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The Great Recession that followed the financial crisis of 2007 is not only the largest economic crisis after the Great Depression of the 1930s, it also signals a crisis of economics as a discipline. This is not only the consequence of the inadequacy of mainstream macroeconomics, and specifically the Dynamic Stochastic General Equilibrium (DSGE) workhorse model, to forecast such a huge event, or at least to detect the worrying tendencies towards it. Even more relevant is the choice to explicitly avoid the modeling of large crises (that for someone is a motivation for not attacking pre-crisis DSGE models focused on the analysis of small deviations from the steady-state), so denying the intrinsic nature of capitalism, a system that necessarily proceeds through cycles and (extended) crises. The replies of the DSGE approach to critics have led to extensions regarding for instance the role of financial frictions, heterogeneous agents, and bounded rationality (though typically in the form of quasi-rational expectations). The alternative paradigm of agent-based (AB) macroeconomics can take into account all these elements at once within an evolutionary modeling framework based on heterogeneity and interaction, so capable to endogenously reproduce complex dynamics, from small fluctuations to large crises, due to innovation and industrial dynamics, rising inequality and financial instability, and so on. The integration between AB macroeconomics and the (post-Keynesian) stock–flow consistent approach represents a promising way for the future development of this research field. [ABSTRACT FROM AUTHOR]

This article studies coordination between firms in a multi-sectoral macroeconomic model with endogenous business cycles. Firms are both in competition and interdependent, and set their prices with a markup over unit costs. Markups are heterogeneous and evolve under market pressure. We observe a systematic coordination between firms of each sector, and between each sector. The resulting pattern of relative prices is fairly consistent with the labor theory of value. These emerging features are robust to technology shocks. [ABSTRACT FROM AUTHOR]

This article presents an application of recent management theories concerning the effect of pre-entry experience and knowledge transfer within the context of creative industries. The setting of the empirical research is the television situation comedy (sitcom) industry in the United States between 1949 and 2011. Specifically, we explore the factors that explain the survival rate of sitcoms and their spin-offs. We develop two sets of indicators to explore the effect of pre-entry experience: team similarity and star power based on the character/actor. Our findings show that spin-offs, or sitcoms that inherit character/actors and theme elements from a successful parent sitcom, have a greater likelihood to survive than de novo sitcoms. Even further, the greater the number of team members that not only worked with each other on previous shows but worked together on the same parent show, the better the performance of the spin-off. By contrast, star power, or the fame of the character/actor(s) that passes from the parent to the spin-off, shows no significant correlation with performance. We suggest that these results provide initial evidence that, consistent with the literature on spinouts in manufacturing industries, knowledge endowments represent an important source of performance heterogeneity in project-based industries. [ABSTRACT FROM AUTHOR]

The Defense Advanced Research Projects Agency (DARPA) was formed in 1958 as a research and development (R&D) agency within the US Department of Defense, while the two newer but closely comparable R&D agencies, the Advanced Research Projects Agency-Energy (ARPA-E) and the Intelligence Advanced Research Projects Agency (IARPA), were formed within the Department of Energy (DOE) and the Office of the Director of National Intelligence in 2009 and 2007, respectively. The three share an ambitious innovation organization model, operating as public sector intermediaries between science and industry to pursue mission-oriented, high-risk/high-reward, breakthrough research. They also actively promote the follow-on development and implementation of technologies they support in their mission areas, achieving what has been termed mission innovation. They are therefore much more activist than more standard American R&D agencies, which do not pursue conscious technology strategies oriented to specific mission technology challenges. The three "ARPA" agencies tend to operate as change agents within the often conservative "legacy" sectors they operate within—defense, energy, and intelligence. Within the context of the overall US innovation system, DARPA and IARPA are leading examples of what can be termed the "extended pipeline" model, while ARPA-E is located within a more traditional R&D "pipeline" model agency, the DOE, trying to reach further down the innovation pipeline. All face the types of innovation barriers common to legacy sectors, which further challenge their efforts to implement their innovations. Despite these challenges, this ARPA model has proven quite dynamic; DARPA has an unparalleled record of technological advance, and the other two are rapidly building their own records. ARPA-E and IARPA show that the DARPA model is now a proven one in the innovation space, clearly relevant for consideration in other technology development mission sectors. [ABSTRACT FROM AUTHOR]

Story-based learning is well recognized as an effective strategy for adult health education. However, there is a scarcity of research on story-based health education among women in South Asian diasporic communities. To address this gap, we undertook a pilot study in Toronto to explore how South Asian women respond to the use of fact-based and story-based materials for HIV/STI prevention. A total of 78 women were recruited from across the city. We engaged nearly half of the women (n =40) using fact sheets on HIV/STIs, and the remainder (n =38) using stories written by South Asian women on HIV/STIs. Surveys and focus groups were used to explore participants' responses in terms of knowledge, attitudes and perspectives. Results indicated that both approaches were effective in increasing participants' knowledge of HIV/STIs. Participants in the fact-based sessions tended to distance themselves from the idea of personal HIV/STI risks. Participants in the story-based groups were emotionally engaged, expressing personal commitments to take a stand against HIV stigma. In summary, within-culture stories are potentially effective tools that enable women to make sense of their own life situations and contextual vulnerabilities. Story-based materials are useful for breaking the silence of taboo topics, addressing stigma and discrimination and raising awareness about collective empowerment. [ABSTRACT FROM AUTHOR]

