Identifying parental and cell-division origins of aneuploidy in the human blastocyst.

Preimplantation genetic testing commonly employs simplistic copy-number analyses to screen for aneuploidy in blastocyst trophectoderm biopsies. Interpreting intermediate copy number alone as evidence of mosaicism has led to suboptimal estimation of its prevalence. Because mosaicism originates from mitotic nondisjunction, utilizing SNP microarray technology to identify the cell-division origins of aneuploidy might provide a more accurate estimation of its prevalence. The present study develops and validates a method of determining the cell-division origin of aneuploidy in the human blastocyst by using both genotyping and copy-number data in parallel. The concordance of predicted origins with expected results was demonstrated in a series of truth models (99%-100%). This included determination of X chromosome origins from a subset of normal male embryos, determination of the origins of translocation chromosome-related imbalances via embryos from couples with structural rearrangements, and prediction of either mitotic or meiotic origins via multiple rebiopsies of embryos with aneuploidy. In a cohort of blastocysts with parental DNA (n = 2,277), 71% were euploid, 27% were meiotic aneuploid, and 2% were mitotic aneuploid, indicating a low frequency of bona fide mosaicism in the human blastocyst (mean maternal age: 34.4). Chromosome-specific trisomies in the blastocyst were also consistent with observations previously established in products of conception. The ability to accurately identify mitotic-origin aneuploidy in the blastocyst could benefit and better inform individuals whose IVF cycle results in all aneuploid embryos. Clinical trials with this methodology might also help provide a definitive answer regarding the reproductive potential of bona fide mosaic embryos.

The independent and combined effects of aerobic exercise intensity and dose differentially increase post-exercise cerebral shear stress and blood flow.

This research examined the impact of aerobic exercise intensity and dose on acute post-exercise cerebral shear stress and blood flow. Fourteen young adults (27 ± 5 years of age, eight females) completed a maximal oxygen uptake ( V ̇ O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_2}\max }}$ ) treadmill test followed by three randomized study visits: treadmill exercise at 30% of V ̇ O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_2}\max }}$ for 30 min, 70% of V ̇ O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_2}\max }}$ for 30 min and 70% of V ̇ O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_2}\max }}$ for a duration that resulted in caloric expenditure equal to that in the 30% V ̇ O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_2}\max }}$ visit (EqEE). A venous blood draw and internal carotid artery (ICA) ultrasound were collected before and immediately following exercise. ICA diameter and blood velocity were determined using automated edge detection software, and blood flow was calculated. Using measures of blood viscosity, shear stress was calculated. Aerobic exercise increased ICA shear stress (time: P = 0.005, condition: P = 0.012) and the increase was greater following exercise at 70% V ̇ O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_2}\max }}$ (∆4.1 ± 3.5 dyn/cm2) compared with 30% V ̇ O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_2}\max }}$ (∆1.1 ± 1.9 dyn/cm2; P = 0.041). ICA blood flow remained elevated following exercise (time: P = 0.002, condition: P = 0.010) with greater increases after 70% V ̇ O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_2}\max }}$ (Δ268 ± 150 mL/min) compared with 30% V ̇ O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_2}\max }}$ (∆125 ± 149 mL/min; P = 0.041) or 70% V ̇ O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_2}\max }}$ EqEE (∆127 ± 177 mL/min; P = 0.004). Therefore, aerobic exercise resulted in both intensity- and dose-dependent effects on acute post-exercise ICA blood flow whereby vigorous intensity exercise provoked a larger increase in ICA blood flow compared to light intensity exercise when performed at a higher dose.

A longitudinal study of breastfeeding relationships at home during the COVID-19 pandemic: A grounded theory method.

