Evaluating individualized treatment effect predictions: A model-based perspective on discrimination and calibration assessment.

In recent years, there has been a growing interest in the prediction of individualized treatment effects. While there is a rapidly growing literature on the development of such models, there is little literature on the evaluation of their performance. In this paper, we aim to facilitate the validation of prediction models for individualized treatment effects. The estimands of interest are defined based on the potential outcomes framework, which facilitates a comparison of existing and novel measures. In particular, we examine existing measures of discrimination for benefit (variations of the c-for-benefit), and propose model-based extensions to the treatment effect setting for discrimination and calibration metrics that have a strong basis in outcome risk prediction. The main focus is on randomized trial data with binary endpoints and on models that provide individualized treatment effect predictions and potential outcome predictions. We use simulated data to provide insight into the characteristics of the examined discrimination and calibration statistics under consideration, and further illustrate all methods in a trial of acute ischemic stroke treatment. The results show that the proposed model-based statistics had the best characteristics in terms of bias and accuracy. While resampling methods adjusted for the optimism of performance estimates in the development data, they had a high variance across replications that limited their accuracy. Therefore, individualized treatment effect models are best validated in independent data. To aid implementation, a software implementation of the proposed methods was made available in R.

Perceived Stigma Toward Cognitive Impairment Among People With Schizophrenia.

OBJECTIVE: Stigma toward schizophrenia spectrum disorders is pervasive and negatively influences service access and delivery. Cognitive impairment associated with schizophrenia (CIAS) is common, but its association with stigma is unknown. In this study, the authors examined whether individuals with CIAS receiving cognitive remediation treatment report experiencing CIAS-related stigma and sought to establish associations between CIAS-related stigma and recovery-relevant outcomes. METHODS: Data from 48 individuals with schizophrenia spectrum diagnoses were drawn from a larger study evaluating cognitive remediation. Participants completed measures of CIAS-related stigma, internalized mental illness stigma, self-perceived cognitive impairment, cognitive performance, and interviewer-rated quality of life. RESULTS: CIAS-related stigma was commonly reported and significantly positively associated with internalized stigma and self-perceived cognitive impairment. CIAS-related stigma was also significantly negatively associated with motivation to engage in goal-directed behavior and daily activities. CONCLUSIONS: CIAS-related stigma exists and warrants additional exploration with regard to implications for psychiatric service delivery.

Rapid species discrimination of similar insects using hyperspectral imaging and lightweight edge artificial intelligence.

Species discrimination of insects is an important aspect of ecology and biodiversity research. The traditional methods based on human visual experience and biochemical analysis cannot strike a balance between accuracy and timeliness. Morphological identification using computer vision and machine learning is expected to solve this problem, but image features have poor accuracy for very similar species and usually require complicated networks that are unfriendly to portable edge devices. In this work, we propose a fast and accurate species discrimination method of similar insects using hyperspectral features and lightweight machine learning algorithm. Feature regions selection, feature spectra selection and model quantification are used for the optimization of discriminating network. The experimental results of six similar butterfly species in the genus of Graphium show that, compared with morphological recognition with machine vision, our work achieves a higher accuracy of 92.36 ± 3.04% and a shorter inference time of 0.6 ms, with the tiny-size convolutional neural network deployed on a neural network chip. This study provides a rapid and high-accuracy species discrimination method for insects with high appearance similarity and paves the way for field discriminations using intelligent micro-spectrometer based on on-chip microstructure and artificial intelligence chip.

An integrated approach for discrimination of Magnoliae officinalis cortex before and after being processed by ginger juice combining LC/MS, GC/MS, intelligent sensors, and chemometrics.

