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Dyadic Developmental Psychotherapy (DDP) is a family-based therapy for adopted children aiming to achieve secure attachment between the child and parent. Due to restrictions under the COVID-19 pandemic, delivery of DDP transitioned from face-to-face to online methods. This study aimed to explore families experience of online DDP compared to face-to-face DDP, looking at the advantages and disadvantages of remote delivery methods and the implications this has on future service delivery for clinicians. Semi-structured interviews with 6 families were conducted online. Analysis of transcripts using Interpretative Phenomenological Analysis (IPA) revealed four superordinate themes: environment and child engagement, non-verbal communication, travel and familiarity with remote interactions. Parents recognised the influence the physical and online environment had on their child's engagement levels, however, varied in their experience and hence preference of delivery method. All families emphasised the importance of non-verbal communication within DDP sessions and majority highlighted this may be lost online. For families who travelled to face-to-face DDP, car journeys provided a unique opportunity to decompress and reflect after sessions. For families where travel is unfeasible, online DDP was a lifeline, demonstrating the ability of remote therapy to widen access to specialist healthcare. Familiarity with online work emerged as a strong indicator of positive attitudes towards remote DDP, especially if the previous experience is positive and the child is confident using technology. Overall, families differed greatly in their experience of remote and face-to-face DDP indicating a new approach must be undertaken with each family beginning therapy, ensuring it is unique and individual to their needs.

Objective: Retention to complete follow-up surveys in extensive longitudinal epidemiological cohort studies is vital yet challenging. All of Us developed pilot interventions to improve response rates for follow-up surveys. Study design and setting: The pilot interventions occurred from April 27, 2020, to August 3, 2020. The three arms were: (1) telephone appointment [staff members calling participants offering appointments to complete surveys over phone] (2) postal [mail reminder to complete surveys through U.S. Postal Service], and (3) combination of telephone appointment and postal. Controls received digital-only reminders [program-level digital recontact via email or through the participant portal]. Study sites chose their study arm and participants were not randomized. Results: A total of 50 sites piloted interventions with 17,593 participants, while 47,832 participants comprised controls during the same period. Of all participants, 6,828 (10.4%) completed any follow-up surveys (1448: telephone; 522: postal; 486: combination; 4372: controls). Follow-up survey completions were 24% higher in the telephone appointment arm than in controls in bivariate analyses. When controlling for confounders, telephone appointment and combination arms increased rates of completion similarly compared to controls, while the postal arm had no significant effect (odds ratio [95% Confidence Interval], telephone appointment:2.01[1.81–2.23]; combination:1.91[1.66–2.20]; postal:0.92[0.79–1.07]). Although the effects of the telephone appointment and combination arms were similar, differential effects were observed across sub-populations. Conclusion: Telephone appointments appeared to be the most successful intervention in our study. Lessons learned about retention interventions, and improvement in follow-up survey completion rates provide generalizable knowledge for similar cohort studies and demonstrate the potential value of precision reminders and engagement with sub-populations of a cohort. [ABSTRACT FROM AUTHOR]

Technological innovation yielded opportunities to obtain mRNA expression data for prostate cancer (PCa) patients even prior to biopsy, which can be used in a precision medicine approach to treatment decision-making. This can apply in particular to predict the risk of, and time to biochemical recurrence (BCR). Most mRNA-based models currently proposed to this end are designed for risk classification and post-operative prediction. Effective pre-operative prediction would facilitate early treatment decision-making, in particular by indicating more appropriate therapeutic pathways for patient profiles who would likely not benefit from a systematic prostatectomy regime. The aim of this study is to investigate the possibility to leverage mRNA information pre-operatively for BCR-free survival prediction. To do this, we considered time-to-event machine learning (ML) methodologies, rather than classification models at a specific survival horizon. We retrospectively analysed a cohort of 135 patients with clinical follow-up data and mRNA information comprising over 26,000 features (data accessible at NCBI GEO database, accession GSE21032). The performance of ML models including random survival forest, boosted and regularised Cox models were assessed, in terms of model discrimination, calibration, and predictive accuracy for overall, 3-year and 5-year survival, aligning with common clinical endpoints. Results showed that the inclusion of mRNA information could yield a gain in performance for pre-operative BCR prediction. ML-based time-to-event models significantly outperformed reference nomograms that used only routine clinical information with respect to all metrics considered. We believe this is the first study proposing pre-operative transcriptomics models for BCR prediction in PCa. External validation of these findings, including confirmation of the mRNA variables identified as potential key predictors in this study, could pave the way for pre-operative precision nomograms to facilitate timely personalised clinical decision-making. [ABSTRACT FROM AUTHOR]

Oxygen consumption (V˙O2) is an important measure for exercise test, such as walking and running, that can be measured outdoors using portable spirometers or metabolic analyzers. However, these devices are not feasible for regular use by consumers as they intervene with the user's physical integrity, and are expensive and difficult to operate. To circumvent these drawbacks, indirect estimation of V˙O2 using neural networks combined with motion features and heart rate measurements collected with consumer-grade sensors has been shown to yield reasonably accurate V˙O2 for intra-subject estimation. However, estimating V˙O2 with neural networks trained with data from other individuals than the user, known as inter-subject estimation, remains an open problem. In this paper, five types of neural network architectures were tested in various configurations for inter-subject V˙O2 estimation. To analyse predictive performance, data from 16 participants walking and running at speeds between 1.0 m/s and 3.3 m/s were used. The most promising approach was Xception network, which yielded average estimation errors as low as 2.43 ml×min−1×kg−1, suggesting that it could be used by athletes and running enthusiasts for monitoring their oxygen consumption over time to detect changes in their movement economy. [ABSTRACT FROM AUTHOR]

ObjectiveThe All of Us Research Program collects data from multiple information sources, including health surveys, to build a national longitudinal research repository that researchers can use to advance precision medicine. Missing survey responses pose challenges to study conclusions. We describe missingness in All of Us baseline surveys.Study design and settingWe extracted survey responses between May 31, 2017, to September 30, 2020. Missing percentages for groups historically underrepresented in biomedical research were compared to represented groups. Associations of missing percentages with age, health literacy score, and survey completion date were evaluated. We used negative binomial regression to evaluate participant characteristics on the number of missed questions out of the total eligible questions for each participant.ResultsThe dataset analyzed contained data for 334,183 participants who submitted at least one baseline survey. Almost all (97.0%) of the participants completed all baseline surveys, and only 541 (0.2%) participants skipped all questions in at least one of the baseline surveys. The median skip rate was 5.0% of the questions, with an interquartile range (IQR) of 2.5% to 7.9%. Historically underrepresented groups were associated with higher missingness (incidence rate ratio (IRR) [95% CI]: 1.26 [1.25, 1.27] for Black/African American compared to White). Missing percentages were similar by survey completion date, participant age, and health literacy score. Skipping specific questions were associated with higher missingness (IRRs [95% CI]: 1.39 [1.38, 1.40] for skipping income, 1.92 [1.89, 1.95] for skipping education, 2.19 [2.09-2.30] for skipping sexual and gender questions).ConclusionSurveys in the All of Us Research Program will form an essential component of the data researchers can use to perform their analyses. Missingness was low in All of Us baseline surveys, but group differences exist. Additional statistical methods and careful analysis of surveys could help mitigate challenges to the validity of conclusions.

