Longitudinal Study of Physical Functioning in Adults with Chronic Neurological Conditions

There is limited information in the literature comparing gait speed among individuals who are in the chronic stages of Parkinson’s disease (PD), stroke and traumatic brain injury (TBI). The primary aim of this study was to examine the physical functioning of individuals with these chronic neurological conditions over a 12-month period assessed at baseline (time 1) and six month intervals (time 2, 3). This observational research study used descriptive statistics and to describe the physical functioning of individuals with PD, stroke and TBI and was part of a longitudinal study being conducted over five years to describe communication, dietary and physical activity behaviors of adults with neurological diagnoses. Seven community dwelling adults (n=7) between the ages of 34 and 71 years completed the evaluations. The tests used to examine physical function included gait speed, repeated chair stands, short physical performance battery (SPPB), timed up and go (TUG), and the Physical Activity and Disability Scale (PADS). The results were analyzed for the cohort and divided into two groups for comparison: PD and acquired brain injury (ABI). ABI included people with the TBI and stroke diagnoses. Changes in gait speed were determined using analysis of covariance. A Pearson’s product moment correlation coefficient was used to determine association between gait speed and physical function assessments. Statistical significance was set at p < 0.05. Analysis of covariance (ANCOVA) results showed a statistically significant decrease (i.e. improvement) in gait speed (p < 0.03) for the ABI group over 12 months. Although not statistically significant, there was also a decrease in gait speed (p < 0.10) for the PD group. The ANCOVA results also showed a statistically significant increase (i.e. decline) in the TUG test time of 3.33 seconds (p = 0.054) for the ABI group and increases in time for the PD group and cohort. Baseline gait speed for all participants correlated with the total SPPB score r = -0.97, p = 0.001) and the TUG test (r = 0.97, p = 0.001). Time 3 gait speed for all participants also correlated with the PADS score (r = -0.79, p = 0.06) in addition to the SPPB score (r = -0.87, p < 0.01) and TUG test (r = 0.96, p < 0.01). There was a statistically significant decrease in gait speed of adults with ABI measured three times in 12 months. Secondary findings include the significant decline in mobility in adults with ABI measured over 12 months. The significant relationship between gait speed and the physical function, mobility and physical activity scores was also a secondary finding. Future studies should consider interventions aimed at improving physical activity and fall and balance self-efficacy to explore the impact on gait speed in chronic neurological conditions. Future longitudinal research should also be conducted with a larger sample size and broader range of chronic neurological conditions to allow generalization of the study findings.

and stroke can result in disabilities that include decreased ability to communicate, difficulty maintaining a healthy diet, and reduced levels of physical activity and physical function. The TBI and stroke diagnoses are both considered acquired brain injury (ABI).
Individuals with ABI and PD are particularly vulnerable to the damaging effects of physical inactivity and face declines in balance, coordination, strength, mobility and overall quality of life 4 . Gait speed, coined the sixth vital sign, has been suggested to correlate with functional ability and balance confidence and aids in determining rehabilitation potential and fall risk 5 . Additionally, gait speed improvement has been linked to enhanced quality of life 5,6 and is critical to maintaining community ambulation or independent mobility outside the home 7 .
There is limited information in the literature about gait speed in individuals who are in the chronic stages of PD and ABI 8 . There is even less information that jointly examines gait speed in persons with PD or ABI. Therefore, the primary aim of the study was to examine the physical functioning of individuals with chronic neurological conditions of stroke and ABI over a 12-month period assessed at six month intervals. Specifically, the null hypothesis was that there will be no change in gait speed of adults with chronic neurological conditions measured three times over 12 months. Independent predictors of changes in gait speed including the short physical performance battery (SPPB) total score, repeated chair stands, timed up and go (TUG) test, Physical Activity and Disability Scale (PADS) score, and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) delayed memory index were also explored.

METHODOLOGY Study Design
This observational research study used surveys and quantitative evaluations to

Participants
The longitudinal study participants were required to be 1) diagnosed with PD, TBI or stroke, 2) determined to be medically stable by a neurologist, 3) between the ages of 18 and 85 years, and 4) sign an informed consent form. They were recruited equally in an attempt to represent the demographics of Rhode Island. Rolling admission was accomplished through word of mouth and by sending brochures to local physicians, hospitals and support groups. Of the 15 participants currently in the study, seven completed three evaluations in the 12-month period of this study.

