New safety model for the commercial human spaceflight industry

The aviation and space domains have safety guidelines and recommended practices for Design Organisations (DOs) and Operators alike. In terms of Aerospace DOs there are certification criteria to meet and to demonstrate compliance there are Advisory Circulars or Acceptable Means of Compliance to follow. Additionally there are guidelines such as Aerospace Recommended Practices (ARP), Military Standards (MIL-STD 882 series) and System Safety Handbooks to follow in order to identify and manage failure conditions. In terms of Operators there are FAA guidelines and a useful ARP that details many tools and techniques in understanding Operator Safety Risks. However there is currently no methodology for linking the DO and Operator safety efforts. In the space domain NASA have provided safety standards and guidelines to follow and also within Europe there are European Co-operation of Space Standardization (ECSS) to follow. Within the emerging Commercial Human Spaceflight Industry, the FAA’s Office of Commercial Space Transportation has provided hazard analysis guidelines. However all of these space domain safety documents are based on the existing aerospace methodology and once again, there is no link between the DO and Operator’s safety effort. This paper addresses the problematic issue and presents a coherent methodology of joining up the System Safety effort of the DOs to the Operator Safety Risk Management such that a ‘Total System’ approach is adopted. Part of the rationale is that the correct mitigation (control) can be applied within the correct place in the accident sequence. Also this contiguous approach ensures that the Operator is fully aware of the safety risks (at the accident level) and therefore has an appreciation of the Total System Risk. The authors of this paper contend that it is better practice to have a fully integrated safety model as opposed to disparate requirements or guidelines. Our methodology is firstly to review ‘best practice’ approaches from the aviation and space industries, and then to integrate these approaches into a contiguous safety model for the commercial human spaceflight industry

True infliximab resistance in rheumatoid arthritis: a role for lymphotoxin α?

Background: The combination of methotrexate and the anti-tumour necrosis factor (TNF) antibody infliximab is a very effective treatment for rheumatoid arthritis (RA). However, a proportion of patients are not responsive to this treatment. Inefficacy may represent a TNF independent disease or insufficient drug at the site of action. Case report: A patient with RA resistant to repeated high dose infliximab infusions and intra-articular infliximab into an inflamed knee is described. No beneficial clinical effect was observed. Pre-injection arthroscopic biopsy of the study knee demonstrated TNF staining but also confirmed the presence of lymphotoxin (LT or TNFß) on immunohistochemistry. Subsequent treatment with etanercept (which blocks LT as well as TNF) resulted in clinical remission of disease. Conclusion: This case suggests that resistance to TNF blockade may occur when TNF is not the dominant inflammatory cytokine and suggests that LT may have a pathogenic role in RA

Association of FCGR3A and FCGR3B haplotypes with rheumatoid arthritis and primary Sjögren's syndrome [POSTER PRESENTATION]

Background Rheumatoid arthritis (RA) is an autoimmune disease that is thought to arise from a complex interaction between multiple genetic factors and environmental triggers. We have previously demonstrated an association between a Fc gamma receptor (FcγR) haplotype and RA in a cross-sectional cohort of RA patients. We have sought to confirm this association in an inception cohort of RA patients and matched controls. We also extended our study to investigate a second autoanti-body associated rheumatic disease, primary Sjögren's syndrome (PSS). Methods The FCGR3A-158F/V and FCGR3B-NA1/NA2 functional polymorphisms were examined for association in an inception cohort of RA patients (n = 448), and a well-characterised PSS cohort (n = 83) from the United Kingdom. Pairwise disequilibrium coefficients (D') were calculated in 267 Blood Service healthy controls. The EHPlus program was used to estimate haplotype frequencies for patients and controls and to determine whether significant linkage disequilibrium was present. A likelihood ratio test is performed to test for differences between the haplotype frequencies in cases and controls. A permutation procedure implemented in this program enabled 1000 permutations to be performed on all haplotype associations to assess significance. Results There was significant linkage disequilibrium between FCGR3A and FCGR3B (D' = -0.445, P = 0.001). There was no significant difference in the FCGR3A or FCGR3B allele or genotype frequencies in the RA or PSS patients compared with controls. However, there was a significant difference in the FCGR3A-FCGR3B haplotype distributions with increased homozygosity for the FCGR3A-FCGR3B 158V-NA2 haplotype in both our inception RA cohort (odds ratio = 2.15, 95% confidence interval = 1.1–4.2 P = 0.027) and PSS (odds ratio = 2.83, 95% confidence interval = 1.0–8.2, P = 0.047) compared with controls. The reference group for these analyses comprised individuals who did not possess a copy of the FCGR3A-FCGR3B 158V-NA2 haplotype. Conclusions We have confirmed our original findings of association between the FCGR3A-FCGR3B 158V-NA2 haplotype and RA in a new inception cohort of RA patients. This suggests that there may be an RA-susceptibility gene at this locus. The significant increased frequency of an identical haplotype in PSS suggests the FcγR genetic locus may contribute to the pathogenesis of diverse autoantibody-mediated rheumatic diseases

