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Calculus students are taught that an indefinite integral is defined only up to an additive constant, and as a consequence generations of students have assiduously added ‘+C’ to their calculus homework. Although ubiquitous, these constants rarely garner much attention, and typically loiter without intent around the ends of equations, feeling neglected. There is, however, useful work they can do, work which is particularly relevant in the contexts of integral tables and computer algebra systems. We begin, therefore, with a discussion of the context, before returning to coax the constants out of the shadows and assign them their tasks.
Background: Antibiotic overuse contributes to antibiotic resistance and unnecessary adverse drug effects. Antibiotic stewardship interventions have primarily focused on acute-care settings. Most antibiotic use, however, occurs in outpatients with acute respiratory tract infections such as pharyngitis. The electronic health record (EHR) might provide an effective and efficient tool for outpatient antibiotic stewardship. We aimed to develop and validate an electronic algorithm to identify inappropriate antibiotic use for pediatric outpatients with pharyngitis. Methods: This study was conducted within the Children’s Hospital of Philadelphia (CHOP) Care Network, including 31 pediatric primary care practices and 3 urgent care centers with a shared EHR serving >250,000 children. We used International Classification of Diseases, Tenth Revision (ICD-10) codes to identify encounters for pharyngitis at any CHOP practice from March 15, 2017, to March 14, 2018, excluding those with concurrent infections (eg, otitis media, sinusitis), immunocompromising conditions, or other comorbidities that might influence the need for antibiotics. We randomly selected 450 features for detailed chart abstraction assessing patient demographics as well as practice and prescriber characteristics. Appropriateness of antibiotic use based on chart review served as the gold standard for evaluating the electronic algorithm. Criteria for appropriate use included streptococcal testing, use of penicillin or amoxicillin (absent β-lactam allergy), and a 10-day duration of therapy. Results: In 450 patients, the median age was 8.4 years (IQR, 5.5–9.0) and 54% were women. On chart review, 149 patients (33%) received an antibiotic, of whom 126 had a positive rapid strep result. Thus, based on chart review, 23 subjects (5%) diagnosed with pharyngitis received antibiotics inappropriately. Amoxicillin or penicillin was prescribed for 100 of the 126 children (79%) with a positive rapid strep test. Of the 126 children with a positive test, 114 (90%) received the correct antibiotic: amoxicillin, penicillin, or an appropriate alternative antibiotic due to b-lactam allergy. Duration of treatment was correct for all 126 children. Using the electronic algorithm, the proportion of inappropriate prescribing was 28 of 450 (6%). The test characteristics of the electronic algorithm (compared to gold standard chart review) for identification of inappropriate antibiotic prescribing were sensitivity (99%, 422 of 427); specificity (100%, 23 of 23); positive predictive value (82%, 23 of 28); and negative predictive value (100%, 422 of 422). Conclusions: For children with pharyngitis, an electronic algorithm for identification of inappropriate antibiotic prescribing is highly accurate. Future work should validate this approach in other settings and develop and evaluate the impact of an audit and feedback intervention based on this tool.
Background: Antibiotic resistance has increased at alarming rates, driven predominantly by antibiotic overuse. Although most antibiotic use occurs in outpatients, antimicrobial stewardship programs have primarily focused on inpatient settings. A major challenge for outpatient stewardship is the lack of accurate and accessible electronic data to target interventions. We sought to develop and validate an electronic algorithm to identify inappropriate antibiotic use for outpatients with acute bronchitis. Methods: This study was conducted within the University of Pennsylvania Health System (UPHS). We used ICD-10 diagnostic codes to identify encounters for acute bronchitis at any outpatient UPHS practice between March 15, 2017, and March 14, 2018. Exclusion criteria included underlying immunocompromising condition, other comorbidity influencing the need for antibiotics (eg, emphysema), or ICD-10 code at the same visit for a concurrent infection (eg, sinusitis). We randomly selected 300 (150 from academic practices and 150 from nonacademic practices) eligible subjects for detailed chart abstraction that assessed patient demographics and practice and prescriber characteristics. Appropriateness of antibiotic use based on chart review served as the gold standard for assessment of the electronic algorithm. Because antibiotic use is not indicated for this study population, appropriateness was assessed based upon whether an antibiotic was prescribed or not. Results: Of 300 subjects, median age was 61 years (interquartile range, 50–68), 62% were women, 74% were seen in internal medicine (vs family medicine) practices, and 75% were seen by a physician (vs an advanced practice provider). On chart review, 167 (56%) subjects received an antibiotic. Of these subjects, 1 had documented concern for pertussis and 4 had excluding conditions for which there were no ICD-10 codes. One received an antibiotic prescription for a planned dental procedure. Thus, based on chart review, 161 (54%) subjects received antibiotics inappropriately. Using the electronic algorithm based on diagnostic codes, underlying and concurrent conditions, and prescribing data, the number of subjects with inappropriate prescribing was 170 (56%) because 3 subjects had antibiotic prescribing not noted based on chart review. The test characteristics of the electronic algorithm (compared to gold standard chart review) for identification of inappropriate antibiotic prescribing were the following: sensitivity, 100% (161 of 161); specificity, 94% (130 of 139); positive predictive value, 95% (161 of 170); and negative predictive value, 100% (130 of 130). Conclusions: For outpatients with acute bronchitis, an electronic algorithm for identification of inappropriate antibiotic prescribing is highly accurate. This algorithm could be used to efficiently assess prescribing among practices and individual clinicians. The impact of interventions based on this algorithm should be tested in future studies.
