Light Exposure Differs by Gender in the US: Women Have Less Bright Light Exposure than Men.

Light is a salient environmental exposure, serving as the primary entraining cue for the circadian system and having other, non-circadian, effects on health. Gender differences in light exposure patterns could contribute to gender differences in health outcomes and would have important implications for sleep and circadian research. Gender differences in real-world light exposure (measured over a week with wrist-worn ActiGraph GT3X+ devices) were investigated in cross- sectional data from the 2011-2014 National Health and Nutrition Examination Survey (NHANES). Measures of time above light threshold (TALT), individual photoperiod (IP), first and last timing of light (FTL and LTL, respectively), and mean light timing revised (MLiTR) at different light intensity thresholds were derived. Gender differences in light exposure were tested using two-sample t-tests, Watson's two-sample test of homogeneity, and linear regression models. Exploratory analyses to investigate work and physical activity-related factors in relation to bright light exposure were also conducted. A total of 11,318 NHANES participants (age range: 3-80+, 52.2% women) with 6 days of valid actigraphy and light data were included in the analysis. The findings suggest that for every 60 minutes of bright light (≥1,000 lux) that men receive, women receive 39.6 minutes. Men spend approximately 52% more time in bright light than women and this gender difference begins in childhood. The IP of bright light exposure is also longer for men, with earlier first and later last timing of bright light exposure compared to women. These gender differences were robust across ages and between race and ethnicity groups. While further research is needed, these gender differences in light exposure may be due to gender differences in indoor vs. outdoor activities. Future studies of gender differences in response to light exposure should consider light exposure history in study design and analysis. The results of this study may inform future health disparities research and support the importance of the study of light as an important environmental exposure and component of the human exposome.

Racial/ethnic and sex differences in the association between light at night and actigraphy-measured sleep duration in adults: NHANES 2011-2014.

OBJECTIVE: Historically minoritized individuals experience greater exposure to light at night, yet it is unclear whether the association between light at night and sleep duration vary by race/ethnicity or sex. We examined the association between light at night and sleep duration by race/ethnicity and sex. METHODS: Participants (N = 6089, mean age=49.5, 52% women, 13% Asian, 27% Black, 14% Mexican, 46% White) in the 2011-2014 National Health and Nutrition Examination Survey underwent 9-day of actigraphy. Light at night was defined as light exposure within the 5-hour activity nadir (L5). Sleep duration within a 24-hour period was analyzed as short (<7 hours) or long (>9 hours) compared to recommended (≥7 and <9 hours). Poisson models were fit to estimate the association between light at night and sleep duration after adjustment for covariates. RESULTS: Light at night was most common among Black participants, who also had the shortest sleep duration. Overall, light at night was associated with 80% higher prevalence of short sleep duration [1.80 (1.49, 2.18)]. Compared to no-light at night, low and high light at night were associated with higher prevalence of short sleep duration, [1.61 (1.31, 1.98) and 2.01 (1.66, 2.44), respectively]. Associations varied by race/ethnicity and sex. Light at night was associated with shorter sleep duration in Black, Mexican and White females and Mexican and White males only. Black males exposed to light at night vs. no-light at night had lower prevalence of long sleep duration. There were no associations between light at night and sleep duration among Asian participants. CONCLUSION: Light at night was associated with shorter sleep duration, particularly among females. Targeting light exposure may help to improve sleep duration.

Response-adapted, time-limited venetoclax, umbralisib, and ublituximab for relapsed/refractory chronic lymphocytic leukemia.

