Core issues, case studies, and the need for expanded Legacy African American genomics.

Introduction: Genomic studies of Legacy African Americans have a tangled and convoluted history in western science. In this review paper, core issues affecting African American genomic studies are addressed and two case studies, the New York African Burial Ground and the Gullah Geechee peoples, are presented to highlight the current status of genomic research among Africa Americans. Methods: To investigate our target population's core issues, a metadatabase derived from 22 publicly accessible databases were reviewed, evaluated, and synthesized to identify the core bioethical issues prevalent during the centuries of the African American presence in North America. The sequence of metadatabase development included 5 steps: identification of information, record screening and retention of topic relevant information, identification of eligibility via synthesis for concept identifications, and inclusion of studies used for conceptual summaries and studies used for genetic and genomic summaries. To these data we added our emic perspectives and specific insights from our case studies. Results: Overall, there is a paucity of existing research on underrepresent African American genomic diversity. In every category of genomic testing (i.e., diagnostic, clinical predictive, pharmacogenomic, direct-to-consumer, and tumor testing), African Americans are disproportionately underrepresented compared to European Americans. The first of our case studies is from the New York African Burial Ground Project where genomic studies of grave soil derived aDNA yields insights into the causes of death of 17th and 18th Century African Americans. In the second of our case studies, research among the Gullah Geechee people of the Carolina Lowcountry reveals a connection between genomic studies and health disparities. Discussion: African Americans have historically borne the brunt of the earliest biomedical studies used to generate and refine primitive concepts in genetics. As exploited victims these investigations, African American men, women, and children were subjected to an ethics-free western science. Now that bioethical safeguards have been added, underrepresented and marginalized people who were once the convenient targets of western science, are now excluded from its health-related benefits. Recommendations to enhance the inclusion of African Americans in global genomic databases and clinical trials should include the following: emphasis on the connection of inclusion to advances in precision medicine, emphasis on the relevance of inclusion to fundamental questions in human evolutionary biology, emphasis on the historical relevance of inclusion for Legacy African Americans, emphasis on the ability of inclusion to foster expanded scientific expertise in the target population, ethical engagement with their descendants, and increase the number of science researchers from these communities.

Evolutionary perspectives on African North American genetic diversity: Origins and prospects for future investigations.

African-descended peoples of the Americas represent an amalgamation of West, Central, and Southeast African regional and ethnic groups with modest gene flow from specific non-African populations. Despite 16+ generations of residence in the Americas, there is a deficit of evolutionary knowledge about these populations. Focusing on Legacy African American, the African North American descendants of survivors of the transatlantic trade in enslaved Africans, we report on emic evolutionary perspectives of their self-identity gleaned from our interviews of 600 individuals collected over 2 years. Gullah-Geechee peoples of Carolina Coastal regions are a model case study due to their historical antiquity, substantial African retentions, relative geospatial isolation, and proposed progenitor status to other Legacy African American microethnic groups. We identify salient research questions for future studies that will begin to bridge the evolutionary gaps in our knowledge of these diverse peoples and the historical evidence for specific evolutionary processes.

Maternal H-antigen secretor status is an early biomarker for potential preterm delivery.

OBJECTIVE: Pre-pregnancy or first trimester biomarkers predicting preterm delivery are lacking. The purpose of this study was to determine whether maternal H-antigen (secretor status) is a potential biomarker for preterm delivery. METHODS: This cohort study examined maternal saliva samples and birth data gathered by the National Children's Study Vanguard pilot phase (2009-2014) and included 300 women who were ≥18 years old and provided birth data and saliva samples. The maternal secretor status phenotype was determined by quantifying H-antigen in saliva using enzyme-linked immunoassay. Mothers were stratified by secretor status and multivariable analysis estimated adjusted associations with preterm delivery. RESULTS: Maternal lack of H-antigen production was an independent risk factor for preterm delivery after adjusting for known confounders (aOR 4.53; 95% CI: 1.74, 11.81; P = 0.002). CONCLUSIONS: Maternal H-antigen may be a biomarker identifying women at-risk for preterm delivery. Prospective cohort studies validating these findings are needed.

Nursing assessment and management of incontinence among medical and surgical adult patients in a tertiary hospital: a best practice implementation project.

