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Toll-like receptor-induced immune responses during early childhood and their associations with clinical outcomes following acute illness among infants in sub-Saharan Africa
No full textSeverely ill children in low- and middle-income countries (LMICs) experience high rates of mortality from a broad range of infectious diseases, with the risk of infection-related death compounded by co-existing undernutrition. How undernutrition and acute illness impact immune responses in young children in LMICs remains understudied, and it is unclear what aspects of immunity are compromised in this highly vulnerable population. To address this knowledge gap, we profiled longitudinal whole blood cytokine responses to Toll-like receptor (TLR) ligands among severely ill children (n=63; 2-23 months old) with varied nutritional backgrounds, enrolled in the CHAIN Network cohort from Kampala, Uganda, and Kilifi, Kenya, and compared these responses to similar-aged well children in local communities (n=41). Cytokine responses to ligands for TLR-4 and TLR-7/8, as well as Staphylococcus enterotoxin B (SEB), demonstrated transient impairment in T cell function among acutely ill children, whereas innate cytokine responses were exaggerated during both acute illness and following clinical recovery. Nutritional status was associated with the magnitude of cytokine responses in all stimulated conditions. Among children who died following hospital discharge or required hospital re-admission, exaggerated production of interleukin-7 (IL-7) to all stimulation conditions, as well as leukopenia with reduced lymphocyte and monocyte counts, were observed. Overall, our findings demonstrate exaggerated innate immune responses to pathogen-associated molecules among acutely ill young children that persist during recovery. Heightened innate immune responses to TLR ligands may contribute to chronic systemic inflammation and dysregulated responses to subsequent infectious challenges. Further delineating mechanisms of innate immune dysregulation in this population should be prioritized to identify novel interventions that promote immune homeostasis and improve outcomes
A unified genealogy of modern and ancient genomes
No full textThe sequencing of modern and ancient genomes from around the world has
revolutionized our understanding of human history and evolution. However, the problem of how
best to characterize ancestral relationships from the totality of human genomic variation remains
unsolved. Here, we address this challenge with non-parametric methods that enable us to infer a
unified genealogy of modern and ancient humans. This compact representation of multiple
datasets explores the challenges of missing and erroneous data and uses ancient samples to
constrain and date relationships. We demonstrate the power of the method to recover
relationships between individuals and populations, as well as to identify descendants of ancient
samples. Finally, we introduce a simple non-parametric estimator of ancestor geographical
location that recapitulates key events in human histor
Consolidated Health Economic Evaluation Reporting Standards 2022 (CHEERS 2022) statement: updated reporting guidance for health economic evaluations
No full textHealth economic evaluations are comparative analyses of alternative courses of action in terms of their costs and consequences. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement, published in 2013, was created to ensure health economic evaluations are identifiable, interpretable, and useful for decision making. It was intended as guidance to help authors report accurately which health interventions were being compared and in what context, how the evaluation was undertaken, what the findings were, and other details that may aid readers and reviewers in interpretation and use of the study. The new CHEERS 2022 statement replaces previous CHEERS reporting guidance. It reflects the need for guidance that can be more easily applied to all types of health economic evaluation, new methods and developments in the field, as well as the increased role of stakeholder involvement including patients and the public. It is also broadly applicable to any form of intervention intended to improve the health of individuals or the population, whether simple or complex, and without regard to context (such as health care, public health, education, social care, etc). This summary article presents the new CHEERS 2022 28-item checklist and recommendations for each item. The CHEERS 2022 statement is primarily intended for researchers reporting economic evaluations for peer reviewed journals as well as the peer reviewers and editors assessing them for publication. However, we anticipate familiarity with reporting requirements will be useful for analysts when planning studies. It may also be useful for health technology assessment bodies seeking guidance on reporting, as there is an increasing emphasis on transparency in decision making
A special day ay the Acropolis Museum- Family trail
No full textTo Mουσείο Ακρόπολης προσκαλεί τις οικογένειες να περιηγηθούν στις αίθουσές του και να ανακαλύψουν 10 από τα μοναδικά εκθέματά του, με τη βοήθεια του φυλλαδίου «Μια ξεχωριστή μέρα στο Μουσείο Ακρόπολης». Τα παιδιά ολοκληρώνουν την επίσκεψη ζωγραφίζοντας το αγαπημένο τους έκθεμα και στέλνοντας κάρτες στο Μουσείο με τις ευχές τους.Τhe Acropolis Museum invites families to go on a tour in its galleries with the help of the booklet “A special day at the Acropolis Museum”. Children search for 10 unique exhibits, draw their favorite one and send a card to the Museum with their wishes
Ολύμπια Αινίγματα: Αναζητώντας τους θεούς του Ολύμπου στο Μουσείο της Ακρόπολης
Full text linkΣχέδιο προετοιμασίας ανεξάρτητης επίσκεψης στο Μουσείο Ακρόπολης με θέμα "Ολύμπια Αινίγματα: Αναζητώντας τους θεούς του Ολύμπου στο Μουσείο της Ακρόπολης
