Linear Predictive Coding (LPC) and the Discrete Wavelet Transform (DWT). Results are shown for numerical simulations and experiments conducted under controlled conditions with pseudo radio frequency interference. We show that both the LPC and DWT methods have merit.

The interactome of metabolic enzyme carbonic anhydrase IX reveals novel roles in tumor cell migration and invadopodia/MMP14-mediated invasion.

Carbonic anhydrase IX (CAIX) is a hypoxia inducible factor 1-induced, cell surface pH regulating enzyme with an established role in tumor progression and clinical outcome. However, the molecular basis of CAIX-mediated tumor progression remains unclear. Here, we have utilized proximity dependent biotinylation (BioID) to map the CAIX 'interactome' in breast cancer cells in order to identify physiologically relevant CAIX-associating proteins with potential roles in tumor progression. High confidence proteins identified include metabolic transporters, ß1 integrins, integrin-associated protein CD98hc and matrix metalloprotease 14 (MMP14). Biochemical studies validate the association of CAIX with α2ß1 integrin, CD98hc and MMP14, and immunofluorescence microscopy demonstrates colocalization of CAIX with α2ß1 integrin and MMP14 in F-actin/cofilin-positive lamellipodia/pseudopodia, and with MMP14 to cortactin/Tks5-positive invadopodia. Modulation of CAIX expression and activity results in significant changes in cell migration, collagen degradation and invasion. Mechanistically, we demonstrate that CAIX associates with MMP14 through potential phosphorylation residues within its intracellular domain, and that CAIX enhances MMP14-mediated collagen degradation by directly contributing hydrogen ions required for MMP14 catalytic activity. These findings establish hypoxia-induced CAIX as a novel metabolic component of cellular migration and invasion structures, and provide new mechanistic insights into its role in tumor cell biology.

Nuclear-magnetic-resonance relaxation due to the translational diffusion of fluid confined to quasi-two-dimensional pores.

Nuclear-magnetic-resonance (NMR) relaxation experimentation is an effective technique for nondestructively probing the dynamics of proton-bearing fluids in porous media. The frequency-dependent relaxation rate T_{1}^{-1} can yield a wealth of information on the fluid dynamics within the pore provided data can be fit to a suitable spin diffusion model. A spin diffusion model yields the dipolar correlation function G(t) describing the relative translational motion of pairs of ^{1}H spins which then can be Fourier transformed to yield T_{1}^{-1}. G(t) for spins confined to a quasi-two-dimensional (Q2D) pore of thickness h is determined using theoretical and Monte Carlo techniques. G(t) shows a transition from three- to two-dimensional motion with the transition time proportional to h^{2}. T_{1}^{-1} is found to be independent of frequency over the range 0.01-100 MHz provided h≳5 nm and increases with decreasing frequency and decreasing h for pores of thickness h<3 nm. T_{1}^{-1} increases linearly with the bulk water diffusion correlation time τ_{b} allowing a simple and direct estimate of the bulk water diffusion coefficient from the high-frequency limit of T_{1}^{-1} dispersion measurements in systems where the influence of paramagnetic impurities is negligible. Monte Carlo simulations of hydrated Q2D pores are executed for a range of surface-to-bulk desorption rates for a thin pore. G(t) is found to decorrelate when spins move from the surface to the bulk, display three-dimensional properties at intermediate times, and finally show a bulk-mediated surface diffusion (Lévy) mechanism at longer times. The results may be used to interpret NMR relaxation rates in hydrated porous systems in which the paramagnetic impurity density is negligible.

Explicit calculation of nuclear-magnetic-resonance relaxation rates in small pores to elucidate molecular-scale fluid dynamics.

