Plus \ue7a change? Switching lithium preparations

Copyright \ua9 The Author(s), 2022. Published by Cambridge University Press on behalf of the Royal College of Psychiatrists. Aims and method A supply disruption alert in 2020, now rescinded, notified UK prescribers of the planned discontinuation of Priadel\uae (lithium carbonate) tablets. This service evaluation explored lithium dose and plasma levels before and after the switching of lithium brands, in order to determine the interchangeability of different brands of lithium from a pharmacokinetic perspective. Results Data on the treatment of 37 patients switched from Priadel\uae tablets were analysed. Switching to Camcolit\uae controlled-release tablets at the same dose did not result in meaningful differences in plasma lithium levels. Dose adjustment and known or suspected poor medication adherence were associated with greater variability in plasma lithium levels on switching brands. Clinical implications For comparable pre- and post-switch doses in adherent patients, the most common brands of lithium carbonate appear to produce similar plasma lithium levels. British National Formulary guidance relating to switching lithium brands may be unnecessarily complex

Chemical composition of AY Ceti: A flaring, spotted star with a white dwarf companion

The detailed chemical composition of the atmosphere AY Cet (HD 7672) is determined from a high-resolution spectrum in the optical region. The main atmospheric parameters and the abundances of 22 chemical elements, including key species such as 12C, 13C, N, and O, are determined. A differential line analysis gives T_eff=5080 K, log g=3.0, [Fe/H]=-0.33, [C/Fe]=-0.17, [N/Fe]=0.17, [O/Fe]=0.05, C/N=1.58, and 12C/13C=21. Despite the high chromospheric activity, the optical spectrum of AY Cet provides a chemical composition typical for first ascent giants after the first dredge-up.Comment: 11 figure

A Search for Star-Disk Interaction Among the Strongest X-ray Flaring Stars in the Orion Nebula Cluster

The Chandra Orion Ultradeep Project observed hundreds of young, low-mass stars undergoing highly energetic X-ray flare events. The 32 most powerful cases have been modeled with the result that the magnetic structures responsible for these flares can be many stellar radii in extent. In this paper, we model the observed spectral energy distributions of these 32 stars in order to determine, in detail for each star, whether there is circumstellar disk material situated in sufficient proximity to the stellar surface for interaction with the large magnetic loops inferred from the observed X-ray flares. Our spectral energy distributions span the wavelength range 0.3-8 um (plus 24 um for some stars), allowing us to constrain the presence of dusty circumstellar material out to >10 AU from the stellar surface in most cases. For 24 of the 32 stars in our sample the available data are sufficient to constrain the location of the inner edge of the dusty disks. Six of these (25%) have spectral energy distributions consistent with inner disks within reach of the observed magnetic loops. Another four stars may have gas disks interior to the dust disk and extending within reach of the magnetic loops, but we cannot confirm this with the available data. The remaining 14 stars (58%) appear to have no significant disk material within reach of the large flaring loops. Thus, up to ~40% of the sample stars exhibit energetic X-ray flares that possibly arise from a magnetic star-disk interaction, and the remainder are evidently associated with extremely large, free-standing magnetic loops anchored only to the stellar surface.Comment: Accepted to the ApJ; 26 pages, 6 tables, 6 figure

The luminosity of supernovae of type Ia from TRGB distances and the value of H_0

Distances from the tip of the red-giant branch (TRGB) in the halo Population of galaxies - calibrated through RR Lyr stars as well as tied to Hipparcos parallaxes and further supported by stellar models - are used to determine the luminosity of six nearby type Ia supernovae (SN 2011fe, 2007sr, 1998bu, 1989B, 1972E, and 1937C). The result is M_V^corr = -19.41 +/- 0.05. If this value is applied to 62 SNe Ia with 3000< v < 20,000 km/s a large-scale value of the Hubble constant follows of H_0 = 64.0 +/- 1.6 +/- 2.0. The SN HST Project gave H_0 = 62.3 +/- 1.3 +/- 5.0 from ten Cepheid-calibrated SNe Ia (Sandage et al. 2006). The agreement of young Population I (Cepheids) and old, metal-poor Population II (TRGB) distance indicators is satisfactory. The combined weighted result is H_0 = 63.7 +/- 2.3 (i.e. +/-3.6%). The result can also be reconciled with WMAP5 data (Reid et al. 2010).Comment: 9 pages, 3 figures, 3 tables, accepted for publication in Astronomy and Astrophysic

