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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.
This chapter addresses a special category of cases in which an asserted patent is, or has been declared to be, essential to the implementation of a collaboratively developed voluntary consensus standard, and the holder of that patent has agreed to license it to implementers of the standard on terms that are fair, reasonable, and nondiscriminatory (FRAND).This chapter explores how the existence of such a FRAND commitment may affect a patent holder’s entitlement to monetary damages and injunctive relief. In addition to issues of patent law, remedies law, and contracts law, we consider the effect of competition law on this issue.
This chapter discusses the law and policy of monetary awards — including exemplary damages and litigation cost recoveries — that go beyond the compensatory damages to which prevailing parties in patent litigation are normally entitled. Up to treble damages are authorized in the United States for knowing infringement, but attorney fees are awarded only in exceptional cases. The rest of the world tends toward the opposite: Attorney fees are awarded as a matter of course, but punitive damages are generally prohibited as against public policy.This chapter discusses the theory, law, and policy of enhanced damages and attorney fee awards in the United States, Europe, and Asia. While the availability of enhanced damages and fees can bring accused infringers that might otherwise “hold out” to the table, care must also be taken to ensure that it does not discourage productive learning from patents or challenges to overbroad and vague patents. Rather than endorse any single set of doctrinal rules, there is a recommendation for further research into a number of unanswered questions about current and potential future configurations, in order to inform future policymaking.
Patent systems commonly empower courts to order accused or adjudged infringers to refrain from continuing infringing conduct in the future. Some patentees file suit for the primary purpose of obtaining and enforcing an injunction against infringement by a competitor, and even in cases in which the patentee is willing to license an invention to an accused infringer for an agreed price, the indirect monetary value of an injunction against future infringement can dwarf the amount a finder of fact is likely to award as compensation for past infringement. In some of these cases, an injunction, if granted, would impose costs on accused infringers or third parties that go well beyond the more intrinsic value of the patented technology. This chapter explores the theory behind injunctive relief in patent cases, surveys the availability of this remedy in major patent systems, and suggests a general framework for courts to use when deciding whether injunctive relief is appropriate in individual cases.
There is a long history of exploitation of the South American river turtle Podocnemis expansa. Conservation efforts for this species started in the 1960s but best practices were not established, and population trends and the number of nesting females protected remained unknown. In 2014 we formed a working group to discuss conservation strategies and to compile population data across the species’ range. We analysed the spatial pattern of its abundance in relation to human and natural factors using multiple regression analyses. We found that > 85 conservation programmes are protecting 147,000 nesting females, primarily in Brazil. The top six sites harbour > 100,000 females and should be prioritized for conservation action. Abundance declines with latitude and we found no evidence of human pressure on current turtle abundance patterns. It is presently not possible to estimate the global population trend because the species is not monitored continuously across the Amazon basin. The number of females is increasing at some localities and decreasing at others. However, the current size of the protected population is well below the historical population size estimated from past levels of human consumption, which demonstrates the need for concerted global conservation action. The data and management recommendations compiled here provide the basis for a regional monitoring programme among South American countries.
The dynamics of electron-plasma waves is described at arbitrary collisionality by considering the full Coulomb collision operator. The description is based on a Hermite–Laguerre decomposition of the velocity dependence of the electron distribution function. The damping rate, frequency and eigenmode spectrum of electron-plasma waves are found as functions of the collision frequency and wavelength. A comparison is made between the collisionless Landau damping limit, the Lenard–Bernstein and Dougherty collision operators and the electron–ion collision operator, finding large deviations in the damping rates and eigenmode spectra. A purely damped entropy mode, characteristic of a plasma where pitch-angle scattering effects are dominant with respect to collisionless effects, is shown to emerge numerically, and its dispersion relation is analytically derived. It is shown that such a mode is absent when simplified collision operators are used, and that like-particle collisions strongly influence the damping rate of the entropy mode.
