writing personal statement for biosciences

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• Biomedical Sciences
• Biomedical Sciences: How to Apply

Biomedical Sciences: Advice on the Personal Statement

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Your personal statement is an important part of your application to Oxford. It allows you to tell us about your interests, achievements and ambitions in your own words. Although we do not formally score your statement we read it carefully and use the information it contains as part of our short-listing exercise. If you are invited for interview, the statement is likely to provide a focus for the questions that you are asked. It is therefore essential that your statement is an accurate, unembellished account of your activities. We may check the claims that you make on your statement: discovery of fabricated or exaggerated material – during the admissions exercise, or even later on during your time as a student – may bring into question your suitability to study on the course.

Present yourself in the best light: the same basic facts about yourself (in terms of education, interests, experience), when presented differently, can quite dramatically convey positive or negative messages about you to tutors.

For Biomedical Sciences, whilst your academic record and BMAT performance data will come into play when candidates are being short-listed for interview, time spent in drafting an effective personal statement should also help your overall chances of success. Every detail becomes even more important once you have reached the interviews and are being considered for a place.

DO NOT BE SHY IN DECLARING ANY MITIGATING CIRCUMSTANCES

These may help us to put your achievements or personality within a finer context. We actively look for reasons why you may have under-performed in examinations, or performed well against the odds. These may be factors associated with your schooling, health or domestic circumstances. If you are returning to study after a break, or switching vocation, it is even more important to highlight your reasons for choosing a course at Oxford, and for you to demonstrate your determination, resilience, ability and commitment.

DO NOT SIMPLY RECOUNT EVERYTHING YOU HAVE DONE

We’re looking for quality, not quantity! Remember that large numbers of candidates apply for our courses. Tell us in what ways you will stand out from the crowd. In choosing to talk about an activity, describe what you have drawn from the experience: has it changed you as a person? Did it surprise you?

WE WANT TO LEARN ABOUT YOU AS A PERSON, NOT JUST ABOUT YOUR ACADEMIC QUALIFICATIONS

If you have undertaken extra-curricular activities, or hold positions of responsibility at school, tell us why you sought these, and why they are important to you. You will not impress us by simply recounting that you took up a placement in Thailand, but we might be more appreciative if you tell us what you personally learnt from the experience, about your interaction with local people, and about shadowing the medical team working within your village.

Example: I have become involved with a city music and drama group, and work especially with the younger members. I find this exciting and more than occasionally challenging. Coaching for the group has given me experience in organising others, as well as teaching them. Watching group members learn and progress is thrilling, especially in the case of one of them who has ADHD. At first he was incapable of remaining still, silent or attentive for even a few minutes, but eventually became far more focused and calmer, making excellent progress in many areas.

DIRECTLY ADDRESS OUR SELECTION CRITERIA

• Motivation and capacity for sustained and intense work.

Example: My interest has always been in how the body works in the way it does, and why. This was triggered early on by my mother's cancer, and I felt compelled to find out all about this condition, and what could be done to help treat it. I am thirsty for new knowledge, and am fascinated by the interrelatedness of systems in the human body.

• A strong track record of academic achievement, and particular ability and potential in science and/or mathematics. An excellent record at GCSE (or equivalent).
• Intellectual curiosity and enthusiasm and readiness to cope with the academic demands of the course.

Example: I read beyond the syllabus topics covered at A-level extensively, and decided to research and write an extended essay discussing ethics and science, with particular emphasis on 'living wills'. I enjoyed the challenge and discipline of studying independently, and follow recent developments and debate in this area.

• Reasoning and problem solving ability: use of a logical and critical approach, and strong powers of analysis.
• Communication: Good command of the English language. Ability to express ideas clearly and effectively. Ability to listen.

Example 1: I have worked as a hotel waitress during the summer conference season, which allowed me to develop teamwork skills, and work under various time pressures. It also allowed me to interact with many different members of the public.

Example 2: I took part in my school's open day, and demonstrated experiments in the Chemistry lab. During the last year I have also participated in a reading scheme, helping younger pupils with learning difficulties.

• Ability to generate own ideas and proposals. Originality and creativity of thought, lateral thinking and hypothesis-generation.

YOU WILL NOT BE ALONE IN TRYING TO OPEN WITH AN ATTENTION-GRABBING INTRODUCTION...

If you try this, make sure it helps tutors to learn something about what motivates and enthuses you.

Example: My vast collection of books and videos on "How the Body Works" when I was 7 years old first triggered my interest in the functions of the body. Watching the little personified, cartoon blobs that represented red blood cells run around an animated yet functioning body fascinated me and I longed to find out more. As a result, when a friend received a letter explaining their little girl had just been diagnosed with X at just 14 months old, I was intrigued to find out what this was.

THE STATEMENT IS CALLED  PERSONAL  FOR A REASON

It should be written by you, not by your parents, siblings, or teachers. Do not plagiarise material that you find on the web as there is a great chance that such deception will be discovered.

DO NOT FEEL THAT THERE IS A PRECISE TEMPLATE TO FOLLOW THAT WILL SCORE YOU POINTS

We look for bright and independent thinkers, so try to be original!

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Medical Biosciences Personal Statement Example – Imperial College London

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Welcome to our collection of Medicine Personal Statement Examples! We’ve searched far and wide to find personal statements from successful applicants all around the UK and asked them to analyse the strengths and weaknesses of their work for your own inspiration. Today’s subject is from Aneesha, who studies Medical Science at Imperial College London.

Aneesha had applied to a selection of top medical schools in the UK before receiving an offer from both Imperial and King’s College London .

Of course, Aneesha chose the former, so let’s read the personal statement that got her a place at Imperial College London, or skip straight to her feedback to learn what made her personal statement a success!

Please be aware that these examples are meant purely for the sake of inspiration, and should absolutely NOT be used as a model around which to base your own personal statement. UCAS have a rather strict system that detects plagiarism .

Imperial Medicine Personal Statement Example

Whole personal statement.

Medical Science appeals to me because of its mutability. Particularly, the opportunity to continually learn and apply new innovations to help the human body function fascinates me. A teacher opened my eyes to how science is linked with all aspects of our life, prompting me to choose Biology at my A/Level. Human Biology in particular interested me. I realised how the various organ systems need to work in tandem to keep our bodies functioning.   Visiting a Surgical Intensive Care Unit opened my eyes to instances in which congenital disorders destabilised the functioning of the entire body, which I was not able to glean from my textbooks.

Seeing an ETU function highlighted how stressful a medical career can be. Often, a single doctor on shift had to prioritise among patients who had been waiting for hours, and were heckling the doctor. I was impressed by their ability to keep calm and make swift decisions based on a range of symptoms. A highlight of my work experience was being able to see a Caesarean section delivery. I saw how everyone from the nurses to the surgeons contributed towards the procedure. Observing how the team supported the mother, calmly explaining what she could expect, and holding her hand through the pain, opened my eyes to the level of empathy and reliability required in this profession.

Shadowing a consultant in a Paediatric Preliminary Care Unit, I witnessed her dismiss a child’s concerns about an abdominal pain, and spoke to the mother in medical terms which did not effectively communicate the problem to her. On the other hand, another demonstrated how good communication can work wonders in drawing a patient out, with relatively simple questions like, “Have you eaten lunch yet?” This proved to be a highly thought-provoking experience, highlighting the importance of communication in medical practice.

During a project to raise funds for a local orphanage, we visited and spent hours with the children. I realised that what made them happiest was not the items we donated, but the fact that we spent time with them. The realisation that care is more valued than material items was humbling.

I wish to study abroad as repeated closure of local universities due to student unrest is discouraging and challenging. I wish to study in England as I have previously lived in the UK for a period of 5 years, and I am acclimated to the culture and language. English is also the main language of instruction of my current school. I hence believe that England would be a solid environment to be in whilst away from home.

Ranking second in the country at my GCE O/Level and maintaining a high academic level in my A/Level years has given me the confidence that I am able to cope with the academic demands of a medical degree.

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Imperial Medicine Personal Statement Example Analysis

Now, let’s go section by section and see what Aneesha has to say about what she wrote:  

INTRODUCTION

Introduction

Beginning with what fascinates me about the course and including real life experience to back it up demonstrates my enthusiasm and excitement for my chosen degree, as well as an understanding of what a career in medicine could involve. An introduction needs to quickly get the point across that you have a genuine reason for joining this course and that you would be an asset to the university for this reason. This is especially true when your explanation dives deeper into actual subject knowledge rather than staying surface level. If you plan on specialising into a specific area, mention it (although you need to be careful not to come off as stuck in your ways and unable to explore new fields).

In terms of improvements, I could’ve introduced my other reason for studying medicine in my introduction. As I have chosen to write my personal statement in a narrative style, my motivation for studying medicine is laid out chronologically, however I feel that introducing these ideas earlier on could improve the overall structure of my personal statement and make me appear to be a more diverse candidate.

