Attention network dysfunction underlies memory impairment in posterior cortical atrophy

Accumulating evidence suggests that memory is impaired in posterior cortical atrophy (PCA), alongside the early and defining visual disorder. The posterior parietal cortex is a key region of pathology in PCA and memory impairment may be the result of dysfunction of parietally dependent network function rather than the medial temporal lobe dependent dysfunction that defines the storage deficits in typical Alzheimer's disease. We assessed episodic memory performance and network function in16 PCA patients and 19 healthy controls who underwent structural and resting-state functional MRI and neuropsychological testing. Memory was assessed using the Free and Cued Selective Reminding Test (FCSRT), a sensitive test of episodic memory storage and retrieval. We examined correlations between memory performance and functional connectivity in the dorsal attention (DAN) and default mode network (DMN). Immediate recall on the FCSRT was relatively preserved in PCA patients. Total recall performance was impaired in patients relative to healthy controls and performance benefitted from retrieval cues. In patients only, disrupted connectivity in the DAN, but not the DMN, was associated with total recall. Memory impairment may arise from disruption to the dorsal attention network, subserved by the dorsal posterior parietal cortex, a key region of pathology in PCA, rather than classic medial temporal lobe memory circuitry.We propose that functional dysconnectivity in attentional circuits underpins memory impairment in PCA

Analysis of time to regulatory and ethical approval of SATVI TB vaccine trials in South Africa

Background. Tuberculosis (TB) vaccine trials in South Africa must be approved by the Medicines Control Council (MCC) and by a human research ethics committee (HREC). Delays in regulatory and ethical approval may affect operational and budget planning and clinical development of the product. Aim. Our aim was to analyse the time to regulatory and ethical approval for TB vaccine trials conducted by the South African Tuberculosis Vaccine Initiative (SATVI) and to evaluate factors that influence time to final approval. Method. Sixteen new TB vaccine clinical trials conducted by SATVI between 2004 and 2012 on infants, children, and adults were included. The period between submission and final approval was determined for protocols submitted to the MCC and the University of Cape Town HREC. Results. Median approval time following first submission to the MCC was 122 days (IQR 112 - 168; range 71 - 350), and for protocol amendments 103 days (interquartile range (IQR) 76 - 141; range 23 - 191; n=30). Median time following first submission for HREC approval was 60 days (IQR 33 - 81; range 18 - 125), and for amendments 6 days (IQR 4 - 13; range 1 - 37; n=30). There was no significant difference in approval time by trial phase, year of submission, revisions required, study population, sample size, or whether a clinical research organisation (CRO) was used. Conclusion. The time needed for regulatory and ethics approval was highly variable, but MCC approval for first submissions took twice as long as HREC approval and was the primary determinant of time to final approval. National regulatory capacity should be strengthened to facilitate the conduct of new TB vaccine trials in this country with its high burden of TB

Taxonbridge: an R package to create custom taxonomies based on the NCBI and GBIF taxonomies

Biological taxonomies establish conventions by which researchers can catalogue and systematically compare their work using nomenclature such as species binomial names and reference identifiers. The ideal taxonomy is unambiguous and exhaustive; however, no such single taxonomy exists, partly due to continuous changes and contributions made to existing taxonomies. The degree to which a taxonomy is useful furthermore depends on context provided by such variables as the taxonomic neighbourhood of a species (e.g., selecting arthropod or vertebrate species) or the geological time frame of the study (e.g., selecting extinct versus extant species). Collating the most relevant taxonomic information from multiple taxonomies is hampered by arbitrarily defined identifiers, ambiguity in scientific names, as well as duplicated and erroneous entries. The goal of taxonbridge is to provide tools for merging the Global Biodiversity Information Facility (GBIF) Backbone Taxonomy and the United States National Center for Biotechnology Information (NCBI) Taxonomy in order to create consistent, deduplicated and disambiguated custom taxonomies that reference both extant and extinct species

Analysis of time to regulatory and ethical approval of SATVI TB vaccine trials in South Africa

