Body-wave tomographic imaging of the Turkana Depression: Implications for rift development and plume-lithosphere interactions

The Turkana Depression, a topographically-subdued, broadly-rifted zone between the elevated East African and Ethiopian plateaus, disrupts the N–S, fault-bounded rift basin morphology that characterizes most of the East African Rift. The unusual breadth of the Turkana Depression leaves unanswered questions about the initiation and evolution of rifting between the Main Ethiopian and Eastern rifts. Hypotheses explaining the unusually broad, low-lying area include superposed Mesozoic and Cenozoic rifting and a lack of mantle lithospheric thinning and dynamic support. To address these issues, we have carried out the first body-wave tomographic study of the Depression’s upper mantle. Seismically-derived temperatures at 100 km depth exceed petrological estimates, suggesting the presence of mantle melt, although not as voluminous as the Main Ethiopian Rift, contributes to velocity anomalies. A NW–SE-trending high wavespeed band in southern Ethiopia at urn:x-wiley:15252027:media:ggge22580:ggge22580-math-0001200 km depth is interpreted as refractory Proterozoic lithosphere which has likely influenced the localization of both Mesozoic and Cenozoic rifting. At urn:x-wiley:15252027:media:ggge22580:ggge22580-math-0002100 km depth below the central Depression, a single localized low wavespeed zone is lacking. Only in the northernmost Eastern Rift and southern Lake Turkana is there evidence for focused low wavespeeds resembling the Main Ethiopian Rift, that bifurcate below the Depression and broaden approaching southern Ethiopia further north. These low wavespeeds may be attributed to melt-intruded mantle lithosphere or ponded asthenospheric material below lithospheric thin-spots induced by the region's multiple rifting phases. Low wavespeeds persist to the mantle transition zone suggesting the Depression may not lack mantle dynamic support in comparison to the two plateaus

The development of multiple phases of superposed rifting in the Turkana Depression, East Africa: evidence from receiver functions

The Turkana Depression in Eastern Africa separates the elevated plateaus of East Africa to the south and Ethiopia-Yemen to the north. It remains unclear whether the Depression lacks dynamic mantle support, or if the entire East Africa region is dynamically supported and the Depression compensated isostatically by thinned crust. Also poorly understood is how Miocene-Recent extension has developed across the Depression, connecting spatially separated magmatic rift zones in Ethiopia and Kenya. Receiver function analysis is used to constrain Moho depth and bulk-crustal V P /V S ratio below new seismograph networks in the Depression, and on the northern Tanzania craton. Crustal thickness is ∼40 km below northern Uganda and 30–35 km below southern Ethiopia, but 20–30 km below most of the Depression, where mass-balance calculations reveal low elevations can be explained adequately by crustal thinning alone. Despite the fact that magmatism has occurred for 45 Ma across the Depression, more than 15 Ma before East African Rift (EAR) extension initiated, bulk crustal V P /V S across southern Ethiopia and the Turkana Depression (∼1.74) is similar to that observed in areas unaffected by Cenozoic rifting and magmatism. Evidence for voluminous lower crustal intrusions and/or melt, widespread below the Ethiopian rift and Ethiopian plateau to the north, is therefore lacking. These observations, when reviewed in light of high stretching factors (β ≤ 2.11), suggest Cenozoic extension has been dominated until recently by faulting and plate stretching, rather than magma intrusion, which is likely an incipient process, operating directly below seismically-active Lake Turkana. Early-stage EAR basins to the west of Lake Turkana, with associated stretching factors of β ≈ 2, formed in crust only moderately thinned during earlier rifting episodes. Conversely, ∼23 km-thick crust beneath the Kino Sogo Fault Belt (KSFB) has small offset faults and thin sedimentary strata, suggesting almost all of the observed stretching occurred in Mesozoic times. Despite the KSFB marking the shortest path between focused extensional zones to the north and south, seismicity and GPS data show that modern extension is localized below Lake Turkana to the west. Failed Mesozoic rift zones, now characterized by thinned crust and relatively refractory mantle lithosphere, are being circumnavigated, not exploited by EAR rifting