ABSTRACT: Many patients with chronic lymphocytic leukemia (CLL) will develop treatment resistance to Bruton tyrosine kinase (BTK) inhibitors. Phosphatidylinositol-3-kinase (PI3K) inhibitors, including umbralisib, have significant clinical activity in relapsed/refractory CLL, but prolonged exposure is associated with potential toxicities. Owing to the synergistic antitumor effects of combined PI3K and BCL-2 inhibition, we sought to explore the feasibility of response-adapted, time-limited therapy to optimize disease control while mitigating the risks of prolonged treatment. We conducted a phase 1/2 clinical trial to determine the safety and efficacy of venetoclax in combination with umbralisib and the anti-CD20 monoclonal antibody, ublituximab, (U2-VeN) in patients with relapsed/refractory CLL (N = 46) and Richter transformation (N = 5). After 12 cycles, treatment was stopped for patients with CLL who achieved undetectable minimal residual disease (uMRD). Adverse events of special interest included diarrhea in 50% of patients (11% grade 3/4), and aspartate aminotransferase and/or alanine aminotransferase elevation in 15 patients (33%), with 3 (7%) grade 3/4. There were no cases of tumor lysis syndrome related to venetoclax, with outpatient initiation in 96% of patients. The intent-to-treat overall response rate for CLL was 98% with best response of 100% in evaluable patients (42% complete responses). The end-of-treatment rate of uMRD at 10-4 in bone marrow was 77% (30/39), including a 71% uMRD rate among 14 patients refractory to prior BTK inhibitor. Time-limited venetoclax and U2 is safe and highly effective combination therapy for patients with relapsed/refractory CLL including those who have been previously treated with covalent BTK inhibitors. This trial was registered on www.clinicaltrials.gov as #NCT03379051.

Light exposure during sleep is bidirectionally associated with irregular sleep timing: The multi-ethnic study of atherosclerosis (MESA).

Exposure to light at night (LAN) may influence sleep timing and regularity. Here, we test whether greater light exposure during sleep (LEDS) is bidirectionally associated with greater irregularity in sleep onset timing in a large cohort of older adults in cross-sectional and short-term longitudinal (days) analyses. Light exposure and activity patterns, measured via wrist-worn actigraphy (ActiWatch Spectrum), were analyzed in 1933 participants with 6+ valid days of data in the Multi-Ethnic Study of Atherosclerosis (MESA) Exam 5 Sleep Study. Summary measures of LEDS averaged across nights were evaluated in linear and logistic regression analyses to test the association with standard deviation (SD) in sleep onset timing (continuous variable) and irregular sleep onset timing (SD > 90 min, binary). Night-to-night associations between LEDS and absolute differences in nightly sleep onset timing were also evaluated with distributed lag non-linear models and mixed models. In between-individual linear and logistic models adjusted for demographic, health, and seasonal factors, every 5-lux unit increase in LEDS was associated with a 7.8-min increase in sleep onset SD (ß = 0.13 h, 95%CI:0.09-0.17) and 32% greater odds (OR = 1.32, 95%CI:1.17-1.50) of irregular sleep onset. In within-individual night-to-night mixed model analyses, every 5-lux unit increase in LEDS the night prior was associated with a 2.2-min greater deviation of sleep onset the next night (ß = 0.036 h, p < 0.05). Conversely, every 1-h increase in sleep deviation was associated with a 0.35-lux increase in future LEDS (ß = 0.348 lux, p < 0.05). LEDS was associated with greater irregularity in sleep onset in between-individual analyses and subsequent deviation in sleep timing in within-individual analyses, supporting a role for LEDS in irregular sleep onset timing. Greater deviation in sleep onset was also associated with greater future LEDS, suggesting a bidirectional relationship. Maintaining a dark sleeping environment and preventing LEDS may promote sleep regularity and following a regular sleep schedule may limit LEDS.

Light exposure during sleep is associated with irregular sleep timing: the Multi-Ethnic Study of Atherosclerosis (MESA).

