Journal of Parkinson’s Disease
The Journal of Parkinson’s Disease is dedicated to providing an open forum for original research in basic science, translational research and clinical medicine that will expedite our fundamental understanding and improve treatment of Parkinson’s disease. The journal is international and multidisciplinary and aims to promote progress in the epidemiology, etiology, genetics, molecular correlates, pathogenesis, pharmacology, psychology, diagnosis and treatment of Parkinson’s disease. It will publish research reports, reviews, short communications, and letters-to-the-editor and offers very rapid publication and an affordable open access option.
Patrik Brundin, MD, PhD
J. William Langston, MD
Associate Editors for Reviews
M. Angela Cenci Nilsson
Mark R. Cookson
Robert H. Edwards
Jan Petter Larsen
Peter A. LeWitt
Eng King Tan
Social Media Editors
M. Flint Beal
David J. Brooks
K. Ray Chaudhuri
Marie Francoise Chesselet
Ted M. Dawson
Valina L. Dawson
Omar M. El-Agnaf
Ann M. Graybiel
J. Timothy Greenamyre
James G. Greene
Etienne C. Hirsch
Amos D. Korczyn
Jeffrey H. Kordower
Mark P. Mattson
Ronald F. Pfeiffer
David G. Standaert
A. Jon Stoessl
Caroline M. Tanner
John Q. Trojanowski
Mark A. Smith†
Chemical Abstracts Service (CAS)
Web of Science: Journal Citation Reports/Science Edition
Web of Science: Science Citation Index-Expanded (SciSearch®)
23 March 2017 - 26 March 2017
15 Nov 2016 - Although treatment for Parkinson’s disease (PD) is significantly extending the lives of patients, these patients are now being admitted to hospitals at increasing rates. In a study reported in the Journal of Parkinson’s Disease, researchers in Ireland have found that the top five reasons for hospital admission of PD patients are urinary tract infections, pneumonia, lower respiratory tract infections, aspiration pneumonia and femur fracture. More troubling is the stark increase in PD patients requiring long-term nursing home care on discharge, with 27% of the over 65 group discharged to a nursing home compared to 12% admitted from a nursing home....
15 Nov 2016 - A comprehensive review published in the Journal of Parkinson’s Disease confirms that people living with Parkinson’s disease (PD) can benefit from being physically active, especially when it comes to improving gait and balance, and reducing risks of falls. It concludes that health professionals should be confident about prescribing physical activity to improve the health and quality of life of PD patients. ...
13 Jul 2016 - Parkinson’s disease (PD) is the second most common neurodegenerative disorder that causes a range of motor and non-motor symptoms. During the course of the disease, dopamine (DA)-producing neurons are lost and bundles of proteins known as Lewy bodies (LBs) form in the brain. A study reported in the Journal of Parkinson’s Disease provided molecular evidence that the FDA-approved leukemia drug nilotinib may restore brain dopamine and reduce toxic proteins associated with LB formation in PD and dementia patients. ...
23 Jun 2016 - IOS Press has announced that its journal Impact Factors continue to increase, according to the 2015 Journal Citation Reports® (JCR) released by Thomson Reuters © 2016. ...
12 Apr 2016 - Accurate diagnosis of Parkinson’s disease, and the related disease “dementia with Lewy bodies,” can be difficult in the early stages of both conditions. While brain biopsies can be more accurate, the risk of complications has been considered too high. New research published in the Journal of Parkinson’s Disease indicates that a biopsy of the submandibular gland can help identify the same pathology that is seen in the brain, providing some of the increased accuracy of brain biopsy, but not the increased risk....
01 Apr 2016 - Journals and Books...
31 Mar 2016 - The Journal of Parkinson’s Disease (JPD) is proud to announce the launch of the Parkinson’s Disease Funding Analyzer (PDFA) on the JPD website. It is a free service that is part of a new suite of online features that have been designed to serve the needs of the Parkinson’s disease (PD) research community....
29 Mar 2016 - As stem cell-based therapies are moving rapidly towards clinical trials, treatments for Parkinson’s Disease (PD), an incurable condition, may be on the horizon. A recent announcement of a Phase I/IIa clinical trial involving transplantation of stem cells into the first human subjects has raised hope among patients and sparked discussions in the research community. In a commentary published in the Journal of Parkinson’s Disease, authors propose five key questions that should be addressed as this trial begins....
