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1.
Evol Psychol ; 22(2): 14747049241262712, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38881307

RESUMEN

Many researchers have proposed that women perceive men with masculine face shapes to be less suitable as parents and long-term partners than men with feminine face shapes, causing women to find masculine men more attractive for short-term than long-term relationships. However, recent work shows that results obtained using the type of experimentally manipulated stimuli that were employed in studies presenting evidence for these claims are not necessarily observed when natural (i.e., unmanipulated) face stimuli were used to suggest that the evidence for these claims may need to be revaluated. Consequently, we tested for possible relationships between ratings of natural male faces for parenting- and relationship-related traits and shape masculinity (Study 1) and also tested whether women's preferences for shape masculinity were stronger when natural male faces were rated for short-term relationships than when natural male faces were rated for long-term relationships (Studies 2 and 3). We saw no evidence for either of these predictions, instead finding that men with more attractive faces were perceived to be better parents and better long-term partners. Thus, our findings do not support the widely held view that masculine men are more attractive for short-term relationships because they are perceived to be unlikely to invest time and effort in their romantic partners and offspring.


Asunto(s)
Reconocimiento Facial , Masculinidad , Parejas Sexuales , Percepción Social , Humanos , Femenino , Masculino , Adulto , Adulto Joven , Parejas Sexuales/psicología , Reconocimiento Facial/fisiología , Conducta de Elección , Cara , Relaciones Interpersonales , Adolescente
2.
Sci Rep ; 14(1): 10488, 2024 05 07.
Artículo en Inglés | MEDLINE | ID: mdl-38714709

RESUMEN

Vocal attractiveness influences important social outcomes. While most research on the acoustic parameters that influence vocal attractiveness has focused on the possible roles of sexually dimorphic characteristics of voices, such as fundamental frequency (i.e., pitch) and formant frequencies (i.e., a correlate of body size), other work has reported that increasing vocal averageness increases attractiveness. Here we investigated the roles these three characteristics play in judgments of the attractiveness of male and female voices. In Study 1, we found that increasing vocal averageness significantly decreased distinctiveness ratings, demonstrating that participants could detect manipulations of vocal averageness in this stimulus set and using this testing paradigm. However, in Study 2, we found no evidence that increasing averageness significantly increased attractiveness ratings of voices. In Study 3, we found that fundamental frequency was negatively correlated with male vocal attractiveness and positively correlated with female vocal attractiveness. By contrast with these results for fundamental frequency, vocal attractiveness and formant frequencies were not significantly correlated. Collectively, our results suggest that averageness may not necessarily significantly increase attractiveness judgments of voices and are consistent with previous work reporting significant associations between attractiveness and voice pitch.


Asunto(s)
Belleza , Voz , Humanos , Masculino , Femenino , Voz/fisiología , Adulto , Adulto Joven , Juicio/fisiología , Adolescente
3.
Clin Pharmacol Ther ; 115(2): 299-308, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-37971208

RESUMEN

A physiologically-based pharmacokinetic (PBPK) model was developed to simulate plasma concentrations of tucatinib (TUKYSA®) after single-dose or multiple-dose administration of 300 mg b.i.d. orally. This PBPK model was subsequently applied to support evaluation of drug-drug interaction (DDI) risk as a perpetrator resulting from tucatinib inhibition of CYP3A4, CYP2C8, CYP2C9, P-gp, or MATE1/2-K. The PBPK model was also applied to support evaluation of DDI risk as a victim resulting from co-administration with CYP3A4 or CYP2C8 inhibitors, or a CYP3A4 inducer. After refinement with clinical DDI data, the final PBPK model was able to recover the clinically observed single and multiple-dose plasma concentrations for tucatinib when tucatinib was administered as a single agent in healthy subjects. In addition, the final model was able to recover clinically observed plasma concentrations of tucatinib when administered in combination with itraconazole, rifampin, or gemfibrozil as well as clinically observed plasma concentrations of probe substrates of CYP3A4, CYP2C8, CYP2C9, P-gp, or MATE1/2-K. The PBPK model was then applied to prospectively predict the potential perpetrator or victim DDIs with other substrates, inducers, or inhibitors. To simulate a potential interaction with a moderate CYP2C8 inhibitor, two novel PBPK models representing a moderate CYP2C8 inhibitor and a sensitive CYP2C8 substrate were developed based on the existing PBPK models for gemfibrozil and rosiglitazone, respectively. The simulated population geometric mean area under the curve ratio of tucatinib with a moderate CYP2C8 inhibitor ranged from 1.98- to 3.08-fold, and based on these results, no dose modifications were proposed for moderate CYP2C8 inhibitors for the tucatinib label.


