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1.
Mil Med ; 188(Suppl 4): 32-40, 2023 07 25.
Article in English | MEDLINE | ID: mdl-36342779

ABSTRACT

INTRODUCTION: As the burgeoning roles of women afford them the opportunities to perform in all combat and combat support assignments, the impact of all environmental, occupational, physical, and psychosocial factors inherent in military training and operations on their health must be considered. A robust foundation of knowledge is necessary to ascertain, prevent, and treat the potential impacts on women's health. However, a systematic review of the literature from 2000-2015 revealed widespread gaps in scientific knowledge of the musculoskeletal, psychological, occupational, and reproductive health of military women. The purpose of this study is to determine priorities for military women's health (MWH) research that will serve to fill these gaps in knowledge. METHODS: An advisory group of 11 senior military and women's health experts conducted a structured gap analysis of the results of a scoping review of literature from 2000 to 2015 and Military Health System utilization data to identify 15 topics for prioritization in MWH research. A modified e-Delphi study was conducted and consensus was achieved after two rounds. Participants (N = 32) included subject matter experts (SME) representing various professions enrolled, 23 completed both rounds. In round 1, topics were rated on forced Likert scales for relevance and feasibility to medical readiness and comments were elicited from the SMEs. Relevance and feasibility scores and themes from the comments guided the development of the round 2 survey, in which SMEs categorized the topics in terms of urgency and forced-choice ranked the priority of each topic. The quantitative data were analyzed using multilevel regression methods. Linear mixed models were fit separately on the numeric outcomes for feasibility, relevance, and urgency with research topic as the primary predictor. To analyze the rankings of research topic priority, crude and adjusted linear regression models were fit on the numeric outcome rank. RESULTS: The adjusted top five topics for research priorities as indicated by ranking were: genitourinary health, sleep, physical assault, behavioral health, and menstrual cycle research. The advisory group reviewed the findings in the context of Department of Defense strategic priorities and provided guidance on the design and dissemination of the MWH research agenda. CONCLUSIONS: The MWH research agenda is a validated research agenda of high-priority research topics that will promote enduring efforts to ensure evidence-based practices and health policies for military women through research.


Subject(s)
Military Personnel , Women's Health , Humans , Female , Delphi Technique , Health Services Research , Surveys and Questionnaires
3.
Womens Health Issues ; 31 Suppl 1: S53-S65, 2021 08 25.
Article in English | MEDLINE | ID: mdl-34454704

ABSTRACT

INTRODUCTION: Maintaining military readiness requires integration and delivery of appropriate sex-specific health care services for active duty servicewomen (ADSW). Cervical cancer screening (CCS) provides early detection, intervention, and treatment, allowing for reductions in human papillomavirus (HPV) infections and cervical cancer cases. This scoping review examines existing cervical cancer evidence related to ADSW and identifies research gaps, leverage points, and policy recommendations within the context of the social ecological model for military women's health. METHODS: We conducted a scoping literature search using both indexed databases and nonindexed sources. We managed retrieved records from 2000 to 2018 with Endnote reference and DistillerSR systematic review software. RESULTS: Of 1,006 records from indexed databases and 208 records from nonindexed resources retrieved, 40 publications met the inclusion criteria. Cervical cancer research addressing ADSW is limited. Servicewomen have high rates of known cancer risk factors and face challenges related to deployments and change of duty station that affect continuity of health care and timely follow-up for abnormal CCS. Multimodal interventions with stakeholder support can encourage CCS adherence and increase HPV vaccination rates. CONCLUSION: Maintaining military readiness among ADSW requires robust evidence-based prevention efforts to address risk factors that are reportedly higher among servicewomen, as well as challenges to continuity in health care delivery that may increase the likelihood of cervical cancer incidence. Recognizing the role of HPV vaccination as cancer prevention, collaborations and partnerships, research, best practices, and creative solutions to close ADSW's sex-specific health gaps will help to ensure a fit and ready force.


