Are you a healthy control?

How about becoming a healthy volunteer for research and helping us Discover ~ Conquer ~ Cure? 

Do you have spare time and want to make a difference to people’s lives? Perhaps you’re willing to give up your time and participate in studies right here in Randwick?

I’m Connie Severino and my job at NeuRA is to maintain our healthy volunteer database that provides researchers with an easy way to recruit people for their studies.

We are always looking to recruit healthy volunteers because we want to make a difference to the lives of many who have suffered or are currently suffering neurological illnesses.

Healthy volunteers play an important part in supporting our research programs.

Each group within NeuRA covers a different area of research ranging from Alzheimer’s disease, chronic pain, falls and balance, Frontotemporal dementia, Parkinson’s disease, sleep apnoea, stroke, and many more. We recruit healthy volunteers for all of these areas.

We use data we collect from our healthy volunteers and compare it with the data we have from those affected with a particular neurological condition.

A healthy volunteer, often referred to as a ‘control’ or who sits within a ‘control group’, is simply a standard of comparison for checking or verifying the results of an experiment. Controls are the standard against which experimental observations are evaluated.

Becoming a volunteer does not cost you anything, however we do ask for your time and patience. Initially we ask you to complete a questionnaire and, from there, if you meet the control criteria, we register you on our Healthy Volunteer Registry that allows you to be selected up to three times a year.

What do I need to know? 

Often researchers will ask for clear specifications in controls such as age, gender, right or left handedness or walking ability. Once you are selected for a study, the researchers are notified and will contact you and ask you to participate.

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Jacqui Zheng with a volunteer for a falls and balance study at NeuRA

Each group’s tasks and activities vary but, rest assured, you will be well informed as to the specific tasks required of you before the trial begins. We endeavor to accommodate all your needs from travel arrangements, pick up and parking depending on your location and, at all times, keep you comfortable and informed.

We look for participants housed all over the country, particularly in NSW and the ACT. That said, due to most testing taking place here in Randwick, we typically invite volunteers from the Sydney metro and surrounding areas to join us, for ease of travel.

How do I get involved? 

Once you become a registered volunteer, you are not obliged to accept every invitation you are offered and you are of course free to withdraw from being on the registry at any given time.

Our registry has been active for approximately four years and has been beneficial for 30 studies to date. Some of our volunteers have returned to us multiple times as they enjoy the process and the ability to contribute to medical science in this way.

If you are interested in contributing your time, please see our website for further details or contact me directly on (02) 9399 1155. I am happy to answer any questions you might have.

It’s my belief that ‘A problem shared is a problem halved’… we thank all those who have helped in the past and who continue to volunteer.

The pain – brain relationship

Exactly how does educating patients about pain lead to better outcomes? PhD student at NeuRA, Hopin Lee, is seeking to answer that question.. 

Most of us know, through personal experience or having heard about someone else’s experience, that back pain can be troublesome. For many it’s just a niggle that can be kept under control with simple analgesics and a bit of reassurance that there is nothing sinister happening in their back. However, for some, back pain can cause major disruptions to life. While there may be some periods when symptoms ease, they often recur and eventually a longer period of persistent pain and disability ensues.

There is no doubt that in clinical practice a large number of patients present with back pain, yet it is often the most difficult condition to treat. Clinicians are often faced with a choice of assorted treatment options, ranging from localised injections to generalised physical exercise and psychological interventions. Despite the plethora of available treatments, research suggests that their effectiveness is often modest with short lived benefits.

The black box 

Most research investigating back pain treatments has focused on answering whether the treatment is successful or not. This is the so-called ‘black box’ approach where little or no attention is paid to how the treatment exerts its effect on the outcomes that we strive to improve. A limitation of this approach is that we are left without any knowledge about whether the underlying theories behind these treatments are valid. Without understanding the mechanisms that underpin treatments, we naturally return to the black box approach and move on to test a new set of treatments, without thinking about how we can improve existing ones. However, if we are able to verify or refute the underlying mechanisms of our treatments, we may be able to refine and modify existing treatments to develop better treatments informed by evidence.

Although theories and speculations about treatment mechanisms are bountiful, there has been little attempt to test theories with appropriately designed studies. A way of testing these mechanisms is to design studies so that mediation analysis can be applied. Born out of psychology, mediation analysis is considered to be an efficient method of investigating relationships between variables. This method of analysis will be the central focus of my PhD thesis – to explain how a treatment for lower back pain may have its effects on the outcomes of interest.