OBJECTIVES: The objectives of this implementation project were to review the nursing assessment and management of adult patients with urinary and fecal incontinence, and to develop local guidelines and ward-based continence assessment tools to assist nursing staff in assessing and managing incontinence. INTRODUCTION: Urinary or fecal incontinence in acute care hospitals is a growing issue that can lead to constipation, depression, breakdown of skin integrity, increased nursing home placement of older patients, increased length of hospital stay, and escalated healthcare costs. In many cases, incontinence can be treated and managed effectively; however, it is poorly understood and under-prioritized in many hospital settings. METHODS: A pre-post intervention chart audit was conducted to review compliance with 10 best-practice criteria for incontinence assessment and management. Following baseline data analysis, barriers to compliance with the criteria were identified and subsequently addressed using targeted strategies. The project utilized the JBI Practical Application of Clinical Evidence System (PACES) and the Getting Research into Practice (GRiP) tools. RESULTS: Education on continence strategies was delivered to nursing staff, which resulted in improved compliance for all audit criteria. There were notable improvements in the nursing documentation, and assessment and management of patients with urinary and/or fecal incontinence in the post-intervention analysis. CONCLUSIONS: The results demonstrate that nursing education and formalized assessment pathways in an acute setting can improve nursing compliance with the assessment and management of patients with either urinary or fecal incontinence to ensure safe, compassionate and person-centered care.

Clinical Work Intensity Among Medical Oncologists Practicing in National Community Oncology Research Program Community Sites.

PURPOSE: This study (1) assesses the level of clinical work intensity medical oncologists and oncologic nurse practitioners experience providing care and (2) identifies patient, provider, and practice factors mediating intensity. PATIENTS AND METHODS: Seventeen medical oncologists (12 physicians and five nurse practitioners) from five national sites national reported on the level of work intensity associated with 339 patient visits. Data collection at each site occurred over a 2- to 6 week period; for each provider, five visits were randomly selected from each of 4 randomly selected clinic days, yielding 20 visits per provider. Intensity was measured by the NASA-Task Load Index. Patient and visit characteristics were abstracted from the medical record; provider characteristics were self-reported by questionnaire. RESULTS: Clinical work intensity increased monotonically with level of service and was greatest when the visit involved discussion of either chemotherapy or terminal prognosis. Provider characteristics (including age, sex, and years of experience) were unrelated to intensity. Dimensions of work intensity that correlated directly with level of service included mental, physical, and temporal demand; effort; frustration; and stress. Perceptions of performance and of satisfaction with the visit were unrelated to level of service. Visits related to chemotherapy had greater mental, physical, and temporal demand, and effort, but worse perception of performance. When the visit involved a discussion of a terminal prognosis, greater intensity was reflected in all dimensions; stress was also greater, whereas visit satisfaction was significantly lower. CONCLUSION: Clinical work intensity increases with level of service provided and is greater for visits involving discussion of either terminal prognosis or chemotherapy.

Avoid the Goose! Paramedic Identification of Esophageal Intubation by Ultrasound.

