The current national awakening and acknowledgment that White supremacy, patriarchy, and capitalism are responsible for the disproportionate effect of coronavirus disease 2019 and of police brutality ...on Black or Indigenous people and other people of color, people with disabilities, and sexual and gender minorities have ignited a call to action for public health leaders. As public health researchers, we must go beyond merely acknowledging the presence of structural racism and explicitly assess the effect of interconnected systems of oppression on health outcomes. Intersectionality is an analytic framework that can be used to describe how people marginalized by structural inequities interact with these oppressive systems but only if implemented in the way it was envisioned by Black and Black lesbian feminists.1,2
The aim of this study was to develop and evaluate a machine vision algorithm to assess the pain level in horses, using an automatic computational classifier based on the Horse Grimace Scale (HGS) and ...trained by machine learning method. The use of the Horse Grimace Scale is dependent on a human observer, who most of the time does not have availability to evaluate the animal for long periods and must also be well trained in order to apply the evaluation system correctly. In addition, even with adequate training, the presence of an unknown person near an animal in pain can result in behavioral changes, making the evaluation more complex. As a possible solution, the automatic video-imaging system will be able to monitor pain responses in horses more accurately and in real-time, and thus allow an earlier diagnosis and more efficient treatment for the affected animals. This study is based on assessment of facial expressions of 7 horses that underwent castration, collected through a video system positioned on the top of the feeder station, capturing images at 4 distinct timepoints daily for two days before and four days after surgical castration. A labeling process was applied to build a pain facial image database and machine learning methods were used to train the computational pain classifier. The machine vision algorithm was developed through the training of a Convolutional Neural Network (CNN) that resulted in an overall accuracy of 75.8% while classifying pain on three levels: not present, moderately present, and obviously present. While classifying between two categories (pain not present and pain present) the overall accuracy reached 88.3%. Although there are some improvements to be made in order to use the system in a daily routine, the model appears promising and capable of measuring pain on images of horses automatically through facial expressions, collected from video images.
Introduction
Transgender women (TW) experience an increased risk of human immunodeficiency virus (HIV) acquisition. This study identified patterns of HIV awareness and prevention strategies used by ...TW who were not living with HIV.
Methods
Data were drawn from a baseline survey of the LITE Study, a multi‐site cohort of TW in Eastern and Southern United States (March 2018–August 2020). We conducted a latent class analysis to identify classes of HIV awareness and prevention strategies among TW who reported past 12‐month sexual activity (N = 958) using 10 variables spanning HIV knowledge, receipt and use of HIV prevention strategies, and sexual practices. Due to differences across the cohort arms, classes were estimated separately for TW enrolled in site‐based versus online study arms. We identified demographic characteristics, gender‐affirming indicators and HIV vulnerabilities associated with class membership.
Results
Four parallel classes emerged: class 1 “limited strategies—less sexually active” (15% and 9%, site‐based and online, respectively), class 2 “limited strategies—insertive sex” (16%/36%), class 3 “limited strategies—receptive sex” (33%/37%) and class 4 “multiple strategies—insertive and receptive sex” (36%/18%). Across all classes, condomless sex, pre‐exposure prophylaxis (PrEP)/post‐exposure prophylaxis (PEP) prevention knowledge and awareness were high but reported PrEP/PEP use was low. Compared with class 1, membership in class 4 was associated with being a person of colour (site‐based OR = 2.15, 95% CI = 1.15–4.00, online OR = 4.54, 95% CI = 1.09–18.81) increased odds of self‐perceived medium‐to‐high HIV risk (site‐based OR = 4.12, 95% CI = 2.17–7.80, online OR = 11.73, 95% CI = 2.98–46.13), sexually transmitted infections (STI) diagnosis (site‐based OR = 6.69, 95% CI = 3.42–13.10, online OR = 8.46, 95% CI = 1.71–41.78), current sex work (site‐based OR = 6.49, 95% CI = 2.61–16.11, online OR = 10.25, 95% CI = 1.16–90.60) and 2–4 sexual partners in the last 3 months (site‐based OR = 2.61, 95% CI = 1.33–5.13). Class 3, compared with class 1, had increased odds of current sex work partners (site‐based OR = 3.09, 95% CI = 1.19–8.07) and of having 2–4 sexual partners in the last 3 months (site‐based OR = 3.69, 95% CI = 1.85–7.39).
Conclusions
TW have varied HIV awareness and prevention strategy utilization, with clear gaps in the uptake of prevention strategies. Algorithms derived from latent class membership may be used to tailor HIV prevention interventions for different subgroups and those reached through facility‐based or digital methods.