Nuclear-magnetic-resonance (NMR) spin-lattice (T_{1}^{-1}) and spin-spin (T_{2}^{-1}) relaxation rate measurements can act as effective nondestructive probes of the nanoscale dynamics of ^{1}H spins in porous media. In particular, fast-field-cycling T_{1}^{-1} dispersion measurements contain information on the dynamics of diffusing spins over time scales spanning many orders of magnitude. Previously published experimental T_{1}^{-1} dispersions from a plaster paste, synthetic saponite, mortar, and oil-bearing shale are reanalyzed using a model and associated theory which describe the relaxation rate contributions due to the interaction between spin ensembles in quasi-two-dimensional pores. Application of the model yields physically meaningful diffusion correlation times for all systems. In particular, the surface diffusion correlation time and the surface desorption time take similar values for each system, suggesting that surface mobility and desorption are linked processes. The bulk fluid diffusion correlation time is found to be two to five times the value for the pure liquid at room temperature for each system. Reanalysis of the oil-bearing shale yields diffusion time constants for both the oil and water constituents. The shale is found to be oil wetting and the water T_{1}^{-1} dispersion is found to be associated with aqueous Mn^{2+} paramagnetic impurities in the bulk water. These results escalate the NMR T_{1}^{-1} dispersion measurement technique as the primary probe of molecular-scale dynamics in porous media yielding diffusion parameters and a wealth of information on pore morphology.

Gray free-energy multiphase lattice Boltzmann model with effective transport and wetting properties.

The paper shows that it is possible to combine the free-energy lattice Boltzmann approach to multiphase modeling of fluids involving both liquid and vapor with the partial bounce back lattice Boltzmann approach to modeling effective media. Effective media models are designed to mimic the properties of porous materials with porosity much finer than the scale of the simulation lattice. In the partial bounce-back approach, an effective media parameter or bounce-back fraction controls fluid transport. In the combined model, a wetting potential is additionally introduced that controls the wetting properties of the fluid with respect to interfaces between free space (white nodes), effective media (gray nodes), and solids (black nodes). The use of the wetting potential combined with the bounce-back parameter gives the model the ability to simulate transport and sorption of a wide range of fluid in material systems. Results for phase separation, permeability, contact angle, and wicking in gray media are shown. Sorption is explored in small sections of model multiscale porous systems to demonstrate two-step desorption, sorption hysteresis, and the ink-bottle effect.

Model for the interpretation of nuclear magnetic resonance relaxometry of hydrated porous silicate materials.

Nuclear magnetic resonance (NMR) relaxation experimentation is an effective technique for probing the dynamics of proton spins in porous media, but interpretation requires the application of appropriate spin-diffusion models. Molecular dynamics (MD) simulations of porous silicate-based systems containing a quasi-two-dimensional water-filled pore are presented. The MD simulations suggest that the residency time of the water on the pore surface is in the range 0.03-12 ns, typically 2-5 orders of magnitude less than values determined from fits to experimental NMR measurements using the established surface-layer (SL) diffusion models of Korb and co-workers [Phys. Rev. E 56, 1934 (1997)]. Instead, MD identifies four distinct water layers in a tobermorite-based pore containing surface Ca2+ ions. Three highly structured water layers exist within 1 nm of the surface and the central region of the pore contains a homogeneous region of bulklike water. These regions are referred to as layer 1 and 2 (L1, L2), transition layer (TL), and bulk (B), respectively. Guided by the MD simulations, a two-layer (2L) spin-diffusion NMR relaxation model is proposed comprising two two-dimensional layers of slow- and fast-moving water associated with L2 and layers TL+B, respectively. The 2L model provides an improved fit to NMR relaxation times obtained from cementitious material compared to the SL model, yields diffusion correlation times in the range 18-75 ns and 28-40 ps in good agreement with MD, and resolves the surface residency time discrepancy. The 2L model, coupled with NMR relaxation experimentation, provides a simple yet powerful method of characterizing the dynamical properties of proton-bearing porous silicate-based systems such as porous glasses, cementitious materials, and oil-bearing rocks.

Summary of recommendations on malaria issues in special hosts.

BACKGROUND: On behalf of the Public Health Agency of Canada, the Committee to Advise on Tropical Medicine and Travel (CATMAT) developed the Canadian Recommendations for the Prevention and Treatment of Malaria Among International Travellers for Canadian health care providers who are preparing patients for travel to malaria-endemic areas and treating travellers who have returned ill. OBJECTIVE: To provide guidelines on malaria issues related to special hosts. METHODS: CATMAT reviewed all major sources of information on malaria prevention, as well as recent research and national and international epidemiological data, to tailor guidelines to the Canadian context. The evidence-based medicine recommendations were developed with associated rating scales for the strength and quality of the evidence. RECOMMENDATIONS: All people visiting malaria endemic regions should use effective personal protective measures (PPM; topical repellants, bed nets, behavioural choices) and the prescribed chemoprophylaxis. Chemoprophylaxis for pregnant and breastfeeding women and for children requires careful consideration in the context of the pregnancy trimester, the age or size of the infant/child as well as their glucose-6-phosphate dehydrogenase (G6PD) status. Recommendations for long-term travellers, expatriates and people visiting friends and relatives (VFRs) do not differ markedly from those for short-term travellers. Some underlying medical conditions may make individuals more vulnerable to malaria. In addition, some conditions or their treatment may preclude the use of one or more antimalarial medications.

