Effects of genetically predicted posttraumatic stress disorder on autoimmune phenotypes.

Observational studies suggest that posttraumatic stress disorder (PTSD) increases risk for various autoimmune diseases. Insights into shared biology and causal relationships between these diseases may inform intervention approaches to PTSD and co-morbid autoimmune conditions. We investigated the shared genetic contributions and causal relationships between PTSD, 18 autoimmune diseases, and 3 immune/inflammatory biomarkers. Univariate MiXeR was used to contrast the genetic architectures of phenotypes. Genetic correlations were estimated using linkage disequilibrium score regression. Bi-directional, two-sample Mendelian randomization (MR) was performed using independent, genome-wide significant single nucleotide polymorphisms; inverse variance weighted and weighted median MR estimates were evaluated. Sensitivity analyses for uncorrelated (MR PRESSO) and correlated horizontal pleiotropy (CAUSE) were also performed. PTSD was considerably more polygenic (10,863 influential variants) than autoimmune diseases (median 255 influential variants). However, PTSD evidenced significant genetic correlation with nine autoimmune diseases and three inflammatory biomarkers. PTSD had putative causal effects on autoimmune thyroid disease (p = 0.00009) and C-reactive protein (CRP) (p = 4.3 × 10-7). Inferences were not substantially altered by sensitivity analyses. Additionally, the PTSD-autoimmune thyroid disease association remained significant in multivariable MR analysis adjusted for genetically predicted inflammatory biomarkers as potential mechanistic pathway variables. No autoimmune disease had a significant causal effect on PTSD (all p values > 0.05). Although causal effect models were supported for associations of PTSD with CRP, shared pleiotropy was adequate to explain a putative causal effect of CRP on PTSD (p = 0.18). In summary, our results suggest a significant genetic overlap between PTSD, autoimmune diseases, and biomarkers of inflammation. PTSD has a putative causal effect on autoimmune thyroid disease, consistent with existing epidemiologic evidence. A previously reported causal effect of CRP on PTSD is potentially confounded by shared genetics. Together, results highlight the nuanced links between PTSD, autoimmune disorders, and associated inflammatory signatures, and suggest the importance of targeting related pathways to protect against disease and disability.

Reconfirming HIV serostatus in three West African Military ART clinics.

BACKGROUND: HIV rapid diagnostic test (RDT) algorithms have been successfully employed worldwide to accelerate critically important HIV testing. Deviations from the algorithm and processing errors have been associated with inaccurate algorithm results. Positive RDT algorithm results should be confirmed prior to HIV clinic enrollment, but compliance varies. We sought to retest HIV status of patients in three West African military HIV clinics. SETTING: Military HIV clinics in Lome, Togo; Freetown, Sierra Leone; and Monrovia, Liberia METHODS: Patients coming for routine HIV clinic visits were approached for enrollment. Consenting participants completed a 15-minute questionnaire and provided blood samples for both national and WHO-recommended HIV RDT algorithms, and HIV ELISA (plus HIV PCR if HIV ELISA negative). RESULTS: In total, 817 participants provided data: 374 in Togo, 360 in Sierra Leone, and 83 in Liberia. One participant from Liberia was HIV-negative (although follow-up testing was positive). Two of 807 participants on antiretroviral treatment (ART) had inconclusive algorithms, while 2 of 10 participants not on ART had algorithms, for 4 total based on the WHO-approved algorithm. Using the national algorithms, only 3 were inconclusive. A substantial proportion of the cohort had taken ART for over 6 years (25-46%, depending on the site). CONCLUSION: HIV RDT retesting in three military HIV clinics did not uncover significant numbers of misclassified HIV patients. There was no significant difference between national and WHO-recommended RDT algorithms, although the study was underpowered to detect a difference. Antiretroviral treatment was not associated with increased rates of inconclusive RDT algorithm results.

In Vitro Evaluation of Notch Inhibition to Enhance Efficacy of Radiation Therapy in Melanoma.