This retrospective observational study aimed to gain a better understanding of the protective duration of prior SARS-CoV-2 infection against reinfection. The objectives were two-fold: to assess the durability of immunity to SARS-CoV-2 reinfection among initially unvaccinated individuals with previous SARS-CoV-2 infection, and to evaluate the crude SARS-CoV-2 reinfection rate and associated risk factors. During the pandemic era time period from February 29, 2020, through April 30, 2021, 144,678,382 individuals with SARS-CoV-2 molecular diagnostic or antibody test results were studied. Rates of reinfection among index-positive individuals were compared to rates of infection among index-negative individuals. Factors associated with reinfection were evaluated using multivariable logistic regression. For both objectives, the outcome was a subsequent positive molecular diagnostic test result. Consistent with prior findings, the risk of reinfection among index-positive individuals was 87% lower than the risk of infection among index-negative individuals. The duration of protection against reinfection was stable over the median 5 months and up to 1-year follow-up interval. Factors associated with an increased reinfection risk included older age, comorbid immunologic conditions, and living in congregate care settings; healthcare workers had a decreased reinfection risk. This large US population-based study suggests that infection induced immunity is durable for variants circulating pre-Delta predominance.

Introduction Programmed cell death ligand-1 (PD-L1) expression may help identify patients with non-small cell lung cancer (NSCLC) who would benefit from immunotherapy. We assessed PD-L1 expression, and epidermal growth factor receptor (EGFR) and V-Ki-Ras2 Kirsten rat sarcoma (KRAS) mutations in NSCLC patients receiving adjuvant chemotherapy. Methods Data for stage IB/II/IIIA NSCLC patients (diagnosed: 2001–2012) were retrieved from Danish population-based registries. Tumor tissue samples were tested for PD-L1 expression using VENTANA PD-L1 (SP263) Assay in tumor cells (TC) at ≥25% cutoff and immune cells (IC) at ≥1% and ≥25% cutoffs. KRAS and EGFR mutations were tested using PCR-based assays. Follow-up began 120 days after diagnosis until death/emigration/January 1, 2015, whichever came first. Using Cox proportional hazard regression, hazard ratios (HRs) were computed for overall survival (OS) for each biomarker, adjusting for age, sex, histology, comorbidities, and tissue specimen age. Results Among 391 patients identified, 40.4% had stage IIIA disease, 49.9% stage II, and 8.7% stage IB. PD-L1-TC was observed in 38% of patients, EGFR mutations in 4%, and KRAS mutations in 29%. KRAS mutations were more frequent among patients with PD-L1 TC≥25% versus TCConclusion A prognostic impact for NSCLC patients receiving adjuvant chemotherapy was not associated with PD-L1 expression, or with EGFR and KRAS mutations.

The trade and private ownership of non-domesticated animals has detrimental effects on individual animals and their wild populations. Therefore, there is a need to understand the conditions that motivate and dissuade interest in non-domesticated pet ownership. Past research has demonstrated that the way in which non-domesticated animals are portrayed in images influences the public’s perception that they are suitable as pets. We conducted an online survey of people residing in the United States to investigate how viewing images that could be realistically captured in the zoo and broader tourism industries impact the degree to which people report interest in having that animal as a pet. We focused on two species, reticulated pythons (Malayopython reticulatus) and two-toed sloths (Choloepus hoffmanni), and presented each species in six different visual contexts. After viewing an image, respondents reported interest in pet ownership on a four-point Likert scale. Each species was studied separately in a between-subjects design and results were analyzed using ordinal logistic regression models. Thirty-nine percent of respondents reported interest in sloth pet ownership, and 21% reported interest in python pet ownership. However, contrary to our hypotheses, we found that viewing these species in different visual contexts did not significantly affect survey respondents’ reported interest in having either species as a pet. Generation was a significant predictor of interest in both sloth and python pet ownership, with younger generations reporting more interest in having these species as pets. Male respondents reported more interest in python pet ownership, whereas there were no significant differences between genders regarding interest in sloth ownership. We consider how modern media exposure to animals in unnatural contexts may relate to the generational effect and discuss priorities for future research to better understand the development of individual interests in non-domesticated pet ownership.

BackgroundThere is encouraging evidence that interdisciplinary teams of Health and Social Care Professionals (HSCPs) can enhance patient care in the Emergency Department (ED), especially for older adults with complex needs. However, no formal process evaluations of implementations of ED-based HSCP interventions are available. The study aimed to evaluate the development and delivery of a HSCP team intervention for older adults in the ED of a large Irish teaching hospital.MethodsUsing the Medical Research Council (MRC) Framework for process evaluations, we investigated implementation and delivery, mechanisms of impact, and contextual influences on implementation by analysing the HSCP team's activity notes and participant recruitment logs, and by carrying out six interviews and four focus groups with 26 participants (HSCP team members, ED doctors and nurses, hospital staff). Qualitative insights were analysed thematically.ResultsThe implementation process had three phases (pre-implementation, piloting, and delivery), with the first two described as pivotal to optimise care procedures and build positive stakeholders' involvement. The team's motivation and proactive communication were key to promote acceptability and integration in the ED (Theme 1); also, their specialised skills and interdisciplinary approach enhanced patient and staff's ED experience (Theme 2). The investment and collaboration of multiple stakeholders were described as essential contextual enablers of implementation (Theme 4). Delivering the intervention within a randomised controlled trial fostered credibility but caused frustration among patients and staff (Theme 3).DiscussionThis process evaluation is the first to provide in-depth and practical insights on the complexities of developing and delivering an ED-based HSCP team intervention for older adults. Our findings highlight the importance of establishing a team of HSCPs with a strong interdisciplinary ethos to ensure buy-in and integration in the ED processes. Also, actively involving relevant stakeholders is key to facilitate implementation.Trial registrationClinicalTrials.gov, NCT03739515; registered on 12th November 2018.

