Evaluation of herbal cannabis characteristics by medical users: a randomized trial

BACKGROUND: Cannabis, in herbal form, is widely used as self-medication by patients with diseases such as HIV/AIDS and multiple sclerosis suffering from symptoms including pain, muscle spasticity, stress and insomnia. Valid clinical studies of herbal cannabis require a product which is acceptable to patients in order to maximize adherence to study protocols. METHODS: We conducted a randomized controlled crossover trial of 4 different herbal cannabis preparations among 8 experienced and authorized cannabis users with chronic pain. Preparations were varied with respect to grind size, THC content and humidity. Subjects received each preparation on a separate day and prepared the drug in their usual way in a dedicated and licensed clinical facility. They were asked to evaluate the products based on appearance (smell, colour, humidity, grind size, ease of preparation and overall appearance) and smoking characteristics (burn rate, hotness, harshness and taste). Five-point Likert scores were assigned to each characteristic. Scores were compared between preparations using ANOVA. RESULTS: Seven subjects completed the study, and the product with highest THC content (12%), highest humidity (14%) and largest grind size (10 mm) was rated highest overall. Significant differences were noted between preparations on overall appearance and colour (p = 0.003). DISCUSSION: While the small size of the study precludes broad conclusions, the study shows that medical cannabis users can appreciate differences in herbal product. A more acceptable cannabis product may increase recruitment and retention in clinical studies of medical cannabis

The Direction of Neurite Growth in a Weak DC Electric Field Depends on the Substratum: Contributions of Adhesivity and Net Surface Charge

AbstractWe investigated the influence of the growth surface on the direction ofXenopusspinal neurite growth in the presence of a dc electric field of physiological magnitude. The direction of galvanotropism was determined by the substratum; neurites grew toward the negative electrode (cathode) on untreated Falcon tissue culture plastic or on laminin substrata, which are negatively charged, but neurites growing on polylysine, which is positively charged, turned toward the positive electrode (anode). Growth was oriented randomly on all substrata without an electric field. We tested the hypothesis that the charge of the growth surface was responsible for reversed galvanotropism on polylysine by growing neurons on tissue culture dishes with different net surface charges. Although neurites grew cathodally on both Plastek substrata, the frequency of anodal turning was greater on dishes with a net positive charge (Plastek C) than on those with a net negative charge (Plastek M). The charge of the growth surface therefore influenced the frequency of anodal galvanotropism but a reversal in surface charge was insufficient to reverse galvanotropism completely, possibly because of differences in the relative magnitude of the substratum charge densities. The influence of substratum adhesion on galvanotropism was considered by growing neurites on a range of polylysine concentrations. Growth cone to substratum adhesivity was measured using a blasting assay. Adhesivity and the frequency of anodal turning were graded over the range of polylysine concentrations (0 = 0.1 < 1 < 10 = 100 μg/ml). The direction of neurite growth in an electric field is therefore influenced by both substratum charge and growth cone-to-substratum adhesivity. These data are consistent with the idea that spatial or temporal variation in the expression of adhesion molecules in embryos may interact with naturally occurring electric fields to enhance growth cone pathfinding

Spectroscopy of Nine Cataclysmic Variable Stars

We present optical spectroscopy of nine cataclysmic binary stars, mostly dwarf novae, obtained primarily to determine orbital periods Porb. The stars and their periods are LX And, 0.1509743(5) d; CZ Aql, 0.2005(6) d; LU Cam, 0.1499686(4) d; GZ Cnc, 0.0881(4) d; V632 Cyg, 0.06377(8) d; V1006 Cyg, 0.09903(9) d; BF Eri, 0.2708804(4) d; BI Ori, 0.1915(5) d; and FO Per, for which Porb is either 0.1467(4) or 0.1719(5) d. Several of the stars proved to be especially interesting. In BF Eri, we detect the absorption spectrum of a secondary star of spectral type K3 +- 1 subclass, which leads to a distance estimate of approximately 1 kpc. However, BF Eri has a large proper motion (100 mas/yr), and we have a preliminary parallax measurement that confirms the large proper motion and yields only an upper limit for the parallax. BF Eri's space velocity is evidently large, and it appears to belong to the halo population. In CZ Aql, the emission lines have strong wings that move with large velocity amplitude, suggesting a magnetically-channeled accretion flow. The orbital period of V1006 Cyg places it squarely within the 2- to 3-hour "gap" in the distribution of cataclysmic binary orbital periods.Comment: 31 pages, 5 postscript and one PNG figure. Accepted for PAS

Differing instructional needs for children of similar reading achievement grades two, four, and six

Thesis (Ed.M.)--Boston Universit

The body, health, and healing in alternative and integrated medicine : an ethnography of homeopathy in South London