AIMS: To describe the process of breastfeeding relationships among stay-at-home mother and infant dyads at 1, 3, 5 and 6 months. DESIGN: A longitudinal qualitative online survey design was used. METHODS: Data were obtained at 1, 3, 5 and 6 months from 26 breastfeeding mothers who stayed home with their infants and directly breastfed at least once a day for the first 6 months between June 2022 and August 2023. Mothers' written responses to 3 open-ended questions were analysed to assess breastfeeding experiences at home, thoughts/comments while directly breastfeeding and breastfeeding concerns/problems and strategies they used. Based on grounded theory, inductive content analysis was used to analyse the data. Trustworthiness of results was established by coding to consensus, formal peer debriefing and maintaining an audit trail. RESULTS: 'Breastfeeding Relationships at Home,' the core construct, was identified and organized the process of breastfeeding relationships into 5 domains: (1) mothers' emotional well-being while breastfeeding, (2) infant-led feeding, (3) alternatives to breastfeeding, (4) evaluation of breastfeeding and (5) changes in breastfeeding as infants grow older. CONCLUSION: Breastfeeding is not simply about feeding breast milk but also involves nurturing and developing a relationship between mother and infant. Across the domains, mutual responsiveness, a central element of the breastfeeding relationship was clear. Mothers who were committed to breastfeeding with embedded infant suckling reached emotional well-being in return for their engagement which has potential to reduce maternal stress and prevent postpartum depression. IMPACT: Findings from the current study add to nurses' knowledge about the relationship building process between stay-at-home mothers and their infants in the first 6 months of breastfeeding during the COVID-19 pandemic. Nurses must remain sensitive to aid the development of breastfeeding relationships in the home environment to maximize mutual responsiveness. PATIENT OR PUBLIC CONTRIBUTION: No patients or public involved.

Move and Thrive: Development of an Adolescent Friendly and Inclusive Online Fitness Resource.

While physical activity (PA) is a strong protective factor for adolescents, many youth experience discrimination and intimidation in traditional fitness spaces. This is especially true for youth of color, youth in larger bodies, and transgender youth. This manuscript describes the development of Move and Thrive, an online resource for PA promotion designed specifically for adolescents prioritizing inclusivity and diversity. Working with Community and Youth Advisory Boards, we developed guiding principles of Move and Thrive: to create resources that are 1) youth and community driven; 2) inclusive of diverse representation; 3) body and weight neutral; 4) trauma informed; and 5) accessible. We developed a guide for PA instructors to use trauma informed approaches; avoid mention of weight talk or physical appearance; use gender inclusive language; and offer multiple options to improve accessibility. Specific care was taken to hire instructors diverse in body size, race, ethnicity, and gender identity. The first iteration of Move and Thrive was launched in March 2021, and the current resource contains 72 PA videos. Over the course of 12 months, the site had more than the site had over 9,000 views in over 40 countries, including six continents. Users have reported high levels of satisfaction with Move and Thrive, and physicians have responded enthusiastically to sharing Move and Thrive as a free resource for adolescents. University of Minnesota Move and Thrive Project is currently available on an ad-free YouTube Channel. We believe that Move and Thrive has the potential to reach populations historically excluded from PA resources.

Age at natural menopause impacts cerebrovascular reactivity and brain structure.

Menopause is associated with adverse changes in vascular health coinciding with an increased risk of stroke and vascular cognitive impairment. However, there is significant variation in the age at menopause. The present study examined how the age at natural menopause impacts cerebrovascular reactivity and structural biomarkers of brain aging. Thirty-five healthy postmenopausal women were classified as early-onset menopause (Early; n = 19, age at menopause: 47 ± 2 yr) or later-onset menopause (Late; n = 16, age at menopause: 55 ± 2 yr). Middle cerebral artery blood velocity (MCAv), mean arterial blood pressure (MAP), and end-tidal carbon dioxide (ETCO2) were recorded during a stepped hypercapnia protocol. Reactivity was calculated as the slope of the relationship between ETCO2 and each variable of interest. Brain volumes and white matter hyperintensities (WMHs) were obtained with 3T MRI. Resting MAP was greater in the Early group (99 ± 9 mmHg) compared with the Late group (90 ± 12 mmHg; P = 0.02). Cerebrovascular reactivity, assessed using MCAv, was blunted in the Early group (1.87 ± 0.92 cm/s/mmHg) compared with the Late group (2.37 ± 0.75 cm/s/mmHg; P = 0.02). Total brain volume did not differ between groups (Early: 1.08 ± 0.07 L vs. Late: 1.07 ± 0.06 L; P = 0.66), but the Early group demonstrated greater WMH fraction compared with the Late group (Early: 0.36 ± 0.14% vs. Late: 0.25 ± 0.14%; P = 0.02). These results suggest that age at natural menopause impacts cerebrovascular function and WMH burden in healthy postmenopausal women.