Outcome Measures
The independent variables in this study were the neurological conditions. Gait speed, a component of the SPPB, was the primary outcome measure. Changes in other measures of physical function including the SPPB score, repeated chair stands, and TUG test were examined to determine if there was a relationship or association with changes in gait speed. Dependent variables including the PADS score and RBANS delayed memory index were also analyzed to determine if there is a relationship with changes in gait speed. Following is a description of the instruments and techniques used to collect these data along with the anthropometric data.
Physical Functioning Assessment. The SPPB instrument is widely used to assess lower extremity function and takes fewer than ten minutes to complete. It includes using three low participant-burden activities to assess participant's physical functioning: gait speed, standing balance, and time to rise from a chair and return to the seated position. The score range for each subtest is zero to four points with a maximum cumulative score of 12 points 9, 10 . Each test was timed using a hand held stopwatch.
Gait speed was measured by having the participants walk at their usual pace on a measured and taped course. The distance for this study was four meters and the participants began and ended the test in the standing position. Additional unobstructed space was be marked at the end of the walking course and participants were instructed to continue walking through the finish line to prevent deceleration in pace. The test was repeated and the faster of the two tests was used in the data analysis 9 .
Participants performed side-by-side, semi-tandem (heel of one foot by big toe of other foot) and tandem (feet aligned heel to toe) foot positions for the standing balance tests. They were assisted to the standing position as needed and timed when they were standing independently. The timing ended at 10 seconds or earlier if the participant lost balance by moving their feet or grasping for support 9 .
Five-time repeated chair stands were performed to test lower extremity strength and endurance. A chair was placed against the wall. Participants were instructed to fold their arms over their chests and attempt one stand. If successful, participants were asked to stand and sit as quickly as possible without the use of their arms for five repetitions. Participants were timed from the point when they arose from the chair, stood five times and returned to the seated position 9 .
A TUG test was also conducted. The TUG test is a valid predictor of falls and mobility and measures the time in seconds required for an individual to rise from a chair, walk a prescribed distance, return and sit down in the chair 11 . The TUG test used in this study was conducted according to a standardized protocol where participants were asked to rise from a chair, walk forward four meters at their usual walking pace, turn 180 degrees around a cone, walk four meters back to the chair, and finally sit down. The test was repeated and the better of the two tests was used in the data analysis. The test was timed using a hand held stopwatch.
Physical Activity and Disability Scale. The PADS, a self-reported survey, provides a reliable and valid measure of physical activity for persons with disabilities or chronic health conditions and has been reported to detect intervention related changes in physical activity 12 . It is composed of six subscales: exercise, leisure time, physical activity, general activity, therapy, employment/school and wheelchair users and takes approximately 20 minutes to complete. The survey is known to discriminate between different levels of activity and participants report that it enables them to give an accurate description of their level of exercise 4 . The participants were interviewed to collect the data for the survey. The scores were calculated using a standardized scoring tool.

RESULTS
The results were reviewed for the cohort and divided into two groups for comparison: PD and ABI. A Shapiro-Wilk test supported the normality of the data at baseline (p = 0.28) and time 3 (p = 0.30). Demographic characteristics, anthropometric measures and indicators of physical functioning, physical activity and cognitive function for each group are summarized in Table 1. The participants included six males and one female and were between the ages of 34 and 71 years. The mean age for the PD group was 67.5 years and the ABI group was 43 years. All participants were community dwelling adults living with PD or ABI for greater than three years. Four participants were diagnosed with PD and three were diagnosed with an ABI. Of the three ABI participants, one was diagnosed with stroke, one with TBI and one was diagnosed with both stroke and TBI. There were statistically significant differences (p < 0.05) between the PD and ABI groups in age, SPPB total, gait speed and the TUG test. Table 2 displays the changes that occurred from the baseline to the time 3 measurements in the cohort, PD and ABI groups. Each of the groups experienced a decrease in weight, body fat, BMI and gait speed. There was also an increase in the TUG time and the PADS score for each group. The total SPPB score increased for the ABI and decreased for the cohort and PD groups. Contributing to this score was the decrease in the chair stand time for the ABI group and increase in the cohort and PD groups. The RBANS delayed memory index decreased in the PD group and increased in the cohort and ABI group.
The ANCOVA results for the gait speed changes are displayed in Table 3. The results showed a statistically significant decrease (i.e. improvement) in gait speed (p = 0.032) for the ABI group. Although not statistically significant, there was also a decrease in gait speed for the PD group (p = 0.099) and cohort. The difference between the groups was not significant.
The ANCOVA results displayed in Table 4

Physical functioning (SPPB)
Baseline SPPB scores ranged from 5 -11. At time 3, three of the participants increased their score, one remained the same and three participants had a lower score.
The total score was lowest for the two participants that could not complete the repeated chair stands.

