Efficacy of Varenicline in Patients With Severe Alcohol Dependence: A Pilot Double-Blind Randomized and Controlled Study.

Purpose/Background: Varenicline has proven its efficacy in the treatment of nicotine dependence, and there is also evidence that it could be helpful in the treatment of alcohol dependence. In our pilot study, we investigated the feasibility and acceptability of varenicline for the treatment of a population of patients with severe alcohol dependence and multiple somatic comorbidities after alcohol detoxification. Methods/Procedures: We conducted a phase II, double-blind, placebocontrolled randomized trial of daily oral varenicline versus a placebo in alcohol-dependent men and women after alcohol detoxification (n = 28). Following our study protocol, somatic conditions and adverse events were thoroughly monitored and several study end points were investigated (percentage of abstinent days for both alcohol and nicotine, number of standardized drinks and cigarettes per day, days of heavy drinking). Findings/Results: Compared with the placebo, varenicline did not have more side effects and did not provoke more adverse events. Patients in the varenicline group did not showa significantly higher percentage of alcohol abstinent days or fewer heavy drinking days. A trend significance was found for a reduced number of standard drinks per day (P = 0.06) in the varenicline group. Implications/Conclusions: In this pilot trial, varenicline was shown to be well tolerated by our study population of severely alcohol-dependent patients with somatic conditions. Varenicline did not sustain alcohol abstinence or reduce the number of heavy drinking days, but it did reduce the daily amount of alcohol consumed

Classification of airborne laser scanning point clouds based on binomial logistic regression analysis

This article presents a newly developed procedure for the classification of airborne laser scanning (ALS) point clouds, based on binomial logistic regression analysis. By using a feature space containing a large number of adaptable geometrical parameters, this new procedure can be applied to point clouds covering different types of topography and variable point densities. Besides, the procedure can be adapted to different user requirements. A binomial logistic model is estimated for all a priori defined classes, using a training set of manually classified points. For each point, a value is calculated defining the probability that this point belongs to a certain class. The class with the highest probability will be used for the final point classification. Besides, the use of statistical methods enables a thorough model evaluation by the implementation of well-founded inference criteria. If necessary, the interpretation of these inference analyses also enables the possible definition of more sub-classes. The use of a large number of geometrical parameters is an important advantage of this procedure in comparison with current classification algorithms. It allows more user modifications for the large variety of types of ALS point clouds, while still achieving comparable classification results. It is indeed possible to evaluate parameters as degrees of freedom and remove or add parameters as a function of the type of study area. The performance of this procedure is successfully demonstrated by classifying two different ALS point sets from an urban and a rural area. Moreover, the potential of the proposed classification procedure is explored for terrestrial data

A Nationwide Study of Inpatient Case Rate Incidence of Cannabis-Related Diagnoses in Switzerland.

Objectives: Cannabis is the most commonly used illicit substance and has been associated with mental health issues. In this study, we examined trends in hospitalizations due to cannabis use. Methods: Data were obtained from the Swiss Federal Statistics Office and comprised hospital main diagnoses, gender, age group and region of all psychiatric inpatient cases in Switzerland from 1998 to 2020. We performed trend analyses of annual case rates with cannabinoid-related diagnoses and compared them to trend analyses of alcohol-related and psychotic disorders. Results: Case rates of CRDs significantly increased in the observed time period. From all psychiatric main diagnoses, CRDs were overrepresented in the age groups of 15-24 and 25-44 years. Conclusion: We found a sharp increase in hospitalizations for CRD. Future studies should test whether changes in the upcoming cannabis regulation, which can facilitate the implementation of interventions to address mental health among users, impact future hospitalization rates of CRD

Contrasting magma types and timing of intrusion in the Permian layered mafic complex of Mont Collon (Western Alps, Valais, Switzerland): evidence from U/Pb zircon and 40Ar/39Ar amphibole dating

