The influence of cannabis smoke and cannabis vapour on simulated lung surfactant function under physiologically relevant conditions

The use of cannabis for medicinal/recreational purposes is widespread throughout the world. Smoke inhalation is known to cause airway irritation due to noxious substances (ie, benzene) within the mix. Thus, advanced vaporisation platforms (eg, Davinci IQ) have been developed to circumvent negative health implications. Here, we consider the impact that cannabis smoke and cannabis vapour have on simulated lung surfactant performance within a model pulmonary space (ie, 37°C, elevated humidity and related fluid hydrodynamics). In total, 50 mg of herbal material was ignited or placed within a Davinci IQ vaporiser with subsequent activation. The aliquots were collected and then analysed using gas chromatography‐mass spectroscopy for composition and cannabinoid (eg, Δ9‐tetrahydrocannabinol [Δ9‐THC]) concentration. The average content within cannabis smoke was 2.84% (0.07%, SD) Δ9‐THC, with the same for cannabis vapour being 0.88% (0.14%, SD). Aerosolised samples were transferred to the lung biosimulator. When compared with the pristine Curosurf system, challenge with cannabis smoke and cannabis vapour reduced the surface pressure term by 26% and 7% and increased film compressibility by 60% and 15% at 80% trough area, respectively. The net effect would be enhanced film elasticity and an increased work of breathing, being more pronounced on cannabis smoke inhalation. The trends noted were ascribed to two factors operating synergistically, namely the amount of Δ9‐THC (plus others) within the aerosolised samples and the associated toxicity profile. Further research is required to establish mass‐balance effects (ie, titrated outputs) along with detailed chemical profiling of material generated from the unrelated cannabis activation pathways

Prescription Drugs Associated with Reports of Violence Towards Others

CONTEXT: Violence towards others is a seldom-studied adverse drug event and an atypical one because the risk of injury extends to others. OBJECTIVE: To identify the primary suspects in adverse drug event reports describing thoughts or acts of violence towards others, and assess the strength of the association. METHODOLOGY: From the Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) data, we extracted all serious adverse event reports for drugs with 200 or more cases received from 2004 through September 2009. We identified any case report indicating homicide, homicidal ideation, physical assault, physical abuse or violence related symptoms. MAIN OUTCOME MEASURES: Disproportionality in reporting was defined as a) 5 or more violence case reports, b) at least twice the number of reports expected given the volume of overall reports for that drug, c) a χ2 statistic indicating the violence cases were unlikely to have occurred by chance (p<0.01). RESULTS: We identified 1527 cases of violence disproportionally reported for 31 drugs. Primary suspect drugs included varenicline (an aid to smoking cessation), 11 antidepressants, 6 sedative/hypnotics and 3 drugs for attention deficit hyperactivity disorder. The evidence of an association was weaker and mixed for antipsychotic drugs and absent for all but 1 anticonvulsant/mood stabilizer. Two or fewer violence cases were reported for 435/484 (84.7%) of all evaluable drugs suggesting that an association with this adverse event is unlikely for these drugs. CONCLUSIONS: Acts of violence towards others are a genuine and serious adverse drug event associated with a relatively small group of drugs. Varenicline, which increases the availability of dopamine, and antidepressants with serotonergic effects were the most strongly and consistently implicated drugs. Prospective studies to evaluate systematically this side effect are needed to establish the incidence, confirm differences among drugs and identify additional common features

Illusory temporal binding in meditators

We investigate conditions in which more accurate metacognition may lead to greater susceptibility to illusion; and thus conditions under which mindfulness meditation may lead to less accurate perceptions. Specifically, greater awareness of intentions may lead to an illusory compression of time between a voluntary action and its outcome (“intentional binding”). Here we report that experienced Buddhist mindfulness meditators rather than non-meditators display a greater illusory shift of the timing of an outcome towards an intentional action. Mindfulness meditation involves awareness of causal connections between different mental states, including intentions. We argue that this supports improvements in metacognition targeted at motor intentions. Changes in metacognitive ability may result in an earlier and less veridical experience of the timing of action outcomes either through increased access to sensorimotor pre-representations of an action outcome or by affording greater precision to action timing judgements. Furthermore, as intentional binding is an implicit measure of the sense of agency, these results also provide evidence that mindfulness meditators experience a stronger sense of agency

