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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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Numerous tectonic scenarios have been proposed for terrane growth and accretion within the Archean Dharwar Craton, southern Peninsular India. Previously accepted interpretations involving a two-terrane model—comprising a Western Dharwar Craton (WDC) and Eastern Dharwar Craton (EDC) block—have invoked west-dipping subduction and ocean closure, leading to arc magmatism and accretionary orogeny in the WDC, followed by metamorphic overprinting and collisional orogeny in the EDC. However, recent field investigations have revealed the existence of a previously unrecognized 'central' block (Central Dharwar Craton; CDC) within the craton, which requires revision of this model and reinterpretation of metamorphic and magmatic age data. Five samples of high-pressure, upper amphibolite- and granulite-facies meta-igneous and metasedimentary rocks from the southern portion of the Chitradurga Suture Zone, which divides the WDC and CDC, record minimum peak metamorphic conditions of ∼820–875°C at ∼10 kbar, indicating equilibration at the base of thickened continental crust. U–Pb zircon and Pb–Pb monazite geochronology indicates crystallization of parent mafic magmas at c. 2·61–2·51 Ga and subsequent regional metamorphism of these intrusions to garnet-amphibolite and garnet-granulite facies at c. 2·48–2·44 Ga, bracketing the timing of microblock accretion to the Archean–Proterozoic boundary. Light rare earth element enrichment within these zircon grains indicates magma generation in a suprasubduction-zone environment. In addition, detrital magmatic zircon grains with ages of c. 3·10–3·03 Ga and c. 2·97–2·86 Ga imply contamination of these magmas with Mesoarchean material sourced from the Western Dharwar Craton continental nucleus. Comparison of these metamorphic and magmatic age data with those recorded in the EDC shows that westward-directed subduction is implausible, and that all three terranes (the WDC, CDC, and EDC) must have accreted synchronously, driven by two separate eastward-dipping ocean–continent convergent plate margins. These data further support a recent abundance of observations from the geological record supporting the hypothesis that subduction-driven plate tectonics had initiated on Earth before c. 2·5 Ga, as opposed to a Neoproterozoic onset (c. 0·8–0·9 Ga) reported by numerous studies. [ABSTRACT FROM AUTHOR]

A new transmission strategy based on distributed event-triggered mechanism and average dwell time approach is proposed for consensus of time-delay free linear multi-agent systems with communication constraints. A subset of agents are selected according to the condition of event-triggered mechanism to communicate with its adjacent agents through network channel at certain sampling instant, which reduces the occupation of network bandwidth. The possible combinations of agents' communication are considered as modes of multi-agent systems. Therefore, we modelled multi-agent systems as a class of switched systems. The average dwell time method is applied to determine its dwell-time of each mode, which avoids the frequent mode-switching resulted from event-triggered mechanism. An integrated design scheme is presented to achieve the thresholds of event-triggered mechanism, the average dwell time and the consensus controller gain simultaneously by using Lyapunov–Krasovskii functional and linear matrix inequality (LMI) technique. Finally, a simulation example illustrates the effectiveness of theoretical results. [ABSTRACT FROM AUTHOR]

Proxy-based sliding mode control (PSMC) is a control scheme proposed a decade ago originally as a position controller for robot manipulators. This controller has a unique mathematical structure that combines a proportional-integral-derivative (PID) controller and a sliding mode controller in an algebraic way, and has demonstrated its practical usefulness in various applications. Its theoretical foundation, however, has been quite immature. This article presents a set of stability proofs on PSMC as a minimum requirement for future practical applications. Finite-time stability and asymptotic stability of terminal attractors are proven with the use of a non-smooth Lyapunov function. [ABSTRACT FROM AUTHOR]

This article considers the robust input-to-state stability (ISS) control for a class of uncertain singularly perturbed systems with disturbances. By using the fixed-point principle, we first provide a linear matrix inequality (LMI) sufficient condition to guarantee that the original systems are in a standard form. Secondly, the two-time scale decomposition technique is applied to make the corresponding slow and fast subsystems ISS. Based on the established results, a sufficient condition is presented to guarantee that original systems are also ISS for all sufficiently small values of the perturbation parameter. Finally, a numerical example is given to show the effectiveness of the obtained theoretical results. [ABSTRACT FROM AUTHOR]

This article presents a general solution scheme for finite horizon optimal control of variable order Caputo dynamic systems with specified initial and final conditions. The main approach of the article is using variable order calculus of variations. After deriving the necessary optimality conditions, as the main contribution of the article, a change of variable is used to rearrange the set of conditions as a set of coupled variable order differential equations. Then, a numerical method is introduced to solve the corresponding equations. Finally, a case study shows the effectiveness of the proposed method. [ABSTRACT FROM AUTHOR]