18 Mar 2016 - Cognitive impairment could affect the conversational ability of people with Parkinson's more than physical speech problems - according to research from the University of East Anglia (UEA) and the University of Aberdeen....
17 Feb 2016 - Many patients with Parkinson’s Disease (PD) develop mild cognitive impairment (MCI) or dementia. Identifying biomarkers for cognitive impairment could be instrumental in facilitating both early diagnosis of MCI and developing new cognitive-enhancing treatments. New research published in the Journal of Parkinson’s Disease indicates that lower concentrations of α-synuclein in cerebrospinal fluid (CSF) is associated with reduced performance on several cognitive tests....
12 Jan 2016 - IOS Press is happy to announce its partnership with Kudos (www.growkudos.com), an award winning service that helps researchers maximize the impact and visibility of their research. Kudos allows authors to enrich their articles with lay metadata, add links to related materials and promote their articles through the Kudos system to a wider public. From their personal dashboard, authors can track how often their articles are viewed and shared through Kudos. The service will be available to authors of all IOS Press journal articles starting the first quarter of 2016. ...
08 Jan 2016 - Lewy bodies and Lewy neurites are found in the brains of Parkinson’s disease (PD) patients. They consist primarily of fibrils of the protein alpha-synuclein (α-Syn), which self-assembles into fibrils in vitro. If introduced into the human body, these seeds can act as prions and trigger the formation of toxic protein deposits. Because α-Syn fibrils are often used in research, it is important that they are not accidentally transferred to humans or cell cultures. Researchers reporting in the Journal of Parkinson’s Disease describe three cleaning procedures that effectively remove and disassemble these α-synuclein seeds....
05 Jan 2016 - Recent evidence has shown a greater risk of dementia, in particular Alzheimer’s disease (AD), in individuals using anticholinergic medications regularly. These drugs are widely used by older adults to treat bladder dysfunction, mood, and pain, and many of them are available without prescription. Since these drugs are often used to treat both motor symptoms and non-motor symptoms in patients with Parkinson’s Disease (PD), there is concern for increased risk of dementia. Contrary to expectations, a study in the current issue of the Journal of Parkinson’s Disease determined that the cognitive performance of PD patients taking anticholinergic medications did not differ from those who did not....
10 Nov 2015 - For many years, researchers have been investigating whether there are any associations between Parkinson’s disease (PD) and lifestyle choices such as smoking and coffee and alcohol consumption. In a review published in the Journal of Parkinson’s Disease, the literature concerning alcohol consumption presents conflicting information....
10 Nov 2015 - Parkinson’s Disease (PD) patients have a five-fold greater risk of carrying genetic mutations in the β-glucocerebrosidase gene (GBA), which are commonly associated with Gaucher disease (GD). Patients with both PD and GD tend to experience earlier onset of PD and more serious cognitive changes than PD patients without the mutations. A new study published in the Journal of Parkinson’s Disease suggests that GD or the presence of GBA mutations may actually shield patients from deficiency in visual color discrimination, which is a hallmark of PD. ...
New Study Calls for Partnering of Parkinson’s Disease Research Community with Patient Groups to Improve Effectiveness of Clinical Trials
25 Jun 2015 - Despite an urgent need for new medications, clinical trials in Parkinson’s disease (PD) have a relatively low rate of success. The reasons for this are complex, prompting a group of investigators from PD advocacy groups to conduct a survey of the principle stakeholders, PD scientists, patients, and caregivers, to determine some of the underlying barriers. Their results are published in the Journal of Parkinson’s Disease....
24 Jun 2015 - In recent years, an important Parkinson’s disease (PD) research focus has been on gut-related pathology, pathophysiology, and symptoms. Gastrointestinal dysfunction, in particular constipation, affects up to 80% of PD patients and idiopathic constipation is one of the strongest risk-factors for PD. Lifestyle factors such as smoking and coffee consumption, as well as blood urate levels, have been associated with a decreased PD risk. These factors may also be influenced by the bacteria living in the human gut mediating the effects of various chemicals and nutrients on disease processes. In a contribution in the current issue of the Journal of Parkinson’s Disease, researchers review some of the latest studies linking gut microbiota to PD....
