Limitations in Predicting the Space Radiation Health Risk for Exploration Astronauts

Despite years of research, understanding of the space radiation environment and the risk it poses to long-duration astronauts remains limited. There is a disparity between research results and observed empirical effects seen in human astronaut crews, likely due to the numerous factors that limit terrestrial simulation of the complex space environment and extrapolation of human clinical consequences from varied animal models. Given the intended future of human spaceflight, with efforts now to rapidly expand capabilities for human missions to the moon and Mars, there is a pressing need to improve upon the understanding of the space radiation risk, predict likely clinical outcomes of interplanetary radiation exposure, and develop appropriate and effective mitigation strategies for future missions. To achieve this goal, the space radiation and aerospace community must recognize the historical limitations of radiation research and how such limitations could be addressed in future research endeavors. We have sought to highlight the numerous factors that limit understanding of the risk of space radiation for human crews and to identify ways in which these limitations could be addressed for improved understanding and appropriate risk posture regarding future human spaceflight.Comment: Accepted for publication by Nature Microgravity (2018

Novel Approach to Mass Tort Class Actions: The Billion Dollar Settlement in the Sulzer Artificial Hip and Knee Litigation: A Symposium

This is a transcript of a two hour symposium which deals with the Sulzer knee and hip replacement class action. A copy of the settlement is included as an appendix. The settlement in the U.S. District Court for the N.D. Ohio was unique and creative approach to resolving a mass tort class action. In a novel move, Sulzer agreed to open its books to an independent review firm to determine how much the firm could pay without going bankrupt. The number was $1 billion. As negotiated by the parties and approved by the court, the final settlement provides compensation for each member of the class based on a variety of factors, such as whether the member has undergone - or is likely to undergo - a revision to replace the defective part. Professor Susan Becker made the introductory remarks. The panel members were all involved in the Sulzer knee and hip replacement class action. R. Eric Kennedy served as lead plaintiffs\u27 counsel. The Honorable Kathleen McDonald O\u27Malley of the U.S. District Court for the Northern District of Ohio presided over the Sulzer class action litigation and settlement. Sidney A. Backstrom and Richard F. Scruggs were the defense counsel. James J. McMonagle served as the Claims Administrator overseeing distribution of the Sulzer class action settlement funds

Novel Approach to Mass Tort Class Actions: The Billion Dollar Settlement in the Sulzer Artificial Hip and Knee Litigation: A Symposium

This is a transcript of a two hour symposium which deals with the Sulzer knee and hip replacement class action. A copy of the settlement is included as an appendix. The settlement in the U.S. District Court for the N.D. Ohio was unique and creative approach to resolving a mass tort class action. In a novel move, Sulzer agreed to open its books to an independent review firm to determine how much the firm could pay without going bankrupt. The number was $1 billion. As negotiated by the parties and approved by the court, the final settlement provides compensation for each member of the class based on a variety of factors, such as whether the member has undergone - or is likely to undergo - a revision to replace the defective part. Professor Susan Becker made the introductory remarks. The panel members were all involved in the Sulzer knee and hip replacement class action. R. Eric Kennedy served as lead plaintiffs\u27 counsel. The Honorable Kathleen McDonald O\u27Malley of the U.S. District Court for the Northern District of Ohio presided over the Sulzer class action litigation and settlement. Sidney A. Backstrom and Richard F. Scruggs were the defense counsel. James J. McMonagle served as the Claims Administrator overseeing distribution of the Sulzer class action settlement funds

Recombination and its impact on the genome of the haplodiploid parasitoid wasp Nasonia

