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Plasminogen activator inhibitor-1 (PAI-1) is elevated in women with polycystic ovary syndrome (PCOS), but the regulation in granulosa cells (GCs) is unclear. PAI-1 expression in PCOS ovaries was investigated immunohistologically. PAI-1 expressions in HGrC1, a human GC cell line, were investigated at mRNA and activity levels. The expressions of TGF-β and TNF-α in peritoneal fluid mononuclear cells (PFMCs) were measured with quantitative PCR. Little PAI-1 expression is observed in healthy GCs, whereas GCs of PCOS and atretic follicle exhibit distinct expression in vivo. In vitro study using HGrC1 shows that TGF-β and TNF-α increase PAI-1 mRNA and its activity, and both together exhibit a synergistic effect. The expression of PAI-1 mRNA is suppressed by simvastatin. Moreover, insulin-sensitizing drugs (metformin, pioglitazone, and rosiglitazone) suppress LPS-induced TGF-β and TNF-α mRNA expression in PFMC. Statin and insulin-sensitizing drugs may provide a potential therapy for PCOS via down-regulation of PAI-1 expression in GCs and down-regulation of TGF-β and TNF-α expression in PFMC, respectively. more...

Sport concussion receives substantial attention as a public health concern. Conversely, performing artists, including dancers, sustain concussions, but these aesthetic athletes do not receive the same level of consideration nor care for this injury as that offered to traditional athletes. The concussion literature pertaining to dance is sparse, and, to our knowledge, no recommendations exist for the crucial aspect of care related to returning to dance following a concussion. The purpose of this article is to assimilate the current knowledge about post‐concussion return to activity management in sport—the closest analog of the physical demands required in dance—as a means to delineate a framework for returning to dance following a concussion. Specific guidance is provided based on a review of evidence‐based practice so clinicians can ensure that dancers return safely to both their dance activity and any academic work they are required to undertake. Concussion in dance is not an infrequent occurrence and dancers and healthcare practitioners alike will benefit from dance‐specific guidance for returning to dance post‐concussion. Overall, the principles that form the foundation for return‐to‐sport decisions are remarkably robust for application to dance. [ABSTRACT FROM AUTHOR] more...

There are infinitely many ways the world might be, and there may well be infinitely many people in it. These facts raise moral paradoxes. We explore a conflict between two highly attractive principles: a Pareto principle that says that what is better for everyone is better overall, and a statewise dominance principle that says that what is sure to turn out better is better on balance. We refine and generalize this paradox, showing that the problem is faced by many theories of interpersonal aggregation besides utilitarianism, and by many decision theories besides expected value theory. Considering the range of consistent responses, we find all of them to be quite radical. [ABSTRACT FROM AUTHOR] more...

How should a group with different opinions (but the same values) make decisions? In a Bayesian setting, the natural question is how to aggregate credences: how to use a single credence function to naturally represent a collection of different credence functions. An extension of the standard Dutch-book arguments that apply to individual decision-makers recommends that group credences should be updated by conditionalization. This imposes a constraint on what aggregation rules can be like. Taking conditionalization as a basic constraint, we gather lessons from the established work on credence aggregation, and extend this work with two new impossibility results. We then explore contrasting features of two kinds of rules that satisfy the constraints we articulate: one kind uses fixed prior credences, and the other uses geometric averaging, as opposed to arithmetic averaging. We also prove a new characterisation result for geometric averaging. Finally we consider applications to neighboring philosophical issues, including the epistemology of disagreement. more...

Should we make significant sacrifices to ever‐so‐slightly lower the chance of extremely bad outcomes, or to ever‐so‐slightly raise the chance of extremely good outcomes? Fanaticism says yes: for every bad outcome, there is a tiny chance of extreme disaster that is even worse, and for every good outcome, there is a tiny chance of an enormous good that is even better. I evaluate the prospects for Fanaticism, in connection with two other kinds of general ethical principles. First, separability principles, which say that which option is best does not depend in strange ways on what might be going on in distant space and time—jumping off from a recent argument for Fanaticism from Beckstead and Thomas (2023). Second, reflection principles, about how gaining new information makes a difference to which options are best—jumping off from a recent argument for Fanaticism from Wilkinson (2022). It turns out that the situation is unstable: plausible general separability and reflection principles actually tell against Fanaticism, but restrictions of those same principles (with strengthened auxiliary assumptions) support Fanaticism. All of the consistent views that emerge are very strange. [ABSTRACT FROM AUTHOR] more...

Suppose that, for reasons of animal welfare, it would be better if everyone stopped eating chicken. Does it follow that you should stop eating chicken? Proponents of the 'inefficacy objection' argue that, due to the scale and complexity of markets, the expected effects of your chicken purchases are negligible. So the expected effects of eating chicken do not make it wrong. We argue that this objection does not succeed, in two steps. First, empirical data about chicken production tells us that the expected effects of consuming many chickens are not negligible. Second, this implies that the expected effect of consuming one chicken is ordinarily not negligible. Parity between your purchase and other counterfactual purchases, and uncertainty about others' consumption behaviour, each tend to pull the expected effect of a single purchase toward the average large scale effect. While some purchases do have negligible expected effects, many do not. [ABSTRACT FROM AUTHOR] more...