Objective: Exposure to light at night (LAN) may influence sleep timing and regularity. Here, we test whether greater light exposure during sleep (LEDS) associates with greater irregularity in sleep onset timing in a large cohort of older adults. Methods: Light exposure and activity patterns, measured via wrist-worn actigraphy (ActiWatch Spectrum), were analyzed in 1,933 participants with 6+ valid days of data in the Multi-Ethnic Study of Atherosclerosis (MESA) Exam 5 Sleep Study. Summary measures of LEDS averaged across nights were evaluated in linear and logistic regression analyses to test the association with standard deviation (SD) in sleep onset timing (continuous variable) and irregular sleep onset timing (SD≥1.36 hours, binary). Night-to-night associations between LEDS and absolute differences in nightly sleep onset timing were also evaluated with distributed lag non-linear models and mixed models. Results: In between-individual linear and logistic models adjusted for demographic, health, and seasonal factors, every 5-lux unit increase in LEDS was associated with an increase of 7.8 minutes in sleep onset SD (ß=0.13 hours, 95%CI:0.09-0.17) and 40% greater odds (OR=1.40, 95%CI:1.24-1.60) of irregular sleep onset. In within-individual night-to-night mixed model analyses, every 5-lux unit increase in LEDS the night prior (lag0) was associated with a 2.2-minute greater deviation of sleep onset the next night (ß=0.036 hours, p<0.05). Conversely, every 1-hour increase in sleep deviation (lag0) was associated with a 0.35-lux increase in future LEDS (ß=0.347 lux, p<0.05). Conclusion: LEDS was associated with greater irregularity in sleep onset in between-individual analyses and subsequent deviation in sleep timing in within-individual analyses, supporting a role for LEDS in exacerbating irregular sleep onset timing. Greater deviation in sleep onset was also associated with greater future LEDS, suggesting a bidirectional relationship. Maintaining a dark sleeping environment and preventing LEDS may promote sleep regularity and following a regular sleep schedule may limit LEDS.

Rest-activity rhythms across the lifespan: cross-sectional findings from the US representative National Health and Nutrition Examination Survey.

STUDY OBJECTIVES: Rest-activity rhythms (RAR) may mark development, aging, and physical and mental health. Understanding how they differ between people may inform intervention and health promotion efforts. However, RAR characteristics across the lifespan have not been well-studied. Therefore, we investigated the association between RAR measures with demographic and lifestyle factors in a US nationally representative study. METHODS: RAR metrics of interdaily stability (IS), intradaily variability (IV), relative amplitude (RA), and mean amplitude and timing of high (M10) and low (L5) activity were derived from 2011 to 2012 and 2013 to 2014 National Health and Nutrition Examination Survey (NHANES) actigraphy data. Population-weighted linear and logistic regression models were fit to examine the associations of age, gender, smoking, alcohol, season, body mass index (BMI), income-to-poverty ratio, and race/ethnicity with RAR. Significance was based on a false-discovery rate-corrected P-value of <0.05. RESULTS: Among n = 12 526 NHANES participants (3-≥80 years), IS (higher = greater day-to-day regularity) and RA (higher = greater rhythm strength) generally decreased with age and were lower among males, whereas IV (higher = greater rhythm fragmentation) increased with age (p < 0.05). Dynamic changes in RAR trajectories were observed during childhood and adolescence. Income, BMI, smoking, and alcohol use were associated with RAR metrics, as well as season among children and teenagers (p < 0.05). RAR also differed by race/ethnicity (p < 0.05), with trajectories initially diverging in childhood and continuing into adulthood. CONCLUSIONS: RAR differed by demographic and health-related factors, representing possible windows for public health intervention and sleep health promotion. RAR differences by race/ethnicity begin in childhood, are evident in early adolescence, and persist throughout adulthood.

Is exposure to chemical pollutants associated with sleep outcomes? A systematic review.

Environmental exposures may influence sleep; however, the contributions of environmental chemical pollutants to sleep health have not been systematically investigated. We conducted a systematic review to identify, evaluate, summarize, and synthesize the existing evidence between chemical pollutants (air pollution, exposures related to the Gulf War and other conflicts, endocrine disruptors, metals, pesticides, solvents) and dimensions of sleep health (architecture, duration, quality, timing) and disorders (sleeping pill use, insomnia, sleep-disordered breathing)). Of the 204 included studies, results were mixed; however, the synthesized evidence suggested associations between particulate matter, exposures related to the Gulf War, dioxin and dioxin-like compounds, and pesticide exposure with worse sleep quality; exposures related to the Gulf War, aluminum, and mercury with insomnia and impaired sleep maintenance; and associations between tobacco smoke exposure with insomnia and sleep-disordered breathing, particularly in pediatric populations. Possible mechanisms relate to cholinergic signaling, neurotransmission, and inflammation. Chemical pollutants are likely key determinants of sleep health and disorders. Future studies should aim to evaluate environmental exposures on sleep across the lifespan, with a particular focus on developmental windows and biological mechanisms, as well as in historically marginalized or excluded populations.