OBJECTIVES: Rapid identification of esophageal intubations is critical to avoid patient morbidity and mortality. Continuous waveform capnography remains the gold standard for endotracheal tube (ETT) confirmation, but it has limitations. Point-of-care ultrasound (POCUS) may be a useful alternative for confirming ETT placement. The objective of this study was to determine the accuracy of paramedic-performed POCUS identification of esophageal intubations with and without ETT manipulation. METHODS: A prospective, observational study using a cadaver model was conducted. Local paramedics were recruited as subjects and each completed a survey of their demographics, employment history, intubation experience, and prior POCUS training. Subjects participated in a didactic session in which they learned POCUS identification of ETT location. During each study session, investigators randomly placed an ETT in either the trachea or esophagus of four cadavers, confirmed with direct laryngoscopy. Subjects then attempted to determine position using POCUS both without and with manipulation of the ETT. Manipulation of the tube was performed by twisting the tube. Descriptive statistics and logistic regression were used to assess the results and the effects of previous paramedic experience. RESULTS: During 12 study sessions, from March 2014 through December 2015, 57 subjects participated, evaluating a total of 228 intubations: 113 tracheal and 115 esophageal. Subjects were 84.0% male, mean age of 39 years (range: 22 - 62 years), with median experience of seven years (range: 0.6 - 39 years). Paramedics correctly identified ETT location in 158 (69.3%) cases without and 194 (85.1%) with ETT manipulation. The sensitivity and specificity of identifying esophageal location without ETT manipulation increased from 52.2% (95% confidence interval [CI], 43.0-61.0) and 86.7% (95% CI, 81.0-93.0) to 87.0% (95% CI, 81.0-93.0) and 83.2% (95% CI, 0.76-0.90) after manipulation (P<.0001), without affecting specificity (P=.45). Subjects correctly identified 41 previously incorrectly identified esophageal intubations. Paramedic experience, previous intubations, and POCUS experience did not correlate with ability to identify tube location. CONCLUSION: Paramedics can accurately identify esophageal intubations with POCUS, and manipulation improves identification. Further studies of paramedic use of dynamic POCUS to identify inadvertent esophageal intubations are needed. LemaPC, O'BrienM, WilsonJ, St. JamesE, LindstromH, DeAngelisJ, CaldwellJ, MayP, ClemencyB. Avoid the goose! Paramedic identification of esophageal intubation by ultrasound. Prehosp Disaster Med. 2018;33(4):406-410.

The impact of comorbid diagnoses on the course of posttraumatic stress disorder symptoms in residents of battered women's shelters.

OBJECTIVE: The current investigation sought to explore the impact of the comorbidities of substance use disorder (SUD), major depressive disorder (MDD), and borderline personality disorder (BPD) on the trajectory of intimate partner violence (IPV)-related posttraumatic stress disorder (PTSD) symptoms across a 6-month follow-up period in IPV survivors who seek shelter. Research has found significant comorbidity of SUD, MDD, and BPD with PTSD (see Green et al., 2006; Kessler, Sonnega, Bromet, Hughes, & Nelson, 1995; Pagura et al., 2010); however, little to no research has explored these relationships in this unique population over time. METHOD: A sample of 147 residents of battered women's shelters completed study measures at baseline, 1 week, and 3 and 6 months following shelter stay. Participants completed measures assessing for demographics, abuse, and Diagnostic and Statistical Manual of Mental Disorders (4th edition, text revision) diagnoses. RESULTS: Results of latent growth modeling with the time-invariant covariates of SUD, MDD, and BPD yielded a significant effect of SUD (ß = .002, p = .007) on the slope of IPV-related PTSD symptoms controlling for IPV victimization. Significant effects were not identified for BPD (ß = .001, p > .05) or MDD (ß = .002, p > .05). Results suggest IPV survivors with SUD demonstrated less improvement in PTSD symptoms over 6 months after they left shelter as compared to women without SUD. CONCLUSION: Findings emphasize the deleterious effects of SUD, above and beyond MDD and BPD, on IPV-related PTSD and highlight the need for assessment and treatment of SUD and PTSD simultaneously in residents of battered women's shelters. Clinical Impact Statement: Findings suggest the need to go beyond standard shelter services to more effectively address and treat co-occurring SUD-PTSD in IPV survivors. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Binding of anti-GRP78 autoantibodies to cell surface GRP78 increases tissue factor procoagulant activity via the release of calcium from endoplasmic reticulum stores.