INTRODUCTION: Magnoliae officinalis cortex (MOC) is an important traditional Chinese medicine (TCM), and both raw and stir-fried MOC were commonly used in clinic. OBJECTIVES: This study aimed to discriminate MOC and MOC stir-fried with ginger juice (MOCG) using an integrated approach combining liquid chromatography/mass spectrometry (LC/MS), gas chromatography/mass spectrometry (GC/MS), intelligent sensors, and chemometrics. METHODS: The sensory characters of the samples were digitalized using intelligent sensors, i.e., colorimeter, electronic nose, and electronic tongue. Meanwhile, the chemical profiles of the samples were analyzed using LC/MS and GC/MS methods. Chemometric models were constructed to discriminate samples of MOC and MOCG based on not only the sensory data but also the chemical data. RESULTS: The differential sensory characters (L* and b* from colorimeter, ANS from electronic tongue, W1S and W2S from electronic nose) and the differential chemical compounds (26 and 11 compounds from LC/MS and GC/MS, respectively) were discovered between MOC and MOCG. Furthermore, twelve differential compounds showed good relations with differential sensory characters. Finally, artificial neural network models were established to discriminate samples of MOC and MOCG, in which W1S, W2S, ANS, b*, and 10 differential compounds were among the top 10 important variables, respectively. CONCLUSION: Samples of MOC and MOCG can be discriminated not only by the digitalized data of color, taste, and scent detected by intelligent sensors but also by chemical information obtained from LC/MS and GC/MS using chemometrics. The variations in sensory characters and chemical compounds between MOC and MOCG partially resulted from the Maillard reaction products and the oxidation of some compounds in the stir-frying process.

Differential growth rate, water use efficiency and climate sensitivity between males and females of Ilex aquifolium in north-western Spain.

BACKGROUND AND AIMS: Dioecious plant species, i.e., those in which male and female functions are housed in different individuals, are particularly vulnerable to global environmental changes. For long-lived plant species, such as trees, long-term studies are imperative to understand how growth patterns and their sensitivity to climate variability differentially affect the sexes. METHODS: Here, we explore long-term intersexual differences in wood traits, namely radial growth rates, water use efficiency quantified as stable carbon isotope abundance of wood cellulose, and their climate sensitivity in Ilex aquifolium trees growing in a natural population in NW Spain. KEY RESULTS: We found that sex differences in secondary growth rates were variable over time, with males outperforming females in both radial growth rates and water use efficiency in recent decades. Summer water stress significantly reduced the growth of female trees in the following growing season, while the growth of male trees was primarily favoured by cloudy and rainy conditions the previous fall and winter combined with low cloud cover and warm conditions in summer. Sex-dependent lagged correlations between radial growth and water availability were found, with a strong association between tree growth and cumulative water availability in females at 30 months and in males at 10 months. CONCLUSIONS: Overall, our results point to greater vulnerability of female tress to increasing drought, which could lead to sex-ratio biases threatening population viability in the future.

Isobutyryl-carfentanyl has strong acute toxicity and analgesic effects with high addiction potential.

RATIONALE: Isobutyryl-carfentanyl is the most recently discovered fentanyl analogue with a chemical structure that is similar to that of carfentanyl. Its analogue, carfentanyl, is regarded as one of the most lethal drugs in the world, with a potency of 10,000 times that of morphine. Therefore, isobutyryl-carfentanyl may possess a comparably high potency and its harmful effects cannot be ignored. OBJECTIVES: This study was designed to assess the analgesic effect of isobutyryl-carfentanyl and the potential risks associated with its misuse. METHODS: In this study, we assessed the acute toxicity of isobutyryl-carfentanyl by up-and-down-procedure, the analgesic efficacy by hot-plate test, the abuse potential by conditioned place preference (CPP), drug self-administration, and drug discrimination tests, and compared it with fentanyl and carfentanyl. RESULTS: The estimated median lethal dose (LD50) of isobutyryl-carfentanyl administered were 175 mg/kg (intragastric administration, IG), 15.84 mg/kg (intraperitoneal injection, IP), 15.84 mg/kg (subcutaneous injection, SC), and 1.6 mg/kg (intravenous injection, IV), respectively. The 50% maximal analgesic effect (ED50) of isobutyryl-carfentanyl was determined to be 0.00319 mg/kg, with an analgesic potency 14 times that of fentanyl and 0.82 times that of carfentanyl. Isobutyryl-carfentanyl exhibited a significant positional preference at a minimum dose of 0.1 mg/kg, while fentanyl exhibited a significant positional preference at a minimum dose of 0.3 mg/kg. In the heroin (0.05 mg/kg/infusion) self-administration substitution experiment, isobutyryl-carfentanyl showed significant self-administration behaviour at doses of 0.0005-0.001 mg/kg/infusion, with the maximum number of infusions observed at a dose of 0.001 mg/kg. In the heroin (1 mg/kg) drug discrimination experiment, fentanyl (0.005-0.02 mg/kg), carfentanyl (0.0005-0.002 mg/kg), and isobutyryl-carfentanyl (0.001-0.005 mg/kg) were tested in the dose-effect curves. The results showed that all three drugs exhibit dose-dependent increase in the number of drug-associated nose pokes responses and reduction in the rate of nose pokes. The subjective effect potency of isobutyryl-carfentanyl was found to be 4.4 times that of fentanyl and 0.5 times that of carfentanyl. CONCLUSIONS: In summary, isobutyryl-carfentanyl has high acute toxicity and analgesic effect, with strong psychological dependence approximately 5 times that of fentanyl and 0.5 times that of carfentanyl, and has extremely high abuse potency.