Background: Many lines of evidence point to HIV-1 subtype-specific differences in the development of drug resistance mutations. While variation between subtype C and others has been extensively explored, there has been less emphasis on subtypes common to West Africa. We examined a previously described national survey of pretreatment drug resistance in HIV-1-infected Nigerian children aged <18 months, to explore the association between subtypes and patterns of resistance.Methods: Five hundred and forty-nine dried blood spots, from 15 early infant diagnostic facilities in Nigeria, were amplified and HIV-1 polymerase was sequenced. Four hundred and twenty-four were analysed for surveillance drug resistance mutations (SDRMs). Associations between subtype and SDRMs were evaluated by Fisher's exact test and logistic regression analysis, controlling for geographical region and exposure.Results: Using the sub-subtypes of HIV-1 G defined by Delatorre et al. (PLoS One 2014.9: e98908) the most common subtypes were CRF02_AG (174, 41.0%), GWA-I (128, 30.2%), GWA-II (24, 5.7%), GCA (11, 2.6%), A (21, 5.0%) and CRF06_cpx (18, 4.2%). One hundred and ninety infants (44.8%) had ≥1 NNRTI mutation, 92 infants (21.7%) had ≥1 NRTI mutation and 6 infants (1.4%) had ≥1 PI mutation. By logistic regression, 67N was more common in GWA-II/GCA than CRF02_AG (OR 12.0, P = 0.006), as was 70R (OR 23.1, P = 0.007), 184I/V (OR 2.92, P = 0.020), the presence of ≥1 thymidine analogue mutation (TAM) (OR 3.87, P = 0.014), ≥1 type 2 TAM (OR 7.61, P = 0.001) and ≥1 NRTI mutation (OR 3.26, P = 0.005).Conclusions: This dataset reveals differences among SDRMs by subtype; in particular, between the GWA-II and GCA subclades, compared with CRF02_AG and GWA-I. [ABSTRACT FROM AUTHOR]

Background: The Dundee classification is a simple severity assessment tool that could optimize treatment decisions and clinical outcomes in adult patients with cellulitis; however, it has not been validated in a large cohort.Objectives: To determine whether the Dundee classification reliably identified those patients with cellulitis who had a higher mortality, a longer length of hospital stay or an increased risk of readmission.Methods: We performed a retrospective study of all adults with a primary discharge diagnosis of cellulitis admitted to Auckland City Hospital from August 2013 to June 2015. We classified patients by severity using the Dundee scoring system.Results: The 30 day all-cause mortality in adult patients with a discharge diagnosis of cellulitis was 2% (29/1462) overall, and was 1% (10/806), 2% (6/271), 3% (10/353) and 9% (3/32) in Classes 1, 2, 3 and 4 of the Dundee classification, respectively (P = 0.01). Mortality was strongly associated with age >65 years (OR 9.37, 95% CI 3.00-41.23) and with heart failure (OR 6.16, 95% CI 2.73-14.23). There were significant associations between the Dundee classification and the incidence of bacteraemia, the length of hospital stay and the rate of readmission to hospital.Conclusions: The Dundee classification is a simple, reliable tool that can be easily applied in clinical settings to predict risk of mortality in order to determine which patients can be managed in the community with oral or intravenous therapy, and which require inpatient care. [ABSTRACT FROM AUTHOR]

Objectives: The neutropenic murine thigh infection model and a dose-fractionation approach were used to determine the pharmacokinetic/pharmacodynamic (PK/PD) relationship of LYS228, a novel monobactam antibiotic with activity against Enterobacteriaceae including carbapenem-resistant strains.Methods: Mice (n = 4 per group) were inoculated with Enterobacteriaceae strains via intramuscular injection. Two hours post-bacterial inoculation, treatment with LYS228 was initiated. Animals were euthanized with CO2 24 h after the start of therapy and bacterial counts (log10 cfu) per thigh were determined. PK parameters were calculated using free (f) plasma drug levels.Results: Following a dose-fractionation study, non-linear regression analysis determined that the predominant PK/PD parameter associated with antibacterial efficacy of LYS228 was the percentage of the dosing interval that free drug concentrations remained above the MIC (%fT>MIC). In a dose-dependent manner, LYS228 reduced the thigh bacterial burden in models established with Enterobacteriaceae producing β-lactamase enzymes of all classes (e.g. ESBLs, NDM-1, KPC, CMY-2 and OXA-48). The range of the calculated static dose was 86-649 mg/kg/day for the isolates tested, and the magnitude of the driver of efficacy was 37-83 %fT>MIC. %fT>MIC was confirmed as the parameter predominantly driving efficacy as evidenced by a strong coefficient of determination (r2 = 0.68). Neutrophils had minimal impact on the effect of LYS228 in the murine thigh infection model.Conclusions: LYS228 is efficacious in murine thigh infection models using β-lactamase-producing strains of Enterobacteriaceae, including those expressing metallo-β-lactamases, ESBLs and serine carbapenemases, with the PK/PD driver of efficacy identified as %T>MIC. [ABSTRACT FROM AUTHOR]

Protein synthesis inhibitor antibiotics inhibit synthesis of new proteins, including exotoxins and other important virulence determinants in Staphylococcus aureus. A summary of the literature regarding the use of adjunctive protein synthesis inhibitors for toxin suppression in the setting of S. aureus infections is presented. [ABSTRACT FROM AUTHOR]