PURPOSE: The scope of radiation therapy is limited in melanoma. Using in vitro melanoma models, we investigated a Notch signaling inhibitor as a radiosensitizer to explore its potential to improve the efficacy of radiation therapy to widen the clinical application of radiation therapy in melanoma. METHODS AND MATERIALS: Melanoma cell lines A375, SKMEL28, and G361 were grown using standard tissue culture methods. Radiation was delivered with a clinical x-ray unit, and a gamma secretase inhibitor RO4929097 was used to inhibit Notch signaling. Cell viability signal was used to calculate Loewe's combination index to assess the interaction between radiation and RO4929097 and also the effect of scheduling of radiation and RO4929097 on synergy. Clonogenic assays were used to assess the clonogenic potential. An in vitro 3-dimensional culture model, γ-H2AX, and notch intracellular domain assays were used to interrogate potential underlying biological mechanisms of this approach. Scratch and transwell migration assays were used to assess cell migration. RESULTS: A375 and SKMEL28 cell lines showed consistent synergy for most single radiation doses examined, with a tendency for better synergy with the radiation-first schedule (irradiation performed 24 hours before RO4929097 exposure). Clonogenic assays showed dose-dependent reduction in colony numbers. Both radiation and RO4929097 reduced the size of melanospheres grown in 3-dimensional culture in vitro, where RO4929097 demonstrated a significant effect on the size of A375 and SKMEL28 melanospheres, indicating potential modulation of stem cell phenotype. Radiation induced γ-H2AX foci signal levels were reduced after exposure to RO4929097 with a tendency toward reduction in notch intracellular domain levels for all 3 cell lines. RO4929097 impaired both de novo and radiation-enhanced cell migration. CONCLUSIONS: We demonstrate Notch signaling inhibition with RO4929097 as a promising strategy to potentially improve the efficacy of radiation therapy in melanoma. This strategy warrants further validation in vivo.

Hydroxychloroquine and short-course radiotherapy in elderly patients with newly diagnosed high-grade glioma: a randomized phase II trial.

BACKGROUND: Effective treatment for patients at least 70 years with newly diagnosed glioblastoma remains challenging and alternatives to conventional cytotoxics are appealing. Autophagy inhibition has shown promising efficacy and safety in small studies of glioblastoma and other cancers. METHODS: We conducted a randomized phase II trial to compare radiotherapy with or without hydroxychloroquine (2:1 allocation). Patients aged at least 70 years with newly diagnosed high-grade glioma deemed suitable for short-course radiotherapy with an ECOG performance status of 0-1 were included. Radiotherapy treatment consisted of 30 Gy, delivered as 6 fractions given over 2 weeks (5 Gy per fraction). Hydroxychloroquine was given as 200 mg orally b.d. from 7 days prior to radiotherapy until disease progression. The primary endpoint was 1-year overall survival (OS). Secondary endpoints included progression-free survival (PFS), quality of life, and toxicity. RESULTS: Fifty-four patients with a median age of 75 were randomized between May 2013 and October 2016. The trial was stopped early in 2016. One-year OS was 20.3% (95% confidence interval [CI] 8.2-36.0) hydroxychloroquine group, and 41.2% (95% CI 18.6-62.6) radiotherapy alone, with a median survival of 7.9 and 11.5 months, respectively. The corresponding 6-month PFS was 35.3% (95% CI 19.3-51.7) and 29.4% (95% CI 10.7-51.1). The outcome in the control arm was better than expected and the excess of deaths in the hydroxychloroquine group appeared unrelated to cancer. There were more grade 3-5 events in the hydroxychloroquine group (60.0%) versus radiotherapy alone (38.9%) without any clear common causation. CONCLUSIONS: Hydroxychloroquine with short-course radiotherapy did not improve survival compared to radiotherapy alone in elderly patients with glioblastoma.

Association of Race and Major Adverse Cardiac Events (MACE): The Atherosclerosis Risk in Communities (ARIC) Cohort.