Exploring health inequalities in Gypsy and Traveller communities in the UK.

Health inequalities between groups of people are often unjust and avoidable and are influenced by social determinants of health, the non-medical factors that influence health outcomes. Gypsy and Traveller communities experience significant health inequalities, including barriers to accessing healthcare services and suboptimal health outcomes compared with the general population. This article provides an overview of health inequalities in relation to Gypsy and Traveller communities and examines three social determinants of health - discrimination and racism, accommodation and access to healthcare - that influence these inequalities. The authors propose that accurate data collection as well as delivery of culturally competent health services and care may facilitate access to healthcare for Gypsy and Traveller communities and potentially reduce health inequalities.

Testing for Measurement Invariance (MI): Do the Structures of Microaggression, Discrimination, and Resilience Among Black Women Living with HIV Remain the Same Across Time?

Assessing measurement invariance and the interplay of discrimination, microaggressions, and resilience among Black women living with HIV (BWLWH) across time utilizing latent class and repeated measure analysis may provide novel insights. A total of 151 BWLWH in a southeastern U.S. city completed surveys focused on multiple forms of microaggressions and discrimination (race, gender, sexual orientation, or HIV-related) and resilience factors (social support, self-efficacy, post-traumatic growth) at baseline, 3 months, and 6 months. To capture the psychosocial domains of discrimination, microaggressions, and resilience, three latent factors were developed and measured across three time points. Latent class analysis was also conducted to identify and compare meaningful subgroups based on varying levels of discrimination, microaggressions, and resilience reported. Three latent classes were created. MI testing suggested that measurement invariance was partially met (established metric invariance and scalar invariance), and it is possible to compare factor means of discrimination, microaggressions, and resilience across time. Latent factor mean scores of microaggressions and discrimination decreased after 3 and 6 months and increased for resilience after 6 months and varied over time across the three latent classes identified. The subgroup with the lowest level of discrimination and microaggressions and the highest level of resilience reported at baseline, experienced increases in resilience after months 3 and 6. Clinical interventions, research, and policies aimed at promoting resilience and reducing structural and social barriers linked to racism, sexism, HIV stigma, and classism are needed to improve the health and well-being of BWLWH.

Validation of HAND OA US inflammatory and structural damage score (HOUSE) for thumb base joints: Systematic review on truth & discrimination.

OBJECTIVES: Recently, the HAND osteoarthritis (OA) ULTRASOUND (US) Examination (HOUSE) inflammatory and structural damage scores were developed by the OMERACT US working group. However, the thumb base was not or only partly included. This systematic review examines US scoring methods and scanning techniques assessing thumb base OA, alongside existing evidence on validity, reliability, and responsiveness. METHODS: A comprehensive search strategy in three different databases identified 30 eligible studies. RESULTS: In general, studies predominantly focused on US assessment of the carpometacarpal (CMC) 1 joint, with fewer investigating the scaphotrapeziotrapezoid (STT) joint. Most studies utilized a semiquantitative scale for scoring structural and inflammatory features, aligning with the HOUSE scoring system. Validity was supported by a limited number of studies, with one demonstrating a positive association between US structural damage and radiographic damage, and another showing a similar association with function. Associations between US inflammatory features and pain were observed, albeit with some variability. Reliability was from moderate to good for the CMC1 joint but limited for STT joint. Responsiveness varied across studies. The methodological quality of included studies varied, indicating areas for future research improvement. CONCLUSION: While promising, additional research is necessary to validate the HOUSE scoring system and improve its clinical utility for thumb base OA assessment. Future research should concentrate on optimal scanning positions and on the reliability and responsiveness of the HOUSE scoring system.

