US experiment flown on the Soviet biosatellite Cosmos 1667

Two male young-adult rhesus monkeys were flown on the Soviet Biosatellite Cosmos 1667 for seven days from July 10-17, 1985. Both animals were instrumented to record neurophysiological parameters. One animal, Gordyy, was additionally instrumented to record cardiovascular changes. Space capsule and environmental parameters were very similar to those of previous missions. On Cosmos 1514, which flew for five days in 1983, one animal was fitted with a left carotid artery cuff to measure blood pressure and flow velocity. An additional feature of Cosmos 1667 was a postflight control study using the flight animal. Intermittent postural tilt tests were also conducted before and after spaceflight and synchronous control studies, to simulate the fluid shifts associated with spaceflight. The experiment results support the conclusion derived from Cosmos 1514 that significant cardiovascular changes occur with spaceflight. The changes most clearly seen were rapid initial decreases in heart rate and further decreases with continued exposure to microgravity. The triggering mechanism appeared to be a headward shift in blood and tissue fluid volume which, in turn, triggered adaptive cardiovascular changes. Adaptive changes took place rapidly and began to stabilize after the first two days of flight. However, these changes did not plateau in the animal by the last day of the mission

Overlap of heritable influences between Cannabis Use Disorder, frequency of use and opportunity to use cannabis: Trivariate twin modelling and implications for genetic design

Background: The genetic component of Cannabis Use Disorder may overlap with influences acting more generally on early stages of cannabis use. This paper aims to determine the extent to which genetic influences on the development of cannabis abuse/dependence are correlated with those acting on the opportunity to use cannabis and frequency of use. Methods: A cross-sectional study of 3303 Australian twins, measuring age of onset of cannabis use opportunity, lifetime frequency of cannabis use, and lifetime DSM-IV cannabis abuse/dependence. A trivariate Cholesky decomposition estimated additive genetic (A), shared environment (C) and unique environment (E) contributions to the opportunity to use cannabis, the frequency of cannabis use, cannabis abuse/dependence, and the extent of overlap between genetic and environmental factors associated with each phenotype. Results: Variance components estimates were A = 0.64 [95% confidence interval (CI) 0.58–0.70] and E = 0.36 (95% CI 0.29–0.42) for age of opportunity to use cannabis, A = 0.74 (95% CI 0.66–0.80) and E = 0.26 (95% CI 0.20–0.34) for cannabis use frequency, and A = 0.78 (95% CI 0.65–0.88) and E = 0.22 (95% CI 0.12–0.35) for cannabis abuse/dependence. Opportunity shares 45% of genetic influences with the frequency of use, and only 17% of additive genetic influences are unique to abuse/dependence from those acting on opportunity and frequency. Conclusions: There are significant genetic contributions to lifetime cannabis abuse/dependence, but a large proportion of this overlaps with influences acting on opportunity and frequency of use. Individuals without drug use opportunity are uninformative, and studies of drug use disorders must incorporate individual exposure to accurately identify aetiology

GNOM v1.0: an optimized steady-state model of the modern marine neodymium cycle

Spatially distant sources of neodymium (Nd) to the ocean that carry different isotopic signatures (εNd) have been shown to trace out major water masses and have thus been extensively used to study large-scale features of the ocean circulation both past and current. While the global marine Nd cycle is qualitatively well understood, a complete quantitative determination of all its components and mechanisms, such as the magnitude of its sources and the paradoxical conservative behavior of εNd, remains elusive. To make sense of the increasing collection of observational Nd and εNd data, in this model description paper we present and describe the Global Neodymium Ocean Model (GNOM) v1.0, the first inverse model of the global marine biogeochemical cycle of Nd. The GNOM is embedded in a data-constrained steady-state circulation that affords spectacular computational efficiency, which we leverage to perform systematic objective optimization, allowing us to make preliminary estimates of biogeochemical parameters. Owing to its matrix representation, the GNOM model is additionally amenable to novel diagnostics that allow us to investigate open questions about the Nd cycle with unprecedented accuracy. This model is open-source and freely accessible, is written in Julia, and its code is easily understandable and modifiable for further community developments, refinements, and experiments.</p

Discovery of an 86 AU Radius Debris Ring Around HD 181327

HST/NICMOS PSF-subtracted coronagraphic observations of HD 181327 have revealed the presence of a ring-like disk of circumstellar debris seen in 1.1 micron light scattered by the disk grains, surrounded by a di use outer region of lower surface brightness. The annular disk appears to be inclined by 31.7 +/- 1.6 deg from face on with the disk major axis PA at 107 +/-2 deg . The total 1.1 micron flux density of the light scattered by the disk (at 1.2" < r < 5.0") of 9.6 mJy +/- 0.8 mJy is 0.17% +/- 0.015% of the starlight. Seventy percent of the light from the scattering grains appears to be confined in a 36 AU wide annulus centered on the peak of the radial surface brightness (SB) profile 86.3 +/- 3.9 AU from the star, well beyond the characteristic radius of thermal emission estimated from IRAS and Spitzer flux densities assuming blackbody grains (~ 22 AU). The light scattered by the ring appears bilaterally symmetric, exhibits directionally preferential scattering well represented by a Henyey-Greenstein scattering phase function with g = 0.30 +/- 0.03, and has an azimuthally medianed SB at the 86.3 AU radius of peak SB of 1.00 +/- 0.07 mJy arcsec^-2. No photocentric offset is seen in the ring relative to the position of the central star. A low surface brightness diffuse halo is seen in the NICMOS image to a distance of ~ 4" Deeper 0.6 micron HST/ACS PSF-subtracted coronagraphic observations reveal a faint outer nebulosity, asymmetrically brighter to the North of the star. We discuss models of the disk and properties of its grains, from which we infer a maximum vertical scale height of 4 - 8 AU at the 87.6 AU radius of maximum surface density, and a total maximum dust mass of collisionally replenished grains with minimum grain sizes of ~ 1 micron of ~ 4 M(moon).Comment: 45 pages, 15 figures, accepted for publication in Ap

