Understanding how COVID-19 affected black pregnant women early in the pandemic: A cross-sectional survey.

OBJECTIVE: Previous research has shown that the COVID-19 pandemic significantly increased anxiety among pregnant women, and at the same time, COVID-19 has disproportionately affected communities of color in the United States. We sought to understand how self-identied Black pregnant women in the United States were affected in the early days of the COVID-19 pandemic. DESIGN: Cross-sectional, online survey distributed via social media SETTING: Online PARTICIPANTS: Non-probability, convenience sample of self-identified Black pregnant women in the United States between April 3 and 24, 2020 who responded to an online inquiry seeking women who were pregnant at the outset of the COVID-19 pandemic. MEASUREMENTS AND FINDINGS: An anonymous, self-administered, online survey of pregnant women was conducted, including both quantitative assessment of demographics, COVID-related anxiety, and pregnancy-related anxiety as well as open-ended prompts for qualitative assessment of the impact of COVID on prenatal care, birth plans, anxiety and overall experience of pregnancy. Quantitative data were analyzed using Stata 15.0, qualitative data were thematically analyzed using NVivo12.1. Results were compared using joint display methodology. Of 87 self-identified Black or African-American women who responded, the most common concerns related to fear of getting infected with COVID (89.7 %, N = 78) and concerns related to loss of job/income (67.8 %, N = 59). More than half (55.2 %, N = 48) reported either themselves or their family members working in essential services. Findings indicate that uncertainty, lack of support, perceived quality of care, and heightened anxiety worked together to define Black women's experiences of pregnancy in the early days of the COVID-19 pandemic in the U.S. While quantitative data did not explicitly capture reports of discrimination as impacting perceived quality of care, the qualitative data suggest a link between fears of discrimination, the need for self-advocacy, and heightened anxiety. KEY CONCLUSIONS: Despite being a relatively well-educated sample of Black women from around the United States, many respondents spoke of the fears of discrimination, the need for self-advocacy, and heightened anxiety, reinforcing that discrimination and fear of discrimation for Black women in healthcare settings are pervasive, regardless of a woman's level of education or other socioeconomic status indicators. IMPLICATIONS FOR PRACTICE: These findings suggest that in times of uncertainty, such as the early days of the COVID-19 pandemic, it is more important than ever to provide thoughtful, supportive care to pregnant women of color who are primed for negative experiences in the healthcare settting.

Advanced Age in Humans and Mouse Models of Glioblastoma Show Decreased Survival from Extratumoral Influence.

PURPOSE: Glioblastoma (GBM) is the most common aggressive primary malignant brain tumor in adults with a median age of onset of 68 to 70 years old. Although advanced age is often associated with poorer GBM patient survival, the predominant source(s) of maladaptive aging effects remains to be established. Here, we studied intratumoral and extratumoral relationships between adult patients with GBM and mice with brain tumors across the lifespan. EXPERIMENTAL DESIGN: Electronic health records at Northwestern Medicine and the NCI SEER databases were evaluated for GBM patient age and overall survival. The commercial Tempus and Caris databases, as well as The Cancer Genome Atlas were profiled for gene expression, DNA methylation, and mutational changes with varying GBM patient age. In addition, gene expression analysis was performed on the extratumoral brain of younger and older adult mice with or without a brain tumor. The survival of young and old wild-type or transgenic (INK-ATTAC) mice with a brain tumor was evaluated after treatment with or without senolytics and/or immunotherapy. RESULTS: Human patients with GBM ≥65 years of age had a significantly decreased survival compared with their younger counterparts. While the intra-GBM molecular profiles were similar between younger and older patients with GBM, non-tumor brain tissue had a significantly different gene expression profile between young and old mice with a brain tumor and the eradication of senescent cells improved immunotherapy-dependent survival of old but not young mice. CONCLUSIONS: This work suggests a potential benefit for combining senolytics with immunotherapy in older patients with GBM.

Elevating Women's Voices: The Illinois Maternal Health Digital Storytelling Project.