BACKGROUND AND AIMS: To evaluate the association of self-reported race with major adverse cardiac events (MACE) and modification of this association by paraoxonase gene (PON1, PON2, and PON3) single nucleotide polymorphisms (SNPs). METHODS: Included in this longitudinal study were 12,770 black or white participants from the Atherosclerosis Risk in Communities (ARIC) cohort who completed a baseline visit (1987-1989) with PON genotyping. Demographic, behavioral, and health information was obtained at baseline. MACE was defined as first occurrence of myocardial infarction, stroke, or CHD-related death through 2004. Cox proportional hazards regression was used to evaluate the association between race and MACE after adjustment for age, gender, and other demographic and cardiovascular risk factors such as diabetes and hypertension. Modification of the association between PON SNPs and MACE was also assessed. RESULTS: Blacks comprised 24.6% of the ARIC cohort; overall, 14.0% of participants developed MACE. Compared with whites, blacks had 1.24 times greater hazard of MACE (OR = 1.24,95%CI = 1.10,1.39) than whites after adjusting for age, gender, BMI, cigarette and alcohol use, educational and marital status, and aspirin use. This association became nonsignificant after further adjustment for high cholesterol, diabetes, and hypertension. None of the evaluated SNPs met the significance level (p < 0.001) after Bonferroni correction for multiple comparisons. CONCLUSIONS: No association between race and MACE was identified after adjusting for high cholesterol, diabetes, and hypertension, suggesting that comorbidities are major determinants of MACE; medical intervention with focus on lifestyle and health management could ameliorate the development of MACE. Further studies are needed to confirm this observation.

Longitudinal survey of condom use across a US Navy and Marine Corps shipboard deployment.

OBJECTIVES: Condoms are highly effective in preventing sexually transmitted infections (STIs) but implementation is often inconsistent with use rarely examined across travel transition periods. We examined the prevalence of condom use among ship-assigned US military personnel across an overseas deployment cycle and identified factors associated with condom non-use. METHODS: Longitudinal survey data were collected from ship-assigned US Navy/Marine Corps personnel on 11 ships before (T1), during (T2) and after (T3) an overseas deployment. The anonymous, self-completed survey included demographics, condom use at last sex, STI diagnosis, alcohol misuse and drug use with sex. Descriptive and generalised regression model analyses were conducted. RESULTS: Analysis included 1900 (T1), 549 (T2) and 1168 (T3) personnel who reported age, sex and condom use/non-use at last sex. The proportion reporting condom use was significantly higher during T2 (53%, p<0.0001) than T1 (27%) or T3 (28%), with STI prevalences of 1% (T1), 7% (T2) or 2% (T3), with fewer (29%) sexually active individuals at T2. In adjusted models, condom non-use was associated with hazardous alcohol use (OR 1.44, 95% CI 1.21 to 1.71), or drug use to enhance sex (OR 1.37, 95% CI 1.06 to 1.77), but transactional sex was negatively associated (OR 0.69, 95% CI 0.50 to 0.84). CONCLUSIONS: Condom use was highest during deployment, as was STI prevalence (among non-users), possibly reflecting concentration of high-risk sexual activities/individuals and/or sexual partners more likely to be infected. Higher condom use with transactional sex likely reflects awareness of higher STI risk. These data can be used to facilitate targeted interventions to reduce STI transmission and may extend to similarly aged cohorts travelling outside the US (eg, college students on spring break).

A Phase I Study of Pegylated Arginine Deiminase (Pegargiminase), Cisplatin, and Pemetrexed in Argininosuccinate Synthetase 1-Deficient Recurrent High-grade Glioma.

