Recurring types of variability and transitions in the ∼620 kyr record of climate change from the Chew Bahir basin, southern Ethiopia

The Chew Bahir Drilling Project (CBDP) aims to test possible linkages between climate and hominin evolution in Africa through the analysis of sediment cores that have recorded environmental changes in the Chew Bahir basin (CHB). In this statistical project we used recurrence plots (RPs) together with a recurrence quantification analysis (RQA) to distinguish two types of variability and transitions in the Chew Bahir aridity record and compare them with the ODP Site 967 wetness index from the eastern Mediterranean. The first type of variability is one of slow variations with cycles of ∼20 kyr, reminiscent of the Earth's precession cycle, and subharmonics of this orbital cycle. In addition to these cyclical wet-dry fluctuations in the area, extreme events often occur, i.e. short wet or dry episodes, lasting for several centuries or even millennia, and rapid transitions between these wet and dry episodes. The second type of variability is characterized by relatively low variation on orbital time scales, but significant century-millennium-scale variations with progressively increasing frequencies. Within this type of variability there are extremely fast transitions between dry and wet within a few decades or years, in contrast to those within Type 1 with transitions over several hundreds of years. Type 1 variability probably reflects the influence of precessional forcing in the lower latitudes at times with maximum values of the long (400 kyr) eccentricity cycle of the Earth's orbit around the sun, with the tendency towards extreme events. Type 2 variability seems to be linked with minimum values of this cycle. There does not seem to be a systematic correlation between Type 1 or Type 2 variability with atmospheric CO2 concentration. The different types of variability and the transitions between those types had important effects on the availability of water, and could have transformed eastern Africa's environment considerably, which would have had important implications for the shaping of the habitat of H. sapiens and the direct ancestors of this species

Using multiple chronometers to establish a long, directly-dated lacustrine record:Constraining >600,000 years of environmental change at Chew Bahir, Ethiopia

Despite eastern Africa being a key location in the emergence of Homo sapiens and their subsequent dispersal out of Africa, there is a paucity of long, well-dated climate records in the region to contextualize this history. To address this issue, we dated a ∼293 m long composite sediment core from Chew Bahir, south Ethiopia, using three independent chronometers (radiocarbon, 40Ar/39Ar, and optically stimulated luminescence) combined with geochemical correlation to a known-age tephra. The site is located in a climatically sensitive region, and is close to Omo Kibish, the earliest documented Homo sapiens fossil site in eastern Africa, and to the proposed dispersal routes for H. sapiens out of Africa. The 30 ages generated by the various techniques are internally consistent, stratigraphically coherent, and span the full range of the core depth. A Bayesian age-depth model developed using these ages results in a chronology that forms one of the longest independently dated, high-resolution lacustrine sediment records from eastern Africa. The chronology illustrates that any record of environmental change preserved in the composite sediment core from Chew Bahir would span the entire timescale of modern human evolution and dispersal, encompassing the time period of the transition from Acheulean to Middle Stone Age (MSA), and subsequently to Later Stone Age (LSA) technology, making the core well-placed to address questions regarding environmental change and hominin evolutionary adaptation. The benefits to such studies of direct dating and the use of multiple independent chronometers are discussed. Highlights • Four independent dating methods applied to ∼293 m lake core from southern Ethiopia. • Reveals 620 ka high-resolution sedimentary record near key fossil hominin sites. • Mean accumulation rate of 0.47 mm/a comparable to other African lacustrine sediments. • Accumulation rate fell to 0.1 mm/a during MIS 2, likely due to reduced sediment supply. • Use of multiple independent chronometers is a powerful approach in lake settings