Asunto(s)
Inhibidores del Citocromo P-450 CYP2C8 , Gemfibrozilo , Oxazoles , Piridinas , Quinazolinas , Humanos , Gemfibrozilo/farmacocinética , Citocromo P-450 CYP3A , Citocromo P-450 CYP2C8 , Citocromo P-450 CYP2C9 , Interacciones Farmacológicas , Modelos Biológicos , Inhibidores del Citocromo P-450 CYP3A
4.
Evol Psychol ; 21(3): 14747049231175073, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37735893

RESUMEN

Facial femininity in men is purportedly used as a cue by women as a signal of parental quality and willingness to provide resources. Accordingly, in contexts where choosing a partner that will provide resources is more beneficial (e.g., when resources are scarce), women have shown an increase preference for facial femininity in male faces. However, domains of scarcity often covary, and it is, therefore, unclear whether these contextual shifts in facial masculinity/femininity preferences are specific to material scarcity (as implied by previous theory), or due to an unrelated domain of scarcity (e.g., time or psychological scarcity). Here, a sample of 823 women completed the Perceived Scarcity Scale, which measures three separate domains of scarcity: material scarcity, time scarcity, and psychological scarcity. Participants also rated the attractiveness of 42 male faces, which were measured on objective sexual dimorphism and perceived masculinity. Consistent with theory, material scarcity, and not time or psychological scarcity, was associated with a decreased preference for objective sexual dimorphism (i.e., an increased preference for facial femininity). This study provides evidence that women use sexual dimorphism as a cue to material resource provisioning potential when assessing men as a mate.


Asunto(s)
Cara , Masculinidad , Masculino , Humanos , Femenino , Conducta de Elección , Feminidad , Caracteres Sexuales , Conducta Sexual
5.
Sci Rep ; 13(1): 12620, 2023 08 03.
Artículo en Inglés | MEDLINE | ID: mdl-37537340

RESUMEN

Dominance perceptions play an important role in social interactions. Although many researchers have proposed that shape masculinity is an important facial cue for dominance perceptions, evidence for this claim has come almost exclusively from studies that assessed perceptions of experimentally manipulated faces using forced-choice paradigms. Consequently, we investigated the role of masculine shape characteristics in perceptions of men's facial dominance (1) when shape-manipulated stimuli were presented in a forced-choice paradigm and (2) when unmanipulated face images were rated for dominance and shape masculinity was measured from face images. Although we observed large effects of masculinity on dominance perceptions when we used the forced-choice method (Cohen's ds = 2.51 and 3.28), the effect of masculinity on dominance perceptions was considerably smaller when unmanipulated face images were rated and shape masculinity measured from face images (Cohen's ds = 0.44 and 0.62). This pattern was observed when faces were rated separately for physical dominance, social dominance, and masculinity, and was seen for two different sets of stimuli. Collectively, these results suggest that shape masculinity may not be a particularly important cue for dominance perceptions when faces vary simultaneously on multiple dimensions, as is the case during everyday social interactions.


Asunto(s)
Cara , Masculinidad , Masculino , Humanos , Proyectos de Investigación , Predominio Social , Conducta de Elección
6.
Sci Rep ; 13(1): 10245, 2023 06 23.
Artículo en Inglés | MEDLINE | ID: mdl-37353614

RESUMEN

Although many researchers have proposed that women will show stronger preferences for male facial masculinity when conception probability is high, empirical tests of this hypothesis have produced mixed results. One possible explanation for these inconsistent findings is that effects of conception probability on women's preferences for facial masculinity are moderated by additional factors not typically considered in these empirical tests. One such potential moderator is individual differences in women's openness to uncommitted sexual relationships (i.e., individual differences in women's sociosexual orientation); women who are more open to uncommitted sexual relationships might show stronger positive effects of conception probability on masculinity preferences, as their sexuality is more overt and sexual attitudes and behaviours are more diversified. Consequently, we analysed data from three independent samples (N = 2304, N = 483, and N = 339) to assess whether sociosexual orientation moderates the hypothesised positive effect of conception probability on women's facial masculinity preferences. Analyses showed no evidence that higher conception probability increased preferences for facial masculinity or that sociosexual orientation moderated the effect of conception probability on women's preferences for facial masculinity. While it remains possible that factors other than sociosexual orientation moderate effects of conception probability on masculinity preferences, our null results suggest that the mixed results for the effects of conception probability on facial masculinity preferences in previous studies are unlikely to be a consequence of failing to consider the moderating role of sociosexual orientation.