Numerous initiatives at the national, state, and local levels are focused on addressing the U.S. maternal health crisis. However, most efforts fail to center women's voices and personal perspectives about pregnancy experiences and complications. This article describes the Illinois Maternal Health Digital Storytelling Project conducted by the University of Illinois at Chicago, in partnership with StoryCenter, a storytelling nonprofit organization based in Berkeley, California. The project aimed to elevate voices (stories) to complement other sources of data on maternal outcomes. We relied on partners to help recruit storytellers with a self-identified perinatal-related challenge. We screened interested individuals using a trauma-informed approach and a social worker provided storytellers with support during the project. Two groups participated in this project, one in 2021 and another in 2022, culminating with 10 digital stories. Both instances were conducted virtually and included group and individual skills-based sessions where storytellers learned to create and edit their digital stories. The storytellers own their digital stories and provided consent to include them in ongoing dissemination efforts. In September 2021, a webpage was launched to house the stories, and this resource is being shared widely. Evaluation efforts of the webpage are ongoing to understand how these digital stories are being used to inform maternal health efforts. Digital stories add richness to ongoing maternal health prevention work and may serve as a powerful tool to elicit understanding among providers, practitioners, and constituents.

Identification and Characterization of a Novel Indoleamine 2,3-Dioxygenase 1 Protein Degrader for Glioblastoma.

Indoleamine 2,3-dioxygenase 1 (IDO1) is a potent immunosuppressive enzyme that inhibits the antitumor immune response through both tryptophan metabolism and non-enzymatic functions. To date, most IDO1-targeted approaches have focused on inhibiting tryptophan metabolism. However, this class of drugs has failed to improve the overall survival of patients with cancer. Here, we developed and characterized proteolysis targeting chimeras (PROTACs) that degrade the IDO1 protein. IDO1-PROTACs were tested for their effects on IDO1 enzyme and non-enzyme activities. After screening a library of IDO1-PROTAC derivatives, a compound was identified that potently degraded the IDO1 protein through cereblon-mediated proteasomal degradation. The IDO1-PROTAC: (i) inhibited IDO1 enzyme activity and IDO1-mediated NF-κB phosphorylation in cultured human glioblastoma (GBM) cells, (ii) degraded the IDO1 protein within intracranial brain tumors in vivo, and (iii) mediated a survival benefit in mice with well-established brain tumors. This study identified and characterized a new IDO1 protein degrader with therapeutic potential for patients with glioblastoma.

A systematic review of pharmacologic treatment efficacy for depression in older patients with cancer.

Background: Older adults ≥65 years of age represent the majority of new cancer diagnoses and are vulnerable to developing depression-like symptoms. Evaluation and management of depression in older cancer patients is underappreciated despite its high prevalence and impact on health-related quality of life. Although antidepressants are the primary pharmacologics used to treat depressive-like symptoms, the efficacy and overall benefit(s) are not well-characterized in older adult patients with cancer. The objective of this investigation was to review what is known about the efficacy of pharmacologic treatment for older adults with depression and cancer. Methods: PubMed (Medline) and EMBASE (Elsevier) databases were analyzed for relevant literature in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: 1,919 unique studies were identified for title and abstract screening. Forty-eight publications were retrieved for full review. None of the identified studies evaluated the potential for benefit after pharmacological treatment among older adults with cancer and depression. Twenty-seven publications met all study criteria except for an analysis focused on older patients. Conclusion: We discovered a universal absence of literature with a relevance to pharmacologic antidepressant treatment effects in older adult patients with cancer. This included a lack of evaluation in patients with brain tumors who have an unusually high predilection for developing depression. Our findings suggest that new research is critically needed for understanding optimal clinical management strategies in older adults with cancer and depression who are treated with antidepressants.

The association of COVID-19 infection in pregnancy with preterm birth: A retrospective cohort study in California.