Summary of recommendations for the prevention of malaria by the Committee to Advise on Tropical Medicine and Travel (CATMAT).

BACKGROUND: On behalf of the Public Health Agency of Canada, the Committee to Advise on Tropical Medicine and Travel (CATMAT) developed the Canadian Recommendations for the Prevention and Treatment of Malaria Among International Travellers for Canadian health care providers who are preparing patients for travel to malaria-endemic areas and treating travellers who have returned ill. OBJECTIVE: To provide guidelines on risk assessment and prevention of malaria. METHODS: CATMAT reviewed all major sources of information on malaria prevention, as well as recent research and national and international epidemiological data, to tailor guidelines to the Canadian context. The evidence-based medicine recommendations were developed with associated rating scales for the strength and quality of the evidence. RECOMMENDATIONS: Used together and correctly, personal protective measures (PPM) and chemoprophylaxis very effectively protect against malaria infection. PPM include protecting accommodation areas from mosquitoes, wearing appropriate clothing, using bed nets pre-treated with insecticide and applying topical insect repellant (containing 20%-30% DEET or 20% icaridin) to exposed skin. Selecting the most appropriate chemoprophylaxis involves assessment of the traveller's itinerary to establish his/her malaria risk profile as well as potential drug resistance issues. Antimalarials available on prescription in Canada include chloroquine (or hydroxychloroquine), atovaquone-proguanil, doxycycline, mefloquine and primaquine.

Summary of recommendations for the diagnosis and treatment of malaria by the Committee to Advise on Tropical Medicine and Travel (CATMAT).

BACKGROUND: On behalf of the Public Health Agency of Canada, the Committee to Advise on Tropical Medicine and Travel (CATMAT) developed the Canadian Recommendations for the Prevention and Treatment of Malaria Among International Travellers for Canadian health care providers who are preparing patients for travel to malaria-endemic areas and treating travellers who have returned ill. These recommendations aim to achieve appropriate diagnosis and management of malaria, a disease that is still uncommon in Canada. OBJECTIVE: To provide recommendations on the appropriate diagnosis and treatment of malaria. METHODS: CATMAT reviewed all major sources of information on malaria diagnosis and treatment, as well as recent research and national and international epidemiological data, to tailor guidelines to the Canadian context. The evidence-based medicine recommendations were developed with associated rating scales for the strength and quality of the evidence. RECOMMENDATIONS: Malarial management depends on rapid identification of the disease, as well as identification of the malaria species and level of parasitemia. Microscopic identification of blood samples is both rapid and accurate but can be done only by trained laboratory technicians. Rapid diagnostic tests are widely available, are simple to use and do not require specialized laboratory equipment or training; however, they do not provide the level of parasitemia and do require verification. Polymerase chain reaction (PCR), although still limited in availability, is emerging as the gold standard for high sensitivity and specificity in identifying the species.

Gamma knife radiosurgery for high grade glial neoplasms: a Canadian experience.

OBJECT: To review our institutional experience with Gamma Knife (GK) stereotactic radiosurgery in treating focally recurrent high grade glial neoplasms of World Health Organization (WHO) grade III or IV. METHODS: We conducted a retrospective cohort review of all patients treated with GK for focally recurrent high grade gliomas at our institution between November 2003 and April 2013. Data on age, sex, tumor volume, location and maximal diameter, presenting clinical status, complications and clinical outcome was recorded. RESULTS: A total of 33 patients were identified. Four were lost to follow-up. Average post-GK and overall survival was 20.4 months (range: 3­72) and 63.3 months (range: 10­214) respectively. For WHO grade IV gliomas, the average post-GK and overall survival was 15.8 months (range: 3­77) and 40.1 months (range: 13­148) respectively. Similarily, for WHO grade III gliomas, the average post-GK and overall survival was 34.9 months (range: 6­72) and 136.4 months (range: 22­214) respectively. Twenty-two patients (75.9%) had post-GK edema, with 14 requiring dexamethasone and eight being asymptomatic. Four patients (13.8%) had imaging defined radiation necrosis. CONCLUSIONS: Gamma Knife SRS affords an extension of local tumor control, acceptable morbidity, and potentially prolonged survival, for highly selected patients with focally recurrent high grade glial neoplasms.Radiochirurgie par scalpel gamma pour les néoplasies gliales de haut grade de malignité : une expérience canadienne.

