Space flight-associated neuro-ocular syndrome (SANS)

Re: Stenger et al.: Focus on the optic nerve head in spaceflight-associated neuro-ocular syndrome (Ophthalmology. 2019;126:1604–1606)

Spaceflight-associated neuro-ocular syndrome (SANS) involves unilateral or bilateral optic disc edema, widening of the optic nerve sheath, and posterior globe flattening. Owing to posterior globe flattening, it is hypothesized that microgravity causes a disproportionate change in intracranial pressure (ICP) relative to intraocular pressure. Countermeasures capable of reducing ICP include thigh cuffs and breathing against inspiratory resistance. Owing to the coupling of central venous pressure (CVP) and intracranial pressure, we hypothesized that both ICP and CVP will be reduced during both countermeasures. In four male participants (32 ± 13 yr) who were previously implanted with Ommaya reservoirs for treatment of unrelated clinical conditions, ICP was measured invasively through these ports. Subjects were healthy at the time of testing. CVP was measured invasively by a peripherally inserted central catheter. Participants breathed through an impedance threshold device (ITD, -7 cmH2O) to generate negative intrathoracic pressure for 5 min, and subsequently, wore bilateral thigh cuffs inflated to 30 mmHg for 2 min. Breathing through an ITD reduced both CVP (6 ± 2 vs. 3 ± 1 mmHg; P = 0.02) and ICP (16 ± 3 vs. 12 ± 1 mmHg; P = 0.04) compared to baseline, a result that was not observed during the free breathing condition (CVP, 6 ± 2 vs. 6 ± 2 mmHg, P = 0.87; ICP, 15 ± 3 vs. 15 ± 4 mmHg, P = 0.68). Inflation of the thigh cuffs to 30 mmHg caused no meaningful reduction in CVP in all four individuals (5 ± 4 vs. 5 ± 4 mmHg; P = 0.1), coincident with minimal reduction in ICP (15 ± 3 vs. 14 ± 4 mmHg; P = 0.13). The application of inspiratory resistance breathing resulted in reductions in both ICP and CVP, likely due to intrathoracic unloading.NEW & NOTEWORTHY Spaceflight causes pathological changes in the eye that may be due to the absence of gravitational unloading of intracranial pressure (ICP) under microgravity conditions commonly referred to as spaceflight-associated neuro-ocular syndrome (SANS), whereby countermeasures aimed at lowering ICP are necessary. These data show that impedance threshold breathing acutely reduces ICP via a reduction in central venous pressure (CVP). Whereas, acute thigh cuff inflation, a popular known spaceflight-associated countermeasure, had little effect on ICP and CVP.

Spaceflight associated neuro-ocular syndrome (SANS) alters the vision of astronauts during long-duration spaceflights. There is controversy regarding SANS being similar to patients with idiopathic intracranial hypertension (IIH). IIH has been shown to be due to an elevation in venous sinus pressure. The literature suggests an increase in jugular vein pressure secondary to a headward shift of fluid occurs in SANS but this may not be enough to significantly alter the intracranial pressure (ICP). The literature regarding cardiac output and cerebral blood flow (CBF) in long-duration spaceflight is contradictory, however, more recent data suggests increased flow. Recent modelling has shown that an increase in CBF can significantly increase sinus pressure. The purpose of the present paper is to review the SANS vascular dynamics literature and through mathematical modelling suggest the possible underlying cause of SANS as an elevation in venous sinus pressure, secondary to the redistribution of fluids towards the head, together with a significant increase in pressure drop across the venous system related to the CBF.

