GDNF and Parkinson's Disease : Where Next? A Summary from a Recent Workshop

The concept of repairing the brain with growth factors has been pursued for many years in a variety of neurodegenerative diseases including primarily Parkinson's disease (PD) using glial cell line-derived neurotrophic factor (GDNF). This neurotrophic factor was discovered in 1993 and shown to have selective effects on promoting survival and regeneration of certain populations of neurons including the dopaminergic nigrostriatal pathway. These observations led to a series of clinical trials in PD patients including using infusions or gene delivery of GDNF or the related growth factor, neurturin (NRTN). Initial studies, some of which were open label, suggested that this approach could be of value in PD when the agent was injected into the putamen rather than the cerebral ventricles. In subsequent double-blind, placebo-controlled trials, the most recent reporting in 2019, treatment with GDNF did not achieve its primary end point. As a result, there has been uncertainty as to whether GDNF (and by extrapolation, related GDNF family neurotrophic factors) has merit in the future treatment of PD. To critically appraise the existing work and its future, a special workshop was held to discuss and debate this issue. This paper is a summary of that meeting with recommendations on whether there is a future for this therapeutic approach and also what any future PD trial involving GDNF and other GDNF family neurotrophic factors should consider in its design.Peer reviewe

The Ghost of Sagittarius and Lumps in the Halo of the Milky Way

We identify new structures in the halo of the Milky Way Galaxy from positions, colors and magnitudes of five million stars detected in the Sloan Digital Sky Survey. Most of these stars are within 1.26 degrees of the celestial equator. We present color-magnitude diagrams (CMDs) for stars in two previously discovered, tidally disrupted structures. The CMDs and turnoff colors are consistent with those of the Sagittarius dwarf galaxy, as had been predicted. In one direction, we are even able to detect a clump of red stars, similar to that of the Sagittarius dwarf, from stars spread across 110 square degrees of sky. Focusing on stars with the colors of F turnoff objects, we identify at least five additional overdensities of stars. Four of these may be pieces of the same halo structure, which would cover a region of the sky at least 40 degrees in diameter, at a distance of 11 kpc from the Sun (18 kpc from the center of the Galaxy). The turnoff is significantly bluer than that of thick disk stars, and closer to the Galactic plane than a power-law spheroid. We suggest two models to explain this new structure. One possibility is that this new structure could be a new dwarf satellite of the Milky Way, hidden in the Galactic plane, and in the process of being tidally disrupted. The other possibility is that it could be part of a disk-like distribution of stars which is metal-poor, with a scale height of approximately 2 kpc and a scale length of approximately 10 kpc. The fifth overdensity, which is 20 kpc away, is some distance from the Sagittarius dwarf streamer orbit and is not associated with any known structure in the Galactic plane. It is likely that there are many smaller streams of stars in the Galactic halo.Comment: ApJ, in press; 26 figures including several in colo

The sixth data release of the Radial Velocity Experiment (RAVE). I. Survey description, spectra and radial velocities

The Radial Velocity Experiment (RAVE) is a magnitude-limited (9<I<12) spectroscopic survey of Galactic stars randomly selected in the southern hemisphere. The RAVE medium-resolution spectra (R~7500) cover the Ca-triplet region (8410-8795A). The 6th and final data release (DR6 or FDR) is based on 518387 observations of 451783 unique stars. RAVE observations were taken between 12 April 2003 and 4 April 2013. Here we present the genesis, setup and data reduction of RAVE as well as wavelength-calibrated and flux-normalized spectra and error spectra for all observations in RAVE DR6. Furthermore, we present derived spectral classification and radial velocities for the RAVE targets, complemented by cross matches with Gaia DR2 and other relevant catalogs. A comparison between internal error estimates, variances derived from stars with more than one observing epoch and a comparison with radial velocities of Gaia DR2 reveals consistently that 68% of the objects have a velocity accuracy better than 1.4 km/s, while 95% of the objects have radial velocities better than 4.0 km/s. Stellar atmospheric parameters, abundances and distances are presented in subsequent publication. The data can be accessed via the RAVE Web (http://rave-survey.org) or the Vizier database.Comment: 32 pages, 11 figures, accepted for publication to A

Exercise behaviour, physical fitness, and Coronary Heart Disease risk factor status: evidence from a worksite-screening programme.

Londonsch_phypub1488pu

Assessment of the stage of exercise behaviour change in young adult females.