Levodopa-Carbidopa Intestinal Gel May Prove More Effective for Long-Term Treatment of Parkinson’s Disease than Standard Levodopa
27 Feb 2015 - Although levodopa remains the “gold standard” to effectively control motor deficits in the treatment of early stage Parkinson’s disease (PD), it loses effectiveness as the disease progresses. After four to six years of treatment with oral medications for Parkinson’s disease, about 40% of patients experience lack of muscle control (dyskinesias), end-of-dose wearing off, and fluctuations in “On/Off” states. By nine years of treatment, about 90% will suffer these effects....
26 Feb 2015 - Patients with Parkinson’s disease (PD) often have difficulties with visual acuity in low-contrast images. Because they may have normal high-contrast vision, this is often overlooked during routine eye exams. In the current issue of the Journal of Parkinson’s Disease, researchers report that PD patients had significantly worse vision for low-contrast images at close (40 cm) and far (2 m) distances. Even for high-contrast images, PD patients’ vision was deficient at far distances....
18 Nov 2014 - Two simple tests conducted during the neurological exam can help clinicians differentiate between early-stage Parkinson’s disease (PD) and atypical parkinsonism. By asking patients to perform a tandem gait test and inquiring whether they are still able to ride a bicycle, clinicians can ascertain whether medio-lateral balance is impaired, a defining characteristic of atypical parkinsonism. These findings are published in the Journal of Parkinson’s Disease....
11 Sep 2014 - Patients with Parkinson’s disease (PD) can experience difficulties with food preparation and ingestion, which could contribute to poor nutrition and place them at risk for malnourishment. Published studies have also suggested that PD is associated with low weight, however, few studies included control groups. A report published in the Journal of Parkinson’s Disease counters this conclusion in patients with mild-to-moderate PD, finding that the incidence or risk of malnutrition is no different for patients with mild-to-moderate PD compared to healthy controls....
11 Jul 2014 - Up to 70% of Parkinson’s disease (PD) patients experience sleep problems that negatively impact their quality of life. Some patients have disturbed sleep/wake patterns such as difficulty falling asleep or staying asleep, while other patients may be subject to sudden and involuntary daytime sleep “attacks.” In the extreme, PD patients may exhibit REM-sleep behavior disorder (RBD), characterized by vivid, violent dreams or dream re-enactment, even before motor symptoms appear. A review in the Journal of Parkinson’s Disease discusses the underlying causes of sleep problems in PD, as well as medications, disease pathology, and comorbidities, and describes the most appropriate diagnostic tools and treatment options....
03 Jul 2014 - Deep brain stimulation (DBS) has become a well-recognized non-pharmacologic treatment that improves motor symptoms of patients with early and advanced Parkinson’s disease. Evidence now indicates that DBS can decrease the number and severity of non motor symptoms of patients with Parkinson’s disease (PD) as well, according to a review published in the Journal of Parkinson’s Disease....
06 May 2014 -
A follow-up study of patients with Parkinson’s disease (PD) who participated in an earlier “proof of concept” clinical trial using exenatide showed that improvements persisted twelve months after discontinuing exenatide therapy. These data provide strong encouragement for the further study of this drug in patients with PD, report researchers in the Journal of Parkinson’s Disease.
Several recent discoveries have highlighted common cellular pathways that potentially relate neurodegenerative processes with abnormal mitochondrial function and abnormal glucose metabolism.
Exenatide, a glucagon-like peptide-1 agonist (GLP-1 agonist) medication marketed as Byetta® and Bydureon® and used in the treatment of insulin resistance in patients with Type 2 diabetes, has been proposed as a disease modifying drug in PD. Earlier studies had shown that exenatide is neuroprotective and promotes functionally beneficial neuroplasticity in animal models of neurodegeneration. Furthermore, exenatide has a favorable safety profile, with only relatively mild gastrointestinal side effects (including nausea and weight loss) as frequent adverse events.
In an earlier “proof of concept” randomized controlled trial published in May 2013, participants were randomized to either self-administer exenatide in addition to their regular PD medications or to act as controls, i.e., receive their conventional PD treatment only. All of the participants had moderate severity PD. In total, 44 patients (20 in the exenatide group and 24 controls) completed the trial. After 12 months the results showed significant and clinically meaningful differences in both motor and cognitive symptoms between those patients receiving exenatide and the controls. At 14 months, when the patients had discontinued exenatide for two months, the exenatide-treated and control groups still differed from each other. The authors concluded that the study supported potential disease-modifying benefits of exenatide in PD, while acknowledging the lack of a placebo arm.
