Visual Impairment/Intracranial Pressure Risk Assessment

Since 2006 there have been 6 reported cases of altered visual acuity and intracranial pressure (ICP) in long duration astronauts. In order to document this risk and develop an integrated approach to its mitigation, the NASA Space Life Sciences Directorate (SLSD) and Human Research Program (HRP) have chosen to use the Human System Risk Board (HSRB) and the risk management analysis tool (RMAT). The HSRB is the venue in which the stakeholders and customers discuss and vet the evidence and the RMAT is the tool that facilitates documentation and comparison of the evidence across mission profiles as well as identification of risk factors, and documentation of mitigation strategies. This process allows for information to be brought forward and dispositioned so that it may be properly incorporated into the RMAT and contribute to the design of the research and mitigation plans. The evidence thus far has resulted in the identification of a visual impairment/intracranial pressure (VIIP) project team, updating of both short and long duration medical requirements designed to assess visual acuity, and a research plan to characterize this issue further. In order to understand this issue more completely, a plan to develop an Accelerated Research Collaboration (ARC) has been approved by the HSRB. The ARC is a novel research model pioneered by the Myelin Repair Foundation. It is a patient centered research model that brings together researchers and clinicians, under the guidance of a scientific advisory panel, to collaborate and produce results much quickly than accomplished through traditional research models. The data and evidence from the updated medical requirements and the VIIP ARC will be reviewed at the HSRB on a regular basis. Each review package presented to the HSRB will include an assessment and recommendation with respect to continuation of research, countermeasure development, occupational surveillance modalities, selection criteria, etc. This process will determine the course of the VIIP project and ultimately how SLSD and HRP mitigate this emerging human health and performance risk

Student, instructor, and observer agreement regarding frequencies of scientific teaching practices using the Measurement Instrument for Scientific Teaching-Observable (MISTO)

Background: The Scientific Teaching (ST) pedagogical framework encompasses many of the best practices recommended in the literature and highlighted in national reports. Understanding the growth and impact of ST requires instruments to accurately measure the extent to which practitioners implement ST in their courses. Researchers have typically relied on students, instructors, or observers to document course teaching practices, but it remains unclear whether and how these perspectives differ from each other. To address this issue, we modified our previously published instrument to generate the Measurement Instrument for Scientific Teaching-Observable (MISTO), which can be completed by students, instructors, and observers, and we investigated the degree of similarity between these three perspectives across 70 undergraduate science courses at seven different institutions in the USA. Results: We found that the full MISTO and Active Learning subcategory scores showed the highest correlations among the three perspectives, but the degree of correlation between perspectives varied for the other subcategories. Match scores between students and instructors were significantly higher than observer matches for the full MISTO and for the Active Learning, Inclusivity, and Responsiveness subcategories. Conclusions: We find that the level and type of agreement between perspectives varies across MISTO subcategories and that this variation likely stems from intrinsic differences in the course access and scoring decisions of the three perspectives. Building on this data, we recommend MISTO users consider their research goals, available resources, and potential artifacts that may arise when deciding which perspective best fits their needs in measuring classroom teaching practices

HIV-Related Knowledge and Practices among Asian and African Migrants Living in Australia: Results from a Cross-Sectional Survey and Qualitative Study

Australian HIV notification rates are higher for people born in Northeast Asia, Southeast Asia and sub-Saharan Africa compared to Australian-born people. The Migrant Blood-Borne Virus and Sexual Health Survey represents the first attempt to build the national evidence base regarding HIV knowledge, risk behaviors and testing among migrants in Australia. To inform survey development, preliminary qualitative research was conducted with a convenience sample of n = 23 migrants. A survey was developed with reference to the qualitative data and existing survey instruments. Non-probability sampling of adults born in Northeast Asia, Southeast Asia and sub-Saharan Africa was undertaken (n = 1489), and descriptive and bivariate analyses of data were conducted. Knowledge of pre-exposure prophylaxis was low (15.59%), and condom use at last sexual encounter was reported by 56.63% of respondents engaging in casual sex, and 51.80% of respondents reported multiple sexual partners. Less than one-third (31.33%) of respondents reported testing for any sexually transmitted infection or blood-borne virus in the previous two years and, of these, less than half (45.95%) tested for HIV. Confusion surrounding HIV testing practices was reported. These findings identify policy interventions and service improvements critically needed to reduce widening disparities regarding HIV in Australia

The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility.

