Entrepreneurs’ achieved success: developing a multi-faceted measure

Firm performance is typically measured via objective financial indicators. However, researchers increasingly acknowledge that entrepreneurs do not measure their success solely in financial terms but that a range of often subjective indicators matter to them. This article contributes to the debate on entrepreneurial performance by studying how entrepreneurs assess their achieved success. ‘Entrepreneurs’ achieved success’ was conceptualized as a multi-faceted construct that includes entrepreneurs’ self-reported achievement of firm performance, workplace relationships, personal fulfilment, community impact, and personal financial rewards. It was measured via the Subjective Entrepreneurial Success–Achievement Scale (SES-AS). Over the course of three studies (N = 390) the factorial structure of ‘entrepreneurs’ achieved success’ was established and largely replicated in two cultures. Based on a nomological network, we documented relationships among ‘entrepreneurs’ achieved success’, quasi-objective indicators of firm performance, and entrepreneurs’ financial satisfaction, creativity, and health. Based on our research, we propose a new conceptual framework to study performance in the context of entrepreneurship. This framework acknowledges both the success criteria that entrepreneurs wish to achieve and those that they actually achieve, and extends our understanding of firm performance

High specificity of line-immunoassay based algorithms for recent HIV-1 infection independent of viral subtype and stage of disease

ABSTRACT: BACKGROUND: Serologic testing algorithms for recent HIV seroconversion (STARHS) provide important information for HIV surveillance. We have shown that a patient's antibody reaction in a confirmatory line immunoassay (INNO-LIATM HIV I/II Score, Innogenetics) provides information on the duration of infection. Here, we sought to further investigate the diagnostic specificity of various Inno-Lia algorithms and to identify factors affecting it. METHODS: Plasma samples of 714 selected patients of the Swiss HIV Cohort Study infected for longer than 12 months and representing all viral clades and stages of chronic HIV-1 infection were tested blindly by Inno-Lia and classified as either incident (up to 12 m) or older infection by 24 different algorithms. Of the total, 524 patients received HAART, 308 had HIV-1 RNA below 50 copies/mL, and 620 were infected by a HIV-1 non-B clade. Using logistic regression analysis we evaluated factors that might affect the specificity of these algorithms. RESULTS: HIV-1 RNA <50 copies/mL was associated with significantly lower reactivity to all five HIV-1 antigens of the Inno-Lia and impaired specificity of most algorithms. Among 412 patients either untreated or with HIV-1 RNA ≥50 copies/mL despite HAART, the median specificity of the algorithms was 96.5% (range 92.0-100%). The only factor that significantly promoted false-incident results in this group was age, with false-incident results increasing by a few percent per additional year. HIV-1 clade, HIV-1 RNA, CD4 percentage, sex, disease stage, and testing modalities exhibited no significance. Results were similar among 190 untreated patients. CONCLUSIONS: The specificity of most Inno-Lia algorithms was high and not affected by HIV-1 variability, advanced disease and other factors promoting false-recent results in other STARHS. Specificity should be good in any group of untreated HIV-1 patients

Respiratory Viruses Dynamics and Interactions: {T}en Years of Surveillance in Central Europe

&lt;jats:title&gt;Abstract&lt;/jats:title&gt;&lt;jats:sec&gt; &lt;jats:title&gt;Background&lt;/jats:title&gt; &lt;jats:p&gt;Lower respiratory tract infections are among the main causes of death. Although there are many respiratory viruses, diagnostic efforts are focused mainly on influenza. The Respiratory Viruses Network (RespVir) collects infection data, primarily from German university hospitals, for a high diversity of infections by respiratory pathogens. In this study, we computationally analysed a subset of the RespVir database, covering 217,150 samples tested for 17 different viral pathogens in the time span from 2010 to 2019.&lt;/jats:p&gt; &lt;/jats:sec&gt;&lt;jats:sec&gt; &lt;jats:title&gt;Methods&lt;/jats:title&gt; &lt;jats:p&gt;We calculated the prevalence of 17 respiratory viruses, analysed their seasonality patterns using information-theoretic measures and agglomerative clustering, and analysed their propensity for dual infection using a new metric dubbed average coinfection exclusion score (ACES).&lt;/jats:p&gt; &lt;/jats:sec&gt;&lt;jats:sec&gt; &lt;jats:title&gt;Results&lt;/jats:title&gt; &lt;jats:p&gt;After initial data pre-processing, we retained 206,814 samples, corresponding to 1,408,657 performed tests. We found that Influenza viruses were reported for almost the half of all infections and that they exhibited the highest degree of seasonality. Coinfections of viruses are frequent; the most prevalent coinfection was rhinovirus/bocavirus and most of the virus pairs had a positive ACES indicating a tendency to exclude each other regarding infection.&lt;/jats:p&gt; &lt;/jats:sec&gt;&lt;jats:sec&gt; &lt;jats:title&gt;Conclusions&lt;/jats:title&gt; &lt;jats:p&gt;The analysis of respiratory viruses dynamics in monoinfection and coinfection contributes to the prevention, diagnostic, treatment, and development of new therapeutics. Data obtained from multiplex testing is fundamental for this analysis and should be prioritized over single pathogen testing.&lt;/jats:p&gt; &lt;/jats:sec&gt