Background: Current inhaled polymyxin therapy is empirical and often large doses are administered, which can lead to pulmonary adverse effects. There is a dearth of information on the mechanisms of polymyxin-induced lung toxicity and their intracellular localization in lung epithelial cells.Objectives: To investigate the intracellular localization of polymyxins in human lung epithelial A549 cells.Methods: A549 cells were treated with polymyxin B and intracellular organelles (early and late endosomes, endoplasmic reticulum, mitochondria, lysosomes and autophagosomes), ubiquitin protein and polymyxin B were visualized using immunostaining and confocal microscopy. Fluorescence intensities of the organelles and polymyxin B were quantified and correlated for co-localization using ImageJ and Imaris platforms.Results: Polymyxin B co-localized with early endosomes, lysosomes and ubiquitin at 24 h. Significantly increased lysosomal activity and the autophagic protein LC3A were observed after 0.5 and 1.0 mM polymyxin B treatment at 24 h. Polymyxin B also significantly co-localized with mitochondria (Pearson's R = 0.45) and led to the alteration of mitochondrial morphology from filamentous to fragmented form (n = 3, P < 0.001). These results are in line with the polymyxin-induced activation of the mitochondrial apoptotic pathway observed in A549 cells.Conclusions: Accumulation of polymyxins on mitochondria probably caused mitochondrial toxicity, resulting in increased oxidative stress and cell death. The formation of autophagosomes and lysosomes was likely a cellular response to the polymyxin-induced stress and played a defensive role by disassembling dysfunctional organelles and proteins. Our study provides new mechanistic information on polymyxin-induced lung toxicity, which is vital for optimizing inhaled polymyxins in the clinic. [ABSTRACT FROM AUTHOR]

Objectives: To describe the pharmacokinetics of isoniazid and acetyl-isoniazid in TB/HIV-coinfected patients, and assess the effects of efavirenz co-administration and a 50% increase in the dose of rifampicin on the pharmacokinetic parameters of isoniazid and acetyl-isoniazid.Methods: TB/HIV-coinfected patients participating in the three-treatment-arm RAFA randomized controlled trial conducted in West Africa were recruited into the pharmacokinetics sub-study. Five serial blood samples were collected on a single visit between 4 and 8 weeks after initiation of antituberculosis treatment. Concentration-time data for isoniazid and acetyl-isoniazid were analysed using non-linear mixed-effects models.Results: Isoniazid concentrations from 150 patients were available for analysis, and 79 of these (53%) also had concentrations of acetyl-isoniazid. Isoniazid pharmacokinetics was best described with a two-compartment disposition model with lagged first-order absorption and elimination using a semi-mechanistic model describing hepatic extraction. The model identified two elimination pathways, separating formation of acetyl-isoniazid from other routes of metabolism. The predicted AUC0-24 is reduced by 29% in patients who are fast acetylators of isoniazid and receiving efavirenz-based ART (6.73 versus 4.68 mg·h/L). In slow acetylators, efavirenz-based ART had no effect on isoniazid exposure (AUC0-24 = 17.5 mg·h/L).Conclusions: Efavirenz-based ART affects the acetylation metabolic pathway amongst rapid acetylators, resulting in reduced exposure to isoniazid. Pharmacokinetics of isoniazid and acetyl-isoniazid were not influenced by the 50% increase in rifampicin dose. [ABSTRACT FROM AUTHOR]

Evaluators play a central role in assessments of researchers' performance for reward, but the nature of their role and influence is not well understood. Ongoing reliance on evaluator judgement is typically justified as a need for referees in contests for reward, because quantitative performance measures alone can be subject to distortion. Yet, if evaluators are able to privately establish or interpret the performance standards utilized in evaluation, it may inhibit equality of opportunity, limit applicant pools, and reinforce existing inequalities. This article untangles the different roles played by evaluators through the development of a typology of systems of performance evaluation from existing literature. The typology is then applied to one type of evaluation system—promotion in a public research organization (PRO)—to investigate how and why particular evaluator roles emerge, and what contextual factors influence their implementation. Data are drawn from a mixed-method case study of a large Australian PRO, which includes data from one focus group, 22 in-depth interviews and 803 survey responses. The case study finds that evaluators' role can extend to sponsorship of researchers through the promotion system when diversity in research specializations inhibits the establishment of uniform performance standards. It also demonstrates that reporting lines and evaluator workload impact how and to whom sponsoring support is given. [ABSTRACT FROM AUTHOR]

The use of indicators in research policy and evaluation is widely perceived as problematic. Responding to demands for explicit normative framings in STI governance, I propose an agenda for transforming the place and role of indicators in policy. Given that expert advice should not separate knowledge formation from decision-making under conditions of uncertainty and lack of value consensus, I argue that current scientometrics is too focused on technical issues, too reductionist, and too isolated from the contexts and values of its use. Using Callon's analytical framework of 'secluded research' vs. 'research in the wild', I propose three moves for improving design and use of science, technology, and innovation (STI) indicators. First, to continue ongoing trends towards pluralizing the data sources, processing and visualization techniques, and expand the research communities involved in scientometrics. Second, to develop forms of quantitative evidence that can be contextualized with the participation of a more diverse set of stakeholders. Third, to open up the policy framings implicit in measurement, and use quantitative analyses to reveal more balanced perspectives of existing and alternative STI options. I conclude by arguing that these shifts are necessary to preserve epistemic diversity and pluralism in the face of ongoing managerial push for standardization via 'platforms' run by commercial oligopolies. [ABSTRACT FROM AUTHOR]

Challenge-led interdisciplinary research is a relatively new way of bringing together disciplinary expertise in response to complex societal and environmental problems. Common difficulties include how to define 'interdisciplinary research'; how to improve the participation and flourishing of early-career researchers; and how to manage projects with disparate teams of researchers while deepening external collaborations. This article reports from a major initiative of this type. It interrogates qualitative data generated from program evaluation among participating researchers, identifying insights on beneficial structural (program design) and 'soft' infrastructure (human capital) variables, as well as on-going barriers and tensions. Notwithstanding the difficulties of communicating and collaborating across epistemic domains, the program in question exceeded expectations in building interdisciplinary research and early research careers—though not necessarily in ways initially imagined. Staggered funding pools meant it was acceptable in early phases for low-cost projects to 'fail safely', while strict funding guidelines on distal interdisciplinarity compelled unlikely and novel researcher combinations and projects. Moreover, such program design features 'granted permission' to early-career researchers to approach more senior, cross-faculty researchers as potential collaborators, hence building leadership capacity. Human capital variables included a dialogic approach to project development ('curating' projects as they evolve), inclusive program leadership, and promotion of the benefits of a collaborative rather than competitive research culture. Distal interdisciplinarity not only nourishes novel and unlikely research projects that respond to complex problems; with good program design and meaningful relationships it can, we argue, also build research careers differently from an early phase. [ABSTRACT FROM AUTHOR]