A Journey of understanding.. 

PhD student Hopin Lee

PhD student Hopin Lee

Our group (Moseley group) at NeuRA is conducting a NHMRC funded randomised controlled trial (PREVENT) to evaluate the effectiveness of an educational intervention for patients with acute low back pain. My PhD will investigate the theories that underpin this intervention to see if they are valid and supported by the data.

PREVENT tests, in a randomised controlled trial, whether patient education that focuses on reconceptualising how a patient thinks about pain during the acute stages can prevent their low back pain from becoming persistent. The patient education provides patients with the understanding that pain is a protective output of the brain, rather than a direct measure of tissue damage. Conveying these messages in relation to their existing beliefs and attitudes towards pain may modulate their painful experience, which may lead to better outcomes. These are some of the theories I will test in my PhD.

So how might educating patients about pain lead to better outcomes? For example one of my hypotheses is that if patients are taught to think about their pain as a protective response of the brain rather than a signal of harm to their back, this might reduce catastrophising thoughts (having a negative outlook, thinking the worst will happen). This is a plausible theory, considering that catastrophising thoughts are related to pain intensity and disability. Patients who catastrophise about the prognosis of their back pain tend to have higher levels of pain and disability which coincide with slower recovery rates. The challenge is to decipher whether PREVENT can change these mediating variables (e.g. catastrophising, beliefs and attitudes about pain) and whether this then leads to better outcomes for patients.

My vision for the future is that we seek to open the mysterious black box and peek into some of the complex mechanisms that are at work. This may allow us to move forward to logically refine our treatments based on scientific theory and reason. I think most of us would agree that a clear box provides better insight as opposed to an opaque black box… don’t you?

We are currently recruiting participants to this study. If you are you currently suffering an acute (less than 4 weeks) episode of low back pain, live in Sydney and would like to join the study please email us at prevent@neura.edu.au

 

 

The Social Brain

Dr Muireann Irish uncovers the part of the brain that underpins social cognitive deficits in semantic dementia, further unraveling mysteries behind the disease.

It may sound like the subject matter of a science fiction movie, but mind-reading is a process in which we regularly engage. On a daily basis, whenever we interact in social scenarios, we go beyond our own perspective to infer the thoughts, beliefs, and feelings of other people. This innate skill to appreciate perspectives distinct from our own allows us to function effectively within the social world. For example, we can instinctively understand how a colleague may feel when their latest publication is rejected, or we can intuitively place ourselves in a friend’s shoes when they experience a joyous event like the birth of a first child.

Theory of Mind

My latest study sheds light on the brain regions that need to be functional in order to support this ability to empathise with others. The study, published in the journal Brain, reveals that structures in the right hemisphere of the brain are essential to enable us to read the minds of others and to consider their beliefs and feelings. ‘theory of mind’ is the term used to refer to our uniquely human ability to make these inferences and is crucial for our successful functioning in the social world.

By understanding that other people think and feel in ways that are distinct from our own perspective, we can appreciate differences between individuals. This capacity to infer the mental state of others confers immense flexibility in our approach to various social scenarios. Without this ability, we would appear rigid, egocentric, and unfeeling towards others.

While appreciating the mental state of others may come relatively easy to us, the capacity for theory of mind relies upon a complex network of structures in the brain. Research on healthy individuals has revealed that when we successfully consider another person’s psychological perspective, regions in the frontal, temporal and parietal lobes of the brain activate. Such widespread brain activation reveals how complex this function truly is.

It follows that damage to any one of these brain regions will block the capacity to take another person’s perspective. Theory of mind abilities are disrupted across a number of clinical conditions such as traumatic brain injury, autism, and dementia.

Semantic dementia

In frontotemporal dementia, it is commonly reported that patients are unable to understand how their actions affect other people, or to consider that the reactions of others may differ from their own. However, up until recently, we knew relatively little regarding the capacity for theory of mind in the syndrome of semantic dementia. My recently published research reveals, for the first time, that individuals with semantic dementia experience severe difficulties in considering the mental states of others, and that such deficits are attributable to atrophy of structures in the right hemisphere of the brain.

