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US Outpatient Antibiotic Prescribing Variation According to Geography, Patient Population, and Provider Specialty in 2011
Background. Appropriate antibiotic prescribing is an essential strategy to reduce the spread of antibiotic resistance. US prescribing practices have not been thoroughly characterized. We analyzed outpatient antibiotic prescribing data to identify where appropriate antibiotic prescribing interventions could have the most impact. Methods. Oral antibiotic prescriptions dispensed during 2011 were extracted from the IMS Health Xponent database. The number of prescriptions and census denominators were used to calculate prescribing rates. Prescription totals were calculated for each provider specialty. Regression modeling was used to examine the association between socioeconomic and population health factors and prescribing rates. Results. Healthcare providers prescribed 262.5 million courses of antibiotics in 2011 (842 prescriptions per 1000 persons). Penicillins and macrolides were the most common antibiotic categories prescribed. The most commonly prescribed individual antibiotic agent was azithromycin. Family practitioners prescribed the most antibiotic courses (24%). The prescribing rate was higher in the South census region (931 prescriptions per 1000 persons) than in the West (647 prescriptions per 1000 persons; P<.001); this pattern was observed among all age groups, including children ≤2 and persons ≥65 years of age. Counties with a high proportion of obese persons, infants and children ≤2 years of age, prescribers per capita, and females were more likely to be high prescribing by multivariable analysis (adjusted odds ratio, >1.0). Conclusions. Efforts to characterize antibiotic prescribing practices should focus on the South census region and family practitioners. Further understanding of the factors leading to high prescribing among key target populations will inform appropriate prescribing interventions.
Journal Article
The diffusion of social movements : actors, mechanisms, and political effects
\"It is widely recognized that social movements may spread - or \"diffuse\" - from one site to another. Such diffusion, however, is a complex and multidimensional process that involves different actors, networks, and mechanisms. This complexity has spawned a large body of literature on different aspects of the diffusion process, yet a comprehensive framework remains an elusive target. This book is a response to that need, and its framework focuses on three basic analytical questions. First, what is being diffused? This question directs attention to both the protest repertoires and interpretive frames that actors construct to define issues and mobilize political claims. Second, how does diffusion occur? This book focuses attention on the activist networks and communication channels that facilitate diffusion, including dialogue, rumors, the mass media, the internet, NGOs, and organizational brokers. Finally, what is the impact of diffusion on organizational development and shifts in the scale of contentious politics? This volume suggests that diffusion is not a simple matter of political contagion or imitation; rather, it is a creative and strategic process marked by political learning, adaptation, and innovation\"--Provided by publisher.
Book
Functional Characterization Supports Multiple Evolutionary Origins of Pheromone Receptors in Bark Beetles
Abstract
Chemical communication using pheromones is thought to have contributed to the diversification and speciation of insects. The species-specific pheromones are detected by specialized pheromone receptors (PRs). Whereas the evolution and function of PRs have been extensively studied in Lepidoptera, only a few PRs have been identified in beetles, which limits our understanding of their evolutionary histories and physiological functions. To shed light on these questions, we aimed to functionally characterize potential PRs in the spruce bark beetle Ips typographus (“Ityp”) and explore their evolutionary origins and molecular interactions with ligands. Males of this species release an aggregation pheromone comprising 2-methyl-3-buten-2-ol and (4S)-cis-verbenol, which attracts both sexes to attacked trees. Using two systems for functional characterization, we show that the highly expressed odorant receptor (OR) ItypOR41 responds specifically to (4S)-cis-verbenol, with structurally similar compounds eliciting minor responses. We next targeted the closely related ItypOR40 and ItypOR45. Whereas ItypOR40 was unresponsive, ItypOR45 showed an overlapping response profile with ItypOR41, but a broader tuning. Our phylogenetic analysis shows that these ORs are present in a different OR clade as compared to all other known beetle PRs, suggesting multiple evolutionary origins of PRs in bark beetles. Next, using computational analyses and experimental validation, we reveal two amino acid residues (Gln179 and Trp310) that are important for ligand binding and pheromone specificity of ItypOR41 for (4S)-cis-verbenol, possibly via hydrogen bonding to Gln179. Collectively, our results shed new light on the origins, specificity, and ligand binding mechanisms of PRs in beetles.