Entrepreneurs’ mental health and well-being:A review and research agenda

Interest in entrepreneurs’ mental health and well-being (MWB) is growing in recognition of the role of MWB in entrepreneurs’ decision making, motivation, and action. Yet relevant knowledge is dispersed across disciplines, which makes what we currently understand about entrepreneurs’ MWB unclear. In this systematic review I integrate insights from 144 empirical studies. These studies show that research is focused on three research questions: (1) Do different types of entrepreneurs differ in their MWB? What are the (2) antecedents and (3) consequences of entrepreneurs’ MWB? The review systematizes evidence on known antecedents and consequences of entrepreneurs’ MWB but also reveals overlooked and undertheorized sources and outcomes of entrepreneurs’ MWB. The review provides a mapping and framework that advance research on entrepreneurs’ MWB and help to position entrepreneurs’ MWB more centrally in management and entrepreneurship research. It calls for researchers to go beyond applying models developed for employees to understand entrepreneurs. Instead, the findings point the way to developing a dedicated theory of entrepreneurial work and MWB that is dynamic, socialized, and open to considering context and acknowledges variability and fluidity across entrepreneurs’ life domains, as well as the centrality of work for entrepreneurs’ identity

Population pharmacokinetic modelling and evaluation of different dosage regimens for darunavir and ritonavir in HIV-infected individuals

Objectives Darunavir is a protease inhibitor that is administered with low-dose ritonavir to enhance its bioavailability. It is prescribed at standard dosage regimens of 600/100 mg twice daily in treatment-experienced patients and 800/100 mg once daily in naive patients. A population pharmacokinetic approach was used to characterize the pharmacokinetics of both drugs and their interaction in a cohort of unselected patients and to compare darunavir exposure expected under alternative dosage regimens. Methods The study population included 105 HIV-infected individuals who provided darunavir and ritonavir plasma concentrations. Firstly, a population pharmacokinetic analysis for darunavir and ritonavir was conducted, with inclusion of patients' demographic, clinical and genetic characteristics as potential covariates (NONMEM®). Then, the interaction between darunavir and ritonavir was studied while incorporating levels of both drugs into different inhibitory models. Finally, model-based simulations were performed to compare trough concentrations (Cmin) between the recommended dosage regimen and alternative combinations of darunavir and ritonavir. Results A one-compartment model with first-order absorption adequately characterized darunavir and ritonavir pharmacokinetics. The between-subject variability in both compounds was important [coefficient of variation (CV%) 34% and 47% for darunavir and ritonavir clearance, respectively]. Lopinavir and ritonavir exposure (AUC) affected darunavir clearance, while body weight and darunavir AUC influenced ritonavir elimination. None of the tested genetic variants showed any influence on darunavir or ritonavir pharmacokinetics. The simulations predicted darunavir Cmin much higher than the IC50 thresholds for wild-type and protease inhibitor-resistant HIV-1 strains (55 and 550 ng/mL, respectively) under standard dosing in >98% of experienced and naive patients. Alternative regimens of darunavir/ritonavir 1200/100 or 1200/200 mg once daily also had predicted adequate Cmin (>550 ng/mL) in 84% and 93% of patients, respectively. Reduction of darunavir/ritonavir dosage to 600/50 mg twice daily led to a 23% reduction in average Cmin, still with only 3.8% of patients having concentrations below the IC50 for resistant strains. Conclusions The important variability in darunavir and ritonavir pharmacokinetics is poorly explained by clinical covariates and genetic influences. In experienced patients, treatment simplification strategies guided by drug level measurements and adherence monitoring could be propose