The effects of media exposure differ when people are given the opportunity to choose content compared to when they are forced to view it. Contemporary explanations propose that differences between forced and selected exposure occur because of between-subject differences. We propose that differences also result from within-subject psychological reactions. Using a novel experimental design, a representative sample of U.S. adults (N = 1,967) provided their content preferences in a first session and then, in a second session, were randomly assigned to choose content or to view randomly-assigned content. Results confirm that forced exposure yields different psychological reactions than selected exposure, even in some cases among participants forced to view their preferred content. [ABSTRACT FROM AUTHOR]

In this study, we used age–crime statistics from India to investigate the two core tenets of Hirschi and Gottfredson's (HG) invariance thesis that the age distribution of crime is always and everywhere adolescent spiked and thereafter declines continuously into elder ages. Besides comparisons to the inverted J-shaped distribution projected by HG, we further compared Indian age–crime patterns with those in United States (Western nation; main evidential source for HG invariance projection) and Taiwan (like India, a non-Western collectivist society). Findings suggest considerable divergence in India's age–crime patterns compared with HG invariance norm and US age–crime distributions, but overall similarity with Taiwan's age–crime schedules. Implications for research and theory on the age–crime relation more broadly are discussed. [ABSTRACT FROM AUTHOR]

This paper introduces and studies jumping pure grammars, which are conceptualized just like classical pure grammars except that during the applications of their productions, they can jump over symbols in either direction within the rewritten strings. The paper compares the generative power of jumping pure grammars with that of classical pure grammars while distinguishing between their versions with and without erasing productions. Apart from sequential versions, the paper makes an analogical study in terms of parallel versions of jumping pure grammars represented by 0L grammars. [ABSTRACT FROM AUTHOR]

A subset D of vertices of a graph G is a total dominating set if every vertex of G is adjacent to at least one vertex of D. The total dominating set D is called a total co-independent dominating set if the subgraph induced by V − D is edgeless and has at least one vertex. The minimum cardinality of any total co-independent dominating set is the total co-independent domination number of G and is denoted by γ t, c o i (G) ⁠. In this work we study some complexity and combinatorial properties of γ t, c o i (G) ⁠. Specifically, we prove that deciding whether γ t, c o i (G) ≤ k for a given integer k is an NP-complete problem and give several bounds on γ t, c o i (G) ⁠. Moreover, since any total co-independent dominating set is a total dominating set, we characterize all the trees having equal total co-independent domination number and total domination number. [ABSTRACT FROM AUTHOR]

The effects of plant species richness on the function and stability of ecosystems have been an area of focus in recent decades. Arthropod community is one of the most important components in agroecosystems and can provide multiple ecosystem services, including biocontrol and pollination. In particular, species composition and biocontrol function can be sensitive to changes in plant species richness. Here, we designed 50 plots with five levels of plant species richness to examine arthropod distribution and composition over 4 yr. Arthropod richness was found to be positively correlated with plant species richness. High plant species richness can enhance the temporal stability of the arthropod community but can also lead to a decline in the population stability of some species. The species richness and biomass of environmentally friendly insects (EFI), such as honeybees, ants and flies, were found to be positively correlated with those of the natural enemies. As such, high levels of EFI could sustain food web robustness by serving as alternative prey/hosts for natural enemies. The mediation of EFI in the interaction between crops and pests has implications for successful biocontrol practices using natural enemies. Planting diverse plant species with a certain level of spatial turnover could benefit the biocontrol function of natural enemies and safeguard multiple ecosystem services. [ABSTRACT FROM AUTHOR]

Introduction: E-cigarettes may be positively used in tobacco cessation treatments. However, neither the World Health Organization nor the American Food and Drug Administration has recognized them as effective cessation aids. Data about the efficacy and safety of e-cigarettes are still limited and controversial.Methods: This was a double-blind randomized controlled study. The main focus of this article is on a secondary outcome of the study, that is, the assessment of effectiveness and safety of e-cigarettes in achieving smoking cessation in a group of chronic smokers voluntarily involved in long-term lung cancer screening. Participants were randomized into three arms with a 1:1:1 ratio: e-cigarettes (Arm 1), placebo (Arm 2), and control (Arm 3). All subjects also received a low-intensity counseling.Results: Two hundred ten smokers were randomized (70 to nicotine e-cigarettes, 70 nicotine-free placebo e-cigarettes, and 70 to control groups). About 25% of participants who followed a cessation program based on the use of e-cigarettes (Arm 1 and Arm 2) were abstinent after 3 months. Conversely, only about 10% of smokers in Arm 3 stopped. A Kruskal-Wallis test showed significant differences in daily cigarettes smoking across the three arms (K-W = 6.277, p = .043). In particular, participants in Arm 1 reported a higher reduction rate (M = -11.6441, SD = 7.574) than participants in Arm 2 (M = -10.7636, SD = 8.156) and Arm 3 (M = -9.1379, SD = 8.8127).Conclusions: Our findings support the efficacy and safety of e-cigarettes in a short-term period. E-cigarettes use led to a higher cessation rate. Furthermore, although all participants reported a significant reduction of daily cigarette consumption compared to the baseline, the use of e-cigarettes (including those without nicotine) allowed smokers to achieve better results.Implications: E-cigarettes increased the stopping rate as well as the reduction of daily cigarettes in participants who continued smoking. In fact, although all participants reported a significant reduction of tobacco consumption compared to the baseline, the use of e-cigarettes allowed smokers to achieve a better result. It could be worthwhile to associate this device with new ICT-driven models of self-management support in order to enable people to better handle behavioral changes and side effects. This is true for ready-to-quit smokers (such as our participants) but can also be advantageous for less motivated smokers engaged in clinical settings. [ABSTRACT FROM AUTHOR]