Asunto(s)
Conducta de Elección , Masculinidad , Humanos , Masculino , Femenino , Conducta Sexual , Fertilización , Sexualidad
7.
Adapt Human Behav Physiol ; : 1-16, 2023 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-37360188

RESUMEN

Purpose: Facial femininity in men is purportedly used as a cue by women as a signal of paternal involvement. However, evidence for this claim is questionable. Previous findings have shown that paternal involvement is linked to testosterone, but have not investigated facial masculinity directly, while other studies have found that facial masculinity is negatively associated with perceptions of paternal involvement but do not assess the accuracy of this judgement. Here, we assess whether facial masculinity in men is used as a cue to paternal involvement, and whether this cue is accurate. Methods: We collected facial photographs of 259 men (156 of which were fathers) who also completed self-report measures of paternal involvement. Facial images were then rated by a separate group of raters on facial masculinity, attractiveness, and perceived paternal involvement. Shape sexual dimorphism was also calculated from the images using geometric morphometrics. Results: We found that facial masculinity was not associated with perceptions of paternal involvement, nor was it related with self-reported paternal involvement. Interestingly, facial attractiveness was negatively associated with perceptions of paternal involvement, and we found partial evidence that facial attractiveness was also negatively associated with self-reported paternal involvement. Conclusion: These findings challenge the hypothesis that sexual dimorphism is used as a cue to paternal involvement, and perhaps indicate that facial attractiveness is more important for this judgement instead. Supplementary Information: The online version contains supplementary material available at 10.1007/s40750-023-00217-y.

8.
Clin Pharmacokinet ; 61(12): 1761-1770, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36471222

RESUMEN

BACKGROUND AND OBJECTIVE: Tucatinib, a highly selective tyrosine kinase inhibitor of the human epidermal growth factor receptor 2 (HER2) approved for HER2-positive metastatic breast cancer, is cleared by hepatic metabolism and subsequent biliary excretion. Liver disease can alter drug disposition and pharmacokinetics (PK). The objective of this study is to characterize PK and safety of tucatinib in volunteers with hepatic impairment. METHODS: This Phase 1 study compared the PK and safety of a single 300-mg oral dose of tucatinib in volunteers with mild, moderate, and severe hepatic impairment (Child-Pugh A/B/C) to healthy volunteers matched for sex, age, and body mass index. Pharmacokinetic parameters were determined for tucatinib and its predominant metabolite ONT-993. RESULTS: Compared with healthy volunteers, tucatinib exposure was similar in volunteers with mild impairment and increased in those with moderate or severe impairment without reaching statistical significance. Respective fold increases in geometric mean ratios for AUC0-t and AUC0-∞ were 1.13 and 1.15 in moderate impairment, and 1.43 and 1.61 in severe impairment compared with healthy volunteers. Three treatment-emergent adverse events (nausea, dermatitis, and increased transaminases) were reported in three volunteers and showed no obvious association with hepatic impairment status. CONCLUSION: The 1.61-fold geometric mean ratio AUC0-∞ increase in volunteers with severe hepatic impairment supports the recommendation in the tucatinib prescribing information to reduce the dose from 300 mg twice daily to 200 mg twice daily in patients with severe impairment; no dose adjustment is recommended for patients with mild or moderate hepatic impairment. This trial (NCT03722823) was registered on October 29, 2018.


