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In tectonic maps of Variscan Europe, allochthonous pieces of Cadomian basement clearly stand out with their predominant metabasic to ultrabasic elements, the so-called exotic terranes with ophiolites. Most of these domains are observed in basements of the Central Iberian Allochthone, the South Armorican domain, the nappe structures of the French Massif Central, the Saxothuringian Zone and the Bohemian Massif. Similar relics can be recognized in many Alpine basement areas, and correlations with supposedly more autochthonous basements, such as the Ossa Morena Zone and the Central Iberian basement, can be envisaged. All of these relics are thought to represent the interrupted trace of a former continuous or discontinuous structure, characterized by the presence of ocean-derived proto-Rheic rock suites. These can be interpreted as pieces of former magmatic arcs of Ediacaran to Cambrian age accreted to the Gondwana margin, which later were scattered as allochthonous units during the Variscan plate-tectonic processes. The presence of similar rock suites of Ordovician age in the Alpine realm is explained by the accretion of exotic China-derived basements and their collision with the Gondwana margin during the opening of the Rheic Ocean.

Base metal mining in the Rhenohercynian Zone has a long history. Middle-Upper Devonian to Lower Carboniferous sediment-hosted massive sulfide deposits (SHMS), volcanic-hosted massive sulfide deposits (VHMS) and Lahn-Dill-type iron, and base metal ores occur at several sites in the Rhenohercynian Zone that stretches from the South Portuguese Zone, through the Lizard area, the Rhenish Massif and the Harz Mountain to the Moravo-Silesian Zone of SW Bohemia. During Devonian to Early Carboniferous times, the Rhenohercynian Zone is seen as an evolving rift system developed on subsiding shelf areas of the Old Red continent. A reappraisal of the geotectonic setting of these ore deposits is proposed. The Middle-Upper Devonian to Early Carboniferous time period was characterized by detrital sedimentation, continental intraplate and subduction-related volcanism. The large shelf of the Devonian Old Red continent was the place of thermal subsidence with contemporaneous mobilization of rising thermal fluids along activated Early Devonian growth faults. Hydrothermal brines equilibrated with the basement and overlying Middle-Upper Devonian detrital deposits forming the SHMS deposits in the southern part of the Pyrite Belt, in the Rhenish Massif and in the Harz areas. Volcanic-hosted massive sulfide deposits (VHMS) formed in the more eastern localities of the Rhenohercynian domain. In contrast, since the Tournaisian period of ore formation, dominant pull-apart triggered magmatic emplacement of acidic rocks, and their metasomatic replacement in the apical zones of felsic domes and sediments in the northern part of the Iberian Pyrite belt, thus changing the general conditions of ore precipitation. This two-step evolution is thought to be controlled by syn- to post-tectonic phases in the Variscan framework, specifically by the transition of geotectonic setting dominated by crustal extension to a one characterized by the subduction of the supposed northern slab of the Rheic Ocean preceding the general Late Variscan crustal shortening and oroclinal bending.

More than 50% of the Alps expose fragments of Palaeozoic basement which were assembled during the Alpine orogeny. Although the tectonic and metamorphic history of the basement units can be compared to that of the Variscan crust in the Alpine foreland, most of the basement pieces of the Alps do not represent the direct southern continuation of Variscan structural elements evident in the Massif Central, the Vosges–Black Forest or the Bohemian massif. The basement units of the Alps all originated at the Gondwana margin. They were derived from a Precambrian volcanic arc suture fringing the northern margin of Gondwana, from which they were rifted during the Cambrian–Ordovician and Silurian. A short-lived Ordovician orogenic event interrupted the general rifting tendency at the Gondwana active margin. After the Ordovician, the different blocks drifted from the Gondwana margin to their Pangea position, colliding either parallel to Armorica with Laurussia or with originally peri-Gondwanan blocks assembled presently in Armorica. From the Devonian onwards, many basement subunits underwent the complex evolution of apparently oblique collision and nappe stacking. Docking started in the External massifs, the Penninic and Lower and middle Austroalpine units in approximately Devonian/early Carboniferous times, followed by the Upper Austroalpine and the South Alpine domains, in the Visean and the Namurian times, respectively. Wrenching is probably the best mechanism to explain all syn and post-collisional phenomena since the Visean followed by post-orogenic collapse and extension. It explains the occurrence of strike-slip faults at different crustal levels, the formation of sedimentary troughs as well as the extrusion and intrusion of crustal and mantle-derived magmas, and allows for contemporaneous rapid uplift of lower crustal levels and their erosion. From the Stephanian onwards, all regions were deeply eroded by large river systems.

