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This essay surveys the literate culture of the antebellum and Civil War eras among marginal southerners – African Americans, both free and enslaved, and poor and middle-class whites – and explores examples of the ways reading and writing, though quite distinct in formal pedagogies, blended together in the literary lives of the self-educated. Focused especially on Basil Armstrong Thomasson, a yeoman farmer in North Carolina whose diary records his reading practices as well as original verse, and John M. Washington, a Virginia man who kept a diary while enslaved, the essay presents a study in the surprising complexity and variegation of the textual landscape such people inhabited and helped create. It also discusses the scarcer archival traces of the literacy practices of ordinary southern women.
Throughout the history of Christianity, the four canonical gospels have proven to be vital resources for Christian thought and practice, and an inspiration for humanistic culture generally. Indeed, the gospels and their interpretation have had a profound impact on theology, philosophy, the sciences, ethics, worship, architecture, and the creative arts. Building on the strengths of the first edition, The Cambridge Companion to the Gospels, 2nd edition, takes account of new directions in gospels research, notably: the milieu in which the gospels were read, copied, and circulated alongside non-canonical gospels; renewed debates about the sources of the gospels and their interrelations; how central gospel themes are illuminated by a variety of critical approaches and theological readings; the reception of the gospels over time and in various media; and how the gospels give insight into the human condition.
Frank Schechter introduced the concept of trademark dilution to American readers in his 1927 Harvard Law Review article “The Rational Basis of Trademark Protection.”2 He concluded the article by noting that his formulation of the concept “is fortified by the doctrine that has developed within recent years in German law on this same point.”3 In waiting until the end of his article to refer to the German case law, Schechter effectively implied that dilution was a home-grown American idea – indeed, that it was Schechter’s own, original idea – and that the German courts just happened to have come up with a similar notion. In fact, Schechter appears to have taken the concept of trademark dilution and much of the rhetoric he used in describing it – including “selling power” and the very term “dilution” – from a single German trial court opinion, specifically, the opinion of the Elberfeld Landgericht in the 1924 Odol case.4 The enormous significance of the Odol opinion for American and global trademark law still remains unappreciated. In honor of Annette Kur’s path-breaking and decades-long work in forging mutual understanding between the European and American trademark law systems, presented here is the first full translation into English of the Odol opinion, trademark dilution’s “ur-case.”5
In this paper, we address how the COVID-19 pandemic has impacted informed consent for clinical research through examining experiences within Clinical and Translation Science Award (CTSA) institutions. We begin with a brief overview of informed consent and the challenges that existed prior to COVID-19. Then, we discuss how informed consent processes were modified or changed to address the pandemic, consider what lessons were learned, and present research and policy steps to prepare for future research and public health crises. The experiences and challenges for CTSA institutions offer an important perspective for examining what we have learned about informed consent and determining the next steps for improving the consent process.
Biospecimen repositories play a vital role in enabling investigation of biologic mechanisms, identification of disease-related biomarkers, advances in diagnostic assays, recognition of microbial evolution, and characterization of new therapeutic targets for intervention. They rely on the complex integration of scientific need, regulatory oversight, quality control in collection, processing and tracking, and linkage to robust phenotype information. The COVID-19 pandemic amplified many of these considerations and illuminated new challenges, all while academic health centers were trying to adapt to unprecedented clinical demands and heightened research constraints not witnessed in over 100 years. The outbreak demanded rapid understanding of SARS-CoV-2 to develop diagnostics and therapeutics, prompting the immediate need for access to high quality, well-characterized COVID-19-associated biospecimens. We surveyed 60 Clinical and Translational Science Award (CTSA) hubs to better understand the strategies and barriers encountered in biobanking before and in response to the COVID-19 pandemic. Feedback revealed a major shift in biorepository model, specimen-acquisition and consent process from a combination of investigator-initiated and institutional protocols to an enterprise-serving strategy. CTSA hubs were well equipped to leverage established capacities and expertise to quickly respond to the scientific needs of this crisis through support of institutional approaches in biorepository management.
In the context of a stark discrepancy in the educational outcomes of Aboriginal Australians compared to non-Aboriginal Australians, this article aims to contribute the voices of rural Aboriginal high school students to the discourse. This article utilises an appreciative enquiry approach to analyse the opinions and aspirations of 12 Aboriginal high school students in a South Australian regional centre. Drawing on student perspectives from semi-structured interviews, this article contributes to and contextualises the growing body of literature regarding educational aspirations. It demonstrates how rurality influences a complex system of intrinsic attributes, relationship networks and contextual factors. It offers an important counterpoint to discourses surrounding academic disadvantage and highlights the lived experience of rural Aboriginal Australians.