Nuclear magnetic resonance relaxometry of water in two and quasi-two dimensions.

Molecular dynamics (MD) and Monte Carlo (MC) methods are used to determine the spin-pair correlation function G(*)(t) for the diffusion of bulk water in three dimensions (3D) and pore water in two dimensions (2D) and quasi-two dimensions (Q2D). The correlation function is required for the determination of the nuclear magnetic resonance spin-lattice and spin-spin relaxation times T(1) and T(2). It is shown that the analytic form of the powder-average correlation function, introduced by Sholl [Sholl, J. Phys. C: Solid State Phys. 7, 3378 (1974)] for the diffusion of spins on a 3D lattice, is of general validity. An analytic expression for G(*)(t) for a uniform spin fluid is derived in 2D. An analytic expression for the long-time behavior of G(*)(t) is derived for spins diffusing on 3D, 2D, and Q2D lattices. An analytic correction term, which accounts for spin pairs outside the scope of the numerical simulations, is derived for 3D and 2D and shown to improve the accuracy of the simulations. The contributions to T(1) due to translational and rotational motion obtained from the MD simulation of bulk water at 300 K are 7.4 s and 10±1 s, respectively, at 150 MHz, leading to an overall time of 4.3±0.4 s compared to the experimental value of 3.8 s. In Q2D systems, in which water is confined by alpha-quartz surfaces to thicknesses of 1-5 nm, T(1) for both translational and rotational relaxation is reduced due to the orientation and adsorption of spins at the surfaces. A method of parametrizing the MC lattice-diffusion simulations in 3D, 2D, and Q2D systems is presented. MC results for G(*)(t) for 3D and 2D systems are found to be consistent with an analytic uniform fluid model for t~/>40 ps. The value of TT(1) for translational diffusion obtained from the MC simulation of bulk water is found to be 4.8 s at 15 MHz. G(*)(t) obtained from MC simulations of Q2D systems, where water is confined by hard walls, is found to execute a distinct transition from 3D to 2D behavior. The T(1) is found to be similar to the 3D bulk water result at all pore thicknesses.

Gamma knife in the treatment of pituitary adenomas: results of a single center.

INTRODUCTION: Gamma Knife (GK) radiosurgery for pituitary adenomas can offer a means of tumor and biologic control with acceptable risk and low complication rates. METHODS: Retrospective review of all the patients treated at our center with GK for pituitary adenomas from Nov 2003 to June 2011. RESULTS: We treated a total of 86 patients. Ten were lost to follow-up. Mean follow was 32.8 months. There were 21 (24.4%) growth hormone secreting adenomas (GH), 8 (9.3%) prolactinomas (PRL), 8 (9.3%) adrenocorticotropic hormone secreting (ACTH) adenomas, 2 (2.3%) follicle stimulating hormone/luteinizing hormone secreting (FSH/LH) adenomas, and 47 (54.7%) null cell pituitary adenomas that were treated. Average maximum tumor diameter and volume was 2.21cm and 5.41cm³, respectively. The average dose to the 50% isodose line was 14.2 Gy and 23.6 Gy for secreting and non-secreting adenomas respectively. Mean maximal optic nerve dose was 8.87 Gy. Local control rate was 75 of 76 (98.7%), for those with followup. Thirty-three (43.4%) patients experienced arrest of tumor growth, while 42 (55.2%) patients experienced tumor regression. Of the 39 patients with secreting pituitary tumors, 6 were lost to follow-up. Improved endocrine status occurred in 16 (50.0%), while 14 (43.8%) demonstrated stability of hormone status on continued pre-operative medical management. Permanent complications included: panhypopituitarism (4), hypothyroidism (4), hypocortisolemia (1), diabetes insipidus (1), apoplexy (1), visual field defect (2), and diplopia (1). CONCLUSIONS: Gamma Knife radiosurgery is a safe and effective means of achieving tumor growth control and endocrine remission/stability in pituitary adenomas.