These two paragraphs both cover my ‘work experiences’ and generally have a similar format, so I felt it was best to discuss them together. In these paragraphs, I have reflected on my experiences in hospital and a clinical environment, which demonstrates that I am able to learn from experience. It also demonstrates a realistic understanding of a career in medicine and its challenges. A general rule of thumb is that any work experience like this needs to be discussed in-depth when writing a personal statement. It’s the most relevant and some of the most challenging work experience you can do pre-med school. It’s also good to focus more on what you learnt and witnessed compared to the work you actually did. The lessons learnt from the professionals are more valuable than any amount of assisting and busy-work you likely had to do during your time there!

The biggest flaw with this section is with the structure. I feel that these paragraphs may seem a little disjointed, as I have taken different experiences and written them without including any statement tying these experiences together. These experiences aren’t too different from each other, so it shouldn’t have been too hard to find a theme that links them together and explains how everything discussed helped me grow as a person.

In my “work in a local orphanage” paragraph, I have demonstrated that I am able to work in a professional capacity, which is always a sign of a good candidate early on ( voluntary work is always a good look as well). I have also reflected on this experience and tied it back to how this experience is of value to develop skills necessary in my career of choice. Best of all, it shows the humility that anyone needs when working in medicine, as it is primarily a human subject.

It’s a very short section though, so I could have brought in more examples of work placements and how these experiences have shaped me, and reflected further on how these experiences helped me develop my understanding of myself and my capabilities. These wouldn’t have had to have been as in-depth as my work experience discussion, but mention more examples of learning experiences will show a more well-rounded character on the page.

In my “why do I want to study abroad” paragraph, I have highlighted a few reasons why I have chosen to leave home and learn in a completely new environment. I have also demonstrated that I feel confident in being able to acclimatise myself to this new environment. This may not be the most relevant information to provide in a personal statement, although it does display a great strength of my character and the skill of perseverance.

However, I feel that I could have highlighted what about the education system and course delivery in the UK interests me, and how I feel that this academic environment would be the best place for me to complete my degree and develop my skills. One piece of advice I can definitely give is this: UK applicant’s don’t really need to add a section like this to their personal statements!

As a school prefect, dealing with my peers who faced issues such as stress, mental health concerns, and coming to terms with a horrific terrorist bombing, I was required to be an empathic listener and someone who was willing to actively help my fellow students. I understood my capacity to help, but knew my limitations. The emotional demand also taught me how to keep myself healthy whilst helping.

Music is my outlet, and I find time to play in a number of orchestras and sing chorally. Playing with the Sri Lanka Symphony Orchestra, I have been able to meet people of various social strata, ethnicities, religions and sexualities. As leader of my school orchestra, I learned the value of being organized and punctual, and how to lead a team, which I feel are transferable in my career of choice.

These paragraphs again link together fairly closely, so it’s easier to analyse them together. In this “school/extra-curricular activities” section, I have demonstrated my academic capabilities as well as the skills I have developed in teamwork, communication , leadership and resilience , all of which are invaluable . While I have not gone too in-depth into any of these, it’s not really that necessary as they are all just smaller things that combine into a larger selection of skills and life lessons.

This paragraph could have been improved if I had linked it back to my paragraph on my work experience, and how the characteristics I developed linked back to my observations and reflections of a clinical environment. Having many individual experiences only gets you so far in your personal statement, almost anyone can go and do some of these things. The strength of them come from what you learn from them and how you can use all these experiences together to become a better medical worker. There are also some areas here that aren’t strictly necessary. If I had needed more space in other areas of the statement, this would have been the first place to make cuts.

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Having seen the emotional and intellectual demand associated with medicine I feel it is a career which is both stimulating and ultimately rewarding. This is why I hope to follow this discipline through my life.

In my conclusion, I have briefly summed up all of the ideas I brought out through my personal statement, which links my paragraphs together and highlights what I feel are the key aspects of this statement. This is exactly what a conclusion should do. There’s no need to add extra information or anything else in the last moments of you statement, all you need to do is reflect upon and summarise what you’ve said.

This conclusion could have been further strengthened if I had mentioned a few key areas of my statement more specifically, in order to further demonstrate my understanding of what I feel are the most important segments. The reader wants to know that you fully understand what you’ve written and are genuine about the points you’ve made. The conclusion is the perfect place to do this, so being more specific, although not overly detailed, is a good idea.

Final Thoughts

I think my personal statement is honest and reflective, and the narrative style I have written it in demonstrates my journey in arriving at the conclusion I have. I feel that I have addressed several important questions such as why I have chosen this degree, what I have done to further my understanding of my chosen career, and how my personal experiences have shaped me in a way that lead to my choices. I also feel the answers I have provided are effective and convincing, using my real world experience to prove my commitment and skill in the field of medicine.

I feel that the structure of my personal statement is a little disjointed at times, as I have written about a number of experiences without linking them together. Providing the links in your development is the best way to legitimise what you have said and make for a more believable and engaging story. This problem is highlighted in my conclusion, which could have pointed out the key points in my statement better. This would have helped round out the statement and make the important parts of what I said stick out in the reader’s mind after they finished reading.

So there you have it! This personal statement helped Aneesha get a place at imperial College London! Everyone has different experiences and abilities, so you may not be able to relate to everything that was said in this personal statement. However, the information and advice provided by Aneesha is universal and will help any applicant write a better personal statement!  

Be sure to check out more Medicine Personal Statement Analyses to see advice from all different kinds of applicants, including Ali Abdaal himself! Or if you want to get started on your own statement, check out 6med’s Medicine Mastery Bundle for all the support and resources you’ll ever need for your medicine application!

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• Aug 8, 2019

Writing Your Personal Statement: Biomedical Sciences

Now we’ve entered August I know a lot of year 12s will be thinking about the university application process and wondering how to make their personal statement stand out, especially to the top universities. So, I thought it might be helpful to talk about the personal statement I did for Biomedical Sciences, although it will hopefully be helpful for other subjects too!

What a personal statement has to convey is how interested you are in the subject, it doesn’t have to make you look like an expert of course - that’s what university is for! As long as you show that you’re interested in your subject beyond what you learn as part of your A-levels you’re on the right track.

In my personal statement, I showed my interest by talking mostly about the EPQ I was doing (which was about gestational diabetes) and a few articles I had read for it. If you haven’t done an EPQ, other things you can talk about are books you’ve read, podcasts you’ve listened to or documentaries you’ve watched, if it inspired an interest in a topic relating to Biomed then it's relevant. If you’re stuck for ideas look at the books under ‘preparatory reading’ here:https://www.ox.ac.uk/sites/files/oxford/media_wysiwyg/Introductory_Reading_for_Biomedical_Sciences1.pdf. You’ll see a lot of these actually read like novels,so are great for introducing you to a topic you might never have looked at before like neuroscience!

It’s also important you don’t just list things you’ve read/seen/listened to: you need to talk about what you took away from it and, if you can, try to offer some critical analysis. When doing this, make sure to justify any opinions you put forward to strengthen your statement. It's probably better to only mention a few of these ‘supra-curricular’ activities so you can better develop them.

You’ll also need to talk about your A-levels, and while it may be helpful to mention a topic or two from Biology that you’re hoping to expand on at university, the main thing I spoke about in relation to my A-levels was the transferrable skills they’d developed that would help me to thrive at university. This is particularly important if one of your A-levels isn’t as relevant to your subject - for example, I did English Literature at A-level, so in my personal statement one thing I mentioned was how I’d had to work in groups and so had grown more confident and developed teamwork skills.

The most important thing, though, is to not stress too much and overthink it - if you are truly interested in your subject it will definitely shine through. Also, it’s a personal statement, so don’t try to write as someone else! This is a chance for tutors/admissions teams to get an insight into you as a person - so definitely make sure it's all your own work! Don’t stress - as long as you write truthfully (and remember to spellcheck!) your personal statement will be more than fine!

#PersonalStatement #science #biomedicalsciences #biomed #application

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A successful biology personal statement

University of Southampton admissions tutor, Dr Malcom East, outlines two key ingredients he would like to see evidenced in your biological sciences statement:

You understand something about the course you’re applying for, with a realistic perception of what it involves.

You’re enthusiastic about the subject and can show some commitment to it. You can demonstrate this by writing about your wider reading, Extended Project, work experience or any other way you have engaged with biological science beyond the syllabus.

Your commitment and appetite for the subject

Admissions tutors at the University of Birmingham are looking out for something you’ve done, or something you think, that conveys your commitment to the subject:

• What topics do you find particularly intriguing?
• Have you done anything interesting or unusual that has involved engaging with the subject beyond the syllabus, or through your extracurricular interests or voluntary work?
• Have you been on an interesting field course or visited a university laboratory and learned something from it?

A paragraph where you explain what you gained from one or two interests or activities like these would be very effective. Remember to explain things in your own words, ensure it has a good structure, and steer clear of poor grammar and spelling.

Cardiff University’s selectors are no different. They want you to demonstrate a commitment, motivation, and determination to further your knowledge in biosciences, along with any experience or other non-academic interests that highlight your personal qualities in general. They also want to see from your statement that you can communicate this in a way that’s concise and coherent.

See our in-depth guide to studying biological sciences for some inspiration.