Gait Speed
Baseline gait speeds for the four meter test ranged from 4.16 to 9.68 seconds or 0.41 to 0.96 m/s. All of the participants demonstrated an increase in the m/s; however, six of the seven participants demonstrated a meaningful change that ranged from 0.11 to 0.48 m/s.

Lower Extremity Performance (Repeated Chair Stands)
Two participants were unable to complete the repeated chair stands and two participants increased the time required to complete the test suggesting a decline in lower extremity performance. Three of the participants decreased the time that they required to complete the repeated chair stands.

Mobility (TUG Test)
Baseline scores for the TUG test ranged from 8.16 seconds to 18.31 seconds or 1.02 to 2.29 seconds per meter respectively. One participant was unable to complete the test at time 3, one participant experienced a minimal decrease in score and the remaining five participants demonstrated an increase in the time needed to complete the test.

Physical Activity (PADS)
Four of the seven participants improved from their baseline PADS score during the course of the study. One participant did not complete the survey at time 3; however, the participant did show improvement at time 2. Baseline scores ranged from 26.4 to 310.9. Scores at time 3 ranged from -21 to 302.2 with a variable change of -6 to 705%.

Recall and Recognition (RBANS Delayed Memory Index)
The RBANS scores ranged from 40 to 102 at baseline with a variable change of -8 to 21% at the time 3 evaluation. No correlation was observed between gait speed and the delayed memory index in the cohort.

DISCUSSION
To our knowledge, this is the first study to compare gait speed in adults with PD and ABI in the chronic stages of recovery. The primary finding of the study rejects the null hypothesis that there will be no change in gait speed of adults with chronic neurological conditions measured three times in 12 months. The results indicated that there was a decrease (i.e. improvement) in gait speed in adults with chronic neurological conditions and statistically significant improvements in participants with ABI measured three times in 12 months.
The time required to complete the 4-m gait speed test improved for the ABI group The mean ages of the PD and ABI groups were also considered as confounding variables on the gait speed and mobility results. The mean age for the PD group was 24.5 years greater than the mean age of the ABI group. Thus, this could have had an effect on these results as the aging process is accompanied by sarcopenia or a gradual loss of skeletal muscle mass and function that typically begins after age 30 that is associated with worsened physical functioning 23 . In a three year study by Trombetti et al. 24 , participants with age-associated declines in muscle mass, strength, power and physical performance were found to have decreased SPPB scores and increased walk times 24 . The PD group (mean age 67.5, SD 3.8) had higher scores on the SPPB and walked faster than the ABI group (mean age 43, SD 13) over the course of the study.
However, the ABI group exhibited greater improvements in their SPPB scores and walking speed at time 3 possibly due to their younger age.
Major findings of the study also included the statistically significant relationship identified between gait speed at baseline and time 3, and the total SPPB score and TUG test for all participants. At time 3, there was also significant correlation PADS score. The PADS has been reported to detect changes in physical activity in persons with disabilities and chronic health conditions 12 . There was an increase in the PADS score for each group. Although this study did not involve an intervention, the majority of the participants were engaged in physical therapy, occupational therapy or physical training and an increase in physical activity was reported via the PADS interview for five of the seven participants. The increase in physical activity may have contributed to the previously mentioned improvement in gait speed times, but this is merely Limitations of the study included the small sample size, multiple examiners, the participants being exposed to different medical interventions during the study (physical therapy, occupational therapy, physical training) and the effects of repeated testing. The small sample size limited the ability to detect statistical significance and the generalizability of the results to individuals with PD, TBI and stroke. Although there were multiple examiners, a study strength included using defined protocols and trained observers for each of the tests. For the self-reported physical activity survey, interviews were used to obtain the information and the examiner was able to rephrase questions or ask additional questions to clarify responses. As part of this survey, information was also collected on the time each participant spent in therapy or physical training and the activities that resulted in an increased PADS score. Repeated testing could be also be seen as a threat to internal validity as individuals become familiar with the test items and perform better on subsequent tests; however, periodic evaluations over time were also a strength of the 12-month study 28 .
The key barriers to adopting physical activity include self-efficacy; fear of falling; and disability, balance and environmental concerns 29-32 . Although not examined in this study, evaluating these behaviors in future research may provide additional insight into the barriers that result in reduced levels of physical activity in the PD, TBI and stroke populations. Additionally, future research should expand recruitment across the three conditions, to compare differences between PD, TBI and stroke, rather than just PD and ABI. Future longitudinal studies should consider adding an intervention designed to ameliorate gait speed, mobility and self-efficacy and monitor the long term changes in physical function.