A unique constellation of ocular structural changes and visual anomalies known as Spaceflight Associated Neuro-ocular Syndrome (SANS) affects 70 % of crew members after long-duration spaceflight. Current hypotheses regarding the etiology of SANS discuss cephalad fluid shifts and venous congestion, which are correlated with elevated intra-cranial pressure (ICP) and enlarged perivascular spaces (PVS). These PVS comprise the glymphatic system (GS), a recently discovered network of influx and efflux pathways for cerebrospinal fluid (CSF) and metabolites in the central nervous system (CNS). Both glymphatic clearance and traditionally understood CSF circulation are affected by sleep-wake cycles, displaying a significant increase in fluid flow during sleep. Natural sleep has been associated with a 60 % increase in interstitial space in animal studies, which likely enhances GS exchange and outflow. Corresponding studies in humans using contrast-enhanced MRI associate sleep with greater glymphatic clearance compared to wakefulness. The sleep problems of astronauts during long-duration spaceflight have been well documented, ranging from sleep disruption and decreased quality to insufficient sleep duration. With recent terrestrial studies providing evidence that sleep deprivation impairs molecular clearance from the human brain, it follows that similar glymphatic dysfunction may arise due to these conditions in astronauts. Thus, in addition to impairing crew member work performance on long-duration space missions, sleep deprivation may exert long-term neuro-ocular effects via decreased glymphatic efficiency and clearance. The adverse impact of the resulting cognitive and visual disturbances presents a major future performance risk to astronauts. This work discusses the existing body of literature regarding the connections between circadian disruption and glymphatic disruption as a potential contributing mechanism for the development of SANS. This association should receive focused attention in future research as a potential risk factor for SANS. In addition, interventions that enhance extraterrestrial sleep quality and duration may prove to be practical countermeasures for the prevention of this syndrome.

Spaceflight associated neuro-ocular syndrome (SANS) is one of the potential barriers to human long-duration spaceflight (LDSF), including a manned mission to Mars. While a large barrier, the pathophysiology of SANS is not well understood, and functional and structural findings from SANS continue to be further characterized. Currently on the International Space Station (ISS), scheduled visual assessments are static visual acuity, Amsler grid, and a self-reported survey. Additional visual assessments may help the understanding of this neuro-ophthalmic phenomenon, as well as the effects of spaceflight of overall ocular health. In this paper, a case is made for expanding scheduled visual assessments to include dynamic visual, contrast sensitivity (CS), visual field testing, and virtual reality-based metamorphopsia assessment during spaceflight. These further assessments may play a key role in helping to determine the structural and functional changes associated with SANS, which are crucial to maintain astronaut vision during LDSF, as well as for developing countermeasures. Finally, a brief discussion is provided about current challenges to expanding visual testing during spaceflight and potential solutions to these barriers, specifically head-mounted visual assessment technology.

Over the last decade, the National Aeronautics and Space Administration's (NASA) Space Medicine Division has documented a variety of unusual physiological and pathological neuro-ophthalmic findings in astronauts during and following long duration space flight. These ndings include optic disc swelling, globe flattening, choroidal folds, and hyperopic shifts in refraction. Cephalad fluid shift has been proposed as a possible unifying etiology, but the specific mechanism responsible for these changes remains obscure. This manuscript reviews the history, clinical findings, and potential neurophysiological etiologies for spaceflight-associated neuro-ocular syndrome.

Jumping at a chance to control cerebral blood flow in astronauts.

