Impaired upper respiratory tract barrier function during postnatal development predisposes to invasive pneumococcal disease

Infants are highly susceptible to invasive respiratory and gastrointestinal infections. To elucidate the age-dependent mechanism(s) that drive bacterial spread from the mucosa, we developed an infant mouse model using the prevalent pediatric respiratory pathogen, Streptococcus pneumoniae (Spn). Despite similar upper respiratory tract (URT) colonization levels, the survival rate of Spn-infected infant mice was significantly decreased compared to adults and corresponded with Spn dissemination to the bloodstream. An increased rate of pneumococcal bacteremia in early life beyond the newborn period was attributed to increased bacterial translocation across the URT barrier. Bacterial dissemination in infant mice was independent of URT monocyte or neutrophil infiltration, phagocyte-derived ROS or RNS, inflammation mediated by toll-like receptor 2 or interleukin 1 receptor signaling, or the pore-forming toxin pneumolysin. Using molecular barcoding of Spn, we found that only a minority of bacterial clones in the nasopharynx disseminated to the blood in infant mice, indicating the absence of robust URT barrier breakdown. Rather, transcriptional profiling of the URT epithelium revealed a failure of infant mice to upregulate genes involved in the tight junction pathway. Expression of many such genes was also decreased in early life in humans. Infant mice also showed increased URT barrier permeability and delayed mucociliary clearance during the first two weeks of life, which corresponded with tighter attachment of bacteria to the respiratory epithelium. Together, these results demonstrate a window of vulnerability during postnatal development when altered mucosal barrier function facilitates bacterial dissemination

Adaptations to Climate-Mediated Selective Pressures in Humans

Humans inhabit a remarkably diverse range of environments, and adaptation through natural selection has likely played a central role in the capacity to survive and thrive in extreme climates. Unlike numerous studies that used only population genetic data to search for evidence of selection, here we scan the human genome for selection signals by identifying the SNPs with the strongest correlations between allele frequencies and climate across 61 worldwide populations. We find a striking enrichment of genic and nonsynonymous SNPs relative to non-genic SNPs among those that are strongly correlated with these climate variables. Among the most extreme signals, several overlap with those from GWAS, including SNPs associated with pigmentation and autoimmune diseases. Further, we find an enrichment of strong signals in gene sets related to UV radiation, infection and immunity, and cancer. Our results imply that adaptations to climate shaped the spatial distribution of variation in humans

CDKN2B-AS1 Genotype–Glaucoma Feature Correlations in Primary Open-Angle Glaucoma Patients From the United States

To assess the association between single nucleotide polymorphisms (SNPs) of the gene region containing cyclin dependent kinase inhibitor 2B antisense noncoding RNA (CDKN2B-AS1) and glaucoma features among primary open-angle glaucoma (POAG) patients

Acquiring, Applying and Retaining Knowledge Through Debriefing for Meaningful Learning

Abstract Acquiring, Retaining and Applying Knowledge Through Use of Debriefing for Meaningful Learning (DML). Background Developing competence in nursing care is a critical expectation of nursing students. Knowledge acquisition, application and retention are the primary building blocks of competence. DML debriefing offers an opportunity to ensure that students master critical components of nursing they might not otherwise learn and to remove epistemological roadblocks to knowledge development. Methods Eighty-two traditional prelicensure baccalaureate nursing students from a single school participated in the study. This quasi-experimental pretest, posttest study explored the impact of the use of Debriefing for Meaningful Learning compared with customary debriefing on the development of knowledge about care of the patient with a neurologic condition and knowledge retention 4 weeks later. Results There was a significant difference in knowledge acquisition, knowledge retention, with DML compared to customary debriefing. Conclusions These findings are significant for nurse educators using simulation to potentiate clinical competence in prelicensure students and add to the growing evidence regarding the impact of debriefing

Using the demand for hunting licences to evaluate contingent valuation estimates of willingness to pay

Taking advantage of differences in inflation adjusted licence prices over time, the demand for hunting licences is estimated. This introduces a different type of validity test which compares willingness to pay derived from actual licence demand to estimates of hunting benefits derived by the contingent valuation method. Willingness to pay estimates for deer and elk hunting derived from contingent valuation are statistically less than corresponding estimates from the actual licence sale demand analysis.

