Sirt6 regulates lifespan in Drosophila melanogaster.

Sirt6 is a multifunctional enzyme that regulates diverse cellular processes such as metabolism, DNA repair, and aging. Overexpressing Sirt6 extends lifespan in mice, but the underlying cellular mechanisms are unclear. Drosophila melanogaster are an excellent model to study genetic regulation of lifespan; however, despite extensive study in mammals, very little is known about Sirt6 function in flies. Here, we characterized the Drosophila ortholog of Sirt6, dSirt6, and examined its role in regulating longevity; dSirt6 is a nuclear and chromatin-associated protein with NAD+-dependent histone deacetylase activity. dSirt6 overexpression (OE) in flies produces robust lifespan extension in both sexes, while reducing dSirt6 levels shortens lifespan. dSirt6 OE flies have normal food consumption and fertility but increased resistance to oxidative stress and reduced protein synthesis rates. Transcriptomic analyses reveal that dSirt6 OE reduces expression of genes involved in ribosome biogenesis, including many dMyc target genes. dSirt6 OE partially rescues many effects of dMyc OE, including increased nuclear size, up-regulation of ribosome biogenesis genes, and lifespan shortening. Last, dMyc haploinsufficiency does not convey additional lifespan extension to dSirt6 OE flies, suggesting dSirt6 OE is upstream of dMyc in regulating lifespan. Our results provide insight into the mechanisms by which Sirt6 OE leads to longer lifespan.

A phase 1 study of regorafenib and sildenafil in adults with advanced solid tumors.

The purpose of this study is to establish the recommended phase 2 dose for regorafenib in combination with sildenafil for patients with advanced solid tumors. Secondary outcomes included identification of antitumor effects of regorafenib and sildenafil, toxicity of the combination, determination of PDE5 expression in tumor samples, and the impact of sildenafil on the pharmacokinetics of regorafenib. This study was a phase 1, open-label single-arm dose-escalation trial using a 3 + 3 design. Additional patients were enrolled at the maximum tolerated dose (MTD) until a total of 12 patients were treated at the MTD. A total of 29 patients were treated in this study. The median duration of treatment was 8 weeks. The recommended phase 2 doses determined in this study are regorafenib 160 mg daily with sildenafil 100 mg daily. The most common toxicities included palmar-plantar erythrodysesthesia syndrome (20 patients, 69%) and hypophosphatemia (18 patients, 62%). Two patients (7%) experienced grade 4 lipase increase. Objective responses were not observed; however, 14 patients (48%) had a period of stable disease during the study. Stable disease for up to 12 months was observed in patients with ovarian cancer as well as up to 20 months for a patient with cervical cancer. The combination of regorafenib and sildenafil at the recommended phase 2 dose is safe and generally well tolerated. Disease control in patients with gynecologic malignancies was especially encouraging. Further evaluation of the combination of regorafenib and sildenafil in gynecologic malignancies is warranted. Clinical Trial Registration Number: NCT02466802.

Equity and unmet need of non-communicable diseases services in Saudi Arabia using a National Household Survey (2019).

BACKGROUND: Saudi Arabia is implementing a comprehensive health system transformation in health services provision, governance, and financing. Given the high burden of non-communicable diseases (NCD), a key objective of the transformation is to integrate NCD prevention and treatment into primary care. The study objectives were to assess primary care service use for treatment of NCDs, to quantify existing inequities in preventive services utilization, and to identify regional and sociodemographic factors associated with these inequities. METHODS: Using the 2019 Kingdom of Saudi Arabia World Health Survey, multivariable logistic regression models were conducted to identify predictors of utilization of primary care services for NCD prevention and treatment, unmet need among those with a diagnosis of diabetes, hypertension, or dyslipidemia, and unmet need in breast and cervical cancer screening. RESULTS: Among those with an NCD diagnosis, living in a high-income household was associated with a lower probability of having an unmet need compared to those in low-income households. Furthermore, rural residents were less likely to have an unmet need compared to urban residents (OR 0.58, p=0.029). Individuals without a perceived need for healthcare within the last 12 months had three times the probability of unmet need in comparison to those with such a perceived need (p<0.001). Women in all regions had a lower probability of ever having a mammogram compared to women in the central regions around Riyadh. Women with an education above a secondary level had five times the odds of undergoing cervical cancer screening and three times the likelihood of ever having a mammogram (P=0.012, p=0.02) than other women. Compared to women in low-income households, those in middle (OR 1.99, P=0.026), upper middle (OR 3.47, p<0.001), or high-income households (OR 2.59, p<0.001) had a higher probability of having had cervical cancer screening. CONCLUSIONS: Inequities in NCD treatment and prevention services' utilization in Saudi Arabia are strongly associated with region of living, population density, wealth, income, education and perceived need for health care. More research is needed to better understand the extent of unmet primary care needs for NCD and how to address the underlying contributing factors to access inequities.

