Author Correction: Epoxyeicosatrienoic acids enhance embryonic haematopoiesis and adult marrow engraftment.

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.

Technology, data, people, and partnerships in addressing unmet social needs within Medicaid Managed Care.

BACKGROUND: Individuals with unmet social needs experience adverse health outcomes and are subject to greater inequities in health and social outcomes. Given the high prevalence of unmet needs among Medicaid enrollees, many Medicaid managed care organizations (MCOs) are now screening enrollees for unmet social needs and connecting them to community-based organizations (CBOs) with knowledge and resources to address identified needs. The use of screening and referral technology and data sharing are often considered key components in programs integrating health and social services. Despite this emphasis on technology and data collection, research suggests substantial barriers exist in operationalizing effective systems. METHODS: We used qualitative methods to examine cross-sector perspectives on the use of data and technology to facilitate MCO and CBO partnerships in Kentucky, a state with high Medicaid enrollment, to address enrollee social needs. We recruited participants through targeted sampling, and conducted 46 in-depth interviews with 26 representatives from all six Kentucky MCOs and 20 CBO leaders. Qualitative descriptive analysis, an inductive approach, was used to identify salient themes. RESULTS: We found that MCOs and CBOs have differing levels of need for data, varying incentives for collecting and sharing data, and differing valuations of what data can or should do. Four themes emerged from interviewees' descriptions of how they use data, including 1) to screen for patient needs, 2) to case manage, 3) to evaluate the effectiveness of programs, and 4) to partner with each other. Underlying these data use themes were areas of alignment between MCOs/CBOs, areas of incongruence, and areas of tension (both practical and ideological). The inability to interface with community partners for data privacy and ownership concerns contributes to division. Our findings suggest a disconnect between MCOs and CBOs regarding terms of their technology interfacing despite their shared mission of meeting the unmet social needs of enrollees. CONCLUSIONS: While data and technology can be used to identify enrollee needs and determine the most critical need, it is not sufficient in resolving challenges. People and relationships across sectors are vital in connecting enrollees with the community resources to resolve unmet needs.

Preparing community pharmacy teams for health information exchange (HIE).

BACKGROUND: Health information exchanges (HIEs) facilitate health care professionals' electronic sharing of patient information across different organizations. When community pharmacists have access to HIE, they can further contribute to improved patient outcomes. However, several implementation challenges are noted, which impede sustained pharmacist access to HIE. To our knowledge, no bidirectional HIE interface design and pharmacy team-informed implementation process has been documented. In response, our research team designed and developed an HIE interface prototype for use specifically by community pharmacy teams to access local HIE data through their pharmacy dispensing software. OBJECTIVES: To 1) identify barriers, facilitators, and recommendations for using HIE data in community pharmacies and 2) create a curated list of resources addressing identified implementation needs to aid future implementation of a fully functional, bidirectional HIE interface by community pharmacy teams. METHODS: Pharmacists, pharmacy technicians, and patients from three pharmacy sites within the Community Pharmacy Enhanced Services Network of Indiana participated in individual semi-structured interviews. Interview questions were mapped to select constructs across all domains of the Consolidated Framework for Implementation Research. Interview transcripts were deductively coded. A subset of participants participated in Evidence-Based Quality Improvement sessions to iteratively update planned resource items needed to support future HIE implementation. RESULTS: We interviewed 23 total participants: 8 pharmacists, 8 pharmacy technicians, and 7 patients. Five facilitators, four barriers, and two recommendations were identified. These were further characterized into four key implementation needs: instruction on how to use HIE; guidance on workflow and team roles; resources that are patient-facing; and resources that are provider-facing, resulting in 16 planned implementation resources. CONCLUSION: Our study provides the first-of-its-kind list of pharmacy team-informed resources to facilitate sustainability and scalability of HIE implementation in community pharmacies.

Remote Virtual Simulation With Prelicensure Nursing Students During Rapid Course Transition.

ABSTRACT: The advent of COVID-19 required educational programs to rapidly transition courses to the remote environment. A postpartum hemorrhage simulation used within a traditional prelicensure bachelor of science in nursing program was rapidly transitioned to the remote virtual format to meet required social distancing guidelines. This quasi-experimental study examined student knowledge before and after participation in a remote virtual simulation (RVS) with a postanalysis of student confidence and satisfaction. RVS can increase student knowledge and provide adequate student satisfaction. However, hands-on learning appears to result in higher student confidence and satisfaction compared to RVS.