Orbital controls on eastern African hydroclimate in the Pleistocene

Understanding eastern African paleoclimate is critical for contextualizing early human evolution, adaptation, and dispersal, yet Pleistocene climate of this region and its governing mechanisms remain poorly understood due to the lack of long, orbitally-resolved, terrestrial paleoclimate records. Here we present leaf wax hydrogen isotope records of rainfall from paleolake sediment cores from key time windows that resolve long-term trends, variations, and high-latitude effects on tropical African precipitation. Eastern African rainfall was dominantly controlled by variations in low-latitude summer insolation during most of the early and middle Pleistocene, with little evidence that glacial–interglacial cycles impacted rainfall until the late Pleistocene. We observe the influence of high-latitude-driven climate processes emerging from the last interglacial (Marine Isotope Stage 5) to the present, an interval when glacial–interglacial cycles were strong and insolation forcing was weak. Our results demonstrate a variable response of eastern African rainfall to low-latitude insolation forcing and high-latitude-driven climate change, likely related to the relative strengths of these forcings through time and a threshold in monsoon sensitivity. We observe little difference in mean rainfall between the early, middle, and late Pleistocene, which suggests that orbitally-driven climate variations likely played a more significant role than gradual change in the relationship between early humans and their environment

Paleo-ENSO influence on African environments and early modern humans

Our results identify the prime driver of climate variation in Africa’s low latitudes over the past 620 ky—the key time frame for the evolution of our species. Warming and cooling of the tropical Pacific Ocean paced by insolation changes modulated the tropical Walker circulation, driving opposing wet–dry states in eastern and western Africa. We show that the effects of glacial/interglacial cycles were not the predominant source of environmental change in most of the continent. Africa’s environmental patchwork driven by low-latitude climate processes should therefore be a critical component in conceptual models of human evolution and early demography over the past 620 ky.In this study, we synthesize terrestrial and marine proxy records, spanning the past 620 ky, to decipher pan-African climate variability and its drivers and potential linkages to hominin evolution. We find a tight correlation between moisture availability across Africa to El Niño Southern Ocean oscillation (ENSO) variability, a manifestation of the Walker Circulation, that was most likely driven by changes in Earth’s eccentricity. Our results demonstrate that low-latitude insolation was a prominent driver of pan-African climate change during the Middle to Late Pleistocene. We argue that these low-latitude climate processes governed the dispersion and evolution of vegetation as well as mammals in eastern and western Africa by increasing resource-rich and stable ecotonal settings thought to have been important to early modern humans.All study data are included in the article and/or supporting information.Results Discussion Conclusion Materials and Methods - pwPCA. - Breakpoint Analysis. - Median Calculation

Forschendes Lernen. Konzeptuelle Grundlagen und Potenziale digitaler Medien

Im folgenden Artikel wird dargelegt, was unter dem Konzept des forschenden Lernens zu verstehen ist und welche Einsatzmöglichkeiten sich für das forschende Lernen im Kontext Universität ergeben. Dabei werden speziell diejenigen Merkmale theoretisch herausgearbeitet, die aus Lehrendenperspektive Anknüpfungspunkte für einen prozessbegleitenden Medieneinsatz bieten. Exemplarisch wird eine Lehrveranstaltung angeführt, die auf Fallebene zeigt, wie ein forschungsorientiertes Seminar um digitale Medien angereichert werden kann und welche Chancen und Grenzen sich bei der selbstgesteuerten Verwendung digitaler Medienangebote ergeben. Die Evaluation des Seminars zeigt, dass die Studierenden einen großen Lernzuwachs erleben, jedoch teilweise durch die Offenheit des Lernens überfordert sind. Diese und andere Gründe führen dazu, dass die von Lehrenden vorgeschlagenen Medienangebote selten bis kaum genutzt werden. Zudem sehen Lernende die Qualität virtuell distribuierter Inhalte kritisch, was sich auf die Akzeptanz und die Nutzung der vorhandenen digitalen Medienangebote auswirkt. (DIPF/Orig.

G-CSF Prevents the Progression of Structural Disintegration of White Matter Tracts in Amyotrophic Lateral Sclerosis: A Pilot Trial

