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Background: Antibiotic time outs (ABTOs), formal reassessments of all new antimicrobial regimens by the care team, can optimize antimicrobial regimens, reducing antimicrobial overuse and potentially improving outcomes. Implementation of ABTOs is a substantial challenge. We used quality improvement methods to implement robust, meaningful, team-driven ABTOs in general medicine ward services. Methods: We identified and engaged stakeholders to serve as champions for the quality improvement initiative. On October 1, 2018, 2 internal medicine teaching services (services A and B), began conducting ABTOs on all patients admitted to their services receiving systemic antimicrobials for at least 36 hours. Eligible patients were usually identified by the team pharmacist. ABTOs were completed within 72 hours of antibiotic initiation and were documented in the electronic medical record (EMR) by providers using a template. The process was modified as necessary in response to feedback from frontline clinicians using plan-do-study-act (PDSA) methods. We subsequently spread the project to 2 additional internal medicine services (services C and D); 2 family medicine teams (services E and F); and 1 general pediatric service (service G). The project is ongoing. We collected data for the following metrics: (1) proportion of ABTO-eligible patients with an ABTO; (2) proportion of ABTOs conducted within the recommended time frame; (3) documented plan changes as a result of ABTO (eg, change IV antibiotics to PO); (4) proportion of documented plan changes actually completed within 24 hours. Results: Within 12 weeks, services A and B were successfully completing time outs in >80% of their patients. This target was consistently reached by services C, D, E, F, and G almost immediately following launch on those services. As of June 29, 2019, >80% of eligible patients across all participating services have had a time out conducted for 16 consecutive weeks. ABTOs have resulted in a change in management in 35% of cases, including IV-to-PO change in 19% of cases and discontinuation in 5%. Overall, 77% of time outs occurred during the 36–72-hour window. Ultimately, 95% of documented plan changes were completed within 24 hours. Conclusions: ABTOs are effective but implementation is challenging. We achieved high compliance with ABTOs without using electronic reminders. Our results suggest that ABTOs were impactful in the non–critical-care general medicine setting. Next steps include (1) development of EMR-based tools to facilitate identifying eligible patients and ABTO documentation; (2) continued spread through our health care system; and (3) analysis of ABTO impact using ABTO-unexposed patients as a control group.
The link between trade and inequality has been of central importance in analysing international trade since the seminal work of Stolper and Samuelson (1941). While early work on the topic was primarily theoretic, with improved data availability more recent contributions have examined it empirically, with examples using aggregate data including Bergh and Nilsson (2010) and those with micro data including Cosar, Guner, and Tybout (2016). Some studies, such as Jaumotte, Lall, and Papageorgiou (2013), find that the inequality impact of trade is secondary when compared to factors such as technological change while others such as Lim and McNelis (2014) find that the impact is conditional on other factors. In any case, the evidence consistently points to a significant potential for increased trade to exacerbate inequality. More recent contributions, however, discuss the role in inequality itself in determining trade when preferences are non-homothetic. In particular, a growing literature has replaced homothetic preferences with Stone-Geary preferences. Examples include Francois and Kaplan (1996), Bekkers, Francois, and Manchin (2012), Markusen (2013), Caron, Fally, and Markusen (2014), and Bertoletti and Etro (2016). In particular, Bekkers et al. (2012) find evidence in the data on prices of tradeables and inequality that is consistent with the hierarchical demand patterns predicted by the Stone-Geary approach to incorporating non-homothetic preferences in a trade model. Within these models, the key is that the consumption of certain goods (luxuries) only begins when a given consumer reaches a minimum income level. The empirical work also finds that income distribution within a country can be a driving force in trade patterns (e.g. Francois and Kaplan, 1996; Hummels and Klenow, 2005; Dalgin, Trindade, and Mitra, 2008; Fieler, 2011; and Tasarov, 2012).
