Critical terms in future studies

publishedVersio

The utility of efavirenz-based prophylaxis against HIV infection. A systems pharmacological analysis

Pre-exposure prophylaxis (PrEP) is considered one of the five “pillars” by UNAIDS to reduce HIV transmission. Moreover, it is a tool for female self-protection against HIV, making it highly relevant to sub-Saharan regions, where women have the highest infection burden. To date, Truvada is the only medication for PrEP. However, the cost of Truvada limits its uptake in resource-constrained countries. Similarly, several currently investigated, patent-protected compounds may be unaffordable in these regions. We set out to explore the potential of the patent-expired antiviral efavirenz (EFV) as a cost-efficient PrEP alternative. A population pharmacokinetic model utilizing data from the ENCORE1 study was developed. The model was refined for metabolic autoinduction. We then explored EFV cellular uptake mechanisms, finding that it is largely determined by plasma protein binding. Next, we predicted the prophylactic efficacy of various EFV dosing schemes after exposure to HIV using a stochastic simulation framework. We predicted that plasma concentrations of 11, 36, 1287 and 1486ng/mL prevent 90% sexual transmissions with wild type and Y181C, K103N and G190S mutants, respectively. Trough concentrations achieved after 600 mg once daily dosing (median: 2017 ng/mL, 95% CI:445–9830) and after reduced dose (400 mg) efavirenz (median: 1349ng/mL, 95% CI: 297–6553) provided complete protection against wild-type virus and the Y181C mutant, and median trough concentrations provided about 90% protection against the K103N and G190S mutants. As reduced dose EFV has a lower toxicity profile, we predicted the reduction in HIV infection when 400 mg EFV-PrEP was poorly adhered to, when it was taken “on demand” and as post-exposure prophylaxis (PEP). Once daily EFV-PrEP provided 99% protection against wild-type virus, if ≥50% of doses were taken. PrEP “on demand” provided complete protection against wild-type virus and prevented ≥81% infections in the mutants. PEP could prevent >98% infection with susceptible virus when initiated within 24 h after virus exposure and continued for at least 9 days. We predict that 400 mg oral EFV may provide superior protection against wild-type HIV. However, further studies are warranted to evaluate EFV as a cost-efficient alternative to Truvada. Predicted prophylactic concentrations may guide release kinetics of EFV long-acting formulations for clinical trial design

Restricted loss of olivocochlear but not vestibular efferent neurons in the senescent gerbil (Meriones unguiculatus)

Degeneration of hearing and vertigo are symptoms of age related auditory and vestibular disorders reflecting multrfactorial changes in the peripheral and central nervous system whose interplay remains largely unknown. Originating bilaterally in the brain stem, vestibular and auditory efferent cholinergic projections exert feedback control on the peripheral sensory organs, and modulate sensory processing. We studied age-related changes in the auditory and vestibular efferent systems by evaluating number of cholinergic efferent neurons in young adult and aged gerbils, and in cholinergic trigeminal neurons serving as a control for efferents not related to the inner ear. We observed a significant loss of olivocochlear (OC) neurons in aged compared to young adult animals, whereas the overall number of lateral superior olive (LSO) cells was not reduced in aging. Although the loss of lateral and medial olivocochlear (MOC) neurons was uniform and equal on both sides of the brain, there were frequency-related differences within the lateral olivocochlear (LOC) neurons, where the decline was larger in the medial limb of the superior olivary nucleus (high frequency representation) than in the lateral limb (middle-to-low frequency representation). In contrast, neither the number of vestibular efferent neurons, nor the population of motor trigeminal neurons were significantly reduced in the aged animals. These observations suggest differential effects of aging on the respective cholinergic efferent brainstem systems

Exploring the drivers behind experience accumulation – The role of secondary experiences consumed through the eyes of social media influencers

Author's accepted version (postprint).This is an Accepted Manuscript of an article published by Elsevier in Journal of Hospitality and Tourism Management on 04/10/2019.Available online: https://www.sciencedirect.com/science/article/pii/S1447677019302311?via%3DihubacceptedVersio

Online Students’ Expectations Differ: The advantage of assessing students’ expectations in online education

[EN] Students’ feedback on online education has become of major importance for many higher education institutions. While researchers already identified students’ success factors and analyzed students’ satisfaction in online study programs and courses, the role of expectations in students’ online educational experience has been very often neglected in previous research. Our study adds here as it captures students’ expectations at the beginning of an online study program, highlighting the differences to traditional on-campus students. Our results reveal that expectations of on-line students differ from the expectations of on-campus students and must therefore not be confused. Furthermore, the assessment of student expectations is not only a way to consider and satisfy students’ needs in order to improve online programs or courses, but also a means to track the institutions own performance.Keywords: Online Education; Student Experience; Expectations, Retention, Higher Education ManagementWieser, D.; Seeler, J.; Sixl-Daniell, K.; Zehrer, A. (2017). Online Students’ Expectations Differ: The advantage of assessing students’ expectations in online education. En Proceedings of the 3rd International Conference on Higher Education Advances. Editorial Universitat Politècnica de València. 1113-1120. https://doi.org/10.4995/HEAD17.2017.55251113112