A Framework for Reliability and Safety Analysis of Complex Space Missions

Long duration and complex mission scenarios are characteristics of NASA's human exploration of Mars, and will provide unprecedented challenges. Systems reliability and safety will become increasingly demanding and management of uncertainty will be increasingly important. NASA's current pioneering strategy recognizes and relies upon assurance of crew and asset safety. In this regard, flexibility to develop and innovate in the emergence of new design environments and methodologies, encompassing modeling of complex systems, is essential to meet the challenges

A Clinical Update and Radiologic Review of Pediatric Orbital and Ocular Tumors

While pediatric orbital tumors are most often managed in tertiary care centers, clinicians should be aware of the signs of intraocular and orbital neoplasms. In the pediatric population, a delay in diagnosis of orbital and intraocular lesions, even if benign, can lead to vision loss and deformity. Intraocular lesions reviewed are retinoblastoma, medulloepithelioma, and retinal astrocytic hamartoma. Orbital neoplasms reviewed are rhabdomyosarcoma, neuroblastoma metastases, optic pathway glioma, plexiform neurofibroma, leukemia, lymphoprolipherative disease, orbital inflammatory syndrome, dermoid and epidermoid inclusion cysts, and Langerhans’ cell histiocytosis. Vascular lesions reviewed are infantile hemangioma and venous lymphatic malformation. In conjunction with clinical examination, high-resolution ophthalmic imaging and radiologic imaging play an important role in making a diagnosis and differentiating between benign and likely malignant processes. The radiologic imaging characteristics of these lesions will be discussed to facilitate prompt diagnosis and treatment. The current treatment modalities and management of tumors will also be reviewed

Global analyses of human immune variation reveal baseline predictors of postvaccination responses.

A major goal of systems biology is the development of models that accurately predict responses to perturbation. Constructing such models requires the collection of dense measurements of system states, yet transformation of data into predictive constructs remains a challenge. To begin to model human immunity, we analyzed immune parameters in depth both at baseline and in response to influenza vaccination. Peripheral blood mononuclear cell transcriptomes, serum titers, cell subpopulation frequencies, and B cell responses were assessed in 63 individuals before and after vaccination and were used to develop a systematic framework to dissect inter- and intra-individual variation and build predictive models of postvaccination antibody responses. Strikingly, independent of age and pre-existing antibody titers, accurate models could be constructed using pre-perturbation cell populations alone, which were validated using independent baseline time points. Most of the parameters contributing to prediction delineated temporally stable baseline differences across individuals, raising the prospect of immune monitoring before intervention

Randomized trial examining the effect of exercise and wellness interventions on preventing postpartum depression and perceived stress

Background Approximately 13–19% of postpartum women experience postpartum depression and a majority report at least some stress during the postpartum phase. Traditional interventions such as psychotherapy and antidepressant medications are often not feasible or desirable. The purpose of this study was to examine two low cost, brief, accessible interventions designed to prevent postpartum depression and perceived stress among women at high risk. Methods Participants (n = 450) who were on average four weeks postpartum, had a history of depression before pregnancy, and exercised less than 60 min per week were randomly assigned to one of the following three conditions: (1) 6-month telephone-based exercise intervention; (2) 6-month telephone-based wellness/support intervention (e.g., healthy eating, sleep, and perceived stress); or (3) usual care. Results Overall, 2.4% of participants met criteria for depression at 6 months and 3.6% at 9 months with no differences between groups. At 6 months following randomization, median symptoms of depression were significantly lower among wellness participants compared to usual care participants (b = − 1.00, SE = 0.46, p = .03). Perceived stress at 6 months post-randomization was significantly lower among exercise vs. usual care participants (b = − 2.00, SE = .98, p = .04) and exercise vs. wellness participants (b = − 2.20, SE = 1.11, p = .04). Conclusions The wellness intervention was efficacious for preventing symptoms of depression; however, postpartum depression that met the diagnostic criteria was surprisingly low in all conditions among this at risk sample of postpartum women. Exercise interventions may have a protective effect on perceived stress among women at risk for postpartum depression. Practitioners should consider integrating exercise and wellness interventions into postpartum care. Trial registration Clinical Trials Number: NCT01883479 (06/21/2013)

A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants.

This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.3448Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 × 10(-8)) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 × 10(-10)). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.We thank all participants of all the studies included for enabling this research by their participation in these studies. Computer resources for this project have been provided by the high-performance computing centers of the University of Michigan and the University of Regensburg. Group-specific acknowledgments can be found in the Supplementary Note. The Center for Inherited Diseases Research (CIDR) Program contract number is HHSN268201200008I. This and the main consortium work were predominantly funded by 1X01HG006934-01 to G.R.A. and R01 EY022310 to J.L.H