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Stroke research funding versus burden of disease (World Stroke Organisation funded STARBUD Project)
Get PDFEvidence for transient, uncoupled power and functional connectivity dynamics
Get PDFThere is growing interest in studying the temporal structure in brain network activity, in particular, dynamic functional connectivity (FC), which has been linked in several studies with cognition, demographics and disease states. The sliding window approach is one of the most common approaches to compute dynamic FC. However, it cannot detect cognitively relevant and transient temporal changes at time scales of fast cognition, that is, on the order of 100 ms, which can be identified with model-based methods such as the HMM (Hidden Markov Model) and DyNeMo (Dynamic Network Modes) using electrophysiology. These new methods provide time-varying estimates of the ‘power’ (i.e., variance) and of the functional connectivity of the brain activity, under the assumption that they share the same dynamics. But there is no principled basis for this assumption. Using a new method that allows for the possibility that power and FC networks have different dynamics (Multi-dynamic DyNeMo) on resting-state magnetoencephalography (MEG) data, we show that the dynamics of the power and the FC networks are not coupled. Using a (visual) task MEG dataset, we show that the power and FC network dynamics are modulated by the task, such that the coupling in their dynamics changes significantly during the task. This work reveals novel insights into evoked network responses and ongoing activity that previous methods fail to capture, challenging the assumption that power and FC share the same dynamics
Direct circMAN1A2(2,3,4,5)-CENPB mRNA interaction regulates cell proliferation and cancer progression
Get PDFNumerous covalently closed circular RNAs (circRNAs) are produced from back-splicing of eukaryotic exons, and multiple circRNAs can be generated from a single gene locus through alternative circularization (AC). However, functions of most AC circRNAs remain poorly understood. Here, we profile the landscape of AC across multiple cell lines and colorectal cancer (CRC) tissues, identifying predominantly expressed circRNAs (pe-circRNA) in each AC gene locus. Other than cell-type-specific expression of most top pe-circRNAs, circMAN1A2(2,3,4,5), a universally expressed pe-circRNA in examined samples, plays an important role in cell proliferation and CRC progression. Mechanistically, circMAN1A2(2,3,4,5) directly interacts with the 3' untranslated region of Centromere Protein B (CENPB) mRNA via its characteristic back-splicing junction site, which enhances IGF2BP2-mediated CENPB mRNA stability. Inhibition of circMAN1A2(2,3,4,5) expression with locked nucleic acids represses CRC progression. These results uncover the prevalence of AC and the regulatory role of a specific AC circRNA, circMAN1A2(2,3,4,5), in cell proliferation and tumor progression
Multinational transfusion practices and outcomes in haematology patients admitted to the intensive care unit
Get PDFBackground and Objectives: The number of critically ill patients with haematological conditions is increasing, yet transfusion practices in this population remain poorly defined. This study aimed to compare transfusion strategies in critically ill patients with versus without haematological conditions. Study Design and Methods: This international, prospective observational substudy of the International Point Prevalence Study of Intensive Care Unit [ICU] Transfusion Practices (InPUT) evaluated transfusion use in ICU patients with and without haematological conditions, including benign or malignant diseases or a history of stem cell transplantation. Outcomes included use of red blood cells (RBCs), platelets, plasma, haemostatic interventions, transfusion indications and thresholds. Results: Of 3643 ICU patients, 131 (3.6%) had a haematological condition. These patients were more likely to receive RBC (odds ratio [OR] 1.58, 95% confidence interval [CI] 1.09–2.29) and platelet transfusions (OR 8.32, 95% CI 5.09–13.6), primarily due to low haemoglobin rather than physiological triggers. Platelet thresholds were lower (median 23 × 109/L vs. 64 × 109/L) compared to non‐haematology patients. Both platelet and plasma transfusions were more frequently administered prophylactically rather than for active bleeding. Haemostatic interventions were more often used in haematology patients, at higher doses and typically without viscoelastic testing. Transfused haematology patients had higher 28‐day mortality and longer ICU stays. Conclusion: ICU patients with haematological conditions receive transfusions differently, particularly regarding platelet and plasma use. These findings underscore the need for prospective studies to define optimal transfusion thresholds in this growing and vulnerable patient population, although the study's limited sample size and lack of diagnostic granularity may affect interpretation
Redefining endpoints in heart failure clinical trials: the emerging role of wearable technologies in contemporary trial design
Get PDFRandomised controlled trials (RCTs) in heart failure (HF) have progressively broadened their primary endpoints over recent decades. Early landmark HF trials demonstrated the life-saving effects of new therapies using all-cause mortality as the definitive endpoint. As HF therapies improved survival, trial designers incorporated additional endpoints such as HF hospitalisations and quality of life. Most recently, advances in digital health have introduced wearable devices for collecting digital endpoints, enabling continuous monitoring of patient activity and physiology. This review critically examines the evolution of HF trial endpoints from a sole focus on mortality alone to modern composite and patient-reported outcomes and discusses the current challenges and opportunities of using wearable-derived endpoints in HF RCTs. Finally, we consider future directions for HF trial methodology, including regulatory and methodological considerations for integrating novel digitally collected endpoints alongside traditional measures to enhance a broad evaluation of new therapies