Association between serum prostacyclin and cerebrovascular reactivity in healthy young and older adults.

NEW FINDINGS: What is the central question of this study? What is the relationship between prostacyclin and cerebrovascular reactivity to hypercapnia before and after administration of a cyclooxygenase inhibitor, indomethacin, in healthy young and older adults? What is the main finding and importance? Serum prostacyclin was not related to cerebrovascular reactivity to hypercapnia before or after administration of indomethacin. However, in older adults, serum prostacyclin was related to the magnitude of change in cerebrovascular reactivity from before to after indomethacin administration. This suggests that older adults with higher serum prostacyclin may rely more on cyclooxygenase products to mediate cerebrovascular reactivity. ABSTRACT: Platelet activation may contribute to age-related cerebrovascular dysfunction by interacting with the endothelial cells that regulate the response to vasodilatory stimuli. This study evaluated the relationship between a platelet inhibitor, prostacyclin, and cerebrovascular reactivity (CVR) in healthy young (n = 35; 25 ± 4 years; 17 women, 18 men) and older (n = 12; 62 ± 2 years; 8 women, 4 men) adults, who were not daily aspirin users, before and after cyclooxygenase inhibition. Prostacyclin was determined by levels of 6-keto-prostaglandin F1α (6-keto PGF1α) in the blood. CVR was assessed by measuring the middle cerebral artery blood velocity response to hypercapnia using transcranial Doppler ultrasound before (CON) and 90 min after cyclooxygenase inhibition with indomethacin (INDO). In young adults, there were no associations between prostacyclin and middle cerebral artery CVR during CON (r = -0.14, P = 0.415) or INDO (r = 0.27, P = 0.118). In older adults, associations between prostacyclin and middle cerebral artery CVR during CON (r = 0.53, P = 0.075) or INDO (r = -0.45, P = 0.136) did not reach the threshold for significance. We also evaluated the relationship between prostacyclin and the change in CVR between conditions (ΔCVR). We found no association between ΔCVR and prostacyclin in young adults (r = 0.27, P = 0.110); however, in older adults, those with higher baseline prostacyclin levels demonstrated significantly greater ΔCVR (r = -0.74, P = 0.005). In conclusion, older adults with higher serum prostacyclin, a platelet inhibitor, may rely more on cyclooxygenase products for cerebrovascular reactivity to hypercapnia.

Photopolymerizable Biomaterials and Light-Based 3D Printing Strategies for Biomedical Applications.

Since the advent of additive manufacturing, known commonly as 3D printing, this technology has revolutionized the biofabrication landscape and driven numerous pivotal advancements in tissue engineering and regenerative medicine. Many 3D printing methods were developed in short course after Charles Hull first introduced the power of stereolithography to the world. However, materials development was not met with the same enthusiasm and remained the bottleneck in the field for some time. Only in the past decade has there been deliberate development to expand the materials toolbox for 3D printing applications to meet the true potential of 3D printing technologies. Herein, we review the development of biomaterials suited for light-based 3D printing modalities with an emphasis on bioprinting applications. We discuss the chemical mechanisms that govern photopolymerization and highlight the application of natural, synthetic, and composite biomaterials as 3D printed hydrogels. Because the quality of a 3D printed construct is highly dependent on both the material properties and processing technique, we included a final section on the theoretical and practical aspects behind light-based 3D printing as well as ways to employ that knowledge to troubleshoot and standardize the optimization of printing parameters.

3D bioprinting of complex tissues in vitro: state-of-the-art and future perspectives.