Homologous meiotic recombination occurs in most sexually reproducing organisms, yet its evolutionary advantages are elusive. Previous research explored recombination in the honeybee, a eusocial hymenopteran with an exceptionally high genome-wide recombination rate. A comparable study in a non-social member of the Hymenoptera that would disentangle the impact of sociality from Hymenoptera-specific features such as haplodiploidy on the evolution of the high genome-wide recombination rate in social Hymenoptera is missing. Utilizing single-nucleotide polymorphisms (SNPs) between two Nasonia parasitoid wasp genomes, we developed a SNP genotyping microarray to infer a high-density linkage map for Nasonia. The map comprises 1,255 markers with an average distance of 0.3 cM. The mapped markers enabled us to arrange 265 scaffolds of the Nasonia genome assembly 1.0 on the linkage map, representing 63.6% of the assembled N. vitripennis genome. We estimated a genome-wide recombination rate of 1.4-1.5 cM/Mb for Nasonia, which is less than one tenth of the rate reported for the honeybee. The local recombination rate in Nasonia is positively correlated with the distance to the center of the linkage groups, GC content, and the proportion of simple repeats. In contrast to the honeybee genome, gene density in the parasitoid wasp genome is positively associated with the recombination rate; regions of low recombination are characterized by fewer genes with larger introns and by a greater distance between genes. Finally, we found that genes in regions of the genome with a low recombination frequency tend to have a higher ratio of non-synonymous to synonymous substitutions, likely due to the accumulation of slightly deleterious non-synonymous substitutions. These findings are consistent with the hypothesis that recombination reduces interference between linked sites and thereby facilitates adaptive evolution and the purging of deleterious mutations. Our results imply that the genomes of haplodiploid and of diploid higher eukaryotes do not differ systematically in their recombination rates and associated parameters.Publisher PDFPeer reviewe

Hyaline Arteriolosclerosis in 30 Strains of Aged Inbred Mice.

During a screen for vascular phenotypes in aged laboratory mice, a unique discrete phenotype of hyaline arteriolosclerosis of the intertubular arteries and arterioles of the testes was identified in several inbred strains. Lesions were limited to the testes and did not occur as part of any renal, systemic, or pulmonary arteriopathy or vasculitis phenotype. There was no evidence of systemic or pulmonary hypertension, and lesions did not occur in ovaries of females. Frequency was highest in males of the SM/J (27/30, 90%) and WSB/EiJ (19/26, 73%) strains, aged 383 to 847 days. Lesions were sporadically present in males from several other inbred strains at a much lower (<20%) frequency. The risk of testicular hyaline arteriolosclerosis is at least partially underpinned by a genetic predisposition that is not associated with other vascular lesions (including vasculitis), separating out the etiology of this form and site of arteriolosclerosis from other related conditions that often co-occur in other strains of mice and in humans. Because of their genetic uniformity and controlled dietary and environmental conditions, mice are an excellent model to dissect the pathogenesis of human disease conditions. In this study, a discrete genetically driven phenotype of testicular hyaline arteriolosclerosis in aging mice was identified. These observations open the possibility of identifying the underlying genetic variant(s) associated with the predisposition and therefore allowing future interrogation of the pathogenesis of this condition

Fungal Rhinosinusitis: A Retrospective Microbiologic and Pathologic Review of 400 Patients at a Single University Medical Center

Fungal Rhinosinusitis (FRS) is a well known entity, but only in more recent times have the types of FRS been more fully defined. In this study, we evaluate the diagnosis of FRS in a single medical center. Cases were divided into 2 main categories, non-invasive and invasive. Non-invasive FRS included fungus ball (FB) and allergic fungal rhinosinusitis (AFRS). Invasive FRS included acute invasive fungal rhinosinusitis (AIFRS), chronic invasive fungal rhinosinusitis (CIFRS), and chronic invasive granulomatous fungal rhinosinusitis (CGFRS). Fungal culture data, if available was reviewed. 400 patients with FRS were identified. 87.25% were non-invasive (45% AFRS, 40% FB, and 2% combined AFRS and FB and 12.5% were invasive 11% AIFRS 1.2% CIFRS 0.5% CGFRS. One patient (0.25%) had combined FB/CGFRS. Aspergillus sp. or dematiaceous species were the most common fungi isolated in AFS while Aspergillus sp. was most common in FB and AIFRS. In our experience, most FRS is non-invasive. In our patient population, invasive FRS is rare with AIFRS representing >90% of cases. Culture data supports that a variety of fungal agents are responsible for FRS, but Aspergillus sp. appears to be one of the most common organisms in patients with FRS

Keratinocyte-specific deletion of SHARPIN induces atopic dermatitis-like inflammation in mice.