HIV involvement of the CNS continues to be a significant problem despite successful use of combination antiretroviral therapy (cART). Drugs of abuse can act in concert with HIV proteins to damage glia and neurons, worsening the neurotoxicity caused by HIV alone. Methamphetamine (METH) is a highly addictive psychostimulant drug, abuse of which has reached epidemic proportions and is associated with high-risk sexual behavior, increased HIV transmission, and development of drug resistance. HIV infection and METH dependence can have synergistic pathological effects, with preferential involvement of frontostriatal circuits. At the molecular level, epigenetic alterations have been reported for both HIV-1 infection and drug abuse, but the neuropathological pathways triggered by their combined effects are less known. We investigated epigenetic changes in the brain associated with HIV and METH. We analyzed postmortem frontal cortex tissue from 27 HIV seropositive individuals, 13 of which had a history of METH dependence, in comparison to 14 cases who never used METH. We detected changes in the expression of DNMT1, at mRNA and protein levels, that resulted in the increase of global DNA methylation. Genome-wide profiling of DNA methylation in a subset of cases, showed differential methylation on genes related to neurodegeneration; dopamine metabolism and transport; and oxidative phosphorylation. We provide evidence for the synergy of HIV and METH dependence on the patterns of DNA methylation on the host brain, which results in a distinctive landscape for the comorbid condition. Importantly, we identified new epigenetic targets that might aid in understanding the aggravated neurodegenerative, cognitive, motor and behavioral symptoms observed in persons living with HIV and addictions.

Accurate SARS-CoV-2 diagnosis is essential to guide prevention and control of COVID-19. Here we examine SARS-CoV-2 molecular-based test performance characteristics and summarize case-level data related to COVID-19 diagnosis. From January 11 through April 22, 2020, Public Health Ontario conducted SARS-CoV-2 testing of 86,942 specimens collected from 80,354 individuals, primarily using real-time reverse-transcription polymerase chain reaction (rRT-PCR) methods. We analyzed test results across specimen types and for individuals with multiple same-day and multi-day collected specimens. Nasopharyngeal compared to throat swabs had a higher positivity (8.8% vs. 4.8%) and an adjusted estimate 2.9 Ct lower (SE = 0.5, p

Ischemia reperfusion injury (IRI) is a critical problem in liver transplantation that can lead to life-threatening complications and substantially limit the utilization of livers for transplantation. However, because there are no early diagnostics available, fulminant injury may only become evident post-transplant. Mitochondria play a central role in IRI and are an ideal diagnostic target. During ischemia, changes in the mitochondrial redox state form the first link in the chain of events that lead to IRI. In this study we used resonance Raman spectroscopy to provide a rapid, non-invasive, and label-free diagnostic for quantification of the hepatic mitochondrial redox status. We show this diagnostic can be used to significantly distinguish transplantable versus non-transplantable ischemically injured rat livers during oxygenated machine perfusion and demonstrate spatial differences in the response of mitochondrial redox to ischemia reperfusion. This novel diagnostic may be used in the future to predict the viability of human livers for transplantation and as a tool to better understand the mechanisms of hepatic IRI.

Ostracoda (bivalved Crustacea) comprise a significant part of the benthic meiofauna in the Pacific-Arctic region, including more than 50 species, many with identifiable ecological tolerances. These species hold potential as useful indicators of past and future ecosystem changes. In this study, we examined benthic ostracodes from nearly 300 surface sediment samples, >34,000 specimens, from three regions-the northern Bering, Chukchi and Beaufort Seas-to establish species' ecology and distribution. Samples were collected during various sampling programs from 1970 through 2018 on the continental shelves at 20 to ~100m water depth. Ordination analyses using species' relative frequencies identified six species, Normanicythere leioderma, Sarsicytheridea bradii, Paracyprideis pseudopunctillata, Semicytherura complanata, Schizocythere ikeyai, and Munseyella mananensis, as having diagnostic habitat ranges in bottom water temperatures, salinities, sediment substrates and/or food sources. Species relative abundances and distributions can be used to infer past bottom environmental conditions in sediment archives for paleo-reconstructions and to characterize potential changes in Pacific-Arctic ecosystems in future sampling studies. Statistical analyses further showed ostracode assemblages grouped by the summer water masses influencing the area. Offshore-to-nearshore transects of samples across different water masses showed that complex water mass characteristics, such as bottom temperature, productivity, as well as sediment texture, influenced the relative frequencies of ostracode species over small spatial scales. On the larger biogeographic scale, synoptic ordination analyses showed dominant species-N. leioderma (Bering Sea), P. pseudopunctillata (offshore Chukchi and Beaufort Seas), and S. bradii (all regions)-remained fairly constant over recent decades. However, during 2013-2018, northern Pacific species M. mananensis and S. ikeyai increased in abundance by small but significant proportions in the Chukchi Sea region compared to earlier years. It is yet unclear if these assemblage changes signify a meiofaunal response to changing water mass properties and if this trend will continue in the future. Our new ecological data on ostracode species and biogeography suggest these hypotheses can be tested with future benthic monitoring efforts.

Different HIV vaccine regimens elicit distinct plasma antibody responses in both human and nonhuman primate models. Previous studies in human and non-human primate infants showed that adjuvants influenced the quality of plasma antibody responses induced by pediatric HIV envelope vaccine regimens. We recently reported that use of the 3M052-SE adjuvant and longer intervals between vaccinations are associated with higher magnitude of antibody responses in infant rhesus macaques. However, the impact of different adjuvants in HIV vaccine regimens on the developing infant B cell receptor (BCR) repertoire has not been studied. This study evaluated whether pediatric HIV envelope vaccine regimens with different adjuvants induced distinct antigen-specific memory B cell repertoires and whether specific immunoglobulin (Ig) immunogenetic characteristics are associated with higher magnitude of plasma antibody responses in vaccinated infant rhesus macaques. We utilized archived preclinical pediatric HIV vaccine studies PBMCs and tissue samples from 19 infant rhesus macaques immunized either with (i) HIV Env protein with a squalene adjuvant, (ii) MVA-HIV and Env protein co-administered using a 3-week interval, (iii) MVA-HIV prime/ protein boost with an extended 6-week interval between immunizations, or (iv) with HIV Env administered with 3M-052-SE adjuvant. Frequencies of vaccine-elicited HIV Env-specific memory B cells from PBMCs and tissues were similar across vaccination groups (frequency range of 0.06–1.72%). There was no association between vaccine-elicited antigen-specific memory B cell frequencies and plasma antibody titer or avidity. Moreover, the epitope specificity and Ig immunogenetic features of vaccine-elicited monoclonal antibodies did not differ between the different vaccine regimens. These data suggest that pediatric HIV envelope vaccine candidates with different adjuvants that previously induced higher magnitude and quality of plasma antibody responses in infant rhesus macaques were not driven by distinct antigen-specific memory BCR repertoires.