Conveying your enthusiasm

Dr Devlin also told us all their applicants are invited for interview and 'the personal statement is the basis of that interview'. So he recommends that you write about things you would like them to ask you about.

So if you're fascinated by the machinery of the cell, human health or disease, the natural environment, any other specific aspects of biology, or just the science of living organisms in general, then make sure you include it. By reflecting on one or two of these interests in your statement, you’re likely to make a strong impression.

It’s good to include some non-academic content

Admissions tutors at King’s College London like to see an element in your statement that reflects on your general reading, debating, contributing to school, college or community life, or any cultural or sporting interests, as they are keen for you to continue this at uni and to contribute to the 'vitality of the College community'.

However, if your home or personal circumstances mean it has been difficult to extend your knowledge or experiences outside of school or college, don’t worry. As Cardiff points out, universities will usually be sympathetic to this.

How critical is the personal statement?

If you achieve the required grades and can genuinely demonstrate that you’ve got the necessary enthusiasm and commitment, then you should be in a strong position. Your personal statement, in combination with your academic reference, will be very important for demonstrating those qualities.

If your statement clearly shows you have also applied for a clinical programme like medicine, veterinary science or dentistry, that lack of commitment to biology is likely to be a turn-off to some universities, including University of Bristol. However, others take a different view on that, or may consider a separate statement sent directly to them. Do research this in advance!

According to University of Southampton, it’s if you don’t quite get the grades you need that the personal statement becomes especially critical. If you find yourself in this position, then your statement could turn out to be your lifeline on results day. As Dr East put it: 'If we have a few places left, then the statement will probably determine whether you’re in or out'.

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Personal Statement - BSc (Hons) Biomedical Science

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07 July, 2022

Personal statement - bsc (hons) biomedical science share.

• 12 May, 2013

The human body is one of the most amazing things on earth. The desire to study biomedical science came from my school life when I was studying biology and was greatly fascinated by the biology of the human body. My goal in studying biomedical science is to gain a deeper understanding of the human body. I am willing to pursue a BSc (Hons) Biomedical Science with International Foundation programme (Malvern House) at the University of East London. By studying this course, I will have an in-depth understanding of the basic study of the structure, properties, and reactions of biomedical science and it will help to understand the causes of the disease in depth. This Biomedical Science degree will open the door for me to learn more about the vast field of biology and the depth of its disciplines. Moreover, I believe that this course will help me demonstrate my academic and intellectual abilities.

I have seen the course modules, syllabus, and learning outcomes of the BSc (Hons) Biomedical Science with International Foundation programme at the University of East London this course is based on the study of biology which is important for developing new medicine for the treatment of current and unknown diseases. This course is designed to develop skills through to human disease, laboratory training experience, the study of specialist areas of biomedical science, and clinical training in the laboratory. This course teaching method includes lectures, tutorials, seminars, workshops, laboratory practicals, web learning, and guided reading. The course will cover four areas in the first year namely Essential Chemistry, Cell Biology, Biochemistry, and Human Anatomy and Physiology. Finishing in the second year will undoubtedly help my career towards potential. In the final year, I will study clinical infection and immunity as well as learn about the causes of disease. The assessment methods used across this course include opportunities for coursework, examinations, project work, group work, presentations, and laboratory practical work. Having the opportunity to study this course I am looking forward to improving my skills and knowledge. This course will help me gain an understanding of the biomedical science method and provide career opportunities through the techniques and skills used. After completing this course, I would like to join the reputed institutes of my country as a Biomedical Scientist or Clinical Research Associate to build my professional career. So, I believe this course will be suitable for my career planning and professional development objectives.

I completed my Secondary and Intermediate from the science groups respectively. While I studied in school and college, I was involved in various types of curriculum activities such as Attend Seminars and Workshops, Debating, Volunteering, Socializing, and Fund Rising. Since I am interested to expand my knowledge in biomedical science, I have come to the conclusion that I need a higher degree from abroad that will enrich my knowledge and skills. I think I should gain more knowledge in the field of Biomedical Science so I decided to continue my further studies with this course. It will help me develop a broader and more balanced understanding of basic Biomedical Science. In addition, I am eager to gain complete knowledge and skills from this course. Moreover, this course applies the standard method for understanding and evaluating risks and for working safely and solving problems with practical skills in the laboratory. So, I believe this course will be the right choice for me as I am looking for a successful career in this course.

By researching the university website I noticed that for my four-year programme the foundation year courses modules include Essential Skills for Higher Education (Mental Wealth), Essential Maths & ICT, Career & Professional Skills (Mental Wealth), Human Biology, Introduction to the Study of Cell, Chemistry of Life, Professional Practice in Science (Mental Wealth), Essential Chemistry, Cell Biology, Introduction to Biochemistry and Molecular Biology, Fundamentals in Human Anatomy and Physiology, Fundamentals in Microbiology, Human Disease and Clinical Practice, Molecular Biology and Genetics, Infection and Immunity, Cellular Biochemistry, Haematology and Transfusion Science, Research and Career Development (Mental Wealth), Clinical Biochemistry, Medical Microbiology, Cellular Pathology, Clinical Immunology, Clinical Genetics, Research Project and Career Enhancement Portfolio (Mental Wealth). As a science student, studying these course modules would not be difficult for me. So, I hope my chosen course will make me better and further open doors for my profession.

I chose the UK for my higher studies because this country has had a great reputation for quality higher education since its inception. It is true that the UK is a well-known country and has huge popularity. In recent years, most reputed companies in Bangladesh are emphasizing hiring Bangladeshi graduates with degrees from abroad. Where the study environment in my country follows theoretical systems of education and no practical skills are gained. Academically the UK prepares students and provides soft skills that are useful for future careers. However, this university is better than others by offering the best career-oriented education and training and relatively low tuition fees. UK accommodation and living expenses are also reasonable. The affordable tuition fees attracted me the most. Furthermore, an academic degree from the UK is recognized and appreciated by employers around the world. This is why I chose the UK as my preferred destination and goal. According to a recent study of international graduation results in 2019 by iGraduate by Universities UK International 82% of overseas graduates believe their UK degree is beneficial for financial investment, and a similar number of graduates said they were satisfied or very satisfied with their careers. Approximately 83 % believe a UK degree helped them get a job. So, it will be a big achievement for me if I can study this course at the University of East London.

I like the University of East London because it is incredibly welcoming to international students and includes content and structure with a distinct focus on the international context and professional level. In addition, the University of East London is dedicated to supporting international students to develop the skills, emotional intelligence, and creativity needed to thrive in a constantly changing world and the competitive job market. Universities have invested heavily in their facilities to support students in order to create a physical and intellectual environment for learning. Also, the university has a reputation for teaching, research, and business partnerships. According to the working- age population, 91% of UEL graduates and postgraduates are in employment (DLHE 2017) compared with 70 percent of non-graduates. The university is ranked 801st in the QS World University Rankings by Top Universities. This course will help me take my knowledge and skills to the next level of Biomedical Science. So, if I get the chance to study this course at the University of East London I will never look back and it will be a great achievement for me.

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How To Tackle The Weirdest Supplemental Essay Prompts For This Application Cycle

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Writing the college essay

How do you write a letter to a friend that shows you’re a good candidate for the University of Pennsylvania? What reading list will help the Columbia University admissions committee understand your interdisciplinary interests? How can you convey your desire to attend Yale by inventing a course description for a topic you’re interested in studying?

These are the challenges students must overcome when writing their supplemental essays . Supplemental essays are a critical component of college applications—like the personal statement, they provide students with the opportunity to showcase their authentic voice and perspective beyond the quantitative elements of their applications. However, unlike the personal essay, supplemental essays allow colleges to read students’ responses to targeted prompts and evaluate their candidacy for their specific institution. For this reason, supplemental essay prompts are often abstract, requiring students to get creative, read between the lines, and ditch the traditional essay-writing format when crafting their responses.

While many schools simply want to know “why do you want to attend our school?” others break the mold, inviting students to think outside of the box and answer prompts that are original, head-scratching, or downright weird. This year, the following five colleges pushed students to get creative—if you’re struggling to rise to the challenge, here are some tips for tackling their unique prompts:

University of Chicago

Prompt: We’re all familiar with green-eyed envy or feeling blue, but what about being “caught purple-handed”? Or “tickled orange”? Give an old color-infused expression a new hue and tell us what it represents. – Inspired by Ramsey Bottorff, Class of 2026

What Makes it Unique: No discussion of unique supplemental essay prompts would be complete without mentioning the University of Chicago, a school notorious for its puzzling and original prompts (perhaps the most well-known of these has been the recurring prompt “Find x”). This prompt challenges you to invent a new color-based expression, encouraging both linguistic creativity and a deep dive into the emotional or cultural connotations of color. It’s a prompt that allows you to play with language, think abstractly, and show off your ability to forge connections between concepts that aren’t typically linked—all qualities that likewise demonstrate your preparedness for UChicago’s unique academic environment.