Point of care coagulometry in prehospital emergency care: an observational study

Background: Haemostatic impairment can have a crucial impact on the outcome of emergency patients, especially in cases of concomitant antithrombotic drug treatment. In this prospective observational study we used a point of care (POC) coagulometer in a prehospital physician-based emergency medical system in order to test its validity and potential value in the treatment of emergency patients. Methods: During a study period of 12 months, patients could be included if venous access was mandatory for further treatment. The POC device CoaguChek® was used to assess international normalized ratio (INR) after ambulance arrival at the scene. Results were compared with in-hospital central laboratory assessment of INR. The gain of time was analysed as well as the potential value of POC testing through a questionnaire completed by the responsible prehospital emergency physician. Results: A total of 103 patients were included in this study. POC INR results were highly correlated with results of conventional assessment of INR (Bland-Altman-bias: 0.014). Using a cutoff value of INR >1.3, the device’s sensitivity to detect coagulopathy was 100 % with a specificity of 98.7 %. The median gain of time was 69 min. Treating emergency physicians considered the value of prehospital POC INR testing ‘high’ in 9 % and ‘medium’ in 21 % of all patients. In patients with tracer diagnosis ‘neurology’, the value of prehospital INR assessment was considered ‘high’ or ‘medium’ (63 %) significantly more often than in patients with non-neurological tracer diagnoses (24 %). Conclusions: Assessment of INR through a POC coagulometer is feasible in prehospital emergency care and provides valuable information on haemostatic parameters in patients. Questionnaire results suggest that POC INR testing may present a valuable technique in selected patients. Whether this information translates into an improved management of respective patients has to be evaluated in further studies

Combined oral triglyceride and glucose tolerance test after acute ischemic stroke to predict recurrent vascular events: the Berlin "Cream&Sugar" study

Background: Elevated triglyceride and glucose levels are associated with an increased cardiovascular disease risk including ischemic stroke. It is not known whether the response to a combined oral triglyceride and glucose challenge after ischemic stroke improves identification of patients with increased risk for recurrent vascular events. Methods: The prospective, observational Berlin "Cream&Sugar" study was conducted at 3 different university hospital sites of the Charite-Universitatsmedizin Berlin, Germany, between January 24, 2009 and July 31, 2017. Patients with first-ever ischemic stroke were recruited 3 to 7 days after stroke. An oral triglyceride tolerance test (OTTT) and consecutive blood tests before (t(0)) as well as 3 (t(1)), 4 (t(2)), and 5 hours (t(3)) after OTTT were performed in fasting patients. An oral glucose tolerance test was performed in all nondiabetic patients 3 hours after the start of OTTT. Outcomes of the study were recurrent fatal or nonfatal stroke as well as a composite vascular end point including stroke, transient ischemic attack, myocardial infarction, coronary revascularization, and cardiovascular death assessed 1 year after stroke. Cox regression models were used to estimate hazard ratios and corresponding 95% CIs between patients with high versus low levels of triglyceride and glucose levels. Results: Overall 755 patients were included; 523 patients completed OTTT and 1-year follow-up. Patients were largely minor strokes patients with a median National Institutes of Health Stroke Scale score of 1 (0-3). Comparing highest versus lowest quartiles of triglyceride levels, neither fasting (adjusted hazard ratio(t0), 1.24 [95% CI, 0.45-3.42]) nor postprandial triglyceride levels (adjusted hazard ratio(t3), 0.44 [95% CI, 0.16-1.25]) were associated with recurrent stroke. With regard to recurrent vascular events, results were similar for fasting triglycerides (adjusted hazard ratio(t0), 1.09 [95% CI, 0.49-2.43]), however, higher postprandial triglyceride levels were significantly associated with a lower risk for recurrent vascular events (adjusted hazard ratio(t3), 0.42 [95% CI, 0.18-0.95]). No associations were observed between fasting and post-oral glucose tolerance test blood glucose levels and recurrent vascular risk. All findings were irrespective of the diabetic status of patients. Conclusions: In this cohort of patients with first-ever, minor ischemic stroke, fasting triglyceride or glucose levels were not associated with recurrent stroke at one year after stroke. However, higher postprandial triglyceride levels were associated with a lower risk of recurrent vascular events which requires further validation in future studies. Overall, our results do not support the routine use of a combined OTTT/oral glucose tolerance test to improve risk prediction for recurrent stroke.Clinical epidemiolog