The pharmacology and toxicology of a broad variety of therapies and chemicals have significantly improved with the aid of the increasing in vitro models of complex human tissues. Offering versatile and precise control over the cell population, extracellular matrix (ECM) deposition, dynamic microenvironment, and sophisticated microarchitecture, which is desired for the in vitro modeling of complex tissues, 3D bio-printing is a rapidly growing technology to be employed in the field. In this review, we will discuss the recent advancement of printing techniques and bio-ink sources, which have been spurred on by the increasing demand for modeling tactics and have facilitated the development of the refined tissue models as well as the modeling strategies, followed by a state-of-the-art update on the specialized work on cancer, heart, muscle and liver. In the end, the toxicological modeling strategies, substantial challenges, and future perspectives for 3D printed tissue models were explored.

Peer sexual harassment, affect, and substance use: Daily level associations among adolescents.

INTRODUCTION: Peer sexual harassment is associated with adolescent substance use at the global level; however, it is unknown whether substance use occurs proximal in time to the sexual harassment experience. This study used daily reports to examine the proximal relations between sexual harassment victimization and affect and substance use. Based on theories of self-medication, we hypothesized that negative affect and substance use (cigarettes, electronic cigarettes, alcohol, and marijuana) would be higher than typical on days when sexual harassment occurred relative to nonvictimization days. METHOD: A community sample of 13-16-year-old adolescents (N = 204, 55.4% female) from a metropolitan area in the northeastern United States completed 56 days of online reports assessing experiences with peer sexual harassment, substance use (cigarettes, electronic cigarettes, alcohol, and marijuana), and positive and negative affect. RESULTS: Multilevel modeling revealed that experiencing sexual harassment on a given day was associated with higher than typical negative affect on that day, relative to nonvictimization days. The likelihood of cigarette and alcohol use (but not electronic cigarettes, marijuana, or positive affect) was greater on days when sexual harassment occurred. CONCLUSION: Sexual harassment victimization is proximally associated with negative affect and alcohol and cigarette use, suggesting that adolescents may be using substances to cope with sexual harassment victimization. The co-occurrence of sexual harassment with negative affect and substance use points to the need for prevention efforts that conjointly address sexual harassment victimization, coping, and substance use.

Impact of age and cyclooxygenase inhibition on the hemodynamic response to acute cognitive challenges.

Structural and functional changes in the cerebral vasculature occur with advancing age, which may lead to impaired neurovascular coupling (NVC) and cognitive decline. Cyclooxygenase (COX) inhibition abolishes age-related differences in cerebrovascular reactivity, but it is unclear if COX inhibition impacts NVC. The purpose of this study was to examine the influence of aging on NVC before and after COX inhibition. Twenty-three young (age = 25 ± 4 yr) and 21 older (age = 64 ± 5 yr) adults completed two levels of difficulty of the Stroop and n-back tests before and after COX inhibition. Middle cerebral artery blood velocity (MCAv) was measured using transcranial Doppler ultrasound and mean arterial blood pressure (MAP) was measured using a finger cuff. Hemodynamic variables were measured at rest and in response to cognitive challenges. During the Stroop test, older adults demonstrated a greater increase in MCAv (young: 2.2 ± 6.8% vs. older: 5.9 ± 5.8%; P = 0.030) and MAP (young: 2.0 ± 4.9% vs. older: 4.8 ± 4.9%; P = 0.036) compared with young adults. There were no age-related differences during the n-back test. COX inhibition reduced MCAv by 30% in young and 26% in older adults (P < 0.001 for both). During COX inhibition, there were no age-related differences in the percent change in MCAv or MAP in response to the cognitive tests. Our results show that older adults require greater increases in MCAv and MAP during a test of executive function compared with young adults and that any age-related differences in NVC were abolished during COX inhibition. Collectively, this suggests that aging is associated with greater NVC necessary to accomplish a cognitive task.

Exercise, Arterial Stiffness, and Cerebral Vascular Function: Potential Impact on Brain Health.