CONCLUSIONS
In summary, this is the first study to compare gait speed in adults with PD and ABI in the chronic stages of recovery. The results indicated that there was a statistically significant improvement in gait speed of adults with ABI over the 12month period studied. Secondary findings included the significant decline in mobility in adults with ABI measured three times in 12 months and the relationship between gait speed and the physical function, mobility and physical activity scores. Future studies should consider interventions aimed at improving physical activity and fall and balance self-efficacy to explore the impact on gait speed in chronic neurological conditions. Future longitudinal research should be conducted with a larger sample size and broader range of chronic neurological conditions to verify the study findings. All data are expressed as means with (standard deviations). Exceptiongender P-value was calculated using an unpaired t-test and represents the between PD and ABI group differences. P-value for gender was calculated using a Fisher's Exact Test.
SPPB (4m walk, balance, repeated chair stands) -physical function SPPB Gait Speed -4 meter walk measured in seconds SPPB Chair Stand -repeated chair stands measured in seconds TUG Test -8 meter mobility test measured in seconds PADS score -physical activity level RBANS delayed memory index (list recall, list recognition, story recall, and figure recall) -recall and recognition All outcome variable data are expressed as means. P-value was calculated using an unpaired t-test and represents the between PD and ABI group differences. SPPB (4m walk, balance, repeated chair stands) -physical function SPPB Gait Speed -4 meter walk measured in seconds SPPB Chair Stand -repeated chair stands measured in seconds TUG Test -8 meter mobility test measured in seconds PADS score -physical activity level RBANS delayed memory index (list recall, list recognition, story recall, and figure recall) -recall and recognition    The purpose of this literature review is to describe the epidemiology of PD, TBI and stroke and their association with physical function, specifically gait speed, in the chronic stages of the diseases. The report will also review current research that examined gait speed as a measure of physical performance and function in these populations.

Parkinson's Disease
Parkinson's disease is a chronic and progressive movement disorder that worsens over time and affects two percent of individuals age 60 years and older 5 . Older males have a higher risk of developing PD 6 . The prevalence and incidence increases with age and peaks after 80 years of age. The male to female ratio for disease is approximately 3:2 7 . Family history has also been found to be a strong predictor 5 .
Ethnicity is a risk factor with Hispanics having the highest risk followed by non-Hispanic whites, Asians and Blacks 7 . With the aging of the population, a 50 percent increase in adults with the disease is expected by 2030 7 .
The cause of PD is not completely understood and there is presently no cure 3 .
The The primary risk factors for stroke include hypertension, diabetes mellitus, hyperlipidemia, atrial fibrillation, smoking, heredity and physical inactivity 2, 14 . The American Stroke Association has identified hypertension as the leading cause of stroke and also described the following risk factors.
 Diabetes mellitus is an independent risk factor and is also associated with high blood pressure, hyperlipidemia and obesity. Stroke prevention involves managing the enabling factors listed above.
Pharmacological therapies may also be required to control and manage hypertension, diabetes mellitus, hyperlipidemia and atrial fibrillation in high risk individuals.
Additionally, medical procedures including carotid endarterectomy may be required to remove plaque from effected arteries 14 .
Immediate treatment may minimize the effects of ischemic strokes. The gold standard for treatment is the FDA approved tissue plasminogen activator (tPA). This thrombolytic treatment is delivered intravenously and works by dissolving the clot to improve blood flow in the affected area of the brain. Forty participants had a total SPPB scores of less than 10; an accepted threshold for functional impairment. Thirty two participants scored one or zero on the chair stand test. There was a significant correlation between the SPPB and the 6-minute walk (r = 0.76, P < .001) and peak treadmill test (r = 0.52, p < .001). The 6-minute walk relationship indicated that long distance walking capacity is captured by the SPPB.
The participants with higher SPPB scores were also found to walk a greater distance the 6-m walk test. The study results indicated that the SPPB may be reflective of endurance based, longer distance measures in chronic stroke patients 18  Several studies have suggested that postural instability contributes to slow gait speed in TBI patients 28 . However, a study by Williams et al. 29 found that postural stability did not decrease with increasing gait speed and attributed reduced gait speed to biomechanical deficiencies. In the study, individuals with TBI were assessed using three dimensional gait analysis at self-selected (n=55) and fast walking (n=36) speeds over a 12 meter walkway and compared to 10 healthy control (HC) individuals that were speed matched to the mean TBI speeds. When compared to the HCs, the individuals with TBI were found to walk with similar cadence (self-selected speed - In summary, gait speed was also used to assess physical function in individuals with TBI. Postural stability was found to be stable with increasing gait speed and reduced gait speed was attributed to biomechanical deficiencies 29 . Intensive mobility training (IMT) was found to improve balance, mobility and gait speed in individuals with chronic TBI. The gait speed and mobility gains were also maintained at three