Asunto(s)
Neoplasias de la Mama , Hepatopatías , Femenino , Humanos , Área Bajo la Curva , Hepatopatías/metabolismo , Inhibidores de Proteínas Quinasas/efectos adversos
9.
Sci Rep ; 12(1): 22479, 2022 12 28.
Artículo en Inglés | MEDLINE | ID: mdl-36577918

RESUMEN

There is growing concern that artificial intelligence conversational agents (e.g., Siri, Alexa) reinforce voice-based social stereotypes. Because little is known about social perceptions of conversational agents' voices, we investigated (1) the dimensions that underpin perceptions of these synthetic voices and (2) the role that acoustic parameters play in these perceptions. Study 1 (N = 504) found that perceptions of synthetic voices are underpinned by Valence and Dominance components similar to those previously reported for natural human stimuli and that the Dominance component was strongly and negatively related to voice pitch. Study 2 (N = 160) found that experimentally manipulating pitch in synthetic voices directly influenced dominance-related, but not valence-related, perceptions. Collectively, these results suggest that greater consideration of the role that voice pitch plays in dominance-related perceptions when designing conversational agents may be an effective method for controlling stereotypic perceptions of their voices and the downstream consequences of those perceptions.


Asunto(s)
Inteligencia Artificial , Voz , Humanos , Comunicación , Percepción Social , Estereotipo
10.
Pers Soc Psychol Bull ; : 1461672221135955, 2022 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-36541343

RESUMEN

Individuals are thought to seek the best possible romantic partner in exchange for their own desirability. We investigated whether individuals' self-evaluations were related to their partner choices and whether the accuracy of these self-evaluations was associated with mating outcomes. Participants (N = 1,354) took part in a speed-dating study where they rated themselves and others on mate value and indicated their willingness to date each potential partner. Individuals were somewhat accurate in their self-evaluations, and these self-evaluations were associated with individuals' revealed minimum and maximum standards for a potential partner, but not the number of partners they were interested in. Participants who overestimated their mate value were accepted by an equivalent number of partners compared with under-estimators, but the over-estimators were choosier and thus ended up with fewer (but similarly attractive) reciprocal matches. Results support social exchange theory and the matching hypothesis, and contrast findings that self-enhancement facilitates positive social outcomes.

11.
Clin Cancer Res ; 28(15): 3329-3341, 2022 08 02.
Artículo en Inglés | MEDLINE | ID: mdl-35727144

RESUMEN

PURPOSE: This study evaluated the central nervous system (CNS) pharmacokinetics and target engagement of lapatinib, neratinib, and tucatinib in patients with cancer, using a physiologically based pharmacokinetic (PBPK) modeling approach. EXPERIMENTAL DESIGN: Drug-specific parameters for in vitro metabolism, binding to plasma proteins and brain tissues, transcellular passive permeability, and interactions with efflux transporters were determined. Whole-body PBPK models integrated with a 4-compartment permeability-limited brain model was developed and verified for predicting plasma and CNS pharmacokinetics. Target engagement ratio (TER), defined as the ratio of the average steady-state unbound drug brain concentration (Css,ave,br) to in vitro IC50 for HER2 inhibition, was used as a predictor of intracranial efficacy. RESULTS: PBPK models predicted that following 1 cycle of standard dosing, tucatinib and lapatinib achieved similar Css,ave,br (14.5 vs. 16.8 nmol/L), while neratinib Css,ave,br (0.68 nmol/L) was 20-fold lower. Tucatinib and neratinib were equally potent for HER2 inhibition (IC50, 6.9 vs. 5.6 nmol/L), while lapatinib was less potent (IC50, 109 nmol/L). The model-predicted population mean TER in the human normal brain was 2.1 for tucatinib, but < 0.20 for lapatinib and neratinib. CONCLUSIONS: The PBPK modeling suggests that tucatinib induces sufficient HER2 inhibition (TER > 2.0) in not only brain metastases with a disrupted blood-brain barrier (BBB), but also micrometastases where the BBB largely remains intact. These findings, in line with available clinical pharmacokinetics and efficacy data, support the therapeutic value of tucatinib for treatment of brain metastases and warrant further clinical investigation for the prevention of brain metastases in patients with HER2-positive breast cancer.


Asunto(s)
Neoplasias Encefálicas , Neoplasias de la Mama , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Encefálicas/secundario , Neoplasias de la Mama/patología , Sistema Nervioso Central , Femenino , Humanos , Lapatinib/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Receptor ErbB-2/metabolismo
12.
Cancer Chemother Pharmacol ; 89(6): 737-750, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35435471