Did George Floyd's murder shape the public's felt obligation to obey the police?

OBJECTIVE: Our goal in the present study was to use longitudinal data to assess how normative (i.e., consensually motivated) and instrumental (i.e., coercively motivated) obligation to obey police changed after police murdered George Floyd and whether these changes differed by political ideology. HYPOTHESES: Using procedural justice theory, we hypothesized that after Floyd's murder, participants would feel less normatively obligated and more instrumentally obligated to obey police. We also hypothesized that these trends would be stronger for liberal-leaning than conservative-leaning participants. METHOD: Adults (N = 645) were recruited through Prolific from four politically diverse U.S. states. Participants reported their normative and instrumental obligation across three waves of data collection, each separated by 3 weeks. The first two waves were collected prior to the Floyd's murder, and the third was collected after. RESULTS: Hierarchical linear models indicated that although normative obligation remained stable before Floyd's murder, it declined after Floyd's murder (b = -0.19, 95% CI [-0.24, -0.14], p < .001). In contrast, coercive obligation to obey increased consistently across all three waves. Liberal-leaning participants drove most of the effects. CONCLUSIONS: For researchers, these findings help strengthen our understanding of procedural justice theory by differentiating normative and instrumental obligation and by distinguishing differences by political ideology within the context of a historic police-brutality event. For policymakers and law enforcement, our research suggests that police brutality may undermine the public's normative felt obligation to obey the police, which would be problematic for police reformation efforts grounded in governing by mutual consent versus by fear and coercion. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Rituximab induced cytokine release with high serum IP-10 (CXCL10) concentrations is associated with infusion reactions.

Monoclonal antibody induced infusion reactions (IRs) can be serious and even fatal. We used clinical data and blood samples from 37 treatment naïve patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) initiating therapy for progressive disease with a single 50 mg dose of intravenous (IV) rituximab at 25 mg/h. Twenty-four (65 %) patients had IRs at a median of 78 min (range 35-128) and rituximab dose of 32 mg (range 15-50). IR risk did not correlate with patient or CLL characteristics, CLL counts or CD20 levels, or serum rituximab or complement concentrations. Thirty-five (95 %) patients had cytokine release response with a ≥ 4-fold increase in serum concentration of ≥ 1 inflammatory cytokine. IRs were associated with significantly higher post-infusion serum concentrations of gamma interferon induced cytokines IP-10, IL-6 and IL-8. IP-10 concentrations increased ≥ 4-fold in all patients with an IR and were above the upper limit of detection (40,000 pg/ml) in 17 (71 %). In contrast, to only three (23 %) patients without an IR had an ≥ 4-fold increase in serum concentrations of IP-10 (highest 22,013 pg/ml). Our data suggest that cytokine release could be initiated by activation of effector cells responsible for clearance of circulating CLL cells with IRs occurring in those with higher levels of gamma interferon induced cytokines. These novel insights could inform future research to better understand and manage IRs and understand the role of cytokines in the control of cytotoxic immune responses to mAb.

Captive breeding in the endangered alpine tree frog, Litoria verreauxii alpina.

Amphibians are experiencing dramatic worldwide declines and many species are reliant on captive breeding programs to ensure continued survival. However, captive breeding in amphibians is not always successful because many species, especially ones in decline, have particular and specific breeding needs. The endangered alpine tree frog, Litoria verreauxii alpina, has never been bred in captivity before. Due to its dramatic declines across the Australian Alps caused by the global pandemic chytridiomycosis, the species is a potential candidate for captive assurance colonies, which rely on captive breeding. For this study we tested hormone induction using two hormones that have had some success in other amphibian species, to no avail. We then tried outdoor breeding mesocosms during the winter/spring at temperatures similar to their natural breeding season, which was successful. Sixty-five percent of the egg masses laid successfully hatched tadpoles. Females laid more than one clutch over the experiment indicating either a shorter than annual ovulation cycle, or that females are capable of partial ovulation during breeding events. Outdoor breeding mesocosms are a possibility outside the native climate of a species, provided that temperatures overlap with their natural environment. Here, we highlight that troubleshooting is essential before embarking on a captive breeding program of a species that has not been bred before. Hormonal induction of breeding is not always successful; therefore, outdoor mesocosms might be required to achieve healthy tadpoles.