An Investigation of a Mixer-Ejector Nozzle for Jet Noise Reduction

An experimental study is conducted assessing the performance of an ejector together with an 8:1 aspect ratio rectangular nozzle with the eventual goal of noise reduction for jet engines. Wall static pressure and Pitot probe surveys are conducted to evaluate the performance of the ejector, and sound pressure level measurements are made to assess the impact on noise radiation. It is found that addition of vortex generating tabs at the lip of the nozzle causes large increases in secondary flow entrainment. The baseline ejector (without tabs) often encounters flow resonance with accompanying tones. The tabs have the additional benefit of eliminating those tones. In most cases tried so far, pockets of high-speed fluid remain unmixed. Since jet noise scales as velocity to the eighth power, such hot spots defeat the noise reduction goal. In some cases, there is a reduction in noise amplitudes in the mid-frequency range (5-30 kHz), however, an increase occurs on the low frequency end apparently due to flow unsteadiness. This together with a high frequency noise increase caused by the tabs results in minimal reductions in the overall sound pressure level. The focus of ongoing and future efforts is to achieve sufficient mixing and desirable noise reduction while keeping the hard-ware short and lightweight

Measurement of the 58Ni(α, γ) 62Zn reaction and its astrophysical impact

Funding Details: PHY 08-22648, NSF, National Science Foundation; PHY 0969058, NSF, National Science Foundation; PHY 1102511, NSF, National Science FoundationCross section measurements of the 58Ni(α,γ)62Zn reaction were performed in the energy range Eα=5.5to9.5 MeV at the Nuclear Science Laboratory of the University of Notre Dame, using the NSCL Summing NaI(Tl) detector and the γ-summing technique. The measurements are compared to predictions in the statistical Hauser-Feshbach model of nuclear reactions using the SMARAGD code. It is found that the energy dependence of the cross section is reproduced well but the absolute value is overestimated by the prediction. This can be remedied by rescaling the α width by a factor of 0.45. Stellar reactivities were calculated with the rescaled α width and their impact on nucleosynthesis in type Ia supernovae has been studied. It is found that the resulting abundances change by up to 5% when using the new reactivities. © 2014 American Physical Society.Peer reviewe

Interleukin-7 deficiency in rheumatoid arthritis: consequences for therapy-induced lymphopenia

We previously demonstrated prolonged, profound CD4+ T-lymphopenia in rheumatoid arthritis (RA) patients following lymphocyte-depleting therapy. Poor reconstitution could result either from reduced de novo T-cell production through the thymus or from poor peripheral expansion of residual T-cells. Interleukin-7 (IL-7) is known to stimulate the thymus to produce new T-cells and to allow circulating mature T-cells to expand, thereby playing a critical role in T-cell homeostasis. In the present study we demonstrated reduced levels of circulating IL-7 in a cross-section of RA patients. IL-7 production by bone marrow stromal cell cultures was also compromised in RA. To investigate whether such an IL-7 deficiency could account for the prolonged lymphopenia observed in RA following therapeutic lymphodepletion, we compared RA patients and patients with solid cancers treated with high-dose chemotherapy and autologous progenitor cell rescue. Chemotherapy rendered all patients similarly lymphopenic, but this was sustained in RA patients at 12 months, as compared with the reconstitution that occurred in cancer patients by 3–4 months. Both cohorts produced naïve T-cells containing T-cell receptor excision circles. The main distinguishing feature between the groups was a failure to expand peripheral T-cells in RA, particularly memory cells during the first 3 months after treatment. Most importantly, there was no increase in serum IL-7 levels in RA, as compared with a fourfold rise in non-RA control individuals at the time of lymphopenia. Our data therefore suggest that RA patients are relatively IL-7 deficient and that this deficiency is likely to be an important contributing factor to poor early T-cell reconstitution in RA following therapeutic lymphodepletion. Furthermore, in RA patients with stable, well controlled disease, IL-7 levels were positively correlated with the T-cell receptor excision circle content of CD4+ T-cells, demonstrating a direct effect of IL-7 on thymic activity in this cohort

Long-lived excited-state dynamics of i-motif structures probed by time-resolved infrared spectroscopy

UV-generated excited states of cytosine (C) nucleobases are precursors to mutagenic photoproduct formation. The i-motif formed from C-rich sequences is known to exhibit high yields of long-lived excited states following UV absorption. Here the excited states of several i-motif structures have been characterized following 267 nm laser excitation using time-resolved infrared spectroscopy (TRIR). All structures possess a long-lived excited state of ∼300 ps and notably in some cases decays greater than 1 ns are observed. These unusually long-lived lifetimes are attributed to the interdigitated DNA structure which prevents direct base stacking overlap

On manifolds with nonhomogeneous factors

We present simple examples of finite-dimensional connected homogeneous spaces (they are actually topological manifolds) with nonhomogeneous and nonrigid factors. In particular, we give an elementary solution of an old problem in general topology concerning homogeneous spaces

Dermatophylosis in Santa Inês sheep from Distrito Federal

Relataram-se quatro casos de dermatofilose em ovinos da raça Santa Inês, no período de um ano. Microscopicamente observaram-se filamentos na forma de "trilho de bonde" e zoósporos nos quatro casos. A tentativa do isolamento do microrganismo foi realizada por meio do método de Haalstra e em apenas um caso obteve-se sucesso, observando-se colônias de aparência lisa, formato circular, cor amarelada e hemolítica em ágar sangue. O exame direto com coloração de Gram mostrou-se um método bastante eficiente na confirmação da presença do microrganismo afetando a epiderme em razão da morfologia típica do agente.Four cases of dermatophylosis were reported in Santa Inês sheep in a study period of one year. Microscopically, septate filaments and coccoid forms zoospores were observed. Attempts to isolate the microorganisms were accomplished using Haastra's method and it was successful in only one case. Dermatophilus congolensis samples have grown on blood agar, colonies where hemolytic, small, round and pigmentation vary from yellow to orange. The gram staining method was efficient to confirm the presence of the microorganism affecting the epidermis due to typical morphology of the agent