Background: The hematopoietic protein Granulocyte-colony stimulating factor (G-CSF) has neuroprotective and regenerative properties. The G-CSF receptor is expressed by motoneurons, and G-CSF protects cultured motoneuronal cells from apoptosis. It therefore appears as an attractive and feasible drug candidate for the treatment of amyotrophic lateral sclerosis (ALS). The current pilot study was performed to determine whether treatment with G-CSF in ALS patients is feasible.Methods: Ten patients with definite ALS were entered into a double-blind, placebo-controlled, randomized trial. Patients received either 10 mu g/kg BW G-CSF or placebo subcutaneously for the first 10 days and from day 20 to 25 of the study. Clinical outcome was assessed by changes in the ALS functional rating scale (ALSFRS), a comprehensive neuropsychological test battery, and by examining hand activities of daily living over the course of the study (100 days). The total number of adverse events (AE) and treatment-related AEs, discontinuation due to treatment-related AEs, laboratory parameters including leukocyte, erythrocyte, and platelet count, as well as vital signs were examined as safety endpoints. Furthermore, we explored potential effects of G-CSF on structural cerebral abnormalities on the basis of voxel-wise statistics of Diffusion Tensor Imaging (DTI), brain volumetry, and voxel-based morphometry.Results: Treatment was well-tolerated. No significant differences were found between groups in clinical tests and brain volumetry from baseline to day 100. However, DTI analysis revealed significant reductions of fractional anisotropy (FA) encompassing diffuse areas of the brain when patients were compared to controls. On longitudinal analysis, the placebo group showed significant greater and more widespread decline in FA than the ALS patients treated with G-CSF.Conclusions: Subcutaneous G-CSF treatment in ALS patients appears as feasible approach. Although exploratory analysis of clinical data showed no significant effect, DTI measurements suggest that the widespread and progressive microstructural neural damage in ALS can be modulated by G-CSF treatment. These findings may carry significant implications for further clinical trials on ALS using growth factors

Acute camptocormia induced by olanzapine: a case report

<p>Abstract</p> <p>Introduction</p> <p>Camptocormia refers to an abnormal posture with flexion of the thoraco-lumbar spine which increases during walking and resolves in supine position. This symptom is an increasingly recognized feature of parkinsonian and dystonic disorders, but may also be caused by neuromuscular diseases. There is recent evidence that both central and peripheral mechanisms may be involved in the pathogenesis of camptocormia. We report a case of acute onset of camptocormia, a rare side effect induced by olanzapine, a second-generation atypical anti-psychotic drug with fewer extra-pyramidal side-effects, increasingly used as first line therapy for schizophrenia, delusional disorders and bipolar disorder.</p> <p>Case presentation</p> <p>A 73-year-old Caucasian woman with no history of neuromuscular disorder, treated for chronic delusional disorder for the last ten years, received two injections of long-acting haloperidol. She was then referred for fatigue. Physical examination showed a frank parkinsonism without other abnormalities. Routine laboratory tests showed normal results, notably concerning creatine kinase level. Fatigue was attributed to haloperidol which was substituted for olanzapine. Our patient left the hospital after five days without complaint. She was admitted again three days later with acute back pain. Examination showed camptocormia and tenderness in paraspinal muscles. Creatine kinase level was elevated (2986 UI/L). Magnetic resonance imaging showed necrosis and edema in paraspinal muscles. Olanzapine was discontinued. Pain resolved quickly and muscle enzymes were normalized within ten days. Risperidone was later introduced without significant side-effect. The camptocormic posture had disappeared when the patient was seen as an out-patient one year later.</p> <p>Conclusions</p> <p>Camptocormia is a heterogeneous syndrome of various causes. We believe that our case illustrates the need to search for paraspinal muscle damage, including drug-induced rhabdomyolysis, in patients presenting with acute-onset bent spine syndrome. Although rare, the occurrence of camptocormia induced by olanzapine must be considered.</p

Intensive heart rhythm monitoring to decrease ischemic stroke and systemic embolism - the Find-AF 2 study - rationale and design