BackgroundThe p6 region of the HIV-1 structural precursor polyprotein, Gag, contains two motifs, P7TAP11 and L35YPLXSL41, designated as late (L) domain-1 and -2, respectively. These motifs bind the ESCRT-I factor Tsg101 and the ESCRT adaptor Alix, respectively, and are critical for efficient budding of virus particles from the plasma membrane. L domain-2 is thought to be functionally redundant to PTAP. To identify possible other functions of L domain-2, we examined this motif in dominant viruses that emerged in a group of 14 women who had detectable levels of HIV-1 in both plasma and genital tract despite a history of current or previous antiretroviral therapy.ResultsRemarkably, variants possessing mutations or rare polymorphisms in the highly conserved L domain-2 were identified in seven of these women. A mutation in a conserved residue (S40A) that does not reduce Gag interaction with Alix and therefore did not reduce budding efficiency was further investigated. This mutation causes a simultaneous change in the Pol reading frame but exhibits little deficiency in Gag processing and virion maturation. Whether introduced into the HIV-1 NL4-3 strain genome or a model protease (PR) precursor, S40A reduced production of mature PR. This same mutation also led to high level detection of two extended forms of PR that were fairly stable compared to the WT in the presence of IDV at various concentrations; one of the extended forms was effective in trans processing even at micromolar IDV.ConclusionsOur results indicate that L domain-2, considered redundant in vitro, can undergo mutations in vivo that significantly alter PR function. These may contribute fitness benefits in both the absence and presence of PR inhibitor

Plasmonic lenses for ultrafast electron nanoemission

We show the capability of plasmonic lenses for next-generation ultrafast electron sources. Using electromagnetic simulations, we design structures capable of femtosecond, nanoscale electron pulses. Plasmonic properties of template-stripped gold prototypes are characterized using cathodoluminescence spectromicroscopy

Antagonists of retinoic acid receptors (RARs) are potent growth inhibitors of prostate carcinoma cells

Novel synthetic antagonists of retinoic acid receptors (RARs) have been developed. To avoid interference by serum retinoids when testing these compounds, we established serum-free grown sub-lines (>3 years) of the prostate carcinoma lines LNCaP, PC3 and DU145. A high affinity pan-RAR antagonist (AGN194310, Kd for binding to RARs = 2–5 nM) inhibited colony formation (by 50%) by all three lines at 16–34 nM, and led to a transient accumulation of flask-cultured cells in G1 followed by apoptosis. AGN194310 is 12–22 fold more potent than all-trans retinoic acid (ATRA) against cell lines and also more potent in inhibiting the growth of primary prostate carcinoma cells. PC3 and DU145 cells do not express RARβ, and an antagonist with predominant activity at RARβ and RARγ (AGN194431) inhibited colony formation at concentrations (∼100 nM) commensurate with a Kd value of 70 nM at RARγ. An RARα antagonist (AGN194301) was less potent (IC50 ∼200 nM), but was more active than specific agonists of RARα and of βγ. A component(s) of serum and of LNCaP-conditioned medium diminishes the activity of antagonists: this factor is not the most likely candidates IGF-1 and EGF. In vitro studies of RAR antagonists together with data from RAR-null mice lead to the hypothesis that RARγ-regulated gene transcription is necessary for the survival and maintenance of prostate epithelium. The increased potencies of RAR antagonists, as compared with agonists, suggest that antagonists may be useful in the treatment of prostate carcinoma. © 2001 Cancer Research Campaign http://www.bjcancer.co

Electronic structure and x-ray magnetic dichroism in random substitutional alloys of f-electron elements

The Koringa-Kohn-Rostoker —coherent-potential-approximation method combines multiple-scattering theory and the coherent-potential approximation to calculate the electronic structure of random substitutional alloys of transition metals. In this paper we describe the generalization of this theory to describe f-electron alloys. The theory is illustrated with a calculation of the electronic structure and magnetic dichroism curves for a random substitutional alloy containing rare-earth or actinide elements from first principles