Objective: This pilot study explored the feasibility and preliminary efficacy of a therapist-facilitated telecare cognitive behavioural anxiety program delivered through schools to children within rural communities. Method: Sixteen children aged 9–12 years (82.5% male), with a principal diagnosis of an anxiety disorder, and their mothers participated in the pilot study. The treatment program was an adaption of the Cool Kids Child and Adolescent Anxiety Management Program. Treatment was delivered by clinical psychologists and involved 10 weekly sessions with children via an interactive, real-time videoconferencing online platform at their school. Parents also received 4 phone calls during the treatment program. Outcome measures included clinician-rated diagnostic status and child- and parent-reported symptoms and interference. Results: According to combined parent and child reports, 62.5% of children no longer met diagnostic criteria for their primary anxiety disorder, and 31.25% did not meet diagnostic criteria for any anxiety disorder post-treatment. Results indicated that the severity of anxiety symptoms, functional impact of anxiety symptoms, externalising difficulties, and depressive symptoms in children decreased significantly post-treatment, as reported by both parents and children. Conclusions: A telecare model of therapy could be a feasible and effective way of delivering evidence-based intervention to children in rural communities.
Our laboratory is investigating ivermectin (IVM) and other members of the avermectin family as new pharmaco-therapeutics to prevent and/or treat alcohol use disorders (AUDs). Earlier work found that IVM significantly reduced ethanol intake in mice and that this effect likely reflects IVM's ability to modulate ligand-gated ion channels. We hypothesized that structural modifications that enhance IVM's effects on key receptors and/or increase its brain concentration should improve its anti-alcohol efficacy. We tested this hypothesis by comparing the abilities of IVM and two other avermectins, abamectin (ABM) and selamectin (SEL), to reduce ethanol intake in mice, to alter modulation of GABAARs and P2X4Rs expressed in Xenopus oocytes and to increase their ability to penetrate the brain. IVM and ABM significantly reduced ethanol intake and antagonized the inhibitory effects of ethanol on P2X4R function. In contrast, SEL did not affect either measure, despite achieving higher brain concentrations than IVM and ABM. All three potentiated GABAAR function. These findings suggest that chemical structure and effects on receptor function play key roles in the ability of avermectins to reduce ethanol intake and that these factors are more important than brain penetration alone. The direct relationship between the effect of these avermectins on P2X4R function and ethanol intake suggest that the ability to antagonize ethanol-mediated inhibition of P2X4R function may be a good predictor of the potential of an avermectin to reduce ethanol intake and support the use of avermectins as a platform for developing novel drugs to prevent and/or treat AUDs.
There are many biological macro-molecules such as nucleic acids, lipids, carbohydrates and proteins. While each of them plays a vital (and interesting) part in life but there is something special about the proteins. Proteins are the key link between the processes of information and replication that take place on a genetic level and the infrastructure of living features. Understanding the properties of proteins is the key to understanding the spark of the life. In this paper we describe our study of various electrical properties of protein when performing measurements at the nanoscale. To achieve this goal we designed and fabricated a nanoelectronic probe. This nano structure consists of four thin film layers. There are two conductive layers and an insulative layer in between. There is also a protective oxide layer as the top most layer. This layer is to prevent the exposure of conductive electrodes to the solution. Underneath the bottom electrode, there is another oxide layer, which can be a thermally grown oxide. This layer insulates the first electrode from the substrate. In this study, while we use non-specific detection of streptavidin protein as a proof of concept, we emphasize that the findings of this study can be extended to specific detection of target proteins, where in this case a specific probe molecule would also be immobilized on the sensor surface.
Purinergic ionotropic P2X receptors are a family of cation-permeable channels that bind extracellular adenosine 5′-triphosphate. In particular, convergent lines of evidence have recently highlighted P2X4 receptors as a potentially critical target in the regulation of multiple nervous and behavioural functions, including pain, neuroendocrine regulation and hippocampal plasticity. Nevertheless, the role of the P2X4 receptor in behavioural organization remains poorly investigated. To study the effects of P2X4 activation, we tested the acute effects of its potent positive allosteric modulator ivermectin (IVM, 2.5–10 mg/kg i.p.) on a broad set of paradigms capturing complementary aspects of perceptual, emotional and cognitive regulation in mice. In a novel open field, IVM did not induce significant changes in locomotor activity, but increased the time spent in the peripheral zone. In contrast, IVM produced anxiolytic-like effects in the elevated plus maze and marble burying tasks, as well as depression-like behaviours in the tail-suspension and forced swim tests. The agent induced no significant behavioural changes in the conditioned place preference test and in the novel object recognition task. Finally, the drug induced a dose-dependent decrease in sensorimotor gating, as assessed by pre-pulse inhibition (PPI) of the acoustic startle reflex. In P2X4 knockout mice, the effects of IVM in the open field and elevated plus maze were similar to those observed in wild type mice; conversely, the drug significantly increased startle amplitude and failed to reduce PPI. Taken together, these results suggest that P2X4 receptors may play a role in the regulation of sensorimotor gating.