PURPOSE: Patients with recurrent high-grade gliomas (HGG) are usually managed with alkylating chemotherapy ± bevacizumab. However, prognosis remains very poor. Preclinically, we showed that HGGs are a target for arginine depletion with pegargiminase (ADI-PEG20) due to epimutations of argininosuccinate synthetase (ASS1) and/or argininosuccinate lyase (ASL). Moreover, ADI-PEG20 disrupts pyrimidine pools in ASS1-deficient HGGs, thereby impacting sensitivity to the antifolate, pemetrexed. PATIENTS AND METHODS: We expanded a phase I trial of ADI-PEG20 with pemetrexed and cisplatin (ADIPEMCIS) to patients with ASS1-deficient recurrent HGGs (NCT02029690). Patients were enrolled (01/16-06/17) to receive weekly ADI-PEG20 36 mg/m2 intramuscularly plus pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 intravenously once every 3 weeks for up to 6 cycles. Patients with disease control were allowed ADI-PEG20 maintenance. The primary endpoints were safety, tolerability, and preliminary estimates of efficacy. RESULTS: Ten ASS1-deficient heavily pretreated patients were treated with ADIPEMCIS therapy. Treatment was well tolerated with the majority of adverse events being Common Terminology Criteria for Adverse Events v4.03 grade 1-2. The best overall response was stable disease in 8 patients (80%). Plasma arginine was suppressed significantly below baseline with a reciprocal increase in citrulline during the sampling period. The anti-ADI-PEG20 antibody titer rose during the first 4 weeks of treatment before reaching a plateau. Median progression-free survival (PFS) was 5.2 months (95% confidence interval (CI), 2.5-20.8) and overall survival was 6.3 months (95% CI, 1.8-9.7). CONCLUSIONS: In this recurrent HGG study, ADIPEMCIS was well tolerated and compares favorably to historical controls. Additional trials of ADI-PEG20 in HGG are planned.

Self-reported HIV-positive status but subsequent HIV-negative test result using rapid diagnostic testing algorithms among seven sub-Saharan African military populations.

HIV rapid diagnostic tests (RDTs) combined in an algorithm are the current standard for HIV diagnosis in many sub-Saharan African countries, and extensive laboratory testing has confirmed HIV RDTs have excellent sensitivity and specificity. However, false-positive RDT algorithm results have been reported due to a variety of factors, such as suboptimal quality assurance procedures and inaccurate interpretation of results. We conducted HIV serosurveys in seven sub-Saharan African military populations and recorded the frequency of personnel self-reporting HIV positivity, but subsequently testing HIV-negative during the serosurvey. The frequency of individuals who reported they were HIV-positive but subsequently tested HIV-negative using RDT algorithms ranged from 3.3 to 91.1%, suggesting significant rates of prior false-positive HIV RDT algorithm results, which should be confirmed using biological testing across time in future studies. Simple measures could substantially reduce false-positive results, such as greater adherence to quality assurance guidelines and prevalence-specific HIV testing algorithms as described in the World Health Organization's HIV testing guidelines. Other measures to improve RDT algorithm specificity include classifying individuals with weakly positive test lines as HIV indeterminate and retesting. While expansion of HIV testing in resource-limited countries is critical to identifying HIV-infected individuals for appropriate care and treatment, careful attention to potential causes of false HIV-positive results are needed to prevent the significant medical, psychological, and fiscal costs resulting from individuals receiving a false-positive HIV diagnosis.

Leisure-time physical activity and leukocyte telomere length among older women.

BACKGROUND: Shortened leukocyte telomere length (LTL), a purported marker of cellular aging, is associated with morbidity and mortality. However, the association of physical activity, a modifiable lifestyle behavior, with LTL has not been adequately studied among older adults. METHODS: In this cross-sectional study, we examined associations of various intensity levels of leisure-time physical activity with LTL among 1476 older white and African American women from the Women's Health Initiative Objective Physical Activity and Cardiovascular Health study. Self-reported physical activity was assessed by questionnaire, and LTL was measured by Southern blot. The association between physical activity and LTL was evaluated using multiple linear regression models adjusted for demographic characteristics, lifestyle behaviors, and health-related variables. RESULTS: Women were on average aged 79.2 (standard deviation 6.7) years old. In the final model adjusted for age, race/ethnicity, education, marital status, smoking, alcohol, body mass index, a history of chronic diseases, and hormone therapy use, LTL was on average 110 (95% confidence interval, 20-190) base pairs longer among women in the highest (≥17.00MET-hours/week) compared with the lowest (<1.25MET-hours/week) level of total leisure-time physical activity (P for trend=0.02). Higher levels of moderate-to-vigorous physical activity (P for trend=0.04) and faster walking speed (P for trend=0.03) were also associated with longer LTL in the fully-adjusted models. CONCLUSION: Older women participating in greater amounts of total leisure-time physical activity and moderate-to-vigorous physical activity had longer LTL.