The interaction between affective lability and eating expectancies predicts binge eating.

Both affective lability and eating expectancies have been found to predict binge eating. There is the additional possibility that the joint effect of affective lability and eating expectancies incurs further risk: perhaps expectancies for affective relief from eating operate more strongly in those experiencing frequent, rapid shifts in emotion. In the current study, we tested whether such a joint effect predicts binge eating prospectively in college students. We assessed affective lability, eating expectancies, and binge eating in 358 college students at two time points during the first year of college (e.g., December and April). The interaction of affective lability and eating expectancies in December predicted binge eating 4 months later in April. The influence of eating expectancies on binge eating was stronger at higher levels of affective lability. Findings offer support to the hypothesis that risk factors may transact to further elevate risk for eating disorder behaviors.Clinical implicationsThe interaction of affective lability and eating expectancies predicts binge eatingRisk factors may interact to further increase binge eatingIdentification of co-occurring risk factors may have vital treatment implications.

Estimates of locus coeruleus function with functional magnetic resonance imaging are influenced by localization approaches and the use of multi-echo data.

The locus coeruleus (LC) plays a central role in regulating human cognition, arousal, and autonomic states. Efforts to characterize the LC's function in humans using functional magnetic resonance imaging have been hampered by its small size and location near a large source of noise, the fourth ventricle. We tested whether the ability to characterize LC function is improved by employing neuromelanin-T1 weighted images (nmT1) for LC localization and multi-echo functional magnetic resonance imaging (ME-fMRI) for estimating intrinsic functional connectivity (iFC). Analyses indicated that, relative to a probabilistic atlas, utilizing nmT1 images to individually localize the LC increases the specificity of seed time series and clusters in the iFC maps. When combined with independent components analysis (ME-ICA), ME-fMRI data provided significant improvements in the temporal signal to noise ratio and DVARS relative to denoised single echo data (1E-fMRI). The effects of acquiring nmT1 images and ME-fMRI data did not appear to only reflect increases in power: iFC maps for each approach overlapped only moderately. This is consistent with findings that ME-fMRI offers substantial advantages over 1E-fMRI acquisition and denoising. It also suggests that individually identifying LC with nmT1 scans is likely to reduce the influence of other nearby brainstem regions on estimates of LC function.

A Phase II Trial of Once Weekly Hypofractionated Breast Irradiation for Early Stage Breast Cancer.

PURPOSE: To report an interim analysis of a phase II trial of once weekly, hypofractionated breast irradiation (WH-WBI) following breast conserving surgery (BCS). METHODS: Patients had stage 0-II breast cancer treated with breast BCS with negative margins. WH-WBI was 28.5 or 30Gy delivered to the whole breast using tangential beams with no elective coverage of lymph nodes. The primary endpoint was ipsilateral breast tumor recurrence (IBTR). Secondary endpoints were distant disease-free survival (DDFS), recurrence free survival (RFS), overall survival (OS), adverse events and cosmesis. RESULTS: From 2011 to 2015, 158 patients received WH-WBI. Median follow up was 4.4 years (range 0.2-8.1). Stage distribution was DCIS 22%; invasive pN0 68%; invasive pN1 10%. 80 patients received 30 Gy and 78 received 28.5 Gy with median follow up times of 5.6 and 3.7 years, respectively. There were 5 IBTR events, all in the 30 Gy group. The 5- and 7- year risks of IBRT for all patients were 2.2% (95% CI 0.6-5.8) and 6.0% (95% CI 1.1-17.2), respectively. The 7-year rates of DDFS, RFS, and OS were 96.3%, 91.5% and 89.8%, respectively. Improvement in IBTR-free time was seen in DCIS, lobular histology, low grade tumors, Her2 negative tumors and 28.5 Gy dose (all p < 0.0001). CONCLUSIONS: Disease-specific outcomes after WH-WBI are favorable and parallel those seen with conventional radiation techniques for stage 0-II breast cancer.

Epoxyeicosatrienoic acids enhance embryonic haematopoiesis and adult marrow engraftment.