Conclusions
Individuals with chronic PD, TBI and stroke face declines in balance, coordination, strength, mobility and overall quality of life. Gait speed, coined the sixth vital sign, has been suggested to correlate with functional ability and balance confidence and aids in determining rehabilitation potential and fall risk. Additionally, gait speed progression has been linked to improvement in quality of life and is critical to maintaining community ambulation or independent mobility outside the home.
There is limited information in the literature about longitudinal changes in gait speed in individuals who are in the chronic stages of Parkinson's disease, stroke and traumatic brain injury. There is even less information that jointly examines gait speed in PD, stroke and TBI. The majority of studies reviewed measured gait speed using cross sectional analysis.
Research has yet to examine the long term status of physical function and gait speed across the three chronic conditions.

Appendix B: Extended Methodology
An individual's ability to complete functional tasks can be predicted by examining physical performance. Objective tests that evaluate performance include the SPPB, gait speed and TUG test. The PADS provides a reliable and valid measure of physical activity for persons with disabilities. Cognition has also been associated with physical function and can be evaluated using the RBANS.
The SPPB was studied by Guralnik et al. 1  Gait speed alone has been suggested to correlate with functional ability and balance confidence and aids in determining rehabilitation potential and fall risk 4 .
Additionally, gait speed progression has been linked to improvement in quality of life 4, 5 . Coined the sixth vital sign, gait speed can provide a functional perspective to health status similar to temperature, pulse, respirations, blood pressure and pain 4 . Gait speed has also been identified as an important concern when determining the ability to

Resources Cited
What will be done: If you agree to take part in this study, you will be asked to complete up to 11 evaluations over five years. Evaluations will take place every six months. The evaluations will include a variety of tasks such as reading sentences and describing a picture, an assessment of how your muscles move, a cognitive screening, an interview, a clinical swallowing evaluation, and questionnaires regarding swallowing, diet and physical activity. The total time for each evaluation will be approximately 3½ hours. All evaluations will be conducted in a quiet private room at one of the University of Rhode Island Speech and Hearing Clinic locations (Kingston or Pawtucket).
With your permission, we will request health information from your physician about the following specific items only:  Date of diagnosis  Current medications  Imaging information about where the brain damage is located (if appropriate)  Stage of Parkinson disease (if applicable) You will sign a separate form to indicate whether you give your permission to release this health information for the study.

Potential risks and discomforts:
There are minimal foreseeable risks associated with these evaluations. There have been no reported adverse affects from clinical evaluation of speech and swallowing. There may be some unknown or unanticipated risks, but every precaution will be taken to ensure your personal safety. Even though experienced personnel will obtain the blood samples from a finger prick, there is a chance of discomfort and minor bruising from the finger stick. For physical function testing there is a risk of muscle soreness or other muscle injury as well as skeletal injury but we will minimize these risks by using standard safety practices.