Human antibody VH domains targeting uPAR as candidate therapeutics for cancers

The high expression of uPAR has been linked to tumor progression, invasion, and metastasis in several types of cancer. Such overexpression of uPAR makes it a potential target for immunotherapies across common cancers such as breast, colorectal, lung, ovarian cancer, and melanoma. In our study, two high-affinity and specific human VH domain antibody candidates, designed as clones 3 and 115, were isolated from a phage-displayed human VH antibody library. Domain-based bispecific T- cell engagers (DbTE) based on these two antibodies exhibited potent killing of uPAR-positive cancer cells. Thus, these two anti-uPAR domain antibodies are promising candidates for treating uPAR positive cancers

The state of the focus and image quality of the Spitzer Space Telescope as measured in orbit

We describe the process by which the NASA Spitzer Space Telescope (SST) Cryogenic Telescope Assembly (CTA) was brought into focus after arrival of the spacecraft in orbit. The ground rules of the mission did not allow us to make a conventional focus sweep. A strategy was developed to determine the focus position through a program of passive imaging during the observatory cool-down time period. A number of analytical diagnostic tools were developed to facilitate evaluation of the state of the CTA focus. Initially, these tools were used to establish the in-orbit focus position. These tools were then used to evaluate the effects of an initial small exploratory move that verified the health and calibration of the secondary mirror focus mechanism. A second large move of the secondary mirror was then commanded to bring the telescope into focus. We present images that show the CTA Point Spread Function (PSF) at different channel wavelengths and demonstrate that the telescope achieved diffraction limited performance at a wavelength of 5.5 μm, somewhat better than the level-one requirement

Loss associated with subtractive health service change: The case of specialist cancer centralization in England

OBJECTIVE: Major system change can be stressful for staff involved and can result in 'subtractive change' - that is, when a part of the work environment is removed or ceases to exist. Little is known about the response to loss of activity resulting from such changes. Our aim was to understand perceptions of loss in response to centralization of cancer services in England, where 12 sites offering specialist surgery were reduced to four, and to understand the impact of leadership and management on enabling or hampering coping strategies associated with that loss. METHODS: We analysed 115 interviews with clinical, nursing and managerial staff from oesophago-gastric, prostate/bladder and renal cancer services in London and West Essex. In addition, we used 134 hours of observational data and analysis from over 100 documents to contextualize and to interpret the interview data. We performed a thematic analysis drawing on stress-coping theory and organizational change. RESULTS: Staff perceived that, during centralization, sites were devalued as the sites lost surgical activity, skills and experienced teams. Staff members believed that there were long-term implications for this loss, such as in retaining high-calibre staff, attracting trainees and maintaining autonomy. Emotional repercussions for staff included perceived loss of status and motivation. To mitigate these losses, leaders in the centralization process put in place some instrumental measures, such as joint contracting, surgical skill development opportunities and trainee rotation. However, these measures were undermined by patchy implementation and negative impacts on some individuals (e.g. increased workload or travel time). Relatively little emotional support was perceived to be offered. Leaders sometimes characterized adverse emotional reactions to the centralization as resistance, to be overcome through persuasion and appeals to the success of the new system. CONCLUSIONS: Large-scale reorganizations are likely to provoke a high degree of emotion and perceptions of loss. Resources to foster coping and resilience should be made available to all organizations within the system as they go through major change

A rational framework for evaluating the next generation of vaccines against Mycobacterium avium subspecies paratuberculosis

Since the early 1980s, several investigations have focused on developing a vaccine against Mycobacterium avium subspecies paratuberculosis (MAP), the causative agent of Johne\u27s disease in cattle and sheep. These studies used whole-cell inactived vaccines that have proven useful in limiting disease progression, but have not prevented infection. In contrast, modified live vaccines that invoke a Th1 type immune response, may improve protection against infection. Spurred by recent advances in the ability to create defined knockouts in MAP, several independent laboratories have developed modified live vaccine candidates by transcriptional mutation of virulence and metablolic genes in MAP. In order to accelerate the process of identification and comparative elvaluation of he most promising modified live MAP vaccine candidates, members of a multi-institutional USDA- funded research consortium, the Johne\u27s disease integrated program (JDIP), met to established a standardized testing platform using agreed upon protocols. A total of 22 candidates vaccine strains developed in five independent laboratories in the United States and New Zealand voluntarily entered into a double blind gated trial pipeline. In Phase I, the survival characteristics of each candidate were determined in bovine macrophages. Attenuated strains moved to Phase II, where tissue colonization of C57/BL6 mice were evaluated in a challenge model. In Phase III, five promising candidates from Phase I and II were evaluated for their ability to reduce fecal shedding, tissue colonization and pathology in a baby goat challenge model. Formation of a multi-institutional consortium for vaccine strain evaluation has revealed insights for the implementation of vaccine trials for Johne\u27s disease and other animals pathogens. We conclude by suggesting the best way forward based on this 3-phase trial experience and challenge the rationale for use of a macrophage-to-mouse-to native host pipeline for MAP vaccine development