Victoria, BC, Canadasch_phypub1490pu

How applicable is the stages of change model to exercise behaviour?

sch_phy55pub1497pub

Evidence for the validity and utility of the Stages of Exercise Behaviour Change scale in young adults

This study examined the validity and utility of the Stages of Exercise Behaviour Change (SEBC) scale in 244 young British adults. One-way ANOVA revealed significant differences (F &lt; 7.34, P &gt; 0.01) between the Exercise Behaviour Change Categories of Precontemplation/Contemplation (n = 49), Preparation (n equals 87) and Action/Maintenance (n = 108) in self-report levels of exercise behaviour. Significant differences (F &gt; 3.14, P &lt; 0.05) were also revealed in exercise self-efficacy, physical self-perception sub-domains and global self-esteem scores. Subsequent step-wise discriminant analyses revealed that discrimination between the Categories of Exercise Behaviour Change was possible on the basis of selected behavioural and psychological parameters (Canonical r equals 0.76-0.82, Wilks' lambda = 0.30-0.33, 2 = 60.3-94.6, d.f. = 14, P &lt; 0.0001). In both males and females, the most dominant discriminatory variables in the first Function were revealed to be perceived physical conditioning and 'strenuous' exercise behaviour. For males, the second Function comprised exercise self-efficacy and perceived bodily attractiveness, whilst for females it comprised perceived bodily attractiveness, perceived sports competence and perceived physical strength. Subsequent cross-validation analysis, using a randomly selected 40% sub-sample, revealed that 67.8-70.7% of subjects were assigned to the correct Category. These results appear to confirm the concurrent validity of the SEBC scale in terms of self-report of exercise behaviour. Furthermore, the utility of the SEBC scale was demonstrated via the ability to predict membership of specific Categories of Exercise Behaviour Change using a selection of behavioural and psychological parameters.sch_phyADNFS (1992) Allied Dunbar National Fitness Survey. Sports Council & Health Education Authority, London. Astrand,P.-O. and Rodahl.K. (1986) Textbook of Work Physiology, 3rd edn. McGraw-Hill, New York. Baecke,J.A.H., Burema,J. and Frijters,J.E.R. (1982) A short questionnaire for the measurement of habitual physical activity in epidemiological studies. American Journal of Clinical Nutrition, 36, 932-942. Baranowski,T. (1988) Validity and reliability of self report measures of physical activity: an information-processing perspective. Research Quarterly for Exercise and Sport, 59, 314-327. Baranowski.T., Bouchard.C, Bar-Or,0., Bricker.T., Heath.G., Kimm.S.Y.S., Malina.R., Obarzanek,E., Pate.R., Strong.W.B., Truman.B. and Washington.R. (1992) Assessment, prevalence, and cardiovascular benefits of physical activity and fitness in youth. Medicine and Science in Sports and Exercise, 24 (Suppl.), S237-S247. Biddle,S.J.H. and Mutrie.N. (1991) Psychology of Physical Activity and Exercise: A Health-Related Perspective. Springer, London. Blair.S.N., Haskell.W.L., Ho,P., Paffenbarger,R.S.,Jr, Vranizan.K.M., FarquharJ.W. and Wood.P.D. (1985) Assessment of habitual physical activity by a seven-day recall in a community survey and in controlled experiments. American Journal of Epidemiology, 122, 794-804. Brooks,C. (1988) A causal modeling analysis of sociodemographics and moderate to vigorous physical activity behaviour of American adults. Research Quarterly for Exercise and Sport, 59, 328-338. Buxton,K.E. and Ashford.B. (1994) Participation motives and physical self-perceptions in high and low frequency female aerobic dance participants. Journal of Sport Sciences, 12, 184. Buxton.K.E., Mercer.T.H., Hale.B., Wyse.J.P. and Ashford.B. (1994) Evidence for the concurrent validity and measurement reliability of a Stages of Exercise Behaviour Change instrument. Journal of Sport & Exercise Psychology, 16, S35. Buxton.K.E., Wyse,J.P., Mercer.T.H. and Hale.B. (1995) Assessing the stages of exercise behaviour change and the stages of physical activity behaviour change. Journal of Sport Science, 13, 50-51. Campbell.R.N. (1984) The New Science: Self-Esteem Psychology. University Press of America, Lanham, MD. Cardinal.B.J. (1993) Validation of a stages of exercise adoption scale. Research Quarterly for Exercise and Sport, 67 (Suppl.), A50-A51. Carusco.C.M. and Gill.D.L. (1992) Strengthening physical selfperceptions through exercise. The Journal of Sports Medicine and Physical Fitness, 32, 416-427. Caspersen.CJ., Powell.K.E. and Christenson.G.M. (1985) Physical activity, exercise, and physical fitness: definitions and distinctions for health-related research. Public Health Reports. 