Abstract.: We have selected and dated three contrasting rock-types representative of the magmatic activity within the Permian layered mafic complex of Mont Collon, Austroalpine Dent Blanche nappe, Western Alps. A pegmatitic gabbro associated to the main cumulus sequence yields a concordant U/Pb zircon age of 284.2 ±0.6Ma, whereas a pegmatitic granite dike crosscutting the latter yields a concordant age of 282.9 ±0.6Ma. A Fe-Ti-rich ultrabasic lamprophyre, crosscutting all other lithologies of the complex, yields an 40Ar/39Ar plateau age of 260.2 ±0.7Ma on a kaersutite concentrate. All ages are interpreted as magmatic. Sub-contemporaneous felsic dikes within the Mont Collon complex are ascribed to anatectic back-veining from the country-rock, related to the emplacement of the main gabbroic body in the continental crust, which is in accordance with new isotopic data. The lamprophyres have isotopic compositions typical of a depleted mantle, in contrast to those of the cumulate gabbros, close to values of the Bulk Silicate Earth. This indicates either contrasting sources for the two magma pulses - the subcontinental lithospheric mantle for the gabbros and the underlying asthenosphere for the lamprophyres - or a single depleted lithospheric source with variable degrees of crustal contamination of the gabbroic melts during their emplacement in the continental crust. The Mont Collon complex belongs to a series of Early Permian mafic massifs, which emplaced in a short time span about 285-280Ma ago, in a limited sector of the post-Variscan continental crust now corresponding to the Austroalpine/Southern Alpine domains and Corsica. This magmatic activity was controlled in space and time by crustal-scale transtensional shear zone

Comparing Attitudes to Containment Measures of Patients, Health Care Professionals and Next of Kin

Background: In clinical psychiatric practice, health care professionals (HCP) must decide in exceptional circumstances after the weighing of interests, which, if any, containment measures including coercion are to be used. Here, the risk for patients, staff, and third parties, in addition to therapeutic considerations, factor into the decision. Patients' preference and the inclusion of relatives in these decisions are important; therefore, an understanding of how patients and next of kin (NOK) experience different coercive measures is crucial for clinical decision making. The aim of this study is to compare how patients, HCP, and NOK assess commonly used coercive measures.Methods: A sample of 435 patients, 372 HCP, and 230 NOK completed the Attitudes to Containment Measures Questionnaire (ACMQ). This standardized self-rating questionnaire assessed the degree of acceptance or rejection of 11 coercive measures.Results: In general, HCPs rated the coercive measures as more acceptable than did NOK and patients. The largest discrepancy in the ratings was found in regard to the application of coercive intramuscular injection of medication (effect size: 1.0 HCP vs. patients). However, the ratings by NOK were significantly closer to the patients' ratings compared to patients and HCP. The only exception was the acceptance of treatment in a closed acute psychiatric ward, which was deemed significantly more acceptable by NOK than by patients. Also, patients who had experienced coercive measures themselves more strongly refused other measures.Conclusion: Patients most firmly rejected intramuscular injections, and the authors agree that these should only be used with reservation considering a high threshold. This knowledge about the discrepancy of the ratings should therefore be incorporated into professional training of HCP

Construction of a Peptide Microarray for Auto-anti- body Detection: FH - HES

Peptide and protein microarrays provide a multiplex approach to identification and quantification of protein–protein interactions (PPI), useful to study for instance antigen–antibody properties. Multivariate serology assays detecting multiple tumor auto-antibodies (TAA) is an emerging class of blood tests for cancer detection. Here we describe the efficient coupling of peptide baits derived from the BRCA1-associated RING domain protein 1 (BARD1) to a solid surface and detection of a commercially available anti-BARD1 antibody with this newly designed peptide microarray. Analytical sensitivity and specificity were shown to be comparable to a microtiter plate based enzyme-linked immunosorbent assay (ELISA)