All of the participants took part in a repeat assessment 12 months after the trial ended. The motor and cognitive advantages persisted in the exenatide group. Compared with the control group, those in the exenatide group had an advantage of 5.6 when using the blinded MDS-UPDRS motor subscale and 5.3 points on the Mattis Dementia Rating scale.
“We found that patients on exenatide appeared essentially unchanged throughout and beyond the trial period, while the control group had the expected rate of gradual decline in movement and cognitive ability,” comments senior investigator Thomas Foltynie, MRCP, PhD, of the Sobell Department of Motor Neuroscience, UCL Institute of Neurology, London, UK.
The investigators did not find evidence in their data to suggest that glucose tolerance is different in PD patients who received exenatide for 12 months.
“Aside from the changes in MDS-UPDRS scores, there was also persistent divergence in cognitive performance between the groups, with significant differences which were sustained along the trial period, far beyond the 12-month period of drug exposure,” says Foltynie. “These data provide continued support for formal double blind trials of GLP-1 agonists as disease modifying drugs in PD.”
“The present study could represent a milestone if future controlled trials provide evidence supporting a disease-modifying effect of exenatide and could lead to a revolution in PD therapy,” comment Tanya Simuni, MD, of Northwestern University Feinberg School of Medicine, Chicago, and Patrik Brundin, MD, PhD, of the Van Andel Research Institute, Grand Rapids, MI. Writing in the same issue, they warn however that: “Notwithstanding the promising nature of the results, it has to be emphasized that placebo effects can be highly significant and long-standing in PD. Therefore one should not jump to premature conclusions, While placebo effects ought to have diminished 12 months after drug withdrawal so that the exenatide-treated and control groups no longer differed, a lingering placebo effect cannot be excluded.”
Tom Isaacs, Co-founder and President of The Cure Parkinson's Trust which funded the follow-up study, says: "Although we have to remain cautious on the estimation of these results, we are encouraged by the findings. This is the first time that I have come across a program that has the potential to make an enduring change for Parkinson’s patients and we are excited by the potential of this scientific research.”
# # #
NOTES FOR EDITORS
“Motor and Cognitive Advantages Persist 12 Months After Exenatide Exposure in Parkinson’s Disease,” by Iciar Aviles-Olmos, MD, PhD; John Dickson, PhD, Zinovia Kefalopoulou, MD, PhD; Atbin Djamshidian, MD, PhD; Joshua Kahan, BSc; Peter Ell, FmedSci; Peter Whitton PhD; Richard Wyse; Tom Isaacs; Andrew Lees, MD, FRCP; Patricia Limousin, MD, PhD; and Thomas Foltynie, MRCP, PhD (DOI: 10.3233/JPD-140364).
Commentary: “Is Exenatide the next big thing in Parkinson’s disease?” By Tanya Simuni, MD, and Patrik Brundin, MD, PhD (DOI: 10.3233/JPD-149001). Openly available at http://iospress.metapress.com/content/c54026233vj43342/fulltext.pdf
Journal of Parkinson’s Disease, published by IOS Press
Contact Daphne Watrin, IOS Press, +31 20 688 3355, firstname.lastname@example.org for additional information. Journalists wishing to interview the authors should contact Dr. Thomas Foltynie at T.Foltynie@ucl.ac.uk or Patrik Brundin at email@example.com.
ABOUT THE JOURNAL OF PARKINSON’S DISEASE (JPD)
Launched in June 2011 the Journal of Parkinson’s Disease is dedicated to providing an open forum for original research in basic science, translational research and clinical medicine that will expedite our fundamental understanding and improve treatment of Parkinson’s disease. The journal is international and multidisciplinary and aims to promote progress in the epidemiology, etiology, genetics, molecular correlates, pathogenesis, pharmacology, psychology, diagnosis and treatment of Parkinson’s disease. It publishes research reports, reviews, short communications, and letters-to-the-editor and offers very rapid publication and an affordable open access option.
ABOUT IOS PRESS
Commencing its publishing activities in 1987, IOS Press serves the information needs of scientific and medical communities worldwide. IOS Press now (co-)publishes over 100 international journals and about 90 book titles each year on subjects ranging from computer sciences and mathematics to medicine and the natural sciences.