RESUMEN

PURPOSE: Tucatinib, a small molecule for the treatment of metastatic HER2-positive breast cancer, was extensively metabolized in humans to multiple oxidative metabolites. To fully understand the elimination and biotransformation pathways of tucatinib, we investigated the in vitro and in vivo metabolism of tucatinib, and also conducted a Phase I trial using [14C]tucatinib. METHODS: To identify the responsible enzymes for tucatinib clearance, we investigated the in vitro metabolism of tucatinib including enzyme phenotyping, which facilitated the discovery of several metabolites in human and monkey plasma and excreta, in particular M1 (ONT-993, an aliphatic hydroxylated metabolite). Stereoselective formation of M1 was further investigated in vitro, in vivo, and in silico. RESULTS: In humans, approximately 86% of the total radiolabeled dose was recovered in feces and 4% in urine; in plasma, approximately 76% of radioactivity circulated as parent drug, with 19% attributed to multiple metabolites. The primary isoforms responsible for the elimination of tucatinib were CYP2C8 and CYP3A4/5. CYP2C8 was shown to possess sole catalytic activity for the formation of M1, whereas CYP3A4/5 and aldehyde oxidase catalyzed the formation of the remaining metabolites. Subsequent investigation revealed that M1 was formed in a stereoselective manner. Examination of the enantiomeric ratio of M1 stereoisomers observed in humans relative to cynomolgus monkeys revealed comparable results, suggesting that the enantiomers that comprise M1 were not considered to be unique or disproportionately high in human. CONCLUSION: CYP2C8 and CYP3A4/5 are the primary drug-metabolizing enzymes involved in the in vitro metabolism of tucatinib, which provided the basis to describe human disposition of tucatinib and formation of the observed metabolites.


Asunto(s)
Antineoplásicos , Citocromo P-450 CYP3A , Antineoplásicos/metabolismo , Citocromo P-450 CYP2C8/metabolismo , Citocromo P-450 CYP3A/metabolismo , Humanos , Microsomas Hepáticos/metabolismo , Oxazoles , Inhibidores de Proteínas Quinasas/metabolismo , Piridinas , Quinazolinas , Estereoisomerismo
13.
Evol Hum Sci ; 4: e47, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-37588927

RESUMEN

Mate preferences and mating-related behaviours are hypothesised to change over the menstrual cycle to increase reproductive fitness. Recent large-scale studies suggest that previously reported hormone-linked behavioural changes are not robust. The proposal that women's preference for associating with male kin is down-regulated during the ovulatory (high-fertility) phase of the menstrual cycle to reduce inbreeding has not been tested in large samples. Consequently, we investigated the relationship between longitudinal changes in women's steroid hormone levels and their perceptions of faces experimentally manipulated to possess kinship cues (Study 1). Women viewed faces displaying kinship cues as more attractive and trustworthy, but this effect was not related to hormonal proxies of conception risk. Study 2 employed a daily diary approach and found no evidence that women spent less time with kin generally or with male kin specifically during the fertile phase of the menstrual cycle. Thus, neither study found evidence that inbreeding avoidance is up-regulated during the ovulatory phase of the menstrual cycle.

14.
Clin Pharmacol Ther ; 112(4): 754-769, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-34657311

RESUMEN

Antibody-drug conjugates (ADCs) represent a rapidly evolving area of drug development and hold significant promise. To date, nine ADCs have been approved by the US Food and Drug Administration (FDA). These conjugates combine the target specificity of monoclonal antibodies with the anticancer activity of small-molecule therapeutics (also referred to as payload). Due to the complex structure, three analytes, namely ADC conjugate, total antibody, and unconjugated payload, are typically quantified during drug development; however, the benefits of measuring all three analytes at later stages of clinical development are not clear. The cytotoxic payloads, upon release from the ADC, are considered to behave like small molecules. Given the relatively high potency and low systemic exposure of cytotoxic payloads, drug-drug interaction (DDI) considerations for ADCs might be different from traditional small molecule therapeutics. The International Consortium for Innovation and Quality in Pharmaceutical Development (IQ Consortium) convened an ADC working group to create an IQ ADC database that includes 26 ADCs with six unique payloads. The analysis of the ADC data in the IQ database, as well as nine approved ADCs, supports the strategy of pharmacokinetic characterization of all three analytes in early-phase development and progressively minimizing the number of analytes to be measured in the late-phase studies. The systemic concentrations of unconjugated payload are usually too low to serve as a DDI perpetrator; however, the potential for unconjugated payloads as a victim still exists. A data-driven and risk-based decision tree was developed to guide the assessment of a circulating payload as a victim of DDI.


