Death after smoking of fentanyl, 5F-ADB, 5F-MDMB-P7AICA and other synthetic cannabinoids with a bucket bong

Purpose: We report a case of a polydrug user who consumed various synthetic cannabinoids and fentanyl from a transdermal patch via a bucket bong. Toxicological results from postmortem matrices with special focus on synthetic cannabinoids are discussed in terms of their relevance to the death. Methods: The samples were analyzed by toxicological screening procedures involving immunoassays and gas chromatography–mass spectrometry (GC–MS) as well as quantitative analyses by means of GC–MS and high-performance liquid chromatography–tandem mass spectrometry (LC–MS/MS). Results: At the autopsy, coronary artery disease and signs of liver congestion were noted, in the absence of acute myocardial ischemic changes. Femoral blood concentrations of fentanyl and pregabalin were 14 ng/mL and 3,200 ng/mL, respectively. In addition, 2.7 ng/mL 5F-ADB and 13 ng/mL 5F-MDMB-P7AICA were detected together with relatively low amounts of 5 other synthetic cannabinoids in cardiac blood. A total number of up to 17 synthetic cannabinoids were detected in kidney, liver, urine and hair. Fentanyl and 5F-ADB were also detected in the water of the bucket bong. Conclusions: The cause of death could be attributed to an acute mixed intoxication by fentanyl and 5F-ADB (both Toxicological Significance Score (TSS) = 3) with a contribution of pregabalin and 5F-MDMB-P7AICA (TSS = 2), in a subject suffering from pre-existing heart damage. The most plausible mechanism of death consists in a respiratory depression. This case report demonstrates that use of opioids in combination with synthetic cannabinoids might be particularly dangerous

On the commutability of homogenization and linearization in finite elasticity

We study non-convex elastic energy functionals associated to (spatially) periodic, frame indifferent energy densities with a single non-degenerate energy well at SO(n). Under the assumption that the energy density admits a quadratic Taylor expansion at identity, we prove that the Gamma-limits associated to homogenization and linearization commute. Moreover, we show that the homogenized energy density, which is determined by a multi-cell homogenization formula, has a quadratic Taylor expansion with a quadratic term that is given by the homogenization of the quadratic term associated to the linearization of the initial energy density

Cardiac biomarkers of prognostic importance in chronic obstructive pulmonary disease

Background: Ischemic heart disease is common in COPD and associated with worse prognosis. This study aimed to investigate the presence and prognostic impact of biomarkers of myocardial injury and ischemia among individuals with COPD and normal lung function, respectively. Methods: In 2002–04, all individuals with airway obstruction (FEV1/VC < 0.70, n = 993) were identified from population-based cohorts, together with age and sex-matched non-obstructive referents. At re-examination in 2005, spirometry, Minnesota-coded ECG and analyses of high-sensitivity cardiac troponin I (hs-cTnI) were performed in individuals with COPD (n = 601) and those with normal lung function (n = 755). Deaths were recorded until December 31st, 2010. Results: Hs-cTnI concentrations were above the risk stratification threshold of ≥5 ng/L in 31.1 and 24.9% of those with COPD and normal lung function, respectively. Ischemic ECG abnormalities were present in 14.8 and 13.4%, while 7.7 and 6.6% had both elevated hs-cTnI concentrations and ischemic ECG abnormalities. The 5-year cumulative mortality was higher in those with COPD than those with normal lung function (13.6% vs. 7.7%, p < 0.001). Among individuals with COPD, elevated hs-cTnI both independently and in combination with ischemic ECG abnormalities were associated with an increased risk for death (adjusted hazard ratio [HR]; 95% confidence interval [CI] 2.72; 1.46–5.07 and 4.54; 2.25–9.13, respectively). Similar associations were observed also among individuals with COPD without reported ischemic heart disease. Conclusions: In this study, elevated hs-cTnI concentrations in combination with myocardial ischemia on the electrocardiogram were associated with a more than four-fold increased risk for death in a population-based COPD-cohort, independent of disease severity

Comparison of target enrichment strategies for ancient pathogen DNA

In ancient DNA research, the degraded nature of the samples generally results in poor yields of highly fragmented DNA; targeted DNA enrichment is thus required to maximize research outcomes. The three commonly used methods ? array-based hybridization capture and in-solution capture using either RNA or DNA baits ? have different characteristics that may influence the capture efficiency, specificity and reproducibility. Here we compare their performance in enriching pathogen DNA of Mycobacterium leprae and Treponema pallidum from 11 ancient and 19 modern samples. We find that in-solution approaches are the most effective method in ancient and modern samples of both pathogens and that RNA baits usually perform better than DNA baits

Mycobacterium leprae diversity and population dynamics in medieval Europe from novel ancient genomes

Hansen’s disease (leprosy), widespread in medieval Europe, is today mainly prevalent in tropical and subtropical regions with around 200,000 new cases reported annually. Despite its long history and appearance in historical records, its origins and past dissemination patterns are still widely unknown. Applying ancient DNA approaches to its major causative agent, Mycobacterium leprae, can significantly improve our understanding of the disease’s complex history. Previous studies have identified a high genetic continuity of the pathogen over the last 1500 years and the existence of at least four M. leprae lineages in some parts of Europe since the Early Medieval period

Mycobacterium leprae diversity and population dynamics in medieval Europe from novel ancient genomes