Semantic dementia is a subtype of frontotemporal dementia, characterised by the progressive loss of general knowledge about the world. It is conceptualised as a language disorder whereby patients experience a profound loss of the meaning of words and concepts. The patient is unable to recall the names of objects, places, people, and experiences difficulties in correctly labeling popular musical tunes, or basic emotional expressions. While the predominant complaint of the patient is that of language disruption, carers of patients with semantic dementia report alterations in social functioning and interpersonal behaviour.

The Protocol

Images taken from Lough et al. (2006) Neuropsychologia,

Images taken from Lough et al. (2006) Neuropsychologia,

I used a new task to explore if patients with semantic dementia could infer the thoughts, beliefs, and feelings of the main characters in humorous cartoon scenarios. Patients were asked to describe why a selection of cartoon scenes were funny and their descriptions were analysed for language that reflected consideration of different mental states, for example “he thinks”, or “she feels”. In the cartoon scene to the left, a correct answer would be something like, “The gentleman thinks he is being held up. The lady is not aware that she is frightening the man.”

A patient with semantic dementia tended to respond as follows, “The woman is hitting the man in the back. He is putting his hands in the air”. These responses indicated that the ability to spontaneously consider the mental state of others was disrupted in semantic dementia. Importantly, I demonstrated that the failure to successfully appreciate the viewpoints of others was not a result of the language difficulties that are typically found in semantic dementia.

Using neuroimaging analysis of structural MRIs, I found that shrinkage of the right temporal lobe of the brain underpinned the theory of mind deficits in semantic dementia. This finding is surprising, as these patients are typified by damage to the left side of the brain. As the disease progresses however, pathology spreads from the left to the right hand side of the brain. The semantic dementia patient displays impairments across multiple domains, beginning with language disruption and gradually progressing to include social dysfunction.

Why is this important?

The findings of this study are unique as they reveal, for the first time, that degeneration of right temporal regions in the brain is associated with social dysfunction in semantic dementia. The right temporal lobes have been consistently implicated in studies of social functioning in healthy individuals.

Our study illuminates the complexity of social cognition and how we achieve sophisticated acts of social inference in our everyday lives. By incorporating brain mapping techniques with new experimental tasks, we can continue to unravel the mystery of mind-reading and build a coherent picture of how humans navigate within the social world.

Technology and Science, a recipe for independent living..

Dr Kim Delbaere, originally trained as a physiotherapist, has merged her passion for the physical body with technology and envisions a future where older adults can stay independent for longer using app based technology.

From the age of 65 years and older, falls happen frequently and affect quality of life. About one in three older people fall at least once a year, and about half of the falls lead to injuries that can cause mobility restriction during daily activities. Older people are often aware of the consequences of falling, with over half reporting a fear of falling.

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Thomas Davis, Dr Kim Delbaere and Ashley Woodbury design apps at NeuRA

Clinical trials have taught us that falls can be prevented at all ages. The single most effective way to prevent falls is to do specific exercises. However, in order for exercises to reduce a person’s fall risk, the person must do challenging balance training for at least two hours per week for a minimum of 6 months.

Long-term participation with these types of exercise programs can be poor due to the often boring nature of repetitive exercises. Also, many older people are not aware that exercise is a proven effective strategy for preventing falls.

Embracing technology to enable independent living for longer

We are focussed on finding solutions to support active and healthy ageing. We want to help older people do the necessary exercises so they can live independently for longer. Our pioneering work has led to the development of various new technology-based solutions that we hope to release on the market soon.

We are using new technologies to design exercise programs, individualised for each person, as no one person is the same. Our programs seek to offer a greater choice of exercises for people to keep things interesting. We have already released a range of mobile apps that assist in the assessment of fall risk, therefore working towards reducing falls. The use of technology in this area has opened up a world of possibilities like the convenience of doing the right training in the comfort of your own home wherever you are. As long as you have occasional access to the Internet, you can use our programs.

Standing Tall, we’re working on it!

We are particularly excited about one of our apps that is currently being tested, called Standing Tall. This unique program offers individually-tailored, progressive, high-intensity balance exercises, and includes an in-built coach and activity planner to encourage you to do your exercises more frequently. The activity planner lets you set your own goals and has optional reminders if you need to exercise more. The program also lets you to monitor your own progress.