IOS Press continues its rapid growth, embracing new technologies for the timely dissemination of information. All journals are available electronically and an e-book platform was launched in 2005.
Headquartered in Amsterdam with satellite offices in the USA, Germany, India and China, IOS Press has established several strategic co-publishing initiatives. Notable acquisitions included Delft University Press in 2005 and Millpress Science Publishers in 2008....
31 Jan 2014 - Download the 2014 Neuroscience Neurology Brochure here. ...
17 Jan 2014 - A new study exploring vitamin D levels in patients with Parkinson’s disease (PD) opens up the possibility of a new avenue of early intervention that may delay or prevent the onset of cognitive impairment and depression. The findings are published in the Journal of Parkinson’s Disease....
New Research Suggests Changes in Parietal Brain Gray Matter Volume Associated with Memory Deficits in Early PD
17 Jan 2014 - Research by a team of investigators in Finland suggests that the free recall memory deficits common even in early stages Parkinson’s disease (PD) are related to structural changes in the brain, specifically parietal cortical gray matter volume. Their findings are published in the current issue of the Journal of Parkinson’s Disease....
New Study Links Depression in Newly Diagnosed Parkinson’s Disease Patients to Reduced Striatal Dopamine Synthesis
10 Oct 2013 - According to the Parkinson’s Disease Foundation, up to 60% of individuals with Parkinson’s disease (PD) exhibit mild to moderate depression, which is often underdiagnosed. It is unclear whether depression results from having a debilitating disease or reflects a parallel abnormal change in the brain caused by PD pathophysiology. ...
11 Jun 2013 - The presence of Lewy bodies in nerve cells, formed by intracellular deposits of the protein α-synuclein, is a characteristic pathologic feature of Parkinson’s Disease (PD). In the quest for an animal model of PD that mimics motor and non-motor symptoms of human PD, scientists have developed strains of mice that overexpress α-synuclein. By studying a strain of mice bred to overexpress α-synuclein via the Thy-1 promoter, scientists have found these mice develop many of the age-related progressive motor symptoms of PD and demonstrate changes in sleep and anxiety. Their results are published in the latest issue of Journal of Parkinson’s Disease....
02 Apr 2013 - In a mouse model of early Parkinson’s disease (PD), animals displayed movement deficits, loss of tyrosine-hydroxylase (TH)-positive fibers in the striatum, and astro-gliosis and micro-gliosis in the substantia nigra (SN), without the loss of nigral dopaminergic neurons. These findings, which may cast light on the molecular processes involved in the initial stages of PD, are available in the current issue of Restorative Neurology and Neuroscience....
21 Jan 2013 - Parkinson's disease (PD) is a progressive neurological condition. At present, it is usually diagnosed only when motor features are present. Hence, there is a need to develop objective and measurable biomarkers to improve PD diagnostics during its earlier stage, prior to its motor onset. In this pilot study, researchers identified and tested the first blood-based circulating microRNA (miRNA) biomarkers for PD. Their results are published in the latest issue of Journal of Parkinson’s Disease....
27 Nov 2012 - Download the 2013 Neuroscience Neurology Brochure here. ...
02 Jul 2012 - Growing evidence suggests that Parkinson’s disease (PD) often starts with non-motor symptoms that precede diagnosis by several years. In the first study to examine patterns in the quality of life of Parkinson’ disease patients prior to diagnosis, researchers have documented declines in physical and mental health, pain, and emotional health beginning several years before the onset of the disease and continuing thereafter. Their results are reported in the latest issue of Journal of Parkinson’s Disease. ...
20 Jun 2012 - Some Parkinson’s patients report that their motor function is better upon awakening in the morning, which is contrary to what would be expected after a night without medication. This phenomenon, known as sleep benefit, has been studied but no consistent variables have been found and in the last decade there has been little new research. A new study, published in the June issue of the Journal of Parkinson’s Disease, assesses a large sample of Parkinson’s disease (PD) patients and confirms that some patients experience sleep benefit, both overnight and following afternoon naps, but finds no significant variables between those who do benefit and those who do not. ...
