Continent-wide decoupling of Y-chromosomal genetic variation from language and geography in native South Americans

Numerous studies of human populations in Europe and Asia have revealed a concordance between their extant genetic structure and the prevailing regional pattern of geography and language. For native South Americans, however, such evidence has been lacking so far. Therefore, we examined the relationship between Y-chromosomal genotype on the one hand, and male geographic origin and linguistic affiliation on the other, in the largest study of South American natives to date in terms of sampled individuals and populations. A total of 1,011 individuals, representing 50 tribal populations from 81 settlements, were genotyped for up to 17 short tandem repeat (STR) markers and 16 single nucleotide polymorphisms (Y-SNPs), the latter resolving phylogenetic lineages Q and C. Virtually no structure became apparent for the extant Y-chromosomal genetic variation of South American males that could sensibly be related to their inter-tribal geographic and linguistic relationships. This continent-wide decoupling is consistent with a rapid peopling of the continent followed by long periods of isolation in small groups. Furthermore, for the first time, we identified a distinct geographical cluster of Y-SNP lineages C-M217 (C3*) in South America. Such haplotypes are virtually absent from North and Central America, but occur at high frequency in Asia. Together with the locally confined Y-STR autocorrelation observed in our study as a whole, the available data therefore suggest a late introduction of C3* into South America no more than 6,000 years ago, perhaps via coastal or trans-Pacific routes. Extensive simulations revealed that the observed lack of haplogroup C3* among extant North and Central American natives is only compatible with low levels of migration between the ancestor populations of C3* carriers and non-carriers. In summary, our data highlight the fact that a pronounced correlation between genetic and geographic/cultural structure can only be expected under very specific conditions, most of which are likely not to have been met by the ancestors of native South Americans

Modulation of neural correlates of visual scene processing by reward, emotion and animacy