Co-creating a global shared research agenda on violence against women in low- and middle-income countries.

BACKGROUND: Despite a large growth in evidence on violence against women (VAW) over the last 25 years, VAW persists, as do gaps in the field's knowledge of how to prevent and respond to it. To ensure that research on VAW in low- and middle-income countries (LIMCs) is addressing the most significant gaps in knowledge, and to prioritise evidence needs to reduce VAW and better support victims/survivors, the Sexual Violence Research Initiative (SVRI) and Equality Institute (EQI) led a process of developing a global shared research agenda (GSRA) on VAW in LMICs. METHODS: The GSRA was developed through a six-stage adaptation of the Child Health and Nutrition Research Initiative (CHNRI) method, which draws on the principle of the 'wisdom of the crowd'. These steps included: a review of the literature on VAW in LMICs and development of domains; the generation of research questions within four domains by an Advisory Group; the consolidation of research questions; scoring of research questions by a Global Expert Group and the Advisory Group according to three criteria (applicability, effectiveness and equity); consultation and validation of the findings with the Advisory Group; and wide dissemination of the findings. RESULTS: The highest ranked research questions in the GSRA pertain to the domain of Intervention research, with some highly ranked questions also pertaining to the domain of Understanding VAW in its multiple forms. Questions under the other two domains, Improving existing interventions, and Methodological and measurement gaps, were not prioritised as highly by experts. There was strong consistency in top ranked research questions according to experts' characteristics, albeit with some important differences according to experts' gender, occupation and geographical location. CONCLUSIONS: The GSRA findings suggest that currently the VAW field is shifting towards intervention research after several decades of building evidence on understanding VAW, including prevalence, drivers and impacts of violence. The findings also suggest a strong emphasis on under-served populations, and under-researched forms of VAW. Future priority setting exercises in LMICs that seek to decolonise knowledge should ensure that methodologies, and modalities of engagement, put diverse voices at the centre of engagement. Trial registration Not applicable.

The Wisdom of Hindsight: Allies Reflections on Their Role in Supporting the Implementation of Expert by Experience Positions in Academia.

Experts by experience involvement in mental health education has consistently demonstrated positive attitudinal outcomes including a greater appreciation for recovery-focused practice. Mental health academic allies have played a crucial role in supporting implementation of expert by experience academic positions. To date the inclusion of their views in research is limited. The aim of this study was to explore and present allies' reflections on their involvement in supporting expert by experience academic roles in relation to "hindsight" and "foresight." A qualitative descriptive design was used, involving in-depth semi-structured interviews with allies who had supported the implementation of academic roles for experts by experience. Participants described the wisdom of hindsight. Based on their own experiences they emphasised the importance of, laying the groundwork, facilitating a supportive environment, contributing to meaningful, credible, and sustainable roles, and vision for the future as key to successful implementation. They also described a vision for the expansion of expert by experience roles in mental health education in the future. Allies' reflections suggest the importance of preparation to facilitate a smooth as possible implementation process and enhance the likelihood of successful outcomes. The transition to recovery-focused mental health services requires the attitudes of health professionals to change. The potential of experts by experience to influence attitudinal change can be enhanced by understanding the experiences and reflections of academic allies.

Using Modernized Medicaid Data to Advance Evidence-Based Improvements in Maternal Health.

Medicaid is the primary payor for nearly half of all births in the United States and plays a disproportionate role in covering maternity care for low-income people, rural people, and minoritized racial groups. Newly available, modernized Medicaid claims data-the Transformed Medicaid Statistical Information System Analytic Files (TAF)-offer a significant opportunity to conduct novel research that can drive the development of evidence-based programs and policies for Medicaid beneficiaries before, during, and after pregnancy. Yet, the public health research community has so far underused the TAF for maternal health research. We provide an overview of the TAF and how they compare to other major data sets available to study maternal health. We highlight some major limitations of the TAF and offer strategies to maximize the potential of these novel data to accelerate timely, rigorous research to improve maternal health and health equity. (Am J Public Health. 2023;113(7):805-810. https://doi.org/10.2105/AJPH.2023.307287).