The increased risk of venous thromboembolism in cancer patients has been attributed to enhanced tissue factor (TF) procoagulant activity (PCA) on the surface of cancer cells. Recent studies have shown that TF PCA can be modulated by GRP78, an endoplasmic reticulum (ER)-resident molecular chaperone. In this study, we investigated the role of cell surface GRP78 in modulating TF PCA in several human cancer cell lines. Although both GRP78 and TF are present on the cell surface of cancer cells, there was no evidence of a stable interaction between recombinant human GRP78 and TF, nor was there any effect of exogenously added recombinant GRP78 on cell surface TF PCA. Treatment of cells with the ER stress-inducing agent thapsigargin, an inhibitor of the sarco(endo)plasmic reticulum Ca(2+) pump that causes Ca(2+) efflux from ER stores, increased cytosolic [Ca(2+)] and induced TF PCA. Consistent with these findings, anti-GRP78 autoantibodies that were isolated from the serum of patients with prostate cancer and bind to a specific N-terminal epitope (Leu(98)-Leu(115)) on cell surface GRP78, caused a dose-dependent increase in cytosolic [Ca(2+)] and enhanced TF PCA. The ability to interfere with cell surface GRP78 binding, block phospholipase C activity, sequester ER Ca(2+), or prevent plasma membrane phosphatidylserine exposure resulted in a significant decrease in the TF PCA induced by anti-GRP78 autoantibodies. Taken together, these findings provide evidence that engagement of the anti-GRP78 autoantibodies with cell surface GRP78 increases TF PCA through a mechanism that involves the release of Ca(2+) from ER stores. Furthermore, blocking GRP78 signaling on the surface of cancer cells attenuates TF PCA and has the potential to reduce the risk of cancer-related venous thromboembolism.

Development of a continuous assay for the measurement of tissue factor procoagulant activity on intact cells.

Tissue factor (TF) is the major physiological initiator of the coagulation cascade and has an important function in the morbidity and mortality associated with many disease states, including cancer-associated thrombosis and atherosclerosis. TF normally exists in a partially encrypted state and its de-encryption on circulating monocytes, platelets or endothelial cells by inflammatory mediators can lead to thrombosis. Furthermore, many cancer cells express large amounts of TF and these cells communicate readily with the circulation through the fenestrated tumor endothelium. To assess agents or conditions that modulate the encryption state of TF, we developed a continuous assay for the determination of TF procoagulant activity (PCA) in a cell-based system. We have shown the use of this assay at detecting agents that de-encrypt TF thereby leading to an increase in TF PCA in three cancer cell lines, namely, T24/83 bladder carcinoma cells and PC-3 and DU145 prostate cancer cells. Further, through use of this assay, we have shown that the endoplasmic reticulum calcium pump inhibitor, thapsigargin, stimulates the de-encryption of TF. The continuous assay for the determination of TF PCA proved to have inherently less intra- and inter-assay variability than the widely used discontinuous assay and is considerably less labor intensive. Further, the continuous assay produced progress curves that were compatible with curve fitting to allow for the determination of the nature of reaction as well as rate constants for the underlying enzymes, TF/FVIIa and FXa. The continuous assay for the assessment of TF PCA on intact cells is applicable for high-throughput screening to allow for the determination of compounds that modulate TF PCA.

Integrating direct electronic collection of data from patients into the process of care for eye care professionals.

Enabling collection of clinical data directly from patients has the potential to increase data accuracy and augment patient engagement in the care process. Most patient data entry systems have been created independent of electronic health records, and few studies have explored how patient entered data can be integrated in the documentation of a clinical encounter. In this paper we describe a formative evaluation study using three different methodologies through which we identified requirements for direct data entry by patients and the subsequent incorporation of these data into the documentation process. The greatest challenges included ensuring confidentiality of records between patients, capturing medication histories from patients, displaying and distinguishing new and previously entered data for provider review, and supporting patient educational needs. The resulting computer tablet-based data collection tool has been deployed to 30 primary care optometry practices where it is successfully used to document care for patients with glaucoma.

Why I Hit Him: Women's Reasons for Intimate Partner Violence.

This study examines motives for intimate partner violence (IPV) among a community sample of 412 women who used IPV against male partners. A "Motives and Reasons for IPV scale" is proposed, and exploratory factor analyses identified five factors: expression of negative emotions, self-defense, control, jealousy, and tough guise. To our knowledge, the study is the first to investigate the relationship between women's motives for IPV and their perpetration of physical, psychological, and sexual aggression, as well as coercive control, toward partners. Hierarchical regression analyses revealed participants' aggression was driven by complex, multiple motives. All five motives were related to a greater frequency of perpetrating IPV. Treatment programs focusing on women's IPV perpetration should address both defensive and proactive motives.

A review of research on women's use of violence with male intimate partners.