Context: Proprioception is an individual's awareness of body position in 3-dimensional space. How proprioceptive acuity changes under varying conditions such as joint position, load, and concentric or eccentric contraction type is not well understood. In addition, a limitation of the variety of techniques to assess proprioception is the lack of clinically feasible methods to capture proprioceptive acuity. The purpose of this study was to implement a readily available instrument, a smartphone, in the clinical evaluation of knee active joint position sense and to determine how joint angle, joint loading, and quadriceps contraction type affect an individual's active joint position sense. Design: Cross-over study. Methods: Twenty healthy, physically active university participants (10 women and 10 men: 21.4 [2.0] y; 1.73 [0.1] m; 70.9 [14.3] kg) were recruited. Individuals were included if they had no neurological disorder, no prior knee surgery, and no recent knee injury. The participants were given a verbal instruction to locate a target angle and then were tasked with reproducing the target angle without visual or verbal cues. An accelerometer application on a smartphone was used to assess the angle to the nearest tenth of a degree. Three variables, each with 2 levels, were analyzed in this study: load (weighted and unweighted), contraction type (eccentric and concentric), and joint position (20° and 70°). A repeated-measures analysis of variance was conducted to assess the within-subjects factors of load, contraction, and position. Results: A significant difference of 0.50° (0.19°) of greater error with eccentric versus concentric contraction (P =.02) type was identified. In addition, a significant interaction was found for contraction × position, with a mean increase in error of 0.98° (0.33°) at the 20° position when contracting eccentrically (P =.03). Conclusions: Contraction type, specifically eccentric contraction at 20°, showed significantly greater error than concentric contraction. This suggests that, during eccentric contractions of the quadriceps, there may be decreased proprioceptive sensitivity compared with concentric contractions. [ABSTRACT FROM AUTHOR] more...

This paper proposes a new approach to modeling financial transactions data. A new model for discrete valued time series is proposed in the context of generalized linear models. Since the model is specified conditional on both the previous state, as well as the historic distribution, we call the model the Autoregressive Conditional Multinomial (ACM) model. When the data are viewed as a marked point process, the ACD model proposed in Engle and Russell (1998) allows for joint modeling of the price transition probabilities and the arrival times of the transactions. In this marked point process context, the transition probabilities vary continuously through time and are therefore duration dependent. Finally, variations of the model allow for volume and spreads to impact the conditional distribution of price changes. Impulse response studies show the long run price impact of a transaction can be very sensitive to volume but is less sensitive to the spread and transaction rate. more...

Competent project managers (PMs) are the backbone of any construction project. It is extremely important to constantly develop and enhance their competencies. However, to establish effective training and development plans for PMs, the relative importance of the key competencies that define a PM's performance should be first understood. Instead of subjectively weighting the relative importance of differing competencies, this paper aims at developing an automated model that uses real-life data to compute the PM competency weights. The rationale behind the model is to maximize the distance in a higher dimensional space between average and exceptional PM performances. The model solves an eigenvalue problem, and identifies a single data-based weight for each competency. The model is generic and can be applied to various research settings to alleviate the problems associated with opinion-based assessment and reduce individuals' subjectivity. Findings within this paper reveal the most critical competencies that enable PMs to perform their roles in construction projects exceptionally. Key words: modeling, decision support systems, eigenvalues, eigenvectors, project managers, competence, construction management. Des gestionnaires de projet (GP) competents sont la pierre angulaire de n'importe quel projet de construction. Il est extremement important de constamment developper et ameliorer leurs competences. Cependant, afin d'etablir des plans de formation et de perfectionnement efficaces pour les GP, l'importance relative des competences cles qui definissent le rendement d'un GP devrait d'abord etre comprise. Au lieu de subjectivement ponderer l'importance relative des differentes competences, dans cet article, on vise a developper un modele automatise qui utilise des donnees reelles pour calculer les ponderations de competence de GP. Le raisonnement qui sous-tend le modele est de maximiser la distance, dans un espace de dimensions superieures, entre les rendements moyens et exceptionnels des GP. Le modele resout un probleme de valeurs propres et etablit une seule ponderation a partir des donnees pour chaque competence. Le modele est generique et peut etre applique a differents contextes de recherche afin d'attenuer les problemes associes a l'evaluation d'apres les opinions et de reduire la subjectivite des intervenants. Les resultats de cette etude revelent les competences les plus critiques qui permettent aux GP de remplir leurs fonctions de facon exceptionnelle dans le cadre de projets de construction. [Traduit par la Redaction] Mots-cles: modelisation, systemes d'aide a la decision, valeurs propres, vecteurs propres, gestionnaires de projets, competence, gestion de construction., Introduction Project managers (PMs) maintain ultimate responsibility for completing construction projects in compliance with owner requirements, as well as within budget and time constraints. Project managers must be competent to [...] more...