INTRODUCTION: Our understanding of the association between coronavirus disease 19 (COVID-19) and preterm or early term birth among racially and ethnically diverse populations and people with chronic medical conditions is limited. METHODS: We determined the association between COVID-19 and preterm (PTB) birth among live births documented by California Vital Statistics birth certificates between July 2020 and January 2021 (n=240,147). We used best obstetric estimate of gestational age to classify births as very preterm (VPTB, <32 weeks), PTB (< 37 weeks), early term (37 and 38 weeks), and term (39-44 weeks), as each confer independent risks to infant health and development. Separately, we calculated the joint effects of COVID-19 diagnosis, hypertension, diabetes, and obesity on PTB and VPTB. FINDINGS: COVID-19 diagnoses on birth certificates increased for all racial/ethnic groups between July 2020 and January 2021 and were highest for American Indian/Alaska Native (12.9%), Native Hawaiian/Pacific Islander (11.4%), and Latinx (10.3%) birthing people. COVID-19 diagnosis was associated with an increased risk of VPTB (aRR 1.6, 95% CI [1.4, 1.9]), PTB (aRR 1.4, 95% CI [1.3, 1.4]), and early term birth (aRR 1.1, 95% CI [1.1, 1.2]). There was no effect modification of the overall association by race/ethnicity or insurance status. COVID-19 diagnosis was associated with elevated risk of PTB in people with hypertension, diabetes, and/or obesity. INTERPRETATION: In a large population-based study, COVID-19 diagnosis increased the risk of VPTB, PTB, and early term birth, particularly among people with medical comorbidities. Considering increased circulation of COVID-19 variants, preventative measures, including vaccination, should be prioritized for birthing persons. FUNDING: UCSF-Kaiser Department of Research Building Interdisciplinary Research Careers in Women's Health Program (BIRCWH) National Institute of Child Health and Human Development (NICHD) and the Office of Research on Women's Health (ORWH) [K12 HD052163] and the California Preterm Birth Initiative, funded by Marc and Lynn Benioff.

Glioblastoma as an age-related neurological disorder in adults.

BACKGROUND: Advanced age is a major risk factor for the development of many diseases including those affecting the central nervous system. Wild-type isocitrate dehydrogenase glioblastoma (IDHwt GBM) is the most common primary malignant brain cancer and accounts for ≥90% of all adult GBM diagnoses. Patients with IDHwt GBM have a median age of diagnosis at 68-70 years of age, and increasing age is associated with an increasingly worse prognosis for patients with this type of GBM. METHODS: The Surveillance, Epidemiology, and End Results, The Cancer Genome Atlas, and the Chinese Glioma Genome Atlas databases were analyzed for mortality indices. Meta-analysis of 80 clinical trials was evaluated for log hazard ratio for aging to tumor survivorship. RESULTS: Despite significant advances in the understanding of intratumoral genetic alterations, molecular characteristics of tumor microenvironments, and relationships between tumor molecular characteristics and the use of targeted therapeutics, life expectancy for older adults with GBM has yet to improve. CONCLUSIONS: Based upon the results of our analysis, we propose that age-dependent factors that are yet to be fully elucidated, contribute to IDHwt GBM patient outcomes.

Tumor Cell IDO Enhances Immune Suppression and Decreases Survival Independent of Tryptophan Metabolism in Glioblastoma.

PURPOSE: Glioblastoma (GBM) is an incurable primary brain tumor that has not benefited from immunotherapy to date. More than 90% of GBM expresses the tryptophan (Trp) metabolic enzyme, indoleamine 2,3-dioxygenase 1 (IDO). This observation supported the historical hypothesis that IDO suppresses the antitumor immune response solely through a mechanism that requires intratumoral Trp depletion. However, recent findings led us to investigate the alternative hypothesis that IDO suppresses the anti-GBM immune response independent of its association with Trp metabolism. EXPERIMENTAL DESIGN: IDO-deficient GBM cell lines reconstituted with IDO wild-type or IDO enzyme-null cDNA were created and validated in vitro and in vivo. Microarray analysis was conducted to search for genes that IDO regulates, followed by the analysis of human GBM cell lines, patient GBM and plasma, and The Cancer Genome Atlas (TCGA) database. Ex vivo cell coculture assays, syngeneic and humanized mouse GBM models, were used to test the alternative hypothesis. RESULTS: Nonenzymic tumor cell IDO activity decreased the survival of experimental animals and increased the expression of complement factor H (CFH) and its isoform, factor H like protein 1 (FHL-1) in human GBM. Tumor cell IDO increased CFH and FHL-1 expression independent of Trp metabolism. Increased intratumoral CFH and FHL-1 levels were associated with poorer survival among patients with glioma. Similar to IDO effects, GBM cell FHL-1 expression increased intratumoral regulatory T cells (Treg) and myeloid-derived suppressor cells while it decreased overall survival in mice with GBM. CONCLUSIONS: Our study reveals a nonmetabolic IDO-mediated enhancement of CFH expression and provides a new therapeutic target for patients with GBM.

Police brutality and unmet need for mental health care.