Haematopoietic stem and progenitor cell (HSPC) transplant is a widely used treatment for life-threatening conditions such as leukaemia; however, the molecular mechanisms regulating HSPC engraftment of the recipient niche remain incompletely understood. Here we develop a competitive HSPC transplant method in adult zebrafish, using in vivo imaging as a non-invasive readout. We use this system to conduct a chemical screen, and identify epoxyeicosatrienoic acids (EETs) as a family of lipids that enhance HSPC engraftment. The pro-haematopoietic effects of EETs were conserved in the developing zebrafish embryo, where 11,12-EET promoted HSPC specification by activating a unique activator protein 1 (AP-1) and runx1 transcription program autonomous to the haemogenic endothelium. This effect required the activation of the phosphatidylinositol-3-OH kinase (PI(3)K) pathway, specifically PI(3)Kγ. In adult HSPCs, 11,12-EET induced transcriptional programs, including AP-1 activation, which modulate several cellular processes, such as migration, to promote engraftment. Furthermore, we demonstrate that the EET effects on enhancing HSPC homing and engraftment are conserved in mammals. Our study establishes a new method to explore the molecular mechanisms of HSPC engraftment, and discovers a previously unrecognized, evolutionarily conserved pathway regulating multiple haematopoietic generation and regeneration processes. EETs may have clinical application in marrow or cord blood transplantation.

Affect-Based Problem Drinking Risk: The Reciprocal Relationship between Affective Lability and Problem Drinking.

AIMS: Negative affect has been implicated in risk for the development of problematic drinking behavior. Furthermore, there is evidence for reciprocal relationships between negative affect and problem drinking, such that engagement in problem drinking also predicts increases in negative affect. However, affective models of risk often fail to consider affective lability-the experience of rapidly changing mood. Although affective lability appears to increase risk for problem drinking, it is unknown if this relationship persists above and beyond other affect-related constructs (e.g. depression, anxiety) and if it is reciprocal in nature. Accordingly, we used a longitudinal survey design to examine (a) if affective lability predicts problem drinking above and beyond depression and anxiety and (b) if affective lability and problem drinking demonstrate a reciprocal relationship. METHODS: First-year college students (n = 358) participated in a three wave longitudinal study. We constructed a structural equation model (SEM) of a random intercept cross-lagged panel model to test our hypotheses. RESULTS: Consistent with our hypotheses, affective lability predicted increases in problem drinking while anxiety and depression did not. Problem drinking and affective lability demonstrated a reciprocal relationship in which increases in one predicted increases in the other at subsequent time points. This relationship was present beyond the predictive effects of anxiety or depression. CONCLUSIONS: Affective lability appears to be an important affect-based predictor of problem drinking, and there may be a reciprocal, risk-enhancing relationship between affective lability and problem drinking.Components of negative affect, such as depression or anxiety, have been shown to predict risk for problem drinking, and vice versa. A less considered construct, affective lability, predicted problem drinking while anxiety and depression did not add any predictive power. Problem drinking and affective lability also appeared to demonstrate a reciprocal relationship.

Transitioning Newly Licensed Nurses Into Practice Through an Academic-Practice Partnership.

ABSTRACT: Research illustrates a clear gap between academic and practice facilities concerning new graduate nurses. Nursing programs are charged with training nursing graduates who can provide safe, quality patient care. One way to enhance the quality of patient care and aid with retention of new graduate nurses in health care facilities is through academic-practice partnerships. This article describes the planning, implementation, and evaluation of a partnership between a health care facility and an associate of applied science nursing degree program to aid with registered nurse retention and quality patient care.

The General Factor of Psychopathology.

An important advance in understanding and defining mental disorders has been the development of empirical approaches to mapping dimensions of dysfunction and their interrelatedness. Such empirical approaches have consistently observed intercorrelations among the many forms of psychopathology, leading to the identification of a general factor of psychopathology (the p factor). In this article, we review empirical support for p, including evidence for the stability and criterion validity of p. Further, we discuss the strong relationship between p and both the general factor of personality and the general factor of personality disorder, substantive interpretations of p, and the potential clinical utility of p. We posit that proposed substantive interpretations of p do not explain the full range of symptomatology typically included in p. The most plausible explanation is that p represents an index of impairment that has the potential to inform the duration and intensity of a client's mental health treatment.