100, 126-131. DiClemente.C.C. and Hughes.S.O. (1990) Stages of change profiles in outpatient alcoholism treatment. Journal of Substance Abuse, 2, 217-235. DiClemente.C.C., Prochaska.J.O. and Gilbertini.M. (1985) Selfefficacy and the stages of self-change of smoking. Cognitive Therapy and Research, 9, 181-200. DiClemente.C.C., Prochaska.J.0., Fairhurst.S.K.. Velicer.W.F., Velasquez,M.M. and Rossi.J.S. (1991) The process of smoking cessation: an analysis of precontemplation, contemplation, and preparation stages of change. Journal of Consulting and Clinical Psychology, 59, 295-304. Dishman.R.K. (1990) Determinants of participation in physical activity. In Bouchard.C.B., Shephard.R.J. and Stephens.T. (eds), Physical Activity, Fitness, and Health: A Consensus of Current Knowledge. Human Kinetics, Champaign, IL, pp. 75-101. Dishman.R.K. and Gettman.L.R. (1980) Psychobiologic influences on exercise adherence. Journal of Sport Psychology, 2, 295-310. Folsom.A.R., Caspersen.C.J., Taylor.H.L., Jacobs.D.R., Luepeker.R.V, Gomez-Marin.O., Gillum.R.F. and Blackburn,H. (1985) Leisure time physical activity and its relationship to coronary risk factors in a population-based sample: the Minnesota Health Heart Survey. American Journal of Epidemiology, 121, 570-579. Fox.K.R. (1990) The Physical Self-Perception Profile Manual. Office for Health Promotion, Northern Illinois University, DeKalb, IL. Fox,K.R. and Corbin.C.B. (1989) The physical self-perception profile: development and preliminary validation. Journal of Sport and Exercise Psychology, 11, 408-430. Fox,K.R. and Vehnekamp.T.J. (1990) Gender comparisons of self-perceptions, physical fitness, exercise and dietary habits in college students. Journal of Sport Sciences, 8 282-283. Godin,G. and Shephard.R.J. (1985) A simple method to assess exercise behaviour in the community. Canadian Journal of Applied Sport Sciences, 10, 141-146. Gorely.T. and Gordon.S. (1993) Self-efficacy, decision-making and exercise behaviour change. Paper presented at the Association for the Advancement of Applied Sport Psychology and the Canadian Society for Psychomotor Learning and Sport Psychology Annual Conference, Montreal, Canada, October. Gorely.T, Gordon.S. and Bull.F. (1993) The stages and processes of exercise behaviour change. Paper presented at the Association for the Advancement of Applied Sport Psychology and the Canadian Society for Psychomotor Learning and Sport Psychology Annual Conference, Montreal, Canada, October. Harter,S. (1978) Effectance motivation reconsidered: toward a developmental model. Human Development, 1, 34-64. Haskell.W.L., Leon.A.S., Caspersen.C.J., Froelicher.V.F, HagbergJ.M., Harlan.W., Holloszy.J.0., RegensteinerJ.G., Thompson.P.D., Washburn,R.A. and Wilson.P.W.F. (1992) Cardiovascular benefits and assessment of physical activity and physical fitness in adults. Medicine and Science in Sports and Exercise, 24 (Suppl.), S2O1-S22O. Health Education Authority (1993) Helping People Change Project: Training and Resources for Primary Health Care Professionals. Health Education Authority, Oxford. Jackson,A.S., Blair.S.N., Mahar.M.T., Weir.L.T., Ross.R.M. and StutevilleJ.E. (1990) Prediction of functional aerobic capacity without exercise testing. Medicine and Science in Sports and Exercise, 22, 863-870. Jacobs,D.R.,Jr, Ainsworth.B.E., Hartman,T.J. and Leon,A.S. (1993) A simultaneous evaluation of 10 commonly used physical activity questionnaires. Medicine and Science in Sports and Exercise, 25, 81-91. King,A.C., Blair.S.N., Bild,D.E., Dishman.R.K., Dubbert,P.M., Marcus.B.H., Oldridge,N.B., Paffenbarger.R.S.Jr, Powell, K.E. and Yaeger.K.K. (1992) Determinants of physical activity and interventions in adults. Medicine and Science in Sports and Exercise, 24 (Suppl.), S221-S236. LaPorte.R.E., Montoye.H.L. and Caspersen.C.J. (1985) Assessment of physical activity in epidemiological research: problems and prospects. Public Health Reports, 100, 131- 146. Marcus.B.H. and Owen.N. (1992) Motivational readiness, selfefficacy and decision-making for exercise. Journal of Applied Social Psychology, 22, 3-16. Marcus.B.H. and Simkin,L.R. (1993) The stages of exercise behaviour. The Journal of Sports Medicine and Physical Fitness, 33, 83-88. Marcus.B.H., Banspach.S.W., Lefebvre.R.C, Rossi.J.S., Carleton,R.A. and