Objective: To explore the understandings of and engagement with e-cigarettes, of young adults from disadvantaged backgrounds, and how these may have an impact on existing smoking identities.Methods: Twenty-two small group and 11 individual qualitative interviews were conducted in Central Scotland with 72 16-24 year olds between September 2015 and April 2016. Participants were mostly smokers and ex-smokers from socioeconomically disadvantaged backgrounds.Results: Although most participants had tried e-cigarettes, they generally held ambivalent views about e-cigarettes and vaping. Two overarching themes were identified which helped in understanding this. Firstly, e-cigarettes were understood by the participants in relation to their existing smoking identities. Vaping was viewed as less controllable and more addictive than smoking, which did not fit with their self-identity as controlled smokers. Secondly, they felt that vaping could not replace the social and cultural importance that smoking had in their lives.Conclusion: This study suggests that though young adults from disadvantaged areas are trying e-cigarettes for various reasons, vaping is rarely sustained. Through their own experiences of vaping and their observations of others vaping, the participants perceive the behavior as endangering an existing acceptable and controlled smoking identity. Additionally, e-cigarettes were considered to be a jarring presence in existing social situations where smoking was valued. This study, therefore, provides insights into how young adults may be rationalizing their continued smoking in the face of potentially less harmful alternatives.Implications: As new and novel nicotine delivery devices, and due to their similarity to smoking, e-cigarettes have the potential to help smokers in their quit attempts. However, the findings from this study raise questions about whether e-cigarettes are regarded as having this potential by young adult smokers from disadvantaged socioeconomic environments where smoking is more commonplace and acceptable. [ABSTRACT FROM AUTHOR]

Objectives: As pathologists and laboratorians, we can enhance patient care by promoting the appropriate ordering of diagnostic tests. Our goal was to improve the ordering of BCR-ABL1 tests by using the EPIDEM model of quality improvement.Methods: We applied the EPIDEM model, which emphasizes understanding local context, culture, and resources, to explore inappropriate BCR-ABL1 ordering, promote and implement a new reflexive testing strategy in-house, document and evaluate effectiveness, and make stepwise modifications.Results: Multiple quality improvement interventions correlated with cost savings and decreased total errors and incorrect orders for both BCR-ABL1 major and minor positive patients. Furthermore, our laboratory built stronger collaborative relationships with colleagues within and outside of pathology.Conclusions: Our molecular pathology laboratory successfully used the EPIDEM model of quality improvement to improve the ordering of BCR-ABL1 tests and promote better patient care by focusing on educational efforts and modification of laboratory workflow. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the effectiveness of anemia management and audit with feedback practices in reducing overuse of RBC transfusion. Methods This review follows the Centers for Disease Control and Prevention's Laboratory Medicine Best Practice Systematic Review (A-6) method. We searched the literature and solicited unpublished studies on practices to reduce overuse of RBC transfusions as measured by reductions in units transfused and proportion of patients transfused. Results Thirteen studies on preoperative anemia management and three studies on audit feedback practices met inclusion criteria. Strength of evidence was high to moderate for reducing the number of units and proportion of patients transfused. Conclusions Preoperative anemia management reduces the proportion of patients transfused and units of RBCs transfused. Audit with feedback across cases, physicians, and/or service areas, as part of a continuous quality improvement practice, reduces the proportion of patients and units of RBCs transfused. [ABSTRACT FROM AUTHOR]

Objectives Point-of-care (POC) testing is generally less precise and has higher reagent costs per test than laboratory-based assays. However, POC hemostasis testing can offer significant advantages in particular situations: patient-managed warfarin therapy as well as rapid turnaround time heparin management for intraoperative patients. Of note, POC hemostasis testing is generally approved for the purposes of anticoagulation monitoring and is inferior to laboratory coagulation testing for the diagnosis of congenital or acquired coagulopathy. Methods The frequently used POC coagulation instruments for POC international normalized ratio and activated clotting time are reviewed, as well as their typical performance relative to central laboratory testing (where available). Results Several cases are discussed that highlight the benefits, as well as pitfalls, of POC coagulation testing. Conclusions POC coagulation testing for anticoagulation monitoring offers advantages in particular situations. Clear policies and protocols must be developed to guide proper use of POC versus central laboratory hemostasis testing. [ABSTRACT FROM AUTHOR]

Objectives To determine clinical utility of Onclarity human papillomavirus (HPV) assay for atypical squamous cells-undetermined significance (ASC-US) triage, and the value of HPV genotyping within ASC-US. Methods Women (n = 33,858; 21 years or older) had HPV testing using Onclarity and Hybrid Capture 2 (HC2). ASC-US individuals (n = 1,960, 5.8%) were referred to colposcopy. Results Of ASC-US, 39.1% were HPV positive by Onclarity; HPV 16 was the most prevalent genotype (7.4%). Cervical intraepithelial neoplasia grade 2 (CIN 2) and CIN 3+ prevalences were 4.4% and 2.2%, respectively. Onclarity had sensitivity for CIN 2+ (85.7%) and CIN 3+ (91.4%), and specificities for CIN 2+ (64.1%) and CIN 3+ (62.0%), similar to HC2. Risks for CIN 3+ were 16.1%, 2.8%, 2.5%, and 2.7% with HPV 16, 18, 45, and 11 other genotypes, respectively. Conclusions Onclarity is clinically validated for ASC-US triage. Through risk stratification, genotyping could help identify women at highest risk for CIN 3+. [ABSTRACT FROM AUTHOR]