Law N° 2015-295 of 29 July 2015 (as amended) on the right of asylum was adopted at a time when the issue of immigration was dramatically politicised, in particular, the right of asylum. By studying the provisions in the new law regarding the housing of asylum-seekers, we can see that despite its stated purpose, the implicit intention of French asylum policy has at times been to discourage asylum-seekers from coming to France. The focus of this article is on the right of asylum-seekers to housing. First, we highlight the ambiguity of the Law of 29 July 2015, which has enabled those in power to claim an improvement in the reception of asylum-seekers while at the same time attaching more conditions to the rights of these asylum-seekers. Second, we review the application of this law before providing a prognosis of the "Achieving a controlled migration and a more effective right of asylum" Bill as presented to the Council of Ministers on Wednesday 21 February 2018. [ABSTRACT FROM AUTHOR]

In this study, tribal members from an American Indian (AI) community in the midwestern United States used photovoice, a community-based participatory method, to document their perceptions and beliefs about water and health on their reservation. The study infused photovoice's seminal theoretical influences within an environmental justice framework to explore the impact of environmental changes in water on human health and well-being. Study participants included two men and nine women who self-identified as tribal members and either worked or lived (or both) on their tribe's reservation. During the photovoice project, participants took photographs and engaged in face-to-face interviews using the SHOWeD technique to reflect on the images they had captured. An In Vivo coding method was used to code the data using participants' own words, followed by a thematic analysis to contextualize the codes within the cultural realities of the tribal community. Study findings detail how water is fundamental to the lives of the AI study participants and expose the scope of health concerns they have related to water circumstances on their reservation. The article concludes with a discussion about the use of photovoice with AI communities and implications of using the method for social work practice and research. [ABSTRACT FROM AUTHOR]

This paper extends the comparative literature on divorce by theorizing how international institutions and norms influence societal divorce rates. Drawing on developmental idealism and world society theory, the paper argues that global institutions legitimize cultural principles such as individualism, human rights, and gender equality, which reshape "modern" understandings of marriage and family relations. Formal international institutions and treaties do not explicitly proclaim or codify the right to divorce, but we suggest that new norms regarding divorce emerge from the "penumbras" of world culture and diffuse globally. Panel regression models covering 84 countries between 1970 and 2008 find a strong association between global cultural influence and divorce rates, controlling for other factors. Results highlight the effects of world society on the private lives of individuals, and suggest that world society affects a wider set of outcomes than the conventional literature would predict. [ABSTRACT FROM AUTHOR]

In the wake of college-for-all policy, college aspirations among working-class and middle-class young adults have converged, yet class gaps in enrollment and completion persist. Building on previous literature that uncovers the structural barriers that block working-class mobility, we examine the specific narrative content that working-class and middle-class young adults and their parents attach to the broad "college for all" message. We investigate how their narratives of imagined futures shape how they perceive the riskiness of college decisions. In-depth interviews with 51 young adult-parent dyads suggest that working-class young adults envision college as a route to moral worth and an escape from their current grim reality—what we term "salvation." Their narratives lend self-efficacy and optimism to their lives, but are not organized in ways that protect them from the increasingly risky college landscape. Middle-class parents assume control over the meanings of college and deploy a narrative of insecurity about downward mobility in a competitive economy. By contesting the meaning of college as a vehicle for self-realization, this narrative buffers youth from risk even as it constrains feelings of self-determination in the transition to adulthood. [ABSTRACT FROM AUTHOR]

Time-to-event outcomes are often evaluated on the hazard scale, but interpreting hazards may be difficult. Recently in the causal inference literature concerns have been raised that hazards actually have a built-in selection bias that prevents simple causal interpretations. This is a problem even in randomized controlled trials, where hazard ratios have become a standard measure of treatment effects. Modelling on the hazard scale is nevertheless convenient, for example to adjust for covariates; using hazards for intermediate calculations may therefore be desirable. In this paper we present a generic method for transforming hazard estimates consistently to other scales at which these built-in selection biases are avoided. The method is based on differential equations and generalizes a well-known relation between the Nelson–Aalen and Kaplan–Meier estimators. Using the martingale central limit theorem, we show that covariances can be estimated consistently for a large class of estimators, thus allowing for rapid calculation of confidence intervals. Hence, given cumulative hazard estimates based on, for example, Aalen's additive hazard model, we can obtain many other parameters without much more effort. We give several examples and the associated estimators. Coverage and convergence speed are explored via simulations, and the results suggest that reliable estimates can be obtained in real-life scenarios. [ABSTRACT FROM AUTHOR]