Metabolic Rift or Metabolic Shift? Dialectics, Nature, and the World-Historical Method

Abstract In the flowering of Red-Green Thought over the past two decades, metabolic rift thinking is surely one of its most colorful varieties. The metabolic rift has captured the imagination of critical environmental scholars, becoming a shorthand for capitalism’s troubled relations in the web of life. This article pursues an entwined critique and reconstruction: of metabolic rift thinking and the possibilities for a post-Cartesian perspective on historical change, the world-ecology conversation. Far from dismissing metabolic rift thinking, my intention is to affirm its dialectical core. At stake is not merely the mode of explanation within environmental sociology. The impasse of metabolic rift thinking is suggestive of wider problems across the environmental social sciences, now confronted by a double challenge. One of course is the widespread—and reasonable—sense of urgency to evolve modes of thought appropriate to an era of deepening biospheric instability. The second is the widely recognized—but inadequately internalized—understanding that humans are part of nature

Factors affecting continuation of clean intermittent catheterisation in people with multiple sclerosis: results of the COSMOS mixed-methods study

Background:  Clean intermittent catheterisation (CIC) is often recommended for people with multiple sclerosis (MS).  Objective:  To determine the variables that affect continuation or discontinuation of the use of CIC.  Methods:  A three-part mixed-method study (prospective longitudinal cohort (n = 56), longitudinal qualitative interviews (n = 20) and retrospective survey (n = 456)) was undertaken, which identified the variables that influenced CIC continuation/discontinuation. The potential explanatory variables investigated in each study were the individual’s age, gender, social circumstances, number of urinary tract infections, bladder symptoms, presence of co-morbidity, stage of multiple sclerosis and years since diagnosis, as well as CIC teaching method and intensity.  Results:  For some people with MS the prospect of undertaking CIC is difficult and may take a period of time to accept before beginning the process of using CIC. Ongoing support from clinicians, support at home and a perceived improvement in symptoms such as nocturia were positive predictors of continuation. In many cases, the development of a urinary tract infection during the early stages of CIC use had a significant detrimental impact on continuation.  Conclusion:  Procedures for reducing the incidence of urinary tract infection during the learning period (i.e. when being taught and becoming competent) should be considered, as well as the development of a tool to aid identification of a person’s readiness to try CIC

Emergent synergistic lysosomal toxicity of chemical mixtures in molluscan blood cells (hemocytes)

The problem of effective assessment of risk posed by complex mixtures of toxic chemicals in the environment is a major challenge for government regulators and industry. The biological effect of the individual contaminants, where these are known, can be measured; but the problem lies in relating toxicity to the multiple constituents of contaminant cocktails. The objective of this study was to test the hypothesis that diverse contaminant mixtures may cause a greater toxicity than the sum of their individual parts, due to synergistic interactions between contaminants with different intracellular targets. Lysosomal membrane stability in hemocytes from marine mussels was used for in vitro toxicity tests; and was coupled with analysis using the isobole method and a linear additive statistical model. The findings from both methods have shown significant emergent synergistic interactions between environmentally relevant chemicals (i.e., polycyclic aromatic hydrocarbons, pesticides, biocides and a surfactant) when exposed to isolated hemocytes as a mixture of 3 & 7 constituents. The results support the complexity-based hypothesis that emergent toxicity occurs with increasing contaminant diversity, and raises questions about the validity of estimating toxicity of contaminant mixtures based on the additive toxicity of single components. Further experimentation is required to investigate the potential for interactive effects in mixtures with more constituents (e.g., 50 –100) at more environmentally realistic concentrations in order to test other regions of the model, namely, very low concentrations and high diversity. Estimated toxicant diversity coupled with tests for lysosomal damage may provide a potential tool for determining the toxicity of estuarine sediments, dredge spoil or contaminated soil