BackgroundSocio-economic growth in many low and middle-income countries has resulted in more available, though not equitably accessible, healthcare. Such growth has also increased demands from citizens for their health systems to be more responsive to their needs. This paper shares a protocol for the RESPONSE study which aims to understand, co-produce, implement and evaluate context-sensitive interventions to improve health systems responsiveness to health needs of vulnerable groups in Ghana and Vietnam.MethodsWe will use a realist mixed-methods theory-driven case study design, combining quantitative (household survey, secondary analysis of facility data) and qualitative (in-depth interviews, focus groups, observations and document and literature review) methods. Data will be analysed retroductively. The study will comprise three Phases. In Phase 1, we will understand actors' expectations of responsive health systems, identify key priorities for interventions, and using evidence from a realist synthesis we will develop an initial theory and generate a baseline data. In Phase 2, we will co-produce jointly with key actors, the context-sensitive interventions to improve health systems responsiveness. The interventions will seek to improve internal (i.e. intra-system) and external (i.e. people-systems) interactions through participatory workshops. In Phase 3, we will implement and evaluate the interventions by testing and refining our initial theory through comparing the intended design to the interventions' actual performance.DiscussionThe study's key outcomes will be: (1) improved health systems responsiveness, contributing to improved health services and ultimately health outcomes in Ghana and Vietnam and (2) an empirically-grounded and theoretically-informed model of complex contexts-mechanisms-outcomes relations, together with transferable best practices for scalability and generalisability. Decision-makers across different levels will be engaged throughout. Capacity strengthening will be underpinned by in-depth understanding of capacity needs and assets of each partner team, and will aim to strengthen individual, organisational and system level capacities.

The ability to track microbes in real time in vivo is of enormous value for preclinical investigations in infectious disease or gene therapy research. Bacteria present an attractive class of vector for cancer therapy, possessing a natural ability to grow preferentially within tumours following systemic administration. Bioluminescent Imaging (BLI) represents a powerful tool for use with bacteria engineered to express reporter genes such as lux. BLI is traditionally used as a 2D modality resulting in images that are limited in their ability to anatomically locate cell populations. Use of 3D diffuse optical tomography can localize the signals but still need to be combined with an anatomical imaging modality like micro-Computed Tomography (μCT) for interpretation.In this study, the non-pathogenic commensal bacteria E. coli K-12 MG1655 and Bifidobacterium breve UCC2003, or Salmonella Typhimurium SL7207 each expressing the luxABCDE operon were intravenously (i.v.) administered to mice bearing subcutaneous (s.c) FLuc-expressing xenograft tumours. Bacterial lux signal was detected specifically in tumours of mice post i.v.-administration and bioluminescence correlated with the numbers of bacteria recovered from tissue. Through whole body imaging for both lux and FLuc, bacteria and tumour cells were co-localised. 3D BLI and μCT image analysis revealed a pattern of multiple clusters of bacteria within tumours. Investigation of spatial resolution of 3D optical imaging was supported by ex vivo histological analyses. In vivo imaging of orally-administered commensal bacteria in the gastrointestinal tract (GIT) was also achieved using 3D BLI. This study demonstrates for the first time the potential to simultaneously image multiple BLI reporter genes three dimensionally in vivo using approaches that provide unique information on spatial locations.

In vivo measurements of muscle architecture (i.e. the spatial arrangement of muscle fascicles) are routinely included in research and clinical settings to monitor muscle structure, function and plasticity. However, in most cases such measurements are performed manually, and more reliable and time-efficient automated methods are either lacking completely, or are inaccessible to those without expertise in image analysis. In this work, we propose an ImageJ script to automate the entire analysis process of muscle architecture in ultrasound images: Simple Muscle Architecture Analysis (SMA). Images are filtered in the spatial and frequency domains with built-in commands and external plugins to highlight aponeuroses and fascicles. Fascicle dominant orientation is then computed in regions of interest using the OrientationJ plugin. Bland-Altman plots of analyses performed manually or with SMA indicate that the automated analysis does not induce any systematic bias and that both methods agree equally through the range of measurements. Our test results illustrate the suitability of SMA to analyse images from superficial muscles acquired with a broad range of ultrasound settings.

Background and objectivesSleep-disordered breathing (SDB) affects up to one third of women during late pregnancy and is associated with adverse pregnancy outcomes, including hypertension, diabetes, impaired fetal growth, and preterm birth. However, it is unclear if SDB is associated with late stillbirth (≥28 weeks' gestation). The aim of this study was to investigate the relationship between self-reported symptoms of SDB and late stillbirth.MethodsData were obtained from five case-control studies (cases 851, controls 2257) from New Zealand (2 studies), Australia, the United Kingdom, and an international study. This was a secondary analysis of an individual participant data meta-analysis that investigated maternal going-to-sleep position and late stillbirth, with a one-stage approach stratified by study and site. Inclusion criteria: singleton, non-anomalous pregnancy, ≥28 weeks' gestation. Sleep data ('any' snoring, habitual snoring ≥3 nights per week, the Berlin Questionnaire [BQ], sleep quality, sleep duration, restless sleep, daytime sleepiness, and daytime naps) were collected by self-report for the month before stillbirth. Multivariable analysis adjusted for known major risk factors for stillbirth, including maternal age, body mass index (BMI kg/m2), ethnicity, parity, education, marital status, pre-existing hypertension and diabetes, smoking, recreational drug use, baby birthweight centile, fetal movement, supine going-to-sleep position, getting up to use the toilet, measures of SDB and maternal sleep patterns significant in univariable analysis (habitual snoring, the BQ, sleep duration, restless sleep, and daytime naps). Registration number: PROSPERO, CRD42017047703.ResultsIn the last month, a positive BQ (adjusted odds ratio [aOR] 1.44, 95% confidence interval [CI] 1.02-2.04), sleep duration >9 hours (aOR 1.82, 95% CI 1.14-2.90), daily daytime naps (aOR 1.52, 95% CI 1.02-2.28) and restless sleep greater than average (aOR 0.62, 95% CI 0.44-0.88) were independently related to the odds of late stillbirth. 'Any' snoring, habitual snoring, sleep quality, daytime sleepiness, and a positive BQ excluding the BMI criterion, were not associated.ConclusionA positive BQ, long sleep duration >9 hours, and daily daytime naps last month were associated with increased odds of late stillbirth, while sleep that is more restless than average was associated with reduced odds. Pregnant women may be reassured that the commonly reported restless sleep of late pregnancy may be physiological and associated with a reduced risk of late stillbirth.