Sliced inverse regression is a popular tool for sufficient dimension reduction, which replaces covariates with a minimal set of their linear combinations without loss of information on the conditional distribution of the response given the covariates. The estimated linear combinations include all covariates, making results difficult to interpret and perhaps unnecessarily variable, particularly when the number of covariates is large. In this paper, we propose a convex formulation for fitting sparse sliced inverse regression in high dimensions. Our proposal estimates the subspace of the linear combinations of the covariates directly and performs variable selection simultaneously. We solve the resulting convex optimization problem via the linearized alternating direction methods of multiplier algorithm, and establish an upper bound on the subspace distance between the estimated and the true subspaces. Through numerical studies, we show that our proposal is able to identify the correct covariates in the high-dimensional setting. [ABSTRACT FROM AUTHOR]

Prediction is often the primary goal of data analysis. In this work, we propose a novel model averaging approach to the prediction of a functional response variable. We develop a crossvalidation model averaging estimator based on functional linear regression models in which the response and the covariate are both treated as random functions. We show that the weights chosen by the method are asymptotically optimal in the sense that the squared error loss of the predicted function is as small as that of the infeasible best possible averaged function. When the true regression relationship belongs to the set of candidate functional linear regression models, the averaged estimator converges to the true model and can estimate the regression parameter functions at the same rate as under the true model. Monte Carlo studies and a data example indicate that in most cases the approach performs better than model selection. [ABSTRACT FROM AUTHOR]

In paired randomized experiments, individuals in a given matched pair may differ on prognostically important covariates despite the best efforts of practitioners. We examine the use of regression adjustment to correct for persistent covariate imbalances after randomization, and present two regression-assisted estimators for the sample average treatment effect in paired experiments. Using the potential outcomes framework, we prove that these estimators are consistent for the sample average treatment effect under mild regularity conditions even if the regression model is improperly specified, and describe how asymptotically conservative confidence intervals can be constructed. We demonstrate that the variances of the regression-assisted estimators are no larger than that of the standard difference-in-means estimator asymptotically, and illustrate the proposed methods by simulation. The analysis does not require a superpopulation model, a constant treatment effect, or the truth of the regression model, and hence provides inference for the sample average treatment effect with the potential to increase power without unrealistic assumptions. [ABSTRACT FROM AUTHOR]

Multiple types of data measured on a common set of subjects arise in many areas. Numerous empirical studies have found that integrative analysis of such data can result in better statistical performance in terms of prediction and feature selection. However, the advantages of integrative analysis have mostly been demonstrated empirically. In the context of two-class classification, we propose an integrative linear discriminant analysis method and establish a theoretical guarantee that it achieves a smaller classification error than running linear discriminant analysis on each data type individually. We address the issues of outliers and missing values, frequently encountered in integrative analysis, and illustrate our method through simulations and a neuroimaging study of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

We consider a heteroscedastic regression model in which some of the regression coefficients are zero but it is not known which ones. Penalized quantile regression is a useful approach for analysing such data. By allowing different covariates to be relevant for modelling conditional quantile functions at different quantile levels, it provides a more complete picture of the conditional distribution of a response variable than mean regression. Existing work on penalized quantile regression has been mostly focused on point estimation. Although bootstrap procedures have recently been shown to be effective for inference for penalized mean regression, they are not directly applicable to penalized quantile regression with heteroscedastic errors. We prove that a wild residual bootstrap procedure for unpenalized quantile regression is asymptotically valid for approximating the distribution of a penalized quantile regression estimator with an adaptive |$L_1$| penalty and that a modified version can be used to approximate the distribution of a |$L_1$| -penalized quantile regression estimator. The new methods do not require estimation of the unknown error density function. We establish consistency, demonstrate finite-sample performance, and illustrate the applications on a real data example. [ABSTRACT FROM AUTHOR]

La transmission d'infections au cabinet du pédiatre est une source de préoccupation croissante. Le présent document traite des voies de transmission des infections et des principes de contrôle des infections actuellement en vigueur. La prévention englobe un aménagement du cabinet et des politiques administratives appropriés, le triage, les pratiques de soins habituelles pour tous les patients (p. ex. hygiène des mains; port de gants, de masques, d'un dispositif de protection oculaire et de blouses pour certaines interventions; nettoyage, désinfection et stérilisation des surfaces et de l'équipement, y compris les jouets; technique d'asepsie pour les interventions invasives), ainsi que les précautions additionnelles en cas d'infections particulières. Les membres du personnel doivent avoir reçu les vaccins nécessaires, et ceux qui sont atteints d'une infection doivent respecter les politiques de restriction au travail. [ABSTRACT FROM AUTHOR]