Oxytocin receptor control social information about fear expression of others in mice.

The social functions of oxytocin are diverse, and the specific aspects of information processing involved in emotional contagion remain unclear. We compared some fear-related behaviors among oxytocin receptor knockout mice and oxytocin-receptor-reduced mice with that of wild-type mice. In the observational fear assay, which reflects fear emotional contagion, mice that observed other individuals receiving electric shocks exhibited vicarious freezing. Mice with reduced or knockout oxytocin receptor expression showed reduced vicarious freezing. In the emotional discrimination assay, which reflects the ability to perceive others' emotional cues, we compared approach and scent-sniffing behaviors toward fear and emotionally neutral individuals. While wild-type mice were able to detect the fear emotion of others, mice with reduced or knocked-out oxytocin receptors showed reduced discrimination ability. In the fear behavior assays, which do not present social cues, we did not find these differences in oxytocin receptor expression in the brain. These findings indicate that oxytocin plays a role in emotional contagion by perceiving the emotions of others.

Discrimination against Roma women during childbirth? Unraveling the underlying effects of ethnic and socio-economic factors.

OBJECTIVE: This study aims to identify discrimination in maternity care experienced by Roma women in Hungary, due to ethnic and socio-economic factors. METHODS: We used data from the Cohort'18 Hungarian Birth Cohort Study, covering births in 2018-2019 (n = 7805). Face-to-face interviews were conducted by health visitors during pregnancy and six months postpartum. Differences in obstetric care were tested using Welch's ANOVA. Logistic regression models estimated the influence of Roma ethnicity on birth position, adjusting for socio-economic variables. Odds ratios with 95 % confidence intervals and adjusted predictions were calculated. RESULTS: Roma mothers had a lower rate of caesarean section due to fewer planned interventions (13.3% vs. 19.1% for non-Roma mothers). Roma women were less likely than non-Roma women to have a birth attended by a private obstetrician (15% vs. 52.6%) and less likely to have a family member present at the birth (40% vs. 65.5%). For vaginal births, 61.3% of Roma women had their birth position dictated by hospital staff, compared with 40.6% of non-Roma women. Ethnic background significantly influenced the choice of birth position, but these associations were attenuated after adjustment for socio-economic and territorial factors. Variables such as the presence of a private obstetrician, family support, and residence in Central Hungary reduced the likelihood of giving birth in a fixed position. CONCLUSION: Roma women face significant disadvantages in maternity care in Hungary. Ethnic background has a negative impact on the quality of care, but it is also significantly influenced by adverse socio-economic and regional factors.

Methamphetamine dependence in Australia-why is 'ice' (crystal meth) so addictive?

Australia has one of the highest rates in the world of the use of the crystalline form of methamphetamine, a highly addictive stimulant that is often associated with a chronic, relapsing dependency. Methamphetamine use is associated with both acquisitive and violent offending, which cause substantial personal and societal costs. Whilst the short-term euphoria and stimulation provide a positive reinforcement to methamphetamine use, the aversive states of withdrawing from methamphetamine and the associated craving, which may last up to five weeks into abstinence, underlie the negative reinforcement to continued methamphetamine use. Although many methamphetamine-dependent users experience high levels of psychological distress, it is likely that less than half engage with treatment or support services, and current intervention and treatment programmes have high discontinuation rates. Stigma and discrimination, even from paramedics and health clinicians, are prominent barriers to methamphetamine-dependent users accessing treatment in Australia.

Discriminatory, racist and xenophobic policies and practice against child refugees, asylum seekers and undocumented migrants in European health systems.