Here we present the development of an array of electrical nano-biosensors in a microfluidic channel, called Nanoneedle biosensors. Then we present the proof of concept study for protein detection. A Nanoneedle biosensor is a real-time, label-free, direct electrical detection platform, which is capable of high sensitivity detection, measuring the change in ionic current and impedance modulation, due to the presence or reaction of biomolecules such as proteins or nucleic acids. We show that the sensors which have been fabricated and characterized for the protein detection. We have functionalized Nanoneedle biosensors with receptors specific to a target protein using physical adsorption for immobilization. We have used biotinylated bovine serum albumin as the receptor and sterptavidin as the target analyte. The detection of streptavidin binding to the receptor protein is also presented.
With the aid of negative dielectrophoresis (nDEP) force in conjunction with shear force and at an optimal sodium hydroxide (NaOH) concentration we demonstrated a switch-like functionality to elute immuno-bound beads from the surface. At an optimal flow rate and NaOH concentration, nDEP turned on results in bead detachment, whereas when nDEP is off, the beads remain attached. This platform offers the potential for performing a bead-based multiplexed immunoassay where in a single channel various regions are immobilized with a different antibody, each targeting a different antigen. As a proof of concept we demonstrated the ability of nDEP to provide this switching behavior in a singleplex assay for the interactions that were in the same order of magnitude in strength as typical antibody-antigen interactions.
Three-dimensional (3-D) geometry can be described in many ways, with both a varying syntax and a varying semantics. As a result, several very diverse schemas and file formats can be deployed to describe geometry, depending on the application domain in question. In a multidisciplinary domain such as the domain of architecture, engineering, and construction, this range of specialized schemas makes file format conversions inevitable. The approach adopted by current conversion tools, however, often results in a loss of information, most often due to a “mistranslation” between different syntaxes and/or semantics, leading to errors and limitations in the design conception stage and to inefficiency due to the required remodeling efforts. An approach based on semantic web technology may reduce the loss of information significantly, leading to an improved processing of 3-D information and hence to an improved design practice in the architecture, engineering, and construction domain. This paper documents our investigation of the nature of this 3-D information conversion problem and how it may be encompassed using semantic web technology. In an exploratory double test case, we show how the specific deployment of semantic rule languages and an appropriate inference engine are to be adopted to improve this 3-D information exchange. It shows how semantic web technology allows the coexistence of diverse descriptions of the same 3-D information, interlinked through explicit conversion rules. Although only a simple example is used to document the process, and a more in-depth investigation is needed, the initial results indicate the suggested approach to be a useful alternative approach to obtain an improved 3-D information exchange.
This paper gives an extensive characterization of the range of validity of the Compton and Raman approximations to the exact free electron laser dispersion relation for a cold, relativistic electron beam propagating through a constantamplitude helical wiggler magnetic field. The electron beam is treated as infinite in transverse extent. Specific properties of the exact and approximate dispersion relations are investigated analytically and numerically. In particular, a detailed numerical analysis is carried out to determine the range of validity of the Compton approximation.
This paper contains an analysis of pulse shapes produced by a delta-function disturbance of the equilibrium state of a relativistic electron beam propagating through a constant-amplitude, helical magnetic wiggler field. Pulse shapes are determined by using the relativistic pinch-point techniques developed by Bers, Ram and Francis. Two pulses are produced corresponding to a convective upshifted pulse (representing the production of the high-frequency radiation desired in a free electron laser) and a downshifted pulse. The downshifted instability may be convective or absolute, depending upon the beam density and momentum spread. Parameter regimes in which the downshifted instability is convective are investigated. It is found that momentum spreads sufficiently large to suppress the absolute instability reduce the growth rate of the upshifted pulse to negligible values. Pulse shapes computed by using the Raman and Compton approximations are compared with exact pulse shapes. It is found that the Raman approximation should be applied to the downshifted regime for most systems of practical interest.