The All of Us Research Program (All of Us) is a national effort to accelerate health research by exploring the relationship between lifestyle, environment, and genetics. It is set to become one of the largest research efforts in U.S. history, aiming to build a national resource of data from at least one million participants. All of Us aims to address the need for more diversity in research and set the stage for that diversity to be leveraged in precision medicine research to come. This paper describes how the program assessed demographic characteristics of participants who have enrolled in other U.S. biomedical research cohorts to better understand which groups are traditionally represented or underrepresented in biomedical research. We 1) reviewed the enrollment characteristics of national cohort studies like All of Us, and 2) surveyed the literature, focusing on key diversity categories essential to the program's enrollment aims. Based on these efforts, All of Us emphasizes enrollment of racial and ethnic minorities, and has formally designated the following additional groups as historically underrepresented: individuals-with inadequate access to medical care; under the age of 18 or over 65; with an annual household income at or below 200% of the federal poverty level; who have a cognitive or physical disability; have less than a high school education or equivalent; are intersex; identify as a sexual or gender minority; or live in rural or non-metropolitan areas. Research accounting for wider demographic variability is critical. Only by ensuring diversity and by addressing the very barriers that limit it, can we position All of Us to better understand and tackle health disparities.

In ecological studies it is often assumed that predator foraging strategies and resource use are geographically and seasonally homogeneous, resulting in relatively static trophic relationships. However, certain centrally placed foragers (e.g. seals) often have terrestrial sites for breeding, resting, and moulting that are geographically distinct, and associated with different habitat types. Therefore, accurate estimations of predator diet at relevant spatial and temporal scales are key to understanding energetic requirements, predator-prey interactions and ecosystem structure. We investigate geographic variation in the diet of grey seals (Halichoerus grypus), a relatively abundant and widely distributed central place forager, to provide insights into geographic variation in resource use. Prey composition was identified using scat samples collected over concurrent timescales and a multivariate approach was used to analyse diet from two contrasting habitats. Regional differences in prey assemblages occurred within all years (2011-2013) and all seasons (ANOSIM, all p

Background and objectivesEncouraging awareness of fetal movements is a common strategy used to prevent stillbirths. Information provided to pregnant women about fetal movements is inconsistent perhaps due to limited knowledge about normal fetal movement patterns in healthy pregnancies. We aimed to describe maternally perceived fetal movement strength, frequency, and pattern in late pregnancy in women with subsequent normal outcomes.MethodsParticipants were ≥28 weeks' gestation, with a non-anomalous, singleton pregnancy who had been randomly selected from hospital booking lists and had consented to participate. Fetal movement data was gathered during pregnancy via a questionnaire administered face-to-face by research midwives. Participants remained eligible for the study if they subsequently gave birth to a live, appropriate-for-gestational-age baby at ≥37 weeks.ResultsParticipants were 274 women, with normal pregnancy outcomes. The majority (59.3%, n = 162) of women reported during antenatal interview that the strength of fetal movements had increased in the preceding two weeks. Strong fetal movements were felt by most women in the evening (72.8%, n = 195) and at night-time including bedtime (74.5%, n = 199). The perception of fetal hiccups was also reported by most women (78.8%). Women were more likely to perceive moderate or strong fetal movements when sitting quietly compared with other activities such as having a cold drink or eating.ConclusionsOur data support informing women in the third trimester that as pregnancy advances it is normal to perceive increasingly strong movement, episodes of movements that are more vigorous than usual, fetal hiccups, and a diurnal pattern involving strong fetal movement in the evening. This information may help pregnant women to better characterise normal fetal movement and appropriately seek review when concerned about fetal movements. Care providers should be responsive to concerns about decreased fetal movements in the evening, as this is unusual.

ObjectivesCompare the molecular epidemiology of tuberculosis (TB) between two large Canadian provinces-Ontario and British Columbia (BC)-to identify genotypic clusters within and across both provinces, allowing for an improved understanding of genotype data and providing context to more accurately identify clusters representing local transmission.DesignWe compared 24-locus Mycobacterial Interspersed Repetitive Units-Variable Number of Tandem Repeats (MIRU-VNTR) genotyping for 3,314 Ontario and 1,602 BC clinical Mycobacterium tuberculosis isolates collected from 2008 through 2014. Laboratory data for each isolate was linked to case-level records to obtain clinical and demographic data.ResultsThe demographic characteristics of persons with TB varied between provinces, most notably in the proportion of persons born outside Canada, which was reflected in the large number of unique genotypes (n = 3,461). The proportion of clustered isolates was significantly higher in BC. Substantial clustering amongst non-Lineage 4 TB strains was observed within and across the provinces. Only two large clusters (≥10 cases/cluster) representing within province transmission had interprovincial genotype matches.ConclusionWe recommend expanding analysis of shared genotypes to include neighbouring jurisdictions, and implementing whole genome sequencing to improve identification of TB transmission, recognize outbreaks, and monitor changing trends in TB epidemiology.

Tests for attention bias potentially offer more rapid assessment of affective state in animals than existing cognitive methods. An attention bias test has previously been developed for sheep and validated as a measure of anxious states. The 3 minute test assessed behavioural responses of sheep in an enclosed arena after brief exposure to the threat of a dog. Experiment 1 of the current study aimed to refine the previously developed method, removing the need for a habituation period and shortening the test duration. Sheep were given either an anxiolytic drug, an anxiogenic drug or a control treatment prior to testing to induce contrasting affective states. Differences in behaviour were found between the treatment groups within the first 45s of the test, indicating the original test duration could be shortened from 180 s. During testing, 36 of 40 animals in the control and anxiolytic groups ate the novel feed offered in the test, indicating it is not necessary to habituate animals to a feed container. Experiment 2 aimed to confirm the responses measured in the test were primarily towards the dog rather than other aspects of the test environment. Sheep exposed to an empty window at the beginning of the test behaved differently to those which were exposed to a dog, indicating sheep behaviour in the test is at least partially a response to the dog. A third group of sheep were also tested with the dog immediately after having small data loggers attached to their necks. Behaviour of these sheep did not differ from the sheep tested without loggers, indicating data logger attachment did not impact their behaviour in the test. In both experiments, treatments did not appear to modify activity (zones crossed), which we propose indicates the test was primarily detecting valence of the affective state rather than arousal.