Subject(s)
Military Personnel , Papillomavirus Infections , Uterine Cervical Neoplasms , Early Detection of Cancer , Female , Humans , Papillomavirus Infections/diagnosis , Papillomavirus Infections/prevention & control , Risk Factors , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/prevention & control
5.
Nurs Outlook ; 69(3): 311-321, 2021.
Article in English | MEDLINE | ID: mdl-33579514

ABSTRACT

BACKGROUND: Military nurse scientists are embedded in service-affiliated branches (Army, Navy, Air Force) with different missions, but with the singular purpose of generating and disseminating research impacting the health and well-being of DoD beneficiaries. PURPOSE: This project examines collaboration among TriService Nursing Research Program (TSNRP) members, seeking opportunities to strengthen, diversify, and expand research collaboration. METHOD: Social network analysis (SNA) is the empirical inquiry of relations among social actors at different levels of analysis. An electronic SNA assessment and total enumerative sampling were used to explore current collaborations among PhD-prepared military nurse scientists (N = 136). FINDINGS: The TSNRP collaboration network has a complex service-driven structure with high status actors whose advice, knowledge, or skills are sought by others, and who function as connectors or bridges across service branches. DISCUSSION: For military scientists, SNA is instrumental in identifying influential individuals, visualizing opportunities for intraservice mentoring, designing responsive policy, and directing career opportunities for novice scientists.


Subject(s)
Military Nursing/organization & administration , Military Personnel/education , Military Personnel/psychology , Nursing Research/organization & administration , Research Personnel/education , Research Personnel/psychology , Social Networking , Adult , Female , Humans , Intersectoral Collaboration , Male , Middle Aged , Military Nursing/education , Military Personnel/statistics & numerical data , Nursing Research/education , United States
6.
Mil Med ; 186(9-10): e932-e942, 2021 08 28.
Article in English | MEDLINE | ID: mdl-33382426

ABSTRACT

BACKGROUND: Although combat stress and psychiatric casualties of war have consistently contributed to the need for deployed patient transport to higher echelons of care, little is known regarding specific evidence-based strategies for providing psychological support and optimal transport interventions for warriors. STUDY OBJECTIVE: The purpose of this scoping review is to map existing literature related to considerations for deployed mental health patient transport. The review's primary aims are to identify the existing scientific research evidence, determine research and training gaps, and recommend critical areas for future military research. METHODS: We used Arksey and O'Malley's six-stage scoping review methodological framework (identify the research question, identify relevant studies, select studies, chart data, report results, and consultation). Using a systematic search strategy, we evaluated peer-reviewed literature from five databases (PubMed, CINAHL, PsycINFO, Web of Science, and Embase) and gray literature from the Defense Technical Information Center. All publications were independently screened for eligibility by two researchers during three review rounds (title, abstract, and full text). RESULTS: We identified 1,384 publications, 61 of which met our inclusion criteria. Most publications and technical reports were level IV evidence and below, primarily retrospective cohort studies and epidemiologic surveillance reports. Few rigorously designed studies were identified. Eight research themes and a variety of research and critical training gaps were derived from the reviewed literature. Themes included (1) characterizing mental health patients aeromedically evacuated from theater; (2) in-flight sedation medications; (3) need for aeromedical evacuation (AE) in-theater education, training, and guidelines for staff; (4) epidemiological surveillance of AE from theater; (5) mental health management in deployed settings; (6) suicide-related event management; (7) transport issues for mental health patients; and (8) psychological stressors of AE. Research is needed to establish clinical practice guidelines for mental health condition management in theater and throughout the continuum of en route care.