Adherence to anti-estrogen therapy in women with hormone receptor-positive breast cancer utilizing bubble packaging: a pilot study.

PURPOSE: This pilot study evaluated adherence to anti-estrogen therapy in women with hormone receptor-positive breast cancer utilizing bubble packaging. METHODS: This was a single-arm prospective investigational pilot study that enrolled 86 patients between August 2012 and April 2014. Descriptive statistics for patient age, race, insurance, stage, duration of treatment, and comorbidities were computed. All patients received routine prescriptions in a "bubble" pack or daily blister pack dispensed by one pharmacy. Participants were considered adherent if they had taken ≥ 80% of the dispensed drug. Disease-free survival (DFS) and overall survival (OS) data were obtained at 78 months. RESULTS: Fifty patients were included in the analysis. The overall adherence rate was 97%. None of the variables examined (race, age, insurance status, and stage) had an impact on adherence rate. Only duration of endocrine therapy had a marginal effect on adherence (p value = 0.06). The late cohort (duration of therapy 37-60 months) was least likely to be compliant at 89.53%. Our 5-year DFS was 94% and 5-year OS was 96%. There was no statistically significant difference in DFS and OS between patients with adherence rate > 90% and < 90%. CONCLUSION: Adherence rate to bubble packaging was higher than that in historical studies. Although this is a single-arm pilot study, these data suggest bubble packaging of anti-estrogen may be a reasonable option to improve adherence in hormone receptor-positive breast cancer patients.

What about the family in youth gender diversity? A literature review.

Background: Previous research has suggested that gender diversity affects everyone in the family, with positive mental health and global outcomes for gender diverse youth reliant on receiving adequate family support and validation. Although the individual mental health, treatment and outcomes for gender diverse youth have received recent research attention, much less is known about a family perspective. Hence, a review of the literature exploring youth gender diversity from a family perspective is warranted. Aims: To systematically identify, appraise and summarize all published literature primarily exploring gender diversity in young people under the age of 18 years, as well as selected literature pertaining to a family understanding. Methods: Six electronic databases (CINAHL, MEDLINE, EMBASE, PsycINFO, SCOPUS, Web of Science) were searched for relevant literature pertaining to youth under the age of 18 years. Results: Research evidence was consistently found to support the beneficial effects of a supportive family system for youth experiencing gender diversity, and a systemic understanding and approach for professionals. Conversely, lack of family support was found to lead to poorer mental health and adverse life outcomes. Few articles explored the experience of siblings under the age of 18 years. Discussion: This literature review is the first to critically evaluate and summarize all published studies which adopted a family understanding of youth gender diversity. The review highlighted a lack of current research and the need for further targeted research, which utilizes a systemic clinical approach to guide support for gender diverse youth and family members.

Comparing treatment fidelity between study arms of a randomized controlled clinical trial for stroke family caregivers.

OBJECTIVE: To compare treatment fidelity among treatment arms in the Telephone Assessment and Skill-Building Kit study for stroke caregivers (TASK II) with respect to: 1) protocol adherence; 2) intervention dosage and 3) nurse intervener perspectives. DESIGN: A randomized controlled clinical trial design. SETTING: Urban, community, midwestern United States. SUBJECTS: A total of 254 stroke caregivers (mean ±SD age, 54.4 ±11.8 years), 55 (22.0%) males and 199 (78.4%) females) randomized to the TASK II intervention (n=123) or an Information, Support, and Referral comparison group (n=131). INTERVENTIONS: TASK II participants received the TASK II Resource Guide; Information, Support, and Referral participants received a standard caregiver brochure. At approximately 8 weeks after discharge, both groups received 8 weekly calls from a nurse, with a booster call 4 weeks later. MEASURES: Protocol adherence was evaluated with the TASK II Checklist for Monitoring Adherence. Intervention dosage was measured by the number of minutes caregivers spent reading materials and talking with the nurse. Nurse intervener perspectives were obtained through focus groups. RESULTS: Protocol adherence was 80% for the TASK II and 92% for the Information, Support, and Referral. As expected, intervention dosage differed between TASK II and Information, Support, and Referral with respect to caregiver time spent reading materials (t=-6.49; P<.001) and talking with the nurse (t=-7.38; P<.001). Focus groups with nurses yielded further evidence for treatment fidelity and recommendations for future trials. CONCLUSIONS: These findings substantiate treatment fidelity in both study arms of the TASK II stroke caregiver intervention trial (NIH R01NR010388; ClinicalTrials.govNCT01275495).