Background: Delayed or in vitro inactive empiric antibiotic therapy may be detrimental to survival in patients with bloodstream infections (BSIs). Understanding the landscape of delayed or discordant empiric antibiotic therapy (DDEAT) across different patient, pathogen, and hospital types, as well as by their baseline resistance milieu, may enable providers, antimicrobial stewardship programs, and policy makers to optimize empiric prescribing. Methods: Inpatients with clinically suspected serious infection (based on sampling of blood cultures and receiving systemic antibiotic therapy on the same or next day) found to have BSI were identified in the Cerner Healthfacts EHR database. Patients were considered to have received DDEAT when, on culture sampling day, they received either no antibiotic(s) or none that displayed in vitro activity against the pathogenic bloodstream isolate. Antibiotic-resistant phenotypes were defined by in vitro resistance to taxon-specific prototype antibiotics (eg, methicillin/oxacillin resistance in S. aureus) and were used to estimate baseline resistance prevalence encountered by the hospital. The probability of DDEAT was examined by bacterial taxon, by time of BSI onset, and by presence versus absence of antibiotic-resistance phenotypes, sepsis or septic shock, hospital type, and baseline resistance. Results: Of 26,036 assessable patients with a BSI at 131 US hospitals between 2005 and 2014, 14,658 (56%) had sepsis, 3,623 (14%) had septic shock, 5,084 (20%) had antibiotic-resistant phenotypes, and 8,593 (33%) received DDEAT. Also, 4,428 (52%) recipients of DDEAT received no antibiotics on culture sampling day, whereas the remaining 4,165 (48%) received in vitro discordant therapy. DDEAT occurred most often in S. maltophilia (87%) and E. faecium (80%) BSIs; however, 75% of DDEAT cases and 76% of deaths among recipients of DDEAT collectively occurred among patients with S. aureus and Enterobacteriales BSIs. For every 8 bacteremic patients presenting with septic shock, 1 patient did not receive any antibiotics on culture day (Fig. 1A). Patients with BSIs of hospital (vs community) onset were twice as likely to receive no antibiotics on culture day, whereas those with bloodstream pathogens displaying antibiotic-resistant (vs susceptible) phenotypes were 3 times as likely to receive in vitro discordant therapy (Fig. 1B). The median proportion of DDEAT ranged between 25% (14, 37%) in eight <300-bed teaching hospitals in the lowest baseline resistance quartile and 40% (31, 50%) at five ≥300-bed teaching hospitals in the third baseline resistance quartile (Fig. 2). Conclusions: Delayed or in vitro discordant empiric antibiotic therapy is common among patients with BSI in US hospitals regardless of hospital size, teaching status, or local resistance patterns. Prompt empiric antibiotic therapy in septic shock and hospital-onset BSI needs more support. Reliable detection of S. aureus and Enterobacteriales bloodstream pathogens and their resistance patterns earlier with rapid point-of-care diagnostics may mitigate the population-level impact of DDEAT in BSI.
Funding: This study was funded in part by the National Institutes of Health Clinical Center, National Institutes of Allergy and Infectious Diseases, National Cancer Institute (NCI contract no. HHSN261200800001E) and the Agency for Healthcare Research and Quality.
The otoliths (ear stones) of fishes are commonly used to describe the age and growth of marine and freshwater fishes. These non-skeletal structures are fortuitous in their utility by being composed of mostly inorganic carbonate that is inert through the life of the fish. This conserved record functions like an environmental chronometer and bomb-produced radiocarbon (14C)—a 14C signal created by atmospheric testing of thermonuclear devices—can be used as a time-specific marker in validating fish age. However, complications from the hydrogeology of nearshore marine environments can complicate 14C levels, as was the case with gray snapper (Lutjanus griseus) along the Gulf of Mexico coast of Florida. Radiocarbon of these nearshore waters is influenced by freshwater input from the karst topography of the Upper Floridan Aquifer—estuarine waters that are 14C-depleted from surface and groundwater inputs. Some gray snapper likely recruited to this kind of environment where 14C levels were depleted in the earliest otolith growth, although age was validated for individuals that were not exposed to 14C-depleted waters to an age of at least 25 years with support for a 30-year lifespan.