Global HIV Prevention, Testing, and Counseling in Military Populations.

BACKGROUND: Compared with the general population in low- and middle-income countries, military members tend to be male, young, travel more frequently away from their main sexual partners, drink more alcohol and have a consistent source of income. All of these factors may lead to an increased risk of contracting HIV. OBJECTIVE: In response, the Department of Defense HIV/AIDS Prevention Program advocates for the integration of HIV prevention "building blocks" into military health services to reduce the risk of acquiring HIV among foreign uniformed services. METHOD: The building blocks include basic HIV education including outreach, condom promotion, enabling HIV policies, HIV testing services, screening for sexually transmitted infections, voluntary medical male circumcision where appropriate, prevention of mother-to-child transmission, and other supportive services. CONCLUSION: The Department of Defense HIV/AIDS Prevention Programs supports implementation of these building blocks though partnerships with foreign militaries. This comprehensive prevention package, when closely linked with HIV treatment services, is the cornerstone of creating an HIVfree generation in military and surrounding communities worldwide.

Conducting HIV Seroprevalence and Behavioral Epidemiology Risk Surveys (SABERS) Among Partner Military Populations.

BACKGROUND: Characterizing HIV infection and associated risk behaviors within military populations is critical for understanding the epidemic and informing prevention activities. However, the prevalence of HIV and related risk behaviors is often unknown. Further, militaries may not have the systems in place or the staff expertise to conduct HIV surveillance and risk behavior studies. METHODS: The Department of Defense HIV/AIDS Prevention Program (DHAPP), funded by the President's Emergency Plan for AIDS Relief and the US Department of Defense, provides technical assistance, management and administrative support for HIV/AIDS prevention, care and treatment for approximately 65 partner militaries. Collaborating with partner militaries in conducting Seroprevalence and Behavioral Epidemiology Risk Surveys (SABERS) and using the data to monitor the epidemic and inform activities is a key component of DHAPP. CONCLUSION: This paper describes the methodology used to plan, adapt, implement and report SABERS studies.

Prevalence and Risk Factors for Human Immunodeficiency Virus (HIV) and Syphilis Infections Among Military Personnel in Sierra Leone.

CONTEXT: HIV and syphilis infections are common in military personnel in sub-Saharan Africa, which impact combat preparedness and increase demands on the military health care system. The prevalence of HIV is estimated at 1.5% among the general population (15-49 years of age) of Sierra Leone, and the estimated syphilis prevalence ranged from 1.5% to 5.2% based on regional studies. We examined the prevalence and risk factors for these two common sexually transmitted infections in the Sierra Leone military personnel. METHODS: This cross-sectional study examined 1157 randomly selected soldiers from the Republic of Sierra Leone Armed Forces in 2013 using computer-assisted personal interviews and rapid testing algorithms. Descriptive statistics and logistic regression models were implemented to identify risk factors for HIV and syphilis separately. RESULTS: The mean age of participants was 38 years, 11.1% were female, and 86.5% were married. The seroprevalence of HIV and syphilis were 3.3% (95% confidence interval [CI]: 2.3%-4.3%) and 7.3% (95% CI: 5.9%-8.8%), respectively. Lower educational attainment in women, multiple sexual partners, unintended sex after alcohol use and use of condoms were independently associated with HIV status (p<0.05). After adjustment, HIV infection was associated with female gender, unintended sex after alcohol use, condom use at last sex, having multiple sexual partnerships in the same week and HIV testing outside of military facilities (p<0.05). Increasing age, positive HIV status and rural regions of residence were associated with syphilis seropositivity. CONCLUSION: The prevalence of sexually transmitted infections among military personnel was higher than the general population of Sierra Leone. Several high-risk sexual behaviors that expose soldiers to HIV and syphilis could be addressed through prevention interventions.

HIV/AIDS Securitization: Outcomes and Current Challenges.

