MethParquet: an R package for rapid and efficient DNA methylation association analysis adopting Apache Parquet.

SUMMARY: Genome-wide DNA methylation (DNAm) profiling is indispensable for unveiling how DNAm regulates biological pathways and individual phenotypes. However, managing and analyzing extensive DNAm data generated from large cohort studies present computational obstacles. Apache Parquet is a data file format that allows for efficient data storage, retrieval, and manipulation, alleviating computational hurdles associated with conventional row-based formats. We here introduce MethParquet, the first R package leveraging the columnar Parquet format for efficient DNAm data analysis. It can be used for data extraction, methylation risk score calculation, epigenome-wide association analyses, and other standard post-quality control tasks. The package flexibly implements diverse regression models. Via a public methylation dataset, we show the efficiency of this package in reducing running time and RAM usage in large-scale EWAS. AVAILABILITY AND IMPLEMENTATION: The MethParquet R package is publicly available on the GitHub repository https://github.com/ZWangTen/MethParquet. It includes a vignette and a toy dataset derived from a public resource.

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).

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.

Early Progressing Follicular Lymphoma.

PURPOSE OF REVIEW: Follicular lymphoma is an indolent lymphoma which does not limit life expectancy in most patients; however, approximately 20% of patients will experience progression of disease within 24 months (POD24) of diagnosis and have inferior survival outcomes. To date, no clinical, genetic, or tumor microenvironment prediction models have been able to definitively predict which patients will experience POD24 which limits the ability to alter frontline management of patients suspected to be at high risk of early progression. Here, we review recent literature regarding novel prediction models and management recommendations for POD24 patients. RECENT FINDINGS: Recent studies have revealed novel clinicopathologic prediction models which may be closer to identifying patients at risk of POD24. In addition, several clinical trials utilizing novel therapies such as tazemetostat, obinutuzumab, PI3K inhibitors, and lenalidomide have been performed which help further guide treatment. Ongoing trials seek to identify the optimal management of these patients, and data from bispecific antibodies and CAR T cell therapies is forthcoming. With ongoing research efforts, hope remains that we are closer to being able to predict which patients will experience early progressing follicular lymphoma and have an improved management plan for those who do in order to improve survival outcomes.

An experimental investigation into perceptions of disrespect during interpersonal conflict.

Perceptions of disrespect are central to everyday life. Despite the importance of disrespect across various social arenas, prior research has failed to empirically examine the factors influencing these perceptions. This problem is magnified when considering that perceptions or disrespect may vary across individuals and social situations alike. Drawing from theories of social geometry and symbolic interaction, this study examines the individual and situational characteristics that inform perceptions of disrespect. Using factorial vignettes, and a large sample of students, respondents were asked to assess actors in various conflicts. Results from a series of hierarchical linear models show that perceptions of disrespect vary across individuals. The content of situations appears to drive perceptions of disrespect more than individual characteristics. Implications for future research on disrespect are discussed.

Testing the temporal nature of social disorder through abandoned buildings and interstitial spaces.

With the recent housing crisis, studying abandoned buildings has once again become important. However, it has been some time since abandoned buildings were the subject of direct study, leaving scholars with scant knowledge about the characteristics of abandoned buildings, how they change, and their relationship to neighborhood processes. To fill this gap, we employed longitudinal photographic and SSO evaluations of 36 abandoned buildings and their immediate surroundings in Chicago for one year (n=587). Results demonstrate the presence and severity of social disorder cues vary across time points and the time of day of observation. There is a relationship between abandoned buildings and social disorder, though the relationship is not a trend. Also, social disorder is diminished around extremely decayed buildings. Lastly, we find that our results are driven by the measurement of places ignored by most SSO studies, including alleys and the rear side of buildings.

Do you see what I see? Perceptual variation in reporting the presence of disorder cues.

A growing body of literature considers the causes of variation in perceptions of disorder; thus far, few explanations are adequate. We ask: when exposed to the same environment, do individuals homogenously report the presence of the same disorder cues? Using a dataset that cluster samples residents within city blocks and hierarchal logistic regression, we assess whether individuals residing within 1-2 blocks of each other report the same disorder cues. We find that (1) there is significant variation in reports, (2) individuals tend to disagree on the presence of disorder, not its absence, and (3) that reporting various disorder cues has significant ties to an individual's characteristics, their routine activities, and how attached they are to their neighborhood. How individuals report and interpret disorder seems to be dependent on the confluence of social, historical, economic, and place-based factors. Our results suggest revisiting the theorization of how individuals report on and interact with disorder.