From the chemical imbalance to the power imbalance: A psychiatry trainee's perspectives on service-user supervision.

OBJECTIVE: This paper describes perspectives and insights of a trainee's experience of service-user supervision. This includes the background to this novel approach, outlining its process and content, key themes arising, applications in practice, limitations of the approach, and future considerations. CONCLUSIONS: Service-user supervision promotes education and experiences at this important stage of professional development and can promote clinical, cultural, and systemic changes required to support the paradigm shift towards recovery-oriented and human rights-based practice.

Changing 'the world for the better': motivations of mental health academics for supporting expert by experience roles in mental health education.

BACKGROUND: Despite demonstrating positive outcomes in education, academic positions for Experts by Experience in mental health have not been widely implemented. To date positions have been driven by individual champions (allies). Their motivation for this support has not yet been researched. AIMS: To deepen understanding of motivations of mental health academics who have championed and supported implementation of EBE positions. METHODS: A Qualitative exploratory, study was undertaken involving in-depth individual interviews with 16 academics with experience of actively supporting the implementation of Expert by Experience positions in academia. Data were analysed independently by two researchers using a structured thematic framework. RESULTS: Motivations commonly arose from allies' own experiences of working with or exposure to Experts by Experience. Other motivating factors included: belief in the value of specific knowledge and expertise Experts by Experience contributed to mental health education; and, identifying the essential role Experts by Experience play in meeting policy expectations, and the broader philosophy of the university. CONCLUSIONS: The motivations identified by allies in this study have implications for Expert by Experience roles. Deeper understanding of motivations to support these roles is essential to arguing for their value, and ultimately producing positive outcomes in the education of health professionals.

Epithelium intrinsic vitamin A signaling co-ordinates pathogen clearance in the gut via IL-18.

Intestinal epithelial cells (IECs) are at the forefront of host-pathogen interactions, coordinating a cascade of immune responses to protect against pathogens. Here we show that IEC-intrinsic vitamin A signaling restricts pathogen invasion early in the infection and subsequently activates immune cells to promote pathogen clearance. Mice blocked for retinoic acid receptor (RAR) signaling selectively in IECs (stopΔIEC) showed higher Salmonella burden in colonic tissues early in the infection that associated with higher luminal and systemic loads of the pathogen at later stages. Higher pathogen burden in stopΔIEC mice correlated with attenuated mucosal interferon gamma (IFNγ) production by underlying immune cells. We found that, at homeostasis, the intestinal epithelium of stopΔIEC mice produced significantly lower amounts of interleukin 18 (IL-18), a potent inducer of IFNγ. Regulation of IL-18 by vitamin A was also observed in a dietary model of vitamin A supplementation. IL-18 reconstitution in stopΔIEC mice restored resistance to Salmonella by promoting epithelial cell shedding to eliminate infected cells and limit pathogen invasion early in infection. Further, IL-18 augmented IFNγ production by underlying immune cells to restrict pathogen burden and systemic spread. Our work uncovers a critical role for vitamin A in coordinating a biphasic immune response to Salmonella infection by regulating IL-18 production by IECs.

Expanding the genotype and phenotype spectrum of SYT1-associated neurodevelopmental disorder.

PURPOSE: Synaptotagmin-1 (SYT1) is a critical mediator of neurotransmitter release in the central nervous system. Previously reported missense SYT1 variants in the C2B domain are associated with severe intellectual disability, movement disorders, behavioral disturbances, and electroencephalogram abnormalities. In this study, we expand the genotypes and phenotypes and identify discriminating features of this disorder. METHODS: We describe 22 individuals with 15 de novo missense SYT1 variants. The evidence for pathogenicity is discussed, including the American College of Medical Genetics and Genomics/Association for Molecular Pathology criteria, known structure-function relationships, and molecular dynamics simulations. Quantitative behavioral data for 14 cases were compared with other monogenic neurodevelopmental disorders. RESULTS: Four variants were located in the C2A domain with the remainder in the C2B domain. We classified 6 variants as pathogenic, 4 as likely pathogenic, and 5 as variants of uncertain significance. Prevalent clinical phenotypes included delayed developmental milestones, abnormal eye physiology, movement disorders, and sleep disturbances. Discriminating behavioral characteristics were severity of motor and communication impairment, presence of motor stereotypies, and mood instability. CONCLUSION: Neurodevelopmental disorder-associated SYT1 variants extend beyond previously reported regions, and the phenotypic spectrum encompasses a broader range of severities than initially reported. This study guides the diagnosis and molecular understanding of this rare neurodevelopmental disorder and highlights a key role for SYT1 function in emotional regulation, motor control, and emergent cognitive function.