OBJECTIVE: National movements have raised awareness of the adverse mental health effects of police brutality. This study examines the relationship between perceived police brutality and unmet need for mental health care. DATA SOURCES: We used the 2018 Survey of the Health of Urban Residents (N = 4338), a quota sample survey of adults in urban areas in the contiguous United States. STUDY DESIGN: Multivariate regressions were used to understand the association between police brutality and unmet need for mental health care. Unmet need was regressed on police brutality (the independent variable), controlling for sociodemographic and health status characteristics of respondents and access to care. We then stratified the sample by experiences of police brutality (no negative encounters with the police, encounters that were perceived as necessary, and encounters that were considered unnecessary) and described how medical mistrust and perceived respect within health care settings were associated with odds of unmet need for each subsample. DATA COLLECTION: Data were collected online. PRINCIPAL FINDINGS: Negative police encounters perceived as necessary were associated with greater odds of unmet need compared to no negative police encounters (odds ratio [OR] = 1.98, confidence interval [CI] = 1.30-2.65). Odds of unmet need were also higher among persons with negative and unnecessary police encounters (OR = 1.28, CI = 1.05-1.56). Greater respect was associated with lower odds of unmet need among persons who reported negative unnecessary encounters with the police (OR = 0.88, CI = 0.72-0.97). Medical mistrust was associated with greater odds of unmet need among those with negative unnecessary police encounters (OR = 1.52, CI = 1.12-1.93). CONCLUSIONS: Persons who are exposed to police brutality are also likely to be those who experience unmet need for mental health care. Ensuring that they feel respected within medical settings and establishing conditions that build trust in medical institutions are important for eliminating unmet need for mental health care.

'Asram is really killing us here': attribution for pregnancy losses and newborn mortality in the Ashanti Region of Ghana.

While overall neonatal mortality rates are improving in Ghana, the Ashanti Region has the highest mortality rate in the country. The clinical causes of newborn deaths are well known, yet local beliefs about illness aetiology, cause of death and care-seeking are less well understood. This exploratory qualitative study sought to understand how community members perceive and respond to neonatal illness. Researchers worked with public health nurses, community health nurses and opinion leaders in the Ashanti Region of Ghana to identify women who had lost a baby, either during pregnancy or after delivery. In-depth interviews and focus group discussions were conducted about knowledge, attitudes and beliefs regarding neonatal mortality. The transcripts were coded and analysed using NVivo 10.0. A total of 100 participants were interviewed: 24% reported a previous stillbirth; 37% reported a previous miscarriage; and 45% reported losing a baby who was born alive. Nine per cent experienced more than one type of loss. The local illness of asram - an illness with supernatural causes - was cited as a leading cause of death of newborns. Every participant reported hearing of, knowing someone, or having a child who had become ill with asram. While women gave varying information on symptoms, method of contraction and treatment, all participants agreed that asram was common and often fatal. Four overarching themes emerged: 1) asram is not a hospital sickness; 2) there is both a fear of traditional healers as a source of asram, as well as a reliance upon them to cure asram; 3) there are rural/urban differences in perceptions of asram; and 4) asram may serve as a mechanism of social control for pregnant women and new mothers. Local beliefs and practices must be better understood and incorporated into health education campaigns if neonatal mortality is to be reduced in Ghana.

Immunosuppressive IDO in Cancer: Mechanisms of Action, Animal Models, and Targeting Strategies.

Indoleamine 2, 3-dioxygenase 1 (IDO; IDO1; INDO) is a rate-limiting enzyme that metabolizes the essential amino acid, tryptophan, into downstream kynurenines. Canonically, the metabolic depletion of tryptophan and/or the accumulation of kynurenine is the mechanism that defines how immunosuppressive IDO inhibits immune cell effector functions and/or facilitates T cell death. Non-canonically, IDO also suppresses immunity through non-enzymic effects. Since IDO targeting compounds predominantly aim to inhibit metabolic activity as evidenced across the numerous clinical trials currently evaluating safety/efficacy in patients with cancer, in addition to the recent disappointment of IDO enzyme inhibitor therapy during the phase III ECHO-301 trial, the issue of IDO non-enzyme effects have come to the forefront of mechanistic and therapeutic consideration(s). Here, we review enzyme-dependent and -independent IDO-mediated immunosuppression as it primarily relates to glioblastoma (GBM); the most common and aggressive primary brain tumor in adults. Our group's recent discovery that IDO levels increase in the brain parenchyma during advanced age and regardless of whether GBM is present, highlights an immunosuppressive synergy between aging-increased IDO activity in cells of the central nervous system that reside outside of the brain tumor but collaborate with GBM cell IDO activity inside of the tumor. Because of their potential value for the in vivo study of IDO, we also review current transgenic animal modeling systems while highlighting three new constructs recently created by our group. This work converges on the central premise that maximal immunotherapeutic efficacy in subjects with advanced cancer requires both IDO enzyme- and non-enzyme-neutralization, which is not adequately addressed by available IDO-targeting pharmacologic approaches at this time.