Glutamine depletion by crisantaspase hinders the growth of human hepatocellular carcinoma xenografts

Background: A subset of human hepatocellular carcinomas (HCC) exhibit mutations of β-catenin gene CTNNB1 and overexpress Glutamine synthetase (GS). The CTNNB1-mutated HCC cell line HepG2 is sensitive to glutamine starvation induced in vitro with the antileukemic drug Crisantaspase and the GS inhibitor methionine-L-sulfoximine (MSO). Methods: Immunodeficient mice with subcutaneous xenografts of the CTNNB1-mutated HCC cell lines HepG2 and HC-AFW1 were treated with Crisantaspase and/or MSO, and tumour growth was monitored. At the end of treatment, tumour weight and histology were assessed. Serum and tissue amino acids were determined by HPLC. Gene and protein expression were estimated with RT-PCR and western blot and GS activity with a colorimetric method. mTOR activity was evaluated from the phosphorylation of p70S6K1. Results: Crisantaspase and MSO depleted serum glutamine, lowered glutamine in liver and tumour tissue, and inhibited liver GS activity. HepG2 tumour growth was significantly reduced by either Crisantaspase or MSO, and completely suppressed by the combined treatment. The combined treatment was also effective against xenografts of the HC-AFW1 cell line, which is Crisantaspase resistant in vitro. Conclusions: The combination of Crisantaspase and MSO reduces glutamine supply to CTNNB1-mutated HCC xenografts and hinders their growth

Diffuse Glioneuronal tumour with Oligodendroglioma‐like features and Nuclear Clusters (DGONC) – a molecularly‐defined glioneuronal CNS tumour class displaying recurrent monosomy 14

Aims: DNA methylation-based central nervous system (CNS) tumour classification has identified numerous molecularly distinct tumour types, and clinically relevant subgroups among known CNS tumour entities that were previously thought to represent homogeneous diseases. Our study aimed at characterizing a novel, molecularly defined variant of glioneuronal CNS tumour. Patients and methods: DNA methylation profiling was performed using the Infinium MethylationEPIC or 450 k BeadChip arrays (Illumina) and analysed using the 'conumee' package in R computing environment. Additional gene panel sequencing was also performed. Tumour samples were collected at the German Cancer Research Centre (DKFZ) and provided by multinational collaborators. Histological sections were also collected and independently reviewed. Results: Genome-wide DNA methylation data from >25 000 CNS tumours were screened for clusters separated from established DNA methylation classes, revealing a novel group comprising 31 tumours, mainly found in paediatric patients. This DNA methylation-defined variant of low-grade CNS tumours with glioneuronal differentiation displays recurrent monosomy 14, nuclear clusters within a morphology that is otherwise reminiscent of oligodendroglioma and other established entities with clear cell histology, and a lack of genetic alterations commonly observed in other (paediatric) glioneuronal entities. Conclusions: DNA methylation-based tumour classification is an objective method of assessing tumour origins, which may aid in diagnosis, especially for atypical cases. With increasing sample size, methylation analysis allows for the identification of rare, putative new tumour entities, which are currently not recognized by the WHO classification. Our study revealed the existence of a DNA methylation-defined class of low-grade glioneuronal tumours with recurrent monosomy 14, oligodendroglioma-like features and nuclear clusters