Einleitung Eine wichtige Bedingung zielgerichteten menschlichen Verhaltens liegt bereits in der Wahrnehmung und Verarbeitung visueller Reize. Zeichnet man neuronale Aktivität auf, beobachtet man, dass bekannte, im Vergleich zu unbekannten, visuellen Reizen, zu einer reduzierten neuronalen Aktivierung in stimulusrelevanten, kortikalen Arealen führen. Dieses Phänomen, auch Repetition Suppression (RS) genannt, scheint keinem automatisierten Prozess, sondern einem kortikalen Lernvorgang zu entsprechen. Um den Einfluss von Belohnungserwartung, Emotion und Belebtheit auf die kortikale Verarbeitung visueller Reize zu charakterisieren, führten wir zwei Studien mit ereigniskorrelierter funktioneller Magnetresonanztomografie (fMRT) durch. Die Hypothesen waren, dass 1) Belohnungserwartung, ähnlich wie Aufmerksamkeit und Emotion, zu verstärkter RS in stimulusspezifischen Gehirnarealen führt. Wir nahmen an, dass 2) Belohnungserwartung mit verstärkter RS im ventralen Striatum einhergeht. Nicht zuletzt stellten wir 3) die Frage, ob saliente Stimuluseigenschaften, wie Belebtheit und Emotion, nicht-überlappend kortikal verarbeitet werden, oder ob dies überlappend und möglicherwiese additiv, in Form eines Gradienten geschieht. Methoden Im ersten Experiment untersuchten wir anhand eines monetary incentive delay – Paradigmas in 30 jungen, gesunden Probanden die neuronalen Wiederholungs-effekte während der Verarbeitung visueller Szenen, die in belohntem oder unbelohntem Kontext präsentiert wurden. In einem zweiten Experiment betrachteten wir die neuronalen Wiederholungseffekte bei der Verarbeitung visueller Szenen, die teilweise emotionale und belebte Motive darstellten, während 29 junge, gesunde Probanden eine visuelle Arbeitsgedächtnisaufgabe ausführten. Ergebnisse Wie erwartet, führte 1) Belohnungserwartung zu einer Aktivierung des ventralen Striatums und des orbitofrontalen Kortex. Entgegen unserer Hypothese 2), zeigte das ventrale Striatum ein konstantes Maß an RS, ungeachtet der belohnungsprädizierenden Eigenschaften eines Stimulus. Erstmalig konnte jedoch eine Interaktion von Wiederholung und Belohnungserwartung im rechten anterioren Hippocampus und eine gesteigerte funktionelle Konnektivität zwischen dem rechten anterioren Hippocampus, dem parahippocampalen Kortex und dem orbitofrontalen Kortex für belohnungsprädizierende Reize gezeigt werden. Anhand des zweiten Experimentes konnte gezeigt werden, dass RS durch die salienten Stimuluseigenschaften Emotion und Belebtheit in unterschiedlichen, nicht überlappenden Regionen innerhalb des Gyrus fusiformis beeinflusst wird, dass es jedoch im lateralen okzipitotemporalen Kortex (lOTC) Areale gibt, deren Wiederholungsmuster in einem additiven Muster auf Emotion und Belebtheit reagieren. Schlussfolgerung Anhand der beiden Experimente gelang es, mögliche neuronale Korrelate der Verarbeitung salienter visueller Stimuli zu charakterisieren. Während der Verhaltensvorteil im Kontext von Belohnungserwartung, also top-down Salienz, durch RS im Hippocampus und der verstärkten Konnektivität zum orbitofrontalen Kortex vermittelt zu sein scheint, beeinflussen Reize mit belebten und emotionalen Komponenten, also bottom-up Salienz, polymodale sensorische Kortexareale. Die Ergebnisse werfen Licht auf mögliche neuronale Prozesse bei belohnungsabhängigem Lernen und sind vereinbar mit Konzepten von rascher Extraktion relevanter Information aus natürlichen Szenen.Introduction Processing and perception of visual stimuli is a crucial requirement for goal-directed behavior. One robust finding in recordings of neuronal activity upon repeated presentation of visual stimuli is the decrease of signal in stimulus-related cortical areas. This phenomenon, called Repetition Suppression (RS), seems to reflect a cortical learning mechanism rather than a passive process. In order to investigate the influence of reward anticipation, emotion and animacy on processing of visual stimuli, we conducted two experiments using event-related functional magnetic resonance imaging. Hypotheses were that 1) reward anticipation would lead to RS in stimulus-related brain regions with 2) more pronounced RS in the ventral striatum for stimuli predicting reward. Another aim was to 3) characterize the modulatory effect of salient stimulus features such as emotion and animacy on localization and pattern of cortical activity upon repeated stimulus presentation. Methods In the first experiment, 30 young and healthy volunteers performed a numerical discrimination task. Visual scenes indicated whether the participants’ performance would be rewarded or not. In a second experiment, 29 young and healthy participants performed a visual working memory task during the presentation of scenes, partially containing emotional and animate elements. Results In line with hypothesis 1), the ventral striatum showed enhanced activity during reward anticipation. Hypothesis 2) was not confirmed, since no enhanced RS for the rewarded condition was observed in the ventral striatum. Interestingly, activity in the right anterior hippocampus showed an interaction of repetition and reward anticipation with pronounced RS and enhanced functional connectivity for the rewarded condition. Regarding question 3), results indicate a dissociable, non-overlapping processing of the salient stimulus features emotion and animacy within the fusiform gyrus. Furthermore, a specific region within the lateral occipitotemporal cortex showed an additive effect of salient stimulus features with the most pronounced RS for emotional and animate scenes. Conclusion The results of these two experiments shed new light on the modulation of visual processing by salient stimulus features. Whereas enhanced task performance in the context of top-down salience (reward anticipation) seems to be mediated by the anterior hippocampus and enhanced connectivity between hippocampal, parahippocampal and orbitofrontal regions, bottom-up salience (emotional and animate scenes) modulated activity in polymodal visual cortices with partly dissociable and partly additive effects within the ventral visual stream. These observations support concepts of fast and efficient extraction of relevant information of natural scenes

Revascularization Techniques for Acute Basilar Artery Occlusion Technical Considerations and Outcome in the Setting of Severe Posterior Circulation Steno-Occlusive Disease

