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Background Carbapenem-resistant Enterobacterales (CRE) are an urgent public health threat in the United States. Objective Describe the clinical and molecular epidemiology of CRE in a multicenter pediatric cohort. Methods CRACKLE-1 and CRACKLE-2 are prospective cohort studies with consecutive enrollment of hospitalized patients with CRE infection or colonization between 24 December 2011 and 31 August 2017. Patients younger than age 18 years and enrolled in the CRACKLE studies were included in this analysis. Clinical data were obtained from the electronic health record. Carbapenemase genes were detected using polymerase chain reaction and whole-genome sequencing. Results Fifty-one children were identified at 18 healthcare system study sites representing all U.S. census regions. The median age was 8 months, with 67% younger than age 2 years. Median number of days from admission to culture collection was 11. Seventy-three percent of patients had required intensive care and 41% had a history of mechanical ventilation. More than half of children had no documented comorbidities (Q1, Q3 0, 2). Sixty-seven percent previously received antibiotics during their hospitalization. The most common species isolated were Enterobacter species (41%), Klebsiella pneumoniae (27%), and Escherichia coli (20%). Carbapenemase genes were detected in 29% of isolates tested, which was lower than previously described in adults from this cohort (61%). Thirty-four patients were empirically treated on the date of culture collection, but only 6 received an antibiotic to which the CRE isolate was confirmed susceptible in vitro. Thirty-day mortality was 13.7%. Conclusions CRE infection or colonization in U.S. children was geographically widespread, predominantly affected children younger than age 2 years, associated with significant mortality, and less commonly caused by carbapenemase-producing strains than in adults. [ABSTRACT FROM AUTHOR]

Storytelling can stimulate learning by delivering scientific content within a narrative that increases comprehension and engagement. In this article I describe the coevolutionary arms race between toxic newts and predatory garter snakes. This engaging story centers on the use of a deadly neurotoxin called tetrodotoxin (TTX) as an antipredator defense. Some species of newts contain TTX in their tissues, but resistance to TTX has developed through convergent evolution in garter snakes and other species. TTX resistance results from mutated voltage-gated sodium channels. These channels, whether TTX resistant or not, are found in all animals and are vital to the function of nervous and muscle tissues. Through reciprocal selection, coevolution has created phenotypic matching between toxic newts and TTX-resistant garter snakes across their range in the western United States. In other words, as newts became more poisonous, garter snakes became more resistant. These results and the scientific process behind them are discussed in detail. This story can be used by educators to provide a unifying and engaging backdrop as students learn multiple aspects of biology, such as protein structure, genetics, phylogenetics, electrical signaling, evolution, and the process of science. [ABSTRACT FROM AUTHOR]

Open textbooks are free, online resources that can replace traditional textbooks and save students money. The costs of traditional textbooks continue to increase, and this can particularly affect at-risk, low-income students. Few studies have analyzed student perceptions of open textbooks and how they influence academic achievement, but the emerging trend is positive. In the present study, I assessed student perceptions of an open textbook and calculated the subsequent cost savings. Although there were some limitations to my study, such as a low sample size, my results closely mirror previous studies in that most students had favorable opinions of the open textbook and would prefer to use them over traditional textbooks. The average cost savings per student was $81 for one course, determined using a novel method that does not assume all students buy new textbooks. These savings were likely important to the students, the majority of whom worked five hours or more and have received Pell Grants or other tuition waivers. [ABSTRACT FROM AUTHOR]

Traditional free speech doctrine is inadequate to account for modern terrorist speech. Unprotected threats and substantially protected lawful advocacy are not mutually exclusive. This Article proposes recognizing a new hybrid category of speech called "terrorizing advocacy." This is a type of traditionally protected public advocacy of unlawful conduct that simultaneously exhibits the unprotected pathologies of a true threat. This Article explains why this new category confounds existing First Amendment doctrine and details a proposed model for how the doctrine should be reshaped. [ABSTRACT FROM AUTHOR]

Few patent claim formats present more interpretative difficulties than that of the so-called Swiss form. Taking shape as purpose-bound process claims (i.e. claims directed towards a manufacturing process applied for a particular end) the Swiss form was originally conceived as an attempt to navigate treacherous waters—waters bordered by two seemingly immutable prohibitions on patenting: the excluded; and the old. A jury-rigged solution to a thorny problem, the Swiss-form claim promised to extend patent law’s incentives to the discovery of new and useful functions of existing medicaments: repurposing the old to create the new. For inventions known in other fields, inventions with no prior medicinal purpose, a solution had already been given in statute; art 54(5) of the European Patent Convention (EPC) 1973 allowed discovery of the first medical use of a known compound to be claimed as a purpose-bound product. Once, however, a first medical use was known: that was it. Secondary indications, arguably no less beneficial than the first, were left out in the cold. The Swiss form was devised to bridge this gap: its purpose undoubtedly noble; its proposed effects glittering. However, this virtuous facade conceals a darker [ABSTRACT FROM AUTHOR]