Acalabrutinib and high-frequency low-dose subcutaneous rituximab for initial therapy of chronic lymphocytic leukemia.

Bruton tyrosine kinase inhibitors are an effective therapeutic agent for previously untreated patients with chronic lymphocytic leukemia but require indefinite treatment that can result in cumulative toxicities. Novel combinations of agents that provide deep remissions could allow for fixed duration therapy. Acalabrutinib, unlike ibrutinib, does not inhibit anti-CD20 monoclonal antibody-dependent cellular phagocytosis, making it a suitable partner drug to rituximab. Using standard dosing (375 mg/m2) of rituximab causes loss of target membrane CD20 cells and exhaustion of the finite cytotoxic capacity of the innate immune system. Alternatively, using high-frequency, low-dose (HFLD), subcutaneous rituximab limits loss of CD20 and allows for self-administration at home. The combination of HFLD rituximab 50 mg administered twice a week for 6 cycles of 28 days with the addition of acalabrutinib starting in week 2 was evaluated in a phase II study of 38 patients with treatment naive chronic lymphocytic leukemia. Patients achieving a complete response with undetectable minimal residual disease after 12 or 24 cycles of acalabrutinib could stop therapy. All patient responded, including one with a complete response with undetectable minimal residual disease in the peripheral blood and bone marrow at 12 months who stopped therapy. At a median follow-up of 2.3 years 2 patients with high-risk features have progressed while on acalabrutinib monotherapy. We conclude that HFLD rituximab in combination with acalabrutinib is an effective and tolerable self-administered home combination that provides a platform to build upon regimens that may more reliably allow for fixed-duration therapy. This trial was registered at www.clinicaltrials.gov #NCT03788291.

An integrated multi-omics analysis of sleep-disordered breathing traits implicates P2XR4 purinergic signaling.

Sleep Disordered Breathing (SDB) is a common disease associated with increased risk for cardiometabolic, cardiovascular, and cognitive diseases. How SDB affects the molecular environment is still poorly understood. We study the association of three SDB measures with gene expression measured using RNA-seq in multiple blood tissues from the Multi-Ethnic Study of Atherosclerosis. We develop genetic instrumental variables for the associated transcripts as polygenic risk scores (tPRS), then generalize and validate the tPRS in the Women's Health Initiative. We measure the associations of the validated tPRS with SDB and serum metabolites in Hispanic Community Health Study/Study of Latinos. Here we find differential gene expression by blood cell type in relation to SDB traits and link P2XR4 expression to average oxyhemoglobin saturation during sleep and butyrylcarnitine (C4) levels. These findings can be used to develop interventions to alleviate the effect of SDB on the human molecular environment.

Associations between evening shift work, irregular sleep timing, and gestational diabetes in the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be (nuMoM2b).

STUDY OBJECTIVES: Shift work is a risk factor for cardiometabolic disease, possibly through effects on sleep-wake rhythms. We hypothesized that evening (afternoon and night combined) and irregular (irregular/on-call or rotating combined) shift work during pregnancy is associated with increased odds of preeclampsia, preterm birth, and gestational diabetes mellitus (GDM), mediated by irregular sleep timing. METHODS: The Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be (nuMoM2b) is a prospective cohort study (n = 10 038) designed to investigate risk factors for adverse pregnancy outcomes. Medical outcomes were determined with medical record abstraction and/or questionnaires; sleep midpoint was measured in a subset of participants with ≥5-day wrist actigraphy (ActiWatch). We estimated the association of evening and irregular shift work during pregnancy with preeclampsia, preterm birth, and GDM using logistic regression, adjusted for adversity (cumulative variable for poverty, education, health insurance, and partner status), smoking, self-reported race/ethnicity, and age. Finally, we explored whether the association between shiftwork and GDM was mediated by variability in sleep timing. RESULTS: Evening shift work is associated with approximately 75% increased odds of developing GDM (adjusted OR = 1.75, 95% CI: 1.12-2.66); we did not observe associations with irregular shifts, preterm birth, or preeclampsia after adjustment. Pregnant evening shift workers were found to have approximately 45 minutes greater variability in sleep timing compared to day workers (p < .005); sleep-timing variability explained 25% of the association between evening shift work and GDM in a mediation analysis. CONCLUSIONS: Evening shift work was associated with GDM, and this relationship may be mediated by variability in sleep timing.