Reading difficulties are one of the most significant challenges for children with neurofibromatosis type 1 (NF1). The aims of this study were to identify and categorize the types of reading impairments experienced by children with NF1 and to establish predictors of poor reading in this population.
Children aged 7–12 years with NF1 (n = 60) were compared with typically developing children (n = 36). Poor word readers with NF1 were classified according to impairment type (i.e., phonological, surface, mixed), and their reading subskills were compared. A hierarchical multiple regression was conducted to identify predictors of word reading.
Compared to controls, children with NF1 demonstrated significantly poorer literacy abilities. Of the 49 children with NF1 classified as poor readers, 20 (41%) were classified with phonological dyslexia, 24 (49%) with mixed dyslexia, and 5 (10%) fell outside classification categories. Children with mixed dyslexia displayed the most severe reading impairments. Stronger working memory, better receptive language, and fewer inattentive behaviors predicted better word reading skills.
The majority of children with NF1 experience deficits in key reading skills which are essential for them to become successful readers. Weaknesses in working memory, receptive language, and attention are associated with reading difficulties in children with NF1.
Review a single-centre experience with pulmonary artery sling repair and evaluate risk factors for re-intervention.
Patients with surgically repaired pulmonary artery sling at a single institution between 1996 and 2018 were retrospectively reviewed. A univariate Cox regression analysis was used to evaluate variables for association with freedom from re-intervention.
Eighteen patients had pulmonary artery sling repair. At operation, median age and weight were 6.9 months (interquartile range 4.1–18.1) and 9.5 kg (interquartile range 6.5–14.5), respectively. A median hospital length of stay was 12 days (interquartile range 5.8–55.3). Twelve patients (67%) had complete tracheal rings, of whom six (50%) underwent tracheoplasty (five concurrently with pulmonary artery sling repair). Airway re-intervention was required in five (83%) of the six patients who underwent tracheoplasty. One patient had intraoperative diagnosis and repair of pulmonary artery sling during unrelated lesion repair and required tracheoplasty 24 days post-operatively. One patient died 55 days after pulmonary artery sling repair and tracheoplasty following multiple arrests and re-interventions. Median post-operative follow-up for surviving patients was 6.3 years (interquartile range 11 months–13 years), at which time freedom from re-intervention was 61%. When controlling for patient and tracheal size, initial tracheoplasty was associated with decreased freedom from re-intervention (hazard ratio 21.9, 95% confidence interval 1.7–284.3, p = 0.018).
In patients with pulmonary artery sling, tracheoplasty is associated with decreased freedom from re-intervention. In select patients with pulmonary artery sling and complete tracheal rings, conservative management without tracheoplasty is feasible. Further study is necessary to delineate objective indications for tracheoplasty.
Background: Hospitalized patients are at an increased risk of invasive infection with Staphylococcus aureus when colonized with the bacteria on admission. Rates of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia are directly correlated with overall patient acuity, placing patients in intensive care areas at greatest risk. Universal decolonization with nasal antibiotic ointments has been shown to reduce the incidence of invasive MRSA in critically ill patients; however, debate remains regarding the long-term efficacy of this strategy and the possibility of developing antimicrobial resistance. An alcohol-based nasal antimicrobial may be an effective alternative. This study evaluated the effectiveness of a twice daily alcohol-based product in reducing the rate of MRSA bacteremia in an academic tertiary-care adult intensive care setting. Methods: Our study was an observational design with retrospective and prospective cohorts each consisting of 61 critical care beds. The baseline incidence of MRSA bacteremia was determined from a 7-month period preceding the implementation of the nasal antimicrobial. At implementation, each admission received an electronic order for an alcohol-based nasal antiseptic that was applied twice daily during the intensive care stay. The primary outcome was the incidence of MRSA bacteremia in each group. MRSA bacteremia was defined by the CDC NHSN criteria after review by an infection prevention nurse. The 2 test was used to compare the rates between the 2 groups, and P < .005 was considered significant. Results: The study periods contained similar patient days, with 12,475 in the retrospective group and 12,733 in the prospective group. The rate of MRSA bacteremia in the retrospective cohort was 0.2404 compared to 0 in the prospective cohort. This rate change was statistically significant, with P < .0001. Conclusions: The alcohol-based nasal antiseptic was effective in reducing healthcare-onset MRSA bacteremia in this intensive care population. This approach may be a safe and effective alternative to nasal antibiotic ointment that avoids antibiotic resistance risks.