In the 2015 review paper ‘Petawatt Class Lasers Worldwide’ a comprehensive overview of the current status of high-power facilities of
was presented. This was largely based on facility specifications, with some description of their uses, for instance in fundamental ultra-high-intensity interactions, secondary source generation, and inertial confinement fusion (ICF). With the 2018 Nobel Prize in Physics being awarded to Professors Donna Strickland and Gerard Mourou for the development of the technique of chirped pulse amplification (CPA), which made these lasers possible, we celebrate by providing a comprehensive update of the current status of ultra-high-power lasers and demonstrate how the technology has developed. We are now in the era of multi-petawatt facilities coming online, with 100 PW lasers being proposed and even under construction. In addition to this there is a pull towards development of industrial and multi-disciplinary applications, which demands much higher repetition rates, delivering high-average powers with higher efficiencies and the use of alternative wavelengths: mid-IR facilities. So apart from a comprehensive update of the current global status, we want to look at what technologies are to be deployed to get to these new regimes, and some of the critical issues facing their development.
Nonmammalian cynodonts represent a speciose and ecologically diverse group with a fossil record stretching from the late Permian until the Cretaceous. Because of their role as major components of Triassic terrestrial ecosystems and as the direct ancestors of mammals, cynodonts are an important group for understanding Mesozoic tetrapod diversity. We examine patterns of nonmammalian cynodont species richness and the quality of their fossil record. A supertree of cynodonts is constructed from recently published trees and time calibrated using a Bayesian approach. While this approach pushes the root of Cynodontia back to the earliest Guadalupian, the origins of Cynognathia and Probainognathia are close to their first appearance in the fossil record. Taxic, subsampled, and phylogenetic diversity estimates support a major cynodont radiation following the end-Permian mass extinction, but conflicting signals are observed at the end of the Triassic. The taxic diversity estimate shows high diversity in the Rhaetian and a drop across the Triassic/Jurassic boundary, while the phylogenetic diversity indicates an earlier extinction between the Norian and Rhaetian. The difference is attributed to the prevalence of taxa based solely on teeth in the Rhaetian, which are not included in the phylogenetic diversity estimate. Examining the completeness of cynodont specimens through geological time does not support a decrease in preservation potential; although the median completeness score decreases in the Late Triassic, the range of values remains consistent. Instead, the poor completeness scores are attributed to a shift in sampling and taxonomic practices: an increased prevalence in microvertebrate sampling and the naming of fragmentary material.
To characterise the nutritional status and to identify malnutrition-associated variables of older adults living in Portuguese nursing homes.
Cross-sectional study. Data on demographic and socio-economic characteristics, self-reported morbidity, eating-related problems, nutritional status, cognitive function, depression symptoms, loneliness feelings and functional status were collected by trained nutritionists through a computer-assisted face-to-face structured interview followed by standardised anthropometric measurements. Logistic regression was used to identify factors associated with being at risk of malnutrition/malnourished.
Portuguese nursing homes.
Nationally representative sample of the Portuguese population aged 65 years or over living in nursing homes.
A total of 1186 individuals (mean age 83·4 years; 72·8 % women) accepted to participate. According to the Mini Nutritional Assessment, 4·8 (95 % CI 3·2, 7·3) % were identified as malnourished and 38·7 (95 % CI 33·5, 44·2) % were at risk of malnutrition. These percentages increased with age and were significantly higher for women. Logistic regression showed (OR; 95 % CI) that older adults reporting no or little appetite (6·5; 2·7, 15·3), those revealing symptoms of depression (2·6; 1·6, 4·2) and those who were more dependent in their daily living activities (4·7; 2·0, 11·1) were also at higher odds of being malnourished or at risk of malnutrition.
Malnutrition and risk of malnutrition are prevalent among nursing home residents in Portugal. It is crucial to routinely screen for nutritional disorders, as well as risk factors such as symptoms of depression and lower functional status, to prevent and treat malnutrition.
Despite the advances of molecular tools, new nematode species are still described mainly based on morphological characters. Parapharyngodon and Thelandros are two genera of oxyurids with unclear related taxonomic histories. Here we use morphological characters (linear measurements and categorical variables) and genetic information (18S rRNA, 28S rRNA and COI partial gene sequences) to confirm the relationships between representatives of these two genera and to determine whether they can be discriminated morphologically. Genetic results confirm the existence of two main clades, mostly congruent with Parapharyngodon and Thelandros genera but with several discordances. Thelandros is polyphyletic, with two of the species analysed (T. filiformis and T. tinerfensis) being part of the Thelandros clade, but with a third one (T. galloti) falling within the Parapharyngodon clade. Regarding the Parapharyngodon clade, P. cubensis, P. scleratus and Parapharyngodon sp. from Mexico form congruent lineages, while most P. echinatus samples cluster in another group, with one exception. Interestingly, P. micipsae samples are scattered across the Parapharyngodon clade, suggesting that they were misidentified or rather represent alternative morphotypes of other species. Morphological analysis identified the length of the tail, number of caudal papillae, position of the nerve ring, presence of caudal alae and length of the lateral alae as reliable characters to distinguish between Parapharyngodon and Thelandros genetic clades. Our study highlights the current taxonomic inconsistency in these groups, mainly derived from the exclusive use of morphological data. As such, we advocate for the routine implementation of molecular data in nematode taxonomic studies.