Examining the effect of Libet clock stimulus parameters on temporal binding

Temporal binding refers to the subjective temporal compression between actions and their outcomes. It is widely used as an implicit measure of sense of agency, that is, the experience of controlling our actions and their consequences. One of the most common measures of temporal binding is the paradigm developed by Haggard, Clark and Kalogeras (2002) based on the Libet clock stimulus. Although widely used, it is not clear how sensitive the temporal binding effect is to the parameters of the clock stimulus. Here, we present five experiments examining the effects of clock speed, number of clock markings and length of the clock hand on binding. Our results show that the magnitude of temporal binding increases with faster clock speeds, whereas clock markings and clock hand length do not significantly influence temporal binding. We discuss the implications of these results

Multiparametric prostate MRI quality assessment using a semi-automated PI-QUAL software program

The technical requirements for the acquisition of multiparametric magnetic resonance imaging (mpMRI) of the prostate have been clearly outlined in the Prostate Imaging Reporting and Data System (PI-RADS) guidelines, but there is still huge variability in image quality among centres across the world. It has been difficult to quantify what constitutes a good-quality image, and a first attempt to address this matter has been the publication of the Prostate Imaging Quality (PI-QUAL) score and its dedicated scoring sheet. This score includes the assessment of technical parameters that can be obtained from the DICOM files along with a visual evaluation of certain features on prostate MRI (e.g., anatomical structures). We retrospectively analysed the image quality of 10 scans from different vendors and magnets using a semiautomated dedicated PI-QUAL software program and compared the time needed for assessing image quality using two methods (semiautomated assessment versus manual filling of the scoring sheet). This semiautomated software is able to assess the technical parameters automatically, but the visual assessment is still performed by the radiologist. There was a significant reduction in the reporting time of prostate mpMRI quality according to PI-QUAL using the dedicated software program compared to manual filling (5'54″ versus 7'59″; p = 0.005). A semiautomated PI-QUAL software program allows the radiologist to assess the technical details related to the image quality of prostate mpMRI in a quick and reliable manner, allowing clinicians to have more confidence that the quality of mpMRI of the prostate is sufficient to determine patient care

Anomaly-Free Supersymmetric SO(2N+2)/U(N+1) sigma-Model Based on the SO(2N+1) Lie Algebra of the Fermion Operators

The extended supersymmetric (SUSY) sigma-model has been proposed on the bases of SO(2N+1) Lie algebra spanned by fermion annihilation-creation operators and pair operators. The canonical transformation, extension of an SO(2N) Bogoliubov transformation to an SO(2N+1) group, is introduced. Embedding the SO(2N+1) group into an SO(2N+2) group and using SO(2N+2)/U(N+1) coset variables, we have investigated the SUSY sigma-model on the Kaehler manifold, the coset space SO(2N+2)/U(N+1). We have constructed the Killing potential, extension of the potential in the SO(2N)/U(N) coset space to that in the SO(2N+2)/U(N+1) coset space. It is equivalent to the generalized density matrix whose diagonal-block part is related to a reduced scalar potential with a Fayet-Ilipoulos term. The f-deformed reduced scalar potential is optimized with respect to vacuum expectation value of the sigma-model fields and a solution for one of the SO(2N+1) group parameters has been obtained. The solution, however, is only a small part of all solutions obtained from anomaly-free SUSY coset models. To construct the coset models consistently, we must embed a coset coordinate in an anomaly-free spinor representation (rep) of SO(2N+2) group and give corresponding Kaehler and Killing potentials for an anomaly-free SO(2N+2)/U(N+1) model based on each positive chiral spinor rep. Using such mathematical manipulation we construct successfully the anomaly-free SO(2N+2)/U(N+1) SUSY sigma-model and investigate new aspects which have never been seen in the SUSY sigma-model on the Kaehler coset space SO(2N)/U(N). We reach a f-deformed reduced scalar potential. It is minimized with respect to the vacuum expectation value of anomaly-free SUSY sigma-model fields. Thus we find an interesting f-deformed solution very different from the previous solution for an anomaly-free SO(2.5+2)/(SU(5+1)*U(1)) SUSY sigma-model.Comment: 24 pages, no fiure