508 research outputs found

    Mental health care for parents of babies with congenital heart disease during intensive care unit admission: Systematic review and statement of best practice

    Get PDF
    INTRODUCTION: Congenital heart disease (CHD) is one of the most common causes of infant admission to pediatric intensive care and is associated with profound psychological stress for mothers, fathers and their infants. Intensive care unit admission represents an opportunity to offer evidence-based strategies to prevent or minimize severe psychological distress and promote secure bonding and attachment, alongside high-quality infant medical care. OBJECTIVES: We aimed to identify, synthesize and critically appraise published evidence on the efficacy and cost-effectiveness of mental health interventions delivered in neonatal, pediatric or cardiac intensive care units for parents of infants with CHD. A secondary goal was to develop recommendations for advancing health policy, practice and research in the field. METHODS: In accordance with a prospectively registered protocol (CRD42019114507), six electronic databases were systematically searched for studies reporting results of a controlled trial of a mental health intervention for parents of infants aged 0-12 months with a congenital anomaly requiring intensive care unit admission. To maximize generalizability of results, trials involving infants with any type of structural congenital anomaly requiring surgery were included. Outcomes included intervention type, process, efficacy, and cost-effectiveness. RESULTS: Across all forms of congenital anomaly, only five trials met inclusion criteria (four in CHD, one in gastrointestinal malformation). All interventions engaged parents face-to-face, but each had a distinct therapeutic approach (parent-infant interaction and bonding, early pediatric palliative care, psycho-education, parenting skills training, and family-centered nursing). Four of the five trials demonstrated efficacy in reducing maternal anxiety, although the quality of evidence was low. Positive results were also found for maternal coping, mother-infant attachment, parenting confidence and satisfaction with clinical care, as well as infant mental (but not psychomotor) development at 6 months. Mixed results were found for maternal depression and infant feeding. No evidence of efficacy was found for improving parent, infant or family quality of life, physical health or length of infant hospital stay, and there were no data on cost-effectiveness. CONCLUSIONS: Stronger evidence for the efficacy of mental health interventions to buffer the effects of intensive care unit admission for parents of infants with CHD is urgently needed. Robust, high-quality trials are lacking, despite the established need and demand, and health policies prioritizing parent mental health care in the context of early childhood adversity are needed

    Orbital-selective Kondo lattice and enigmatic f electrons emerging from inside the antiferromagnetic phase of a heavy fermion.

    Get PDF
    Novel electronic phenomena frequently form in heavy-fermions because of the mutual localized and itinerant nature of f-electrons. On the magnetically ordered side of the heavy-fermion phase diagram, f-moments are expected to be localized and decoupled from the Fermi surface. It remains ambiguous whether Kondo lattice can develop inside the magnetically ordered phase. Using spectroscopic imaging with scanning tunneling microscope, complemented by neutron scattering, x-ray absorption spectroscopy, and dynamical mean field theory, we probe the electronic states in antiferromagnetic USb2. We visualize a large gap in the antiferromagnetic phase within which Kondo hybridization develops below ~80 K. Our calculations indicate the antiferromagnetism and Kondo lattice to reside predominantly on different f-orbitals, promoting orbital selectivity as a new conception into how these phenomena coexist in heavy-fermions. Finally, at 45 K, we find a novel first order-like transition through abrupt emergence of nontrivial 5f-electronic states that may resemble the "hidden-order" phase of URu2Si2

    The contribution of genetic variants to disease depends on the ruler

    Get PDF
    Our understanding of the genetic basis of disease has evolved from descriptions of overall heritability or familiality to the identification of large numbers of risk loci. One can quantify the impact of such loci on disease using a plethora of measures, which can guide future research decisions. However, different measures can attribute varying degrees of importance to a variant. In this Analysis, we consider and contrast the most commonly used measures-specifically, the heritability of disease liability, approximate heritability, sibling recurrence risk, overall genetic variance using a logarithmic relative risk scale, the area under the receiver-operating curve for risk prediction and the population attributable fraction-and give guidelines for their use that should be explicitly considered when assessing the contribution of genetic variants to disease

    Recurrent Modification of a Conserved Cis-Regulatory Element Underlies Fruit Fly Pigmentation Diversity

    Get PDF
    The development of morphological traits occurs through the collective action of networks of genes connected at the level of gene expression. As any node in a network may be a target of evolutionary change, the recurrent targeting of the same node would indicate that the path of evolution is biased for the relevant trait and network. Although examples of parallel evolution have implicated recurrent modification of the same gene and cis-regulatory element (CRE), little is known about the mutational and molecular paths of parallel CRE evolution. In Drosophila melanogaster fruit flies, the Bric-à-brac (Bab) transcription factors control the development of a suite of sexually dimorphic traits on the posterior abdomen. Female-specific Bab expression is regulated by the dimorphic element, a CRE that possesses direct inputs from body plan (ABD-B) and sex-determination (DSX) transcription factors. Here, we find that the recurrent evolutionary modification of this CRE underlies both intraspecific and interspecific variation in female pigmentation in the melanogaster species group. By reconstructing the sequence and regulatory activity of the ancestral Drosophila melanogaster dimorphic element, we demonstrate that a handful of mutations were sufficient to create independent CRE alleles with differing activities. Moreover, intraspecific and interspecific dimorphic element evolution proceeded with little to no alterations to the known body plan and sex-determination regulatory linkages. Collectively, our findings represent an example where the paths of evolution appear biased to a specific CRE, and drastic changes in function were accompanied by deep conservation of key regulatory linkages. © 2013 Rogers et al