Subject(s)
Mental Disorders , Military Personnel , Suicide , Humans , Mental Disorders/epidemiology , Mental Disorders/therapy , Mental Health , Retrospective Studies
7.
Adv Neonatal Care ; 21(5): 387-398, 2021 Oct 01.
Article in English | MEDLINE | ID: mdl-33009159

ABSTRACT

BACKGROUND: Parental support in the neonatal intensive care unit (NICU) is critical; yet, the nursing staff may struggle to provide optimal support to NICU fathers. Generally, fathers are not viewed as equally competent caregivers when compared with mothers, and fathers often impart these beliefs on themselves. Increasing the nursing staff's knowledge and understanding of paternal support can change attitudes and foster positive behavior changes, enhancing the perception of support received by NICU fathers. PURPOSE: To implement a needs assessment and educational intervention for the nursing staff designed to increase the perception of nursing support received by NICU fathers. METHODS: The Nurse Parents Support Tool (NPST) was administered to the clinical nursing staff and fathers in a pre/posttest design comparing support given by nurses with the fathers' perception of received support. Data from the preintervention assessment was used to design an educational intervention on improving fathers' support. Following the intervention, a postintervention NPST was administered to fathers to determine whether there was an improvement in support perception. FINDINGS/RESULTS: Improvement in the NICU fathers' perception of nursing staff support was noted between father groups. In addition, the NPST can be used to assess paternal support needs and develop staff education. IMPLICATIONS FOR PRACTICE: Support provided to NICU fathers can enhance the father's perception of himself as an equal and competent caregiver, leading to improved father-infant bonding as the child ages. Educational interventions targeting father support should be a routine part of nursing staff training. IMPLICATIONS FOR RESEARCH: Future research should examine the long-term effects of early paternal support on psychosocial, cognitive, and developmental outcomes of NICU infants.


Subject(s)
Fathers , Intensive Care Units, Neonatal , Child , Father-Child Relations , Female , Humans , Infant , Infant, Newborn , Male , Mothers , Object Attachment
8.
J Am Assoc Nurse Pract ; 32(11): 729-737, 2020 Nov.
Article in English | MEDLINE | ID: mdl-33177334

ABSTRACT

BACKGROUND: An increased incidence in hygiene-related urogenital infections (bacterial vaginitis, vulvovaginal candidiasis, and urinary tract) has been reported in female warfighters serving in austere environments with decreased availability of water and sanitation resources, and when personal safety outweighs concerns for hygiene. Knowledge and access to an innovative kit designed for the female warfighter to self-test, self-identify, and self-treat common urogenital symptoms is critical to force health. PURPOSE: The purpose of this descriptive, cross-sectional, exploratory qualitative study was to explore female warfighters': 1) confidence in seeking sex-specific health care in field and deployment environments and 2) acceptance and willingness to self-test, self-identify, and self-treat urogenital symptoms and infections. METHODOLOGICAL ORIENTATION: Qualitative data for this thematic analysis were collected during administration of the Military Women's Readiness Urogenital Health Questionnaire. Participants provided open-ended comments associated with three survey questions. Braun and Clarke's inductive thematic analysis method guided the narrative analysis. SAMPLE: Our sample included a diverse group of US Army women (USAW; n = 152) from a large, military installation. RESULTS: Narratives and themes demonstrate USAW's desire and need for the availability of a self-test and self-treatment kit. Access, time, mission, and prevention of self-harm by quicker resolve of symptoms are cited as key reasons in support of such a kit. CONCLUSIONS AND PRACTICE IMPLICATIONS: Nurse practitioners (NPs) are ideally positioned to provide sex-specific educational interventions and anticipatory guidance that supports physical health, to include urogenital conditions. As urogenital self-testing becomes available for female warfighters, NPs are the model healthcare provider for educating women on their use.