This article provides a review of research literature on women who use violence with intimate partners. The central purpose is to inform service providers in the military and civilian communities who work with domestically violent women. The major points of this review are as follows: (a) women's violence usually occurs in the context of violence against them by their male partners; (b) in general, women and men perpetrate equivalent levels of physical and psychological aggression, but evidence suggests that men perpetrate sexual abuse, coercive control, and stalking more frequently than women and that women also are much more frequently injured during domestic violence incidents; (c) women and men are equally likely to initiate physical violence in relationships involving less serious "situational couple violence," and in relationships in which serious and very violent "intimate terrorism" occurs, men are much more likely to be perpetrators and women victims; (d) women's physical violence is more likely than men's violence to be motivated by self-defense and fear, whereas men's physical violence is more likely than women's to be driven by control motives; (e) studies of couples in mutually violent relationships find more negative effects for women than for men; and (f) because of the many differences in behaviors and motivations between women's and men's violence, interventions based on male models of partner violence are likely not effective for many women.

Peripheral reticular pigmentary change is associated with complement factor H polymorphism (Y402H) in age-related macular degeneration.

OBJECTIVE: To examine phenotypes of age-related macular degeneration (AMD) patients with the complement factor H (CFH) variant (Y402H, C allele at rs1061170). DESIGN: Clinic-based case series study. PARTICIPANTS: The data set contained a total of 956 unrelated cases of AMD. METHODS: Age-related macular degeneration phenotypes of 796 carriers of the CFH Y402H variant were compared with the AMD phenotypes of 160 noncarriers. MAIN OUTCOME MEASURES: Presence or absence of 34 phenotypic features. RESULTS: Of the 34 features analyzed, only peripheral reticular pigmentary change (PRPC) was associated with this CFH variant (P = 0.0006). The proportion of AMD cases with PRPC correlated with the number of CFH risk C alleles in a dose-response fashion. CONCLUSIONS: The CFH Y402H polymorphism is associated with PRPC, suggesting that AMD changes are not limited to the macula. Current AMD grading methods assess only the macula and should consider incorporating peripheral retinal changes. Phenotypes that suggest a high-risk genotype may prove valuable for diagnostic, therapeutic, and research purposes.

Phenotype analysis of patients with the risk variant LOC387715 (A69S) in age-related macular degeneration.

PURPOSE: To examine phenotypes of age-related macular degeneration (AMD) patients with the LOC387715 variant (T allele at rs10490924, A69S). DESIGN: Retrospective, observational case series. METHODS: This clinic-based case series data set contained 775 unrelated cases of AMD. AMD phenotypes of three groups, determined by the number of LOC387715 risk alleles, were compared regarding the presence or absence of 16 phenotypic features. RESULTS: The number of AMD cases in each group was 164 cases (two risk alleles), 330 cases (one risk allele), and 281 cases (zero risk allele). The mean age at examination for homozygous carriers of the LOC387715 risk allele was significantly lower (73.9 years) than the age for carriers of one (76.4 years) or no (77.1 years) risk allele (P = .0003). Of the 16 features analyzed, only AMD grade (P = .00002) was significantly associated with the LOC387715 variant. As the number of LOC387715 risk alleles increased, the proportion of grade 5 AMD cases increased in a dose-response fashion. CONCLUSIONS: The LOC387715 variant appears to be an independent risk factor for grade 5 (neovascular) AMD. This variant may also be associated with an earlier onset of AMD. Phenotypes that suggest a high-risk genotype may prove valuable for diagnostic, therapeutic, and research purposes.

Neovascular age-related macular degeneration and its association with LOC387715 and complement factor H polymorphism.

OBJECTIVE: To compare phenotypes of 2 age-related macular degeneration (AMD) susceptibility genes: LOC387715 and complement factor H (CFH). METHODS: Phenotypes of 755 AMD cases were characterized. The number of LOC387715 (T allele at rs10490924, or A69S) and CFH (T1277C at rs1061170, or Y402H) risk alleles were determined in each case. Individuals were divided into 5 groups by genotype: group 1, LOC-/- CFH-/-; group 2, LOC+/- CFH-/- or LOC+/+ CFH-/-; group 3, LOC-/- CFH+/- or LOC-/- CFH+/+; group 4, LOC+/- CFH+/-, LOC+/+ CFH+/-, or LOC+/- CFH+/+; and group 5, LOC+/+ CFH+/+. RESULTS: Signs of neovascular AMD including grade (P = .002), pigment epithelial detachment (P = .001), and subretinal hemorrhage (P<.001) demonstrated significant association with groups 2, 4, and 5 vs groups 1 and 3. Group 5 had a significantly younger mean age (72.3 years) compared with other groups (P = .002). CONCLUSIONS: The AMD cases possessing the LOC387715 (rs10490924) variant may have a higher risk of neovascular AMD. Individuals with AMD who are homozygous for both variants might be at greater risk for earlier onset of neovascular AMD.