The SMC Hinge is a Selective Gate for Obstacle Bypass
Get PDFDNA loop-extruding SMC complexes play vital roles in genome maintenance and DNA immunity. However, how these ring-shaped DNA motors navigate large DNA-bound obstacles has remained unclear. Here, we demonstrate that a bacterial SMC Wadjet complex can efficiently bypass obstacles larger than the SMC coiled coil lumen when they are tethered to the extruded DNA by a single-stranded DNA or RNA linker. This bypass is mediated by the selective entrapment of the linker within the SMC hinge channel, which functions as an obligate gate—permitting passage of the linker while retaining double-stranded DNA stably inside the SMC ring and keeping associated obstacles outside. We further show that eukaryotic SMC hinges similarly accommodate ssDNA, and that the hinge is dispensable for loop extrusion by Wadjet, altogether suggesting that obstacle bypass represents the conserved, long-sought function of the SMC hinge toroid. By integrating hinge bypass with loop extrusion, we provide a mechanistic framework for how DNA-entrapping SMC complexes can generate chromosomal loops densely decorated with obstacles
Chasing the storm: investigating the application of high-contrast imaging techniques in producing precise exoplanet light curves
Get PDFSubstellar companions such as exoplanets and brown dwarfs exhibit changes in brightness arising from top-of-atmosphere inhomogeneities, providing insights into their atmospheric structure and dynamics. This variability can be measured in the light curves of high-contrast companions from the ground by combining differential spectrophotometric monitoring techniques with high-contrast imaging. However, ground-based observations are sensitive to the effects of turbulence in Earth’s atmosphere, and while adaptive optics (AO) systems and bespoke data processing techniques help to mitigate these, residual systematics can limit photometric precision. Here, we inject artificial companions to data obtained with an AO system and a vector Apodizing Phase Plate coronagraph to test the level to which telluric and other systematics contaminate such light curves, and thus how well their known variability signals can be recovered. We find that varying companions are distinguishable from non-varying companions, but that variability amplitudes and periods cannot be accurately recovered when observations cover only a small number of periods. Residual systematics remain above the photon noise in the light curves but have not yet reached a noise floor. We also simulate observations to assess how specific systematic sources, such as non-common path aberrations and AO residuals, can impact aperture photometry as a companion moves through pupil-stabilized data. We show that only the lowest order aberrations are likely to affect flux measurements, but that thermal background noise is the dominant source of scatter in raw companion photometry. Predictive control and focal-plane wavefront sensing techniques will help to further reduce systematics in data of this type
The multitaxa functional diversity increases the resilience of biological natural capital in the Amazon - Dataset
No full textDataset containing abundance and functional trait data for bees, frugivorous butterflies, and vascular plants sampled in Carajás National Park (Pará, Brazil). The data were used to compute BNCR (Biological Resilience of Natural Capital) and BNCU (Biological Uniqueness of Natural Capital) indices for Serra dos Carajás via the functions provided in script_BNCU_BNCR_functions
Homogenised models of nutrient transport in a fibrous bioreactor scaffold
Get PDFBioreactor scaffolds must be designed to facilitate adequate nutrient delivery to the growing tissue they support. For perfusion bioreactors, the dominant transport process is determined by the scale of fluid velocity relative to diffusion and the geometry of the scaffold. In this paper, models of nutrient transport in a fibrous bioreactor scaffold are developed using homogenisation via multiscale asymptotics. The scaffold is modelled as an ensemble of aligned strings surrounded by viscous, slowly flowing fluid. Multiple scales analysis is carried out for various parameter regimes which give rise to macroscale transport models that incorporate the effects of advection, reaction and diffusion. Multiple scales in both space and time are employed when macroscale advection balances macroscale diffusion. The microscale model is solved to obtain the effective diffusion coefficient and simple solutions to the macroscale problem are presented for each regime
Asia's wolves and synergies with big cats
Get PDFIn Asia, carnivore conservation is often focused on charismatic big cats. Opportunities to conserve the entire carnivore guild are frequently overlooked by channeling conservation and mitigation efforts into single-species conservation. We synthesize experiences across Asia to explore these challenges and propose mitigations to maximize conservation benefits for the entire carnivore guild. Seven challenges for wolves (Canis lupus) in Asia are highlighted: wolves (1) have been neglected over decades of single-species conservation, (2) receive less cultural appreciation in many regions, (3) are subject to lax legislation and law enforcement, (4) are often blamed disproportionately for livestock depredation, (5) are often considered more abundant than they are, (6), receive disproportionately little attention from the scientific and conservation communities relative to their ecological importance, and (7) are threatened ecologically and genetically by increasing feral dog populations. As a result, the status of wolves across Asia is poorly documented, there is an enhanced risk of losing significant evolutionary lineages, and it detracts from research and conservation opportunities to preserve the entire carnivore guild. We propose various remedies, such as widening the scope of existing conservation programs, building awareness and knowledge of communities and law enforcement agencies, and more research to inform conservation and legislation