Journal Article
Eurasian spruce bark beetle detects lanierone using a highly expressed specialist odorant receptor, present in several functional sensillum types
Background
Insects detect odours using odorant receptors (ORs) expressed in olfactory sensory neurons (OSNs) in the antennae. Ecologically important odours are often detected by selective and abundant OSNs; hence, ORs with high antennal expression. However, little is known about the function of highly expressed ORs in beetles, since few ORs have been functionally characterized. Here, we functionally characterized the most highly expressed OR (ItypOR36) in the bark beetle
Ips typographus
L. (Coleoptera, Curculionidae, Scolytinae), a major pest of spruce. We hypothesized that this OR would detect a compound important to beetle fitness, such as a pheromone component. We next investigated the antennal distribution of this OR using single sensillum recordings (SSR) and in situ hybridization, followed by field- and laboratory experiments to evaluate the behavioural effects of the discovered ligand.
Results
We expressed ItypOR36 in HEK293 cells and challenged it with 64 ecologically relevant odours. The OR responded exclusively to the monoterpene-derived ketone lanierone with high sensitivity. Lanierone is used in chemical communication in North American
Ips
species, but it has never been shown to be produced by
I. typographus
, nor has it been studied in relation to this species’ sensory physiology. Single sensillum recordings revealed a novel and abundant lanierone-responsive OSN class with the same specific response as ItypOR36. Strikingly, these OSNs were co-localized in sensilla together with seven different previously described OSN classes. Field experiments revealed that low release rates of lanierone inhibited beetle attraction to traps baited with aggregation pheromone, with strongest effects on males. Female beetles were attracted to lanierone in laboratory walking bioassays.
Conclusions
Our study highlights the importance of the so-called ‘reverse chemical ecology’ approach to identify novel semiochemicals for ecologically important insect species. Our discovery of the co-localization pattern involving the lanierone OSN class suggests organizational differences in the peripheral olfactory sense between insect orders. Our behavioural experiments show that lanierone elicits different responses in the two sexes, which also depend on whether beetles are walking in the laboratory or flying in the field. Unravelling the source of lanierone in the natural environment of
I. typographus
is required to understand these context-dependent behaviours.
Journal Article
Hospital and Societal Costs of Antimicrobial-Resistant Infections in a Chicago Teaching Hospital: Implications for Antibiotic Stewardship
Background. Organisms resistant to antimicrobials continue to emerge and spread. This study was performed to measure the medical and societal cost attributable to antimicrobial-resistant infection (ARI). Methods. A sample of high-risk hospitalized adult patients was selected. Measurements included ARI, total cost, duration of stay, comorbidities, acute pathophysiology, Acute Physiology and Chronic Health Evaluation III score, intensive care unit stay, surgery, health care-acquired infection, and mortality. Hospital services used and outcomes were abstracted from electronic and written medical records. Medical costs were measured from the hospital perspective. A sensitivity analysis including 3 study designs was conducted. Regression was used to adjust for potential confounding in the random sample and in the sample expanded with additional patients with ARI. Propensity scores were used to select matched control subjects for each patient with ARI for a comparison of mean cost for patients with and without ARI. Results. In a sample of 1391 patients, 188 (13.5%) had ARI. The medical costs attributable to ARI ranged from $18,588 to $29,069 per patient in the sensitivity analysis. Excess duration of hospital stay was 6.4–12.7 days, and attributable mortality was 6.5%. The societal costs were $10.7–$15.0 million. Using the lowest estimates from the sensitivity analysis resulted in a total cost of $13.35 million in 2008 dollars in this patient cohort. Conclusions. The attributable medical and societal costs of ARI are considerable. Data from this analysis could form the basis for a more comprehensive evaluation of the cost of resistance and the potential economic benefits of prevention programs.
Journal Article
Antibiotic Expenditures by Medication, Class, and Healthcare Setting in the United States, 2010–2015
Improving antibiotic use has the potential to decrease healthcare costs by reducing the incidence of antibiotic-resistant infections, antibiotic-associated adverse events, and expenditures due to unnecessary prescriptions. Antibiotic expenditures in 2009 totaled $10.7 billion in the United States. Since then, national and local antibiotic stewardship initiatives have grown. The purpose of this study was to assess trends in antibiotic expenditures by healthcare setting in the United States between 2010 and 2015.
Systemic (nontopical) antibiotic expenditures from January 2010 to December 2015 were extracted from the QuintilesIMS National Sales Perspectives database. These data represent a statistically valid projection of US medication purchases. Regression analyses evaluated trends in expenditures over the study period.
Antibiotic expenditures totaled $56.0 billion over the 6-year period; the majority (59.1%) of expenditures were associated with the outpatient setting. Overall antibiotic expenditures in 2015 ($8.8 billion) were 16.6% lower than in 2010 ($10.6 billion). Antibiotic expenditures similarly decreased in the community by 25.5% (P = .05), but outpatient clinics and mail service pharmacy expenditures experienced significant growth (148% and 67% increase, respectively; P < .01 for both). In 2015, 16.5% of antibiotic expenditures in the community were for parenteral formulations, an increase of 25%.