Asunto(s)
Antineoplásicos , Inmunoconjugados , Anticuerpos Monoclonales , Antígenos , Antineoplásicos/química , Desarrollo de Medicamentos , Interacciones Farmacológicas , Humanos , Inmunoconjugados/farmacocinética
16.
Sci Rep ; 11(1): 16911, 2021 08 19.
Artículo en Inglés | MEDLINE | ID: mdl-34413430

RESUMEN

Although many researchers have argued that facial traits evolved as honest cues to women's current fertility (possibly via changes in facial femininity), evidence that women's facial attractiveness is significantly, positively related to probability of conception throughout menstrual cycle is mixed. These mixed results could reflect differences among studies in the methods used to assess facial attractiveness (i.e., forced choice versus rating-scale methods), differences in how fertility was assessed, differences in perceiver characteristics (e.g., their own attractiveness), and facial preferences possibly being moderated by the characteristics of the living environment. Consequently, the current study investigated the putative effect of cyclical changes in fertility on women's facial attractiveness and femininity (1) using forced choice and rating-scale method, (2) conducting both ovulation tests and repeated daily measures of estradiol assessing the conception probability, (3) based on a culturally diverse sample of perceivers, while (4) controlling for inter-individual variation. Although we found some limited evidence that women's faces became more attractive when conception probability increased, these effects differed depending on the methods used to assess both attractiveness and fertility. Moreover, where statistically significant effects were observed, the effect sizes were extremely small. Similarly, there was little robust evidence that perceivers' characteristics reliably predicted preferences for fertility cues. Collectively, these results suggest that mixed results in previous studies examining cyclical fluctuation in women's facial attractiveness are unlikely to reflect inter-cultural differences and are more likely to reflect differences in the methods used to assess facial attractiveness and fertility.


Asunto(s)
Comparación Transcultural , Señales (Psicología) , Cara/anatomía & histología , Fertilidad/fisiología , Percepción/fisiología , Adolescente , Adulto , Feminidad , Humanos , Juicio , Estimulación Luminosa , Análisis y Desempeño de Tareas , Adulto Joven
17.
Psychol Sci ; 32(8): 1183-1197, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34323639

RESUMEN

On average, men and women differ in brain structure and behavior, raising the possibility of a link between sex differences in brain and behavior. But women and men are also subject to different societal and cultural norms. We navigated this challenge by investigating variability of sex-differentiated brain structure within each sex. Using data from the Queensland Twin IMaging study (n = 1,040) and Human Connectome Project (n = 1,113), we obtained data-driven measures of individual differences along a male-female dimension for brain and behavior based on average sex differences in brain structure and behavior, respectively. We found a weak association between these brain and behavioral differences, driven by brain size. These brain and behavioral differences were moderately heritable. Our findings suggest that behavioral sex differences are, to some extent, related to sex differences in brain structure but that this is mainly driven by differences in brain size, and causality should be interpreted cautiously.


Asunto(s)
Conectoma , Caracteres Sexuales , Encéfalo/diagnóstico por imagen , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Gemelos
18.
Sci Rep ; 11(1): 10905, 2021 05 25.
Artículo en Inglés | MEDLINE | ID: mdl-34035393

RESUMEN

Individuals who are more attractive are thought to show a greater preference for facial sexual dimorphism, potentially because individuals who perceive themselves as more physically attractive believe they will be better able to attract and/or retain sexually dimorphic partners. Evidence for this link is mixed, however, and recent research suggests the association between self-rated attractiveness and preferences for facial sexual dimorphism may not generalise to non-Western cultures. Here, we assess whether self-rated attractiveness and self-rated health predict facial sexual dimorphism preferences in a large and culturally diverse sample of 6907 women and 2851 men from 41 countries. We also investigated whether ecological factors, such as country health/development and inequality, might moderate this association. Our analyses found that men and women who rated themselves as more physically attractive reported stronger preferences for exaggerated sex-typical characteristics in other-sex faces. This finding suggests that associations between self-rated attractiveness and preferences for sexually dimorphic facial characteristics generalise to a culturally diverse sample and exist independently of country-level factors. We also found that country health/development moderated the effect of men's self-rated attractiveness on femininity preferences, such that men from countries with high health/development showed a positive association between self-rated attractiveness and femininity preference, while men from countries with low health/development showed the opposite trend.