Superheated Microdrops as Cold Dark Matter Detectors

It is shown that under realistic background considerations, an improvement in Cold Dark Matter sensitivity of several orders of magnitude is expected from a detector based on superheated liquid droplets. Such devices are totally insensitive to minimum ionizing radiation while responsive to nuclear recoils of energies ~ few keV. They operate on the same principle as the bubble chamber, but offer unattended, continuous, and safe operation at room temperature and atmospheric pressure.Comment: 15 pgs, 4 figures include

Lepton Flavor Non-Conservation

In the present work we review the most prominent lepton flavor violating processes (\mu \ra e\gamma, \mu \ra 3e, $(\mu , e)$ conversion, $M-\bar M$ oscillations etc), in the context of unified gauge theories. Many currently fashionable extensions of the standard model are considered, such as: {\it i)} extensions of the fermion sector (right-handed neutrino); {\it ii)} minimal extensions involving additional Higgs scalars (more than one isodoublets, singly and doubly charged isosinglets, isotriplets with doubly charged members etc.); {\it iii)} supersymmetric or superstring inspired unified models emphasizing the implications of the renormalization group equations in the leptonic sector. Special attention is given to the experimentaly most interesting $(\mu - e)$ conversion in the presence of nuclei. The relevant nuclear aspects of the amplitudes are discussed in a number of fashionable nuclear models. The main features of the relevant experiments are also discussed, and detailed predictions of the above models are compared to the present experimental limits.Comment: (IOA-300/93, review article, 83p, 6 epsf figures , available upon request from [email protected])

Association and Interaction Analyses of GABBR1 and GABBR2 with Nicotine Dependence in European- and African-American Populations

Previous studies have demonstrated that the γ-aminobutyric acid type B (GABAB) receptor plays an essential role in modulating neurotransmitter release and regulating the activity of ion channels and adenyl cyclase. However, whether the naturally occurring polymorphisms in the two GABAB receptor subunit genes interact with each other to alter susceptibility to nicotine dependence (ND) remains largely unknown. In this study, we genotyped 5 and 33 single nucleotide polymorphisms (SNPs) for GABAB receptor subunit 1 and 2 genes (GABBR1, GABBR2), respectively, in a sample of 2037 individuals from 602 nuclear families of African- American (AA) or European-American (EA) origin. We conducted association analyses to determine (1) the association of each subunit gene with ND at both the individual SNP and haplotype levels and (2) the collective effect(s) of SNPs in both GABAB subunits on the development of ND. Several individual SNPs and haplotypes in GABBR2 were significantly associated with ND in both ethnic samples. Two haplotypes in AAs and one haplotype in EAs showed a protective effect against ND, whilst two other haplotypes in AAs and three haplotypes in EAs showed a risk effect for developing ND. Interestingly, these significant haplotypes were confined to two regions of GABBR2 in the AA and EA samples. Additionally, we found two minor haplotypes in GABBR1 to be positively associated with Heaviness of Smoking Index (HSI) in the EA sample. Finally, we demonstrated the presence of epistasis between GABBR1 and GABBR2 for developing ND. The variants of GABBR1 and GABBR2 are significantly associated with ND, and the involvement of GABBR1 is most likely through its interaction with GABBR2, whereas GABBR2 polymorphisms directly alter susceptibility to ND. Future studies are needed with more dense SNP coverage of GABBR1 and GABBR2 to verify the epistatic effects of the two subunit genes

Endometrial apoptosis and neutrophil infiltration during menstruation exhibits spatial and temporal dynamics that are recapitulated in a mouse model.