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How to Answer it: While it may be easy to get distracted by the open-ended nature of the prompt, remember that both the substance and structure of your response should give some insight into your personality, perspective, and characteristics. With this in mind, begin by considering the emotions, experiences, or ideas that most resonate with you. Then, use your imagination to consider how a specific color could represent that feeling or concept. Remember that the prompt is ultimately an opportunity to showcase your creativity and original way of looking at the world, so your explanation does not need to be unnecessarily deep or complex—if you have a playful personality, convey your playfulness in your response; if you are known for your sarcasm, consider how you can weave in your biting wit; if you are an amateur poet, consider how you might take inspiration from poetry as you write, or offer a response in the form of a poem.

The goal is to take a familiar concept and turn it into something new and meaningful through a creative lens. Use this essay to showcase your ability to think inventively and to draw surprising connections between language and life.

Harvard University

Prompt: Top 3 things your roommates might like to know about you.

What Makes it Unique: This prompt is unique in both form and substance—first, you only have 150 words to write about all 3 things. Consider using a form other than a traditional essay or short answer response, such as a bullet list or short letter. Additionally, note that the things your roommate might like to learn about you do not necessarily overlap with the things you would traditionally share with an admissions committee. The aim of the prompt is to get to know your quirks and foibles—who are you as a person and a friend? What distinguishes you outside of academics and accolades?

How to Answer it: First and foremost, feel free to get creative with your response to this prompt. While you are producing a supplemental essay and thus a professional piece of writing, the prompt invites you to share more personal qualities, and you should aim to demonstrate your unique characteristics in your own voice. Consider things such as: How would your friends describe you? What funny stories do your parents and siblings share that encapsulate your personality? Or, consider what someone might want to know about living with you: do you snore? Do you have a collection of vintage posters? Are you particularly fastidious? While these may seem like trivial things to mention, the true creativity is in how you connect these qualities to deeper truths about yourself—perhaps your sleepwalking is consistent with your reputation for being the first to raise your hand in class or speak up about a cause you’re passionate about. Perhaps your living conditions are a metaphor for how your brain works—though it looks like a mess to everyone else, you have a place for everything and know exactly where to find it. Whatever qualities you choose, embrace the opportunity to think outside of the box and showcase something that admissions officers won’t learn about anywhere else on your application.

University of Pennsylvania

Prompt: Write a short thank-you note to someone you have not yet thanked and would like to acknowledge.

What Makes it Unique: Breaking from the traditional essay format, this supplement invites you to write directly to a third party in the form of a 150-200 word long letter. The challenge in answering this distinct prompt is to remember that your letter should say as much about you, your unique qualities and what you value as it does about the recipient—all while not seeming overly boastful or contrived.

How to Answer it: As you select a recipient, consider the relationships that have been most formative in your high school experience—writing to someone who has played a large part in your story will allow the admissions committee some insight into your development and the meaningful relationships that guided you on your journey. Once you’ve identified the person, craft a thank-you note that is specific and heartfelt—unlike other essays, this prompt invites you to be sentimental and emotional, as long as doing so would authentically convey your feelings of gratitude. Describe the impact they’ve had on you, what you’ve learned from them, and how their influence has shaped your path. For example, if you’re thanking a teacher, don’t just say they helped you become a better student—explain how their encouragement gave you the confidence to pursue your passions. Keep the tone sincere and personal, avoid clichés and focus on the unique role this person has played in your life.

University of Notre Dame

Prompt: What compliment are you most proud of receiving, and why does it mean so much to you?

What Makes it Unique: This prompt is unique in that it invites students to share something about themselves by reflecting on someone else’s words in 50-100 words.

How to Answer it: The key to answering this prompt is to avoid focusing too much on the complement itself and instead focus on your response to receiving it and why it was so important to you. Note that this prompt is not an opportunity to brag about your achievements, but instead to showcase what truly matters to you. Select a compliment that truly speaks to who you are and what you value. It could be related to your character, work ethic, kindness, creativity, or any other quality that you hold in high regard. The compliment doesn’t have to be grand or come from someone with authority—it could be something small but significant that left a lasting impression on you, or it could have particular meaning for you because it came from someone you didn’t expect it to come from. Be brief in setting the stage and explaining the context of the compliment—what is most important is your reflection on its significance and how it shaped your understanding of yourself.

Stanford University

Prompt: List five things that are important to you.

What Makes it Unique: This prompt’s simplicity is what makes it so challenging. Stanford asks for a list, not an essay, which means you have very limited space (50 words) to convey something meaningful about yourself. Additionally, the prompt does not specify what these “things” must be—they could be a physical item, an idea, a concept, or even a pastime. Whatever you choose, these five items should add depth to your identity, values, and priorities.

How to Answer it: Start by brainstorming what matters most to you—these could be values, activities, people, places, or even abstract concepts. The key is to choose items or concepts that, when considered together, provide a comprehensive snapshot of who you are. For example, you might select something tangible and specific such as “an antique telescope gifted by my grandfather” alongside something conceptual such as “the willingness to admit when you’re wrong.” The beauty of this prompt is that it doesn’t require complex sentences or elaborate explanations—just a clear and honest reflection of what you hold dear. Be thoughtful in your selections, and use this prompt to showcase your creativity and core values.

While the supplemental essays should convey something meaningful about you, your values, and your unique qualifications for the university to which you are applying, the best essays are those that are playful, original, and unexpected. By starting early and taking the time to draft and revise their ideas, students can showcase their authentic personalities and distinguish themselves from other applicants through their supplemental essays.

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• Biomedical sciences personal statements

Applied biomedical science degree personal statement example (1a)

My interest in bioscience has been growing with me ever since I was teenager. As a student at school I really enjoyed studying Biology, Chemistry and Anatomy. Being a student of Applied Science at college gave me an opportunity to be more familiar with Chemistry, Biology, Physics and Math and I graduated with A level. During the four years at college I developed my knowledge in the field of science particularly in the lab where I was fascinated by chemical and biological procedures. What amazed me most in the lab was the complexity of human body, DNA, organisms, microorganisms and chemical reactions and that was the reason which crystallized my decision to choose a course in relation to science at university.

In 2002 I was accepted at university in Iran as a nurse and I studied four years. At the first year, studying the foundation of the human body structure and Anatomy, Physiology, Biochemistry and immunology helped me to broaden my knowledge in science field. Over the next three years of the course I learned a huge number of skills about diseases and their treatments. In 2006 I graduated as a registered nurse (RN). Three months after graduating I began to work in a burns hospital in my city and worked there for six months. Working with burns patients also taught me how to communicate with patients who have special care requirements.

Then I changed the hospital and started to work in Cardiac Care Unit (CCU). Working in CCU lasted one and half year and was a superb opportunity to obtain experience. I learned to work both in a team and individually. Gradually besides the care, I found out how to diagnose the diseases and identified what kind of medicine is needed for every heart illness. In the CCU the thing was interesting for me was diagnosing heart diseases by analyzing blood and other samples such as blood viscosity, blood sugar, triglyceride, cholesterol and so on which are highly significant in cardiovascular diseases. Over eighteen months working in Heart diseases ward I realized the importance of laboratories and their rules in NHS and other careers like pharmaceutical companies and food industries.

In 2008 I immigrated to the UK because of the political situation in Iran. The UK NARIC organization accepted my degree as a bachelor equivalent and since then I have been improving my English language in ESOL classes in Glasgow and now I am working as an interpreter for Global Language Services Ltd. As the passion in science has always been with me I have decided to expand my knowledge in biomedical science field. At the moment I am doing HNC Applied Science course at North Glasgow College to be ready for doing this course at university. I also work as a volunteer for a Diabetes centre. A career in biomedical science will allow me to integrate thoroughly my passion for science into a public-service framework. As for hobbies, I enjoy reading and surfing the Internet. I research about the medical system in the UK and health standards. As I believe that health is in physical fitness, doing exercise in the gym is another of my interests.

I am hard working and compassionate, but more than anything I am extremely committed to expand my knowledge in biomedical science. I understand that this is a career with many demands, but I know that I possess the energy, determination and to withstand these difficulties and to become a valuable member of the science profession.

Universities Applied to:

• Glasgow Caledonian University
• Strathclyde University
• West of Scotland University
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ORIGINAL RESEARCH article

Application of clinical blood metabogram for diagnosis of early-stage parkinson’s disease: a pilot study.

• 1 Laboratory of Mass Spectrometric Metabolomic Diagnostics, Institute of Biomedical Chemistry, Moscow, Russia
• 2 Laboratory of Neural and Neuroendocrine Regulations, Koltzov Institute of Developmental Biology of the Russian Academy of Sciences, Moscow, Russia

In terms of time, cost, and reproducibility of clinical laboratory tests, a mass spectrometric clinical blood metabogram (CBM) enables the investigation of the blood metabolome. Metabogram’s components provide clinically relevant information by describing related groups of blood metabolites connected to humoral regulation, the metabolism of lipids, carbohydrates and amines, lipid intake into the organism, and liver function. For further development of the CBM approach, the ability of CBM to detect metabolic changes in the blood in the early stages of Parkinson’s disease (PD) was studied in this work. In a case-control study (n = 56), CBM enabled the detection of the signature in blood metabolites related to 1–2.5 clinical stages of PD, according to the modified Hoehn and Yahr scale, which is formed by alterations in eicosanoids, phospholipids and, presumably, in the butadione metabolism. The CBM component-based diagnostic accuracy reached 77%, with a specificity of 71% and sensitivity of 82%. The research results extend the range of disorders for which CBM is applicable and offer new opportunities for revealing PD-specific metabolic alterations and diagnosing early-stage PD.