Space travel: medicine in extremes

Personal computers of the past were limited to running computational fluid dynamics codes in serial mode. With the advent of multicore technology and suitable compilers, personal computers nowadays can execute codes in a parallel fashion similar to that of supercomputers and cluster computer systems. This article investigated what performance can be achieved when executing an aerodynamic code on an Intel quad core based personal computer with an OpenMP compiler in a Windows environment. The code solved the Euler equations to find the flowfield around a NACA0012 aerofoil on an O-type boundary fitted structured grid system. A speedup of up to 350% was obtainable in double precision accuracy. The reduced computation time means that, for small scale problems, more accurate Euler codes can replace commonly used transonic small disturbance codes. For larger problems, this information serves as a reference for developers of hybrid MPI/OpenMP algorithms for cluster computer systems. References Advanced Micro Devices (AMD), AMD FireStream 9170: Industry's First GPU with Double-Precision Floating Point, 2007, http://ati.amd.com/products/streamprocessor/specs.html Allmaras, S. R., Venkatakrishnan, V., and Johnson, F. T., Farfield Boundary Conditions for 2-D Airfoils, AIAA Paper 2005-4711, AIAA, 2005. Bailey, D., Barszcz, E., Barton, J., Browning, D., Carter, R., Dagum, L., Fatoohi, R., Fineberg, S., Frederickson, P., Lasinski, T., Schreiber, R., Simon, H., Venkatakrishnan, V., and Weeratunga, S., The NAS Parallel Benchmarks, National Aeronautics and Space Administration (NASA), Contractor Report 203186, USA, 1994, http://ntrs.nasa.gov/archive/nasa/casi.ntrs.nasa.gov/19970014936_1997021577.pdf Dong, S., and Karniadakis, G. E., Dual-Level Parallelism for High-Order CFD Methods, Parallel Computing, 30, Jan. 2004, pp. 1--20. Hirsch, C., Numerical Computation of Internal and External Flows (Volume 2): Computational Methods for Inviscid and Viscous Flows, John Wiley and Sons, Great Britain, 1992. Hoffmann, K. A., Computational Fluid Dynamics for Engineers, Engineering Educational System, Texas, USA, 1989. Intel, Tera-scale Computing Research Program, c.2007, http://www.intel.com/research/platform/terascale/ Jin, H., Frumkin, M., and Yan, J., The OpenMP Implementation of NAS Parallel Benchmarks and its Performance, National Aeronautics and Space Administration (NASA), Technical Report NAS-99-011, Moffett Field, USA, 1999. Liu, Y., and Vinokur, M., Nonequilibrium Flow Computations 1: An Analysis of Numerical Formulations of Conservation Laws, National Aeronautics and Space Administration (NASA), Contractor Report 177489, California, USA, 1988, http://ntrs.nasa.gov/archive/nasa/casi.ntrs.nasa.gov/19880021000_1988021000.pdf Lock, R. C., Test Cases for Numerical Methods in Two-Dimensional Transonic Flows, Advisory Group for Aerospace Research and Development (AGARD), Report Number 575, 1970. Ly, E., Improved Approximate Factorisation Algorithm for the Steady Subsonic and Transonic Flow over an Aircraft Wing, Proceedings of the 21st Congress of the International Council of the Aeronautical Sciences (ICAS98), ICAS and AIAA, Melbourne, Australia, 1998, Paper A98-31699. Ly, E., and Gear, J. A., Time-Linearized Transonic Computations Including Shock Wave Motion Effects, Journal of Aircraft, 39, 6, Nov/Dec. 2002, pp. 964--972. Ly, E., and Nakamichi, J., Time-Linearised Transonic Computations Including Entropy, Vorticity and Shock Wave Motion Effects, The Aeronautical Journal, Nov. 2003, pp. 687--695. Ly, E., and Norrison, D., Automatic Elliptic Grid Generation by an Approximate Factorisation Algorithm, ANZIAM Journal, 48 (CTAC2006), pp. C188--C202, July 2007, http://anziamj.austms.org.au/ojs/index.php/ANZIAMJ/article/view/48. Ly, E., and Norrison, D., Generating Elliptic Grids in Three Dimensions by a Method of False Transients, ANZIAM Journal, 49 (EMAC2007), pp. C170--C183, Nov. 2007, http://anziamj.austms.org.au/ojs/index.php/ANZIAMJ/article/view/313. Nvidia, The Era of the Personal Supercomputer, 2007, http://www.nvidia.com/content/events/siggraph_2007/supercomputing.html Pope, S. B., A Perspective on Turbulence Modeling, Modeling Complex Turbulent Flows, Kluwer Academic Publishers, The Netherlands, 1999. Pulliam, T., Kutler, P., and Rossow, V., Harvard Lomax: His Quiet Legacy to Computational Fluid Dynamics, 14th AIAA Computational Fluid Dynamics Conference, Norfolk, VA, 28 June-1 July, 1999, http://people.nas.nasa.gov/ pulliam/mypapers/lomax_la.ps Steger, J. L., and Warming, R. F., Flux Vector Splitting of the Inviscid Gasdynamic Equations with Application to Finite Difference Methods, National Aeronautics and Space Administration (NASA) Technical Memorandum 78605, California, USA, 1979, http://ntrs.nasa.gov/archive/nasa/casi.ntrs.nasa.gov/19790020779_1979020779.pdf Thompson, J. R., Warsi, Z. U. A., and Mastin, C. W., Numerical Grid Generation: Foundations and Applications, Elsevier Science Publishing Co. Inc., New York, USA, 1985. Van Leer, B., Flux-Vector Splitting for the Euler Equations, Proceedings of the 8th International Conference on Numerical Methods in Fluid Dynamics, Aachen, West Germany, 1982.

Spaceflight associated neuro-ocular syndrome (SANS) is a mission-critical limitation of long-duration spaceflight. The syndrome is comprised of globe flattening, hyperopic shifts, chorioretinal folds, optic disc edema, and cotton-wool spots; however, not every astronaut develops this pathology. Here, we present a hypothesis regarding one potential mechanism, intraocular pressure fluctuations, for the pathophysiology of the development of SANS. Further, we suggest ways in which this mechanism can be tested terrestrially.