Coverage Disruptions and Transitions Across the ACA's Medicaid/Marketplace Income Cutoff.

BACKGROUND: The Affordable Care Act takes a "patchwork" approach to expanding coverage: Medicaid covers individuals with incomes 138% of the federal poverty level (FPL) in expansion states, while subsidized Marketplace insurance is available to those above this income cutoff. OBJECTIVE: To characterize the magnitude of churning between Medicaid and Marketplace coverage and to examine the impact of the 138% FPL income cutoff on stability of coverage. DESIGN: We measured the incidence of transitions between Medicaid and Marketplace coverage. Then, we used a differences-in-differences framework to compare insurance churning in Medicaid expansion and non-expansion states, before and after the ACA, among adults with incomes 100-200% of poverty. PARTICIPANTS: Non-elderly adult respondents of the Medical Expenditure Panel Survey 2010-2018 MAIN MEASURES: The annual proportion of adults who (1) transitioned between Medicaid and Marketplace coverage; (2) experienced any coverage disruption. KEY RESULTS: One million U.S. adults transitioned between Medicaid and Marketplace coverage annually. The 138% FPL cutoff in expansion states was not associated with an increase in insurance churning among individuals with incomes close to the cutoff. CONCLUSIONS: Transitions between Medicaid and Marketplace insurance are uncommon-far lower than pre-ACA analyses predicted. The 138% income cutoff does not to contribute significantly to insurance disruptions.

Can a combination of interventions accelerate outcomes to deliver on the Sustainable Development Goals for young children? Evidence from a longitudinal study in South Africa and Malawi.

BACKGROUND: This study aimed to identify possible entry points for interventions that can act as development accelerators for children and adolescents in South Africa and Malawi. METHODS: This study was a secondary data analysis. Data were sourced from the Child Community Care longitudinal study which tracked child well-being outcomes among 989 children (4-13 years) and their caregivers affected by HIV and enrolled in community-based organizations in South Africa and Malawi. We examined associations between five hypothesized accelerating services/household provisions-measured as access at baseline and follow-up and 12 child outcomes that relate to indicators within the Sustainable Development Goals (SDGs) framework. We calculated the adjusted probabilities of experiencing each SDG aligned outcome conditional on receipt of single, combined or all identified accelerators. RESULTS: The results show household food security is associated with positive child education and cognitive development outcomes. Cash grants were positively associated with nutrition and cognitive development outcomes. Living in a safe community was positively associated with all mental health outcomes. Experiencing a combination of two factors was associated with higher probability of positive child outcomes. However, experiencing all three accelerators was associated with better child outcomes, compared with any of the individual factors by themselves with substantial improvements noted in child education outcomes. CONCLUSIONS: Combined delivery of specific interventions or services may yield greater improvements in child outcomes across different developmental domains. It is recommended that multiple support avenues in combination like improving food security and safe communities, as well as social protection grants, should be provided for vulnerable children to maximize the impact.

Predictors of COVID-related changes in mental health in a South African sample of adolescents and young adults.

The COVID-19 pandemic has substantially affected the lives of young people living in sub-Saharan Africa (SSA), leading to poorer short-term mental health outcomes. However, longitudinal data investigating changes in mental health from pre-COVID levels and their predictors are lacking. Our longitudinal sample comprised N = 233 young people (mean age: 17.8 years at baseline, 55.6% female) living in a deprived neighbourhood near Cape Town, South Africa. Symptoms of depression (PHQ-9), anxiety (GAD-7) and alcohol use (AUDIT) were assessed during two waves of data collection, pre-pandemic (2018/19) and via phone interviews in June to October 2020, during South Africa's first COVID wave and subsequent case decline. Latent change score models were used to investigate predictors of changes in mental health. Controlling for baseline levels, we found increases in depression and anxiety but not alcohol use symptoms during the COVID-19 pandemic. Higher baseline symptoms were associated with smaller increases on all measures. Socio-economic deprivation (lack of household income, food insecurity) before and during COVID were associated with higher anxiety and depression symptom increases. Having had more positive experiences during COVID was associated with lower post-COVID onset anxiety and depression increases, and marginally with less alcohol use, while negative experiences (household arguments, worries) were linked to stronger symptom increases. Overall, in a sample of young people from an adverse environment in South Africa, we found increased mental health difficulties during the COVID-19 pandemic, though higher baseline symptoms did not necessarily predict stronger increases. Several factors pre- and post-COVID onset were identified that could be relevant for determining risk and resilience. In the long term, it will be key to address these structural drivers of well-being and to ensure mental health needs of young people are being met to support SSA countries in building back successfully from COVID-19 and preparing for future shock events.