Nonsuicidal Self-injury as a Risk Factor for Purging Onset: Negatively Reinforced Behaviours that Reduce Emotional Distress.

Both nonsuicidal self-injury (NSSI) and purging behaviour are thought to involve harm to the self. The acquired capability for self-harm model holds that engaging in one self-harming behaviour increases the capability to tolerate harm to the self, thus increasing risk for engaging on other such behaviours. In addition, both behaviours are thought to serve the similar function of relief from distress. We thus tested whether engagement in one of these behaviours predicts the subsequent onset of the other. In a longitudinal design, 1158 first-year college women were assessed for purging and NSSI at two time points. Engagement in NSSI at time 1 predicted the college onset of purging behaviour 9 months later (OR = 2.20, p < .04, CI = 1.07-4.19) beyond prediction from time 1 binge behaviour, and purging behaviour at time 1 predicted the subsequent onset of NSSI (OR = 6.54, p < .01, CI = 1.71-25.04). These findings are consistent with the acquired capability for harm model and with the possibility that the two behaviours serve a similar function.

Risk factors for the development of uterine cancer in breast cancer survivors: an army of women study.

BACKGROUND: Our study compares breast cancer survivors without a secondary diagnosis of uterine cancer (BC) to breast cancer survivors with a diagnosis of uterine cancer (BUC) to determine clinical characteristics that increase the odds of developing uterine cancer. METHODS: A total of 7,228 breast cancer survivors were surveyed. A case-control study was performed with 173 BUC patients matched by age and race in a 1:5 ratio to 865 BC patients. Multivariable logistic regression examined which factors influence the odds of developing uterine cancer. RESULTS: A total of 5,980 (82.3 %) women did not have a previous hysterectomy at the time of breast cancer diagnosis, of which 173 (2.9 %) subsequently developed uterine cancer. There was no significant difference in body mass index (BMI) (34.4 vs. 34.1, p = 0.388) or age (52.3 vs. 52.3 years, p = 0.999) between the two groups. Increased odds for developing uterine cancer were found in patients with a personal history of hypertension [odds ratio (OR) = 1.62, 95 % confidence interval (CI) 1.45-2.70, p < 0.001], gallbladder disease (OR = 1.30, 95 % CI 1.14-1.55, p = 0.005), and thyroid disease (OR = 1.55, 95 % CI 1.37-1.69, p < 0.001). More than 80 % of women in both groups expressed a desire for a blood test to estimate the risk of uterine cancer (80.4 % BUC vs. 91.2 % BC, p < 0.001). CONCLUSIONS: Hypertension, gallbladder disease, and thyroid disease in breast cancer survivors increase the odds of developing uterine cancer. Breast cancer survivors also express significant interest in potential serum tests to assess the risk of developing uterine cancer.

TiF1-gamma plays an essential role in murine hematopoiesis and regulates transcriptional elongation of erythroid genes.

Transcriptional regulators play critical roles in the regulation of cell fate during hematopoiesis. Previous studies in zebrafish have identified an essential role for the transcriptional intermediary factor TIF1γ in erythropoiesis by regulating the transcription elongation of erythroid genes. To study if TIF1γ plays a similar role in murine erythropoiesis and to assess its function in other blood lineages, we generated mouse models with hematopoietic deletion of TIF1γ. Our results showed a block in erythroid maturation in the bone marrow following tif1γ deletion that was compensated with enhanced spleen erythropoiesis. Further analyses revealed a defect in transcription elongation of erythroid genes in the bone marrow. In addition, loss of TIF1γ resulted in defects in other blood compartments, including a profound loss of B cells, a dramatic expansion of granulocytes and decreased HSC function. TIF1γ exerts its functions in a cell-autonomous manner as revealed by competitive transplantation experiments. Our study therefore demonstrates that TIF1γ plays essential roles in multiple murine blood lineages and that its function in transcription elongation is evolutionally conserved.

Associations between CYP19A1 polymorphisms, Native American ancestry, and breast cancer risk and mortality: the Breast Cancer Health Disparities Study.