Advanced Age Increases Immunosuppression in the Brain and Decreases Immunotherapeutic Efficacy in Subjects with Glioblastoma.

PURPOSE: Wild-type isocitrate dehydrogenase-expressing glioblastoma (GBM) is the most common and aggressive primary brain tumor with a median age at diagnosis of ≥65 years. It accounts for approximately 90% of all GBMs and has a median overall survival (OS) of <15 months. Although immune checkpoint blockade (ICB) therapy has achieved remarkable survival benefits in a variety of aggressive malignancies, similar success has yet to be achieved for GBM among phase III clinical trials to date. Our study aimed to understand the relationship between subject age and immunotherapeutic efficacy as it relates to survival from glioma. EXPERIMENTAL DESIGN: (i) Clinical data: GBM patient datasets from The Cancer Genome Atlas, Northwestern Medicine Enterprise Data Warehouse, and clinical studies evaluating ICB were stratified by age and compared for OS. (ii) Animal models: young, middle-aged, and older adult wild-type and indoleamine 2,3 dioxygenase (IDO)-knockout syngeneic mice were intracranially engrafted with CT-2A or GL261 glioma cell lines and treated with or without CTLA-4/PD-L1 mAbs, or radiation, anti-PD-1 mAb, and/or a pharmacologic IDO enzyme inhibitor. RESULTS: Advanced age was associated with decreased GBM patient survival regardless of treatment with ICB. The advanced age-associated increase of brain IDO expression was linked to the suppression of immunotherapeutic efficacy and was not reversed by IDO enzyme inhibitor treatment. CONCLUSIONS: Immunosuppression increases in the brain during advanced age and inhibits antiglioma immunity in older adults. Going forward, it will be important to fully understand the factors and mechanisms in the elderly brain that contribute to the decreased survival of older patients with GBM during treatment with ICB.

'This sickness is not hospital sickness': a qualitative study of the evil eye as a source of neonatal illness in Ghana.

Previous research has described the evil eye as a source of illness for pregnant women and their newborns. This study sought to explore the perceptions of the evil eye among mothers whose newborns had experienced a life-threatening complication across three regions of Ghana. As part of a larger, quantitative study, trained research assistants identified pregnant and newly delivered women (and their newborns) who had survived a life-threatening complication at three tertiary care hospitals in southern Ghana to participate in open-ended, qualitative interviews about their experiences in March-August 2015. All interviews were audio-recorded and transcribed verbatim into English and analysis using the constant comparative method of theme generation. A total of 37 mothers were interviewed, 20 about neonatal illnesses and 17 about maternal illnesses. Six of the 20 mothers interviewed about their newborn's illnesses spoke at length about the evil eye being a potential cause of newborn illness. The evil eye was described in a variety of terms, but commonalities included a person looking at a pregnant woman, her newborn baby, the baby's clothes and even the mother's food, causing harm, even unintentionally. Prevention required mothers covering themselves while pregnant and keeping the baby away from others until it was old enough to ward off the evil eye. Treatment required traditional medicine, yet some indicated that allopathic medicine could help. The evil eye appears to serve a social control mechanism, encouraging pregnant women to dress modestly, stay indoors as much as possible and behave appropriately. The evil eye is a pervasive, universally understood phenomenon across three regions of Ghana, even amongst a hospitalized population receiving allopathic health care for life-threatening complications of childbirth. Understanding the role of the evil eye in newborn illness attribution is important for clinicians, researchers and programmatic staff to effectively address barriers to care seeking.

Neonatal near-misses in Ghana: a prospective, observational, multi-center study.