Subject(s)
Military Personnel/psychology , Perception , Urogenital System , Warfare , Adult , Candidiasis, Vulvovaginal/diagnosis , Candidiasis, Vulvovaginal/epidemiology , Candidiasis, Vulvovaginal/psychology , Cross-Sectional Studies , Female , Humans , Hygiene/standards , Incidence , Military Personnel/statistics & numerical data , Narration , Nurse's Role , Qualitative Research , Self-Testing , United States/epidemiology , Urinary Tract Infections/diagnosis , Urinary Tract Infections/epidemiology , Urinary Tract Infections/psychology , Vaginosis, Bacterial/diagnosis , Vaginosis, Bacterial/epidemiology , Vaginosis, Bacterial/psychology
9.
Mil Med ; 185(Suppl 2): 7-14, 2020 06 19.
Article in English | MEDLINE | ID: mdl-32373935

ABSTRACT

BACKGROUND: In 2017, the TriService Nursing Research Program completed a strategic planning session, which identified key barriers to implementing evidence-based practice (EBP) within the U.S. Military Health System (MHS) including a focus on readiness training and deployments, frequent staff moves for military members, and relatively junior nurses in clinical roles. To facilitate EBP at individual military treatment facilities (MTFs), an EPB Facilitator role was developed using an evidence-based model and based on validated EBP competencies. METHODS: This new role was implemented at four MTFs in 2018: Naval Medical Center Portsmouth, 59th Medical Wing at Joint Base San Antonio Lackland, Naval Medical Center San Diego, and David Grant USAF Medical Center at Travis Air Force Base. This case series provides a description of the initial implementation of this role. RESULTS: Common enablers and challenges were identified from the experiences at all four sites. These included the importance of incorporating efforts into existing organizational efforts and infrastructure; the value of nurse leaders inviting EBP facilitators to participate and engage in scheduled meetings and committees; the significance of engaging with existing quality, process improvement, and training initiatives; and the benefit of collaborating with advanced practice nurses within the organization. The common challenges for all EBP facilitators were the frequent staff turnover at all levels and a lack of standardization to review and approve EBP initiatives, which makes it difficult to navigate the complete process of project implementation and collaboration across sites. Another challenge has been the difficulty to measure the impact of this role at the MTF and MHS levels. CONCLUSIONS: As EBP efforts continue and the program matures, it is anticipated that the outcomes from the individually completed projects, to include decreases in safety events, fiscal savings, and other improvements in organizational metrics, can be compiled to demonstrate the collective impact of these roles within the MHS.


Subject(s)
Evidence-Based Nursing , Nurses , Evidence-Based Practice , Humans , Organizational Culture
10.
Mil Med ; 184(11-12): e758-e764, 2019 12 01.
Article in English | MEDLINE | ID: mdl-31141136

ABSTRACT

INTRODUCTION: Global health engagement missions are conducted to improve and protect the health of populations worldwide. Recognizing the strong link between health and security, the Armed Forces have increased the number of global health engagement missions over the last decade to support force health protection, medical readiness, enhance interoperability, improve host nation capacity building, combat global health threats (i.e., emerging infectious diseases), support humanitarian assistance and disaster relief efforts, as well as build trust and deepen professional medical relationships worldwide. These missions additionally support the US Global Health Security Agenda, US National Security Strategy, US National Defense Strategy and National Military Strategy.Although global health engagement missions are conducted by armed forces with numerous military units and geographical locations, military healthcare personnel assigned to US Naval hospital ships also perform a wide range of these missions. These missions comprise some of the largest global health engagement missions conducted, encompassing hundreds of subject matter expert exchanges, community health exchanges, medical symposiums, and side-by-side partnered healthcare in countries around the world. Military healthcare personnel who have completed past missions possess valuable knowledge related to ship-based global health engagement missions. Capturing and transferring this knowledge to future deployed personnel is important for future successful missions, but has remained a significant challenge. The purpose of this study was to capture and examine first-person accounts of experiential learning among active duty physicians, nurses, and hospital corpsmen who had participated in recent hospital ship-based global heath engagement missions. MATERIALS AND METHODS: We used the interpretive, ethnographic method of interviewing and data analysis described by Benner. Interviews elicited detailed, narrative examples of experiences from military health care personnel who had participated in previous global health engagement missions aboard hospital ships (N = 141). Our approach to gaining meaning from these narratives was guided by three central strategies: (1) identify paradigm cases, (2) identify themes within and across participant narratives of meaningful patterns, and (3) identify exemplars to represent common patterns of meaning and common situations. Additionally, we collected demographic information. RESULTS: Our findings provide firsthand descriptions of five essential elements to prepare military healthcare personnel for shipboard global health engagement missions. These essential elements are mission clarity, preparedness, experiential knowledge, lessons learned, and flexibility/adaptability. CONCLUSIONS: Widespread dissemination of the lessons learned from military global health engagement missions is crucial to shaping forces that operate effectively in a rapidly changing global environment. Sharing lessons learned increases efficiency, adaptability, and agility, while decreasing variance in processes and the need to relearn mission-specific lessons.