Background Atrial fibrillation (AF) is one of the most frequent causes of stroke. Several randomized trials have shown that prolonged monitoring increases the detection of AF, but the effect on reducing recurrent cardioembolism, i.e. ischemic stroke and systemic embolism, remains unknown. We aim to evaluate whether a risk-adapted, intensified heart rhythm monitoring with consequent guideline conform treatment, which implies initiation of oral anticoagulation (OAC), leads to a reduction of recurrent cardioembolism. Methods Find-AF 2 is a randomized, controlled, open-label parallel multicenter trial with blinded endpoint assessment. 5,200 patients ≥ 60 years of age with symptomatic ischemic stroke within the last 30 days and without known AF will be included at 52 study centers with a specialized stroke unit in Germany. Patients without AF in an additional 24-hour Holter ECG after the qualifying event will be randomized in a 1:1 fashion to either enhanced, prolonged and intensified ECG-monitoring (intervention arm) or standard of care monitoring (control arm). In the intervention arm, patients with a high risk of underlying AF will receive continuous rhythm monitoring using an implantable cardiac monitor (ICM) whereas those without high risk of underlying AF will receive repeated 7-day Holter ECGs. The duration of rhythm monitoring within the control arm is up to the discretion of the participating centers and is allowed for up to 7 days. Patients will be followed for at least 24 months. The primary efficacy endpoint is the time until recurrent ischemic stroke or systemic embolism occur. Conclusions The Find-AF 2 trial aims to demonstrate that enhanced, prolonged and intensified rhythm monitoring results in a more effective prevention of recurrent ischemic stroke and systemic embolism compared to usual care

Granulocyte-Colony Stimulating Factor (G-CSF) in Stroke Patients with Concomitant Vascular Disease—A Randomized Controlled Trial

G-CSF has been shown in animal models of stroke to promote functional and structural regeneration of the central nervous system. It thus might present a therapy to promote recovery in the chronic stage after stroke.Here, we assessed the safety and tolerability of G-CSF in chronic stroke patients with concomitant vascular disease, and explored efficacy data. 41 patients were studied in a double-blind, randomized approach to either receive 10 days of G-CSF (10 µg/kg body weight/day), or placebo. Main inclusion criteria were an ischemic infarct >4 months prior to inclusion, and white matter hyperintensities on MRI. Primary endpoint was number of adverse events. We also explored changes in hand motor function for activities of daily living, motor and verbal learning, and finger tapping speed, over the course of the study.Adverse events (AEs) were more frequent in the G-CSF group, but were generally graded mild or moderate and from the known side-effect spectrum of G-CSF. Leukocyte count rose after day 2 of G-CSF dosing, reached a maximum on day 8 (mean 42/nl), and returned to baseline 1 week after treatment cessation. No significant effect of treatment was detected for the primary efficacy endpoint, the test of hand motor function.These results demonstrate the feasibility, safety and reasonable tolerability of subcutaneous G-CSF in chronic stroke patients. This study thus provides the basis to explore the efficacy of G-CSF in improving chronic stroke-related deficits.ClinicalTrials.gov NCT00298597

Prevention and Intervention Studies with Telmisartan, Ramipril and Their Combination in Different Rat Stroke Models

The effects of AT1 receptor blocker, telmisartan, and the ACE inhibitor, ramipril, were tested head-to head and in combination on stroke prevention in hypertensive rats and on potential neuroprotection in acute cerebral ischemia in normotensive rats. Normotensive Wistar rats were treated s.c. 5 days prior to middle cerebral artery occlusion (MCAO) for 90 min with reperfusion. Groups (n = 10 each): (1) sham, (2) vehicle (V; 0,9% NaCl), (3) T (0,5 mg/kg once daily), (4) R (0,01 mg/kg twice daily), (5) R (0,1 mg/kg twice daily) or (6) T (0,5 mg/kg once daily) plus R (0,01 mg/kg twice daily). Twenty-four and 48 h after MCAO, neurological outcome (NO) was determined. Forty-eight h after MCAO, infarct volume by MRI, neuronal survival, inflammation factors and neurotrophin receptor (TrkB) were analysed.Stroke incidence was reduced, survival was prolonged and neurological outcome was improved in all treated SHR-SP with no differences between treated groups. In the acute intervention study, T and T+R, but not R alone, improved NO, reduced infarct volume, inflammation (TNFα), and induced TrkB receptor and neuronal survival in comparison to V.T, R or T+R had similar beneficial effects on stroke incidence and NO in hypertensive rats, confirming BP reduction as determinant factor in stroke prevention. In contrast, T and T+R provided superior neuroprotection in comparison to R alone in normotensive rats with induced cerebral ischemia