Characterizing the gut microbiome in trauma: significant changes in microbial diversity occur early after severe injury.

Background:Recent studies have demonstrated the vital influence of commensal microbial communities on human health. The central role of the gut in the response to injury is well described; however, no prior studies have used culture-independent profiling techniques to characterize the gut microbiome after severe trauma. We hypothesized that in critically injured patients, the gut microbiome would undergo significant compositional changes in the first 72 hours after injury. Methods:Trauma stool samples were prospectively collected via digital rectal examination at the time of presentation (0 hour). Patients admitted to the intensive care unit (n=12) had additional stool samples collected at 24 hours and/or 72 hours. Uninjured patients served as controls (n=10). DNA was extracted from stool samples and 16S rRNA-targeted PCR amplification was performed; amplicons were sequenced and binned into operational taxonomic units (OTUs; 97% sequence similarity). Diversity was analyzed using principle coordinates analyses, and negative binomial regression was used to determine significantly enriched OTUs. Results:Critically injured patients had a median Injury Severity Score of 27 and suffered polytrauma. At baseline (0 hour), there were no detectable differences in gut microbial community diversity between injured and uninjured patients. Injured patients developed changes in gut microbiome composition within 72 hours, characterized by significant alterations in phylogenetic composition and taxon relative abundance. Members of the bacterial orders Bacteroidales, Fusobacteriales and Verrucomicrobiales were depleted during 72 hours, whereas Clostridiales and Enterococcus members enriched significantly. Discussion:In this initial study of the gut microbiome after trauma, we demonstrate that significant changes in phylogenetic composition and relative abundance occur in the first 72 hours after injury. This rapid change in intestinal microbiota represents a critical phenomenon that may influence outcomes after severe trauma. A better understanding of the nature of these postinjury changes may lead to the ability to intervene in otherwise pathological clinical trajectories. Level of evidence:III. Study type:Prognostic/epidemiological

A Pluralist Account of Knowledge as a Natural Kind

In an attempt to address some long-standing issues of epistemology, Hilary Kornblith proposes that knowledge is a natural kind the identification of which is the unique responsibility of one particular science: cognitive ethology. As Kornblith sees it, the natural kind thus picked out is knowledge as construed by reliabilism. Yet the claim that cognitive ethology has this special role has not convinced all critics. The present article argues that knowledge plays a causal and explanatory role within many of our more fruitful current theories, diverging from the reliabilist conception even in disciplines that are closely related to cognitive ethology, and thus still dealing with knowledge as a natural as opposed to a social phenomenon, where special attention will be given to cognitive neuroscience. However, rather than discarding the natural kind approach altogether, it is argued that many of Kornblith’s insights can in fact be preserved within a framework that is both naturalist and pluralist

Epistemic Schmagency?

Constructivist approaches in epistemology and ethics offer a promising account of normativity. But constructivism faces a powerful Schmagency Objection, raised by David Enoch. While Enoch’s objection has been widely discussed in the context of practical norms, no one has yet explored how the Schmagency Objection might undermine epistemic constructivism. In this paper, I rectify that gap. First, I develop the objection against a prominent form of epistemic constructivism, Belief Constitutivism. Belief Constitutivism is susceptible to a Schmagency Objection, I argue, because it locates the source of normativity in the belief rather than the agent. In the final section, I propose a version of epistemic constructivism that locates epistemic normativity as constitutive of agency. I argue that this version has the resources to respond to the Schmagency Objection

Predictors of Successful Decannulation Using a Tracheostomy Retainer in Patients with Prolonged Weaning and Persisting Respiratory Failure

Background: For percutaneously tracheostomized patients with prolonged weaning and persisting respiratory failure, the adequate time point for safe decannulation and switch to noninvasive ventilation is an important clinical issue. Objectives: We aimed to evaluate the usefulness of a tracheostomy retainer (TR) and the predictors of successful decannulation. Methods: We studied 166 of 384 patients with prolonged weaning in whom a TR was inserted into a tracheostoma. Patients were analyzed with regard to successful decannulation and characterized by blood gas values, the duration of previous spontaneous breathing, Simplified Acute Physiology Score (SAPS) and laboratory parameters. Results: In 47 patients (28.3%) recannulation was necessary, mostly due to respiratory decompensation and aspiration. Overall, 80.6% of the patients could be liberated from a tracheostomy with the help of a TR. The need for recannulation was associated with a shorter duration of spontaneous breathing within the last 24/48 h (p < 0.01 each), lower arterial oxygen tension (p = 0.025), greater age (p = 0.025), and a higher creatinine level (p = 0.003) and SAPS (p < 0.001). The risk for recannulation was 9.5% when patients breathed spontaneously for 19-24 h within the 24 h prior to decannulation, but 75.0% when patients breathed for only 0-6 h without ventilatory support (p < 0.001). According to ROC analysis, the SAPS best predicted successful decannulation {[}AUC 0.725 (95% CI: 0.634-0.815), p < 0.001]. Recannulated patients had longer durations of intubation (p = 0.046), tracheostomy (p = 0.003) and hospital stay (p < 0.001). Conclusion: In percutaneously tracheostomized patients with prolonged weaning, the use of a TR seems to facilitate and improve the weaning process considerably. The duration of spontaneous breathing prior to decannulation, age and oxygenation describe the risk for recannulation in these patients. Copyright (c) 2012 S. Karger AG, Base