During long-duration spaceflights, nearly all astronauts exhibit some change in ocular structure within the spectrum of spaceflight-associated neuro-ocular syndrome. To quantitatively determine in a prospective study whether changes in ocular structures hypothesized to be associated with the development of spaceflight-associated neuro-ocular syndrome occur during 6-month missions on board the International Space Station (ISS). The Ocular Health ISS Study of astronauts is a longitudinal prospective cohort study that uses objective quantitative imaging modalities. The present cohort study investigated the ocular structure of 11 astronauts before, during, and after a 6-month mission on board the ISS. Changes in ocular structure (peripapillary edema, axial length, anterior chamber depth, and refraction) hypothesized to be associated with the development of spaceflight-associated neuro-ocular syndrome during 6-month missions on board the ISS were assessed. Statistical analyses were conducted from August 2018 to January 2019. Before launch, the 11 astronauts were a mean (SD) age of 45 (5) years, a mean (SD) height of 1.76 (0.05) m, and a mean (SD) weight of 75.3 (7.1) kg. Six astronauts did not have prior spaceflight experience, 3 had completed short-duration missions on board the Space Shuttle, and 2 had previous long-duration spaceflight missions on board the ISS. Their mean (SD) duration on board the ISS in the present study was 170 (19) days. Optic nerve head rim tissue and peripapillary choroidal thickness increased from preflight values during early spaceflight, with maximal change typically near the end of the mission (mean change in optic nerve head rim tissue thickness on flight day 150: 35.7 μm; 95% CI, 28.5-42.9 μm; P < .001; mean choroidal thickness change on flight day 150: 43 μm; 95% CI, 35-46 μm; P < .001). The mean postflight axial length of the eye decreased by 0.08 mm (95% CI, 0.10-0.07 mm; P < .001) compared with preflight measures, and this change persisted through the last examination (1 year after spaceflight: 0.05 mm; 95% CI, 0.07-0.03 mm; P < .001). This study found that spaceflight-associated peripapillary optic disc edema and choroid thickening were observed bilaterally and occurred in both sexes. In addition, this study documented substantial peripapillary choroid thickening during spaceflight, which has never been reported in a prospective study cohort population and which may be a contributing factor in spaceflight-associated neuro-ocular syndrome. Data collection on spaceflight missions longer than 6 months will help determine whether the duration of the mission is associated with exacerbating these observed changes in ocular structure or visual function.

The National Aeronautics and Space Administration has formed the Advanced Space Transportation Program (ASTP) at the Marshall Space Flight Center to address advanced space transportation technologies. The main focus of the ASTP Office is directed to those technologies that will be needed to reduce the cost of both Earth-toorbit and in-space transportation. The current focus of the advanced reusable technologies (ART) Project is the development of those critical technologies required to enable a rocket-based combined-cycle (RBCC) engine and ultimately an RBCC-based reusable launch vehicle. Additional effort is also being expended to address those associated technologies that would be required to not only support an RBCC-based vehicle but other advanced reusable transportation systems as well. This paper will describe the work that has been performed since the last project status was presented to the 1997 Joint Propulsion Conference.' Currently, NASA and its industry partners are performing ground testing of hydrogen-fueled rocketbased combined-cycle flowpaths. Successful ramjet and scramjet testing at Mach 6 and scramjet testing at Mach 8 have been performed. Cold flow mixing tests have also been successfully performed as have inlet operability tests. Additional testing of RBCC flowpaths at air augmented rocket and rocket only modes is underway. Additional work will be performed on technologies that will support an RBCC-powered launch vehicle and will be focused in the following areas: structures and materials; avionics and operations; propulsion turbomachinery; and thermal protection systems. Chief Engineer, Advanced Reusable Technologies Project, NASA/ MSFC, Senior Member AIAA Project Manager, Advanced Reusable Technologies Project, NASA/MSFC, Member AIAA Copyright © 1998 by the American Institute of Aeronautics and Astronautics, Inc. No copyright is asserted in the United States under Title 17, U.S. Code. The U.S. Government has a royalty-free license to exercise all rights under the copyright claimed herein for Governmental Purposes. All other rights are reserved by the copyright owner. Introduction The National Aeronautics and Space Administration (NASA) Advanced Space Transportation Program (ASTP), part of the Space Transportation Program (STP) Office at the Marshall Space Flight Center (MSFC), is focusing on those technologies that will be needed to reduce the cost of both Earth-to-orbit and in-space transportation. NASA's strategy is to advance innovative space transportation technology development through the X-33, X-34, ASTP, and the Future-X programs to enable reduction of these costs. The ASTP consists of three major technology areas: focused, core, and research technologies. The ART project currently manages the work that is covered under NASA Research Announcements 8-16 and 8-21. The project's primary focus over the last 2 years has been on rocket-based combined-cycle (RBCC) technology development activities awarded under NRA 8-16. The current aerospace and academic organizations listed in Figure 1 are performing testing and analysis supporting the RBCC propulsion activities. The engine contractors, Aerojet, Pratt & Whitney, and Rocketdyne are currently either testing or preparing to test their RBCC engine flowpaths. Direct connect testing has been performed at Mach 6 flight conditions in both ramjet and scramjet modes and at Mach 8 flight conditions in the scramjet mode. Testing has also been performed at sealevel static conditions and at Mach 3.4 ramjet conditions.

