Pleistocene Homo and the updated Stone Age sequence of South Africa

We provide a brief overview of how the rich South African Pleistocene Homo fossil record correlates with the recently revised Stone Age sequence. The overview and correlation of the data is intended to highlight gaps in the record and/or our understanding thereof, and to stimulate interdisciplinary research and debate on the Homo fossil and archaeological records spanning the Pleistocene. As an updated resource we present a complete inventory of known Pleistocene fossil material assigned to the genus Homo, and, where possible, its association with archaeological material. We demonstrate that (1) anatomical changes are not necessarily paralleled by changes in the archaeological sequence currently based on a range of technocomplexes, (2) the early Homo record of South Africa probably differs from that of East Africa, (3) mid-Pleistocene Homo might be associated with the Earlier to Middle Stone Age transitional phase and (4) the fossil record associated with the Middle Stone Age has wide anatomical variation. Also, hiatuses in the fossil record, such as that associated with the appearance of early Khoe-San-like populations, do not show concurrent hiatuses in the archaeological record. Thus, for a broader understanding of the demographic history of South Africa during the Pleistocene, both sources of information should be considered in tandem.publishedVersio

The drama of Senkatana by S.M. Mofokeng : a speech act exploration

The drama of Senkatana by S.M. Mofokeng is analysed by applying principles provided by speech act theory, using as basis the explication of the theory by Bach and Harnish (1979). The socio-cultural context in the play has as its starting point the realm of myth and legend. From here all categories of relationships within the protagonist/antagonist encounter unfold, as do opposing sets of contextual beliefs characters rely on; these are primarily responsible for the growing conflict in the drama. Enhancing the mythical character of the play is the absorbing role played by the diboni, acting as seers, as prophets and as additional 'authorial voice'. Their and those of other characters' speech acts reflect this and more; they operate in a substantiated sign-system which provides a framework for evaluating each semiotic act from locutionary, illocutionary and perlocutionary dimensions of meaning. Chapter 1 comprises a historical survey of studies on speech act theory, and includes a brief summary of the position of the theory in the field of semiotics. The micro speech act analysis of the play is facilitated by the division of the text into smaller action units (summarised in Addendum 1). Chapter 2, containing the greater part of the exposition, commences the narration of the folktale and offers a clear rendering of the epic rise of the hero. Chapter 3 portrays the rise and progress of the antagonists challenging the hero, coupled with intensifying anxiety among the protagonists. Chapter 4 provides a vivid overview of how the values of the hero triumph over those of the antagonist despite the physical slaying of the hero. Chapter 5 offers a graphic outline of how the macro speech act is accomplished in the play. It is shown how an investigation of the speech act profiles of characters, coupled with the evaluation of illocutionary tactics and illocutionary/perlocutionary dynamics, communicates significant information pertaining to characterisation. A graph illustrating the rise and fall of micro speech acts within the larger macro speech act is provided in Addendum 2. Suggestions are made regarding future research in literary texts.African LanguagesD.Lit. et Phil. (African Languages

Recent developments in the application of flow cytometry to advance our understanding of Mycobacterium tuberculosis physiology and pathogenesis

CITATION: Parbhoo, T., Sampson, S.L. & Mouton, J.M. 2020. Recent developments in the application of flow cytometry to advance our understanding of Mycobacterium tuberculosis physiology and pathogenesis. Cytometry Part A, 97(7):683-693. doi:10.1002/cyto.a.24030The original publication is available at https://onlinelibrary.wiley.com/journal/15524930The ability of the bacterial pathogen Mycobacterium tuberculosis to adapt and survive within human cells to disseminate to other individuals and cause active disease is poorly understood. Research supports that as M. tuberculosis adapts to stressors encountered in the host, it exhibits variable physiological and metabolic states that are time and niche-dependent. Challenges associated with effective treatment and eradication of tuberculosis (TB) are in part attributed to our lack of understanding of these different mycobacterial phenotypes. This is mainly due to a lack of suitable tools to effectively identify/detect heterogeneous bacterial populations, which may include small, difficult-to-culture subpopulations. Importantly, flow cytometry allows rapid and affordable multiparametric measurements of physical and chemical characteristics of single cells, without the need to preculture cells. Here, we summarize current knowledge of flow cytometry applications that have advanced our understanding of the physiology of M. tuberculosis during TB disease. Specifically, we review how host-associated stressors influence bacterial characteristics such as metabolic activity, membrane potential, redox status and the mycobacterial cell wall. Further, we highlight that flow cytometry offers unprecedented opportunities for insight into bacterial population heterogeneity, which is increasingly appreciated as an important determinant of disease outcome. © 2020 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of International Society for Advancement of Cytometry.https://onlinelibrary.wiley.com/journal/15524930Publishers versio

Early time course of major bleeding on antiplatelet therapy after TIA or ischemic stroke