More than a Meme: The Dunning-Kruger Effect as an Opportunity for Positive Change in Nursing Education

The Dunning–Kruger Effect (DKE) describes the cognitive bias in which novices tend to overestimate performance or competence while experts tend to underestimate. Those who are lacking in competence do not have the skills to accurately recognize deficient performance. Subjective assessment is used widely in simulation learning and in nursing curricula, yet often without expert feedback and reflective discussions, which can result in mistakes being overlooked and encoded, which could subsequently result in clinical errors. The prevalence of DKE should not be interpreted solely as a deprecation of the use of subjective measures, but rather as an indicator of the need for improving self-reflection, metacognition, and an opportunity for formative feedback

Assessment and treatment of nonsurgical thumb carpometacarpal joint osteoarthritis: A modified Delphi-based consensus paper of the American Society of Hand Therapists.

BACKGROUND: While the literature is abundant on hand therapy assessment and treatment of nonsurgical thumb carpometacarpal (CMC) osteoarthritis (OA), clarity and uniformity are meager, making it a desirable diagnosis to establish expert consensus. PURPOSE: This study aimed to ascertain if consensus exists for the assessment and treatment of nonsurgical management of thumb CMC OA in the hand therapy clinical setting. STUDY DESIGN: This was a consensus paper via the modified Delphi approach. METHODS: A modified Delphi method was used to determine consensus among an expert panel, including hand therapists and hand surgeons, via two online surveys. A consensus paper steering committee (from the American Society of Hand Therapist\u27s research division) designed the surveys and analyzed responses. Consensus was established as 75% agreement among the expert panel. Demographic information was collected from the expert panel. RESULTS: The expert panel included 34 hand therapists and seven hand surgeons. The survey response rates were 93.6% for the first survey and 90.2% for the second survey. Consensus recommendations were classified according to the World Health Organization categorization. These included evaluating the body structures for clinical signs/clinical testing and body functions for pain, range of motion for palmar abduction, radial abduction, opposition, and thumb metacarpal phalangeal flexion/extension, and grip and tripod pinch strength. Further consensus recommendations were for the assessment of function using a region-specific, upper extremity patient-reported outcome measure (activity and participation), environmental factors, outcome expectation, and illness perception within the patient\u27s unique environmental and social contexts. Treatment recommendations included the use of an orthosis during painful activities, a dynamic stability program (stable C posture, release of tight adductors, and strengthening of stabilizers), patient education, joint protection techniques, adaptive equipment, and functional-based intervention. CONCLUSIONS: The findings describe the consensus of a group of experts and provide a clinical reference tool on the hand therapy assessment and treatment of nonsurgical thumb CMC joint OA

Implications of the Dunning-Kruger Effect: Finding Balance between Subjective and Objective Assessment in Debriefing Professional Development

Background The ability to debrief is considered an essential clinical and simulation teaching skill because of the deep learning cultivated. Regulatory bodies identify the need for debriefing training and professional development followed by formative and summative assessment. Method The Debriefing for Meaningful Learning Evaluation Scale (DMLES) is a behaviorally anchored rating scale developed to assess 20 behaviors aligned with Debriefing for Meaningful Learning (DML). Participants from five baccalaureate pre–licensure nursing programs were recruited to receive DML training, then facilitate and record a debriefing for subjective and objective assessment using the DMLES. Results A total of 52 debriefers submitted 81 recorded debriefings. DMLES subjective ratings at two time points were higher than that of expert raters of the same debriefings demonstrating statistically significant differences between subjective and objective mean scores. Conclusions The difference between subjective and objective scores demonstrated the Dunning-Kruger Effect (DKE), a subjective overestimation of skill performance when compared to objective assessment. The potential for DKE is an important consideration for determining assessment methods