Background: Hansen’s disease (leprosy), widespread in medieval Europe, is today mainly prevalent in tropical and subtropical regions with around 200,000 new cases reported annually. Despite its long history and appearance in historical records, its origins and past dissemination patterns are still widely unknown. Applying ancient DNA approaches to its major causative agent, Mycobacterium leprae, can significantly improve our understanding of the disease’s complex history. Previous studies have identified a high genetic continuity of the pathogen over the last 1500 years and the existence of at least four M. leprae lineages in some parts of Europe since the Early Medieval period. Results: Here, we reconstructed 19 ancient M. leprae genomes to further investigate M. leprae’s genetic variation in Europe, with a dedicated focus on bacterial genomes from previously unstudied regions (Belarus, Iberia, Russia, Scotland), from multiple sites in a single region (Cambridgeshire, England), and from two Iberian leprosaria. Overall, our data confirm the existence of similar phylogeographic patterns across Europe, including high diversity in leprosaria. Further, we identified a new genotype in Belarus. By doubling the number of complete ancient M. leprae genomes, our results improve our knowledge of the past phylogeography of M. leprae and reveal a particularly high M. leprae diversity in European medieval leprosaria. Conclusions: Our findings allow us to detect similar patterns of strain diversity across Europe with branch 3 as the most common branch and the leprosaria as centers for high diversity. The higher resolution of our phylogeny tree also refined our understanding of the interspecies transfer between red squirrels and humans pointing to a late antique/early medieval transmission. Furthermore, with our new estimates on the past population diversity of M. leprae, we gained first insights into the disease’s global history in relation to major historic events such as the Roman expansion or the beginning of the regular transatlantic long distance trade. In summary, our findings highlight how studying ancient M. leprae genomes worldwide improves our understanding of leprosy’s global history and can contribute to current models of M. leprae’s worldwide dissemination, including interspecies transmissions

Mycobacterium leprae diversity and population dynamics in medieval Europe from novel ancient genomes.

Funder: Max-Planck SocietyFunder: St John’s College, CambridgeFunder: Fondation Raoul FollereauFunder: University of Zurich’s University Research Priority Program “Evolution in Action: From Genomes to Ecosystems”Funder: the Senckenberg Centre for Human Evolution and Palaeoenvironment (S-HEP) at the University of TübingenBackgroundHansen's disease (leprosy), widespread in medieval Europe, is today mainly prevalent in tropical and subtropical regions with around 200,000 new cases reported annually. Despite its long history and appearance in historical records, its origins and past dissemination patterns are still widely unknown. Applying ancient DNA approaches to its major causative agent, Mycobacterium leprae, can significantly improve our understanding of the disease's complex history. Previous studies have identified a high genetic continuity of the pathogen over the last 1500 years and the existence of at least four M. leprae lineages in some parts of Europe since the Early Medieval period.ResultsHere, we reconstructed 19 ancient M. leprae genomes to further investigate M. leprae's genetic variation in Europe, with a dedicated focus on bacterial genomes from previously unstudied regions (Belarus, Iberia, Russia, Scotland), from multiple sites in a single region (Cambridgeshire, England), and from two Iberian leprosaria. Overall, our data confirm the existence of similar phylogeographic patterns across Europe, including high diversity in leprosaria. Further, we identified a new genotype in Belarus. By doubling the number of complete ancient M. leprae genomes, our results improve our knowledge of the past phylogeography of M. leprae and reveal a particularly high M. leprae diversity in European medieval leprosaria.ConclusionsOur findings allow us to detect similar patterns of strain diversity across Europe with branch 3 as the most common branch and the leprosaria as centers for high diversity. The higher resolution of our phylogeny tree also refined our understanding of the interspecies transfer between red squirrels and humans pointing to a late antique/early medieval transmission. Furthermore, with our new estimates on the past population diversity of M. leprae, we gained first insights into the disease's global history in relation to major historic events such as the Roman expansion or the beginning of the regular transatlantic long distance trade. In summary, our findings highlight how studying ancient M. leprae genomes worldwide improves our understanding of leprosy's global history and can contribute to current models of M. leprae's worldwide dissemination, including interspecies transmissions

Quantification of ergodicity in stochastic homogenization: optimal bounds via spectral gap on Glauber dynamics

We study the effective large-scale behavior of discrete elliptic equations on the lattice Z d with random coefficients. The theory of stochastic homogenization relates the random but stationary field of coefficients with a deterministic matrix of effective coefficients. This is done via the corrector problem, which can be viewed as a highly degenerate elliptic equation on the infinite-dimensional space of admissible coefficient fields. In this contribution we develop quantitative methods for the corrector problem assuming that the ensemble of coefficient fields satisfies a spectral gap estimate w. r. t. a Glauber dynamics. As a main result we prove an optimal estimate for the decay in time of the parabolic equation associated to the corrector problem (i. e. for the “random environment as seen from a random walker”). As a corollary we obtain existence and moment bounds for stationary correctors (in dimension d> 2) and optimal estimates for regularized versions of the corrector (in dimensions d ≥ 2). We also give a self-contained proof for a new estimate on the gradient of the parabolic, variable-coefficient Green’s function, which is a crucial analytic ingredient in our method. As an application, we study the approximation of the homogenized coefficients via a representative volume element. The approximation introduces two types of errors. Based on our quantitativ