Exercise is associated with higher cognitive function and is a promising intervention to reduce the risk of dementia. With advancing age, there are changes in the vasculature that have important clinical implications for brain health and cognition. Primary aging and vascular risk factors are associated with increases in arterial stiffness and pulse pressure, and reductions in peripheral vascular function. OBJECTIVE: The purpose is to discuss the epidemiological, observational, and mechanistic evidence regarding the link between age-related changes in vascular health and brain health. METHODS: We performed a literature review and integrated with our published data. RESULTS: Epidemiological evidence suggests a link between age-related increases in arterial stiffness and lower cognitive function, which may be mediated by cerebral vascular function, including cerebral vasoreactivity and cerebral pulsatility. Age-associated impairments in central arterial stiffness and peripheral vascular function have been attenuated or reversed through lifestyle behaviors such as exercise. Greater volumes of habitual exercise and higher cardiorespiratory fitness are associated with beneficial effects on both peripheral vascular health and cognition. Yet, the extent to which exercise directly influences cerebral vascular function and brain health, as well as the associated mechanisms remains unclear. CONCLUSION: Although there is evidence that exercise positively impacts cerebral vascular function, more research is necessary in humans to optimize experimental protocols and address methodological limitations and physiological considerations. Understanding the impact of exercise on cerebral vascular function is important for understanding the association between exercise and brain health and may inform future intervention studies that seek to improve cognition.

Physician Assistant's Knowledge and Confidence Regarding Prescribing Preexposure Prophylaxis for HIV Prevention.

Physician assistants (PAs) have an important role to play in increasing preexposure prophylaxis (PrEP) prescriptions. We surveyed PAs regarding knowledge of Centers for Disease Control and Prevention guidelines for PrEP and confidence regarding PrEP. Physician assistants in primary care reported more accurate knowledge and higher confidence. However, knowledge and confidence gaps were present among all PAs, regardless of specialty.

Consensus Guidelines for Perioperative Care in Neonatal Intestinal Surgery: Enhanced Recovery After Surgery (ERAS®) Society Recommendations.

BACKGROUND: Enhanced Recovery After Surgery (ERAS®) Society guidelines integrate evidence-based practices into multimodal care pathways that have improved outcomes in multiple adult surgical specialties. There are currently no pediatric ERAS® Society guidelines. We created an ERAS® guideline designed to enhance quality of care in neonatal intestinal resection surgery. METHODS: A multidisciplinary guideline generation group defined the scope, population, and guideline topics. Systematic reviews were supplemented by targeted searching and expert identification to identify 3514 publications that were screened to develop and support recommendations. Final recommendations were determined through consensus and were assessed for evidence quality and recommendation strength. Parental input was attained throughout the process. RESULTS: Final recommendations ranged from communication strategies to antibiotic use. Topics with poor-quality and conflicting evidence were eliminated. Several recommendations were combined. The quality of supporting evidence was variable. Seventeen final recommendations are included in the proposed guideline. DISCUSSION: We have developed a comprehensive, evidence-based ERAS guideline for neonates undergoing intestinal resection surgery. This guideline, and its creation process, provides a foundation for future ERAS guideline development and can ultimately lead to improved perioperative care across a variety of pediatric surgical specialties.

Augmented cerebral blood velocity in response to isometric handgrip exercise in women with a history of preeclampsia.

Preeclampsia (PE) is a hypertensive disorder of pregnancy described as a condition of excessive sympathoexcitation. PE places a woman at increased risk for lifelong hypertension and cognitive impairment. Cerebral blood velocity is blunted in response to a vasoactive stimulus in women with a history of PE. This study investigated how a sympathoexcitatory stimulus affects cerebral blood velocity in women with a history of PE. Middle cerebral artery blood velocity (MCAv) and beat-to-beat mean arterial blood pressure (MAP) were measured in postmenopausal women with a history of PE (n = 21; age = 59 ± 5 yr) and a history of a normotensive pregnancy (NP; n = 27; age = 58 ± 4 yr), at baseline, during isometric handgrip to fatigue (IHG) followed by postexercise ischemia (PEI), and a recovery period (REC). Baseline MAP and MAP responses to IHG and PEI did not differ between groups. MCAv at baseline and throughout the stimulus was lower in PE women compared with NP women (P < 0.05 for all). MCAv increased during IHG in both groups (P < 0.05). This increase in MCAv was greater in PE compared with NP women during IHG and REC (IHG: PE 13 ± 2% vs. NP 9 ± 2%; REC: PE 3 ± 2% vs. NP -2 ± 2%; P < 0.05 for both). Thus, a history of PE is associated with low baseline cerebral blood velocity but an augmented response to a sympathoexcitatory stimulus. These changes in cerebral blood flow regulation may lead to an increased risk for cognitive impairment in women with a history of PE.

