Flexible vs Dedicated Technology Adoption in the Presence of a Public Firm

We study firms' adoption of flexible versus dedicated technologies in the context of a mixed versus a private duopoly with product differentiation. The flexible technology allows a firm to become multiproduct or multimarket without bearing additional costs. We find that a configuration where both firms adopt flexible technologies is more likely to arise in equilibrium in the private duopoly. A similar result occurs when both firms use a dedicated technology in the case of either almost independent products or products that are close substitutes. Privatization of the public firm is socially beneficial only in limited circumstances.Flexible Technology, Privatization, Public Firm, Mixed Duopoly.

Entry and exit in a liberalised market

We analyze the determinants of entry and exit in the European Airline Markets in the post-liberalization period. Unlike previous studies, we find that the presence of charter or seasonal operators and the level of quality provided by the incumbents are relevant to explain entry and exit. Differential traits in the main low cost airlines' entry and exit behavior are also analysed

Flexible vs dedicated technology adoption in the presence of a public firm

We study firms' adoption of flexible versus dedicated technologies in the context of a mixed versus a private duopoly with product differentiation. The flexible technology allows a firm to become multiproduct or multimarket without bearing additional costs. We find that a configuration where both firms adopt flexible technologies is more likely to arise in equilibrium in the private duopoly. A similar result occurs when both firms use a dedicated technology in the case of either almost independent products or products that are close substitutes. Privatization of the public firm is socially beneficial only in limited circumstances

Public policy towards R&D in a mixed duopoly with spillovers

We investigate the use of subsidies to R&D, both in a mixed and a private duopoly market. We show that the socially optimal R&D subsidy is positive and increasing in the degree of spillovers both in the private and the mixed duopoly, although it is lower for the former than for the latter. We also nd support for the empirical claim that privatization is followed by a scaling down of the R&D activity. A comparative static analysis of welfare levels suggests that privatization is welfare detrimental, which lends some support to the views against the widespread adoption of privatization programs

R&D policy and privatization in a mixed oligopoly

We introduce R&D activity and R&D subsidies in the context of a mixed oligopoly and evaluate the effects of privatization on welfare. We show that when R&D subsidies are employed, privatization is welfare and R&D promoting provided that the number of competitors is sufficiently large

Drug-Drug Interactions with Antiretroviral Drugs in Pregnant Women Living with HIV : Are They Different from Non-Pregnant Individuals?

Although the separate effects of drug-drug interactions and pregnancy on antiretroviral drug pharmacokinetics have been widely studied and described, their combined effect is largely unknown. Physiological changes during pregnancy may change the extent or clinical relevance of a drug-drug interaction in a pregnant woman. This review aims to provide a detailed overview of the mechanisms, magnitude, and clinical significance of antiretroviral drug-drug interactions in pregnant women. We performed a literature search and selected studies that compared the magnitude of drug-drug interactions with antiretroviral drugs in pregnant vs non-pregnant women. Forty-eight papers examining drug-drug interactions during pregnancy were selected, of which the majority focused on pharmacokinetic boosting. Other selected studies examined the drug-drug interactions between efavirenz and lumefantrine, efavirenz and tuberculosis drugs, etravirine and tenofovir disoproxil fumarate, atazanavir and tenofovir disoproxil, and mefloquine and nevirapine in pregnant compared to non-pregnant women. The clinical significance of antiretroviral drug-drug interactions changed during pregnancy from a minimal effect to a contra-indication. In almost all cases, the clinical significance of a drug-drug interaction was more relevant in pregnant women, owing to the combined effects of pregnancy-induced physiological changes and drug-drug interactions leading to a lower absolute drug exposure. Multiple studies show that the clinical relevance of a drug-drug interaction can change during pregnancy. Unfortunately, many potential interactions have not been studied in pregnancy, which may place pregnant women living with human immunodeficiency virus and their newborns at risk

Consistency of pacing profile according to performance level in three different editions of the Chicago, London, and Tokyo marathons

[EN] Running pacing has become a focus of interest over recent years due to its relationship with performance, however, it is still unknown the consistency of each race in different editions. The aim of this study is to analyze the consistency of pacing profile in three consecutive editions of three marathon races. A database of 282,808 runners, compiled from three different races (Chicago, London, and Tokyo Marathon) and three editions (2017, 2018, and 2019) was analyzed. Participants were categorized according to their time performance in the marathon, every 30 min from 2:30 h to sub-6 h. The relative speed of each section for each runner was calculated as a percentage of the average speed for the entire race. The intraclass correlation coefficients (ICC) of relative speed at the different pacing section, taking into account the runner time categories, was excellent over the three marathon editions (ICC > 0.93). The artificial intelligence model showed an accuracy of 86.8% to classify the runners' data in three marathons, suggesting a consistency between editions with identifiable differences between races. In conclusion, although some differences have been observed between editions in certain sections and marathon runner categories, excellent consistency of the pacing profile was observed. The study of pacing profile in a specific marathon can, therefore, be helpful for runners, coaches and marathon organizers for planning the race and improving its organization.Oficial-Casado, F.; Uriel-Molto, J.; Jimenez-Perez, I.; Fagundes Goethel, M.; Pérez-Soriano, P.; Priego-Quesada, JI. (2022). Consistency of pacing profile according to performance level in three different editions of the Chicago, London, and Tokyo marathons. Scientific Reports. 12(1):1-9. https://doi.org/10.1038/s41598-022-14868-61912

Association between control group therapy and magnitude of clinical benefit of cancer drugs