So far, results show that the program is safe and easy for older people to use. Our participants have told us that they really enjoy doing the exercises Standing Tall offers and that it helps them to exercise more regularly. The next step for us is to conduct a randomised controlled trial (the gold standard for a clinical trial) to see if people keep using our program over a longer period and to test its effectiveness in falls prevention.

If successful, Standing Tall will increase the likelihood of older people taking part in, and benefiting from this type of fall prevention strategy.

Our aim is to promote healthy ageing by reducing falls, at a low cost for the health care sector. Following on from our trial, we aim to make the Standing Tall mobile app available to the general public. Watch this space…

Plasticity in the spinal cord

Siobhan Fitzpatrick’s PhD work aims to give back movement.

Conditions that decrease a person’s ability to control their muscles, such as spinal cord injury and stroke, have devastating and debilitating consequences for individuals and their loved ones.

Siobhan_6030_lrImagine not being able to pick up your mug of coffee, or do up the button on your coat. Small daily tasks, that many take for granted, can prove impossible for those with damage to the neural pathways responsible for muscle control.

My PhD, being conducted within the Taylor Group here at NeuRA, is focused on the use of a variety of brain, spinal cord and nerve stimulation techniques to induce changes (plasticity) at the connections (synapses) between nerve cells in the spinal cord, with the ultimate goal of enhancing the control of muscles.

How to stimulate movement 

Two techniques our group uses are known as transcranial magnetic stimulation (TMS), and electrical peripheral nerve stimulation (PNS); both are non-invasive methods that can be used to stimulate parts of the nervous system.

We can use TMS to stimulate parts of the brain that control specific muscles of the arm, and PNS to excite peripheral nerves that supply the arm. Repetitive pairing of these two stimuli at specific timing intervals can induce synaptic plasticity in the spinal cord in pathways that control voluntary muscle activity.

This technique can enhance muscle activity of the biceps in able-bodied participants  and can improve manual dexterity of the hand in participants with incomplete spinal cord injury.

The technique has the potential for enhancing activity at any remaining synapses in the spinal cord that can transmit commands from the brain to the muscles; therefore this protocol would be more relevant for those with incomplete spinal cord injuries, when some spinal nerve fibers are preserved. However, even with clinically diagnosed complete injuries where there is an absence of all sensory and muscle activity below the site of injury, there could be some nerve cells within the spinal cord that have the potential to respond to the technique.

Although there are a large number of studies that investigate plasticity in the brain, there is limited knowledge of the effects of magnetic and electrical stimulation on plasticity of spinal cord pathways. I am interested in optimising the methods we use. For example, I am asking, is more necessarily better? Indeed, in the most recent study for my PhD, we found that by doubling the number of stimulus pairs we could induce more reliable, longer lasting spinal cord plasticity.

What could this mean in the future? 

What we are aiming for with these methods is small, but functionally relevant improvements in muscle control which, as an example, could be the difference between being able to pick up a cup or not.

Work in this area is still in its early days; however my vision for the future is that an optimised technique could be used clinically in conjunction with other forms of rehabilitation, such as physiotherapy, to improve motor control in those with conditions such as incomplete spinal cord injury and stroke.

A blood test for dementia

Lauren Bartley is part of a team developing a blood test to detect dementia.

A blood test can reveal many things about your physical health, such as your blood glucose levels or an iron deficiency. But what if a simple blood test could reveal what’s happening inside your brain?

Blood 1 As the Biomarker Study Coordinator, I see each participant involved in frontotemporal dementia and Alzheimer’s disease research at NeuRA and take a sample of their blood for analysis.

At the moment, if your doctor suspects you have dementia, you are likely to undergo neuroimaging to look for changes to your brain structure and shape, as well as cognitive and behavioural assessments looking for changes in the way you think, act and process information. When people only have mild changes, it can be difficult to accurately predict the underlying disease process, which can be frustrating for the affected person and their families.

Developing a blood test

At NeuRA, we are currently investigating the concept of a blood test for dementia, with the hope that one day clinicians will be able to easily and quickly discriminate between frontotemporal dementia and Alzheimer’s disease, the two most common forms of younger onset dementia.

Our hope is that this test could further reveal if any medications or therapies might be effective in reducing symptoms and halting the progression of illness. This is important because a medicine that benefits someone with Alzheimer’s disease is unlikely to be effective for someone suffering from frontotemporal dementia.

