Loss of microbial diversity and pathogen domination of the gut microbiota in critically ill patients

Among long-stay critically ill patients in the adult intensive care unit (ICU), there are often marked changes in the complexity of the gut microbiota. However, it remains unclear whether such patients might benefit from enhanced surveillance or from interventions targeting the gut microbiota or the pathogens therein. We therefore undertook a prospective observational study of 24 ICU patients, in which serial faecal samples were subjected to shotgun metagenomic sequencing, phylogenetic profiling and microbial genome analyses. Two-thirds of the patients experienced a marked drop in gut microbial diversity (to an inverse Simpson's index of <4) at some stage during their stay in the ICU, often accompanied by the absence or loss of potentially beneficial bacteria. Intravenous administration of the broad-spectrum antimicrobial agent meropenem was significantly associated with loss of gut microbial diversity, but the administration of other antibiotics, including piperacillin/tazobactam, failed to trigger statistically detectable changes in microbial diversity. In three-quarters of ICU patients, we documented episodes of gut domination by pathogenic strains, with evidence of cryptic nosocomial transmission of Enterococcus faecium. In some patients, we also saw an increase in the relative abundance of apparent commensal organisms in the gut microbiome, including the archaeal species Methanobrevibacter smithii. In conclusion, we have documented a dramatic absence of microbial diversity and pathogen domination of the gut microbiota in a high proportion of critically ill patients using shotgun metagenomics

Structural and effective connectivity reveals potential network-based influences on category-sensitive visual areas

Visual category perception is thought to depend on brain areas that respond specifically when certain categories are viewed. These category-sensitive areas are often assumed to be modules (with some degree of processing autonomy) and to act predominantly on feedforward visual input. This modular view can be complemented by a view that treats brain areas as elements within more complex networks and as influenced by network properties. This network-oriented viewpoint is emerging from studies using either diffusion tensor imaging to map structural connections or effective connectivity analyses to measure how their functional responses influence each other. This literature motivates several hypotheses that predict category-sensitive activity based on network properties. Large, long-range fiber bundles such as inferior fronto-occipital, arcuate and inferior longitudinal fasciculi are associated with behavioural recognition and could play crucial roles in conveying backward influences on visual cortex from anterior temporal and frontal areas. Such backward influences could support top-down functions such as visual search and emotion-based visual modulation. Within visual cortex itself, areas sensitive to different categories appear well-connected (e.g., face areas connect to object- and motion sensitive areas) and their responses can be predicted by backward modulation. Evidence supporting these propositions remains incomplete and underscores the need for better integration of DTI and functional imaging

Stay in the game: Gender, family formation and alternative trajectories in the academic life course. Social forces 87

ABSTRACT Academic careers have traditionally been conceptualized as pipelines, through which young scholars move seamlessly from graduate school to tenure-track positions. This model often fails to capture the experiences of female Ph.D. recipients, who become tenure-track assistant professors at lower rates than do their male counterparts. What do these women do instead? We use panel data from the 1983-1995 Surveys of Doctorate Recipients to explore the early careers of Ph.D. recipients. Our results show that female doctorate recipients are disproportionately likely to be employed as adjunct faculty or exit the paid labor force, especially if they have young children. Contrary to conventional wisdom, adjunct professorships provide a better opportunity for getting a tenure-track job down the road than do nonteaching positions inside or outside of academia. Collectively these findings show that the normative academic life course is both complex and permeable

Anticoagulation therapy in children

Thromboembolic disease (TED) is increasingly recognized as a major cause of morbidity and mortality in tertiary pediatrics. Children younger than 1 year of age and teenage girls are at greatest risk of thromboembolism. Although anticoagulation therapy is the treatment of choice for TED, the treatment strategy is often difficult, especially in children. Treatment relies largely on anticoagulation with heparin and warfarin. Recommendations for antithrombotic therapy in children have been loosely extrapolated from recommendations for adults; however, it is likely that optimal treatment of children with TED differs from adults because of important ontogenic features of hemostasis that affect both the pathophysiology of the thrombotic processes and the response to antithrombotic agents. Until recently, the primary treatment for TED has been unfractionated heparin (UFH) in conjunction with warfarin. Warfarin, the most commonly used oral anticoagulant, acts through inhibition of the vitamin K-dependent transcarboxylation reactions that convert precursors of clotting factors into their active form. Appropriate use of UFH and warfarin requires close patient monitoring and dosage adjustments to ensure tolerability and efficacy. In recent years, low molecular weight heparins (LMWH) have become available as alternatives to UFH and warfarin, for both the prevention and treatment of TED. Potentially, LMWH have significant advantages. They have superior pharmacokinetics, which results in minimal laboratory monitoring, offering important benefits to children with poor venous access. Based on available data, LMWHs are at least as effective and well tolerated as UFH, and are more convenient. Although LMWHs are more expensive than UFH, the expense is likely to be offset by savings from a reduced hospital stay