Heavy cannabis use is associated with low bone mineral density and an increased risk of fractures

Purpose: To investigate possible associations between recreational cannabis use and bone health in humans.  Methods: Cross-sectional study of individuals recruited from primary care in the UK between 2011 and 2014. Cases were regular smokers of cannabis divided into moderate (n=56) and heavy user (n=144) subgroups depending on whether they reported fewer or more than 5000 cannabis smoking episodes during their lifetime. Controls comprised 114 cigarette smokers.  Results: Heavy cannabis users had lower total hip bone mineral density (mean ± SD Z-score: -0.20±0.9 vs. +0.2±0.9, p<0.0005), lower spine bone mineral density (-0.5±1.2 vs. 0.0±1.2, p<0.0005) and lower BMI (26.5±6.0 vs 29.0±7.0, p=0.01) than controls. Fracture rate was also increased in heavy users (rate ratio=2.17, 95% confidence interval 1.59 to 2.95; p<0.001). When compared with controls, CTX serum concentrations were raised in heavy cannabis users (0.3±0.1 vs. 0.2±0.1 pg/ml, p=0.045) as were P1NP concentrations (47.1±19.2 vs. 41.2±17.8 pg/ml, p=0.01). Serum 25(OH)D concentrations were reduced in heavy users compared with controls (25.3±16.8 vs. 36.9±26.7 nmol/l, p=0.002). Multiple regression analysis revealed that heavy cannabis use was an independent predictor of spine bone mineral density accounting for 5.4% of the variance (p=0.035) and total hip bone mineral density accounting for 5.8% of the variance (p=0.001) but mediation analysis suggested that the effect on spine bone mineral density was indirect and mediated through low BMI.  Conclusion: Heavy cannabis use is associated with low bone mineral density, low BMI, high bone turnover and an increased risk of fracture. Heavy cannabis use negatively impacts on bone health both directly and indirectly through an effect on BMI

Evaluating the impact of patients' online access to doctors' visit notes: designing and executing the OpenNotes project

Background: Providers and policymakers are pursuing strategies to increase patient engagement in health care. Increasingly, online sections of medical records are viewable by patients though seldom are clinicians' visit notes included. We designed a one-year multi-site trial of online patient accessible office visit notes, OpenNotes. We hypothesized that patients and primary care physicians (PCPs) would want it to continue and that OpenNotes would not lead to significant disruptions to doctors' practices. Methods/Design: Using a mixed methods approach, we designed a quasi-experimental study in 3 diverse healthcare systems in Boston, Pennsylvania, and Seattle. Two sites had existing patient internet portals; the third used an experimental portal. We targeted 3 key areas where we hypothesized the greatest impacts: beliefs and attitudes about OpenNotes, use of the patient internet portals, and patient-doctor communication. PCPs in the 3 sites were invited to participate in the intervention. Patients who were registered portal users of participating PCPs were given access to their PCPs' visit notes for one year. PCPs who declined participation in the intervention and their patients served as the comparison groups for the study. We applied the RE-AIM framework to our design in order to capture as comprehensive a picture as possible of the impact of OpenNotes. We developed pre- and post-intervention surveys for online administration addressing attitudes and experiences based on interviews and focus groups with patients and doctors. In addition, we tracked use of the internet portals before and during the intervention. Results: PCP participation varied from 19% to 87% across the 3 sites; a total of 114 PCPs enrolled in the intervention with their 22,000 patients who were registered portal users. Approximately 40% of intervention and non-intervention patients at the 3 sites responded to the online survey, yielding a total of approximately 38,000 patient surveys. Discussion: Many primary care physicians were willing to participate in this "real world" experiment testing the impact of OpenNotes on their patients and their practices. Results from this trial will inform providers, policy makers, and patients who contemplate such changes at a time of exploding interest in transparency, patient safety, and improving the quality of care

Inverse Scattering for Gratings and Wave Guides

We consider the problem of unique identification of dielectric coefficients for gratings and sound speeds for wave guides from scattering data. We prove that the "propagating modes" given for all frequencies uniquely determine these coefficients. The gratings may contain conductors as well as dielectrics and the boundaries of the conductors are also determined by the propagating modes.Comment: 12 page

The Nucleon ``Tensor Charges'' and the Skyrme Model

The lowest moment of the twist-two, chiral-odd parton distribution $h_1(x)$ of the nucleon can be related to the so-called ``tensor charges'' of the nucleon. We consider the tensor charges in the Skyrme model, and find that in the large-$N_c$, SU(3)-symmetric limit, the model predicts that the octet isosinglet tensor charge, $g^8_T$, is of order $1/N_c$ with respect to the octet isovector tensor charge, $g^3_T$. The predicted $F/D$ ratio is then 1/3, in the large-$N_c$ limit. These predictions coincide with the Skyrme model predictions for the octet ${\it axial}$ charges, $g^8_A$ and $g^3_A$. (The prediction $F/D=1/3$ for the axial charges differs from the commonly quoted prediction of 5/9, which is based on an inconsistent treatment of the large-$N_c$ limit.) The model also predicts that the singlet tensor charge, $g^0_T$, is of order $1/N_c$ with respect to $g^3_T$.Comment: 9 single-spaced pages, no figures, MIT-CTP-212

Raman Spectroscopic Analysis of Fingernail Clippings Can Help Differentiate between Postmenopausal Women Who Have and Have Not Suffered a Fracture