Metacognition as Evidence for Evidentialism

Metacognition is the monitoring and controlling of cognitive processes. I examine the role of metacognition in ‘ordinary retrieval cases’, cases in which it is intuitive that via recollection the subject has a justified belief. Drawing on psychological research on metacognition, I argue that evidentialism has a unique, accurate prediction in each ordinary retrieval case: the subject has evidence for the proposition she justifiedly believes. But, I argue, process reliabilism has no unique, accurate predictions in these cases. I conclude that ordinary retrieval cases better support evidentialism than process reliabilism. This conclusion challenges several common assumptions. One is that non-evidentialism alone allows for a naturalized epistemology, i.e., an epistemology that is fully in accordance with scientific research and methodology. Another is that process reliabilism fares much better than evidentialism in the epistemology of memory

Development of a Consensus-Based Definition of Focused Assessment with Sonography for Trauma in Children

Importance: The wide variation in the accuracy and reliability of the Focused Assessment With Sonography for Trauma (FAST) and the extended FAST (E-FAST) for children after blunt abdominal trauma reflects user expertise. FAST and E-FAST that are performed by experts tend to be more complete, better quality, and more often clinically valuable. Objective: To develop definitions of a complete, high-quality, and accurate interpretation for the FAST and E-FAST in children with injury using an expert, consensus-based modified Delphi technique. Design, Setting, and Participants: This consensus-based qualitative study was conducted between May 1 to June 30, 2021. It used a scoping review and iterative Delphi technique and involved 2 rounds of online surveys and a live webinar to achieve consensus among a 26-member panel. This panel consisted of international experts in pediatric emergency point-of-care ultrasonography. Main Outcomes and Measures: Definitions of complete, high-quality, and accurate FAST and E-FAST studies for children after injury. Results: Of the 29 invited pediatric FAST experts, 26 (15 men [58%]) agreed to participate in the panel. All 26 panelists completed the 2 rounds of surveys, and 24 (92%) participated in the live and asynchronous online discussions. Consensus was reached on FAST and E-FAST study definitions, and the panelists rated these 5 anatomic views as important and appropriate for a complete FAST: right upper-quadrant abdominal view, left upper-quadrant abdominal view, suprapubic views (transverse and sagittal), and subxiphoid cardiac view. For E-FAST, the same FAST anatomic views with the addition of the lung or pneumothorax view were deemed appropriate and important. In addition, the panelists rated a total of 32 landmarks as important for assessing completeness. Similarly, the panelists rated 14 statements on quality and 20 statements on accurate interpretation as appropriate. Conclusions and Relevance: This qualitative study generated definitions for complete FAST and E-FAST studies with high image quality and accurate interpretation in children with injury. These definitions are similar to those in adults with injury and may be used for future education, quality assurance, and research. Future research may focus on interpretation of trace volumes of abdominal free fluid and the use of serial FAST

Financial considerations in the conduct of multi-centre randomised controlled trials: evidence from a qualitative study.

National Coordinating Centre for Research Methodology; Medical Research Council, UK Department of Health; Chief Scientist OfficeNot peer reviewedPublisher PD

Study protocol to investigate the effect of a lifestyle intervention on body weight, psychological health status and risk factors associated with disease recurrence in women recovering from breast cancer treatment

Background Breast cancer survivors often encounter physiological and psychological problems related to their diagnosis and treatment that can influence long-term prognosis. The aim of this research is to investigate the effects of a lifestyle intervention on body weight and psychological well-being in women recovering from breast cancer treatment, and to determine the relationship between changes in these variables and biomarkers associated with disease recurrence and survival. Methods/design Following ethical approval, a total of 100 patients will be randomly assigned to a lifestyle intervention (incorporating dietary energy restriction in conjunction with aerobic exercise training) or normal care control group. Patients randomised to the dietary and exercise intervention will be given individualised healthy eating dietary advice and written information and attend moderate intensity aerobic exercise sessions on three to five days per week for a period of 24 weeks. The aim of this strategy is to induce a steady weight loss of up to 0.5 Kg each week. In addition, the overall quality of the diet will be examined with a view to (i) reducing the dietary intake of fat to ~25% of the total calories, (ii) eating at least 5 portions of fruit and vegetables a day, (iii) increasing the intake of fibre and reducing refined carbohydrates, and (iv) taking moderate amounts of alcohol. Outcome measures will include body weight and body composition, psychological health status (stress and depression), cardiorespiratory fitness and quality of life. In addition, biomarkers associated with disease recurrence, including stress hormones, estrogen status, inflammatory markers and indices of innate and adaptive immune function will be monitored. Discussion This research will provide valuable information on the effectiveness of a practical, easily implemented lifestyle intervention for evoking positive effects on body weight and psychological well-being, two important factors that can influence long-term prognosis in breast cancer survivors. However, the added value of the study is that it will also evaluate the effects of the lifestyle intervention on a range of biomarkers associated with disease recurrence and survival. Considered together, the results should improve our understanding of the potential role that lifestyle-modifiable factors could play in saving or prolonging lives

The genealogical method in epistemology

In 1990 Edward Craig published a book called Knowledge and the State of Nature in which he introduced and defended a genealogical approach to epistemology. In recent years Craig’s book has attracted a lot of attention, and his distinctive approach has been put to a wide range of uses including anti-realist metaepistemology, contextualism, relativism, anti-luck virtue epistemology, epistemic injustice, value of knowledge, pragmatism and virtue epistemology. While the number of objections to Craig’s approach has accumulated, there has been no sustained attempt to develop answers to these objections. In this paper we provide answers to seven important objections in the literature