The cytochrome p450 family 19 gene (CYP19A1) encodes for aromatase, which catalyzes the final step in estrogen biosynthesis and conversion of androgens to estrogens. Genetic variation in CYP19A1 is linked to higher circulating estrogen levels and increased aromatase expression. Using data from the Breast Cancer Health Disparities Study, a consortium of three population-based case-control studies in the United States (n = 3,030 non-Hispanic Whites; n = 2,893 Hispanic/Native Americans (H/NA) and Mexico (n = 1,810), we examined influence of 25 CYP19A1 tagging single-nucleotide polymorphisms (SNPs) on breast cancer risk and mortality, considering NA ancestry. Odds ratios (ORs) and 95 % confidence intervals (CIs) and hazard ratios estimated breast cancer risk and mortality. After multiple comparison adjustment, none of the SNPs were significantly associated with breast cancer risk or mortality. Two SNPs remained significantly associated with increased breast cancer risk in women of moderate to high NA ancestry (≥29 %): rs700518, ORGG 1.36, 95 % CI 1.11-1.67 and rs11856927, ORGG 1.35, 95 % CI 1.05-1.72. A significant interaction was observed for rs2470144 and menopausal status (p adj = 0.03); risk was increased in postmenopausal (ORAA 1.22, 95 % CI 1.05-1.14), but not premenopausal (ORAA 0.78, 95 % CI 0.64-0.95) women. The absence of an overall association with CYP19A1 and breast cancer risk is similar to previous literature. However, this analysis provides support that variation in CYP19A1 may influence breast cancer risk differently in women with moderate to high NA ancestry. Additional research is warranted to investigate the how variation in an estrogen-regulating gene contributes to racial/ethnic disparities in breast cancer.

Two pathways toward impulsive action: an integrative risk model for bulimic behavior in youth.

BACKGROUND: This study provides an integrative review of existing risk factors and models for bulimia nervosa (BN) in young girls. We offer a new model for BN that describes two pathways of risk that may lead to the initial impulsive act of binge eating and purging in children and adolescents. SCOPE: We conducted a selective literature review, focusing on existing and new risk processes for BN in this select population. FINDINGS: We identify two ways in which girls increase their risk to begin engaging in the impulsive behavior of binge eating and purging. The first is state-based: the experience of negative mood, in girls attempting to restrain eating, leads to the depletion of self-control and thus increased risk for loss of control eating. The second is personality-based: elevations on the trait of negative urgency, or the tendency to act rashly when distressed, increase risk, particularly in conjunction with high-risk psychosocial learning. We then briefly discuss how these behaviors are reinforced, putting girls at further risk for developing BN. CONCLUSIONS: We highlight several areas in which further inquiry is necessary, and we discuss the clinical implications of the new risk model we described.

Nonlinear changes in pupillary attentional orienting responses across the lifespan.

The cognitive aging process is not necessarily linear. Central task-evoked pupillary responses, representing a brainstem-pupil relationship, may vary across the lifespan. Thus we examined, in 75 adults ranging in age from 19 to 86, whether task-evoked pupillary responses to an attention task may serve in as an index of cognitive aging. This is because the locus coeruleus (LC), located in the brainstem, is not only among the earliest sites of degeneration in pathological aging, but also supports both attentional and pupillary behaviors. We assessed brief, task-evoked phasic attentional orienting to behaviorally relevant and irrelevant auditory tones, stimuli known specifically to recruit the LC in the brainstem and evoke pupillary responses. Due to potential nonlinear changes across the lifespan, we used a novel data-driven analysis on 6 dynamic pupillary behaviors on 10% of the data to reveal cut off points that best characterized the three age bands: young (19-41 years old), middle aged (42-68 years old), and older adults (69 + years old). Follow-up analyses on independent data, the remaining 90%, revealed age-related changes such as monotonic decreases in tonic pupillary diameter and dynamic range, along with curvilinear phasic pupillary responses to the behaviorally relevant target events, increasing in the middle-aged group and then decreasing in the older group. Additionally, the older group showed decreased differentiation of pupillary responses between target and distractor events. This pattern is consistent with potential compensatory LC activity in midlife that is diminished in old age, resulting in decreased adaptive gain. Beyond regulating responses to light, pupillary dynamics reveal a nonlinear capacity for neurally mediated gain across the lifespan, thus providing evidence in support of the LC adaptive gain hypothesis.