This paper addresses a method to solve a multi-period portfolio selection on the stock market. The portfolio problem seeks an investor to trade stocks with a finite budget and a given integer number ...of stocks to hold in a portfolio. The trade must be performed through a stockbroker that charges its respective transaction cost and has its minimum required trade amount. A mathematical model has been proposed to deal with the constrained problem. The objective function is to find the best risk-return rate; thus, Sharpe Ratio and Treynor Ratio are used as objective functions. The returns are the same for these ratios, but the risks are not Sharpe considering covariance and Treynor systematical risk. The returns are predicted using a Neural Net with Long-Short-Term Memory (LSTM). This neural net is compared with simple forecasting methods through Mean Absolute Percentage Error (MAPE). Computational experiments show the quality prediction performed by LSTM. The heteroskedastic risk is estimated by Generalized Autoregressive Conditional Heteroskedasticity (GARCH), adjusting the variance for every period; this risk measure is used in Sharpe Ratio. The experiment contemplates a weekly portfolio selection with 5 and 10 stocks in 122 weekly periods for each Chilean market ratio. The best portfolio is Sharpe Ratio with ten stocks, performing a 62.28% real return beating the market, represented by the Selective Stock Price Index (IPSA). Even the worst portfolio, Treynor Ratio, overcomes the IPSA cumulative yield with ten stocks.
Summary
Dental‐related sinusitis is a common condition in horses and often involves polymicrobial infection. Tooth extraction followed by sinus lavage and debridement are the recommended treatment. ...However, infection may persist or recur due to incomplete removal of infected material or, in rare cases, potential antimicrobial resistance. Although the use of antibiotics may be considered, evidence supporting their indication is scarce. This systematic literature review sets out to examine existing evidence supporting the use of antimicrobial therapy in dental‐related sinusitis in horses. Five articles (retrospective studies, prospective studies and case series) were included. Doxycycline, sulphadiazine‐trimethoprim, metronidazole and procaine benzylpenicillin combined with neomycin were the most commonly used antimicrobials. Oxytetracycline, gentamicin and cephazolin were used to a lesser extent. Two or more active pharmaceutical substances were often combined. In all studies, antimicrobial therapy was used as an ancillary strategy and criteria for drug selection were not reported. This review highlighted the scarcity of evidence supporting the use of antimicrobials in horses with dental‐related sinusitis. In cases with positive clinical outcomes, it was not possible to determine whether clinical improvement was due to antibiotics or other therapeutic interventions. Therefore, the actual contribution of antimicrobials could not be established.
Introduction
Transgender women in the United States experience high HIV incidence and suboptimal Pre‐exposure prophylaxis (PrEP) engagement. We sought to estimate PrEP initiation and discontinuation ...rates and characterize PrEP discontinuation experiences among a prospective cohort of transgender women.
Methods
Using a sequential, explanatory, mixed‐methods design, 1312 transgender women at risk for HIV acquisition were enrolled from March 2018 to August 2020 and followed through July 2022 (median follow‐up 24 months; interquartile range 15–36). Cox regression models assessed predictors of initiation and discontinuation. In‐depth interviews were conducted among 18 participants, including life history calendars to explore key events and experiences surrounding discontinuations. Qualitative and quantitative data were integrated to generate typologies of discontinuation, inform meta‐inferences and facilitate the interpretation of findings.
Results
21.8% (n = 286) of participants reported taking PrEP at one or more study visits while under observation. We observed 139 PrEP initiations over 2127 person‐years (6.5 initiations/100 person‐years, 95% CI: 5.5–7.7). Predictors of initiation included identifying as Black and PrEP indication. The rate of initiation among those who were PrEP‐indicated was 9.6 initiations/100 person‐years (132/1372 person‐years; 95% CI: 8.1–11.4). We observed 138 PrEP discontinuations over 368 person‐years (37.5 discontinuations/100 person‐years, 95% CI: 31.7–44.3). Predictors of discontinuation included high school education or less and initiating PrEP for the first time while under observation. Four discontinuation typologies emerged: (1) seroconversion following discontinuation; (2) ongoing HIV acquisition risk following discontinuation; (3) reassessment of HIV/STI prevention strategy following discontinuation; and (4) dynamic PrEP use coinciding with changes in HIV acquisition risk.
Conclusions
PrEP initiation rates were low and discontinuation rates were high. Complex motivations to stop using PrEP did not consistently correspond with HIV acquisition risk reduction. Evidence‐based interventions to increase PrEP persistence among transgender women with ongoing acquisition risk and provide HIV prevention support for those who discontinue PrEP are necessary to reduce HIV incidence in this population.