Purpose To describe the clinical and radiological characteristics, frequency, technical aspects and outcome of endovascular treatment of acute basilar artery occlusion (ABO) in the setting of vertebrobasilar steno-occlusive disease. Methods Retrospective analysis of databases of two universitary stroke centers including all consecutive patients from January 2013 until May 2017 undergoing thrombectomy for a) acute stroke due to basilar artery occlusion and either significant basilar artery stenosis or vertebral artery stenosis/occlusion as well as b) presumed embolic basilar artery occlusions. Demographics, stroke characteristics, time metrics, recanalization results and outcome were recorded. Interventional strategies were evaluated concerning the thrombectomy technique, additional angioplasty, type of approach with respect to lesion pattern (ipsilateral to steno-occlusive VA lesion: dirty road or contralateral: clean road) and sequence of actions. Results Out of 157 patients treated for ABO 38 (24.2%) had associated significant vertebrobasilar steno-occlusive lesions. An underlying significant basilar artery stenosis was present in 23.7% and additionally significant steno-occlusive vertebral lesions were present in 81.5%. Thrombectomy was performed with primary aspiration in 15.8% and with stent-retrievers in 84.2%. Successful revascularization (TICI 2b-3) was achieved in 86.8%. In 52.6% additional stent angioplasty was performed, in 7.9% balloon angioplasty only. The clean road approach was used in 22.5% of cases, the dirty road in 77.4%. Final modified Rankin scale (mRS) was 0-2 in 6 patients (15.8%) and 3-5 in 32 (84.2%). The in-hospital mortality was 36.8%. There were no statistically significant differences in outcome compared to presumed cases of embolisms. Conclusion Endovascular treatment of ABO with underlying significant vertebrobasilar steno-occlusive lesions is effective and reasonably safe. Specific procedural strategies apply depending on individual patient pathology and anatomy. Although high rates of recanalization can be achieved, outcomes tend to be poor

Diagnostic and prognostic benefit of arterial spin labeling in subacute stroke

Background and Purpose: Brain perfusion measurement in the subacute phase of stroke may support therapeutic decisions. We evaluated whether arterial spin labeling (ASL), a noninvasive perfusion imaging technique based on magnetic resonance imaging (MRI), adds diagnostic and prognostic benefit to diffusion-weighted imaging (DWI) in subacute stroke. Methods: In a single-center imaging study, patients with DWI lesion(s) in the middle cerebral artery (MCA) territory were included. Onset to imaging time was ≤ 7 days and imaging included ASL and DWI sequences. Qualitative (standardized visual analysis) and quantitative perfusion analyses (region of interest analysis) were performed. Dichotomized early outcome (modified Rankin Scale [mRS] 0-2 vs. 3-6) was analyzed in two logistic regression models. Model 1 included DWI lesion volume, age, vascular pathology, admission NIHSS, and acute stroke treatment as covariates. Model 2 added the ASL-based perfusion pattern to Model 1. Receiver-operating-characteristic (ROC) and area-under-the-curve (AUC) were calculated for both models to assess their predictive power. The likelihood-ratio-test compared both models. Results: Thirty-eight patients were included (median age 70 years, admission NIHSS 4, onset to imaging time 67 hr, discharge mRS 2). Qualitative perfusion analysis yielded additional diagnostic information in 84% of the patients. In the quantitative analysis, AUC for outcome prediction was 0.88 (95% CI 0.77-0.99) for Model 1 and 0.97 (95% CI 0.91-1.00) for Model 2. Inclusion of perfusion data significantly improved performance and outcome prediction (p = 0.002) of stroke imaging. Conclusions: In patients with subacute stroke, our study showed that adding perfusion imaging to structural imaging and clinical data significantly improved outcome prediction. This highlights the usefulness of ASL and noninvasive perfusion biomarkers in stroke diagnosis and management

Continent-wide decoupling of Y-chromosomal genetic variation from language and geography in native South Americans

Numerous studies of human populations in Europe and Asia have revealed a concordance between their extant genetic structure and the prevailing regional pattern of geography and language. For native South Americans, however, such evidence has been lacking so far. Therefore, we examined the relationship between Y-chromosomal genotype on the one hand, and male geographic origin and linguistic affiliation on the other, in the largest study of South American natives to date in terms of sampled individuals and populations. A total of 1,011 individuals, representing 50 tribal populations from 81 settlements, were genotyped for up to 17 short tandem repeat (STR) markers and 16 single nucleotide polymorphisms (Y-SNPs), the latter resolving phylogenetic lineages Q and C. Virtually no structure became apparent for the extant Y-chromosomal genetic variation of South American males that could sensibly be related to their inter-tribal geographic and linguistic relationships. This continent-wide decoupling is consistent with a rapid peopling of the continent followed by long periods of isolation in small groups. Furthermore, for the first time, we identified a distinct geographical cluster of Y-SNP lineages C-M217 (C3*) in South America. Such haplotypes are virtually absent from North and Central America, but occur at high frequency in Asia. Together with the locally confined Y-STR autocorrelation observed in our study as a whole, the available data therefore suggest a late introduction of C3* into South America no more than 6,000 years ago, perhaps via coastal or trans-Pacific routes. Extensive simulations revealed that the observed lack of haplogroup C3* among extant North and Central American natives is only compatible with low levels of migration between the ancestor populations of C3* carriers and non-carriers. In summary, our data highlight the fact that a pronounced correlation between genetic and geographic/cultural structure can only be expected under very specific conditions, most of which are likely not to have been met by the ancestors of native South Americans