Background. Tuberculosis (TB) vaccine trials in South Africa must be approved by the Medicines Control Council (MCC) and by a human research ethics committee (HREC). Delays in regulatory and ethical approval may affect operational and budget planning and clinical development of the product. Aim. Our aim was to analyse the time to regulatory and ethical approval for TB vaccine trials conducted by the South African Tuberculosis Vaccine Initiative (SATVI) and to evaluate factors that influence time to final approval. Method. Sixteen new TB vaccine clinical trials conducted by SATVI between 2004 and 2012 on infants, children, and adults were included. The period between submission and final approval was determined for protocols submitted to the MCC and the University of Cape Town HREC. Results. Median approval time following first submission to the MCC was 122 days (IQR 112 - 168; range 71 - 350), and for protocol amendments 103 days (interquartile range (IQR) 76 - 141; range 23 - 191; n=30). Median time following first submission for HREC approval was 60 days (IQR 33 - 81; range 18 - 125), and for amendments 6 days (IQR 4 - 13; range 1 - 37; n=30). There was no significant difference in approval time by trial phase, year of submission, revisions required, study population, sample size, or whether a clinical research organisation (CRO) was used. Conclusion. The time needed for regulatory and ethics approval was highly variable, but MCC approval for first submissions took twice as long as HREC approval and was the primary determinant of time to final approval. National regulatory capacity should be strengthened to facilitate the conduct of new TB vaccine trials in this country with its high burden of TB

Transcranial ultrasound stimulation to human middle temporal complex improves visual motion detection and modulates electrophysiological responses

Background Transcranial ultrasound stimulation (TUS) holds promise as a novel technology for non-invasive neuromodulation, with greater spatial precision than other available methods and the ability to target deep brain structures. However, its safety and efficacy for behavioural and electrophysiological modulation remains controversial and it is not yet clear whether it can be used to manipulate the neural mechanisms supporting higher cognitive function in humans. Moreover, concerns have been raised about a potential TUS-induced auditory confound. Objectives We aimed to investigate whether TUS can be used to modulate higher-order visual function in humans in an anatomically-specific way whilst controlling for auditory confounds. Methods We used participant-specific skull maps, functional localisation of brain targets, acoustic modelling and neuronavigation to guide TUS delivery to human visual motion processing cortex (hMT+) whilst participants performed a visual motion detection task. We compared the effects of hMT + stimulation with sham and control site stimulation and examined EEG data for modulation of task-specific event-related potentials. An auditory mask was applied which prevented participants from distinguishing between stimulation and sham trials. Results Compared with sham and control site stimulation, TUS to hMT + improved accuracy and reduced response times of visual motion detection. TUS also led to modulation of the task-specific event-related EEG potential. The amplitude of this modulation correlated with the performance benefit induced by TUS. No pathological changes were observed comparing structural MRI obtained before and after stimulation. Conclusions The results demonstrate for the first time the precision, efficacy and safety of TUS for stimulation of higher-order cortex and cognitive function in humans whilst controlling for auditory confounds

The Critical Care Society of Southern Africa guidelines on the allocation of scarce critical care resources during the COVID-19 public health emergency in South Africa

Letter by Gopalan et al. on article by Singh and Moodley (Singh JA, Moodley K. Critical care triaging in the shadow of COVID-19: Ethics considerations. S Afr Med J 2020;110(5):355-359. https://doi.org/10.7196/SAMJ.2020.v110i5.14778); and response by Singh and Moodle

Points in Mental Space: an Interdisciplinary Study of Imagery in Movement Creation