1 Introduction

Parkinson’s disease (PD), which usually affects elderly people, is the second most prevalent neurodegenerative condition of the central nervous system. Due to the aging population, the incidence of PD has substantially grown. Since the first description of PD by James Parkinson in 1817 ( Parkinson, 2002 ), the exact mechanism causing this disease is still unknown. Hallmarked dopaminergic neurons that are destroyed in the substantia nigra and the formation of Lewy bodies that are largely made of fibrillar α-synuclein are pathological characteristics of PD ( Tansey and Goldberg, 2010 ). Genetic studies of familial PD have identified mutations in individual genes in monogenic PD. In particular, mutations leading to the development of PD are localized in the genes encoding α-synuclein, dardarin, vacuolar protein sorting-associated protein 35, parkin ligase, DJ1 deglycase, and acid β-glucosidase ( Ross, 2013 ; Deng et al., 2018 ).

There are evidences that oxidative damage and mitochondrial dysfunction lead to a cascade of events and ultimately contribute to the degeneration of dopaminergic neurons ( Rani and Mondal, 2020 ). Other studies demonstrated that apoptosis plays a substantial role in neurological disorders ( Tompkins et al., 1997 ). Recent studies have linked astrogliosis to the development of PD ( Heo et al., 2020 ).

The neuroinflammatory theory appears to be the most plausible of the potential causes of PD ( Tansey and Goldberg, 2010 ; Gelders et al., 2018 ). The inflammatory process, which is a protective mechanism against various types of damage, when prolonged, enhances the progression of neurodegeneration ( Snyder et al., 2017 ). A role of neuroinflammation in the pathology of PD was demonstrated in a large number of studies, indicating that neuroinflammatory processes may play a causative role in the development of PD ( Salama et al., 2020 ).

Several other factors causing PD, such as reduced Parkin activity, altered metabolism, aberrant epigenetics, exposure to toxins, telomere shortening, or protein misfolding, were reported in a number of studies ( Le et al., 2013 ; Scheffold et al., 2016 ; Wen et al., 2016 ; Rokad et al., 2017 ; Meng et al., 2020 ). According to some studies, PD can be classified as a prion-like disease ( Olanow and Brundin, 2013 ).

Due to the still unclear etiology and pathogenesis of PD, the identification of biomarkers for its diagnosis is challenging and has not been successful yet ( Chen-Plotkin et al., 2018 ). In this situation, the omics technologies, which enable measuring the diversity of a biologic system’s molecules in a single-run analysis (e.g., DNA sequencing in genomics, protein identification technologies in proteomics, and profiling of low-molecular-weight substances in metabolomics), may be helpful ( Omenn et al., 2012 ). Among the omics sciences, metabolomics is the most promising for supplying useful information for disease diagnostics because metabolites form molecular phenotypes directly reflecting physiological and pathological situations in organisms. Thus, in metabolomics studies of blood, the diagnostic accuracy of diseases often reaches 90%–95% ( Trifonova et al., 2013 ). Such results stimulate the introduction of metabolomics technologies in medicine for the diagnosis of difficult-to-diagnose diseases, including PD, the etiology and pathogenesis of which is often associated with low-molecular substances.

A clinical blood metabogram (CBM), a new personalized metabolomics approach that is a simplified single-subject (N-of-1) metabolomics analysis, was recently introduced ( Lokhov et al., 2023b ). Direct-infusion mass spectrometry (DIMS), principal component analysis (PCA), and metabolite set enrichment analysis (MSEA) were used to develop the CBM. The metabogram avoids the complexity of each N-of-1 metabolomics study and is characterized by rapid execution, simple data processing, high reproducibility, and uncomplicated result interpretation, which should make it easier to apply CBM in the clinic in the laboratory-developed test (LDT) format ( Figure 1 ). An LDT is a specific kind of diagnostic test that is created, produced, and utilized in a single laboratory ( Sharfstein, 2015 ; FDA., 2018 ; Genzen, 2019 ; Schreier et al., 2019 ) that is commonly used to implement omics tests.

Figure 1 . Workflow for producing a clinical blood metabogram. Sampled blood, after sample preparation in order to separate the metabolome fraction, is subjected to direct-infusion mass spectrometry (DIMS). The resulting mass peaks are aligned with the predefined sets of mass spectrometric peaks corresponding to the components of the metabogram (predesigned template of personal metabogram). Mass peak intensities are converted into Z-scores and averaged to obtain metabogram component values showing the state (normal, upregulated, or downregulated) of the blood metabolome (i.e., clinically relevant information). Adapted from ( Lokhov et al., 2023b ).

The blood metabolome groups that deal with humoral control, lipid-carbohydrate and lipid-amine metabolism, eicosanoids, amino acids, lipid intake into the body, and liver function are presented in the CBM that makes it clinically valuable. The main objective of this study is to examine the metabogram’s clinical potential in relation to revealing metabolic features and diagnosing early PD. To do this, the blood metabolome of patients with PD 1–2.5 stages, as measured by the modified Hoehn and Yahr scale, was examined using the CBM.

2 Materials and methods

2.1 blood samples.

Samples of blood plasma used in this study were taken from a previously published study, where study participants (n = 56) were recruited at the Republican Clinical Diagnostic Centre of Extrapyramidal Pathology and Botulinum Therapy (Kazan, Russia) ( Balashova et al., 2018 ). Briefly, study cohort included untreated PD patients at 1–2.5 stages according to modified Hoehn and Yahr scale (stage 1 – unilateral involvement only; stage 1.5 – unilateral and axial involvement; stage 2 – bilateral involvement without impairment of balance; stage 2.5 – mild bilateral disease with recovery on pull test) ( Goetz et al., 2004 ) and controls without neurodegenerative diseases. The following exclusion criteria were used for PD patients and control subjects: severe systemic disease, stroke, brain surgery, Alzheimer’s disease or any other medical history central nervous system disease, chronic renal failure, systemic infections, malignancy, cardiac or hepatic dysfunction, and autoimmune disease. Informed consent was obtained from all subjects involved in the study. The study was conducted in accordance with the Declaration of Helsinki, and approved by the Institutional Ethics Committee of Koltzov Institute of Developmental Biology of Russian Academy of Sciences (protocol code 55 and date of approval 9 December 2021).

2.2 Mass spectrometry analysis of blood samples

The same equipment and materials were used as in the previously reported study ( Balashova et al., 2018 ), including venous blood sampling, sample preparation, mass spectrometer analysis, mass spectra processing, and mass list processing (alignment, standardization, and normalizing).

Blood samples were taken from the vein before the morning meal. Samples (3 mL) were placed into glass tubes containing K 2 EDTA (BD Vacutainer; Becton, Dickinson and Company, Franklin Lakes, NJ, United States) and centrifuged within 15 min of blood collection at 1,600 × g and room temperature. The resultant blood plasma was subdivided into aliquots that were pipetted into plastic tubes. These tubes were marked, transported in special thermocontainers, frozen, and then stored at −80°C until analysis. The analyzed samples were subjected to one freeze/thaw cycle.

For plasma deproteinization, aliquots (10 µL) were mixed with 10 µL water (LiChrosolv; Merck KGaA, Darmstadt, Germany) and 80 µL methanol (Fluka, Munich, Germany) and incubated at room temperature. After 15 min, samples were centrifuged at 13,000 × g (MiniSpin plus centrifuge; Eppendorf AG, Hamburg, Germany) for 10 min. Deproteinized supernatants were then transferred to clean plastic Eppendorf tubes, and fifty volumes of methanol containing 0.1% formic acid (Fluka) were added to each tube. The resulting solutions were subjected to mass spectrometry analysis.

Samples were analyzed with a maXis hybrid quadrupole time-of-flight mass spectrometer (Bruker Daltonics, Billerica, MA, United States) equipped with an electrospray ionization (ESI) source. The mass spectrometer was set up to prioritize the detection of ions with a mass-to-charge ratio ( m/z ) ranging from 50 to 1,000 and a mass accuracy of 1–2 parts per million (ppm). Spectra were recorded in the positive ion charge detection mode. Samples were injected into the ESI source using a glass syringe (Hamilton Bonaduz AG, Bonaduz, Switzerland) connected to a syringe injection pump (KD Scientific, Holliston, MA, United States). The flow rate of samples to the ionization source was 180 μL/h, and samples were injected in a randomized order (e.g., control samples were run between case samples). Mass spectra were obtained using DataAnalysis version 3.4 (Bruker Daltonics) to summarize 1-min signals. Ion metabolite masses were determined from the mass spectrum peaks obtained using the DataAnalysis program. All peaks above noise level (signal to noise ratio >1) were selected, and the metabolite ion masses were pooled and processed using Matlab program (version R2019a; MathWorks, Natick, MA, United States). For the recalibration of all the peak m/z values, the internal standard losartan (m/z 423.169) was used.

