107 research outputs found

    How Does Blood-Retinal Barrier Breakdown Relate to Death and Disability in Pediatric Cerebral Malaria?

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    Background In cerebral malaria, the retina can be used to understand disease pathogenesis. The mechanisms linking sequestration, brain swelling and death remain poorly understood. We hypothesized that retinal vascular leakage would be associated with brain swelling. Methods We used retinal angiography to study blood-retinal barrier integrity. We analyzed retinal leakage, histopathology, brain MRI, and associations with death and neurological disability in prospective cohorts of Malawian children with cerebral malaria. Results Three types of retinal leakage were seen: Large focal leak (LFL), punctate leak (PL) and vessel leak. LFL and PL were associated with death (OR 13.20, 95%CI 5.21-33.78 and 8.58, 2.56-29.08 respectively), and brain swelling (p<0.05). Vessel leak and macular non-perfusion were associated with neurological disability (3.71, 1.26-11.02 and 9.06, 1.79-45.90). LFL was observed as an evolving retinal hemorrhage. A core of fibrinogen and monocytes was found in 39 (93%) white-centered hemorrhages. Conclusions Blood-retina barrier breakdown occurs in three patterns in cerebral malaria. Associations between LFL, brain swelling, and death suggest that the rapid accumulation of cerebral hemorrhages, with accompanying fluid egress, may cause fatal brain swelling. Vessel leak from barrier dysfunction, and non-perfusion were not associated with severe brain swelling, but with neurological deficits, suggesting hypoxic injury in survivors

    Demonstration of a timescale based on a stable optical carrier

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    We report on the first timescale based entirely on optical technology. Existing timescales, including those incorporating optical frequency standards, rely exclusively on microwave local oscillators owing to the lack of an optical oscillator with the required frequency predictability and stability for reliable steering. We combine a cryogenic silicon cavity exhibiting improved long-term stability and an accurate 87 Sr lattice clock to form a timescale that outperforms them all. Our timescale accumulates an estimated time error of only 48 ± 94     ps over 34 days of operation. Our analysis indicates that this timescale is capable of reaching a stability below 1 × 10 − 17 after a few months of averaging, making timekeeping at the 10 − 18 level a realistic prospect

    Comprehension Syntax

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    The syntax of comprehensions is very close to the syntax of a number of practical database query languages and is, we believe, a better starting point than first-order logic for the development of database languages. We give an informal account of a language based on comprehension syntax that deals uniformly with a variety of collection types; it also includes pattern matching, variant types and function definition. We show, again informally, how comprehension syntax is a natural fragment of structural recursion, a much more powerful programming paradigm for collection types. We also show that a very small &quot;abstract syntax language&quot; can serve as a basis for the implementation and optimization of comprehension syntax

    B cell–intrinsic signaling through IL-21 receptor and STAT3 is required for establishing long-lived antibody responses in humans

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    Engagement of cytokine receptors by specific ligands activate Janus kinase–signal transducer and activator of transcription (STAT) signaling pathways. The exact roles of STATs in human lymphocyte behavior remain incompletely defined. Interleukin (IL)-21 activates STAT1 and STAT3 and has emerged as a potent regulator of B cell differentiation. We have studied patients with inactivating mutations in STAT1 or STAT3 to dissect their contribution to B cell function in vivo and in response to IL-21 in vitro. STAT3 mutations dramatically reduced the number of functional, antigen (Ag)-specific memory B cells and abolished the ability of IL-21 to induce naive B cells to differentiate into plasma cells (PCs). This resulted from impaired activation of the molecular machinery required for PC generation. In contrast, STAT1 deficiency had no effect on memory B cell formation in vivo or IL-21–induced immunoglobulin secretion in vitro. Thus, STAT3 plays a critical role in generating effector B cells from naive precursors in humans. STAT3-activating cytokines such as IL-21 thus underpin Ag-specific humoral immune responses and provide a mechanism for the functional antibody deficit in STAT3-deficient patients

    From Democratic Peace to Democratic Distinctiveness: A Critique of Democratic Exceptionalism in Peace and Conflict Studies

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    Reviewing horizontalization: the challenge of analysis in Brazilian foreign policy

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    Multiscale Molecular Simulations of Polymer-Matrix Nanocomposites

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