23 Apr 2012 - In the 19th century, the celebrated neurologist, Jean-Martin Charcot, developed a “vibration chair” to relieve symptoms of Parkinson’s disease. He reported improvements in his patients, but he died shortly thereafter and a more complete evaluation of the therapy was never conducted. Now a group of scientists at Rush University Medical Center have replicated his work, and they report that while vibration therapy does significantly improve some symptoms of Parkinson’s disease, the effect is due to placebo or other nonspecific factors, and not the vibration. Their study is published in the April issue of Journal of Parkinson’s Disease. ...
New Findings and Imaging Techniques May Aid Diagnosis of Concomitant Alzheimer’s in Patients with Parkinson’s Disease Dementia
17 Apr 2012 - Dementia is a frequent complication of Parkinson’s disease (PD), but it is clinically impossible to distinguish PD dementia (PDD), which develops from the progression of the Lewy body pathology that underlies PD, from PD with coexistent Alzheimer’s disease (PDAD). Both have similar characteristics. A team of scientists has found that PDAD patients have much denser accumulations of amyloid plaques in the striatal area of the brain than PDD patients. The results suggest that recently developed imaging techniques may be able to identify striatal amyloid plaques in the living brain and could be useful for distinguishing PDD from PDAD. Their results are published in the April issue of the Journal of Parkinson’s Disease....
27 Feb 2012 - Download the Journal of Parkinson's Disease Brochure 2012 here. ...
25 Jan 2012 - Induced pluripotent stem cells (iPSC) are a promising avenue for cell replacement therapy in neurologic diseases. For example, mouse and human iPSCs have been used to generate dopaminergic (DA) neurons that improve symptoms in rat Parkinson’s disease models. Reporting in the current issue of the Journal of Parkinson’s Disease, a group of scientists from Japan evaluated the growth, differentiation, and function of human-derived iPSC-derived neural progenitor cells (NPCs) in a primate model, elucidating their therapeutic potential. ...
19 Jan 2012 - The accumulation of α-synuclein, a small, negatively charged protein, in neural cells, is one of the hallmarks of Parkinson’s disease. It has been suggested that oligomeric α-synuclein causes membranes to become permeable, or to form channels on the outer cell membrane. Now, a group of scientists from Sweden has found a way to reliably replicate α-synuclein aggregation on cell membranes to investigate how different forms of α-synuclein interact with membranes under different conditions and to learn if any of the α-synuclein species can penetrate these membranes. Their results are published in the current issue of the Journal of Parkinson’s Disease....
New Study Supports View that Lewy Bodies Are Not the Primary Cause of Cell Death in Parkinson’s Disease
10 Jan 2012 - The pathology of Parkinson’s disease is characterized by a loss of dopamine-producing neurons in the pars compacta of the substantia nigra (SN), an area of the brain associated with motor control, along with the development of α-synuclein (αS) protein in the form of Lewy bodies (LB) in the neurons that survive. The spread of LB pathology is thought to progress along with the clinical course of Parkinson’s disease, although recent studies suggest that they are not the toxic cause of cell death. A new study published in The Journal of Parkinson’s Disease finds no support for a primary pathogenic role of LBs, as neither their distribution nor density was associated with the severity of nigral cell loss. ...
16 Dec 2011 - Parkinson’s disease is marked by the abnormal accumulation of α-synuclein and the early loss of dopamine neurons in the substantia nigra region of the brain. A polymorphism in the promotor of α-synuclein gene known as NACP-Rep1 has been implicated as a risk factor for the disease. Now, researchers have found that different variants of NACP-Rep1 and its interaction with the microtubule-associated protein tau (MAPT) H1 haplotype can influence the speed of clinical deterioration in patients with Parkinson’s disease. ...
New Study First to Link Mitochondrial Dysfunction and alpha-Synuclein Multiplication in Human Fibroblasts
07 Oct 2011 - A new study in the Journal of Parkinson’s Disease shows for the first time the effects of α-Synuclein (α-syn) gene multiplication on mitochondrial function and susceptibility to oxidative stress in human tissue. Mitochondrial dysfunction has been frequently implicated in the neurodegenerative process that underlies Parkinson’s disease, but the basis for this has not been fully understood. ...
07 Oct 2011 - In a new study published today in the Journal of Parkinson’s Disease, Japanese researchers report that the ability to ride a bike can differentiate between atypical parkinsonism and Parkinson’s disease, regardless of the environment or situations for bicycling. ...