Asunto(s)
Belleza , Autoevaluación (Psicología) , Adulto , Conducta de Elección , Femenino , Feminidad , Humanos , Modelos Lineales , Masculino , Masculinidad , Caracteres Sexuales , Adulto Joven
19.
J Clin Pharmacol ; 61(4): 461-471, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-32989831

RESUMEN

Tucatinib is a potent tyrosine kinase inhibitor selective for human epidermal growth factor receptor 2 (HER2) approved by the US Food and Drug Administration for the treatment of HER2-positive metastatic breast cancer and in development for other HER2-positive solid tumors. Modest, reversible serum creatinine (SCr) elevations have been observed in tucatinib clinical trials. SCr is conveyed by the renal drug transporters organic cation transporter 2 (OCT2) and multidrug and toxin extrusion protein 1 (MATE1) and 2-K (MATE2-K) and can increase in the presence of inhibitors of these transporters. In vitro, tucatinib inhibited OCT2-, MATE1-, and MATE2-K-mediated transport of metformin, with IC50 values of 14.7, 0.340, and 0.135 µM, respectively. Tucatinib also inhibited OCT2- and MATE1-mediated transport of creatinine, with IC50 values of 0.107 and 0.0855 µM, respectively. A phase 1 study with metformin administered orally in the absence and presence of tucatinib was conducted in 18 healthy subjects. Renal function was assessed by measuring glomerular filtration rate (GFR; based on iohexol plasma clearance) and endogenous markers (SCr, cystatin C-based estimated glomerular filtration rate [eGFR]) with and without tucatinib. Metformin exposure increased (1.4-fold) and renal clearance decreased (29.99-17.64 L/h) with tucatinib, with no effect on metformin maximum concentration. Creatinine clearance transiently decreased 23% with tucatinib. GFR and eGFR, which are unaffected by OCT2 and/or MATE1/2-K transport, were unchanged with tucatinib. These data demonstrate that tucatinib inhibits OCT2- and MATE1/2-K-mediated tubular secretion of creatinine, which may manifest as mild SCr elevations that are not indicative of renal impairment.


Asunto(s)
Antineoplásicos/farmacología , Metformina/farmacocinética , Proteínas de Transporte de Catión Orgánico/antagonistas & inhibidores , Transportador 2 de Cátion Orgánico/antagonistas & inhibidores , Oxazoles/farmacología , Piridinas/farmacología , Quinazolinas/farmacología , Adolescente , Adulto , Anciano , Animales , Transporte Biológico/efectos de los fármacos , Creatinina/sangre , Estudios Cruzados , Perros , Femenino , Tasa de Filtración Glomerular , Células HEK293 , Voluntarios Sanos , Humanos , Concentración 50 Inhibidora , Células de Riñón Canino Madin Darby , Masculino , Persona de Mediana Edad , Receptor ErbB-2/antagonistas & inhibidores , Adulto Joven
20.
R Soc Open Sci ; 7(9): 190699, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33047005

RESUMEN

Evidence that affective factors (e.g. anxiety, depression, affect) are significantly related to individual differences in emotion recognition is mixed. Palermo et al. (Palermo et al. 2018 J. Exp. Psychol. Hum. Percept. Perform. 44, 503-517) reported that individuals who scored lower in anxiety performed significantly better on two measures of facial-expression recognition (emotion-matching and emotion-labelling tasks), but not a third measure (the multimodal emotion recognition test). By contrast, facial-expression recognition was not significantly correlated with measures of depression, positive or negative affect, empathy, or autistic-like traits. Because the range of affective factors considered in this study and its use of multiple expression-recognition tasks mean that it is a relatively comprehensive investigation of the role of affective factors in facial expression recognition, we carried out a direct replication. In common with Palermo et al. (Palermo et al. 2018 J. Exp. Psychol. Hum. Percept. Perform. 44, 503-517), scores on the DASS anxiety subscale negatively predicted performance on the emotion recognition tasks across multiple analyses, although these correlations were only consistently significant for performance on the emotion-labelling task. However, and by contrast with Palermo et al. (Palermo et al. 2018 J. Exp. Psychol. Hum. Percept. Perform. 44, 503-517), other affective factors (e.g. those related to empathy) often also significantly predicted emotion-recognition performance. Collectively, these results support the proposal that affective factors predict individual differences in emotion recognition, but that these correlations are not necessarily specific to measures of general anxiety, such as the DASS anxiety subscale.

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