Spontaneous mutations in the SHANK-associated RH domain interacting protein (Sharpin) resulted in a severe autoinflammatory type of chronic proliferative dermatitis, inflammation in other organs, and lymphoid organ defects. To determine whether cell-type restricted loss of Sharpin causes similar lesions, a conditional null mutant was created. Ubiquitously expressing cre-recombinase recapitulated the phenotype seen in spontaneous mutant mice. Limiting expression to keratinocytes (using a Krt14-cre) induced a chronic eosinophilic dermatitis, but no inflammation in other organs or lymphoid organ defects. The dermatitis was associated with a markedly increased concentration of serum IgE and IL18. Crosses with S100a4-cre resulted in milder skin lesions and moderate to severe arthritis. This conditional null mutant will enable more detailed studies on the role of SHARPIN in regulating NFkB and inflammation, while the Krt14-Sharpin-/- provides a new model to study atopic dermatitis

Nail abnormalities identified in an ageing study of 30 inbred mouse strains.

In a large-scale ageing study, 30 inbred mouse strains were systematically screened for histologic evidence of lesions in all organ systems. Ten strains were diagnosed with similar nail abnormalities. The highest frequency was noted in NON/ShiLtJ mice. Lesions identified fell into two main categories: acute to chronic penetration of the third phalangeal bone through the hyponychium with associated inflammation and bone remodelling or metaplasia of the nail matrix and nail bed associated with severe orthokeratotic hyperkeratosis replacing the nail plate. Penetration of the distal phalanx through the hyponychium appeared to be the initiating feature resulting in nail abnormalities. The accompanying acute to subacute inflammatory response was associated with osteolysis of the distal phalanx. Evaluation of young NON/ShiLtJ mice revealed that these lesions were not often found, or affected only one digit. The only other nail unit abnormality identified was sporadic subungual epidermoid inclusion cysts which closely resembled similar lesions in human patients. These abnormalities, being age-related developments, may have contributed to weight loss due to impacts upon feeding and should be a consideration for future research due to the potential to interact with other experimental factors in ageing studies using the affected strains of mice.American Hair Research Society Mentorship Grants (to SL and AM) Ellison Medical Foundation (to JPS) National Institutes of Health (AG025707, for the Shock Aging Center). The Jackson Laboratory Shared Scientific Services were supported in part by a Basic Cancer Center Core Grant from the National Cancer Institute (CA034196)

In a hard spot: Providing group prenatal care in two urban clinics

AbstractObjectivesCenteringPregnancy (Centering) group prenatal care has been demonstrated to improve perinatal outcomes and provide a positive experience of care for women, but it can be difficult to implement and sustain in some clinical settings. The purpose of this study was to examine the challenges encountered when Centering group prenatal care was provided, and the responses of Centering group leaders to these challenges.Designthis was a longitudinal, qualitative study using interpretive description. Data collection included participant-observation and interviews with group leaders and women receiving group prenatal care.Settingtwo urban clinics providing care to low income women in the northeastern United States.Participantsinterview participants were 23 pregnant women (primarily African-American and Hispanic) receiving group prenatal care; other participants were 24 significant others and support staff participating in groups, and two nurse-midwife group leaders.Findingsthe clinics did not always provide full resources for implementing Centering as designed, creating numerous challenges for the group leaders, who were committed to providing group prenatal care. In an attempt to sustain the model in the face of these limitations, the group leaders made a number of compromises and modifications to the Centering model.Key conclusionsthe limited clinic resources and resulting modifications of the model had a number of downstream effects, some of which affected relationships within groups, participation, and group cohesion.Implicationsmodifications of the Centering model should be undertaken with caution. Strategies are needed to enhance the success and sustainability of Centering in varied clinical settings so that the benefits of the model, which have been demonstrated under more controlled circumstances, can be conferred to women receiving routine care during pregnancy