RV1001 is a novel, potent, and selective PI3Kδ inhibitor. The purpose of this study was to evaluate the safety and efficacy of RV1001 in canine Non-Hodgkin lymphoma (NHL).Inhibition of endogenous pAKT by RV1001 in primary canine NHL cells was determined by Western blotting. A phase I study of RV1001 was performed in 21 dogs with naïve and drug resistant T and B-cell NHL to assess safety, pharmacokinetic profile, and response to therapy. The objective response rate was 62% (complete response (CR) n = 3; partial response (PR) n = 10), and responses were observed in both naïve and chemotherapy-resistant B and T cell NHL. This study provided the recommended starting dose for a phase II, non-pivotal, exploratory, open label multi-centered clinical trial in 35 dogs with naïve and drug resistant T and B-cell NHL, to further define the efficacy and safety profile of RV1001. The objective response rate in the phase II study was 77% (CR n = 1; PR n = 26). Clinical toxicities were primarily hepatobiliary and gastrointestinal, and were responsive to dose modifications and/or temporary drug discontinuation. Hepatotoxicity was the primary dose limiting toxicity.RV1001 exhibits good oral bioavailability, an acceptable safety profile, and biologic activity with associated inhibition of pAKT in dogs with B and T cell NHL. Data from these studies can be leveraged to help inform the design of future studies involving isoform-selective PI3K inhibitors in humans.

Cervical cancer outcomes remain poor among disadvantaged populations, including ethnic minorities, low-income, and underinsured women. The aim of this study was to evaluate the mechanisms that underlie the observed association between race/ethnicity and cervical cancer survival. We identified 13,698 women, ages 21 to 64 years, diagnosed with stages I-III primary cervical cancer between 2007-2013 in Surveillance, Epidemiology, and End Results (SEER). Multivariable Cox proportional hazards regression models evaluated associations between race/ethnicity (Non-Hispanic White, Non-Hispanic Black, Hispanic, Other) and cervical cancer-specific mortality. We conducted mediation analysis to calculate the mediation proportion and its 95% confidence interval. Non-Hispanic black women had an increased risk of cervical cancer-specific mortality (HR: 1.23, 95% CI: 1.08-1.39), and Hispanic women a decreased risk of dying from their disease (HR: 0.82, 95% CI: 0.72-0.93), compared with non-Hispanic white. The estimated proportion of excess cervical cancer mortality for non-Hispanic black women relative to non-Hispanic white women that was mediated by insurance was 18.6% and by treatment was 47.2%. Furthermore, non-Hispanic black women were more likely to receive radiation and less likely to receive surgery for early-stage disease. In this population-based study we found that some of the excess cervical cancer-specific mortality for non-Hispanic black women is mediated by factors such as insurance status and treatment. These findings suggest that enhancing existing insurance coverage and ensuring equal and adequate treatment in all women may be a key strategy for improving cervical cancer outcomes.

The transcription factor SOX10 plays an important role in vertebrate neural crest development, including the establishment and maintenance of the melanocyte lineage. SOX10 is also highly expressed in melanoma tumors, and SOX10 expression increases with tumor progression. The suppression of SOX10 in melanoma cells activates TGF-β signaling and can promote resistance to BRAF and MEK inhibitors. Since resistance to BRAF/MEK inhibitors is seen in the majority of melanoma patients, there is an immediate need to assess the underlying biology that mediates resistance and to identify new targets for combinatorial therapeutic approaches. Previously, we demonstrated that SOX10 protein is required for tumor initiation, maintenance and survival. Here, we present data that support phosphorylation as a mechanism employed by melanoma cells to tightly regulate SOX10 expression. Mass spectrometry identified eight phosphorylation sites contained within SOX10, three of which (S24, S45 and T240) were selected for further analysis based on their location within predicted MAPK/CDK binding motifs. SOX10 mutations were generated at these phosphorylation sites to assess their impact on SOX10 protein function in melanoma cells, including transcriptional activation on target promoters, subcellular localization, and stability. These data further our understanding of SOX10 protein regulation and provide critical information for identification of molecular pathways that modulate SOX10 protein levels in melanoma, with the ultimate goal of discovering novel targets for more effective combinatorial therapeutic approaches for melanoma patients.

OBJECTIVE:This randomised clinical trial aimed to compare the impact of two different tooth replacement strategies for partially dentate older patients namely; removable partial dentures (RPDs) and functionally orientated treatment based on the shortened dental arch (SDA) concept, on Oral Health-related Quality of Life (OHrQOL). METHODS:89 patients completed a randomised clinical trial. Patients were recruited in two centres: Cork University Dental Hospital (CUDH) and a Geriatric Day Hospital (SFDH). 44 patients were randomly allocated to the RPD group and 45 to the SDA group where adhesive bridgework was used to provide 10 pairs of occluding contacts. The impact of treatment on OHrQOL was used as the primary outcome measure. Each patient completed the Oral Health Impact Profile (OHIP-14) at baseline, 1, 6, 12 and 24 months after treatment. RESULTS:Both treatment groups reported improvements in OHIP-14 scores at 24 months (p

Protein tyrosine kinase 6 (PTK6, or BRK) is aberrantly expressed in breast cancers, and emerging as an oncogene that promotes tumor cell proliferation, migration and evasion. Both kinase-dependent and -independent functions of PTK6 in driving tumor growth have been described, therefore targeting PTK6 kinase activity by small molecule inhibitors as a therapeutic approach to treat cancers remains to be validated. In this study, we identified novel, potent and selective PTK6 kinase inhibitors as a means to investigate the role of PTK6 kinase activity in breast tumorigenesis. We report here the crystal structures of apo-PTK6 and inhibitor-bound PTK6 complexes, providing the structural basis for small molecule interaction with PTK6. The kinase inhibitors moderately suppress tumor cell growth in 2D and 3D cell cultures. However, the tumor cell growth inhibition shows neither correlation with the PTK6 kinase activity inhibition, nor the total or activated PTK6 protein levels in tumor cells, suggesting that the tumor cell growth is independent of PTK6 kinase activity. Furthermore, in engineered breast tumor cells overexpressing PTK6, the inhibition of PTK6 kinase activity does not parallel the inhibition of tumor cell growth with a >500-fold shift in compound potencies (IC50 values). Overall, these findings suggest that the kinase activity of PTK6 does not play a significant role in tumorigenesis, thus providing important evidence against PTK6 kinase as a potential therapeutic target for breast cancer treatment.