Hot dust-obscured galaxies (hot DOGs), selected from Wide-Field Infrared Survey Explorer’s all-sky infrared&#13;\nsurvey, host some of the most powerful active galactic nuclei known and may represent an important stage in the&#13;\nevolution of galaxies. Most known hot DOGs are located at z &gt; 1.5, due in part to a strong bias against identifying&#13;\nthem at lower redshift related to the selection criteria. We present a new selection method that identifies 153 hot&#13;\nDOG candidates at z ~ 1, where they are significantly brighter and easier to study. We validate this approach by&#13;\nmeasuring a redshift z = 1.009 and finding a spectral energy distribution similar to that of higher-redshift hot&#13;\nDOGs for one of these objects, WISE J1036+0449 ( LBol ~= 8 x 10^46 erg s^-1). We find evidence of a broadened&#13;\ncomponent in Mg II, which would imply a black hole mass of MBH ~= 2 x 10^8 M(solar) and an Eddington ratio of&#13;\nLambdaEdd ~= 2.7. WISE J1036+0449 is the first hot DOG detected by the Nuclear Spectroscopic Telescope Array, and&#13;\nobservations show that the source is heavily obscured, with a column density of NH = 2-15 x 10^23 cm^-2 . The&#13;\nsource has an intrinsic 2–10 keV luminosity of ~ 6 x 10^44 erg s^-1, a value significantly lower than that expected&#13;\nfrom the mid-infrared/X-ray correlation. We also find that other hot DOGs observed by X-ray facilities show a&#13;\nsimilar deficiency of X-ray flux. We discuss the origin of the X-ray weakness and the absorption properties of hot&#13;\nDOGs. Hot DOGs at z ~&lt; 1 could be excellent laboratories to probe the characteristics of the accretion flow and of&#13;\nthe X-ray emitting plasma at extreme values of the Eddington ratio.

Abstract20 July 1969: approximately 240 000 mi away from Earth, two astronauts named Neil Armstrong and Edwin E. Aldrin Jr. landed on the moon. 20 October 2020: approximately 200 million miles away from Earth, the National Aeronautics and Space Administration (NASA) managed to land a spacecraft on an asteroid named Bennu and collect a sample from its surface. Sometime 2030s: approximately 34 million miles away from Earth, NASA is looking to successfully send humans to Mars. So, why is all this important? The effects of climate change are apparent on Earth today—temperatures around the world higher than normal, a rising sea level, natural disasters increasing in frequency and strength—and these effects continue to become ever more apparent as time goes on; thus, there is a need for solutions, which outer space has become one that is simultaneously grown in seriousness over the years. Colonizing space, traveling to distant planets and inhabiting them, these are definite possibilities for humans, as evidenced above by the remarkable progress NASA has made; however, one of the biggest obstacles NASA is dealing with in bringing those possibilities into fruition is their food system—all the actors and interactions within a food chain, meaning those who grow the food, those who process the food, those who transport the food, those who sell the food and finally, those who consume and dispose of the food. The shelf life of NASA's current food system will not last past 18 months in the unique environment of space, where there are the hazards of galactic cosmic rays, solar radiation and microgravity. Recognizing this—essentially recognizing that achieving such aforementioned feats would require a food system that can last much longer—NASA and others have constantly been researching and experimenting with their food system, ranging from how its food is grown, processed and preserved to the focus of this literature review: how it is packaged. Henceforth, the purpose of this literature review is to chronologically look at and discuss the major materials and technologies used in NASA's space food packaging of the past—the 1960s–1970s—look at and discuss those of the present—the 1980s–2000s—and finally, look ahead and discuss those of the future, entailing materials and technologies currently being worked on or considered for future use in NASA space missions. At that, here's to 60 years of activity in space.