    Molecular evolution of HoxA13 and the multiple origins of limbless morphologies in amphibians and reptiles

    Get PDF
    Developmental processes and their results, morphological characters, are inherited through transmission of genes regulating development. While there is ample evidence that cis-regulatory elements tend to be modular, with sequence segments dedicated to different roles, the situation for proteins is less clear, being particularly complex for transcription factors with multiple functions. Some motifs mediating protein-protein interactions may be exclusive to particular developmental roles, but it is also possible that motifs are mostly shared among different processes. Here we focus on HoxA13, a protein essential for limb development. We asked whether the HoxA13 amino acid sequence evolved similarly in three limbless clades: Gymnophiona, Amphisbaenia and Serpentes. We explored variation in ω (dN/dS) using a maximum-likelihood framework and HoxA13sequences from 47 species. Comparisons of evolutionary models provided low ω global values and no evidence that HoxA13 experienced relaxed selection in limbless clades. Branch-site models failed to detect evidence for positive selection acting on any site along branches of Amphisbaena and Gymnophiona, while three sites were identified in Serpentes. Examination of alignments did not reveal consistent sequence differences between limbed and limbless species. We conclude that HoxA13 has no modules exclusive to limb development, which may be explained by its involvement in multiple developmental processes

    The Genetic Interpretation of Area under the ROC Curve in Genomic Profiling

    Get PDF
    Genome-wide association studies in human populations have facilitated the creation of genomic profiles which combine the effects of many associated genetic variants to predict risk of disease. The area under the receiver operator characteristic (ROC) curve is a well established measure for determining the efficacy of tests in correctly classifying diseased and non-diseased individuals. We use quantitative genetics theory to provide insight into the genetic interpretation of the area under the ROC curve (AUC) when the test classifier is a predictor of genetic risk. Even when the proportion of genetic variance explained by the test is 100%, there is a maximum value for AUC that depends on the genetic epidemiology of the disease, i.e. either the sibling recurrence risk or heritability and disease prevalence. We derive an equation relating maximum AUC to heritability and disease prevalence. The expression can be reversed to calculate the proportion of genetic variance explained given AUC, disease prevalence, and heritability. We use published estimates of disease prevalence and sibling recurrence risk for 17 complex genetic diseases to calculate the proportion of genetic variance that a test must explain to achieve AUC = 0.75; this varied from 0.10 to 0.74. We provide a genetic interpretation of AUC for use with predictors of genetic risk based on genomic profiles. We provide a strategy to estimate proportion of genetic variance explained on the liability scale from estimates of AUC, disease prevalence, and heritability (or sibling recurrence risk) available as an online calculator

    Enchantment in Business Ethics Research

    Get PDF
    This article draws attention to the importance of enchantment in business ethics research. Starting from a Weberian understanding of disenchantment, as a force that arises through modernity and scientific rationality, we show how rationalist business ethics research has become disenchanted as a consequence of the normalisation of positivist, quantitative methods of inquiry. Such methods absent the relational and lively nature of business ethics research and detract from the ethical meaning that can be generated through research encounters. To address this issue, we draw on the work of political theorist and philosopher, Jane Bennett, using this to show how interpretive qualitative research creates possibilities for enchantment. We identify three opportunities for reenchanting business ethics research related to: (i) moments of novelty or disruption; (ii) deep, meaningful attachments to things studied; and (iii) possibilities for embodied, affective encounters. In conclusion, we suggest that business ethics research needs to recognise and reorient scholarship towards an appreciation of the ethical value of interpretive, qualitative research as a source of potential enchantment

    New Insights into the Mechanisms of Embryonic Stem Cell Self-Renewal under Hypoxia: A Multifactorial Analysis Approach

    Get PDF
    Previous reports have shown that culturing mouse embryonic stem (mES) cells at different oxygen tensions originated different cell proliferation patterns and commitment stages depending on which signaling pathways are activated or inhibited to support the pluripotency state. Herein we provide new insights into the mechanisms by which oxygen is influencing mES cell self-renewal and pluripotency. A multifactorial approach was developed to rationally evaluate the singular and interactive control of MEK/ERK pathway, GSK-3 inhibition, and LIF/STAT3 signaling at physiological and non-physiological oxygen tensions. Collectively, our methodology revealed a significant role of GSK-3-mediated signaling towards maintenance of mES cell pluripotency at lower O2 tensions. Given the central role of this signaling pathway, future studies will need to focus on the downstream mechanisms involved in ES cell self-renewal under such conditions, and ultimately how these findings impact human models of pluripotency

    A search for the decay modes B+/- to h+/- tau l

    Get PDF
    We present a search for the lepton flavor violating decay modes B+/- to h+/- tau l (h= K,pi; l= e,mu) using the BaBar data sample, which corresponds to 472 million BBbar pairs. The search uses events where one B meson is fully reconstructed in one of several hadronic final states. Using the momenta of the reconstructed B, h, and l candidates, we are able to fully determine the tau four-momentum. The resulting tau candidate mass is our main discriminant against combinatorial background. We see no evidence for B+/- to h+/- tau l decays and set a 90% confidence level upper limit on each branching fraction at the level of a few times 10^-5.Comment: 15 pages, 7 figures, submitted to Phys. Rev.
    • …
    corecore