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.

Baseline haematological parameters in three common Australian frog species.

Amphibians are experiencing declines globally, with emerging infectious diseases as one of the main causes. Haematological parameters present a useful method for determining the health status of animals and the effects of particular diseases, but the interpretation of differential cell counts relies on knowing the normal ranges for the species and factors that can affect these counts. However, there is very little data on either normal haematological parameters or guides for blood cell types for free-ranging frog species across the world. This study aims to 1) create a visual guide for three different Australian frog species: Litoria paraewingi, Limnodynastes dumerilii, and Crinia signifera, 2) determine the proportions of erythrocytes to leukocytes and 3) differential leukocytes within blood smears from these three species and 4) assess the association between parasites and differential counts. We collected blood samples from free-ranging frogs and analysed blood smears. We also looked for ectoparasites and tested for the fungal disease chytridiomycosis. Overall, we found that the differentials of erythrocytes to leukocytes were not affected by species, but the proportions of different leukocytes did vary across species. For example, while lymphocytes were the most common type of leukocyte across the three species, eosinophils were relatively common in Limnodynastes dumerilii but rarely present in the other two species. We noted chytridiomycosis infection as well as ectoparasites present in some individuals but found no effect of parasites on blood parameters. Our results add baseline haematological parameters for three Australian frog species and provide an example of how different frog species can vary in their differential blood cell counts. More information is needed on frog haematological data before these parameters can be used to determine the health status of wild or captive frogs.

Clonally unrelated primary large B-cell lymphomas separated by over a decade involving the central nervous system and testicle: Possible predisposition to lymphomas of immune-privileged sites?

Primary large B-cell lymphomas of immune-privileged sites (IP-LBCLs) comprise LBCLs arising within "immune sanctuaries," including the central nervous system (CNS), vitreoretina, and testes. Although patients present with localized disease, the prognosis remains poor with high relapse rates, either at the originating site or within another immune-privileged site. Generally, in the presence of an antecedent IP-LBCL, subsequent LBCLs are expected to be clonally related. However, we present a primary CNS LBCL and later primary testicular LBCL in a middle-aged man, diagnosed over a decade apart, which proved to be clonally unrelated by targeted ultra-deep next-generation sequencing of the IgH locus.

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.

Untargeted Metabolome Atlas for Sleep Phenotypes in the Hispanic Community Health Study/Study of Latinos.

Sleep is essential to maintaining health and wellbeing of individuals, influencing a variety of outcomes from mental health to cardiometabolic disease. This study aims to assess the relationships between various sleep phenotypes and blood metabolites. Utilizing data from the Hispanic Community Health Study/Study of Latinos, we performed association analyses between 40 sleep phenotypes, grouped in several domains (i.e., sleep disordered breathing (SDB), sleep duration, timing, insomnia symptoms, and heart rate during sleep), and 768 metabolites measured via untargeted metabolomics profiling. Network analysis was employed to visualize and interpret the associations between sleep phenotypes and metabolites. The patterns of statistically significant associations between sleep phenotypes and metabolites differed by superpathways, and highlighted subpathways of interest for future studies. For example, some xenobiotic metabolites were associated with sleep duration and heart rate phenotypes (e.g. 1H-indole-7-acetic acid, 4-allylphenol sulfate), while ketone bodies and fatty acid metabolism metabolites were associated with sleep timing measures (e.g. 3-hydroxybutyrate (BHBA), 3-hydroxyhexanoylcarnitine (1)). Heart rate phenotypes had the overall largest number of detected metabolite associations. Many of these associations were shared with both SDB and with sleep timing phenotypes, while SDB phenotypes shared relatively few metabolite associations with sleep duration measures. A number of metabolites were associated with multiple sleep phenotypes, from a few domains. The amino acids vanillylmandelate (VMA) and 1-carboxyethylisoleucine were associated with the greatest number of sleep phenotypes, from all domains other than insomnia. This atlas of sleep-metabolite associations will facilitate hypothesis generation and further study of the metabolic underpinnings of sleep health.

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.

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.

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.

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.