Sex disparities in re-employment in stroke patients with large vessel occlusion undergoing mechanical thrombectomy

Background: Strokes in the working-age population represent a relevant share of ischemic strokes and re-employment is a major factor for well-being in these patients. Income differences by sex have been suspected a barrier for women in returning to paid work following ischemic stroke. We aim to identify predictors of (not) returning to paid work in patients with large vessel occlusion treated with mechanical thrombectomy (MT) to identify potential areas of targeted vocational rehabilitation. Methods: From 6635 patients enrolled in the German Stroke Registry Endovascular Treatment between 2015 and 2019, data of 606 patients of the working population who survived large vessel occlusion at least 90 days past MT were compared based on employment status at day 90 follow-up. Univariate analysis, multiple logistic regression and analyses of area under the curve were performed to identify predictors of re-employment. Results: We report 35.6% of patients being re-employed 3 months following MT (median age 54.0 years; 36.1% of men, 34.5% of women [P=0.722]). We identified independent negative predictors against re-employment being female sex (odds ratio [OR], 0.427 [95% CI, 0.229–0.794]; P=0.007), higher National Institutes of Health Stroke Scale (NIHSS) score 24 hours after MT (OR, 0.775 [95% CI, 0.705–0.852]; P<0.001), large vessel occlusion due to large-artery atherosclerosis (OR, 0.558 [95% CI, 0.312–0.997]; P=0.049) and longer hospital stay (OR, 0.930 [95% CI, 0.868–0.998]; P=0.043). Positive predictors favoring re-employment were excellent functional outcome (modified Rankin Scale score of 0–1) at 90 day follow-up (OR, 11.335 [95% CI, 4.864–26.415]; P<0.001) and combined treatment with intravenous thrombolysis (OR, 1.904 [95% CI, 1.046–3.466]; P=0.035). Multiple regression modeling increased predictive power of re-employment status significantly over prediction by best single functional outcome parameter (National Institutes of Health Stroke Scale 24 hours after MT ≤5; R2: 0.582 versus 0.432; area under the receiver operating characteristic curve: 0.887 versus 0.835, P<0.001). Conclusions: There is more to re-employment after MT than functional outcome alone. In particular, attention should be paid to possible systemic barriers deterring women from resuming paid work

Sex Differences in Outcome After Thrombectomy for Acute Ischemic Stroke are Explained by Confounding Factors

Purpose!#!The aim of this study was to analyze sex differences in outcome after thrombectomy for acute ischemic stroke in clinical practice in a large prospective multicenter registry.!##!Methods!#!Data of consecutive stroke patients treated with thrombectomy (June 2015-April 2018) derived from an industry-independent registry (German Stroke Registry-Endovascular Treatment) were prospectively analyzed. Multivariable binary logistic regression analyses were applied to determine whether sex is a predictor of functional independence outcome (defined as a modified Rankin scale [mRS] 0-2) 90 days after stroke.!##!Results!#!In total, 2316 patients were included in the analysis, 1170 (50.5%) were female and 1146 (49.5%) were male. Women were older (median age 78 vs. 72 years; p &amp;lt; 0.001) and more frequently had a prestroke functional impairment defined by mRS &amp;gt;1 (24.8% vs. 14.1%; p &amp;lt; 0.001). In unadjusted analyses, independent outcome at 90 days was less frequent in women (33.2%) than men (40.6%; p &amp;lt; 0.001). Likewise, mortality was higher in women than in men (30.7% vs. 26.4%; p = 0.024). In adjusted regression analyses, however, sex was not associated with outcome. Lower age, a lower baseline National Institutes of Health Stroke Scale score, a higher Alberta Stroke Program Early CT score, prestroke functional independence, successful reperfusion, and concomitant intravenous thrombolysis therapy predicted independent outcome.!##!Conclusion!#!Women showed a worse functional outcome after thrombectomy for acute ischemic stroke in clinical practice; however, after adjustment for crucial confounders sex was not a predictor of outcome. The difference in outcome thus appears to result from differences in confounding factors such as age and prestroke functional status