As part of a programme of research that is developing tools to enhance choreographic practice, an interdisciplinary team of cognitive scientists, neuroscientists and dance professionals collaborated on two studies examining the mental representations used to support movement creation. We studied choreographer Wayne McGregor’s approach to movement creation through tasking, in which he asks dancers to create movement in response to task instructions that require a great deal of mental imagery and decision making. In our first experiment, we used experience sampling methods (self-report scales and reports about the current focus of thought) with the full company of Wayne McGregor | Random Dance to describe what the dancers report thinking about while creating movement, and to establish how their experiences change as a function of different task conditions. In particular, we contrasted a conventional ‘active’ condition (where dancers are free to move around) with a ‘static’ condition (where they have to create movement mentally, without moving), because all neuroimaging studies of dance require participants to lie motionless within a scanner. We adapted the static mode from Experiment 1 for the neuroimaging session in Experiment 2. Here we recorded the brain activity of an experienced dancer from Wayne McGregor | Random Dance while she mentally undertook movement creation tasks similar to those used in our experience sampling experiment. Both studies involved imagery tasks of a primarily spatial-praxic nature (involving an imagined object or volume that could be approached and manipulated) and imagery that focused on content invoking emotional narratives. In the first study, the dancers’ awareness was focused more than they had anticipated upon conceptual rather than physical or bodily aspects. The very act of reflecting on, and categorising, their experiences provided the dancers with insights about their mental habits during innovative movement creation. Such insights provide conditions under which habits can be recognised and then altered to adopt alternative points in mental space from which to create movement material. Providing the dancers and McGregor with a means to communicate more productively about the properties of the task-based instructions has been acknowledged by the company to be of clear benefit and a useful addition to their working process. In the second study we assessed the feasibility of using fMRI to study the neural underpinnings of choreographing movement tasks. The experiment enabled us to compare brain activity in imagery and movement creation. The data raise some key questions Points in Mental Space 3 concerning the mental context in which such thinking occurs and, given the clear limitations of the current fMRI and experience sampling work, how future research might usefully be directed. Taken together, these two exploratory studies indicate that the experiential and neural attributes of imagery during movement creation are open to systematic investigation: innovative movement creation can start from alternative points in mental, as well as physical, space. This enables us to look forward to establishing with greater precision how tasks that challenge dancers in different ways may affect mental and neural processes and how variation in imagery use across dancers might contribute to the variety of movement creation that they produce. Notably, the act of reflecting on the experience of movement creation also offers some practical leverage to help dancers develop a wider range of strategies for innovation. These findings are being used to contribute to further work informing the development of personal, notebook-like, Choreographic Thinking Tools

Human newborn bacille Calmette–Guérin vaccination and risk of tuberculosis disease: a case-control study

: An incomplete understanding of the immunological mechanisms underlying protection against tuberculosis (TB) hampers the development of new vaccines against TB. We aimed to define host correlates of prospective risk of TB disease following bacille Calmette-Guérin (BCG) vaccination. : In this study, 5,726 infants vaccinated with BCG at birth were enrolled. Host responses in blood collected at 10 weeks of age were compared between infants who developed pulmonary TB disease during 2 years of follow-up (cases) and those who remained healthy (controls). : Comprehensive gene expression and cellular and soluble marker analysis failed to identify a correlate of risk. We showed that distinct host responses after BCG vaccination may be the reason: two major clusters of gene expression, with different myeloid and lymphoid activation and inflammatory patterns, were evident when all infants were examined together. Cases from each cluster demonstrated distinct patterns of gene expression, which were confirmed by cellular assays. : Distinct patterns of host responses to Mycobacterium bovis BCG suggest that novel TB vaccines may also elicit distinct patterns of host responses. This diversity should be considered in future TB vaccine development

Artificial intelligence for dementia prevention

INTRODUCTION: A wide range of modifiable risk factors for dementia have been identified. Considerable debate remains about these risk factors, possible interactions between them or with genetic risk, and causality, and how they can help in clinical trial recruitment and drug development. Artificial intelligence (AI) and machine learning (ML) may refine understanding.// METHODS: ML approaches are being developed in dementia prevention. We discuss exemplar uses and evaluate the current applications and limitations in the dementia prevention field.// RESULTS: Risk-profiling tools may help identify high-risk populations for clinical trials; however, their performance needs improvement. New risk-profiling and trial-recruitment tools underpinned by ML models may be effective in reducing costs and improving future trials. ML can inform drug-repurposing efforts and prioritization of disease-modifying therapeutics.// DISCUSSION: ML is not yet widely used but has considerable potential to enhance precision in dementia prevention