The island of Gran Canaria is regularly affected by dust falls due to its proximity to the Saharan desert. Climatic oscillations may affect the Saharan dust input to the island. Geochemical, mineralogical, and textural analysis was performed on a well-developed and representative early Pleistocene paleosol to examine Saharan dust contribution to Gran Canaria. Significant and variable Saharan dust content was identified in addition to weathering products such as iron oxides and clay minerals. Variations in quartz and iron oxide concentrations in the paleosol likely reflect different Saharan dust input in more/less-contrasted rhexistasic/biostatic climatic conditions. Linking the quartz content in Canarian soils, the Ingenio paleosol, and two Canarian loess-like deposits to different ages from the Quaternary, we hypothesized that the dust input should be lower (about 33–38%) throughout the early to middle Pleistocene than during the late Quaternary. The Saharan dust input to the Gran Canaria profile in the Pleistocene persisted in spite of climatic variations.
OBJECTIVES/SPECIFIC AIMS: High on-treatment platelet reactivity (HTPR) with clopidogrel imparts an increased risk for ischemic events in adults with coronary artery disease. Although more potent antiplatelet agents are available, clopidogrel remains the most commonly used P2Y12 inhibitor in Puerto Rico. Platelet reactivity varies with ethnicity and is influenced by both clinical and genetic variables; however, no clopidogrel pharmacogenetic studies with Puerto Rican patients have been reported. Therefore, we sought to identify clinical and genetic determinants of on-treatment platelet reactivity in a cohort of Puerto Rican patients with cardiovascular disease. METHODS/STUDY POPULATION: We performed a retrospective study of 111 Puerto Rican patients on 75 mg/day maintenance dose of clopidogrel. Patients were allocated into 2 groups: Group I, without HTPR; and Group II, with HTPR. Clinical data was obtained from the medical record. Platelet function was measured ex vivo using the VerifyNow® P2Y12 assay and HTPR was defined as P2Y12 reaction units (PRU)≥230. Genotyping of CYP2C19, ABCB1, PON1, PY2R12, B4GALT2, CES1, and PEAR1 was performed using Taqman® Genotyping Assays. RESULTS/ANTICIPATED RESULTS: The mean PRU across the cohort was 203±61 PRU (range, 8–324), and 42 (38%) patients had HTPR. One in four individuals carried at least 1 copy of the CYP2C19*2 variant allele. Hematocrit and PON1 p.Q192R variant were inversely correlated with platelet reactivity (p<0.05). Multiple logistic regression showed that 27% of the total variation in PRU was explained by a history of diabetes mellitus, hematocrit, CYP2C19*2, and PON1 p.Q192R. Body mass index (OR=1.15; CI: 1.03–1.27), diabetes mellitus (OR=3.46; CI: 1.05–11.43), hematocrit (OR=0.75; CI: 0.65–0.87), and CYP2C19*2 (OR=4.44; CI: 1.21–16.20) were the only independent predictors of HTPR. DISCUSSION/SIGNIFICANCE OF IMPACT: In a representative sample of Puerto Rican patients with cardiovascular disease, diabetes mellitus, hematocrit, CYP2C19*2, and PON1 p.Q192R were associated with on-treatment platelet reactivity. These factors may identify a subset of patients at higher risk for adverse events on clopidogrel in the Hispanic population.
A drift-kinetic model to describe the plasma dynamics in the scrape-off layer region of tokamak devices at arbitrary collisionality is derived. Our formulation is based on a gyroaveraged Lagrangian description of the charged particle motion, and the corresponding drift-kinetic Boltzmann equation that includes a full Coulomb collision operator. Using a Hermite–Laguerre velocity space decomposition of the gyroaveraged distribution function, a set of equations to evolve the coefficients of the expansion is presented. By evaluating explicitly the moments of the Coulomb collision operator, distribution functions arbitrarily far from equilibrium can be studied at arbitrary collisionalities. A fluid closure in the high-collisionality limit is presented, and the corresponding fluid equations are compared with previously derived fluid models.