Systematic evaluation of stroke thrombectomy in clinical practice: The German Stroke Registry Endovascular Treatment

Background: Endovascular treatment has become standard of care for the treatment of acute ischemic stroke with large vessel occlusion. However, patients treated in clinical practice differ from the selected populations randomized in clinical trials. Aims: The German Stroke Registry Endovascular Treatment (GSR-ET) aims at a systematic evaluation of outcome, safety, and process parameters of endovascular stroke treatment in standard of care in Germany. Methods: The GSR-ET is an academic, independent, prospective, multicenter, observational registry study. Participating stroke centers from all over of Germany consecutively enroll patients transferred to the angiography suite with an intention to be treated with endovascular stroke treatment. Patients receive regular care. Data are collected as part of clinical routine. Baseline clinical and procedural information and clinical follow-up information after 90 days are recorded. Here, we present an analysis of baseline data of the first 1662 patients included in the GSR-ET. Results: The registry was established in June 2015. By 31 December 2017, 1662 patients were enrolled in 23 active sites. Mean age was 72 +/- 13 years, 50% were female, and median National Institutes of Health Stroke Scale on admission was 15 (IQR 10-19), 88% had anterior circulation occlusion. Median ASPECT score was 8 (IQR 7-10) prior to intervention. Fifty-nine percent of patients received intravenous thrombolysis prior to thrombectomy. Mean onset-to-groin time was 224 +/- 176 min. Conclusions: Baseline characteristics of stroke patients undergoing thrombectomy in clinical practice differ from those in the randomized trials. The GSR-ET will provide valuable insights into practices of endovascular treatment in routine care of acute ischemic stroke

Factors Associated with Failure of Reperfusion in Endovascular Therapy for Acute Ischemic Stroke

Aim!#!In acute large vessel occlusions, endovascular therapy (EVT) achieves flow restoration in the majority of cases; however, EVT fails to achieve sufficient reperfusion in a substantial minority of patients. This study aimed to identify predictors of failed reperfusion.!##!Methods!#!In this study 2211 patients from the German Stroke Registry who received EVT for anterior circulation stroke were retrospectively analyzed. Failure of reperfusion was defined as thrombolysis in cerebral infarction (TICI) grades 0/1/2a, and sufficient reperfusion as TICI 2b/3. In 1629 patients with complete datasets, associations between failure of reperfusion and baseline clinical data, comorbidities, location of occlusion, and procedural data were assessed with multiple logistic regression.!##!Results!#!Failure of reperfusion occurred in 371 patients (16.8%) and was associated with the following locations of occlusion: cervical internal carotid artery (ICA, adjusted odds ratio, OR 2.01, 95% confidence interval, CI 1.08-3.69), intracranial ICA without carotid T occlusion (adjusted OR 1.79, 95% CI 1.05-2.98), and M2 segment (adjusted OR 1.86, 95% CI 1.21-2.84). Failed reperfusion was also associated with cervical ICA stenosis (&amp;gt;70% stenosis, adjusted OR 2.90, 95% CI 1.69-4.97), stroke of other determined etiology by TOAST (Trial of ORG 10172 in acute stroke treatment) criteria (e.g. nonatherosclerotic vasculopathies, adjusted OR 2.73, 95% CI 1.36-5.39), and treatment given outside the usual working hours (adjusted OR 1.41, 95% CI 1.07-1.86). Successful reperfusion was associated with higher Alberta stroke program early CT score (ASPECTS) on initial imaging (adjusted OR 0.85, 95% CI 0.79-0.92), treatment with the patient under general anesthesia (adjusted OR 0.72, 95% CI 0.54-0.96), and concomitant ICA stenting in patients with ICA stenosis (adjusted OR 0.20, 95% CI 0.11-0.38).!##!Conclusion!#!Several factors are associated with failure of reperfusion, most notably occlusions of the proximal ICA and low ASPECTS on admission. Conversely, stent placement in the proximal ICA was associated with reperfusion success