Instrumental variable (IV) analysis is an increasingly popular tool for inferring the effect of an exposure on an outcome, as witnessed by the growing number of IV applications in epidemiology, for instance. The majority of IV analyses of time-to-event endpoints are, however, dominated by heuristic approaches. More rigorous proposals have either sidestepped the Cox model, or considered it within a restrictive context with dichotomous exposure and instrument, amongst other limitations. The aim of this article is to reconsider IV estimation under a structural Cox model, allowing for arbitrary exposure and instruments. We propose a novel class of estimators and derive their asymptotic properties. The methodology is illustrated using two real data applications, and using simulated data. [ABSTRACT FROM AUTHOR]

Autoimmune diseases are characterized by highly specific immune responses against molecules in self-tissues. Different autoimmune diseases are characterized by distinct immune responses, making autoantibodies useful for diagnosis and prediction. In many diseases, the targets of autoantibodies are incompletely defined. Although the technologies for autoantibody discovery have advanced dramatically over the past decade, each of these techniques generates hundreds of possibilities, which are onerous and expensive to validate. We set out to establish a method to greatly simplify autoantibody discovery, using a pre-filtering step to define subgroups with similar specificities based on migration of radiolabeled, immunoprecipitated proteins on sodium dodecyl sulfate (SDS) gels and autoradiography [Gel Electrophoresis and band detection on Autoradiograms (GEA)]. Human recognition of patterns is not optimal when the patterns are complex or scattered across many samples. Multiple sources of errors-including irrelevant intensity differences and warping of gels-have challenged automation of pattern discovery from autoradiograms.In this article, we address these limitations using a Bayesian hierarchical model with shrinkage priors for pattern alignment and spatial dewarping. The Bayesian model combines information from multiple gel sets and corrects spatial warping for coherent estimation of autoantibody signatures defined by presence or absence of a grid of landmark proteins. We show the pre-processing creates more clearly separated clusters and improves the accuracy of autoantibody subset detection via hierarchical clustering. Finally, we demonstrate the utility of the proposed methods with GEA data from scleroderma patients. [ABSTRACT FROM AUTHOR]

Small area ecological studies are commonly used in epidemiology to assess the impact of area level risk factors on health outcomes when data are only available in an aggregated form. However, the resulting estimates are often biased due to unmeasured confounders, which typically are not available from the standard administrative registries used for these studies. Extra information on confounders can be provided through external data sets such as surveys or cohorts, where the data are available at the individual level rather than at the area level; however, such data typically lack the geographical coverage of administrative registries. We develop a framework of analysis which combines ecological and individual level data from different sources to provide an adjusted estimate of area level risk factors which is less biased. Our method (i) summarizes all available individual level confounders into an area level scalar variable, which we call ecological propensity score (EPS), (ii) implements a hierarchical structured approach to impute the values of EPS whenever they are missing, and (iii) includes the estimated and imputed EPS into the ecological regression linking the risk factors to the health outcome. Through a simulation study, we show that integrating individual level data into small area analyses via EPS is a promising method to reduce the bias intrinsic in ecological studies due to unmeasured confounders; we also apply the method to a real case study to evaluate the effect of air pollution on coronary heart disease hospital admissions in Greater London. [ABSTRACT FROM AUTHOR]

Many research studies aim to draw causal inferences using data from large, nationally representative survey samples, and many of these studies use propensity score matching to make those causal inferences as rigorous as possible given the non-experimental nature of the data. However, very few applied studies are careful about incorporating the survey design with the propensity score analysis, which may mean that the results do not generate population inferences. This may be because few methodological studies examine how to best combine these methods. Furthermore, even fewer of them investigate different non-response mechanisms. This study examines methods for handling survey weights in propensity score matching analyses of survey data under different non-response mechanisms. Our main conclusions are: (i) whether the survey weights are incorporated in the estimation of the propensity score does not impact estimation of the population treatment effect, as long as good population treated-comparison balance is achieved on confounders, (ii) survey weights must be used in the outcome analysis, and (iii) the transferring of survey weights (i.e., assigning the weights of the treated units to the comparison units matched to them) can be beneficial under certain non-response mechanisms. [ABSTRACT FROM AUTHOR]

We provide an in-depth analysis of the extent and nature of heterogeneity in willingness-to-pay (WTP) for the attributes of higher education institutions (HEIs). Using data from Ireland, mixed logit and generalized multinomial logit models are used to examine heterogeneity in WTP by region, academic ability, and socio-economic status. The analysis shows that regional variation in WTP for the attributes of HEIs is substantial, which suggests that preferences may be shaped by the characteristics of the region in which a student lives. Heterogeneity in WTP is also found based on a student's academic ability, with higher-ability students willing to pay considerably more for a higher-quality institution compared to lower-ability students. We also find that students in the highest socio-economic group are willing to pay more for all attributes. [ABSTRACT FROM AUTHOR]

This paper presents a second-generation Schumpeterian growth model to investigate the existence of possible links between firms' size, competition stiffness and the effectiveness of R&D policy. In the model, the step size of innovation is randomly drawn from a Pareto distribution, and firms are heterogeneous in terms of market power. The paper finds that the optimal R&D policy is to subsidize R&D and not to tax it, and that more intense competition enlarges the gap between free-market R&D investment and the optimal outcome. However, the paper also finds that the short-run impact on welfare of R&D policy is always negative, and that the recovery time of the welfare loss as a result of the subsidy is negatively related to firms' market power. [ABSTRACT FROM AUTHOR]

In a corporate tournament, executive directors are motivated by the prospect of promotion to CEO, with winners receiving large increases in remuneration. Tournament losers by contrast face a discrete loss in their valuation of their position, since the prospect of them becoming CEO is substantially reduced. We argue that this offers an opportunity to test the predictions of tournament theory by observing the quit behaviour and the wages of the losing directors. We find a sharp increase in the likelihood that directors leave the firm when the tournament ends. The directors who remain receive an increase in their remuneration following a rival's promotion. [ABSTRACT FROM AUTHOR]