Child refugees, asylum seekers and undocumented migrants who have been forcibly displaced from their countries of origin have heightened health needs as a consequence of their migration experiences. Host countries have a duty to respond to these needs, yet across Europe we are seeing a rise in potentially harmful discriminative, hostile and restrictive migration policies and practices. Research exploring the role racism, xenophobia and discrimination in European health systems may play in child migrant health inequities is lacking. This Personal View seeks to highlight this knowledge gap and stimulate discourse on how discrimination in health information systems, data sharing practices, national health policy, healthcare entitlements, service access, quality of care, and healthcare workers attitudes and behaviours may infringe upon the rights of, and impact the health of child refugees, asylum-seekers and undocumented migrants. It calls for action to prevent and mitigate against potentially harmful policies and practices.

Discrimination of semantically similar verbal memory traces is affected in healthy aging.

Mnemonic discrimination of highly similar memory traces is affected in healthy aging via changes in hippocampal pattern separation-i.e., the ability of the hippocampus to orthogonalize highly similar neural inputs. The decline of this process leads to a loss of episodic specificity. Because previous studies have almost exclusively tested mnemonic discrimination of visuospatial stimuli (e.g., objects or scenes), less is known about age-related effects on the episodic specificity of semantically similar traces. To address this gap, we designed a task to assess mnemonic discrimination of verbal stimuli as a function of semantic similarity based on word embeddings. Forty young (Mage = 21.7 years) and 40 old adults (Mage = 69.8 years) first incidentally encoded adjective-noun phrases, then performed a surprise recognition test involving exactly repeated and highly similar lure phrases. We found that increasing semantic similarity negatively affected mnemonic discrimination in both age groups, and that compared to young adults, older adults showed worse discrimination at medium levels of semantic similarity. These results indicate that episodic specificity of semantically similar memory traces is affected in aging via less efficient mnemonic operations and strengthen the notion that mnemonic discrimination is a modality-independent process supporting memory specificity across representational domains.

Daily and Ethnic Discriminatory Experiences and Cognitive Control in Mexican-Origin Bilingual Language Brokers.

Few studies have considered bilingualism's impact on cognitive development within the sociolinguistic and cultural context of the immigrant communities where bilingualism is commonly practiced. In the United States, many Mexican-origin bilingual youth practice their bilingual skills by brokering (i.e., translating/interpreting between languages) for their immigrant parents who have low English proficiency. Meanwhile, these youth may also experience discrimination in their daily life. The present study focuses on Mexican-origin bilingual youth brokers (N=334) in order to examine how discriminatory experiences (i.e., daily and ethnic discrimination) and bilingual brokering experiences captured by profiles are related to cognitive control performance (i.e., attentional control and inhibition). We found no significant direct influence of either bilingual broker profiles or discriminatory experiences on cognitive control. However, the associations between discriminatory experiences and cognitive control performance depended upon brokering experiences. Specifically, greater discrimination was associated with lower cognitive control performance among moderate brokers (with moderate bilingual experiences), but the association was attenuated among efficacious brokers (with positive bilingual experiences). Findings highlight the need to consider the sociolinguistic heterogeneity of both discriminatory experiences and language use when investigating cognitive control performance in bilinguals.

Discrimination of healthy oral tissue from oral cancer based on the mean grey value determined by optical coherence tomography.

OBJECTIVE: This study aimed to identify a quantitative index for optical coherence tomography (OCT) images to discriminate tumours from surrounding tissues. SUBJECTS AND METHODS: Based on OCT measurements, mean grey values were determined from 432 locations on fifty-four human tissue specimens (eighteen cancerous, para-cancerous, and normal tissues each). These results were histologically evaluated by hematoxylin and eosin staining (H&E). RESULTS: The mean grey values of oral squamous cell carcinoma (OSCC) measurements were significantly different from those of the surrounding healthy tissue (p value < 0.0001), with the former being higher. The sensitivity and specificity of detecting tumourous tissue using this approach were 93 and 94%, respectively. CONCLUSIONS: OCT as a non-invasive, real-time imaging method, correlates well with H&E pathological images. It can effectively distinguish squamous cell carcinoma from normal tissues with high sensitivity and specificity and is thus expected to assist and guide tumour margin evaluation. CLINICAL RELEVANCE: This discovery highlights the potential of OCT in the objective evaluation of tumour margin during surgery.

Multi-discrimination exposure and biological aging: Results from the midlife in the United States study.