Standardization of mass peak intensities was performed as described previously ( Lokhov et al., 2020 ) by dividing the intensity by the standardization value, which was calculated for each peak separately as follows: the 50 Da range (which started 25 Da before and ended 25 Da after the m/z of the mass peak) was selected; all peaks inside the range were sorted in descending order according to their intensities; the intensity of the 150th peak was selected as the standardization value. Standardized intensities improved further analysis due to the correction of ion suppression of peak intensities ( Lokhov et al., 2020 ). Standardized mass lists were normalized by applying the normalize function (which brings the sum of the intensities of the peaks in the spectrum to 1) of the Matlab program. The alignment of the m/z values of the mass peaks between different mass spectra was performed as described previously ( Lokhov et al., 2011 ). The alignment algorithm used was previously specially developed and tested for the high-resolution mass spectra of blood metabolites obtained by DIMS and implemented as an iterative process based on the detection of correlation of mass spectrometry peak patterns.

2.3 Design of metabogram template for personal metabograms

The details of the metabogram construction using a reference cohort of healthy subjects are described in a previous study ( Lokhov et al., 2023b ). Briefly, DIMS was used to analyze blood plasma samples from 48 healthy people (reference cohort) to develop the metabogram template ( Figure 1 ). The lists of mass peaks that were produced after mass spectra processing (alignment, standardization, and normalization) were analyzed using principal component analysis (PCA). The metabogram components were formed by the mass peaks corresponding to the highest positive or lowest negative coefficients (loadings) of the first seven principal components. The resulting sets of m/z values of mass peaks are presented in Supplementary Table S1 . 70% of blood metabolome variance is explained by these sets of mass peaks, which were used in this study as a template to quickly produce personal metabograms. The composition of metabogram components ( Figure 2 ) was determined by identifying the metabolite classes with which they are enriched. For this, MSEA was used ( Xia and Wishart, 2010 ). Clinical blood tests (n = 71) were also used to determine the biological significance of the metabogram components ( Lokhov et al., 2023b ). Each metabogram component has two Z-score scales reflecting its measure, named the “positive” and “negative” parts, because the principal components involved in the development of the metabogram have both positive and negative coefficients (loadings). In short, the original variables that comprise the principal components are linear combinations of their coefficients. The structure of the data may be seen in the coefficients of each principal component. Larger positive or negative values indicate variables that contribute more to the component. M/z values corresponding to the highest and lowest coefficients of the first seven principal components—referred to the “positive” and “negative” parts of the metabogram components—were used to construct CBM reflecting the underlying data of the blood metabolome. In total, it amounted to about 5% each for the “positive” and “negative” parts of the detected peaks. The Z-score is a common way of representing data on a unitless scale and is the raw score minus the population mean, divided by the population standard deviation. With a normal distribution, the Z-score is connected to the p -values; for example, 1.64 corresponds to p = 0.05 (one-tailed), which is thought to be the cutoff for statistical significance and enables the detection of the sample’s deviation from the population. The metabogram’s Z-scores from −1.64 to +1.64 are considered to be in the normal range; up- and downregulation are represented by higher and lower Z-score values, respectively.

Figure 2 . Composition of the clinical blood metabogram components. The composition of the metabogram components was measured by determining with which classes of metabolites they are enriched. Enrichment reliability expressed in p -values is presented in a previously published paper ( Lokhov et al., 2023b ).

The components of the metabogram are formed by the functionally related metabolites of the blood involved in humoral regulation (component 1, called “regulatory”), lipid -carbohydrate metabolism (component 2), phospholypolysis (component 3, called “phospholipolytic”), lipid-amine metabolism (component 4), oxidized fatty acids (component 5, called “eicosanoid”), lipid intake into the organism (component 6, called “alimentary”), and liver function (component 7, called “hepatic”), thereby providing clinically relevant information. It should be noted that the identity of obtaining a CBM (sampling, sample processing, mass spectrometry, CBM design, and composition of metabogram components as presented in Supplementary Table S1 ), established in the first article that introduced the concept of CBM ( Lokhov et al., 2023b ) and further tested in subsequent studies, allows the obtained data to compare and relate the results obtained to the characteristics of the prototype of the same CBM-based LDT test.

2.4 Personal clinical blood metabograms

The study cohort (see Section 2.1 ), which included control individuals and patients with early-stage PD, was used to obtain personal CBMs. After standardization and normalization, the produced mass lists were aligned with the m/z values of the metabogram template (i.e., with 7 m/z sets corresponding to seven metabogram components; see Section 2.3 ). To obtain Z-scores of the metabogram components, the mass peak intensities belonging to the same metabogram component were converted into Z-scores and averaged ( Lokhov et al., 2023b ).

2.5 Cluster analysis

A cluster analysis was performed to give an overview of the metabograms of patients with the early clinical stage of PD. To do this, the pdist function (Matlab) was used to determine the Euclidian distances between the Z-scores of the metabograms’ components. The linkag e function created an agglomerative hierarchical cluster tree by calculating the distance between clusters using the “ward” algorithm. The dendrogram function was used to plot the dendrogram.

2.6 Diagnostic parameters

To assess the diagnostic potential of the metabogram for early clinical stage PD, the following diagnostic parameters were evaluated: sensitivity—the percentage of correctly identified positive results (the deviation is correctly assigned to metabogram component with Z-score out of normal range, i.e., Z-score < −1.64 or >1.64); specificity—the percentage of correctly identified negative results (the deviation from normal range is correctly not assigned to metabogram component with Z-score in normal range); and accuracy—the percentage of correctly identified positive and negative results.

The ROC curve was built by the perfcurve function (Matlab). The function also returned sensitivity and specificity values for diagnostics depending on the selected threshold Z-score value separating cases from controls and the optimal Z-score value for the highest diagnostic accuracy.

2.7 CBM signature of Parkinson’s disease

Considering the cluster analysis data and using the metabogram components that exhibit the greatest diagnostic power, a PD signature was formed. To confirm the inter-disease specificity of the PD signature, the ROC curves were built to separate control and patients with type 2 diabetes mellitus and obesity from control. Metabogram data for these subjects was taken from previous studies conducted on CBM research ( Lokhov et al., 2023c ; Lokhov et al., 2024 ). In the first case, the PD signature was directly applied to the metabogram data of diabetic patients. In the second case, the difference in the signature of obesity and PD, such as downregulation in the positive part of the first component of CBM at obesity, was additionally taken into consideration. Other differences between signatures were not considered since the absolute unspecificity of the PD signature for obesity was achieved.

3.1 Studied subjects

Equally sized cohorts of patients and control subjects were obtained, aligned by gender and age, allowing for case-control comparison. Table 1 presents the clinical characteristics of the cohorts. The individual characteristics of the subjects are presented in Supplementary Table S2 .

Table 1 . Study cohort characteristics.

3.2 Metabogram data

Mass spectrometry analysis, as the first analytical step of the CBM production ( Figure 1 ), generated typical mass spectra of the low-molecular-weight fraction of blood plasma samples. On average, ∼9.7 thousand peaks were detected in the spectrum, which corresponds to the number of mass peaks in spectra used to design CBM ( Lokhov et al., 2023b ) and in other CBM-related studies ( Lokhov et al., 2023a ; 2023c ; Lokhov et al., 2024 ). Aligned and standardized mass lists are presented in Supplementary Table S3 . These mass spectrometry data were used to obtain personal metabograms for all subjects participating in the study ( Figure 3 ).

Figure 3 . Metabogram data for control subjects and subjects with early-stage PD. Each row corresponds to the Z-scores of the metabogram components for an individual (components 1 to 7 for the “positive” and “negative” parts). Z-score is a measure of the metabogram components (from −1.64 to +1.64 is the normal range; up- and downregulation correspond to higher and lower Z-score values, respectively). Background color coding: red indicates upregulation in the corresponding metabogram component; yellow indicates downregulation in the corresponding metabogram component.

Figure 3 demonstrates that the components of the metabogram of PD patients deviate more frequently than those of controls, as evidenced by the frequencies of these deviations ( Figure 4 ). Metabolites related to the negative components 3 and 5 and the positive component 4 are downregulated most frequently ( Figure 4 ).

Figure 4 . The frequency of deviations in the blood metabogram components for early-stage PD. The metabogram component deviates from the norm if the Z-score of the metabogram component is below −1.64 (indicating downregulation of the metabolites related to the metabogram component) or above 1.64 (indicating upregulation of the metabolites related to the metabogram component).

3.3 Statistical data and diagnostic parameters

The t-test results demonstrating the significance of the difference in the metabogram components in the case-control comparison are presented in Table 2 . The difference for the negative component 5 is statistically significant ( p -value 0.005), which indicates that PD-specific changes in metabogram can be attributed to the downregulation of the eicosanoids ( Figure 2 ).