Pregnancy History, Hypertension, and Cognitive Impairment in Postmenopausal Women.

PURPOSE OF REVIEW: Risks for developing cardiovascular disease and cognitive decline increase with age. In women, these risks may be influenced by pregnancy history. This review provides an integrated evaluation of associations of pregnancy history with hypertension, brain atrophy, and cognitive decline in postmenopausal women. RECENT FINDINGS: Atrophy in the occipital lobes of the brain was evident in women who had current hypertension and a history of preeclampsia. Deficits in visual memory in women with a history of preeclampsia are consistent with these brain structural changes. The blood velocity response to chemical and sympathoexcitatory stimuli were altered in women with a history of preeclampsia linking impairments in cerebrovascular regulation to the structural and functional changes in the brain. Having a history of preeclampsia should require close monitoring of blood pressure and initiation of anti-hypertensive treatment in perimenopausal women. Mechanisms by which preeclampsia affects cerebrovascular structure and function require additional study.

The association between caffeinated alcoholic beverages and the perpetration of intimate partner violence.

Background: Problematic alcohol use is a recognized risk factor for intimate partner violence (IPV) perpetration.Objective: The use of caffeinated alcoholic beverages (CAB) appears to be associated with high-risk drinking behavior but the relationship between CAB use and IPV has yet to be explored.Methods: Sixty male and 40 female married or dating participants responded to an online survey including measures of past-year alcohol use and partner violence.Results: Logistic regression analyses revealed that CAB users were significantly more likely to perpetrate physical assault and partner injury after controlling for age, sex, ethnicity, income, and heavy alcohol use. The relationship between CAB use and perpetration of sexual coercion was better accounted for by heavy alcohol use.Conclusion: Results from the current study suggest that there exists an independent link between CAB use and partner violence perpetration.

New Opioid Analgesic Approvals and Outpatient Utilization of Opioid Analgesics in the United States, 1997 through 2015.

BACKGROUND: The opioid epidemic, driven in part by increased prescribing, is a public health emergency. This study examines dispensed prescription patterns and approvals of new opioid analgesic products to investigate whether the introduction of these new drugs increases prescribing. METHODS: Prescribing patterns based on dispensed prescription claims from the U.S. retail setting were assessed with new brand and generic opioid analgesic products approved in the United States from 1997 through 2015. RESULTS: From 1997 through 2015, the U.S. Food and Drug Administration (Silver Spring, Maryland) approved 263 opioid analgesic products, including 33 brand products. Dispensed prescriptions initially increased 80% from 145 million prescriptions in 1997 to a peak of 260 million prescriptions in 2012 before decreasing by 12% to 228 million prescriptions in 2015. Morphine milligram equivalents dispensed per prescription increased from 486 in 1997 to a peak of 950 in 2010, before decreasing to 905 in 2015. In 2015, generic products accounted for 96% (218/228 million prescriptions) of all opioid analgesic prescriptions dispensed. The remaining prescriptions were dispensed for brand products, of which nearly half were dispensed for one brand product (OxyContin, Purdue, USA). CONCLUSIONS: There has been a dramatic increase in prescriptions dispensed for opioid analgesics since 1997 and an increasing number of opioid analgesic approvals; however, the number of prescriptions dispensed has declined since 2012 despite an increasing number of approvals. Examination of dispensed prescriptions shows a shifting and complex market where multiple factors likely influence prescribing; the approval of new products alone may not be sufficient to be a primary driver of increased prescribing. VISUAL ABSTRACT: An online visual overview is available for this article at http://links.lww.com/ALN/B705.

Intoxication-Related Alcohol Mixed with Energy Drink Expectancies Scale: Initial Development and Validation.