Background: Central venous catheter (CVC) maintenance bundle elements, including labeling IV tubing and dressings, consistently changing them, intact dressings, and dry healthy insertion sites, together have been shown to reduce risks of developing central-line–associated bloodstream infections (CLABSIs).1,2 CLABSIs are a significant, but preventable, cause of mortality among critically ill patients.3 In the last 12 months, the 16-bed medical intensive care unit (MICU) at a large, urban, academic facility had 2,621 central-line days, presenting many opportunities for CLABSI prevention. During that time, weekly observations assessed compliance with CVC maintenance bundle elements. Interventions: Multidisciplinary rounds were conducted to monitor nursing staff adherence to CVC maintenance bundle elements. The following bundle elements observed during rounds: (1) Is central-line dressing occlusive/intact? (2) Is CVC insertion site healthy with no redness/drainage? (3) Is CVC dressing labeled with insertion date? (4) Date/time of last dressing change adheres to policy? (4) All CVC tubing is labeled with date/time? (5) All CVC tubing dates adhere to policy? (6) If stopcock is present, is cap present over unused port? “Just-in-time” staff coaching was employed when noncompliance was observed. Findings were sent to leadership for manager follow-up. Staff were informed about products available within the hospital, which can improve dressing adherence and mitigate insertion-site bleeding. Education was provided to staff defining exact requirements for CVC dressings. The acronym “IDOL” was used to help remind staff of these fundamentals: (1) Intact dressing borders are well adhered, with <50% of the white border detached. (2) Drainage should be within the chlorhexidine square. (3) Occlusive means no bubbles, kinks, or wrinkles in the dressing. (4) Labeling is required and must include insertion date, date/time of change, and initials. Results: In the first 2 months of rounds, overall compliance averaged 85%. Compliance increased to an average of 91% during the subsequent 10 months. Early on, most fallouts were found with dressings not occlusive or intact and excessive drainage from insertion sites. Initially, 71% of sites were without excess drainage, and 57% of dressings were occlusive or intact. These measures increased to 83% and 89%, respectively, after the interventions. A 50% decrease in the number of CLABSIs was observed during the observation period, compared to the previous 12-month period. Conclusions: Consistent use of bundles has been shown to significantly improve patient outcomes with regard to hospital-acquired infections (HAIs).3 Frequent observations, education to define staff expectations, and holding staff accountable have all helped improve compliance with maintenance bundle elements. Preventing CLABSIs is not only important for patient safety and quality of care. Regulatory and accrediting agencies are now increasing their focus on infections and are tying them to reimbursement.
Antimicrobial resistance is an urgent public health threat. Identifying trends in antimicrobial susceptibility can inform public health policy at the state and local levels.
To determine the ability of statewide antibiogram aggregation for public health surveillance to identify changes in antimicrobial resistance trends.
Facility-level trend analysis.
Crude and adjusted trend analyses of the susceptibility of Escherichia coli and Klebsiella pneumoniae to particular antibiotics, as reported by aggregated antibiograms, were examined from 2008 through 2018. Multivariable regression analyses via generalized linear mixed models were used to examine associations between hospital characteristics and trends of E. coli and K. pneumoniae susceptibility to ciprofloxacin and ceftriaxone.
E. coli and K. pneumoniae showed inverse trends in drug susceptibility over time. K. pneumoniae susceptibility to fluoroquinolones increased by 5% between 2008 and 2018 (P < .05). In contrast, E. coli susceptibility declined during the same period to ceftriaxone (6%), gentamicin (4%), and fluoroquinolones (4%) (P < .05). When compared to Boston hospitals, E. coli isolates from hospitals in other regions had a >4% higher proportion of susceptibility to ciprofloxacin and a >3% higher proportion of susceptibility to ceftriaxone (P < .05). Isolates of K. pneumoniae had higher susceptibility to ciprofloxacin (>3%) and ceftriaxone (>1.5%) in all regions when compared to Boston hospitals (P < .05).
Cumulative antibiograms can be used to monitor antimicrobial resistance, to discern regional and facility differences, and to detect changes in trends. Furthermore, because the number of years that hospitals contributed reports to the state-level aggregate had no significant influence on susceptibility trends, other states should not be discouraged by incomplete hospital compliance.
The DHVI Division of Structural Biology seeks to use atomic level structural information for design of an effective HIV-1 vaccine. Through visualization of the HIV-1 envelope (Env) and its interactions with the human immune system, we obtain structural information that we translate into the rational development vaccine immunogens
We use negative stain electron microscopy (NSEM), cryo-electron microscopy (cryo-EM), and x-ray crystallography as the major structural techniques for visualization of HIV-1 Env, and combine these with biochemical and biophysical studies, as well as computational methods to obtain a basic understanding of the functions and interactions of the HIV-1 Env.