BACKGROUND: The securitization (i.e., framing of a health issue as a security threat) of HIV/AIDS by the United Nations Security Council in 2000 changed the belief that HIV/AIDS is only a health issue. Although now accepted that HIV/AIDS represents a security threat, the consequences of securitization are still not widely established. METHODS: The purpose of this paper was to present an evidence-based review of the outcomes and current challenges associated with HIV/AIDS securitization in the context of national security. RESULTS/CONCLUSION: We provided an overview of HIV/AIDS securitization, followed by a discussion of the impact of securitization on peacekeeping personnel and uniformed services. We also reviewed the United States Government's response to securitization and potential risks and benefits of securitization.

Short-Term Transfer of Knowledge Assessment in the Military International HIV Training Program (MIHTP).

BACKGROUND: The Military International HIV Training Program (MIHTP) was established in 2002 to address the overwhelming needs of international military personnel concerning HIV and AIDS prevention, care, and treatment. The purpose of this study was to determine shortterm knowledge transfer in trainees attending the MIHTP by comparing data collected from pretraining and post-training knowledge assessments. METHODS: We used identical 40-question multiple choice pre-training and post-training assessments to determine the short-term transfer of knowledge of international HIV military physicians attending the MIHTP. RESULTS: Findings revealed a statistically significant increase in short-term transfer of knowledge of HIV prevention, care, and treatment in a population of international military physicians, nurses, and auxiliary medical personnel from 47 developing countries (n=136). Trainees had significantly higher post-test scores (67.9%) compared with pre-test scores (50.5%, p<0.001). Trainees showed a similar level of HIV knowledge as assessed by pre-training evaluations (F=1.38). CONCLUSION: We found significant increases in acquired individual knowledge after a 4-week HIV training program. Results of this study are important as many developing countries rely heavily on international training programs to aid in the development of health care systems in an ever-changing infrastructure.

Prevention Interventions for People Living with HIV in Military Settings.

BACKGROUND: Military HIV prevention programs and healthy living programs were developed in the mid-1980s to manage and support newly HIV-positive military personnel in the US military. Since then, a program developed by the Centers for Disease Control and Prevention with support from the Department of Defense HIV/AIDS Prevention Program (DHAPP), called Positive Health, Dignity and Prevention (PHDP), is currently being rolled out by DHAPP in partner militaries. The program, designed to reduce HIV transmission, is a package of interventions for people living with HIV (PLHIV), including risk reduction counseling, condom provision, disclosure counseling, testing of sexual partner(s) and children, adherence counseling, diagnosis and treatment of sexually transmitted infections, and provision of family planning services. METHODS: DHAPP has trained military and civilian personnel caring for military personnel, their families, and the civilians seen at military installations in sub-Saharan Africa, such as Rwanda, Democratic Republic of the Congo, Malawi, and Zambia. These programs have varying degrees of implementing the program with innovative ways of engaging PLHIV. RESULTS/CONCLUSIONS: Many successes are being achieved through the training of military and civilian personnel working for or at military health care settings. In 2015, one of DHAPP's goals for the PHDP program is to enhance the monitoring, evaluation, and reporting of PHDP to demonstrate PHDP service provision to at least 90% of HIV-positive patients over the next 5 years.

Associations of Accelerometer-Measured and Self-Reported Sedentary Time With Leukocyte Telomere Length in Older Women.

Few studies have assessed the association of sedentary time with leukocyte telomere length (LTL). In a cross-sectional study conducted in 2012-2013, we examined associations of accelerometer-measured and self-reported sedentary time with LTL in a sample of 1,481 older white and African-American women from the Women's Health Initiative and determined whether associations varied by level of moderate- to vigorous-intensity physical activity (MVPA). The association between sedentary time and LTL was evaluated using multiple linear regression models. Women were aged 79.2 (standard deviation, 6.7) years, on average. Self-reported sedentary time was not associated with LTL. In a model adjusting for demographic characteristics, lifestyle behaviors, and health-related factors, among women at or below the median level of accelerometer-measured MVPA, those in the highest quartile of accelerometer-measured sedentary time had significantly shorter LTL than those in the lowest quartile, with an average difference of 170 base pairs (95% confidence interval: 4, 340). Accelerometer-measured sedentary time was not associated with LTL in women above the median level of MVPA. Findings suggest that, on the basis of accelerometer measurements, higher sedentary time may be associated with shorter LTL among less physically active women.