BACKGROUND: For every newborn who dies within the first month, as many as eight more suffer life-threatening complications but survive (termed 'neonatal near-misses' (NNM)). However, there is no universally agreed-upon definition or assessment tool for NNM. This study sought to describe the development of the Neonatal Near-Miss Assessment Tool (NNMAT) for low-resource settings, as well as findings when implemented in Ghana. METHODS: This prospective, observational study was conducted at two tertiary care hospitals in southern Ghana from April - July 2015. Newborns with evidence of complications and those admitted to the NICUs were screened for inclusion using the NNMAT. Incidence of suspected NNM at enrollment and confirmed near-miss (surviving to 28 days) was determined and compared against institutional neonatal mortality rates. Suspected NNM cases were compared with newborns not classified as a suspected near-miss, and all were followed to 28 days to determine odds of survival. Confirmed near-misses were those identified as suspected near-misses at enrollment who survived to 28 days. The main outcome measures were incidence of NNM, NNM:mortality ratio, and factors associated with NNM classification. RESULTS: Out of 394 newborns with complications, 341 (86.5%) were initially classified as suspected near-misses at enrollment using the NNMAT, with 53 (13.4%) being classified as a non-near-miss. At 28-day follow-up, 68 (17%) had died, 52 (13%) were classified as a non-near-miss, and 274 were considered confirmed near-misses. Those newborns with complications who were classified as suspected near-misses using the NNMAT at enrollment had 12 times the odds of dying before 28 days than those classified as non-near-misses. While most confirmed near-misses qualified as NNM via intervention-based criteria, nearly two-thirds qualified based on two or more of the four NNMAT categories. When disaggregated, the most predictive elements of the NNMAT were gestational age < 33 weeks, neurologic dysfunction, respiratory dysfunction, and hemoglobin < 10 gd/dl. The ratio of near-misses to deaths was 0.55: 1, yet this varied across the study sites. CONCLUSIONS: This research suggests that the NNMAT is an effective tool for assessing neonatal near-misses in low-resource settings. We believe this approach has significant systems-level, continuous quality improvement, clinical and policy-level implications.

Quantification of IDO1 enzyme activity in normal and malignant tissues.

Indoleamine 2,3-dioxygenase 1 (IDO1) catalyzes the first and rate-limiting reaction of l-tryptophan (Trp) conversion into l-kynurenine (Kyn). The depletion of Trp, and the accumulation of Kyn have been proposed as mechanisms that contribute to the suppression of the immune response-primarily evidenced by in vitro study. IDO1 is therefore considered to be an immunosuppressive modulator and quantification of IDO1 metabolism may be critical to understanding its role in select immunopathologies, including autoimmune- and oncological-conditions, as well as for determining the potency of IDO1 enzyme inhibitors. Because tryptophan 2,3-dioxygenase (TDO), and to a significantly lesser extent, IDO2, also catabolize Trp into Kyn, it's important to differentiate the contribution of each enzyme to Trp catabolism and Kyn generation. Moreover, a great variety of detection methods have been developed for the quantification of Trp metabolites, but choosing the suitable protocol remains challenging. Here, we review the differential expression of IDO1/TDO/IDO2 in normal and malignant tissues, followed by a comprehensive analysis of methodologies for quantifying Trp and Kyn in vitro and in vivo, with an emphasis on the advantages/disadvantages for each application.

Is abortion justified to save the life or health of a woman? Evidence of public opinion from Accra, Ghana.

OBJECTIVE: In this study, we sought to determine to what extent the abortion law in Ghana is reflective of public opinion. METHODS: In a cross-sectional, community-based survey, individuals in two fishing communities in Accra were interviewed about their beliefs on abortion between May and July 2016, and sociodemographic, attitudinal, and experience data were collected. Factors associated with the outcome variable (abortion is justified to save the life/health of the woman: Yes/No) were entered into a multivariate logistic regression. RESULTS: A total of 508 participants completed the survey. Thirty-nine percent (n=198) of the sample agreed that abortion was justified to save the life/health of the woman, with no significant differences in this finding when controlling for understanding of the law, gender, marital status, or personal experience of abortion in multivariate analysis. Higher education (odds ratio [OR] 1.64 [P<0.001]) and older age (OR 1.28 [P<0.001]) are positively associated with abortion being justified to save life/health, while those who have had an experience of unwanted sex are less likely to believe that (OR 0.60 [P=0.029]). CONCLUSION: The participants held conservative views about the justification of abortion to save a woman's life and/or health. Improving access to safe abortion services will require acknowledgment of the broader social and cultural context that may make accessing such services difficult.

"We call them miracle babies": How health care providers understand neonatal near-misses at three teaching hospitals in Ghana.