1.The DHVI NSEM pipeline runs on a daily basis to quality control vaccine immunogens for animal studies and other applications. Offering rapid sample turnover and economical operations, the NSEM pipeline is the most widely utilized resource of the DHVI Division of Structural Biology. Over the last year, the NSEM team has focused efforts on improving operational speed and data processing allowing high-quality visualization of a large variety of samples including HIV-1 Env immunogens, antibodies, nanoparticles, and VLPs. In the last year we have also expanded our NSEM studies to the analyses of serum samples and mucosal fluids.
2. To understand the mechanism of HIV-1 entry we have determined structures of HIV-1 entry intermediates. We have determined a 3.8 Å resolution structure of a single CD4 bound to a closed HIV-1 Env trimer revealing new contacts of CD4 with Env. We have also structurally characterized an Env designed to prevent CD4-induced rearrangements by targeted disruption of an allosteric network modulating Env conformational changes.
3. We have structurally characterized the HIV-1 glycan-V3 targeting DH270 Broadly Neutralizing Antibody Lineage. The structures revealed movements in the V1 loop and interactive glycans, shifts in antibody orientations, antibody VH-VL orientations, and antibody elbow angles, as the lineage progressed to maturation.
4. We have solved a structure in complex with the HIV-1 Env immunogen Man5-enriched CH505.N279K.G458Y.SOSIP.664 of the unmutated common ancestor (UCA) of the HIV-1 CD4-binding site targeting CH235 Broadly Neutralizing Antibody Lineage. The structure revealed interactions of the N279K and G458Y mutations with the CDR L3 loop of CH235 UCA thus providing a structural understanding of the role of these mutations in facilitating binding to the CH235 UCA. (see also Henderson et al abstract)
5. Using NSEM and cryo-EM we have characterized the structural properties of a novel class of 2G12-mimetic, yet non domain-swapped Fab dimer glycan-reactive (FDG) antibodies. These studies showed that the Fab-dimerized 2G12-like motif is more common than previously thought, and that creation of a Fab-dimerized paratope for an HIV-1 neutralizing antibody does not require VH domain-swapping.
6. Finally, the structural team is an integral part of the CHAVD Kalma Immunogen Design Team, wherein we are defining the structural basis of bnAb affinity maturation to guide sequential immunogen design.
These results highlight the power of structural information on HIV-1 vaccine design, from leveraging a basic understanding of HIV-1 entry mechanism for immunogen design, to rapid visualization of Env immunogens by NSEM for quality control, discovery of novel antibody interactions, and atomic level visualization of antibody/Env interactions.
Twin 5-month seasonal forecast experiments are performed to predict the September 2018 mean and minimum ice extent using the fully coupled Navy Earth System Prediction Capability (ESPC). In the control run, ensemble forecasts are initialized from the operational US Navy Global Ocean Forecasting System (GOFS) 3.1 but do not assimilate ice thickness data. Another set of forecasts are initialized from the same GOFS 3.1 fields but with sea ice thickness derived from CryoSat-2 (CS2). The Navy ESPC ensemble mean September 2018 minimum sea ice extent initialized with GOFS 3.1 ice thickness was over-predicted by 0.68 M km2 (5.27 M km2) vs the ensemble forecasts initialized with CS2 ice thickness that had an error of 0.40 M km2 (4.99 M km2), a 43% reduction in error. The September mean integrated ice edge error shows a 18% improvement for the Pan-Arctic with the CS2 data vs the control forecasts. Comparison against upward looking sonar ice thickness in the Beaufort Sea reveals a lower bias and RMSE with the CS2 forecasts at all three moorings. Ice concentration at these locations is also improved, but neither set of forecasts show ice free conditions as observed at moorings A and D.
A central area of current philosophical debate in the foundations of mathematics concerns whether or not there is a single, maximal, universe of set theory. Universists maintain that there is such a universe, while Multiversists argue that there are many universes, no one of which is ontologically privileged. Often model-theoretic constructions that add sets to models are cited as evidence in favor of the latter. This paper informs this debate by developing a way for a Universist to interpret talk that seems to necessitate the addition of sets to V. We argue that, despite the prima facie incoherence of such talk for the Universist, she nonetheless has reason to try and provide interpretation of this discourse. We present a method of interpreting extension-talk (V-logic), and show how it captures satisfaction in ‘ideal’ outer models and relates to impredicative class theories. We provide some reasons to regard the technique as philosophically virtuous, and argue that it opens new doors to philosophical and mathematical discussions for the Universist.