During the recent exponential rise in the use of alternative medicines (AM) in the West and increasing integration into the health service, little research has been done on AM in the context in which it is practised, or over time to look at changing belief systems. This thesis provides an anthropologically informed analysis of one alternative therapy in depth - homeopathy- explored from the multiple perspectives of biomedical and lay homeopaths, users and students of homeopathy. The ethnography comprised 18 months participant observation in 4 settings in south London: the surgery of a homeopathic GP; a homeopathy adult education class; a vaccination support group; and a low cost homeopathy clinic for victims of crime. The fieldwork is contextualised by a critique of the existing research on users of AM; a review of the history and politics of integration of AM and a review of anthropological conceptions of the body and health. Analysis of the empirical data reveals different groups of users of homeopathy with differing beliefs around health, healing and the body. 'Pragmatic users' had a normative biomedical view of health. 'Committed users' moved away from the normative biomedical position and were enculturated into a different view of health and the body through interaction with lay homeopaths. Inherent in these practitioners' and users' beliefs and practices were a number of oppositions to science-based medicine. Prolonged fieldwork enabled the changing views of users to be charted as they moved from biomedical to alternative views. The medical homeopath stayed allied to many biomedical beliefs about the body and health, partly as a result of general practice constraints of time, colleagues and training. Tensions between his biomedical and homeopathic practice lead to paradoxical behaviours that confused his patients. These findings problematise the notion of integration, of trying to incorporate two opposing ideologies into one system. Implications for alternative medicine more widely are discussed.EThOS - Electronic Theses Online ServiceNHS Executive London RegionGBUnited Kingdo

Analysis of Fcγ receptor haplotypes in rheumatoid arthritis: FCGR3A remains a major susceptibility gene at this locus, with an additional contribution from FCGR3B

The Fcγ receptors play important roles in the initiation and regulation of many immunological and inflammatory processes, and genetic variants (FCGR) have been associated with numerous autoimmune and infectious diseases. The data in rheumatoid arthritis (RA) are conflicting and we previously demonstrated an association between FCGR3A and RA. In view of the close molecular proximity with FCGR2A, FCGR2B and FCGR3B, additional polymorphisms within these genes and FCGR haplotypes were examined to refine the extent of association with RA. Biallelic polymorphisms in FCGR2A, FCGR2B and FCGR3B were examined for association with RA in two well characterized UK Caucasian and North Indian/Pakistani cohorts, in which FCGR3A genotyping had previously been undertaken. Haplotype frequencies and linkage disequilibrium were estimated across the FCGR locus and a model-free analysis was performed to determine association with RA. This was followed by regression analysis, allowing for phase uncertainty, to identify the particular haplotype(s) that influences disease risk. Our results reveal that FCGR2A, FCGR2B and FCGR3B were not associated with RA. The haplotype with the strongest association with RA susceptibility was the FCGR3A–FCGR3B 158V-NA2 haplotype (odds ratio 3.18, 95% confidence interval 1.13–8.92 [P = 0.03] for homozygotes compared with all genotypes). The association was stronger in the presence of nodules (odds ratio 5.03, 95% confidence interval 1.44–17.56; P = 0.01). This haplotype was also more common in North Indian/Pakistani RA patients than in control individuals, but not significantly so. Logistic regression analyses suggested that FCGR3A remained the most significant gene at this locus. The increased association with an FCGR3A–FCGR3B haplotype suggests that other polymorphic variants within FCGR3A or FCGR3B, or in linkage disequilibrium with this haplotype, may additionally contribute to disease pathogenesis

Identification of a Novel Staphylococcus aureus Two-Component Leukotoxin Using Cell Surface Proteomics

Staphylococcus aureus is a prominent human pathogen and leading cause of bacterial infection in hospitals and the community. Community-associated methicillin-resistant S. aureus (CA-MRSA) strains such as USA300 are highly virulent and, unlike hospital strains, often cause disease in otherwise healthy individuals. The enhanced virulence of CA-MRSA is based in part on increased ability to produce high levels of secreted molecules that facilitate evasion of the innate immune response. Although progress has been made, the factors that contribute to CA-MRSA virulence are incompletely defined. We analyzed the cell surface proteome (surfome) of USA300 strain LAC to better understand extracellular factors that contribute to the enhanced virulence phenotype. A total of 113 identified proteins were associated with the surface of USA300 during the late-exponential phase of growth in vitro. Protein A was the most abundant surface molecule of USA300, as indicated by combined Mascot score following analysis of peptides by tandem mass spectrometry. Unexpectedly, we identified a previously uncharacterized two-component leukotoxin–herein named LukS-H and LukF-G (LukGH)-as two of the most abundant surface-associated proteins of USA300. Rabbit antibody specific for LukG indicated it was also freely secreted by USA300 into culture media. We used wild-type and isogenic lukGH deletion strains of USA300 in combination with human PMN pore formation and lysis assays to identify this molecule as a leukotoxin. Moreover, LukGH synergized with PVL to enhance lysis of human PMNs in vitro, and contributed to lysis of PMNs after phagocytosis. We conclude LukGH is a novel two-component leukotoxin with cytolytic activity toward neutrophils, and thus potentially contributes to S. aureus virulence

