Stroke is a leading cause of death and disability throughout the world. Although physical and cognitive impairments after stroke have been well studied, little is known about sexual functioning and ...satisfaction in these patients, despite being crucial aspects of quality of life. Post-stroke sexual dysfunctions seem to be common; in men affected by stroke, a decline in libido and poor or curtailed erection and ejaculation are frequently observed. Sexual disorders after stroke are thought to be due to multiple etiologies, including both organic (e.g., lesion localization, premorbid medical conditions, medications) and psychosocial (e.g., fear of recurrences, loss of self-esteem, role changes, anxiety and depression) etiologies. Thus, the exploration of sexual dysfunction and sexual counseling by trained professionals should be part of stroke rehabilitation.
The purpose of this paper is to assess the influence of a novel type of vortex creation device called the leading-edge vortex controller (LEVCON) on the aerodynamic characteristics of a fighter jet. ...LEVCON has become a trending term in modern military aircraft in recent years and is a continuation of an existing and widely used aerodynamic solution called the leading-edge root extension (LERX). LEVCON is designed to operate on the same principles as LERX, but its aim is to generate lift-augmenting vortices, i.e., vortex lift, at higher angles of attack than LERX. To demonstrate the methodology, a custom delta wing fighter aircraft is introduced, and details about its aerodynamic configuration are provided. The LEVCON geometry is designed and then incorporated into an existing three-dimensional (3D) model of the aircraft in question. The research is conducted using OpenFOAM 8, a high-fidelity computational fluid dynamics (CFD) open-source software. The computational cases are designed to simulate the aircraft’s flight at stall velocities within a high range of angles of attack. The results are assessed and discussed in terms of aerodynamic characteristics. A conclusion is drawn from the analysis regarding the perceived improvements in fighter jet aerodynamics. The analysis reveals that both lift and critical angle of attack can be manipulated positively. With the addition of LEVCON, the average lift gain in the high angle of attack (α) range is between 8.5% and 10%, while the peak gain reaches 19.4%. The critical angle of attack has also increased by 2°, and a flatter stall characteristic has been achieved.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
3.
What models can and cannot tell us about COVID-19 Siegenfeld, Alexander F.; Taleb, Nassim N.; Bar-Yam, Yaneer
Proceedings of the National Academy of Sciences - PNAS,
07/2020, Volume:
117, Issue:
28
Journal Article
Peer reviewed
Open access
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Rosacea: New Concepts in Classification and Treatment van Zuuren, Esther J.; Arents, Bernd W. M.; van der Linden, Mireille M. D. ...
American journal of clinical dermatology,
07/2021, Volume:
22, Issue:
4
Journal Article
Peer reviewed
Open access
Rosacea is a chronic inflammatory dermatosis mainly affecting the cheeks, nose, chin, and forehead. Rosacea is characterized by recurrent episodes of flushing or transient erythema, persistent ...erythema, phymatous changes, papules, pustules, and telangiectasia. The eyes may also be involved. Due to rosacea affecting the face, it has a profound negative impact on quality of life, self-esteem, and well-being. In addition to general skin care, there are several approved treatment options available for addressing these features, both topical and systemic. For some features, intense pulse light, laser, and surgery are of value. Recent advances in fundamental scientific research have underscored the roles of the innate and adaptive immune systems as well as neurovascular dysregulation underlying the spectrum of clinical features of rosacea. Endogenous and exogenous stimuli may initiate and aggravate several pathways in patients with rosacea. This review covers the new phenotype-based diagnosis and classification system reflecting pathophysiology, and new and emerging treatment options and approaches. We address new topical and systemic formulations, as well as recent evidence on treatment combinations. In addition, ongoing studies investigating novel therapeutic interventions will be summarized.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The epidemiology of invasive fungal infections is changing, with new populations at risk and the emergence of resistance caused by the selective pressure from increased usage of antifungal agents in ...prophylaxis, empiric therapy, and agriculture. Limited antifungal therapeutic options are further challenged by drug–drug interactions, toxicity, and constraints in administration routes. Despite the need for more antifungal drug options, no new classes of antifungal drugs have become available over the last 2 decades, and only one single new agent from a known antifungal class has been approved in the last decade. Nevertheless, there is hope on the horizon, with a number of new antifungal classes in late-stage clinical development. In this review, we describe the mechanisms of drug resistance employed by fungi and extensively discuss the most promising drugs in development, including fosmanogepix (a novel Gwt1 enzyme inhibitor), ibrexafungerp (a first-in-class triterpenoid), olorofim (a novel dihyroorotate dehydrogenase enzyme inhibitor), opelconazole (a novel triazole optimized for inhalation), and rezafungin (an echinocandin designed to be dosed once weekly). We focus on the mechanism of action and pharmacokinetics, as well as the spectrum of activity and stages of clinical development. We also highlight the potential future role of these drugs and unmet needs.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
Prostaglandin D
2
(PGD
2
) released by degranulating mast cells is believed to play a key role in orchestrating mechanisms of inflammation in allergies and asthma. The biological effects of PGD
2
are ...mediated by D-prostanoid (DP1), CRTH2 (DP2), and thromboxane prostanoid (TP) receptors. The CRTH2 receptor is involved in induction of migration and activation of T helper type 2 (Th