BACKGROUND: Young adult use of alcohol mixed with energy drinks (AmEDs) has been linked with elevated risks of a constellation of problem behaviors. These risks may be conditioned by expectancies regarding the effects of caffeine in conjunction with alcohol consumption. The aim of this study was to describe the construction and psychometric evaluation of the Intoxication-Related AmED Expectancies Scale (AmED_EXPI), 15 self-report items measuring beliefs about how the experience of AmED intoxication differs from the experience of noncaffeinated alcohol (NCA) intoxication. METHODS: Scale development and testing were conducted using data from a U.S. national sample of 3,105 adolescents and emerging adults aged 13 to 25. Exploratory and confirmatory factor analyses were conducted to evaluate the factor structure and establish factor invariance across gender, age, and prior experience with AmED use. Cross-sectional and longitudinal analyses examining correlates of AmED use were used to assess construct and predictive validity. RESULTS: In confirmatory factor analyses, fit indices for the hypothesized 4-factor structure (i.e., Intoxication Management [IM], Alertness [AL], Sociability [SO], and Jitters [JT]) revealed a moderately good fit to the data. Together, these factors accounted for 75.3% of total variance. The factor structure was stable across male/female, teen/young adult, and AmED experience/no experience subgroups. The resultant unit-weighted subscales showed strong internal consistency and satisfactory convergent validity. Baseline scores on the IM, SO, and JT subscales predicted changes in AmED use over a subsequent 3-month period. CONCLUSIONS: The AmED_EXPI appears to be a reliable and valid tool for measuring expectancies about the effects of caffeine during alcohol intoxication.

Value Assessment in the Regulatory Context.

Value assessments are made on new drugs before they even enter the market. Regulators at the Center for Drug Evaluation and Research (CDER) at the US Food and Drug Administration make a clinical benefit-risk assessment to determine whether to approve a new drug. Benefits of a drug are typically quantified directly, as an assessment of efficacy. CDER defines risk as the intersection of the severity of possible harm and the probability of that harm. For a novel drug to be approved, its benefits and risks must be well understood, and the trade-off between the two must be acceptable. To assist with these benefit-risk value assessments, CDER has two ongoing initiatives: the Patient-Focused Drug Development Initiative that aims to substantially increase the role of patient voice in the regulatory process, and a transparency initiative that focuses on creating a structured framework for benefit-risk assessment.

Alcohol Mixed with Energy Drink Use as an Event-Level Predictor of Physical and Verbal Aggression in Bar Conflicts.

BACKGROUND: Young adult use of alcohol mixed with caffeinated energy drinks (AmEDs) has been globally linked with increased odds of interpersonal aggression, compared with the use of alcohol alone. However, no prior research has linked these behaviors at the event level in bar drinking situations. The present study assessed whether AmED use is associated with the perpetration of verbal and physical aggression in bar conflicts at the event level. METHODS: In Fall 2014, a community sample of 175 young adult AmED users (55% female) completed a web survey describing a recent conflict experienced while drinking in a bar. Use of both AmED and non-AmED alcoholic drinks in the incident were assessed, allowing calculation of our main predictor variable, the proportion of AmEDs consumed (AmED/total drinks consumed). To measure perpetration of aggression, participants reported on the occurrence of 6 verbal and 6 physical acts during the bar conflict incident. RESULTS: Linear regression analyses showed that the proportion of AmEDs consumed predicted scores for perpetration of both verbal aggression (ß = 0.16, p < 0.05) and physical aggression (ß = 0.19, p < 0.01) after controlling for gender, age, sensation-seeking and aggressive personality traits, aggressive alcohol expectancies, aggressogenic physical and social bar environments, and total number of drinks. CONCLUSIONS: Results of this study suggest that in alcohol-related bar conflicts, higher levels of young adult AmED use are associated with higher levels of aggression perpetration than alcohol use alone and that the elevated risk is not attributable to individual differences between AmED users and nonusers or to contextual differences in bar drinking settings. While future research is needed to identify motivations, dosages, and sequencing issues associated with AmED use, these beverages should be considered a potential risk factor in the escalation of aggressive bar conflicts.