OBJECTIVES/SPECIFIC AIMS: The objective of this study is to measure the association of CYP2C19 (*1-*8,*17), ABCB1(C3435T; rs1045642), PON1 (p.Q192R; rs662), and B4GALT2 (c.909 C>T and c.366 G>C) gene polymorphisms in the Caribbean Hispanic population with major adverse cardiovascular events (MACE). METHODS/STUDY POPULATION: Patients of Caribbean Hispanic ethnicity from all geographic regions of the Island of Puerto Rico, male and female, aged >21 will be recruited. Cases will consist of patients receiving a daily clopidogrel dose of 75 mg following acute coronary syndrome (ACS) who experience a MACE within the first year of treatment. Control study patients must have received clopidogrel 75 mg daily for a minimum of 1 year without experiencing MACE. Genomic DNA samples will be genotyped to determine the frequency distribution of major CYP2C19, ABCB1, PON1, and B4GALT2 gene polymorphisms. Observed frequencies will be compared with other reported populations. An association study will be performed between genetic variables and MACE and a multivariable logistic regression model (additive) will be constructed. RESULTS/ANTICIPATED RESULTS: We anticipate finding a significant association between major genetic determinants of clopidogrel response and MACE where cases with MACE will carry higher frequency of CYP2C19, ABCB1, PON1, and B4GALT2. DISCUSSION/SIGNIFICANCE OF IMPACT: As the range of multiloci allelic combinations in admixed Caribbean Hispanics is higher than in other populations due to its unique 500-year history of genomic admixture, a wide spectrum of genetic variances is expected to be present in the study population. Determining the prevalence and effect of CYP2C19, ABCB1, PON1, and B4GALT2 polymorphisms holds the potential to personalize anti-platelet treatment for Caribbean Hispanic patients requiring treatment after ACS.
The extent of New Zealand's freshwater fish-parasite diversity has yet to be fully revealed, with host–parasite relationships still to be described from nearly half the known fish community. While advances in the number of fish species examined and parasite taxa described are being made, some parasite groups, such as nematodes, remain poorly understood. In the present study we combined morphological and molecular analyses to characterize a capillariid nematode found infecting the swim bladder of the brown mudfish Neochanna apoda, an endemic New Zealand fish from peat-swamp-forests. Morphologically, the studied nematodes are distinct from other Capillariinae taxa by the features of the male posterior end, namely the shape of the bursa lobes, and shape of spicule distal end. Male specimens were classified into three different types according to differences in the shape of the bursa lobes at the posterior end, but only one was successfully characterized molecularly. Molecular analysis indicated that the studied capillariid is distinct from other genera. However, inferences about the phylogenetic position of the capillariid reported here will remain uncertain, due to the limited number of Capillariinae taxa characterized molecularly. The discovery of this new capillariid, which atypically infects the swim bladder of its host, which itself inhabits a very unique ecosystem, underlines the very interesting evolutionary history of this parasite, which for now will remain unresolved.
Lithium sulfur (Li–S) batteries have the potential to provide higher energy storage density at lower cost than conventional lithium ion batteries. A key challenge for Li–S batteries is the loss of sulfur to the electrolyte during cycling. This loss can be mitigated by sequestering the sulfur in nanostructured carbon–sulfur composites. The nanoscale characterization of the sulfur distribution within these complex nanostructured electrodes is normally performed by electron microscopy, but sulfur sublimates and redistributes in the high-vacuum conditions of conventional electron microscopes. The resulting sublimation artifacts render characterization of sulfur in conventional electron microscopes problematic and unreliable. Here, we demonstrate two techniques, cryogenic transmission electron microscopy (cryo-TEM) and scanning electron microscopy in air (airSEM), that enable the reliable characterization of sulfur across multiple length scales by suppressing sulfur sublimation. We use cryo-TEM and airSEM to examine carbon–sulfur composites synthesized for use as Li–S battery cathodes, noting several cases where the commonly employed sulfur melt infusion method is highly inefficient at infiltrating sulfur into porous carbon hosts.