BackgroundWe herein present a prospective multicenter experience on injectable cabotegravir and rilpivirine from 11 different HIV clinics in Northern Italy (Padova, Bologna, Belluno, Modena, Verona, Trento, Bolzano, Santorso, Rovigo, Treviso, Vicenza), focusing on the regimen durability, safety and tolerability in a real-life setting.Materials and MethodsFrom August 2022, we included all individuals who received at least one dose of injectable cabotegravir and rilpivirine across the 11 participating centers. We recorded demographic data and laboratory results, and assessed factors associated with treatment discontinuation (TD) for any cause and virological failure (VF), defined as two confirmed consecutive values of HIV RNA > 50 copies/ml or one single measurement of HIV RNA > 200 copies/ml. Kaplan-Meier curves were used to assess TD probability and logistic regression to identify significant predictors of TD and VF.Results483 PWH were included, mostly males (81.6%) and Caucasian (91.1%), with a median age of 49 (40–58) years, living with HIV for a median time of 12 (IQR:7–21) years, and a median CD4+ T cell count of 708 cell/mm3 (529–929). 45.5% and 7.5% had multimorbidity and polypharmacy, respectively. For 224 (43.6%) people HIV subtype was not available, 215 (44.5%) and 6 (1.2%) had a B and A subtype, respectively. 45.8% and 12.8% of participants had no genotype resistance test for INI and NNRTI at baseline, respectively, while participants before switching received a median number of 3 (IQR: 2–4) cART lines. 74.1% started LA according to their wish, and 51.8% coming from a dual oral cART (either dolutegravir/lamivudine or dolutegravir/rilpivirine).During a median time of 22 (IQR: 13–26) months of follow-up, 54 (11.1%) people had TD (incidence of TD was 6.24 person-months of follow-up). Figure 1 shows KM curve for TD. Most people discontinued to side effects (31, 6.4%), while 7 (1.4%) due to virological failure. Among these 71.4% reported major resistance mutations both to INI and NNRTI and were switched darunavir/cobicistat/tenofovir alafenamide/emtricitabine. The remaining 28.6% came back to the previous oral regimen. When multivariable analysis was performed, age, years living with HIV, CD4/CD8 ratio, and BMI were significantly associated with TD. Also, we detected that numbers of previous antiretroviral regimens and black-African ethnicity were significantly associated with VF.Abstract OC34 Figure 1ConclusionWhile the regimen demonstrated overall effectiveness, TD was observed in a specific subset of individuals, primarily due to side effects, with a smaller proportion experiencing VF. Factors we detected as associated with both TD and VF underscore the importance of personalized people selection and close monitoring to optimize long-acting ART outcomes. Further studies are warranted to refine strategies for mitigating treatment failure and improving regimen persistence.

Pre-Variscan basement elements of Central Europe appear in polymetamorphic domains juxtaposed through Variscan and/or Alpine tectonic events. Consequently, nomenclatures and zonations applied to Variscan and Alpine structures, respectively, cannot be valid for pre-Variscan structures. Comparing pre-Variscan relics hidden in the Variscan basement areas of Central Europe, the Alps included, large parallels between the evolution of basement areas of future Avalonia and its former peri-Gondwanan eastern prolongations (e.g. Cadomia, Intra-Alpine Terrane) become evident. Their plate-tectonic evolution from the Late Proterozoic to the Late Ordovician is interpreted as a continuous Gondwana-directed evolution. Cadomian basement, late Cadomian granitoids, late Proterozoic detrital sediments and active margin settings characterize the pre-Cambrian evolution of most of the Gondwana-derived microcontinental pieces. Also the Rheic ocean, separating Avalonia from Gondwana, should have had, at its early stages, a lateral continuation in the former eastern prolongation of peri-Gondwanan microcontinents (e.g. Cadomia, Intra-Alpine Terrane). Subduction of oceanic ridge (Proto-Tethys) triggered the break-off of Avalonia, whereas in the eastern prolongation, the presence of the ridge may have triggered the amalgamation of volcanic arcs and continental ribbons with Gondwana (Ordovician orogenic event). Renewed Gondwana-directed subduction led to the opening of Palaeo-Tethys.

THE author acknowledges that these volumes contain nothing like a complete account of the country visited. They merely touch on some particular subjects to which attention has hitherto been little directed; but we are not less satisfied with him on this account, for we escape the discussion of subjects, or the description of things, that are already familiar to us.

Ireland is still the point about which Ministers and Parliaments revolve in singularly complex orbits. Till the proper laws are discovered and applied, Great Britain, notwithstanding all its power, and otherwise healthy state, will never lose a feeling of serious indisposition; nay, this indisposition, if neglected, might increase to a dangerous disease.

Ireland is still the point about which Ministers and Parliaments revolve in singularly complex orbits. Till the proper laws are discovered and applied, Great Britain, notwithstanding all its power, and otherwise healthy state, will never lose a feeling of serious indisposition; nay, this indisposition, if neglected, might increase to a dangerous disease.

Crystal structure (polymorphism) as well as crystal shape (morphology) and size have a huge practical and commercial impact on active substances all the way from research to manufacture of the final product. For an optimal development process, it is important to have an integrated approach to these issues ranging from a systematic polymorphism screening to a controlled scale-up of the crystallization process. The polymorphism program has to be tailored according to the development stage. Particularly suitable for an early development stage is a high-throughput polymorphism screening, which is the basis for a more thorough investigation if the product proceeds further in development. Such a comprehensive polymorphism investigation involves further crystallization experiments and extensive physicochemical characterization of the various forms. In this article the high-throughput polymorphism screening method that we have developed is described. Using carbamazepine as an example, the power of this high-throughput polymorphism screening system is demonstrated. Not only were all published forms found, but also new forms were identified. In the second part of the article, important considerations for crystallization optimization are discussed, again using the example of carbamazepine.