OBJECTIVE:Our objective was to test the primary hypothesis that maternal non-left, in particular supine going-to-sleep position, would be a risk factor for late stillbirth (≥28 weeks of gestation). METHODS:A multicentre case-control study was conducted in seven New Zealand health regions, between February 2012 and December 2015. Cases (n = 164) were women with singleton pregnancies and late stillbirth, without congenital abnormality. Controls (n = 569) were women with on-going singleton pregnancies, randomly selected and frequency matched for health region and gestation. The primary outcome was adjusted odds of late stillbirth associated with self-reported going-to-sleep position, on the last night. The last night was the night before the late stillbirth was thought to have occurred or the night before interview for controls. Going-to-sleep position on the last night was categorised as: supine, left-side, right-side, propped or restless. Multivariable logistic regression adjusted for known confounders. RESULTS:Supine going-to-sleep position on the last night was associated with increased late stillbirth risk (adjusted odds ratios (aOR) 3.67, 95% confidence interval (CI) 1.74 to 7.78) with a population attributable risk of 9.4%. Other independent risk factors for late stillbirth (aOR, 95% CI) were: BMI (1.04, 1.01 to 1.08) per unit, maternal age ≥40 (2.88, 1.31 to 6.32), birthweight

Apolipoprotein D (ApoD) has been proposed as a predictor of breast cancer recurrence among estrogen receptor-positive (ER+), tamoxifen-treated patients.We conducted a population-based case-control study nested in a population of 11,251 women aged 35-69 years at diagnosis with Stage I-III breast cancer between 1985 and 2001 on Denmark's Jutland Peninsula and registered with the Danish Breast Cancer Cooperative Group. We identified 541 recurrent or contralateral breast cancers cases among women with ER+ disease treated with tamoxifen for at least 1 year and 300 cases in women with ER- disease never treated with tamoxifen. We matched one control subject per case and assessed ApoD expression in the tumor cell nucleus and cytoplasm using tissue microarray immunohistochemistry. We computed the odds ratio (OR) associating ApoD expression with recurrence and adjusted for potential confounding using logistic regression.Cytoplasmic ApoD expression was seen in 68% of ER+ tumors, in 66% of ER- tumors, and in 66% of controls across both groups. In women with ER+ tumors, the associations of cytoplasmic ApoD expression with recurrence (OR = 1.0; 95% CI = 0.7 to 1.4) and increasing cytoplasmic expression with recurrence (OR = 1.0; 95% CI = 0.996 to 1.003) were null, as were those for women with ER- tumors. Associations for nuclear ApoD expression and combined nuclear and cytoplasmic expression were similarly near-null.ApoD expression is likely not a predictor of recurrence in tamoxifen-treated patients.This study eliminates the previously suggested marker ApoD as a predictor of recurrence among tamoxifen-treated women.

Bacillus cereus isolates have been described harboring Bacillus anthracis toxin genes, most notably B. cereus G9241, and capable of causing severe and fatal pneumonias. This report describes the characterization of a B. cereus isolate, BcFL2013, associated with a naturally occurring cutaneous lesion resembling an anthrax eschar. Similar to G9241, BcFL2013 is positive for the B. anthracis pXO1 toxin genes, has a multi-locus sequence type of 78, and a pagA sequence type of 9. Whole genome sequencing confirms the similarity to G9241. In addition to the chromosome having an average nucleotide identity of 99.98% when compared to G9241, BcFL2013 harbors three plasmids with varying homology to the G9241 plasmids (pBCXO1, pBC210 and pBFH_1). This is also the first report to include serologic testing of patient specimens associated with this type of B. cereus infection which resulted in the detection of anthrax lethal factor toxemia, a quantifiable serum antibody response to protective antigen (PA), and lethal toxin neutralization activity.

Parkinson's disease (PD) is associated with deficits in visuospatial attention. It is as yet unknown whether these attentional deficits begin at a perceptual level or instead reflect disruptions in oculomotor or higher-order processes. In the present study, non-demented individuals with PD and matched normal control adults (NC) participated in two tasks requiring sustained visuospatial attention, both based on a multiple object tracking paradigm. Eye tracking was used to ensure central fixation. In Experiment 1 (26 PD, 21 NC), a pair of identical red dots (one target, one distractor) rotated randomly for three seconds at varied speeds. The task was to maintain the identity of the sole target, which was labeled prior to each trial. PD were less accurate than NC overall (p = .049). When considering only trials where fixation was maintained, however, there was no significant group difference, suggesting that the deficit's origin is closely related to oculomotor processing. To determine whether PD had additional impairment in multifocal attention, in Experiment 2 (25 PD, 15 NC), two targets were presented along with distractors at a moderate speed, along with a control condition in which dots remained stationary. PD were less accurate than NC for moving (p = 0.02) but not stationary targets. This group difference remained significant when considering only trials where fixation was maintained, suggesting the source of the PD deficit was independent from oculomotor processing. Taken together, the results implicate separate mechanisms for single vs. multiple object tracking deficits in PD.

Glucagon-like Peptide-1 mimetics increase insulin secretion and reduces body weight in humans. In lean, healthy cats, short-term treatment has produced similar results, whereas the effect in obese cats or with extended duration of treatment is unknown. Here, prolonged (12 weeks) treatment with the Glucagon-like Peptide-1 mimetic, exenatide, was evaluated in 12 obese, but otherwise healthy, client-owned cats. Cats were randomized to exenatide (1.0 μg/kg) or placebo treatment twice daily for 12 weeks. The primary endpoint was changes in insulin concentration; the secondary endpoints were glucose homeostasis, body weight, body composition as measured by dual-energy x-ray absorptiometry and overall safety. An intravenous glucose tolerance test (1 g/kg body weight) was conducted at week 0 and week 12. Exenatide did not change the insulin concentration, plasma glucose concentration or glucose tolerance (P>0.05 for all). Exenatide tended to reduce body weight on continued normal feeding. Median relative weight loss after 12 weeks was 5.1% (range 1.7 to 8.4%) in the exenatide group versus 3.2% (range -5.3 to 5.7%) in the placebo group (P = 0.10). Body composition and adipokine levels were unaffected by exenatide (P>0.05). Twelve weeks of exenatide was well-tolerated, with only two cases of mild, self-limiting gastrointestinal signs and a single case of mild hypoglycemia. The long-term insulinotropic effect of exenatide appeared less pronounced in obese cats compared to previous short-term studies in lean cats. Further investigations are required to fully elucidate the effect on insulin secretion, glucose tolerance and body weight in obese cats.