Rapid radiocarbon (14C) analysis of coral and carbonate samples using a continuous-flow accelerator mass spectrometry (CFAMS) system

Author Posting. © American Geophysical Union, 2011. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Paleoceanography 26 (2011): PA4212, doi:10.1029/2011PA002174.Radiocarbon analyses of carbonate materials provide critical information for understanding the last glacial cycle, recent climate history and paleoceanography. Methods that reduce the time and cost of radiocarbon (14C) analysis are highly desirable for large sample sets and reconnaissance type studies. We have developed a method for rapid radiocarbon analysis of carbonates using a novel continuous-flow accelerator mass spectrometry (CFAMS) system. We analyzed a suite of deep-sea coral samples and compared the results with those obtained using a conventional AMS system. Measurement uncertainty is <0.02 Fm or 160 Ryr for a modern sample and the mean background was 37,800 Ryr. Radiocarbon values were repeatable and in good agreement with those from the conventional AMS system. Sample handling and preparation is relatively simple and the method offered a significant increase in speed and cost effectiveness. We applied the method to coral samples from the Eastern Pacific Ocean to obtain an age distribution and identify samples for further analysis. This paper is intended to update the paleoceanographic community on the status of this new method and demonstrate its feasibility as a choice for rapid and affordable radiocarbon analysis.This work was performed under NSF Cooperative Agreement OCE‐0753487, and also NSF‐OPP awards 0636787 and 0944474

Developing specialist leaders of education: a research engagement approach

There has been little research to date on the continuing professional development needs of the several thousand Specialist Leaders of Education (SLE) now designated by the National College for Teaching and Leadership in England to work across schools as consultants on school-to-school support. This case study reports on the second and third stages of a four-stage research process designed to address these needs. The fi rst stage reported on the creation of a professional devel- opment framework for SLE ’ s using consultancy research. These middle stages test out this framework with a stakeholder group of SLEs, head- teachers and broker in a Teaching Schools Alliance. The fourth stage will track the implementation of professional development activities arising from these fi ndings. Apart from the speci fi c needs of SLE, this study will have wider relevance for all practitioners and researchers working in and with schools on leadership development using Research Engagement strategies and Joint Practice Development approaches in a so-called ‘ self- improving ’ school system

Multi-omics investigation of Clostridioides difficile-colonized patients reveals pathogen and commensal correlates of C. difficile pathogenesis

Clostridioides difficile infection (CDI) imposes a substantial burden on the health care system in the United States. Understanding the biological basis for the spectrum of C. difficile-related disease manifestations is imperative to improving treatment and prevention of CDI. Here, we investigate the correlates of asymptomatic C. difficile colonization using a multi-omics approach. We compared the fecal microbiome and metabolome profiles of patients with CDI versus asymptomatically colonized patients, integrating clinical and pathogen factors into our analysis. We found that CDI patients were more likely to be colonized by strains with the binary toxin (CDT) locus or strains of ribotype 027, which are often hypervirulent. We find that microbiomes of asymptomatically colonized patients are significantly enriched for species in the class Clostridia relative to those of symptomatic patients. Relative to CDI microbiomes, asymptomatically colonized patient microbiomes were enriched with sucrose degradation pathways encoded by commensal Clostridia, in addition to glycoside hydrolases putatively involved in starch and sucrose degradation. Fecal metabolomics corroborates the carbohydrate degradation signature: we identify carbohydrate compounds enriched in asymptomatically colonized patients relative to CDI patients. Further, we reveal that across C. difficile isolates, the carbohydrates sucrose, rhamnose, and lactulose do not serve as robust growth substrates in vitro, consistent with their enriched detection in our metagenomic and metabolite profiling of asymptomatically colonized individuals. We conclude that pathogen genetic variation may be strongly related to disease outcome. More interestingly, we hypothesize that in asymptomatically colonized individuals, carbohydrate metabolism by other commensal Clostridia may prevent CDI by inhibiting C. difficile proliferation. These insights into C. difficile colonization and putative commensal competition suggest novel avenues to develop probiotic or prebiotic therapeutics against CDI