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The Volgo-Uralia segment, which constitutes one fourth of the East European Craton, is covered by sedimentary deposits. From geophysical studies and examination of thousands of drillcores, Volgo-Uralia has been recognised as a vast high-grade terrain with a complex crustal history extending from the Palaeoarchaean to the Palaeoproterozoic. Our recent studies are focused on the search for the oldest crust formation event by extracting whole rock Sm-Nd and zircon U-Th-Pb and Lu-Hf isotope information from samples recovered by drilling in southern Volgo-Uralia. Particular attention is devoted to the Kolyvan charnockitoid rock suite, which makes up several large areas of gneisses and granitoids of enderbite, charnockite and tonalite composition.\ud \ud \ud \ud The zircon from the granitoids show complex internal structures and consists of large magmatic cores with oscillatory zoning, surrounded by CL black-and-bright bands of metamorphic rims. The crystallisation age of the cores is defined as 3140 ± 7 Ma (SHRIMP) and 3127 ± 46 Ma (LA-ICPMS), while the CL-bright rims are dated at 1950 ± 25 Ma (LA-ICPMS). The ingressive recrystallisation of primary magmatic zircon correlates with depletion in REE, which is observed in each studied core-rim pair. No differences in O-isotopic compositions have been detected between the cores and the rims. δO18 values with an average of 5.8 ± 0.3‰ (1SD) implying that no supracrustal rocks were involved in the source of the Kolyvan melts. The Hf-isotope compositions of magmatic cores (−3 to −9 εHfT) and metamorphic rims (−14 to −28 εHfT), and their similar crustal model ages from 3.42 to 3.86 Ga indicate Eo- to Palaeoarchaean crustal sources for the charnockitic magmas. Sm-Nd model ages of ca 3.46 Ga for the Kolyvan rocks are consistent with the zircon Hf-isotope data and indicate a long crustal prehistory of a source of the Mesoarchaean magmas.\ud \ud \ud \ud We conclude that the Mesoarchaean Kolyvan suite rocks was formed by reworking of Eo- to Palaeoarchaean lithosphere, which probably had been widespread throughout Volgo-Uralia. The obtained geochemical and isotope data can be reconciled in a model of deep mantle-plume activity at 3.1 Ga causing mantle underplating, extension of the Palaeoarchaean crust and high-T magmatism.

Introduction In this study we characterized disease progression over 48 weeks among boys receiving deflazacort vs prednisone/prednisolone placebo arm treatment in two recent Duchenne muscular dystrophy (DMD) clinical trials. Methods Ambulatory boys with DMD receiving placebo in the phase 3 ataluren (N = 115) and tadalafil (N = 116) trials were included. The trials required at least 6 months of prior corticosteroid use and stable baseline dosing. Associations between corticosteroid use and 48‐week changes in ambulatory function were estimated using mixed models. Adjusted differences between corticosteroid groups were pooled in a meta‐analysis. Results In the meta‐analysis, deflazacort‐treated patients vs prednisone/prednisolone‐treated patients experienced, on average, lower declines of 28.3 meters on 6‐minute walk distance (95% confidence interval [CI], 5.7, 50.9; 2.9 seconds on rise from supine [95% CI, 0.9, 4.9 seconds]; 2.3 seconds on 4‐stair climb [95% CI, 0.5, 4.1 seconds]; and 2.9 [95% CI, 0.1, 5.8] points on the North Star Ambulatory Assessment linearized score). Discussion Deflazacort‐treated patients experienced significantly lower functional decline over 48 weeks.

This non-interventional post-authorisation safety study (PASS) assessed the long-term safety of everolimus in patients with tuberous sclerosis complex (TSC) who participated in the TuberOus SClerosis registry to increase disease Awareness (TOSCA) clinical study and received everolimus for the licensed indications in the European Union. The rate of adverse events (AEs), AEs that led to dose adjustments or treatment discontinuation, AEs of potential clinical interest, treatment-related AEs (TRAEs), serious AEs (SAEs), and deaths were documented. One hundred seventy-nine patients were included in the first 5 years of observation; 118 of 179 patients had an AE of any grade, with the most common AEs being stomatitis (7.8%) and headache (7.3%). AEs caused dose adjustments in 56 patients (31.3%) and treatment discontinuation in nine patients (5%). AEs appeared to be more frequent and severe in children. On Tanner staging, all patients displayed signs of age-appropriate sexual maturation. Twenty-two of 106 female (20.8%) patients had menstrual cycle disorders. The most frequent TRAEs were stomatitis (6.7%) and aphthous mouth ulcer (5.6%). SAEs were reported in 54 patients (30.2%); the most frequent SAE was pneumonia (>3% patients; grade 2, 1.1%, and grade 3, 2.8%). Three deaths were reported, all in patients who had discontinued everolimus for more than 28 days, and none were thought to be related to everolimus according to the treating physicians. The PASS sub-study reflects the safety and tolerability of everolimus in the management of TSC in real-world routine clinical practice.

Ophiolitic rocks of the Lachlan Orogen are important because they can provide key information used to refine existing tectonic models for the orogen. This study focuses on the serpentinite belts within the greater Tumut region of the Lachlan Orogen in southeastern Australia. U���Pb, Lu���Hf, O isotopic and trace-element data collected on zircons from a plagiogranite of the Wambidgee Serpentinite Belt are consistent with their crystallisation from mantle-derived melts. Their juvenile Hf-isotope compositions, with ��Hf ranging from +7 to +14, and ��18O values ranging from 4.35 to 5.07���, are close to typical mantle values and clearly within the range defined for zircons from plagiogranites of ophiolitic complexes worldwide. When combined with zircon data available for the Coolac Serpentinite and recent petrogenetic modelling for the Coolac Serpentinite Belt, a new U���Pb age of 486 �� 3 Ma of the Wambidgee zircons constrains the age of formation of oceanic lithosphere in the greater Tumut region to Cambro-Ordovician.KEY POINTSAn age of 486 �� 3 Ma is reported for zircons from plagiogranite of the Wambidgee Serpentinite Belt in the Tumut region, southern Lachlan Orogen.We tentatively conclude that all serpentinite belts of the Tumut region may be of the same age, at the Cambrian���Ordovician boundary.This Cambro-Ordovician age provides the best estimate for oceanic crust formation in the greater Tumut region. An age of 486 �� 3 Ma is reported for zircons from plagiogranite of the Wambidgee Serpentinite Belt in the Tumut region, southern Lachlan Orogen. We tentatively conclude that all serpentinite belts of the Tumut region may be of the same age, at the Cambrian���Ordovician boundary. This Cambro-Ordovician age provides the best estimate for oceanic crust formation in the greater Tumut region.