Abstract Menstruation is characterised by synchronous shedding and restoration of tissue integrity. An in vivo model of menstruation is required to investigate mechanisms responsible for regulation of menstrual physiology and to investigate common pathologies such as heavy menstrual bleeding (HMB). We hypothesised that our mouse model of simulated menstruation would recapitulate the spatial and temporal changes in the inflammatory microenvironment of human menses. Three regulatory events were investigated: cell death (apoptosis), neutrophil influx and cytokine/chemokine expression. Well-characterised endometrial tissues from women were compared with uteri from a mouse model (tissue recovered 0, 4, 8, 24 and 48 h after removal of a progesterone-secreting pellet). Immunohistochemistry for cleaved caspase-3 (CC3) revealed significantly increased staining in human endometrium from late secretory and menstrual phases. In mice, CC3 was significantly increased at 8 and 24 h post-progesterone-withdrawal. Elastase+ human neutrophils were maximal during menstruation; Ly6G+ mouse neutrophils were maximal at 24 h. Human endometrial and mouse uterine cytokine/chemokine mRNA concentrations were significantly increased during menstrual phase and 24 h post-progesterone-withdrawal respectively. Data from dated human samples revealed time-dependent changes in endometrial apoptosis preceding neutrophil influx and cytokine/chemokine induction during active menstruation. These dynamic changes were recapitulated in the mouse model of menstruation, validating its use in menstrual research

Genetic correlations between diabetes and glaucoma: an analysis of continuous and dichotomous phenotypes

Purpose: A genetic correlation is the proportion of phenotypic variance between traits that is shared on a genetic basis. Here we explore genetic correlations between diabetes- and glaucoma-related traits.Design: Cross-sectional study.Methods: We assembled genome-wide association study summary statistics from European-derived participants regarding diabetes-related traits like fasting blood sugar (FBS) and type 2 diabetes (T2D) and glaucoma-related traits (intraocular pressure (IOP), central corneal thickness (CCT), corneal hysteresis (CH), corneal resistance factor (CRF), cup-disc ratio (CDR), and primary open-angle glaucoma (POAG)). We included data from the National Eye Institute Glaucoma Human Genetics Collaboration Heritable Overall Operational Database, the UK Biobank and the International Glaucoma Genetics Consortium. We calculated genetic correlation (rg) between traits using linkage disequilibrium score regression. We also calculated genetic correlations between IOP, CCT and selected diabetes-related traits based on individual level phenotype data in two Northern European population-based samples using pedigree information and Sequential Oligogenic Linkage Analysis Routines (SOLAR).Results: Overall, there was little rg between diabetes- and glaucoma-related traits. Specifically, we found a non-significant negative correlation between T2D and POAG (rg=-0.14; p=0.16). Using SOLAR, the genetic correlations between measured IOP, CCT, FBS, fasting insulin and hemoglobin A1c, were null. In contrast, genetic correlations between IOP and POAG (rg ≥0.45; p≤3.0E-04) and between CDR and POAG were high (rg =0.57; p=2.8E-10). However, genetic correlations between corneal properties (CCT, CRF and CH) and POAG were low (rg range: -0.18 - 0.11) and non-significant (p≥0.07).Conclusion: These analyses suggest there is limited genetic correlation between diabetes- and glaucoma-related traits

Organizational impact of evidence-informed decision making training initiatives : a case study comparison of two approaches

Background The impact of efforts by healthcare organizations to enhance the use of evidence to improve organizational processes through training programs has seldom been assessed. We therefore endeavored to assess whether and how the training of mid- and senior-level healthcare managers could lead to organizational change. Methods We conducted a theory-driven evaluation of the organizational impact of healthcare leaders’ participation in two training programs using a logic model based on Nonaka’s theory of knowledge conversion. We analyzed six case studies nested within the two programs using three embedded units of analysis (individual, group and organization). Interviews were conducted during intensive one-week data collection site visits. A total of 84 people were interviewed. Results We found that the impact of training could primarily be felt in trainees’ immediate work environments. The conversion of attitudes was found to be easier to achieve than the conversion of skills. Our results show that, although socialization and externalization were common in all cases, a lack of combination impeded the conversion of skills. We also identified several individual, organizational and program design factors that facilitated and/or impeded the dissemination of the attitudes and skills gained by trainees to other organizational members. Conclusions Our theory-driven evaluation showed that factors before, during and after training can influence the extent of skills and knowledge transfer. Our evaluation went further than previous research by revealing the influence—both positive and negative—of specific organizational factors on extending the impact of training programs