A study of SARS-COV-2 outbreaks in US federal prisons: the linkage between staff, incarcerated populations, and community transmission.

BACKGROUND: Since the novel coronavirus SARS-COV-2 was first identified to be circulating in the US on January 20, 2020, some of the worst outbreaks have occurred within state and federal prisons. The vulnerability of incarcerated populations, and the additional threats posed to the health of prison staff and the people they contact in surrounding communities underline the need to better understand the dynamics of transmission in the inter-linked incarcerated population/staff/community sub-populations to better inform optimal control of SARS-COV-2. METHODS: We examined SARS-CoV-2 case data from 101 non-administrative federal prisons between 5/18/2020 to 01/31/2021 and examined the per capita size of outbreaks in staff and the incarcerated population compared to outbreaks in the communities in the counties surrounding the prisons during the summer and winter waves of the SARS-COV-2 pandemic. We also examined the impact of decarceration on per capita rates in the staff/incarcerated/community populations. RESULTS: For both the summer and winter waves we found significant inter-correlations between per capita rates in the outbreaks among the incarcerated population, staff, and the community. Over-all during the pandemic, per capita rates were significantly higher in the incarcerated population than in both the staff and community (paired Student's t-test p = 0.03 and p < 0.001, respectively). Average per capita rates of incarcerated population outbreaks were significantly associated with prison security level, ranked from lowest per capita rate to highest: High, Minimum, Medium, and Low security. Federal prisons decreased the incarcerated population by a relative factor of 96% comparing the winter to summer wave (one SD range [90%,102%]). We found no significant impact of decarceration on per capita rates of SARS-COV-2 infection in the staff community populations, but decarceration was significantly associated with a decrease in incarcerated per capita rates during the winter wave (Negative Binomial regression p = 0.015). CONCLUSIONS: We found significant evidence of community/staff/incarcerated population inter-linkage of SARS-COV-2 transmission. Further study is warranted to determine which control measures aimed at the incarcerated population and/or staff are most efficacious at preventing or controlling outbreaks.

A Multicentered Academic Medical Center Experience of a Simulated Root Cause Analysis (RCA) for Hematology/Oncology Fellows.

Quality improvement and patient safety education is an Accreditation Council for Graduate Medical Education (ACGME) common program requirement for hematology/oncology fellowships. Interprofessional clinical patient safety activities, such as root cause analyses (RCA), can be challenging to incorporate into busy schedules. We report on a multicentered experience utilizing a simulated RCA educational module in an attempt to provide fellows with the tools needed to participate in a live RCA and to increase awareness of the need to analyze patient safety events. The 2-h module included a didactic session explaining the basics of an RCA including common terminology, effective chart review, and personal interviews. The fellows assessed a patient safety event of a missed coagulopathy and created an event flow map and fishbone analysis. They then formed root cause/contributing factor statements and proposed a solution. Twenty-three fellows from two institutions completed the experience. There was a significant difference in fellow reported comfort with participating in a live RCA (p = 0.03), and in utilizing the tools of an RCA following the mock RCA experience (p = 0.005). About 70% of respondents felt that as a result of the mock RCA, they were more likely to report a near miss or adverse event and were more likely to be thorough in their documentation. Mock RCAs are a feasible method of incorporating ACGME-required patient safety activities into hematology/oncology fellow education and are effective in increasing their comfort and understanding of important quality improvement skills.