Objective: To study the early time course of major bleeding and its subtypes in patients with cerebral ischemia on dual and single antiplatelet therapy. Methods: We performed a post hoc analysis on individual patient data from 6 randomized clinical trials (Clopidogrel Versus Aspirin in Patients at Risk of Ischaemic Events [CAPRIE], Second European Stroke Prevention Study [ESPS-2], Management of Atherothrombosis With Clopidogrel in High Risk Patients [MATCH], Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance [CHARISMA], European/Australasian Stroke Prevention in Reversible Ischaemia Trial [ESPRIT], and Prevention Regimen for Effectively Avoiding Second Strokes [PRoFESS]) including 45,195 patients with a TIA or noncardioembolic ischemic stroke. We studied incidence rates of bleeding per antiplatelet regimen stratified by time from randomization (≤30, 31–90, 91–180, 181–365, >365 days). We calculated incidence rates per trial and pooled estimates with random-effects meta-analysis. We performed Poisson regression to assess differences between time periods with adjustment for age and sex. Results: The incidence of major bleeding on aspirin plus clopidogrel and aspirin plus -dipyridamole was highest in the first 30 days, 5.8 and 4.9 per 100 person-years, respectively, and was significantly higher than at 31 to 90 days (rate ratio 1.98, 95% confidence interval 1.16–3.40 for aspirin plus clopidogrel; rate ratio 1.94, 95% confidence interval 1.24–3.03 for aspirin plus dipyridamole). Incidence rates on aspirin and clopidogrel monotherapy were 2.8 and 2.5 per 100 person-years, respectively, in the first 30 days, with no significant change over time. The time course was similar for gastrointestinal bleeds. There was no early excess of intracranial hemorrhage in patients on either dual or single antiplatelet therapy. Conclusion: Dual antiplatelet therapy is associated with high early risks of major and gastrointestinal bleeding that decline after the first month in trial cohorts

Rating of pre-injury symptoms over time in patients with mild traumatic brain injury:The good-old-days-bias revisited

Objective Post-concussion syndrome (PCS) occurs following mild traumatic brain injury (mTBI). Patients with mTBI are often assessed using self-report instruments that rely on perception of current symptoms compared to how they felt and functioned pre-injury. The objective was to examine reliability of patients’ post-injury reporting of their pre-injury symptoms. Methods We included two control groups (trauma patients without brain injury history and healthy controls) who were recruited at an outpatient surgical clinic and among the working and social environment of the researchers, respectively. The Head Injury Symptom Checklist (HISC) was used to assess pre-injury and current symptoms at four time points post injury. We included 836 patients with mTBIs, 191 trauma patients without brain injury history, and 100 healthy controls. Results Patients with mTBI reported significantly more pre-injury symptoms than both control groups (p < .001). Forty-five percent of patients with mTBI were inconsistent in their pre-injury ratings across four assessments. Patients with post-injury PCS reported much greater pre-injury symptoms and were more often inconsistent. Conclusion Accurately assessing PCS by comparing pre with post-injury complaints is difficult, and may have implications for diagnosis when using self-report instruments. Therefore, post-injury PCS diagnosis should be interpreted with caution and PCS should ideally be examined using clinical examination

An integrated perspective linking physiological and psychological consequences of mild traumatic brain injury

Despite the often seemingly innocuous nature of a mild traumatic brain injury (mTBI), its consequences can be devastating, comprising debilitating symptoms that interfere with daily functioning. Currently, it is still difficult to pinpoint the exact cause of adverse outcome after mTBI. In fact, extensive research suggests that the underlying etiology is multifactorial. In the acute and early sub-acute stages, the pathophysiology of mTBI is likely to be dominated by complex physiological alterations including cellular injury, inflammation, and the acute stress response, which could lead to neural network dysfunction. In this stage, patients often report symptoms such as fatigue, headache, unstable mood and poor concentration. When time passes, psychological processes, such as coping styles, personality and emotion regulation, become increasingly influential. Disadvantageous, maladaptive, psychological mechanisms likely result in chronic stress which facilitates the development of long-lasting symptoms, possibly via persistent neural network dysfunction. So far, a systemic understanding of the coupling between these physiological and psychological factors that in concert define outcome after mTBI is lacking. The purpose of this narrative review article is to address how psychophysiological interactions may lead to poor outcome after mTBI. In addition, a framework is presented that may serve as a template for future studies on this subject

Frontotemporal dementia, music perception and social cognition share neurobiological circuits:A meta-analysis