Neonatal mortality is a significant problem in many low-resource countries, yet for every death there are many more newborns who suffer a life-threatening complication but survive. These "near-misses" are not well defined, nor are they well understood. This study sought to explore how health care providers at three tertiary care centers in Ghana (each with neonatal intensive care units (NICUs)) understand the term "near-miss." Eighteen providers from the NICUs at three teaching hospitals in Ghana (Korle Bu Teaching Hospital in Accra, Komfo Anokye Teaching Hospital in Kumasi, and Cape Coast Teaching Hospital in Cape Coast) were interviewed in depth regarding their perceptions of neonatal morbidity, mortality, and survival. Near the end of the interview, they were specifically asked what they understood the term "near-miss" to mean. Participants included nurses and physicians at various levels and with varying years of practice (mean years of practice = 9.33, mean years in NICU = 3.66). Results indicate that the concept of "near-misses" is not universally understood, and providers differ on whether a baby is a near-miss or not. Providers disagreed on the utility of a near-miss classification for clinical practice, with some suggesting it would be helpful to draw their attention to those at highest risk of dying, with others suggesting that the acuity of illness in a NICU means any baby could become a 'near-miss' at any moment. Further efforts are needed to standardize the definitions of neonatal near-misses, including developing criteria that are able to be assessed in a low-resource setting. In addition, further research is warranted to determine the practical implications of using a near miss tool in the process of providing care in a resource-limited setting and whether it might be best reserved as a retrospective indicator of overall quality of care provided.

Murine thymic NK cells are distinct from ILC1s and have unique transcription factor requirements.

Group 1 innate lymphoid cells include natural killer (NK) cells and ILC1s, which mediate the response to intracellular pathogens. Thymic NK (tNK) cells were described with hybrid features of immature NK cells and ILC1 but whether these cells are related to NK cells or ILC1 has not been fully investigated. We report that murine tNK cells expressed the NK-cell associated transcription factor EOMES and developed independent of the essential ILC1 factor TBET, confirming their placement within the NK lineage. Moreover, tNK cells resemble NK cells rather than ILC1 in their requirements for the E protein transcription factor inhibitor ID2. We provide further insight into the mechanisms governing tNK-cell development by showing that the transcription factor ETS1 prevented tNK cell acquisition of the conventional NK-cell maturation markers CD11b and KLRG1. Our data reveal few ILC1 in the thymus and clarify the identity and developmental requirements of tNK cells.

Predictors of stillbirths and neonatal deaths in rural western Uganda.

OBJECTIVE: To explore pregnancy outcomes at a referral hospital in rural western Uganda. METHODS: A retrospective study was undertaken using data for all deliveries at Virika Hospital, Fort Portal, Uganda, between July 1, 2009, and October 22, 2011. A detailed review of delivery logs was conducted. Categories were created for obstetric risk factors (e.g. grand multipara, history of hypertension), maternal delivery complications (e.g. eclampsia, hemorrhage), and neonatal complications (e.g. fetal distress, birth defects). RESULTS: Overall, 4883 deliveries were included. Of the 517 neonates who did not survive, 430 (83.2%) had been stillborn. After controlling for parity, gestational age, obstetric risk factors, and neonatal complications, risk factors for stillbirth included maternal delivery complications (risk ratio [RR] 3.32, 95% confidence interval [CI] 2.34-4.71; P<0.001) and living 51-100km from the hospital (RR 3.37, 95% CI 2.41-4.74; P<0.001). Risk factors for neonatal death included neonatal complications (RR 5.79, 95% CI 2.49-13.46; P=0.001) and maternal delivery complications (RR 3.17, 95% CI 1.47-6.82; P=0.003). CONCLUSION: Qualified providers need to be deployed to rural areas of Uganda to facilitate the prompt identification and management of pregnancy, delivery, and neonatal complications.

Experience implementing electronic health records in the antenatal clinic of a teaching and referral hospital in Kenya.

INTRODUCTION: Electronic health records (EHRs) are receiving a lot of attention for their potential to improve care. OBJECTIVE: To develop and implement EHRs in the antenatal clinic (ANC) of a teaching and referral hospital in Western Kenya. RESULTS: A multidisciplinary team developed a phased implementation of EHRs in the ANC as part of a CDC-funded effort to develop and implement primary care EHRs in lower level and referral facilities in Kenya comprising a clinic registration system and initial- and return-visit encounter forms that captured and reported data required for reporting. This was successfully done, the EHR fully implemented in the ANC including a reminder system to enhance adherence to care guidelines. CONCLUSIONS: It is possible to implement EHRs in a referral hospital ANC.