Consolidated Health Economic Evaluation Reporting Standards 2022 (CHEERS 2022) statement: updated reporting guidance for health economic evaluations
No full textHealth economic evaluations are comparative analyses of alternative courses of action in terms of their costs and consequences. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement, published in 2013, was created to ensure health economic evaluations are identifiable, interpretable, and useful for decision making. It was intended as guidance to help authors report accurately which health interventions were being compared and in what context, how the evaluation was undertaken, what the findings were, and other details that may aid readers and reviewers in interpretation and use of the study. The new CHEERS 2022 statement replaces previous CHEERS reporting guidance. It reflects the need for guidance that can be more easily applied to all types of health economic evaluation, new methods and developments in the field, as well as the increased role of stakeholder involvement including patients and the public. It is also broadly applicable to any form of intervention intended to improve the health of individuals or the population, whether simple or complex, and without regard to context (such as health care, public health, education, social care, etc). This summary article presents the new CHEERS 2022 28-item checklist and recommendations for each item. The CHEERS 2022 statement is primarily intended for researchers reporting economic evaluations for peer reviewed journals as well as the peer reviewers and editors assessing them for publication. However, we anticipate familiarity with reporting requirements will be useful for analysts when planning studies. It may also be useful for health technology assessment bodies seeking guidance on reporting, as there is an increasing emphasis on transparency in decision making
Memory modification and authenticity: a narrative approach
No full textThe potential of memory modification techniques (MMTs) has raised concerns and sparked a debate in neuroethics, particularly in the context of identity and authenticity. This paper addresses the question whether and how MMTs influence authenticity. I proceed by drawing two distinctions within the received views on authenticity. From this, I conclude that an analysis of MMTs based on a dual-basis, process view of authenticity is warranted, which implies that the influence of MMTs on authenticity crucially depends on the specifics of how memory modification would eventually work. Therefore, I continue with a systematic analysis of possible properties of MMTs in which I distinguish between the dimensions of memories and the kinds of experiences that can be modified as well as the properties of the process of memory modification. The impact of MMTs on authenticity is analyzed regarding the possible properties of MMTs and based on a narrative approach to authenticity which fulfills the requirements of a dual-basis, process view of authenticity. Lastly, I explore the potential of MMTs to shift the balance between self-discovery and self-creation within authenticity and thereby alter the concept itself as well as the value of authenticity
The first adult mantis lacewing from Baltic amber, with an evaluation of the post-Cretaceous loss of morphological diversity of raptorial appendages in Mantispidae
No full textMantis lacewings (Neuroptera: Mantispidae) are prominent and charismatic predatory representatives of Insecta. Nevertheless, representatives of the group are surprisingly scarce in Paleogene deposits after a relative abundance of specimens known from Cretaceous. Here we present Mantispa? damzenogedanica sp. nov., representing the first adult of Mantispidae described from Baltic amber and the only Eocene adult mantispid hitherto preserved in amber. The new fossil species is also among the earliest representatives of Mantispinae, certainly the oldest adult of this group described from amber. Additionally, we discuss the changes through time in the ecological morphospace within Mantispidae based on the morphological diversity (≈disparity) of the raptorial legs. Possible explanations for the post-Cretaceous decline in the morphological diversity of mantis lacewings are posited
Linking DNA repair and cell cycle progression through serine ADP-ribosylation of histones
No full textAlthough serine ADP-ribosylation (Ser-ADPr) by Poly(ADP-ribose)-polymerases is a cornerstone of the DNA damage response, how this regulates DNA repair and genome stability is unknown. Here, we exploit the ability to manipulate histone genes in Dictyostelium to identify that ADPr of the histone variant H3b at S10 and S28 maintains genome stability by integrating double strand break (DSB) repair with mitotic entry. Given the critical requirement for mitotic H3S10/28 phosphorylation, we develop separation of function mutations that maintain S10 phosphorylation whilst disrupting ADPr. Mechanistically, this reveals a requirement for H3bS10/28 ADPr in non-homologous end-joining by recruiting Ku to DSBs. Moreover, this also identifies H3bS10/S28 ADPr is critical to prevent premature mitotic entry with unresolved DNA damage, thus maintaining genome stability. Together, these data demonstrate how serine ADPr of histones coordinates DNA repair with cell cycle progression to maintain genome stability
Ag-catalyzed insertion of alkynyl carbenes into C-C bonds of β-ketocarbonyls: a formal C(sp2) insertion
No full textHere we report a silver-catalyzed alkynyl carbene insertion into β-ketocarbonyls using alkynyl N-nosylhydrazones as alkynyl carbene precursors, which provides access to trisubstituted allenyl ketones. This reaction represents the first example of an alkynyl carbene insertion into a C–C σ bond, affording products homologated with an sp2 carbon center. The products are useful substrates for further transformations. Experimental investigations and theoretical calculations suggest the reaction proceeds through a stepwise enol cyclopropanation/retro-aldol pathway