Raman spectroscopy was applied to nail clippings from 633 postmenopausal British and Irish women, from six clinical sites, of whom 42% had experienced a fragility fracture. The objective was to build a prediction algorithm for fracture using data from four sites (known as the calibration set) and test its performance using data from the other two sites (known as the validation set). Results from the validation set showed that a novel algorithm, combining spectroscopy data with clinical data, provided area under the curve (AUC) of 74% compared to an AUC of 60% from a reduced QFracture score (a clinically accepted risk calculator) and 61% from the dual-energy X-ray absorptiometry T-score, which is in current use for the diagnosis of osteoporosis. Raman spectroscopy should be investigated further as a noninvasive tool for the early detection of enhanced risk of fragility fracture

Meaning behind measurement : self-comparisons affect responses to health related quality of life questionnaires

Purpose The subjective nature of quality of life is particularly pertinent to the domain of health-related quality of life (HRQOL) research. The extent to which participants’ responses are affected by subjective information and personal reference frames is unknown. This study investigated how an elderly population living with a chronic metabolic bone disorder evaluated self-reported quality of life. Methods Participants (n = 1,331) in a multi-centre randomised controlled trial for the treatment of Paget’s disease completed annual HRQOL questionnaires, including the SF-36, EQ-5D and HAQ. Supplementary questions were added to reveal implicit reference frames used when making HRQOL evaluations. Twenty-one participants (11 male, 10 female, aged 59–91 years) were interviewed retrospectively about their responses to the supplementary questions, using cognitive interviewing techniques and semi-structured topic guides. Results The interviews revealed that participants used complex and interconnected reference frames to promote response shift when making quality of life evaluations. The choice of reference frame often reflected external factors unrelated to individual health. Many participants also stated that they were unclear whether to report general or disease-related HRQOL. Conclusions It is important, especially in clinical trials, to provide instructions clarifying whether ‘quality of life’ refers to disease-related HRQOL. Information on selfcomparison reference frames is necessary for the interpretation of responses to questions about HRQOL.The Chief Scientist Office of the Scottish Government Health Directorates, The PRISM funding bodies (the Arthritis Research Campaign, the National Association for the Relief of Paget’s disease and the Alliance for Better Bone Health)Peer reviewedAuthor final versio

Glutamine repeat variants in human RUNX2 associated with decreased femoral neck BMD, broadband ultrasound attenuation and target gene transactivation

RUNX2 is an essential transcription factor required for skeletal development and cartilage formation. Haploinsufficiency of RUNX2 leads to cleidocranial displaysia (CCD) a skeletal disorder characterised by gross dysgenesis of bones particularly those derived from intramembranous bone formation. A notable feature of the RUNX2 protein is the polyglutamine and polyalanine (23Q/17A) domain coded by a repeat sequence. Since none of the known mutations causing CCD characterised to date map in the glutamine repeat region, we hypothesised that Q-repeat mutations may be related to a more subtle bone phenotype. We screened subjects derived from four normal populations for Q-repeat variants. A total of 22 subjects were identified who were heterozygous for a wild type allele and a Q-repeat variant allele: (15Q, 16Q, 18Q and 30Q). Although not every subject had data for all measures, Q-repeat variants had a significant deficit in BMD with an average decrease of 0.7SD measured over 12 BMD-related parameters (p = 0.005). Femoral neck BMD was measured in all subjects (&minus;0.6SD, p = 0.0007). The transactivation function of RUNX2 was determined for 16Q and 30Q alleles using a reporter gene assay. 16Q and 30Q alleles displayed significantly lower transactivation function compared to wild type (23Q). Our analysis has identified novel Q-repeat mutations that occur at a collective frequency of about 0.4%. These mutations significantly alter BMD and display impaired transactivation function, introducing a new class of functionally relevant RUNX2 mutants.<br /

Seminar on Securities Law

Materials from the UK/CLE Seminar on Securities Law held February 14-15, 1986

Control of intestinal stem cell function and proliferation by mitochondrial pyruvate metabolism.

Most differentiated cells convert glucose to pyruvate in the cytosol through glycolysis, followed by pyruvate oxidation in the mitochondria. These processes are linked by the mitochondrial pyruvate carrier (MPC), which is required for efficient mitochondrial pyruvate uptake. In contrast, proliferative cells, including many cancer and stem cells, perform glycolysis robustly but limit fractional mitochondrial pyruvate oxidation. We sought to understand the role this transition from glycolysis to pyruvate oxidation plays in stem cell maintenance and differentiation. Loss of the MPC in Lgr5-EGFP-positive stem cells, or treatment of intestinal organoids with an MPC inhibitor, increases proliferation and expands the stem cell compartment. Similarly, genetic deletion of the MPC in Drosophila intestinal stem cells also increases proliferation, whereas MPC overexpression suppresses stem cell proliferation. These data demonstrate that limiting mitochondrial pyruvate metabolism is necessary and sufficient to maintain the proliferation of intestinal stem cells

Nucleon Charge and Magnetization Densities from Sachs Form Factors

Relativistic prescriptions relating Sachs form factors to nucleon charge and magnetization densities are used to fit recent data for both the proton and the neutron. The analysis uses expansions in complete radial bases to minimize model dependence and to estimate the uncertainties in radial densities due to limitation of the range of momentum transfer. We find that the charge distribution for the proton is significantly broad than its magnetization density and that the magnetization density is slightly broader for the neutron than the proton. The neutron charge form factor is consistent with the Galster parametrization over the available range of Q^2, but relativistic inversion produces a softer radial density. Discrete ambiguities in the inversion method are analyzed in detail. The method of Mitra and Kumari ensures compatibility with pQCD and is most useful for extrapolating form factors to large Q^2.Comment: To appear in Phys. Rev. C. Two new figures and accompanying text have been added and several discussions have been clarified with no significant changes to the conclusions. Now contains 47 pages including 21 figures and 2 table