This statement provides guidance for health care providers to ensure the safe discharge of healthy term infants who are born in hospital and who are ≥37 weeks' gestational age. Hospital care for mothers and infants should be family-centred, with healthy mothers and infants remaining together and going home at the same time. The specific length of stay for newborn infants depends on the health of their mother, infant health and stability, the mother's ability to care for her infant, support at home, and access to follow-up care. Many mother–infant dyads are ready to go home 24 h after birth. Parent or guardian education and assessment of discharge readiness are important components of discharge planning. Each infant must have an appropriate discharge plan, including identification of the infant's primary health care provider and assessment by a health care provider 24 h to 72 h after discharge. [ABSTRACT FROM AUTHOR]

Objectives To conduct a clinicopathologic study of male breast carcinoma with Magee equation recurrence score (RS). Methods Seventy-four cases of male invasive breast cancers (MBCs) were studied, including 63 hormone receptor (HR)-positive, 10 human epidermal growth factor receptor 2-positive, and one triple-negative breast cancers. Results Among 63 HR-positive MBC patients, nine patients developed distal metastasis. Statistical analysis demonstrated distal metastasis was significantly associated with positive lymph node, high Nottingham grade, and increased Magee equation RS. All HR-positive MBCs were further stratified into two categories (low RS <18; intermediate/high RS ≥18). There was a significantly increased risk for distal metastasis in MBCs with intermediate/high Magee equation RS, but no increased risk for lymph node metastasis. Conclusions Our data suggest Magee equation RS may be useful to predict distal metastatic risk in MBC patients. [ABSTRACT FROM AUTHOR]

Objectives: To analyze consistency of reference limits and widths of reference intervals (RIs) calculated by six procedures and evaluate a protocol for merging intrainstitutional reference data.Methods: The differences between reference limits were compared with "optimal" bias goals. Also, widths of the RIs were compared. RIs were calculated using Mayo-SAS quantile, EP Evaluator, and four International Federation of Clinical Chemistry and Laboratory Medicine methods: parametric and nonparametric (NP) with and without latent abnormal values exclusion (LAVE). Regression parameters from cotested samples were evaluated for harmonizing intrainstitutional reference data.Results: Mayo-SAS quintile, LAVE(-)NP, and EP Evaluator generated similar RIs, but these RIs often were wider than RIs from parametric procedures. LAVE procedures generated narrower RIs for nutritional and inflammatory markers. Transformation with regression parameters did not ensure homogeneity of merged data.Conclusions: Parametric methods are recommended when inappropriate values cannot be excluded. The nonparametric procedures may generate wider RIs. Data sets larger than 200 are recommended for robust estimates. Caution should be exercised when merging intrainstitutional data. [ABSTRACT FROM AUTHOR]

Objectives: Ethanol is a widely consumed drug in almost every society. In this study, the potential interfering effect of ethanol on routine biochemical tests was evaluated.Methods: Serum pools were prepared from blood samples collected from patients seeking treatment at the emergency department. Five separate groups were formed by adding ethanol to the samples, so the final concentrations were negative: 50 mg/dL, 100 mg/dL, 200 mg/dL, and 400 mg/dL. Each group was divided into 20 portions, and routine biochemical tests were measured from each portion. The coefficient of variation (CV), bias, and total error values were calculated for the measured parameters.Results: Alanine aminotransferase (ALT; EC 2.6.1.2) and lactate dehydrogenase (LDH; EC 1.1.1.27) activities decreased in proportion to the ethanol level. High negative biases were observed, suggesting a dose-dependent negative interference. The total error values calculated for direct bilirubin and urea were higher than the allowable total error reported in the Clinical Laboratory Improvement Amendments of 1988. For direct bilirubin, it was observed that the cause of this shift was due to the increase in CV values.Conclusions: We conclude that ethanol may cause interference in the measurement of some biochemical tests, whereas the most prominent effect was observed for LDH and ALT. [ABSTRACT FROM AUTHOR]

Objectives: The eighth edition of the American Joint Committee on Cancer staging manual now stratifies nonmucinous lung adenocarcinomas (nmLACAs) by the size of the invasive component only. This is determined by direct gross or microscopic measurement; however, a calculated invasive size based on the percentage of invasive growth patterns has been proposed as an alternative option.Methods: To compare radiologic with different pathologic assessments of invasive tumor size, we retrospectively reviewed a cohort of resected nmLACAs with a part-solid appearance on computed tomography (CT) scan (n = 112).Results: The median direct microscopic pathologic invasive measurements were not significantly different from the median calculated pathologic invasive measurements; however, the median CT invasive measurements were 0.26 cm larger than the median direct pathologic measurements (P < .001).Conclusions: Our results show that pathologic calculated invasive tumor measurements are comparable to direct microscopic measurements of invasive tumor, thereby supporting the recommendation for use of calculated invasive tumor size by the pathologist if necessary. [ABSTRACT FROM AUTHOR]