2
) lymphocytes, eosinophils, and basophils; up-regulation of adhesion molecules; and promotion of pro-inflammatory Th
2
-type cytokines (interleukin IL-4, 5, 13), whereas the DP receptor is associated with relaxation of smooth muscles, vasodilation, inhibition of cell migration, and apoptosis of eosinophils. A number of CRTH2/PGD
2
receptor antagonists have been investigated in asthma and allergic diseases. The CRTH2 antagonist (OC000459) or dual CRTH2 and TP receptor antagonist (ramatroban) were effective in reducing eosinophilia, nasal mucosal swelling, and clinical symptoms of allergic rhinitis, with the latter drug registered for clinical use in this indication. OC000459 and setipiprant reduced the late but not early phase of response in an allergen challenge in atopic asthmatics. In persistent asthma, some molecules induced limited improvement in lung function, quality of life, and asthma symptoms (OC000459, BI671800), but in other trials with AMG 853 and AZ1981 these findings were not confirmed. The clear discrepancy between animal studies and clinical efficacy of CRTH2 antagonism in allergic rhinitis, and lack of efficacy in a general cohort of asthmatics, highlight the issue of patient phenotyping. There is no doubt that the PGD
2
/CATH2/DP1 pathway plays a key role in allergic inflammation and further studies with selective or combined antagonisms in well defined cohorts of patients are needed.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
•This research presents new theoretical insight which will augment the promulgation of leading indicators’ use in safety management.•An extensive and thorough literature analysis is conducted using ...two consecutive data analysis methods viz. thematic and content analyses.•A new theoretical explanation of leading and lagging indicators is proffered which incorporates safety management dynamics.•The work serves to engender renewed polemic debate and discussion on how to create a step change in safety performance improvement in the workplace.
With the aim of developing a new theoretical insight which will augment the promulgation of leading indicators’ use, this present research studies pertinent literature. Associated study objectives are to: 1) generate insight into potential challenges, use and benefits of adopting leading indicators in safety management from pertinent literature; and 2) elucidate upon existing abstruseness between safety leading and lagging indicators. For an extensive and thorough literature analysis, two consecutive data analysis methods are adopted (viz., thematic and content analyses). Through thematic analysis, 13 clusters (each representing different uses of leading indicators) emerged, from which the ‘health and safety’ cluster was selected for a deeper analysis in content analysis. In addition, by reviewing the compendium of leading indicator examples collected from extant safety leading indicator literature, novel types of dichotomous leading indicators were identified, viz., generic and specific leading indicators. Subsequently, a synthesis of challenges and benefits of safety leading indicator adoption was generated through deductive content analysis. Furthermore, a new theoretical explanation into the relationship of safety leading and lagging indicators is proffered which also incorporates safety management dynamics representing different levels of safety maturity. This study constitutes a first attempt to: provide a structured synthesis of safety leading indicators’ functions along with their challenges in development, implementation and adoption stages; shed a new light into the theoretical explication of safety lagging and leading indicators’ relationship; and introduce safety management dynamics that establish different levels of safety maturity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The ‘centre–periphery hypothesis’ (CPH) is a long‐standing postulate in ecology that states that genetic variation and demographic performance of a species decrease from the centre to the edge of its ...geographic range. This hypothesis is based on an assumed concordance between geographical peripherality and ecological marginality such that environmental conditions become harsher towards the limits of a species range. In this way, the CPH sets the stage for understanding the causes of distribution limits. To date, no study has examined conjointly the consistency of these postulates. In an extensive literature review we discuss the birth and development of the CPH and provide an assessment of the CPH by reviewing 248 empirical studies in the context of three main themes. First, a decrease in species occurrence towards their range limits was observed in 81% of studies, while only 51% demonstrated reduced abundance of individuals. A decline in genetic variation, increased differentiation among populations and higher rates of inbreeding were demonstrated by roughly one in two studies (47, 45 and 48%, respectively). However, demographic rates, size and population performance less often followed CPH expectations (20–30% of studies). We highlight the impact of important methodological, taxonomic, and biogeographical biases on such validation rates. Second, we found that geographic and ecological marginality gradients are not systematically concordant, which casts doubt on the reliability of a main assumption of the CPH. Finally, we attempt to disentangle the relative contribution of geographical, ecological and historical processes on the spatial distribution of genetic and demographic parameters. While ecological marginality gradients explain variation in species' demographic performance better than geographic gradients, contemporary and historical factors may contribute interactively to spatial patterns of genetic variation. We thereby propose a framework that integrates species' ecological niche characteristics together with current and past range structure to investigate spatial patterns of genetic and demographic variation across species ranges.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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