Ages at menarche and menopause and reproductive lifespan as predictors of exceptional longevity in women: the Women's Health Initiative.

OBJECTIVE: The aim of the present study was to investigate associations between reproductive factors and survival to age 90 years. METHODS: This was a prospective study of postmenopausal women from the Women's Health Initiative recruited from 1993 to 1998 and followed until the last outcomes evaluation on August 29, 2014. Participants included 16,251 women born on or before August 29, 1924 for whom survival to age 90 during follow-up was ascertained. Women were classified as having survived to age 90 (exceptional longevity) or died before age 90. Multivariable logistic regression models were used to evaluate associations of ages at menarche and menopause (natural or surgical) and reproductive lifespan with longevity, adjusting for demographic, lifestyle, and reproductive characteristics. RESULTS: Participants were on average aged 74.7 years (range, 69-81 y) at baseline. Of 16,251 women, 8,892 (55%) survived to age 90. Women aged at least 12 years at menarche had modestly increased odds of longevity (odds ratio [OR], 1.09; 95% CI, 1.00-1.19). There was a significant trend toward increased longevity for later age at menopause (natural or surgical; Ptrend = 0.01), with ORs (95% CIs) of 1.19 (1.04-1.36) and 1.18 (1.02-1.36) for 50 to 54 and at least 55 compared with less than 40 years, respectively. Later age at natural menopause as a separate exposure was also significantly associated with increased longevity (Ptrend = 0.02). Longer reproductive lifespan was significantly associated with increased longevity (Ptrend = 0.008). The odds of longevity were 13% (OR 1.13; 95% CI, 1.03-1.25) higher in women with more than 40 compared with less than 33 reproductive years. CONCLUSIONS: Reproductive characteristics were associated with late-age survival in older women.

International chicken trade and increased risk for introducing or reintroducing highly pathogenic avian influenza A (H5N1) to uninfected countries.

Every year billions of chickens are shipped thousands of miles around the globe in order to meet the ever increasing demands for this cheap and nutritious protein source. Unfortunately, transporting chickens internationally can also increase the chance for introducing zoonotic viruses, such as highly pathogenic avian influenza A (H5N1) to new countries. Our study used a retrospective analysis of poultry trading data from 2003 through 2011 to assess the risk of H5N1 poultry infection in an importing country. We found that the risk of infection in an importing country increased by a factor of 1.3 (95% CI: 1.1-1.5) for every 10-fold increase in live chickens imported from countries experiencing at least one H5N1 poultry case during that year. These results suggest that the risk in a particular country can be significantly reduced if imports from countries experiencing an outbreak are decreased during the year of infection or if biosecurity measures such as screening, vaccination, and infection control practices are increased. These findings show that limiting trade of live chickens or increasing infection control practices during contagious periods may be an important step in reducing the spread of H5N1 and other emerging avian influenza viruses.

Maternal Age at Childbirth and Parity as Predictors of Longevity Among Women in the United States: The Women's Health Initiative.

OBJECTIVES: To examine associations of maternal age at childbirth and parity with survival to age 90 years (longevity). METHODS: We performed a prospective study among a multiethnic cohort of postmenopausal US women in the Women's Health Initiative recruited from 1993 to 1998 and followed through August 29, 2014. We adjusted associations with longevity for demographic, lifestyle, reproductive, and health-related characteristics. RESULTS: Among 20 248 women (mean age at baseline, 74.6 years), 10 909 (54%) survived to age 90 years. The odds of longevity were significantly higher in women with later age at first childbirth (adjusted odds ratio = 1.11; 95% confidence interval = 1.02, 1.21 for age 25 years or older vs younger than 25 years; P for trend = .04). Among parous women, the relationship between parity and longevity was significant among White but not Black women. White women with 2 to 4 term pregnancies compared with 1 term pregnancy had higher odds of longevity. CONCLUSIONS: Reproductive events were associated with longevity among women. Future studies are needed to determine whether factors such as socioeconomic status explain associations between reproductive events and longevity.