Abrams.D.B. (1992a) Using the stages of change model to increase the adoption of physical activity among community participants. American Journal of Health Promotion, 6, 424-429. Marcus.B.H., Rakowski.W. and Rossi,J.S. (1992b) Assessing motivational readiness and decision-making for exercise. Health Psychology, 11, 257-261. Marcus.B.H., Rossi.J.S., Selby.V.C, Niaura.R.S. and Abrams.D.B. (1992c) The stages and processes of exercise adoption and maintenance in a worksite sample. Health Psychology, 11, 386-395. Marcus.B.H., Selby.V.C, Niaura.R.S. and Rossi.J.S. (1992d) Self-efficacy and the stages of exercise behaviour change. Research Quarterly for Exercise and Sport, 63, 60-66. Massie,J.F. and Shephard.R.J. (1971) Physiological and psychological effects of training: a comparison of individual and gymnasium programs, with a characterization of the exercise 'dropout'. Medicine and Science in Sports, 3, 110-117. McConnaughy.E.A., ProchaskaJ.O. and Velicer.W.F. (1983) Stages of change in psychotherapy: measurement and sample profiles. Psychotherapy: Theory, Research and Practice, 20, 368-375. McConnaughy.E.A., DiClemente.C.C, ProchaskaJ.O. and Velicer,W.F. (1989) Stages of change in psychotherapy: a follow-up report. Psychotherapy: Theory, Research and Practice, 26, 494-503. Mutrie,N. and Caddell.C. (1994) Stages of exercise behaviour in corporate employees. Journal of Sports Science, 12, 202-203. Page.A., Ashford,B., Fox.K. and Biddle.S. (1993) Evidence of cross-cultural validity for the physical self-perception profile. Personality and Individual Differences, 14, 585-590. ProchaskaJ.O. and DiClemente.C.C. (1982) Transtheoretical therapy: toward a more integrative model of change. Psychotherapy: Theory, Research and Practice, 19, 276-288. ProchaskaJ.O. and DiClemente.C.C. (1983) Stages and processes of self-change in smoking: towards an integrative model of change. Journal of Consulting and Clinical Psychology, 51, 390-395. ProchaskaJ.O., DiClemente.C.C., Velicer.W.F, Ginpil.S.E. and NorcrossJ.C. (1985) Predicting change in smoking status for self-changers. Addictive Behaviours, 10, 395-406. ProchaskaJ.O., Velicer.W.F., DiClemente.C.C. and FavaJ. (1988) Measuring processes of change: applications to the cessation of smoking. Journal of Consulting and Clinical Psychology, 56, 520-528. Rosenburg.M. (1965) Society and the Adolescent Self-Image. Princeton University Press, Princeton, NJ. SallisJ.F, Haskell.W.L., Wood.P.D., Fortmann.S.R, Roger.T, Blair.S.N. and Paffenbarger.R.S.Jr (1985) Physical activity assessment methodology in the Five-City Project. American Journal of Epidemiology, 121, 91-106. SallisJ.F, Haskell.W.L., Fortmann.S.P., Vranizan.K.M., Taylor.K.B. and Solomon.D.S. (1986) Predictors of adoption and maintenance of physical activity in a community sample. Preventive Medicine, 15, 331-341. SallisJ.F, Hovell,M.F, Hofstetter.C.R., Faucher.P, ElderJ.R, BlanchardJ., Caspersen.C.J., Powell.K.E. and Christenson, G.M. (1989) A multivariate study of determinants of vigorous exercise in a community sample. Preventive Medicine, 18, 20-34. SallisJ.F, Hovell.M.F. and Hofstetter,C.R. (1992) Explanation of vigorous activity during two years using social learning variables. Social Science and Medicine, 34, 25-32. SPSS (1988) SPSS/PC+ Advanced Statistics, Version 2.0. SPSS, Chicago, IL. StephensJ., Jacobs.D.R. and White.C.C. (1985) A descriptive epidemiology of leisure-time physical activity. Public Health Reports, 100, 147-158. Taylor,C.B., Coffey,T, Berra.K., Iaffaldano,R., Casey.D. and Haskell.W.L. (1984) Seven day activity and self-report compared to a direct measure of physical activity. American Journal of Epidemiology, 120, 818-824. Teague.M. (1988) Vigorous physical activity for adults: a descriptive epidemiology. Journal of Physical Education, Recreation and Dance, 59, 4749. WillisJ., Layne,B.H., Owen.S., McCalep.G.O. and Elliott.M.B. (1993) Applying 'stage' theory of behaviour change to exercise: a replication and extension. Paper presented at the Association for the Advancement of Applied Sport Psychology and the Canadian Society for Psychomotor Learning and Sport Psychology Annual Conference, Montreal, Canada, October. Wooten,W.J., Long.B., Patrick.K., SallisJ., Calfas.K. and VanCamp.S. (1991) Project P.A.C.E.: physician-based activity assessment and counselling for exercisethe theoretical rationale. Medicine and Science in Sports and Exercise. 23 (Suppl.), SI20.10pub1047pub