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R-lineage mitochondrial DNA represents over 90% of the European population and is significantly present all around the planet (North Africa, Asia, Oceania, and America). This lineage played a major role in migration “out of Africa” and colonization in Europe. In order to determine an accurate dating of the R lineage and its sublineages, we analyzed 1173 individuals and complete mtDNA sequences from Mitomap. This analysis revealed a new coalescence age for R at 54.500 years, as well as several limitations of standard dating methods, likely to lead to false interpretations. These findings highlight the association of a striking under-accumulation of synonymous mutations, an over-accumulation of non-synonymous mutations, and the phenotypic effect on haplogroup J. Consequently, haplogroup J is apparently not a Neolithic group but an older haplogroup (Paleolithic) that was subjected to an underestimated selective force. These findings also indicated an under-accumulation of synonymous and non-synonymous mutations localized on coding and non-coding (HVS1) sequences for haplogroup R0, which contains the major haplogroups H and V. These new dates are likely to impact the present colonization model for Europe and confirm the late glacial resettlement scenario.

In situ fracture mechanical deformation and fluid flow interactions are investigated through a series of hydraulic pulse injection tests, using specialized borehole equipment that can simultaneously measure fluid pressure and fracture displacements. The tests were conducted in two horizontal boreholes spaced one meter apart vertically and intersecting a near-vertical highly permeable fault located within a shallow fractured carbonate rock. The field data were evaluated by conducting a series of coupled hydromechanical numerical analyses, using both distinct-element and finite-element modeling techniques and both two- and three-dimensional model representations that can incorporate various complexities in fracture network geometry. One unique feature of these pulse injection experiments is that the entire test cycle, both the initial pressure increase and subsequent pressure fall-off, is carefully monitored and used for the evaluation of the in situ hydromechanical behavior. Field test data are evaluated by plotting fracture normal displacement as a function of fluid pressure, measured at the same borehole. The resulting normal displacement-versus-pressure curves show a characteristic loop, in which the paths for loading (pressure increase) and unloading (pressure decrease) are different. By matching this characteristic loop behavior, the fracture normal stiffness and an equivalent stiffness (Young's modulus) of the surrounding rock mass can be back-calculated. Evaluation of the field tests by coupled numerical hydromechanical modeling shows that initial fracture hydraulic aperture and normal stiffness vary by a factor of 2 to 3 for the two monitoring points within the same fracture plane. Moreover, the analyses show that hydraulic aperture and the normal stiffness of the pulse-tested fracture, the stiffness of surrounding rock matrix, and the properties and geometry of the surrounding fracture network significantly affect coupled hydromechanical responses during the pulse injection test. More specifically, the pressure-increase path of the normal displacement-versus-pressure curve is highly dependent on the hydromechanical parameters of the tested fracture and the stiffness of the matrix near the injection point, whereas the pressure-decrease path is highly influenced by mechanical processes within a larger portion of the surrounding fractured rock.

Objectives: Since little is currently known about predictors of response to direct-acting antiviral agents (DAAs) in people who inject drugs, we undertook an analysis of patients attending a hepatitis clinic with addiction services (outpatient clinics and inpatient services) to examine the outcomes associated with the treatment of difficult-to-manage patients with substance use. Our experience was based on integrated care. Method: A retrospective analysis was undertaken of 50 patients with hepatitis C virus (HCV) and a history of addiction who received treatment with DAAs, according to European guidelines. These regimens were sofosbuvir/ledipasvir for 8 weeks (n=3), sofosbuvir/ ledipasvir±ribavirin for 12 weeks (n=19), sofosbuvir/daclatasvir for 12 weeks (n=20), sofosbuvir/simeprevir (n=1), or sofosbuvir/daclatasvir for 24 weeks (n=7). Characteristics of patients who did versus did not achieve a sustained virologic response (SVR) 12 weeks after treatment were compared by univariate analysis. Results: Forty-two patients (84%) were male; mean age was 46.2±7.3 years. Genotypes were 1 (n=21), 2 (n=4), 3 (n=18), 4 (n=6), or 6 (n=1). Most patients were treatment-naïve (n=38). Five patients had coinfection with human immunodeficiency virus (n=4) or hepatitis B (n=1), 28 (56%) had evidence of cirrhosis on FibroScan (>12.5 kPa), and 34 (68%) were receiving opioid substitution therapy. Psychiatric disease, illicit drug use, unemployment, and homelessness/precarious housing were common. Forty-five patients (90%) achieved SVR, 2 were lost to follow-up, and 3 had treatment relapse. Conclusions: SVR was not significantly associated with sociodemographic or virological characteristics, treatment, social environment, alcohol/drug use, and adherence. Although adherence was slightly worse than in "usual" patients, it did not affect the SVR rate. In these difficult-to-manage patients with HCV and substance use disorder, the real-world SVR rate (90%) was similar to that in nonaddicted populations. [ABSTRACT FROM AUTHOR]

This investigation surveyed the potential and established outcomes for future 19-passenger fixed-wing commuter transport aircraft concepts employing battery-based Voltaic-Joule/Brayton motive power systems with no additional electrical energy drawn from generators mechanically coupled to thermal engines. The morphological approach was that of a tri-prop (two on-wing podded turbo-props and one aft-fuselage mounted electric motor configured as a pusher-on-pylon installation). A Battery System-level Gravimetric Specific Energy (referred to as “battery energy density”) of at least 500 Wh/kg yielded 39%, 25% and 10% block fuel reductions for 150-nm (Design Service Goal), 430-nm (85th percentile) and 700-nm (maximum range) stage lengths, respectively. All quoted comparisons are against a suitably projected turbo-prop only year-2030 aircraft. In contrast to the reference Beech 1900D, block fuel reductions of up to 44-49% were predicted, which could facilitate a significantly lower deficit in relation to the Advisory Council for Aviation Research and Innovation in Europe (ACARE) Strategic Research and Innovation Agenda (STRIA) 55% target for year 2030. This investigation also indicated that, in the future, suitably flexible hybrid-electric architectures could be fashioned allowing possibility for the aircraft to complete any required city-pair operations (within the legitimate payload-range working capacity) irrespective of exchangeable batteries being available at a given station. Finally, it was also established, assuming such a tri-prop morphology, Normal conducting machines delivering maximum shaft power output of 1.1 MW would be required. [ABSTRACT FROM PUBLISHER]