Table 2 . Statistical significance of the deviation of the metabogram components in early PD (1–2.5 stages) from the control.

To assess the diagnostic capabilities of the CBM, generally used diagnostic parameters were calculated. Table 3 displays sensitivity, specificity, and accuracy calculated based on the divergence of metabogram’s components from the normal range. The data in the table show the metabogram’s negative component 5 demonstrates the most diagnostic power for detecting the early clinical stage of PD with an accuracy of 62.5% (sensitivity of 32.1%, specificity of 92.9%) when a Z-score of −1.64 (corresponds to p = 0.05) is used to separate cases from controls. The lower diagnostic capability was demonstrated by the positive part of component 4 and the negative part of component 3, with diagnostic accuracy of 55.3% and 57.1%, respectively.

Table 3 . Diagnostic parameters of the metabogram components for the detection of early-stage PD.

The diagnostic potential of these components of the CBM was also assessed by building an ROC curve to determine the optimal threshold for separating cases from controls that provides the best diagnostic parameters. Figure 5A demonstrates that the accuracy of diagnostics was increased for the above-mentioned metabogram components to 76.8%, 67.9%, and 64.3%. This result confirms the diagnostic power of the CBM by a generally accepted method and shows that the Z-scores of the metabogram components can be further processed to improve diagnostic parameters.

Figure 5 . ROC curves based on the Z-score of the clinical blood metabogram (CBM) components for the diagnosis of Parkinson’s disease (PD). (A) ROC curves for the three metabogram components, which consist of the PD-specific signature: the negative parts of components 3 and 5, and the positive part of component 4. (B) ROC curve for the PD-specific signature, which consists of three metabogram components. Z-score −1.64 is used to distinguish between PD cases and controls. The PD signature was applied to patients with obesity and type 2 diabetes mellitus to show its inter-disease specificity.

In addition to the fact that individual components of the metabogram are associated with PD, and some of them even have diagnostic power, the combinations formed by these components of the metabogram are also an important diagnostic feature—a signature of the disease. To identify such signatures, the patterns formed by deviating metabogram components were identified by cluster analysis ( Figure 6 ). Clusters associated with stages of PD development were not revealed. One cluster, which can be seen as typical for PD, was created by various combinations of the most often deviating metabogram components (see cluster 2 on Figure 6 ). Therefore, it may be claimed that for a significant part of patients with early-stage PD, the CBM will show a PD-specific signature reflecting disease-associated metabolic alterations.

Figure 6 . Cluster analysis of blood metabograms of PD patients involved in the study. Each row corresponds to the metabogram components for an individual (components 1 to 7 for the “ positive ” and “ negative ” parts). Color coding: red indicates upregulation in the corresponding metabogram component; yellow indicates downregulation in the corresponding metabogram component. The metabograms with no deviations ( ❶ ) in components and metabograms considered PD-specific ( ❷ ) are selected.

To confirm the inter-disease specificity of the PD signature, the ROC curves were built and compared with the ROC curves separating control from patients with type 2 diabetes mellitus and obesity ( Figure 5B ). The PD signature showed high sensitivity to PD at low specificity, while for other diseases the AUC was 0.49 and 0.5, which confirmed the inter-disease specificity of the PD signature. Therefore, if a PD signature is detected, early-stage PD is likely to be suspected. However, the absence of the PD signature does not exclude the underlying pathological condition. Perhaps the signature has not yet been formed at an early stage of disease in many patients, or it reflects only the dominant form of metabolic alterations in PD.

4 Discussion

The basic methods for diagnosing PD, a progressive degenerative condition of the central nervous system, are a medical history and a neurological examination ( Jankovic, 2008 ). While effective treatment for PD depends on an early diagnosis ( Gelb et al., 1999 ), a clinical diagnosis cannot be made until there is a large loss of dopaminergic neurons ( Gibb and Lees, 1988 ). Moreover, the cost of the imaging of dopamine (Dopa) uptake efficiency diagnostic test based on positron emission tomography (PET) is high. As a result, a novel diagnostic laboratory test is needed. Biomarker discovery for such tests is hampered by PD’s ambiguous pathophysiology and complex character, and the use of panoramic techniques, as suggested, is more promising in this situation. Unfortunately, because of the consistency needed for clinical test registration, the clinical use of such ‘panoramic’ procedures, to which metabolomic analysis is related, is quite difficult. LDT usage gets around this problem. LDTs are defined by the Food and Drug Administration (United States) as tests that are created, produced, and used in the same laboratory ( FDA, 2018 ). Therefore, the execution of metabolomics analysis in LDT format is sufficiently streamlined due to putting protocol development and standardization tasks under the purview of a single laboratory.

Although metabolomics, which measures the groups of metabolites that make up the metabolome, has been around for more than 20 years and the technologies it uses are nearly perfect, its application in medicine, even as LDT, is quite limited. Main cause of this is the preciseness of measurements, which allows for the precise measurement of numerous metabolites in a single run. Widely used in metabolomics, mass spectrometry techniques are typically capable of detecting hundreds of metabolites, which is essential for gathering biochemical data ( Viant et al., 2017 ). Despite the use of cutting-edge mass spectrometry-based metabolomics technologies, the vast majority of the sample’s metabolites remain unknown ( de Jong et al., 2017 ). Typically, only highly abundant and well-separated metabolites are identified. This is due to the difficulty of producing a clear mass spectrometric image of low-abundance metabolites, which constitute the majority of any metabolome. This means that the complexity of metabolomic measurements restricts the use of metabolomics in LDT format ( Nalbantoglu, 2019 ; Lichtenberg et al., 2021 ; Lokhov et al., 2021 ).

The concept of the metabogram—a simplified single-subject metabolomics study—was developed to address this issue. The metabogram technique eliminates metabolite identification step ( Lokhov et al., 2023b ). Only groups of related metabolites are processed in the metabogram for this reason, and the use of MSEA ( Xia and Wishart, 2010 ) quickly determines the enrichment of these groups with metabolite classes. As a result, group analysis takes the place of the challenging identification of individual metabolites. Additionally, data repeatability is improved by averaging metabolite data (peak intensities) within groups. For metabogram components, the coefficient of variation can be as low as 1.8% ( Lokhov et al., 2023b ), which is much lower than what is often found for individual metabolites ( Crews et al., 2009 ). In order to validate the clinical utility of CBM for PD diagnosis, people with early PD were evaluated using CBM in this study.

According to the data obtained, it can be argued that, in terms of the frequency of occurrence and the joint appearance, PD-specific changes can be attributed to the downregulation of metabolites related to the eicosanoid component (negative part of component 5), the phospholipolytic component (negative part of component 3), and the positive part of component 4 (called the “phospholipid-amine” because of the co-directed changes in phospholipids and amino acids described by its negative part).

The most frequent deviation from the norm was revealed in the eicosanoid component of the metabogram ( Figure 4 ). This deviation in patients with early-stage PD occurred 4.5 times more often than in the control group. A distinctive feature of this component of the metabogram is its enrichment with eicosanoids such as prostaglandins and leukotrienes. The close involvement of various eicosanoids in the development of PD can be read in the review by Chiurchiù V. et al. (2022) . A variety of studies using both different biomaterials for research and the diversity of eicosanoids themselves led to the observation of multidirectional changes in their concentrations in PD. However, it can be argued that a group of eicosanoids in the blood decreases with PD ( Zhang et al., 2021 ; Chistyakov et al., 2023 ) and even some eicosanoids exhibit neuroprotective effects ( Rajan et al., 2020 ). Perhaps this group of eicosanoids is responsible for the decreased Z-score of this component of the metabogram.

The association of blood phospholipids with PD is an established fact and was already proposed for diagnostic purposes ( Li et al., 2015 ). Oxidative stress is a significant factor in the onset and course of PD. Important elements of cellular membranes, phospholipids are essential for preserving the integrity and functionality of cells. Patients with PD have much higher lipid peroxidation products in their brains, which may be a connection between membrane damage and changes in phospholipid levels. However, it is possible that the detected changes in the phospholipolytic component may be due to a change in the concentration of phospholipids or may be associated with the activity of phospholipases. Previously, it was found that there is a link between phospholipases and PD ( Mendez-Gomez et al., 2018 ; Wu et al., 2021 ). Thus, phosphatidic acid, a product of phospholipase PLD2 activity, is a second messenger in many cellular pathways and appears to be key to PLD2-induced neurodegeneration. The fact that α-synuclein is a regulator of PLD2 activity suggests that regulation of PLD2 activity may be important in the progression of PD.