Purpose and benefits of the study:
The purpose of this study is to describe communication, nutrition, and physical activity behaviors over time to see how they change and affect quality of life. The information obtained is important because it will help us to understand how to provide services to meet the needs of people with neurological diagnoses. This is an investigational study and there is no guaranteed benefit to your communication or nutrition or physical function as a result of participation in this research study. You will receive personal health information such as your height and weight, physical function determined by a physical assessment, your blood lipids such as cholesterol and triglycerides. In addition, you will receive information about your thinking skills and language skills and dietary choices.
Drugs, devices or instruments to be used: Drugs will not be used in this study. The equipment for the evaluations include: microphone, sound level meter, tongue blade, a digital tuner, tape recorder, and video cameras. All equipment used to collect cognitive-linguistic and physical function data is considered non-invasive. A lancet and capillary tube will be used to obtain the blood sample from a finger prick and the sample will be analyzed on a small portable machine that is on a table.

Cost to participant:
There is no cost to you for participation in the evaluations. Parking is available for free.

Confidentiality:
Your part in this study is confidential. Your individual privacy will be maintained in all published and written data resulting from this study. No names of participants will be published or included in written data resulting from this study. Results of this study may be used for purposes of research, educational lectures, and/or professional presentations. When you are entered into the study you will be assigned a code that does not include any identifying information. For example, the first participant will be coded as Long01. The code number will be used on all response forms and in the analysis of the data.
Dr. Mahler and her research team will have sole access to all contact information and evaluation results containing your name. This information will be kept in a locked filing cabinet in a locked office. However, the U.S. Department of Health and Human Services, and the University of Rhode Island Institutional Review Board have the right to inspect all of your records relating to this research for the purpose of verifying data. Because of the need to release information to these parties, absolute confidentiality cannot be guaranteed. Following completion of this project, contact information will be destroyed for those participants who wish, for any reason, not to be contacted in the future. All other information will be archived and kept in a locked filing cabinet with the study results at the University of Rhode Island. All research data will be retained for a minimum of three years following completion of the study and then will be destroyed. Research data will be located in a locked filing cabinet in the principal investigator's locked office.
Cognitive-linguistic evaluations will be audio and video recorded to allow for data analyses. At times these recordings can be useful for teaching students or professionals about the disorders of people with a neurological diagnosis such as yours. Please indicate by signing below whether you give your permission to use your samples for lectures and presentations. Audio and/or videotapes may be used for teaching for up to 3 years after completion of the study. If you agree, you will never be identified by name in the presentations or lectures. Your decision to give permission to use audio and/or video samples in lectures has no impact on your participation in the study. In case there is any injury to you during the study: If this study causes you any injury, you should immediately contact Dr. Leslie Mahler at (401) 874-2490 or contact the University of Rhode Island Speech and Hearing Clinic at (401) 874-5969. You may also call the office of the Vice President for Research Integrity, 70 Lower College Road, University of Rhode Island, Kingston, RI at (401) 874-4328. If you are injured during an evaluation or during treatment every effort will be made to get you medical attention but you will be responsible for paying for the medical treatment needed.

Decision to quit at any time:
The decision to take part in this study is up to you. You do not have to participate. If you decide to take part in the study, you may quit and stop participating in this study at any time. You have the right to refuse to answer any question(s) or participate in any procedure for any reason. Deciding not to participate will have no effect on your potential to receive services from a speech-language pathologist. If you wish to quit, simply inform Leslie Mahler at 874-2490 of your decision. If you wish to pursue an alternative treatment instead of completing the study you will be provided with information on how to obtain those services.

Rights and complaints:
If you are not satisfied with the way this study is performed, you may discuss your complaints with Dr. Leslie Mahler (lmahler@uri.edu; 401-874-2490), Dr. Ingrid Lofgren (ingridlofgren@uri.edu, 401-874-5706), or Dr. Matthew Delmonico (delmonico@uri.edu; 401-874-5440), or you may contact the office of the Vice President for Research for concerns or any questions about your rights as a research subject at: 70 Lower College Road, University of Rhode Island, Kingston, RI at (401) 874-4328 and speak to them anonymously if you choose.

Authorization:
Your authorization means that you have read this paper and know the purpose of the study and the possible risks and benefits. It also means you know that being in this study is voluntary and you choose to be in this study. You can also withdraw at any time. Your questions have been answered. Your signature on this form means that you understand the information and you agree to participate in this study.