From 2010 to 2015, antibiotic expenditures decreased. The majority of antibiotic expenditures were in the outpatient setting, specifically community pharmacies. Expenditures for intravenous agents in the community are increasing and may represent increased use. These results reinforce the importance of antibiotic stewardship efforts across the spectrum of healthcare.
Journal Article
Identification of putative olfactory G-protein coupled receptors in Crown-of-Thorns starfish, Acanthaster planci
Background
In marine organisms, and in particular for benthic invertebrates including echinoderms, olfaction is a dominant sense with chemosensation being a critical signalling process. Until recently natural product chemistry was the primary investigative approach to elucidate the nature of chemical signals but advances in genomics and transcriptomics over the last decade have facilitated breakthroughs in understanding not only the chemistry but also the molecular mechanisms underpinning chemosensation in aquatic environments. Integration of these approaches has the potential to reveal the fundamental elements influencing community structure of benthic ecosystems as chemical signalling modulates intra- and inter-species interactions. Such knowledge also offers avenues for potential development of novel biological control methods for pest species such as the predatory Crown-of-Thorns starfish (COTS),
Acanthaster planci
which are the primary biological cause of coral cover loss in the Indo-Pacific.
Results
In this study, we have analysed the COTS sensory organs through histological and electron microscopy. We then investigated key elements of the COTS molecular olfactory toolkit, the putative olfactory rhodopsin-like G protein-protein receptors (GPCRs) within its genome and olfactory organ transcriptomes. Many of the identified
Acanthaster planci
olfactory receptors (
ApORs
) genes were found to cluster within the COTS genome, indicating rapid evolution and replication from an ancestral olfactory GPCR sequence. Tube feet and terminal sensory tentacles contain the highest proportion of
ApORs
. In situ hybridisation confirmed the presence of four
ApORs
,
ApOR15, 18, 25 and 43
within COTS sensory organs, however expression of these genes was not specific to the adhesive epidermis, but also within the nerve plexus of tube feet stems and within the myomesothelium. G alpha subunit proteins were also identified in the sensory organs, and we report the spatial localisation of Gαi within the tube foot and sensory tentacle.
Conclusions
We have identified putative COTS olfactory receptors that localise to sensory organs. These results provide a basis for future studies that may enable the development of a biological control not only for COTS, but also other native pest or invasive starfish.
Journal Article
Putative ligand binding sites of two functionally characterized bark beetle odorant receptors
Background
Bark beetles are major pests of conifer forests, and their behavior is primarily mediated via olfaction. Targeting the odorant receptors (ORs) may thus provide avenues towards improved pest control. Such an approach requires information on the function of ORs and their interactions with ligands, which is also essential for understanding the functional evolution of these receptors. Hence, we aimed to identify a high-quality complement of ORs from the destructive spruce bark beetle
Ips typographus
(Coleoptera, Curculionidae, Scolytinae) and analyze their antennal expression and phylogenetic relationships with ORs from other beetles. Using 68 biologically relevant test compounds, we next aimed to functionally characterize ecologically important ORs, using two systems for heterologous expression. Our final aim was to gain insight into the ligand-OR interaction of the functionally characterized ORs, using a combination of computational and experimental methods.
Results
We annotated 73 ORs from an antennal transcriptome of
I. typographus
and report the functional characterization of two ORs (ItypOR46 and ItypOR49), which are responsive to single enantiomers of the common bark beetle pheromone compounds ipsenol and ipsdienol, respectively. Their responses and antennal expression correlate with the specificities, localizations, and/or abundances of olfactory sensory neurons detecting these enantiomers. We use homology modeling and molecular docking to predict their binding sites. Our models reveal a likely binding cleft lined with residues that previously have been shown to affect the responses of insect ORs. Within this cleft, the active ligands are predicted to specifically interact with residues Tyr84 and Thr205 in ItypOR46. The suggested importance of these residues in the activation by ipsenol is experimentally supported through site-directed mutagenesis and functional testing, and hydrogen bonding appears key in pheromone binding.
Conclusions
The emerging insight into ligand binding in the two characterized ItypORs has a general importance for our understanding of the molecular and functional evolution of the insect OR gene family. Due to the ecological importance of the characterized receptors and widespread use of ipsenol and ipsdienol in bark beetle chemical communication, these ORs should be evaluated for their potential use in pest control and biosensors to detect bark beetle infestations.
Journal Article