Background: In the United States, hip fracture rates have declined by 30% coincident with bisphosphonate use. However, bisphosphonates are associated with sporadic cases of atypical femoral fracture. Atypical femoral fractures are usually atraumatic, may be bilateral, are occasionally preceded by prodromal thigh pain, and may have delayed fracture-healing. This study assessed the occurrence of bisphosphonate-associated nonhealing femoral fractures through a review of data from the U.S. FDA (Food and Drug Administration) Adverse Event Reporting System (FAERS) (1996 to 2011), published case reports, and international safety efforts. Methods: We analyzed the FAERS database with use of the proportional reporting ratio (PRR) and empiric Bayesian geometric mean (EBGM) techniques to assess whether a safety signal existed. Additionally, we conducted a systematic literature review (1990 to February 2012). Results: The analysis of the FAERS database indicated a PRR of 4.51 (95% confidence interval [Cl], 3.44 to 5.92) for bisphosphonate use and nonhealingfemoral fractures. Most cases (n = 317) were attributed to use of alendronate (PRR = 3.32; 95% CI, 2.71 to 4.17). In 2008, international safety agencies issued warnings and required label changes. In 2010, the FDA issued a safety notification, and the American Society for Bone and Mineral Research (ASBMR) issued recommendations about bisphosphonate-associated atypical femoral fractures. Conclusions: Nonhealing femoral fractures are unusual adverse drug reactions associated with bisphosphonate use, as up to 26% of published cases of atypical femoral fractures exhibited delayed healing or nonhealing. [ABSTRACT FROM AUTHOR]

Studies the pathogenic fungus, Coccidioides immitis, which is endemic to semi-arid soils in southwestern United States, Central and South America. Molecular analysis indicating C. immitis is not just a single species, but a pair now referred to as the Californian and non-Californian type; Study describing the characterization and isolation of two classes of polymorphic genetic markers from the California species of C. immitis.

An outbreak of SARS-CoV-2 involving four residents of a United States Veterans Affairs long term care facility occurred following administration of the first dose of the mRNA-1273 vaccine (Moderna) to thirty out of 33 residents. Three out of 4 positive cases were partially vaccinated and remained asymptomatic. One of 2 partially vaccinated patients who were tested for anti-spike protein antibodies had detectable levels at the time of diagnosis. The mortality rate was lower compared to a prior outbreak reported in this facility., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Promising therapies for cartilage repair are translated through large animal models toward human application. To guide this work, regulatory agencies publish recommendations ("guidance documents") to direct pivotal large animal studies. These are meant to aid in study design, outline metrics for judging efficacy, and facilitate comparisons between studies. To determine the penetrance of these documents in the field, we synthesized the recommendations of the American Society for Testing and Materials, U.S. Food and Drug Administration, and European Medicines Agency into a scoring system and performed a systematic review of the past 20 years of preclinical cartilage repair studies. Our hypothesis was that the guidance documents would have a significant impact on how large animal cartilage repair studies were performed. A total of 114 publications meeting our inclusion criteria were reviewed for adherence to 24 categories extracted from the guidance documents, including 11 related to study design and description and 13 related to study outcomes. Overall, a weak positive trend was observed over time (P = 0.004, R(2) = 0.07, slope = 0.63%/year), with overall adherence (the sum of study descriptors and outcomes) ranging from 32 ± 16% to 58 ± 14% in any individual year. There was no impact of the publication of the guidance documents on adherence (P = 0.264 to 0.50). Given that improved adherence would expedite translation, we discuss the reasons for poor adherence and outline approaches to increase and promote their more widespread adoption., (Copyright © 2015, American Association for the Advancement of Science.)

Introduction: In 1998, a multidisciplinary team of investigators initiated the Research on Adverse Drug events And Reports (RADAR) project, a post-marketing surveillance effort that systematically investigates and disseminates information describing serious and previously unrecognized serious adverse drug and device reactions (sADRs)., Objective: Herein, we describe the findings, dissemination efforts, and lessons learned from the first decade of the RADAR project., Methods: After identifying serious and unexpected clinical events suitable for further investigation, RADAR collaborators derived case information from physician queries, published and unpublished clinical trials, case reports, US FDA databases and manufacturer sales figures., Study Selection: All major RADAR publications from 1998 to the present are included in this analysis., Data Extraction: For each RADAR publication, data were abstracted on data source, correlative basic science findings, dissemination and resultant safety information., Results: RADAR investigators reported 43 serious ADRs. Data sources included case reports (17 sADRs), registries (5 sADRs), referral centers (8 sADRs) and clinical trial reports (13 sADRs). Correlative basic science findings were reported for ten sADRs. Thirty-seven sADRS were described as published case reports (5 sADRs) or published case-series (32 sADRs). Related safety information was disseminated as warnings or boxed warnings in the package insert (17 sADRs) and/or 'Dear Healthcare Professional' letters (14 sADRs)., Conclusion: An independent National Institutes of Health-funded post-marketing surveillance programme can supplement existing regulatory and pharmaceutical manufacturer-supported drug safety initiatives.