Our blood test will screen for particular proteins in the blood associated with dementia: Beta Amyloid, Tau, TDP-43 and FUS. We know these proteins are responsible for causing the brain changes in both Alzheimer’s disease and frontotemporal dementia by having performed previous pathological studies on the brain tissue that has been generously donated by former research participants both in Australia and around the world.

These proteins are in everyone’s brains as they age and they carry out important functions in supporting the brain cells. But in some people, these proteins start aggregating in a harmful way that can kill the brain cells and cause the symptoms of dementia.

Our prediction is that a person who has pathological levels of protein massing in their brain will also have increased concentrations in their blood. It’s important for our study to screen the blood of a significant number of older healthy males and females to act as a comparison and help us understand what the respective protein concentrations are in people with no presentation of dementia symptoms.

The people attending the Frontier research clinic at NeuRA to volunteer for frontotemporal dementia research are generally aged between 50 and 75 when their symptoms begin, so we have a wide range of ages to match for. Often the supporting partners of our participants act as controls in the study, and are happy to be offered the opportunity to contribute to our research.

An update on our progress

Our study is a little more than half way through and so far I have collected blood samples from over 500 dementia-affected participants and controls. It’s important to obtain bloods from people with a variety of symptoms so that we can best correlate these symptoms to a protein profile.

I am also collecting further samples from participants at different in their illness to see if there are changes to this profile as the condition progresses.

The only way to quantify our study and determine the accuracy of our results will be to confirm the pathological protein at the end of the participant’s life through our brain donor program (see my previous blog post). In this way, we can ensure our results are meaningful.

The blood samples that I have collected are now in the very early stages of being analysed by the biomarker team, and over the next 18 months we will learn more about the feasibility of the blood test for dementia in everyday community healthcare. We want to be very certain of the accuracy of the test before its release.

Concerned about your memory?

In the meantime, anyone who has concerns about their memory, or who has had changes in their speech or ability to understand language should discuss them with their GP. Sometimes it’s easier for a loved one to recognise these symptoms, along with other clues like changes in personality or behaviour that might be more than just a ‘mid-life crisis’ or the general process of ageing.

How your support has made a difference to NeuRA in 2013

Your donations to NeuRA this year have helped bring certainty to our research initiatives.

Funding for medical research is a roller coaster… sometimes you’re up and sometimes you’re down. Never knowing for certain where funding for the next trial or research initiative will come from is a very real concern for researchers and, frankly, patients and carers.

You often hear people say that ‘the Government should be doing more’, but the reality is the public purse as it stands cannot support every research opportunity. NeuRA applies for research grants predominately from the Australian Research Council (ARC) and the National Health and Medical Research Council (NHMRC); some applications are successful, others are not. Even when successful, the grants typically only cover a proportion of the true costs of running a research project. In addition, funding for the next generation of the brightest scientists working toward their PhD at NeuRA is a stipend of around $25,000, not enough for them to pay the rent, eat and concentrate on work.

Enter our loyal donors.

How your donations make a difference

In my role at the NeuRA Foundation, I am entrusted to share with our donors (via mail and email) the stories of patients and their carers who live with degenerative and chronic diseases. I see firsthand the generosity of people from all stages of life. I am as touched by the donor who gives thousands of dollars as I am by the one who gives five. Every dollar is important. Every donation helps. Every donor contributes to future discoveries.

Throughout this past year, funds raised through sharing these stories have served two primary purposes:

  1. Supplementing PhD students’ salaries. The top-up to their stipend means students don’t need to find a second (part-time) job just to survive. As future innovators and leaders in brain and nervous system research, it’s critically important that they focus on their work – not on how they’re going to pay the bills.
  2. Providing funds for the Sydney Brain Bank. The Sydney Brain Bank is a vital resource that prepares, stores and distributes brain tissue to research groups at NeuRA and other research organisations in Australia and around the world.

This way of distributing your donations means they have the potential to make an impact across the whole of NeuRA.