Impulsive aggressive (IA, or impulsive aggression) behavior describes an aggregate set of maladaptive, aggressive behaviors occurring across multiple neuropsychiatric disorders. IA is reactive, eruptive, sudden, and unplanned; it provides information about the severity, but not the nature, of its associated primary disorder. IA in children and adolescents is of serious clinical concern for patients, families, and physicians, given the detrimental impact pediatric IA can have on development. Currently, the ability to properly identify, monitor, and treat IA behavior across clinical populations is hindered by two major roadblocks: (1) the lack of an assessment tool designed for and sensitive to the set of behaviors comprising IA, and (2) the absence of a treatment indicated for IA symptomatology. In this review, we discuss the clinical gaps in the approach to monitoring and treating IA behavior, and highlight emerging solutions that may improve clinical outcomes in patients with IA.
One in four cases of acute aortic syndrome are missed. This national survey examined Canadian Emergency physicians’ opinion on risk stratification, the need for a clinical decision aid to risk stratify patients, and the required sensitivity of such a tool.
We surveyed 1,556 members of the Canadian Association of Emergency Physicians. We used a modified Dillman technique with a prenotification email and up to three survey attempts using electronic mail. Physicians were asked 21 questions about demographics, importance of certain high-risk features, investigation options, threshold for investigation, and if a clinical decision tool is required
We had a response rate of 32%. Respondents were 66% male, and 49% practicing >10 years, with 59% in an academic teaching hospital. A total of 93% reported a need for a clinical decision aid to risk stratify for acute aortic syndrome. A total of 99.6% of physicians were pragmatic accepting a non-zero miss-rate, two-thirds accepting <1%, and the remaining accepting a higher miss-rate.
Our national survey determined that emergency physicians would use a highly sensitive clinical decision aid to determine which patients are at low, medium, or high-risk for acute aortic syndrome. The majority of clinicians have a low threshold (<1%) for investigating for acute aortic syndrome, but accept that a zero miss-rate is not feasible.
In this article, we review some of the recent developments in instrumentation and methods that have led to the rise of cryo-electron microscopy (cryo-EM) in the life sciences community, and consider how researchers in the materials community might benefit from these advances. Transmission electron microscopy (TEM) is compared with scanning transmission electron microscopy (STEM) for cryogenic imaging in both biological and materials science applications. We discuss the developments in detector technologies that have in part powered the development of cryo-EM and anticipate exciting areas for productive overlap between life science and materials science cryo-EM applications.
New cryogenic characterization techniques for exploring the nanoscale structure and chemistry of intact solid–liquid interfaces have recently been developed. These techniques provide high-resolution information about buried interfaces from large samples or devices that cannot be obtained by other means. These advancements were enabled by the development of instrumentation for cryogenic focused ion beam liftout, which allows intact solid–liquid interfaces to be extracted from large samples and thinned to electron-transparent thicknesses for characterization by cryogenic scanning transmission electron microscopy or atom probe tomography. Future implementation of these techniques will complement current strides in imaging of materials in fluid environments by in situ liquid-phase electron microscopy, providing a more complete understanding of the morphology, surface chemistry, and dynamic processes that occur at solid–liquid interfaces.
This article discusses prospects and challenges related to the use of meta-regression models (MRMs) for ecosystem service benefit transfer, with an emphasis on validity criteria and post-estimation procedures given sparse attention in the ecosystem services literature. We illustrate these topics using a meta-analysis of willingness to pay for water quality changes that support aquatic ecosystem services and the application of this model to estimate water quality benefits under alternative riparian buffer restoration scenarios in New Hampshire's Great Bay Watershed. These illustrations highlight the advantages of MRM benefit transfers, together with the challenges and data needs encountered when quantifying ecosystem service values.
We demonstrate an application evaluating carbon sequestration benefits from federal policy alternatives. Using detailed forest inventory data, we projected carbon sequestration outcomes in the coterminous 48 states for a baseline scenario and three policy scenarios through 2050. Alternatives included (1) reducing deforestation from development, (2) afforestation in the eastern United States and reforestation in the western United States, and (3) reducing stand-replacing wildfires. We used social cost of carbon estimates to evaluate the present value of carbon sequestration benefits gained with each policy. Results suggest that afforestation and reforestation would provide the greatest marginal increase in carbon benefit, far exceeding policy cost.
This paper examines grass-fed beef producer preferences for cattle traits using data from a mail survey of 384 U.S. grass-fed beef producers. Conjoint analysis and Likert scale questions were used to determine preferences. Generally, results indicated that producers preferred easy-to-handle, heavy, black, and relatively lower-priced feeders raised from their own cows. The Kernel density figures for source, color, and temperament confirm the mixed logit standard deviation estimates that suggest heterogeneity in producer preferences.