Frontotemporal dementia (FTD) is a neurodegenerative disease that presents with profound changes in social cognition. Music might be a sensitive probe for social cognition abilities, but underlying neurobiological substrates are unclear. We performed a meta-analysis of voxel-based morphometry studies in FTD patients and functional MRI studies for music perception and social cognition tasks in cognitively normal controls to identify robust patterns of atrophy (FTD) or activation (music perception or social cognition). Conjunction analyses were performed to identify overlapping brain regions. In total 303 articles were included: 53 for FTD (n = 1153 patients, 42.5% female; 1337 controls, 53.8% female), 28 for music perception (n = 540, 51.8% female) and 222 for social cognition in controls (n = 5664, 50.2% female). We observed considerable overlap in atrophy patterns associated with FTD, and functional activation associated with music perception and social cognition, mostly encompassing the ventral language network. We further observed overlap across all three modalities in mesolimbic, basal forebrain and striatal regions. The results of our meta-analysis suggest that music perception and social cognition share neurobiological circuits that are affected in FTD. This supports the idea that music might be a sensitive probe for social cognition abilities with implications for diagnosis and monitoring

Prediction of Cognitive Recovery after Stroke:The Value of Diffusion-Weighted Imaging–Based Measures of Brain Connectivity

Background and Purpose: Prediction of long-term recovery of a poststroke cognitive disorder (PSCD) is currently inaccurate. We assessed whether diffusion-weighted imaging (DWI)–based measures of brain connectivity predict cognitive recovery 1 year after stroke in patients with PSCD in addition to conventional clinical, neuropsychological, and imaging variables. Methods: This prospective monocenter cohort study included 217 consecutive patients with a clinical diagnosis of ischemic stroke, aged ≥50 years, and Montreal Cognitive Assessment score below 26 during hospitalization. Five weeks after stroke, patients underwent DWI magnetic resonance imaging. Neuropsychological assessment was performed 5 weeks and 1 year after stroke and was used to classify PSCD as absent, modest, or marked. Cognitive recovery was operationalized as a shift to a better PSCD category over time. We evaluated 4 DWI-based measures of brain connectivity: global network efficiency and mean connectivity strength, both weighted for mean diffusivity and fractional anisotropy. Conventional predictors were age, sex, level of education, clinical stroke characteristics, neuropsychological variables, and magnetic resonance imaging findings (eg, infarct size). DWI-based measures of brain connectivity were added to a multivariable model to assess additive predictive value. Results: Of 135 patients (mean age, 71 years; 95 men [70%]) with PSCD 5 weeks after ischemic stroke, 41 (30%) showed cognitive recovery. Three of 4 brain connectivity measures met the predefined threshold of P<0.1 in univariable regression analysis. There was no added value of these measures to a multivariable model that included level of education and infarct size as significant predictors of cognitive recovery. Conclusions: Current DWI-based measures of brain connectivity appear to predict recovery of PSCD but at present have no added value over conventional predictors

Balancing Benefits and Risks of Long-Term Antiplatelet Therapy in Noncardioembolic Transient Ischemic Attack or Stroke

Lifelong treatment with antiplatelet drugs is recommended following a transient ischemic attack or ischemic stroke. Bleeding complications may offset the benefit of antiplatelet drugs in patients at increased risk of bleeding and low risk of recurrent ischemic events. We aimed to investigate the net benefit of antiplatelet treatment according to an individuals’ bleeding risk. METHODS: We pooled individual patient data from 6 randomized clinical trials (CAPRIE [Clopidogrel Versus Aspirin in Patients at Risk of Ischemic Events], ESPS-2 [European Stroke Prevention Study-2], MATCH [Management of Atherothrombosis With Clopidogrel in High-Risk Patients], CHARISMA [Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance], ESPRIT [European/Australasian Stroke Prevention in Reversible Ischemia Trial], and PRoFESS [Prevention Regimen for Effectively Avoiding Second Strokes]) investigating antiplatelet therapy in the subacute or chronic phase after noncardioembolic transient ischemic attack or stroke. Patients were stratified into quintiles according to their predicted risk of major bleeding with the S(2)TOP-BLEED score. The annual risk of major bleeding and recurrent ischemic events was assessed per quintile for 4 scenarios: (1) aspirin monotherapy, (2) aspirin-clopidogrel versus aspirin or clopidogrel monotherapy, (3) aspirin-dipyridamole versus clopidogrel, and (4) aspirin versus clopidogrel. Net benefit was calculated for the second, third, and fourth scenario. RESULTS: Thirty seven thousand eighty-seven patients were included in the analyses. Both risk of major bleeding and recurrent ischemic events increased over quintiles of predicted bleeding risk, but risk of ischemic events was consistently higher (eg, from 0.7%/y (bottom quintile) to 3.2%/y (top quintile) for major bleeding on aspirin and from 2.5%/y to 10.2%/y for risk of ischemic events on aspirin). Treatment with aspirin-clopidogrel led to more major bleedings (0.9%–1.7% per year), than reduction in ischemic events (ranging from 0.4% to 0.9/1.0% per year) across all quintiles. There was no clear preference for either aspirin-dipyridamole or clopidogrel according to baseline bleeding risk. CONCLUSIONS: Among patients with a transient ischemic attack or ischemic stroke included in clinical trials of antiplatelet therapy, the risk of recurrent ischemic events and of major bleeding increase in parallel. Antiplatelet treatment cannot be individualized solely based on bleeding risk assessment