We propose a new class of multivariate volatility models utilizing realized measures of asset variance and covariance extracted from high-frequency data. Dimension reduction for estimation of large covariance matrices is achieved by imposing a factor structure with time-varying conditional factor loadings. Statistical properties of the model, including conditions that ensure covariance stationarity of returns, are established. The performance of the model is assessed using a panel of large U.S. financial institutions during the financial crisis, where empirical results show that the new model has both superior in- and out-of-sample properties. We show that the superior performance applies to a wide range of quantities of interest, including volatilities, covariances, betas, and scenario-based risk measures. The model's performance is particularly strong at short forecast horizons. [ABSTRACT FROM AUTHOR]

This article examines the impact that misreporting adoption status has on the identification and estimation of causal effects on productivity. In particular, by comparing measurement error-ridden self-reported adoption data with measurement-error-free DNA-fingerprinted adoption data, we investigate the extent to which such errors bias the causal effects of adoption on productivity. Taking DNA-fingerprinted adoption data as a benchmark, we find 25% "false negatives" and 10% "false positives" in farmers' responses. Our results show that misreporting of adoption status is not exogenous to household characteristics, and produces a bias of about 22 percentage points in the productivity impact of adoption. Ignoring inherent behavioral adjustments of farmers based on perceived adoption status has a bias of 13 percentage points. The results of this article underscore the crucial role that correct measurement of adoption plays in designing policy interventions that address constraints to technology adoption in agriculture. [ABSTRACT FROM AUTHOR]

This article develops an economic model to analyze how the risk of water shortages affects farmers' land irrigation decision and how the priority-based water sharing arrangement redistributes such a risk among farms with different water rights priorities. The analysis brings together an array of comprehensive data files on irrigation rights, water supplies, and agricultural land use from eastern Idaho. Results indicate that a more left-skewed distribution of streamflow significantly discourages land irrigation among farmers except the most senior rights holders. The priority-based water sharing arrangement redistributes the macroscale risk of water shortages and thus exposes farmers of different water rights priorities to heterogeneous levels of risk: senior water rights holders are affected the least and such a risk is instead passed mostly on to junior water rights holders. The role of water rights in risk redistribution is more significant when the probability distribution of water shortage risk is asymmetric rather than symmetric. The historical development pattern of water rights influences how the priority of water rights takes effect on land irrigation decision. [ABSTRACT FROM AUTHOR]

In this article, we employ Bayesian hierarchical modeling to better capture and communicate the uncertainties surrounding the transformation of U.S. public agricultural research and development (R&D) expenditures to knowledge capital stocks as well as its contribution to the historic growth of U.S. agricultural total factor productivity. Compared to studies based on classical statistics, analytical methods grounded in Bayesian inference explicitly incorporate existing information and permit revision of our knowledge regarding the distribution of the unknown model parameters as additional information becomes available. Bayesian hierarchical modeling is particularly useful in statistically estimating the underlying parameters of the R&D lag weight structure, as well as the R&D knowledge stocks given observed data on agricultural productivity and R&D expenditures. Our results show a significant level of uncertainty on the R&D lag weight structure, indicating that published assumptions about the R&D lag structure can now be tested and validated against available data. Estimating the R&D lag weights and knowledge stocks also make a large difference in the uncertainties surrounding economic returns from R&D investments. Indeed, our results show that the best-fit linear model yields slightly higher mean returns to R&D spending relative to the log model results and have significantly less uncertainty. This suggests that marginal returns to U.S. public agricultural research spending might have remained relatively constant despite a century of growth in expenditure. Furthermore, we find that such investments could take a longer time to bear fruit than previously realized. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Public Health is the property of Oxford University Press / USA and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Public Health is the property of Oxford University Press / USA and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objectives: To determine whether or not fluoroquinolone use increases the incidence of retinal detachment.Design: Self-controlled case series analysis.Participants: Participants were identified using the South Korean National Health Insurance Database between 1 January 2004 and 31 December 2015. A total of 15 134 patients who experienced rhegmatogenous retinal detachment (RRD) with at least one prescription of a fluoroquinolone were included.Methods: Incidence rate ratios (IRRs) and their 95% CIs were calculated using conditional Poisson regression. The main outcome measure was a recorded diagnosis of RRD (ICD-10: H33.0) with a claim for the surgical code for RRD.Results: We found an increased risk of retinal detachment in the first 1-30 days following the initiation of fluoroquinolone therapy (IRR 1.85; 95% CI 1.71-1.95), which rose for the 31-60 days period (IRR 2.05; 95% CI 1.43-2.95) but remained constant after more than 60 days (IRR 1.25; 95% CI 0.75-2.10). However, the elevated risk was also found in the 1-30 day period prior to the initiation of fluoroquinolone therapy (IRR 1.58; 95% CI 1.49-1.68) and also 31-60 days before medication use (IRR 1.11; 95% CI 1.03-1.19).Conclusions: Our case-based study indicated that the risk after fluoroquinolone exposure doubled; however, the risk profile before and after fluoroquinolone use means that the association between fluoroquinolone use and retinal detachment might not be a causal relationship. [ABSTRACT FROM AUTHOR]