"Making It Happen": Supporting the Implementation of Positions for Experts by Experience in Mental Health Education.

Significant changes to mental health policy have positioned consumers of mental health services as active participants in all aspects of service design and delivery, leading to the development and expansion of consumer workforce roles (Experts by Experience [EBE]). Negative attitudes of health professions pose a major limitation to the success of these positions. EBE involvement in mental health education has shown favourable outcomes, particularly enhancing more positive attitudes. Unfortunately, these positions remain limited in number and scope and have largely been supported by individual clinical academic champions (allies). This article presents findings from a qualitative study, involving individual interviews that explored the experiences and perceptions of allies who supported the implementation of academic positions for EBE. Data were analysed thematically. "Making it happen" was the overarching theme identified. It comprised the sub-themes: strategic or opportunistic?; developing an argument; using evidence; showing what EBE bring; getting buy-in and utilising existing relationships. The articulation of these processes provides a useful guide to other allies interested in supporting the implementation of these positions. The implementation of further positions will ultimately improve the attitudes of other health professionals towards Expert by Experience roles.

Supported Decision making teaching in New Zealand postgraduate psychiatry trainees.

OBJECTIVE: To examine psychiatric trainees teaching of supported decision-making (SDM). METHOD: New Zealand psychiatric trainees were surveyed about teaching regarding SDM using a novel tool. The analysis strategy examined the latent structure of the questionnaire and correlates of teaching in these areas. RESULTS: Forty nine trainees participated. Questions related to support from others and consistency of engagement were most highly endorsed while the concept of experiential learning was most poorly endorsed. Three latent factors were identified: 'enabling personhood', 'decision autonomy' and 'experiential learning'. Only gender correlated with the total summed score of the questionnaire, and two latent factors. CONCLUSIONS: Teaching about SDM occurs to some degree throughout New Zealand. The questionnaire captures the experience of learning in this area with a three-factor structure; enabling personhood, enhancing decisional autonomy and experiential learning.

'What's she doing here?' Overcoming barriers to the implementation of Expert by Experience positions in academia.

INTRODUCTION: Experts by Experience involvement in the education of health professionals has gained momentum as an important strategy in ensuring quality, person-centred education. Despite being a requirement for occupational therapy programs in Australia and internationally, involvement is variable and limited. Barriers to the implementation of academic roles have been identified, including negative attitudes of colleagues, systemic barriers, and insufficient evidence of their value. Mental health academics who do not identify as having lived experience (referred to as allies) have provided crucial support for Experts by Experience. Understanding their perspectives on implementation barriers and how they can be addressed is crucial to facilitating a broader level of meaningful involvement. METHODS: A qualitative exploratory research project was conducted, involving in-depth interviews with mental health academic allies (n = 16) from Australia, Ireland, and New Zealand. Participants were from the disciplines of nursing, occupational therapy, social work, and psychiatry. Data were analysed thematically. FINDINGS: Two main themes were identified from the data analysis process: convincing colleagues and dealing with university barriers. Participants described varying attitudes from colleagues towards Experts by Experience, with many not understanding or appreciating their contribution to education and student outcomes. At the university level, reluctance to embrace innovation and funding and other resource shortages presented impediments to the implementation of Expert by Experience roles. Participants described using creative measures to overcome institutional barriers and encourage greater acceptance of such roles by colleagues. CONCLUSION: This research describes how allies experienced and overcame barriers they faced when supporting the implementation of academic positions for Experts by Experience. Allies have an important role to play in overcoming systemic barriers, and the approaches they have taken to achieve this may be an important source of learning for others with similar aspirations.

Disorders of synaptic vesicle fusion machinery.