Hepcidin is the key regulator of iron homeostasis but data are limited regarding its temporal response to iron therapy, and response to intravenous versus oral iron. In the 56-week, open-label, multicenter, prospective, randomized FIND-CKD study, 626 anemic patients with non-dialysis dependent chronic kidney disease (ND-CKD) and iron deficiency not receiving an erythropoiesis stimulating agent were randomized (1:1:2) to intravenous ferric carboxymaltose (FCM), targeting higher (400-600μg/L) or lower (100-200μg/L) ferritin, or to oral iron. Serum hepcidin levels were measured centrally in a subset of 61 patients. Mean (SD) baseline hepcidin level was 4.0(3.5), 7.3(6.4) and 6.5(5.6) ng/mL in the high ferritin FCM (n = 17), low ferritin FCM (n = 16) and oral iron group (n = 28). The mean (SD) endpoint value (i.e. the last post-baseline value) was 26.0(9.1),15.7(7.7) and 16.3(11.0) ng/mL, respectively. The increase in hepcidin from baseline was significantly smaller with low ferritin FCM or oral iron vs high ferritin FCM at all time points up to week 52. Significant correlations were found between absolute hepcidin and ferritin values (r = 0.65, p

Seals and humans often target the same food resource, leading to competition. This is of mounting concern with fish stocks in global decline. Grey seals were tracked from southeast Ireland, an area of mixed demersal and pelagic fisheries, and overlap with fisheries on the Celtic Shelf and Irish Sea was assessed. Overall, there was low overlap between the tagged seals and fisheries. However, when we separate active (e.g. trawls) and passive gear (e.g. nets, lines) fisheries, a different picture emerged. Overlap with active fisheries was no different from that expected under a random distribution, but overlap with passive fisheries was significantly higher. This suggests that grey seals may be targeting the same areas as passive fisheries and/or specifically targeting passive gear. There was variation in foraging areas between individual seals suggesting habitat partitioning to reduce intra-specific competition or potential individual specialisation in foraging behaviour. Our findings support other recent assertions that seal/fisheries interactions in Irish waters are an issue in inshore passive fisheries, most likely at the operational and individual level. This suggests that seal population management measures would be unjustifiable, and mitigation is best focused on minimizing interactions at nets.

Numerous studies have identified the effects of prematurity on the neonate's physical health, however few studies have explored the effects of prematurity on both the physical and mental health of the child as they develop. Secondary analysis of data from the Millennium Cohort Study, a longitudinal study of infants (n = 18 818, born 2000-2002 in the United Kingdom) was performed. Effects of gestational age at birth on health outcomes at 5 years were measured using parental rating of their children's general health and severity of behavior problems. The association between parent's general health ratings and behavior problem ratings was low: 86% of those reporting serious behavior problems (5% of the sample, n = 764) rated their child as being in excellent, very good, or good health. Still, a gradient of increasing risk of poorer outcome with decreasing gestational age was observed for a composite health measure (poor/fair health and/or serious behavior problems), suggesting an association with prematurity for this composite assessment of health status. The greatest contribution to the childhood composite health measure at 5 years was for children born at 32-36 weeks gestation: population attributable fractions for having poor outcomes was 3.4% (Bonferroni-adjusted 95% confidence interval 1.1%-6.2%), compared to 1% (0.2-2.3) for birth at less than 32 weeks. Results suggest that preterm children, by school entry, are not only at high risk of physical health problems, but also of behavioral health problems. The recognition of, and response to comprehensive health and well-being outcomes related to prematurity are important in order to correctly plan and deliver adequate paediatric health services and policies.

Defences against the bacteria that usually infect the endometrium of postpartum cattle are impaired when there is metabolic energy stress, leading to endometritis and infertility. The endometrial response to bacteria depends on innate immunity, with recognition of pathogen-associated molecular patterns stimulating inflammation, characterised by secretion of interleukin (IL)-1β, IL-6 and IL-8. How metabolic stress impacts tissue responses to pathogens is unclear, but integration of energy metabolism and innate immunity means that stressing one system might affect the other. Here we tested the hypothesis that homeostatic pathways integrate energy metabolism and innate immunity in bovine endometrial tissue. Glucose deprivation reduced the secretion of IL-1β, IL-6 and IL-8 from ex vivo organ cultures of bovine endometrium challenged with the pathogen-associated molecular patterns lipopolysaccharide and bacterial lipopeptide. Endometrial inflammatory responses to lipopolysaccharide were also reduced by small molecules that activate or inhibit the intracellular sensor of energy, AMP-activated protein kinase (AMPK). However, inhibition of mammalian target of rapamycin, which is a more global metabolic sensor than AMPK, had little effect on inflammation. Similarly, endometrial inflammatory responses to lipopolysaccharide were not affected by insulin-like growth factor-1, which is an endocrine regulator of metabolism. Interestingly, the inflammatory responses to lipopolysaccharide increased endometrial glucose consumption and induced the Warburg effect, which could exacerbate deficits in glucose availability in the tissue. In conclusion, metabolic energy stress perturbed inflammatory responses to pathogen-associated molecular patterns in bovine endometrial tissue, and the most fundamental regulators of cellular energy, glucose availability and AMPK, had the greatest impact on innate immunity.

Ostracoda (bivalved Crustacea) comprise a significant part of the benthic meiofauna in the Pacific-Arctic region, including more than 50 species, many with identifiable ecological tolerances. These species hold potential as useful indicators of past and future ecosystem changes. In this study, we examined benthic ostracodes from nearly 300 surface sediment samples, >34,000 specimens, from three regions—the northern Bering, Chukchi and Beaufort Seas—to establish species' ecology and distribution. Samples were collected during various sampling programs from 1970 through 2018 on the continental shelves at 20 to ~100m water depth. Ordination analyses using species' relative frequencies identified six species, Normanicythere leioderma, Sarsicytheridea bradii, Paracyprideis pseudopunctillata, Semicytherura complanata, Schizocythere ikeyai, and Munseyella mananensis, as having diagnostic habitat ranges in bottom water temperatures, salinities, sediment substrates and/or food sources. Species relative abundances and distributions can be used to infer past bottom environmental conditions in sediment archives for paleo-reconstructions and to characterize potential changes in Pacific-Arctic ecosystems in future sampling studies. Statistical analyses further showed ostracode assemblages grouped by the summer water masses influencing the area. Offshore-to-nearshore transects of samples across different water masses showed that complex water mass characteristics, such as bottom temperature, productivity, as well as sediment texture, influenced the relative frequencies of ostracode species over small spatial scales. On the larger biogeographic scale, synoptic ordination analyses showed dominant species—N. leioderma (Bering Sea), P. pseudopunctillata (offshore Chukchi and Beaufort Seas), and S. bradii (all regions)—remained fairly constant over recent decades. However, during 2013–2018, northern Pacific species M. mananensis and S. ikeyai increased in abundance by small but significant proportions in the Chukchi Sea region compared to earlier years. It is yet unclear if these assemblage changes signify a meiofaunal response to changing water mass properties and if this trend will continue in the future. Our new ecological data on ostracode species and biogeography suggest these hypotheses can be tested with future benthic monitoring efforts. [ABSTRACT FROM AUTHOR]