Integrated microcavity optomechanics with a suspended photonic crystal mirror above a distributed Bragg reflector

Increasing the interaction between light and mechanical resonators is an ongoing endeavor in the field of cavity optomechanics. Optical microcavities allow for boosting the interaction strength through their strong spatial confinement of the optical field. In this work, we follow this approach by realizing a sub-wavelength-long, free-space optomechanical microcavity on-chip fabricated from an (Al,Ga)As heterostructure. A suspended GaAs photonic crystal mirror is acting as a highly reflective mechanical resonator, which together with a distributed Bragg reflector forms an optomechanical microcavity. We demonstrate precise control over the microcavity resonance by change of the photonic crystal parameters. The interplay between the microcavity mode and a guided resonance of the photonic crystal modifies the cavity response and results in a stronger dynamical backaction on the mechanical resonator compared to conventional optomechanical dynamics.Comment: 11 pages, 6 figures + Supplementary Material with 10 pages, 12 figures, 2 table

Acute cytomegalovirus infection modulates the intestinal microbiota and targets intestinal epithelial cells

Primary and recurrent cytomegalovirus (CMV) infections frequently cause CMV colitis in immunocompromised as well as inflammatory bowel disease (IBD) patients. Additionally, colitis occasionally occurs upon primary CMV infection in patients who are apparently immunocompetent. In both cases, the underlying pathophysiologic mechanisms are largely elusive - in part due to the lack of adequate access to specimens. We employed the mouse cytomegalovirus (MCMV) model to assess the association between CMV and colitis. During acute primary MCMV infection of immunocompetent mice, the gut microbial composition was affected as manifested by an altered ratio of the Firmicutes to Bacteroidetes phyla. Interestingly, these microbial changes coincided with high-titer MCMV replication in the colon, crypt hyperplasia, increased colonic pro-inflammatory cytokine levels, and a transient increase in the expression of the antimicrobial protein Regenerating islet-derived protein 3 gamma (Reg3γ). Further analyses revealed that murine and human intestinal epithelial cell lines, as well as primary intestinal crypt cells and organoids represent direct targets of CMV infection causing increased cell death. Accordingly, in vivo MCMV infection disrupted the intestinal epithelial barrier and increased apoptosis of intestinal epithelial cells. In summary, our data show that CMV transiently induces colitis in immunocompetent hosts by altering the intestinal homeostasis

Quantitative Comparison of Constitutive Promoters in Human ES cells

BACKGROUND: Constitutive promoters that ensure sustained and high level gene expression are basic research tools that have a wide range of applications, including studies of human embryology and drug discovery in human embryonic stem cells (hESCs). Numerous cellular/viral promoters that ensure sustained gene expression in various cell types have been identified but systematic comparison of their activities in hESCs is still lacking. METHODOLOGY/PRINCIPAL FINDINGS: We have quantitatively compared promoter activities of five commonly used constitutive promoters, including the human β-actin promoter (ACTB), cytomegalovirus (CMV), elongation factor-1α, (EF1α), phosphoglycerate kinase (PGK) and ubiquitinC (UbC) in hESCs. Lentiviral gene transfer was used to ensure stable integration of promoter-eGFP constructs into the hESCs genome. Promoter activities were quantitatively compared in long term culture of undifferentiated hESCs and in their differentiated progenies. CONCLUSION/SIGNIFICANCE: The ACTB, EF1α and PGK promoters showed stable activities during long term culture of undifferentiated hESCs. The ACTB promoter was superior by maintaining expression in 75-80% of the cells after 50 days in culture. During embryoid body (EB) differentiation, promoter activities of all five promoters decreased. Although the EF1α promoter was downregulated in approximately 50% of the cells, it was the most stable promoter during differentiation. Gene expression analysis of differentiated eGFP+ and eGFP- cells indicate that promoter activities might be restricted to specific cell lineages, suggesting the need to carefully select optimal promoters for constitutive gene expression in differentiated hESCs