Subject(s)
Health Personnel/trends , Military Personnel/education , Global Health/education , Health Personnel/education , Humans , Military Personnel/psychology , Military Personnel/statistics & numerical data , Naval Medicine/methods , Naval Medicine/trends , Relief Work , Ships/statistics & numerical data , United States
13.
Nurs Outlook ; 65(5S): S17-S25, 2017.
Article in English | MEDLINE | ID: mdl-28800835

ABSTRACT

BACKGROUND: The recent removal of United States military combat exclusion rules resulted in more women serving in forward deployed austere conditions. In the deployed setting, women were diagnosed with genitourinary (GU) conditions five times greater than men. PURPOSE: Describe deployed military women's GU illness behaviors. METHOD: Two qualitative descriptive studies interviewing military women and enlisted medics were synthesized using the Illness Behavior Model. DISCUSSION: Similar and divergent views on the impact of the military culture of the illness behaviors were described by women and medics. Both agreed appropriate attention on managing GU symptoms must continue; however differing strategies were appraised. One agreed option was to offer a health care mentor. CONCLUSION: The Illness Behavior Model provided an excellent framework for evaluation of military women's illness behaviors exposing areas for comparing and contrasting the perspectives provided. While significant changes have been made, additional strategies will continue to improve the women's deployed health care quality.


Subject(s)
Female Urogenital Diseases/psychology , Illness Behavior , Military Personnel , Adaptation, Psychological , Adult , Female , Female Urogenital Diseases/complications , Female Urogenital Diseases/therapy , Humans , Models, Theoretical , Patient Acceptance of Health Care , Qualitative Research , Self Care , United States , War Exposure , Young Adult
14.
Dev Neurosci ; 39(1-4): 287-297, 2017.
Article in English | MEDLINE | ID: mdl-28343223

ABSTRACT

BACKGROUND: Hypoxic-ischemic (HI) injury to the developing brain occurs in 1 out of 1,000 live births and remains a major cause of significant morbidity and mortality. A large number of survivors suffer from long-term sequelae including seizures and neurological deficits. However, the pathophysiological mechanisms of recovery after HI insult are not clearly understood, and preventive measures or clinical treatments are nonexistent or not sufficiently effective in the clinical setting. Sildenafil as a specific phosphodiesterase 5 inhibitor leads to increased levels of the second messenger cyclic guanosine monophosphate (cGMP) and promotes functional recovery and neurogenesis after ischemic injury to the adult brain. OBJECTIVE: Here, we investigated the effect of sildenafil treatment on activation of intracellular signaling pathways, histological and neurogenic response including functional recovery after an ischemic insult to the developing brain. DESIGN/METHODS: Nine-day-old C57BL/6 mice were subjected either to sham operation or underwent ligation of the right common carotid artery followed by hypoxia (8%) for 60 min. Animals were either administered sildenafil (10 mg/kg, i.p.) or vehicle 2 h after hypoxia. A subgroup of animals received multiple injections of 10 mg/kg daily on 5 consecutive days. Pups were either perfusion fixed at postnatal days 14 or 47 for immunohistochemical analysis, or brains were dissected 2, 6, 12, and 24 h after the end of hypoxia and analyzed for cGMP, pAkt, pGSK-3ß, and ß-catenin by means of ELISA or immunoblotting. In addition, behavioral studies using the wire hang test and elevated plus maze were conducted 21 and 38 days after HI injury. RESULTS: Based on cresyl violet staining, single or multiple sildenafil injections did not reveal any differences in injury scoring compared to sham animals. However, cerebral levels of cGMP were altered after sildenafil therapy. Treatment significantly increased numbers of immature neurons, as indicated by doublecortin immunoreactivity in the ipsilateral subventricular zone and striatum. In addition, animals treated with sildenafil after HI insult demonstrated improved functional recovery. pAkt, pGSK-3ß, and ß-catenin levels vary after HI injury but additional sildenafil treatment had no impact on protein expression compared to the level of sham controls. CONCLUSIONS: Here, we report that treatment with sildenafil after HI insult did not improve histological brain injury scores. Nevertheless, our results suggest involvement of the cGMP and PI3K/Akt/GSK-3ß signaling pathway with promotion of a neurogenic response and reduction of neurological deficits. In summary, sildenafil may have a role in promoting recovery from HI injury in the developing brain.