Background: Vancomycin-resistant Enterococcus faecium (VREfm) represent a major source of nosocomial infection worldwide. In Australia, there has been a recent concerning increase in bacteraemia associated with the vanA genotype, prompting investigation into the genomic epidemiology of VREfm.Methods: A population-level study of VREfm (10 November-9 December 2015) was conducted. A total of 321 VREfm isolates (from 286 patients) across Victoria State were collected and sequenced with Illumina NextSeq. SNPs were used to assess relatedness. STs and genes associated with resistance and virulence were identified. The vanA-harbouring plasmid from an isolate from each ST was assembled using long-read data. Illumina reads from remaining isolates were then mapped to these assemblies to identify their probable vanA-harbouring plasmid.Results: vanA-VREfm comprised 17.8% of isolates. ST203, ST80 and a pstS(-) clade, ST1421, predominated (30.5%, 30.5% and 37.2%, respectively). Most vanB-VREfm were ST796 (77.7%). vanA-VREfm were more closely related within hospitals versus between them [core SNPs 10 (IQR 1-357) versus 356 (179-416), respectively], suggesting discrete introductions of vanA-VREfm, with subsequent intra-hospital transmission. In contrast, vanB-VREfm had similar core SNP distributions within versus between hospitals, due to widespread dissemination of ST796. Different vanA-harbouring plasmids were found across STs. With the exception of ST78 and ST796, Tn1546 transposons also varied. Phylogenetic analysis revealed Australian strains were often interspersed with those from other countries, suggesting ongoing cross-continental transmission.Conclusions: Emerging vanA-VREfm in Australia is polyclonal, indicating repeat introductions of vanA-VREfm into hospitals and subsequent dissemination. The close relationship to global strains reinforces the need for ongoing screening and control of VREfm in Australia and abroad. [ABSTRACT FROM AUTHOR]

Objectives: To determine the molecular characteristics of ESBL-producing Escherichia coli (ESBL-E) collected during a longitudinal study on an organic broiler farm in order to investigate clonal expansion and horizontal gene transfer.Methods: Isolates were obtained from a longitudinal study performed previously on an organic broiler fattening farm. Samples from individually followed-up broilers, the broiler house, the transport van and persons that took the samples, taken at several timepoints (days 1, 3, 4, 7, 10, 42 and 70) within a production round and during the consecutive one (days 1, 2, 3 and 70), had been investigated for the occurrence of ESBL-E. In the current study, ESBL genes and MLST STs of these ESBL-E were determined. Plasmids were characterized and subtyped.Results: On arrival in round_1, ESBL-E of ST88 predominated, while on days 3, 4, 7 and 10 ST10 was most often found and at slaughter age ST155 and ST1551 prevailed. A shift in STs was also observed in round_2. None of the 35 individually selected broilers followed up in round_1 was positive for the same ESBL-E ST at all sampling times. All isolates carried CTX-M-1 group genes, confirmed as blaCTX-M-1 in 158 isolates. Further analysis of 36 isolates of different STs showed blaCTX-M-1 on IncI1/ST3 plasmids.Conclusions: The rapid dissemination of ESBL-E on this broiler farm was not due to the spread of one specific E. coli clone, but most likely the result of horizontal transfer of an IncI1/ST3 plasmid carrying blaCTX-M-1 resulting in a shift in the predominant ESBL-E population in broilers. [ABSTRACT FROM AUTHOR]

Objectives To sequence the genomes and determine the genetic mechanisms for linezolid resistance identified in three strains of Enterococcus isolated from cattle and swine caecal contents as part of the US National Antimicrobial Resistance Monitoring System (NARMS) surveillance programme. Methods Broth microdilution was used for in vitro antimicrobial susceptibility testing to assess linezolid resistance. Resistance mechanisms and plasmid types were identified from data generated by WGS on Illumina®and PacBio®platforms. Conjugation experiments were performed to determine whether identified mechanisms were transmissible. Results Linezolid resistance plasmids containing optrA were identified in two Enterococcus faecalis isolates and one Enterococcus faecium. The E. faecium isolate also carried the linezolid resistance gene cfr on the same plasmid as optrA. The linezolid resistance plasmids had various combinations of additional resistance genes conferring resistance to phenicols (fexA), aminoglycosides [ spc and aph(3′)-III ] and macrolides [ erm (A) and erm (B)]. One of the plasmids was confirmed to be transmissible by conjugation, resulting in linezolid resistance in the transconjugant. Conclusions To the best of our knowledge, this is the first identification of linezolid resistance in the USA in bacteria isolated from food animals. The oxazolidinone class of antibiotics is not used in food animals in the USA, but the genes responsible for resistance were identified on plasmids with other resistance markers, indicating that there may be co-selection for these plasmids due to the use of different antimicrobials. The transmissibility of one of the plasmids demonstrated the potential for linezolid resistance to spread horizontally. Additional surveillance is necessary to determine whether similar plasmids are present in human strains of Enterococcus. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the AusDiagnostics MT CRE EU assay for the detection of carbapenemase and acquired colistin resistance genes in Gram-negative bacteria.Methods: The assay allows the detection of blaKPC, blaOXA-48-like, blaNDM, blaVIM, blaIMP, blaSIM, blaGIM, blaSPM, blaFRI, blaIMI, blaGES (differentiating ESBL and carbapenemase variants), blaSME and mcr-1/-2. It was evaluated against a panel of isolates including Enterobacteriaceae, Pseudomonas spp. and Acinetobacter spp. retrospectively (n = 210) and prospectively (n = 182).Results: The CRE EU assay was able to detect 268/268 carbapenemase genes, with 239 belonging to the 'big five' families (KPC, OXA-48-like, NDM, VIM and IMP) and 29 carbapenemase genes of the SIM, GIM, SPM, FRI, IMI, SME and GES families. It could distinguish between ESBL and carbapenemase variants of GES. It also allowed detection of mcr-1/-2 colistin resistance genes on their own or in isolates co-producing a carbapenemase.Conclusions: The AusDiagnostics MT CRE EU assay offered wide coverage for detection of acquired carbapenemase genes. It required minimal hands-on time and delivered results in less than 4 h from bacterial culture. [ABSTRACT FROM AUTHOR]