Defects in epigenetic regulation play a fundamental role in the development of cancer, and epigenetic regulators have recently emerged as promising therapeutic candidates. We therefore set out to ...systematically interrogate epigenetic cancer dependencies by screening an epigenome-focused deep-coverage design shRNA (DECODER) library across 58 cancer cell lines. This screen identified BRM/SMARCA2, a DNA-dependent ATPase of the mammalian SWI/SNF (mSWI/SNF) chromatin remodeling complex, as being essential for the growth of tumor cells that harbor loss of function mutations in BRG1/SMARCA4. Depletion of BRM in BRG1-deficient cancer cells leads to a cell cycle arrest, induction of senescence, and increased levels of global H3K9me3. We further demonstrate the selective dependency of BRG1 -mutant tumors on BRM in vivo. Genetic alterations of the mSWI/SNF chromatin remodeling complexes are the most frequent among chromatin regulators in cancers, with BRG1/SMARCA4 mutations occurring in ∼10–15% of lung adenocarcinomas. Our findings position BRM as an attractive therapeutic target for BRG1 mutated cancers. Because BRG1 and BRM function as mutually exclusive catalytic subunits of the mSWI/SNF complex, we propose that such synthetic lethality may be explained by paralog insufficiency, in which loss of one family member unveils critical dependence on paralogous subunits. This concept of “cancer-selective paralog dependency” may provide a more general strategy for targeting other tumor suppressor lesions/complexes with paralogous subunits.
Small cell lung cancer (SCLC) is an aggressive lung cancer subtype with extremely poor prognosis. No targetable genetic driver events have been identified, and the treatment landscape for this ...disease has remained nearly unchanged for over 30 years. Here, we have taken a CRISPR-based screening approach to identify genetic vulnerabilities in SCLC that may serve as potential therapeutic targets. We used a single-guide RNA (sgRNA) library targeting ~5000 genes deemed to encode "druggable" proteins to perform loss-of-function genetic screens in a panel of cell lines derived from autochthonous genetically engineered mouse models (GEMMs) of SCLC, lung adenocarcinoma (LUAD), and pancreatic ductal adenocarcinoma (PDAC). Cross-cancer analyses allowed us to identify SCLC-selective vulnerabilities. In particular, we observed enhanced sensitivity of SCLC cells toward disruption of the pyrimidine biosynthesis pathway. Pharmacological inhibition of dihydroorotate dehydrogenase (DHODH), a key enzyme in this pathway, reduced the viability of SCLC cells in vitro and strongly suppressed SCLC tumor growth in human patient-derived xenograft (PDX) models and in an autochthonous mouse model. These results indicate that DHODH inhibition may be an approach to treat SCLC.
Young adults who are transgender and/or nonbinary (TNB) experience discrimination, violence, and other social stressors as a result of cissexism, the system of power relations that marginalizes ...people whose genders diverge from sociocultural expectations for the sex they were assigned at birth. However, variation in TNB young adults’ exposure to social stressors across gender groups, particularly specific nonbinary gender groups (e.g., agender, genderqueer), has not been well characterized.
We analyzed data from an online cross-sectional survey of U.S. TNB young adults (N = 667; ages 18–30 years; 44% White, 24% multiracial, 14% Black, 10% Latinx, 7% Asian, 1% another race/ethnicity), assessing gender non-affirmation; cissexist discrimination, rejection, and victimization; general discrimination; sexual assault victimization; and psychological, physical, and sexual abuse in childhood/adolescence. We used generalized linear models to test for variation in stressors across six gender groups (transgender woman n = 259, transgender man n = 141, agender n = 36, gender fluid n = 30, genderqueer n = 51, nonbinary n = 150) and compare each group to the full sample. We performed similar analyses among nonbinary gender groups.
Exposure to stressors was considerable in all groups. Several stressors (e.g., past-year cissexist discrimination) did not vary significantly by gender group. Compared to the full sample, transgender women reported greater lifetime cissexist rejection and lifetime and past-year cissexist victimization. Compared to the full sample, transgender men and women reported greater lifetime cissexist discrimination and lower past-year gender non-affirmation. No stressors varied significantly across nonbinary gender groups.
Among TNB young adults, women, men, and nonbinary people experience distinct patterns of some (though not all) stigma-related stressors. Decisions about (dis)aggregating research participants by gender group, or providing gender-tailored services for TNB people, should account for patterning of pertinent stressors. Efforts to eliminate structural cissexism should address intersections with other systems of power relations, including sexism and binary normativity.
•Online survey of social stressors in 667 US transgender/nonbinary young adults.•Considerable exposure to overt cissexism, sexual assault, child abuse across gender.•Some stressors heightened within specific gender subgroups (e.g., women, nonbinary).•Gender differences in stressors varied by measurement period (lifetime; past year).•No significant differences in stressors across four nonbinary gender labels.
La presente investigación tiene como objetivo comprobar si características de la composición del directorio, tales como porcentaje de mujeres, independencia del directorio o tamaño y concentración de ...propiedad del Mercado Integrado Latinoamericano (MILA), contribuyen en el desempeño económico de las empresas. Como medidas de desempeño se utilizaron los indicadores ROA, ROE y Q de Tobin. Este estudio utiliza análisis de regresión con datos de panel mediante el Modelo Tobit, con paneles dinámicos y estáticos con efectos fijos a una muestra de 83 empresas. Se encontró evidencia de que el tamaño del directorio y la concentración de la propiedad influyen en el desempeño de las empresas.