Subject(s)
Brain/drug effects , Hypoxia-Ischemia, Brain , Phosphodiesterase 5 Inhibitors/pharmacology , Recovery of Function/drug effects , Sildenafil Citrate/pharmacology , Animals , Animals, Newborn , Mice , Mice, Inbred C57BL , Neurons , Random Allocation
15.
J Midwifery Womens Health ; 61(2): 249-56, 2016.
Article in English | MEDLINE | ID: mdl-26849103

ABSTRACT

INTRODUCTION: Recent policy revisions allow greater inclusion of military women in operational and/or deployable positions (ie, shipboard, overseas, and war zone duty assignments), but these positions can create unique health care challenges. Military members are often transient due to deployments and change of duty stations, impacting timely follow-up care for treatable health conditions. There has been minimal research on challenges or strategies in preventive health screening and follow-up for US military women. METHODS: The purpose of this qualitative research study was to describe US Navy women's experiences with abnormal cervical cancer screenings requiring colposcopic follow-up care. Ship- and shored-based women receiving care at a military colposcopy clinic completed interviews about their experience. Two forms of narrative analysis, Labov's sociolinguistic structural analysis and Braun and Clarke's thematic analysis, were employed to gain a more robust understanding of the women's experiences. RESULTS: The sample was comprised of 26 women (16 ship-based, 10 shore-based). Five themes were identified: 1) It's like this bombshell (initial abnormal results notification); 2) I didn't understand (self-discovery process); 3) Freaked (emotional toll); 4) It's kind of like this back and forth (scheduling and navigating care); and 5) It really opened my eyes (lessons learned). DISCUSSION: The women's stories highlighted some issues unique to military health care, such as operational demands and follow-up care; other issues are likely common for most women learning about an abnormal cervical cancer screening result. Areas important for practice and future research include improving notification practices, providing information, understanding women's fear, and continuity of care. Research exploring educational initiatives and self-management practices are critical within military populations.


Subject(s)
Attitude to Health , Early Detection of Cancer , Mass Screening , Military Personnel , Uterine Cervical Neoplasms/diagnosis , Adult , Fear , Female , Humans , Pregnancy , Qualitative Research , Uterine Cervical Neoplasms/psychology , Vaginal Smears , Young Adult
16.
Mil Med ; 181(1): 35-49, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26741475

ABSTRACT

OBJECTIVES: This integrated literature review evaluated research on genitourinary and reproductive health care needs and gender-specific health care delivery for active duty U.S. military women, a growing population in the armed forces. METHODS: A literature search was conducted for publications on genitourinary and reproductive health published between 2008 and 2014 using keywords and terms utilized in previous systematic literature reviews in similar military populations. RESULTS: Previous literature reviews concentrated on broader health care issues of military women. This review updates and expands the literature identified in three previous reviews. Publications were evaluated for relevancy to U.S. military women's health and a sample of 82 publications was included. Five broad categories were addressed across the literature: (1) pregnancy health, (2) deployment and preventive health, (3) sexually transmitted infections, (4) family planning and contraceptive services, and (5) sexual violations. DISCUSSION: Health care challenges are evolving within a changing military environment that includes a greater integration of women. Contraceptive, genitourinary-reproductive health care access, and self-diagnostic tools for easily treatable vulvovaginal conditions can empower military women and improve quality of life. CONCLUSIONS: Studies examining military gender-specific health care delivery are limited. Research to understand factors important for women in a changing military environment can improve health care delivery and outcomes, and military readiness.