The revolution in genetic technology has ushered in a new age for our understanding of the underlying causes of neurodevelopmental, neuromuscular and neurodegenerative disorders, revealing that the presynaptic machinery governing synaptic vesicle fusion is compromised in many of these neurological disorders. This builds upon decades of research showing that disturbance to neurotransmitter release via toxins can cause acute neurological dysfunction. In this review, we focus on disorders of synaptic vesicle fusion caused either by toxic insult to the presynapse or alterations to genes encoding the key proteins that control and regulate fusion: the SNARE proteins (synaptobrevin, syntaxin-1 and SNAP-25), Munc18, Munc13, synaptotagmin, complexin, CSPα, α-synuclein, PRRT2 and tomosyn. We discuss the roles of these proteins and the cellular and molecular mechanisms underpinning neurological deficits in these disorders.

Preface to the Special Issue "Presynaptic Dysfunction and Disease".

The synapse is formed between a presynapse (which releases neurotransmitter) and the postsynapse (which transduces this chemical signal). Over the past decade, presynaptic dysfunction has emerged as a key mediator of a series of neurodevelopmental and neurodegenerative disorders. This special issue will highlight some of the important presynaptic molecules and mechanisms that are disrupted in these conditions and reveal potential routes for therapy.

County-level Predictors of Growth in Community-based Primary Care Use Among Veterans.

BACKGROUND: The 2014 Choice Act expanded the Veterans Health Administration's (VA) capacity to purchase services for VA enrollees from community providers, yet little is known regarding the growth of Veterans' primary care use in community settings. OBJECTIVES: The aim was to measure county-level growth in VA community-based primary care (CBPC) penetration following the Choice Act and to assess whether CBPC penetration increased in rural counties with limited access to VA facilities. DATA AND SAMPLE: A total of 3132 counties from VA administrative data from 2015 to 2018, Area Health Resources Files, and County Health Rankings. ANALYSIS: We defined the county-level CBPC penetration rate as the proportion of VA-purchased primary care out of all VA-purchased primary care (ie, within and outside VA). We estimated county-level multivariate linear regression models to assess whether rurality and supply of primary care providers and health care facilities were significantly associated with CBPC growth. RESULTS: Nationally, CBPC penetration rates increased from 2.7% in 2015 to 7.3% in 2018. The rurality of the county was associated with a 2-3 percentage point (pp) increase in CBPC penetration growth (P<0.001). The presence of a VA facility was associated with a 1.7 pp decrease in CBPC penetration growth (P<0.001), while lower primary care provider supply was associated with a 0.6 pp increase in CBPC growth (P<0.001). CONCLUSION: CBPC as a proportion of all VA-purchased primary care was small but increased nearly 3-fold between 2015 and 2018. Greater increases in CBPC penetration were concentrated in rural counties and counties without a VA facility, suggesting that community care may enhance primary care access in rural areas with less VA presence.

Post hoc analyses of GOG 9923: Does BRCA status affect toxicities?: An NRG oncology study.

OBJECTIVE: To evaluate how women with epithelial ovarian cancer (EOC), dichotomized by BRCA status, tolerate intravenous (IV) or intraperitoneal (IP) chemotherapy given with veliparib and bevacizumab (bev) on a GOG phase I study (GOG 9923, NCT00989651). METHODS: This is an unplanned, post hoc analysis of an IRB approved, multi-institutional, prospective study (GOG 9923). Clinical characteristics and toxicity data based on BRCA status were evaluated and descriptive statistics were used to summarize baseline patient characteristics and toxicities. The Kaplan Meier method was used to generate survival estimates. RESULTS: Four hundred twenty-four patients were evaluable. Patients were treated with IV carboplatin, paclitaxel, and bev every 21 days (regimen 1), weekly IV paclitaxel with carboplatin and bev (regimen 2) or IV paclitaxel and bev with IP cisplatin (regimen 3). Bev was continued as maintenance in all arms. Within each of these regimens, veliparib was given either twice daily for the entirety of each cycle (continuous) or on days -2 to 5 (intermittent). Ten percent of patients treated on regimen 1, 12% on regimen 2, and 19.8% on regimen 3 had BRCA-associated tumors. Patients with BRCA-associated tumors, when compared to wild type, experienced similar rates of anemia, febrile neutropenia (, abdominal pain, colonic perforation, nausea, vomiting, and peripheral sensory neuropathy. Median progression free survival (PFS) was not significantly different between BRCA-associated and wild type cancers (HR 0.96, CI 0.65-1.42), though this study's primary aim was not to evaluate outcomes. CONCLUSIONS: Germline BRCA mutations positively affect chemosensitivity in EOC, but whether differences in toxicities among BRCA-associated and BRCA wild type tumors existed was previously not reported. In this population with newly diagnosed ovarian cancer no differences in reported toxicity between the two groups was observed.