Discrimination is a social determinant of health and health disparities for which the biological mechanisms remain poorly understood. This study investigated the hypothesis that discrimination contributes to poor health outcomes by accelerating biological processes of aging. We analyzed survey and blood DNA methylation data from the Midlife in the United States (MIDUS) study (N = 1967). We used linear regression analysis to test associations of everyday, major, and workplace discrimination with biological aging measured by the DunedinPACE, PhenoAge, and GrimAge2 epigenetic clocks. MIDUS participants who reported more discrimination tended to exhibit a faster pace of aging and older biological age as compared to peers who reported less discrimination. Effect-sizes for associations tended to be larger for the DunedinPACE pace-of-aging clock (effect-size range r = 0.1-0.2) as compared with the PhenoAge and GrimAge2 biological-age clocks (effect-sizes r < 0.1) and for experiences of everyday and major discrimination as compared with workplace discrimination. Smoking status and body-mass index accounted for roughly half of observed association between discrimination and biological aging. Reports of discrimination were more strongly associated with accelerated biological aging among White as compared with Black participants, although Black participants reported more discrimination overall and tended to exhibit older biological age and faster biological aging. Findings support the hypothesis that experiences of interpersonal discrimination contribute to accelerated biological aging and suggest that structural and individual-level interventions to reduce discrimination and promote adaptive coping have potential to support healthy aging and build health equity.

Wage Disparities across Immigrant Generations: Education, Segregation, or Unequal Pay?

Immigrants and their native-born children often face considerable wage penalties relative to natives, but less is known about whether this inequality arises through differences in educational qualifications, segregation across occupations and establishments, or unequal pay for the same work. Using linked employer-employee data from Norway, the authors ask whether immigrant-native wage disparities 1) reflect differences in detailed educational qualifications, labor market segregation, or within-job pay differences; 2) differ by immigrant generation; and 3) vary across different segments of the labor market. They find that immigrant-native wage disparities primarily reflect sorting into lower-paying jobs, and that wage disadvantages are considerably reduced across immigrant generations. When doing the same work for the same employer, immigrant-background workers, especially children of immigrants, earn similar wages to natives. Sorting into jobs seems more meritocratic for university graduates, for professionals, and in the public sector, but within-job pay differences are strikingly similar across market segments.

Phospholipid supplementation inhibits male and female odor discrimination in mice.

Dietary phospholipids (PLs) are promising supplements that are commonly found as natural food ingredients and emulsifier additives. The present study aimed to evaluate the effect of major PLs found in food supplements on social behavior in mice. In this study, the effect of short-term high dietary PL content was studied in terms of social odor discrimination and social interactions with male and female intruders in male mice. We used odor discrimination and habituation tests to demonstrate that PL-fed male mice tend to lose preference toward female odor and fail to discriminate against socially significant scents. At the same time, test animals recognize non-social odors. We also found that PL affected the social behavior of the test males, who tend to behave indiscriminately toward male and female intruders during direct contact. Brain metabolomic profiling revealed no major changes in the intermediary metabolism or neurotransmitter biosynthesis. At the same time, intranasal PL application resembled the effects of dietary supplementation. These data suggest that certain PL might suppress pheromone perception in the olfactory system and affect the sense of socially important odor cues.

Hypothesis tests in ordinal predictive models with optimal accuracy.

In real-world applications involving multi-class ordinal discrimination, a common approach is to aggregate multiple predictive variables into a linear combination, aiming to develop a classifier with high prediction accuracy. Assessment of such multi-class classifiers often utilizes the hypervolume under ROC manifolds (HUM). When dealing with a substantial pool of potential predictors and achieving optimal HUM, it becomes imperative to conduct appropriate statistical inference. However, prevalent methodologies in existing literature are computationally expensive. We propose to use the jackknife empirical likelihood method to address this issue. The Wilks' theorem under moderate conditions is established and the power analysis under the Pitman alternative is provided. We also introduce a novel network-based rapid computation algorithm specifically designed for computing a general multi-sample $U$-statistic in our test procedure. To compare our approach against existing approaches, we conduct extensive simulations. Results demonstrate the superior performance of our method in terms of test size, power, and implementation time. Furthermore, we apply our method to analyze a real medical dataset and obtain some new findings.