HE ownership of resulting from T government financed research and development constitutes a very controversial problem. The federal government mainly the Department of Defense (DOD) has permitted industrial firms to obtain the patent rights to most of the inventions emerging from its contract research, under the so-called with the government acquiring royaltyfree licenses on the inventions. Our task here is an empirical investigation of one of the issues in the controversy over federal patent policy, namely, the concentration of resulting from the operation of the license policy. One of the strongest objections to the license policy rests on the belief that it causes undue concentration of economic power. The objection has been raised repeatedly by attorneys general, by legislators, and by economists who favor the so-called ' under which the government retains ownership of resulting from its contract research. From records of the United States Patent Office, we have compiled data for the period 1946 to 1962 on the numbers of assigned to business firms that have been the research and development (R and D) for the Atomic Energy Commission (AEC), the Department of Defense, and the National Aeronautics and Space Administration (NASA). The data are neither estimates nor samples; they are complete counts. The three agencies account for nearly all of the issued under the license policy to contractors. Henceforth, we shall refer to these as license-policy patents. We also have data on the private patents resulting from the company financed R and D of the same contractors. The major R and D contractors are 177 business firms that were among the first 100 of DOD in any fiscal year from 1955 to 1962, or who had contract awards of $2 million or more from the AEC or from NASA.2 Of these 177 firms, 40 are among the first 100 in Fortune's list for 1962. Another 49 are among Fortune's 500 companies. A further 36 have been officially stamped as small businesses. With the exception of a few of the bigger chemical and oil companies that have done little or no research for the federal government, the names of nearly all the Schumpeterian giants of American industry are on our list. By treating each firm and its subsidiaries as a unit, we overstate patent concen* The research underlying this article was supported by a grant (NsG 425) from the National Aeronautics and Space Administration to The George Washington University. 1 Department of Justice, Investigations of Government Patent Practices and Policies: Report and Recommendations of the Attorney General to the President 1 (Washington, D.C.: U.S. Government Printing Office, 1947), 37; Report of the Attorney General Pursuant to Section 708 (e) of the Defense Production Act of 1950, as Amended (Nov. 9, 1956, mimeo.); Clair Wilcox, Public Policies Toward Business (Homewood, Ill.: Richard D. Irwin, 1960), 191; Walter Adams and Horace M. Gray, Monopoly in America: The Government as Promotor (New York: Macmillan, 1955), 47, 94, and 148-152. Testimony against the license policy and in favor of the title policy was given to a Senate subcommittee in 1963 by Horace M. Gray, Robert F. Lanzillotti, Wassily W. Leontief, Richard R. Nelson, and Lee E. Preston. See Aspects of Government Patent Policies, Hearings before a Subcommittee of the Select Committee on Small Business, United States Senate, 88th Congress, First Session, Impact of Government Patent Policies on Economic Growth, Scientific and Technological Progress, Competition, and Opportunities for Small Business, March 7, 8, 13, and 14, 1963 (Washington, D.C.: U.S. Government Printing Office, 1963). Only Leontief (p. 236), however, addressed himself specifically to the question of concentration. 2 Department of Defense, 500 Contractors Listed According to Net Value of Military Prime Contract Awards for Experimental, Development Test and Research Work (Fiscal years 1955 through 1962, mimeo.); and Files of the Atomic Energy Commission and published reports of the National Aeronautics and Space Administration. 'Usually, government employees are required to assign title to the government. However, if a government employee, with his own resources, produces an invention that his agency wants, the government frequently files the patent application in exchange for a royalty-free license. Also, if an agency does not want a government financed invention made by an employee, the employee often is permitted to acquire title. Regulations governing employees were tightened in 1950. This fact and the relative growth of contract research are the causes of the decline in the number of licenses from employees after 1950.