Subject(s)
Family Planning Services , Military Personnel , Reproductive Health , Women's Health , Contraception , Female , Genital Diseases, Female , Humans , Pregnancy , Preventive Health Services , Sexually Transmitted Diseases , United States
17.
Mil Med ; 180(12): 1247-55, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26633669

ABSTRACT

OBJECTIVES: To examine literature on recruitment and retention of military women in research studies as an underrepresented, and potentially marginalized, population. METHODS: A literature search was conducted to examine challenges, identify potential barriers and facilitators, and to inform strategies for recruitment and retention of military women in research studies. This search was supplemented by findings in military-specific databases and discussions with Military Women's Health Research Interest Group subject matter experts. RESULTS: Ten articles addressed research recruitment and retention challenges and strategies in marginalized/underrepresented populations, providing an effective context to inform research recruitment and retention in military settings. Research with military women is often challenged by logistical, cultural, social, ethical, and methodological issues, which may hinder exploration of potentially sensitive issues. DISCUSSION: Researchers must consider military-specific challenges to conducting research that include lengthy deployments, unpredictable military exercises, and foreign assignments, in accessing research participants. A case example shows strategies used in a military cervical cancer screening study. CONCLUSION: There are few published articles specific to research recruitment and retention in female military populations. Available resources broadly address recruitment challenges for Veterans, marginalized, hard-to-access, and transient research participants, which may provide guidance and strategies for success when applied to military populations.


Subject(s)
Military Personnel/statistics & numerical data , Patient Selection , Clinical Trials as Topic/methods , Female , Humans , Patient Selection/ethics , Research Subjects , Women's Health
18.
Mod Pathol ; 26(9): 1161-71, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23558572

ABSTRACT

The majority of luminal type breast carcinomas are slowly growing tumors with an overall favorable prognosis. However, a proportion of cases (luminal B tumors) are characterized by coactivation of growth factor receptors or non-canonical ER signaling and a poorer clinical outcome. The aim of our study was to evaluate whether the expression of proteins that are part of the ER signaling network may be used to distinguish low-risk from high-risk luminal tumors. Unsupervised hierarchical clustering of a set of proteins either involved in estrogen receptor signaling or associated with resistance to endocrine therapy was performed in a series of 443 postmenopausal breast carcinomas. Using this approach, we were able to reproduce the established classification with two distinct groups of luminal (estrogen receptor positive) tumors, one group of HER2-associated tumors and a group of triple-negative tumors. However, neither proliferation nor the expression of one or more of the ER-co-factors or resistance-associated factors, but PR-expression was identified as the most important stratifier distinguishing between the two luminal groups. In fact, not only the four identified clusters were shown to be significantly associated with patient outcome, PR-expression alone or in combination with Ki-67-stains stratified ER-positive tumors into a low-risk and a high-risk group. Our data indicate that defining luminal B tumors by the presence of high-risk criteria (loss of PR-expression or increased proliferation) provides a robust and highly significant stratification of ER-positive breast carcinomas into luminal A and B.