The Interplay Between Host Genetic Variation, Viral Replication, and Microbial Translocation in Untreated HIV-Infected Individuals

Systemic immune activation, a major determinant of human immunodeficiency virus (HIV) disease progression, is the result of a complex interplay between viral replication, dysregulation of the immune system, and microbial translocation due to gut mucosal damage. Although human genetic variants influencing HIV load have been identified, it is unknown how much the host genetic background contributes to interindividual differences in other determinants of HIV pathogenesis such as gut damage and microbial translocation. Using samples and data from 717 untreated participants in the Swiss HIV Cohort Study and a genome-wide association study design, we searched for human genetic determinants of plasma levels of intestinal fatty acid-binding protein (I-FABP/FABP2), a marker of gut damage, and of soluble CD14 (sCD14), a marker of lipopolysaccharide bioactivity and microbial translocation. We also assessed the correlations between HIV load, sCD14, and I-FABP. Although we found no genome-wide significant determinant of the tested plasma markers, we observed strong associations between sCD14 and both HIV load and I-FABP, shedding new light on the relationships between processes that drive progression of untreated HIV infectio

Ageing with HIV: medication use and risk for potential drug-drug interactions

Objectives To compare the use of co-medication, the potential drug-drug interactions (PDDIs) and the effect on antiretroviral therapy (ART) tolerability and efficacy in HIV-infected individuals according to age, ≥50 years or <50 years. Methods All ART-treated participants were prospectively included once during a follow-up visit of the Swiss HIV Cohort Study. Information on any current medication was obtained by participant self-report and medical prescription history. The complete treatment was subsequently screened for PDDIs using a customized version of the Liverpool drug interaction database. Results Drug prescriptions were analysed for 1497 HIV-infected individuals: 477 age ≥50 and 1020 age <50. Older patients were more likely to receive one or more co-medications compared with younger patients (82% versus 61%; P < 0.001) and thus had more frequent PDDIs (51% versus 35%; P < 0.001). Furthermore, older patients tended to use a higher number of co-medications and certain therapeutic drug classes more often, such as cardiovascular drugs (53% versus 19%; P < 0.001), gastrointestinal medications (10% versus 6%; P = 0.004) and hormonal agents (6% versus 3%; P = 0.04). PDDIs with ART occurred mainly with cardiovascular drugs (27%), CNS agents (22%) and methadone (6%) in older patients and with CNS agents (27%), methadone (15%) and cardiovascular drugs (11%) in younger patients. The response to ART did not differ between the two groups. Conclusions The risk for PDDIs with ART increased in older patients who take more drugs than their younger HIV-infected counterparts. However, medication use in older and younger patients did not differ in terms of effect on antiretroviral tolerability and respons

Obesity trends and body mass index changes after starting antiretroviral treatment : the Swiss HIV Cohort Study

BACKGROUND: The factors that contribute to increasing obesity rates in human immunodeficiency virus (HIV)-positive persons and to body mass index (BMI) increase that typically occurs after starting antiretroviral therapy (ART) are incompletely characterized. METHODS: We describe BMI trends in the entire Swiss HIV Cohort Study (SHCS) population and investigate the effects of demographics, HIV-related factors, and ART on BMI change in participants with data available before and 4 years after first starting ART. RESULTS: In the SHCS, overweight/obesity prevalence increased from 13% in 1990 (n = 1641) to 38% in 2012 (n = 8150). In the participants starting ART (n = 1601), mean BMI increase was 0.92 kg/m(2) per year (95% confidence interval, .83-1.0) during year 0-1 and 0.31 kg/m(2) per year (0.29-0.34) during years 1-4. In multivariable analyses, annualized BMI change during year 0-1 was associated with older age (0.15 [0.06-0.24] kg/m(2)) and CD4 nadir &lt;199 cells/µL compared to nadir &gt;350 (P &lt; .001). Annualized BMI change during years 1-4 was associated with CD4 nadir &lt;100 cells/µL compared to nadir &gt;350 (P = .001) and black compared to white ethnicity (0.28 [0.16-0.37] kg/m(2)). Individual ART combinations differed little in their contribution to BMI change. CONCLUSIONS: Increasing obesity rates in the SHCS over time occurred at the same time as aging of the SHCS population, demographic changes, earlier ART start, and increasingly widespread ART coverage. Body mass index increase after ART start was typically biphasic, the BMI increase in year 0-1 being as large as the increase in years 1-4 combined. The effect of ART regimen on BMI change was limited