How you can get involved

Admittedly, when I started at NeuRA, I was surprised at the numerous ways people could support our research. In addition to one-off or regular donations, you can:

Michael Cartwright, who raised over $16,000 for NeuRA's research into Alzheimer’s disease

Michael Cartwright, who raised over $16,000 for NeuRA’s research into Alzheimer’s disease

  • challenge yourself like Michael Cartwright (pictured) and run to Queensland! Ok, you don’t have to go that far, but you could enter a fun run, climb Mt Kosciuszko or go without social media for a month… and ask people to sponsor you for it.
  • celebrate a milestone (birthdays, wedding anniversaries, retirement parties) by asking people to donate to NeuRA what they otherwise would have spent on a gift.
  • consider a bequest in your Will. Leaving a gift to NeuRA is a great way to support our research. It doesn’t cost you anything now, and it’s a simple and powerful way to support our work into the future.
  • get involved with NeuRA’s annual Bridge for Brains Research Challenge and Books for Brains events.
  • ask people to donate to NeuRA in lieu of flowers at the passing of a loved one.

A final word from carer Wendy Smith

Wendy Smith, holding a picture of her husband George

Wendy Smith, holding a picture of her husband George

You may have read the story about George and Wendy Smith (pictured), who featured in our summer letter (missed it? read it here).

Wendy’s words are straight from the heart:

“When he was diagnosed with frontotemporal dementia, George said we had to help research as much as we could and try to get a breakthrough. With so many types of dementia, we need discoveries or cures so that other families do not have to go through what we had to.”

So, this Christmas, we say thank you to our donors for their loyal support. You are contributing to future breakthroughs and discoveries that we hope will dramatically change the outcomes for people, like George, who suffer from either degenerative brain and nervous system diseases or other chronic illnesses.

Uncomfortably numb: Nerve damage after cancer treatment

Dr Susanna Park is working on ways to prevent one of the lesser known side effects of chemotherapy: nerve damage.

One hundred years ago cancer was invariably fatal. Over the past century, however, we’ve made such huge advances in cancer treatment that today, more than two in three patients diagnosed with cancer will survive their cancer for five years or more. As a researcher, I regularly see patients complete treatment and go on to live their lives cancer free.

One thing I see often, however, as a direct result of more people surviving cancer and cancer treatment, is the long-term side effects of chemotherapy. While nausea and fatigue are well-known to patients, these other side effects seem to take people by surprise. One in particular, nerve damage, is the focus of my research.

Nerve damage first appears in the hands and feet as tingling, numbness and loss of sensation. This damage, known as chemotherapy-induced peripheral neuropathy, is caused by chemotherapy drugs used to treat a number of different cancer types, including colorectal, breast, ovarian and blood cancers.

We don’t yet understand the mechanisms underlying this damage and there is currently no known treatment or cure. The damage can be irreversible and limits the amount of treatment that patients can receive. Unfortunately, nerve damage sometimes develops late in treatment or even after the chemotherapy has stopped, making it harder to identify and treat.

Dr Susanna Park

Living with nerve damage

Neuropathy can become such a significant problem that patients have trouble with everyday activities such as walking and handling objects.

For example, one patient told me that during treatment she couldn’t hold a pen to write. She said her legs felt like they didn’t belong to her and she still has difficulty walking months after her chemotherapy treatment ended.

Another patient told me that he cut his finger on a razor but only noticed when he saw the blood on his finger.

One patient’s feet ached all the time and she couldn’t stand the pressure of shoes and socks.

I’ve also seen patients who have difficulties with typing, buttoning clothes, and many often report stumbling and tripping. The unfortunate reality is that these effects can continue for years after the completion of chemotherapy treatment.

Preventing nerve damage

As there is currently no way of reversing nerve damage, our research team at NeuRA and the Prince of Wales Hospital focus on prevention; we have recently developed a nerve assessment technique to detect and measure early signs of nerve damage, enabling clinicians to identify patients at risk of severe nerve damage early in their treatment. Up until now, clinicians have had to rely on patients reporting symptoms, by which point a great deal of nerve damage may have already occurred.

While this technique is promising, we still need to determine exactly how nerve damage affects the everyday lives of patients. We are only just now starting to look at improving quality of life after cancer; and as a result, the impact of nerve damage on patient function and daily life has been largely underestimated.

I’m currently looking at these day-to-day problems and how we can quantify the difficulties that patients experience. By developing these assessment tools, we will be able to better identify and measure nerve damage, which will hopefully lead to improved outcomes for cancer survivors following chemotherapy treatment in the future.