Subject(s)
Biomarkers, Tumor/analysis , Carcinoma/chemistry , Neoplasms, Hormone-Dependent/chemistry , Receptors, Estrogen/analysis , Receptors, Progesterone/analysis , Signal Transduction , Triple Negative Breast Neoplasms/chemistry , Aged , Biopsy , Carcinoma/classification , Carcinoma/mortality , Carcinoma/pathology , Cell Proliferation , Cluster Analysis , Disease Progression , Disease-Free Survival , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Ki-67 Antigen/analysis , Middle Aged , Multivariate Analysis , Neoplasm Grading , Neoplasm Staging , Neoplasms, Hormone-Dependent/classification , Neoplasms, Hormone-Dependent/mortality , Neoplasms, Hormone-Dependent/pathology , Odds Ratio , Predictive Value of Tests , Proportional Hazards Models , Receptor, ErbB-2/analysis , Risk Assessment , Risk Factors , Triple Negative Breast Neoplasms/classification , Triple Negative Breast Neoplasms/mortality , Triple Negative Breast Neoplasms/pathology
19.
Am J Surg Pathol ; 36(8): 1247-52, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22790863

ABSTRACT

Flat epithelial atypia (FEA) of the breast typically is a localized alteration involving only few, neighboring terminal ducto-lobular units. However, occasionally there are cases with extensive FEA and morphologic evidence of direct transitions between FEA and classical low-grade ductal carcinoma in situ (lg-DCIS). To investigate the relationship between FEA and DCIS in these cases, we microdissected multiple foci of the respective lesions in a series of 10 cases and performed comparative allelotyping using a panel of 14 loss of heterozygosity markers. In addition, phylogenetic tree models were calculated on the basis of mitochondrial DNA sequencing to visualize the clonal relationship of the different lesions. FEA and lg-DCIS shared the majority of chromosomal imbalances; loss of diverging alleles was not detected in any of the 10 cases. Mitochondrial DNA sequencing and phylogenetic tree clustering revealed direct transitions between FEA and lg-DCIS in all 10 cases. However, in 3 patients, additional foci of FEA were present, which were not directly related to the rest of the FEA and the lg-DCIS. Our data demonstrate the presence of direct transitions between FEA and lg-DCIS and support the interpretation of FEA as part of the low-grade pathway in the development of breast cancer.


Subject(s)
Breast Neoplasms/genetics , Breast Neoplasms/pathology , Carcinoma, Intraductal, Noninfiltrating/genetics , Carcinoma, Intraductal, Noninfiltrating/pathology , Precancerous Conditions/genetics , Precancerous Conditions/pathology , DNA, Mitochondrial/genetics , Female , Humans , Loss of Heterozygosity , Middle Aged , Neoplasm Grading
20.
J Am Chem Soc ; 130(20): 6336-7, 2008 May 21.
Article in English | MEDLINE | ID: mdl-18444614

ABSTRACT

Acyl carrier protein (ACP) plays an essential role in fatty acid and polyketide biosynthesis, and most of the fatty acid synthases (FASs) and polyketide synthases (PKSs) known to date are characterized with a single ACP for each cycle of chain elongation. Polyunsaturated fatty acid (PUFA) biosynthesis is catalyzed by the PUFA synthase, and all PUFA synthases known to date contain tandem ACPs (ranging from 5 to 9). Using the Pfa PUFA synthase from Shewanella japonica as a model system, we report here that these tandem ACPs are functionally equivalent regardless of their physical location within the PUFA synthase subunit, but the total number of ACPs controls the overall PUFA titer. These findings set the stage to interrogate other domains and subunits of PUFA synthase for their roles in controlling the final PUFA products and could potentially be exploited to improve PUFA production.


Subject(s)
Acyl Carrier Protein/metabolism , Fatty Acids, Unsaturated/biosynthesis , Docosahexaenoic Acids/metabolism , Eicosapentaenoic Acid/biosynthesis , Escherichia coli/enzymology , Escherichia coli/genetics , Fatty Acid Synthase, Type II/biosynthesis , Fatty Acid Synthase, Type II/genetics , Fatty Acid Synthase, Type II/metabolism , Protein Structure, Tertiary , Recombinant Proteins/biosynthesis , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Shewanella/enzymology , Shewanella/genetics , Shewanella/metabolism
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