Complement factor H increases risk for atrophic age-related macular degeneration.

OBJECTIVE: To determine if the complement factor H gene (CFH) determines risk for development of geographic atrophy (GA). DESIGN: Retrospective case-control study. PARTICIPANTS AND CONTROLS: The independent case-control data set contained 647 age-related macular degeneration (AMD) cases (grades 3, 4, or 5) and 163 controls (grades 1 or 2). METHODS: To determine if CFH had any effect on determining risk for development of GA in an independent case-control data set of 647 AMD cases and 163 controls, the rs1061170 single-nucleotide polymorphism was tested for association, separating grades and analyzing them independently against the controls. Odds ratios were calculated using standard logistic regression models. MAIN OUTCOME MEASURES: The outcome variable was AMD affection status, and genotypes were coded according to a log-additive model. RESULTS: There were 407 grade 5, 107 grade 4, 133 grade 3, 35 grade 2, and 128 grade 1 individuals. There was significant association with AMD when comparing grades 3, 4, and 5 versus the controls. The highest odds ratio was obtained when analyzing the grade-4 cases versus the grade-1 controls (OR = 3.217, P<0.0001). CONCLUSIONS: Our results indicate that CFH increases the risk of developing GA (grade 4) as well as neovascular (grade 5) and milder (grade 3) disease. Although neovascular disease is responsible for the majority of severe vision loss with AMD, GA is also a significant cause of vision loss, and without effective treatment. Therefore, an attempt to clarify its pathogenesis is of the utmost importance.

Active Nercc1 protein kinase concentrates at centrosomes early in mitosis and is necessary for proper spindle assembly.

The Nercc1 protein kinase autoactivates in vitro and is activated in vivo during mitosis. Autoactivation in vitro requires phosphorylation of the activation loop at threonine 210. Mitotic activation of Nercc1 in mammalian cells is accompanied by Thr210 phosphorylation and involves a small fraction of total Nercc1. Mammalian Nercc1 coimmunoprecipitates gamma-tubulin and the activated Nercc1 polypeptides localize to the centrosomes and spindle poles during early mitosis, suggesting that active Nercc has important functions at the microtubular organizing center during cell division. To test this hypothesis, we characterized the Xenopus Nercc1 orthologue (XNercc). XNercc endogenous to meiotic egg extracts coprecipitates a multiprotein complex that contains gamma-tubulin and several components of the gamma-tubulin ring complex and localizes to the poles of spindles formed in vitro. Reciprocally, immunoprecipitates of the gamma-tubulin ring complex polypeptide Xgrip109 contain XNercc. Immunodepletion of XNercc from egg extracts results in delayed spindle assembly, fewer bipolar spindles, and the appearance of aberrant microtubule structures, aberrations corrected by addition of purified recombinant XNercc. XNercc immunodepletion also slows aster assembly induced by Ran-GTP, producing Ran-asters of abnormal size and morphology. Thus, Nercc1 contributes to both the centrosomal and the chromatin/Ran pathways that collaborate in the organization of a bipolar spindle.

Students' perceptions of their acquired knowledge during a problem based learning case study.

Problem based learning (PBL) in occupational therapy education has become very popular, although the efficacy of this teaching method has not been well documented. The purpose of this study was to evaluate the effectiveness of a PBL case in meeting faculty generated learning objectives. A pretest/posttest design was utilized to evaluate students' perceptions of content acquisition. A two-way ANOVA with repeated measures was completed; results yielded a significant difference among the pretest and posttest scores (p-v < 0.01). The posttest mean scores were higher, which indicated that students perceived they acquired the intended knowledge and PBL was an effective method to facilitating learning.