Little is known about the impact of control group therapy on clinical benefit scales such as American Society of Clinical Oncology Value Framework (ASCO-VF), European Society for Medical Oncology Magnitude Clinical Benefit Scale (ESMO-MCBS), National Comprehensive Cancer Network (NCCN) Evidence Blocks and ASCO Cancer Research Committee (ASCO-CRC). We searched Drugs@FDA to identify cancer drugs approved between January 2012 and December 2021 based on randomized trials (RCTs). Definition of substantial clinical benefit was based on recommendations for each scale. Associations between characteristics of control group therapy and clinical benefit were explored using logistic regression. RCTs with a control group of active treatment plus placebo were associated with significantly lower odds of substantial benefit with ESMO-MCBS (OR 0.27, P = 0.003) and ASCO-VF (OR 0.30, P = 0.008) but not with NCCN Evidence Blocks or ASCO-CRC. This effect was attenuated and lost statistical significance without adjustment for quality of life (QoL) and/or toxicity (ESMO-MCBS OR 0.50, P = 0.17; ASCO-VF OR 0.49, P = 0.11). Clinical benefit scales can be sensitive to control group therapy. RCTs with substantial overlap between experimental and control therapy showed lower magnitude of clinical benefit using ESMO-MCBS and ASCO-VF scales; possibly due to differences in the weighting of QoL and toxicity between different frameworks

Drv Concentrations And Viral Load In Csf In Patients On Drv/r 600/100 Or 800/100mg Once Daily Plus Two Nrti

Introduction Darunavir/r (DRV/r) is currently used at a dose of 800/100 mg once daily (OD) in a high proportion of patients. Pharmacokinetic data suggest that 600/100 OD may be effective, reducing toxicity and cost. However, drug concentrations in reservoirs such as cerebrospinal fluid (CSF) might not be adequate to inhibit viral replication. We aimed to evaluate concentrations of DRV and HIV‐1 viral load (VL) in CSF patients receiving DRV 600/100 mg OD. Methods DRV600 is an ongoing randomized open study comparing DRV/r 800/100 mg (DRV800) vs 600/100 mg (DRV600) OD plus TDF/FTC or ABC/3TC in 100 virologically suppressed patients (eudraCT 2011‐006272‐39). Here we present the results of a CSF sub‐study. A lumbar puncture (LP) was performed in participating patients after at least six months of inclusion in the study, 20–28 hours after a dose of DRV/r. VL (PCR, LOD 40 copies/mL) was determined in CSF and in plasma. DRV concentrations were quantified in CSF by liquid chromatography mass spectrometry (LC/MS/MS) and in plasma using high‐performance liquid chromatography (HPLC). Results Sixteen patients were included (eight in each arm). All DRV600 patients and four out of eight DRV800 patients received TDF/FTC, and the other four ABC/3TC. 75% were males, median (range) age was 48 (17–71) years, CD4 cell count 532 cells/mL (190–1,394). Median total time on DRV/r was 30 (11–57) months, and since the beginning of the study 8 (6–12) months in DRV800 and 10 (7–12) months in DRV600 patients. LP was performed a median of 26 (24–28) hours after the last DRV/r+TVD or KVX dose. In DRV600 patients the median DRV plasma levels were 1,674 (326–3,742) ng/mL, CSF levels 17.08 (5.79–30.19) ng/mL and DRV CSF:plasma ratio 0.0084 (0.0028–0.0388), while in the DRV800 arm, median DRV plasma levels were 1,707 (958–3,910) ng/mL, CSF levels 13.23 (3.47–32.98) ng/mL and DRV CSF:plasma ratio 0.0104 (0.0018–0.0262). All patients had VL<40 copies/mL in plasma and 14 patients VL<40 copies/mL in CSF. Two patients (1 in each arm, and taking TDF/FTC) had detectable VL in CSF (280 and 159 c/mL). These patients had the lowest CSF DRV concentrations (5.47 and 3.47 ng/mL), with plasma DRV concentrations of 802 and 958 ng/mL respectively. Conclusions CSF DRV concentrations and CSF VL were similar between patients receiving DRV/r 800/100 mg or 600/100 mg OD. Low CSF DRV concentrations might be associated with viral escape in CNS. This may be taken into account in patients receiving OD DRV/r. Larger studies should confirm these findings

Removal of doravirine by haemodialysis in people living with HIV with end-stage renal disease

ObjectivesTo evaluate the effect of haemodialysis on doravirine concentrations in people living with HIV (PLWH) undergoing routine haemodialysis.MethodsAn exploratory clinical trial that included PLWH undergoing intermittent haemodialysis was undertaken. After enrolment (day 1), doravirine 100 mg once daily was added to stable combined ART for 5 days. On day 6, blood samples were collected from each participant at the beginning and at the end of a dialysis session. Additionally, paired samples of blood entering ('in') and leaving ('out') the dialyser and the resulting dialysate were collected during the dialysis session to evaluate drug removal during dialysis. Doravirine concentrations in plasma and in the dialysate were determined by LC-MS/MS. The ratio of doravirine concentrations in plasma after/before the haemodialysis session and the haemodialysis extraction coefficient were calculated for each participant. The study was registered at https://www.clinicaltrials.gov (NCT04689737).ResultsEight participants (six male) were included. The median (range) age and BMI were 49.5 (28-67) years and 23.6 (17.9-34.2) kg/m2, respectively. The doravirine dialysis extraction ratio was 34.3% (25.8%-41.4%). The ratio of doravirine concentrations in plasma after/before the haemodialysis session was 0.8 (0.6-1.0). At the end of the haemodialysis session (time post-dose 20.8-27.3 h), doravirine concentrations in plasma were 785 (101-1851) ng/mL.ConclusionsDespite moderate removal of doravirine by haemodialysis, trough doravirine concentrations in plasma after the haemodialysis sessions remained in excess of the protein-binding-adjusted EC50 (5 ng/mL). Doravirine dosage adjustments are unnecessary in PLWH undergoing intermittent haemodialysis