Regarding downregulation reflected by the positive component 4, metabolites associated with it were not identified during the CBM design ( Lokhov et al., 2023b ). The list of molecular weights for which potential candidates exist was sparse and included several quasi-ions to which several elemental compositions corresponded (C 2 H 2 O 4 , С 4 Н 6 О 3 , С 4 Н 6 О 3 , С 5 Н 6 О 5 ) ( Lokhov et al., 2024 ). The elemental composition of C 2 H 2 O 4 in the metabolite database corresponds only to oxalic acids, a degradation product of vitamin C, a deficiency of which in the body is associated with the development of PD ( Brown, 2017 ). For the elemental formula C 4 H 6 O 3 , among the candidates are metabolites related to the butanoate metabolism pathway, such as acetoacetic acid (ketone body) and succinic acid semialdehyde. For C 5 H 6 O 5 , there is no alternative to oxoglutaric acid, which also belongs to butanoate metabolism. Interestingly, ketone bodies are associated with the development of PD, attributing neuroprotective properties to them ( Maalouf et al., 2009 ). Moreover, the butadione metabolism pathway includes the formation of gamma-aminobutyric acid (GABA), and the connection between its level decrease and PD is well-known ( Błaszczyk, 2016 ). Since the metabolites of this metabogram component were not reliably identified either according to metabolomics standards or during the design of a metabogram, the connection of this component with the butanoate metabolism pathway is hypothetical.

Based on the results obtained, several types of metabograms can be distinguished in early PD ( Figure 6 ). A metabogram without abnormalities, a metabogram with various non-systematic abnormalities that can be attributed to an individual’s disease course, or an individual health condition defined by other diseases, and a metabogram that can be attributed to a PD-specific metabotype. The last one manifests in the blood level of eicosanoids and is often associated with changes in the phospholipolytic and phospholipid-amine components. Figure 7 shows a metabogram in a simple format, showing the names of the components, the blood metabolome variance explained by each component, and the Z-scores of the components. The figure also provides a PD-specific signature – the components that contribute to the diagnosis of PD and can be potentially used to monitor the level of metabolic alterations during PD development and treatment. The inability to diagnose PD, as well as to monitor its course and the outcome of treatment in patients who do not have a PD-specific metabotype can be attributed to the limitations of CBM.

Figure 7 . An example of the clinical blood metabogram. The percent of blood metabolome variance that the metabogram component explains is indicated by the superscript “Var.” The metabogram components are measured by the Z-score value, whose normal range is from −1.64 to 1.64. Higher and lower Z-scores are related to up- and downregulation of the blood metabolites corresponding to the metabogram component. The metabogram components most often deviated at PD are highlighted by background color. ( Lokhov et al., 2023c ).

As said in the introduction, it's critical to remember that PD has a diverse pathogenesis involving a range of small molecular compounds. The specified metabolite composition of CBM components may cause some PD-specific metabolic alterations in the blood are undetected by CBM. Such alterations either do not have a significant effect on the main groups of blood metabolites reflected in CBM or refer to metabolites assigned to the remaining 30% of the variance of the blood metabolome not covered by CBM. However, modifying the CBM for a specific disease to increase its capabilities is beyond the scope of this work, which consists of testing a previously developed CBM design. The peculiarity of this approach is visible when comparing the results obtained with a previously conducted classical metabolomic study to search for biomarkers or a multimarker diagnostic signature of PD. In contrast to CBM, an AUC of 0.91 was achieved to diagnose PD in this single disease-focused study ( Balashova et al., 2018 ). Contrariwise to such single-disease studies, the same CBM design applied to multiple diseases is more consistent with omics tests that identify changes at a significant portion of the metabolomic level, offering diagnostic capabilities for a variety of diseases.

From the described metabolic alterations, an additional feature of the PD signature can be suggested. The neuroprotective eicosanoids, whose reduction is reflected in the signature, not only inhibit neuroinflammation but also suppress oxidative stress ( Tassoni et al., 2008 ). The change in the phospholipolytic component, as above indicated, can be caused by peroxidase oxidation and activation of phospholipase, which is recognized as an integral component of the oxidant stress response system ( Adibhatla and Hatcher, 2008 ). The change in the metabolism of butadione led to the downregulation of ketone bodies with antioxidative properties ( Kolb et al., 2021 ). Thus, the ketone body β-hydroxybutyrate is a direct antioxidant for hydroxyl radicals, an inhibitor of mitochondrial reactive oxygen species (ROS) production, and promotes the transcriptional activity of antioxidant defenses ( Rojas-Morales et al., 2020 ). It can be assumed that the PD signature not only reflects the role of oxidative stress in PD development but also may indicate the risk of developing PD through the reflection of a reduced level of antioxidant activity in the organism. However, the confirmation of this assumption requires additional research.

The specificity of the identified signature to PD is also confirmed by its difference from previously published signatures of obesity and type 2 diabetes mellitus widespread in the population ( Lokhov et al., 2023c ; Lokhov et al., 2024 ). Moreover, when interpreting a PD-specific signature, the influence of the gut microbiota on CBM can be taken into consideration, the link to which was also described ( Lokhov et al., 2023a ).

The results of this study should also be assessed in the light of atypical parkinsonisms, the differential diagnosis of which from PD remains challenging. Although accurate diagnosis in the early stages of the disease plays an important role in prognosis and treatment strategy, distinguishing PD from, for example, parkinsonian-type multiple system atrophy (MSA-P) due to the similarity of symptoms can be difficult ( Wenning et al., 1997 ; Goetz et al., 2004 ). The existence of the different clusters formed by metabograms in Figure 6 may be caused by MSA-P or other atypical parkinsonisms (progressive supranuclear palsy, corticobasal degeneration, and dementia with Lewy bodies). However, due to the rarity of their occurrence and the small cohort used, such a connection cannot be identified in this study, and this hypothetical statement rather serves as the basis for further research. Further studies in larger cohorts that include different parkinsonisms in sufficient numbers to obtain statistically significant data will demonstrate the potential of CBM in the differential diagnosis of PD and other parkinsonisms.

As for the clinical implications of the results of this work, an interpretation of the CBM can now be made for PD patients. This makes it possible to accurately analyze the metabolic changes in such patients and the dysfunctions of the body caused by these changes, relating or separating them from those specific to PD. Considering the pilot nature of the study, the feasibility of predicting the course of PD, assessing the effectiveness of treatment, and differentiating PD from atypical parkinsonism will become possible after additional research.

5 Conclusion

The measurement of the metabolome for clinical use is eagerly awaited and shows great promise. The metabolome, as its name suggests, is a level of organization of biological systems that is directly related to the global biochemical phenotype. One such attempt is the CBM, which, as demonstrated in previous studies, possesses the performance characteristics of a clinical test, and provides data that is clinically relevant. In this work, CBM was used to diagnose early PD, a condition that is very challenging to diagnose by laboratory testing, and its efficacy was verified. CBM allowed revealing a PD-specific metabotype, the measure of which not only provides diagnostic information but also opens up new opportunities to monitor PD progression and evaluate response to PD treatment.

Data availability statement

Publicly available datasets were analyzed in this study. This data can be found here: FigShare repository at https://doi.org/10.6084/m9.figshare.25487551 .

Ethics statement

The studies involving humans were approved by Institutional Ethics Committee of Koltzov Institute of Developmental Biology of Russian Academy of Sciences (protocol code 55 and date of approval 9 December 2021). The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.

Author contributions

PL: Conceptualization, Methodology, Project administration, Software, Writing–original draft. OT: Data curation, Investigation, Methodology, Writing–review and editing. EB: Investigation, Validation, Writing–review and editing. DM: Formal Analysis, Investigation, Methodology, Writing–review and editing. MU: Data curation, Resources, Supervision, Writing–review and editing. AA: Conceptualization, Funding acquisition, Project administration, Writing–review and editing.

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. The work was performed within the framework of the Program for Basic Research in the Russian Federation for a long-term period (2021–2030) (No. 122030100168-2).

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Supplementary material

The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fmolb.2024.1407974/full#supplementary-material

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Keywords: metabolomics, clinical blood metabogram, Parkinson’s disease, diagnostics, mass spectrometry, blood plasma, clinical metabolomics, personalized metabolomics

Citation: Lokhov PG, Trifonova OP, Balashova EE, Maslov DL, Ugrumov MV and Archakov AI (2024) Application of clinical blood metabogram for diagnosis of early-stage Parkinson’s disease: a pilot study. Front. Mol. Biosci. 11:1407974. doi: 10.3389/fmolb.2024.1407974

Received: 27 March 2024; Accepted: 30 July 2024; Published: 14 August 2024.

Reviewed by:

Copyright © 2024 Lokhov, Trifonova, Balashova, Maslov, Ugrumov and Archakov. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Petr G. Lokhov, [email protected]

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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Biomedical sciences personal statement example 37.

Being born in an era where Science flourishes and is relentlessly used as a base to solve all of mankind's problems makes me yearn for the knowledge it bestows. I first discovered Science at the age of 10, when I read a set of junior encyclopaedias, which introduced me to a world full of diversity.

The amazement of having billions of cells that coherently work together to run a machine most efficient created a sense of awe and admiration in me. My interest for science grew further, as I realised that everything I learnt was interlinked. It was amazing to know how hydrogen bonding between base pairings and the bond angles within a DNA strand related back to Chemistry. This interest has fired in me the desire to study Biomedical Sciences.

Through a Biology discussion I learnt that, when we partake in academic work, the neurotransmitter traffic that governs our thoughts, improve and the new connections formed work more efficiently. This led me to further research and come across Dr. V.S. Ramachandran of California University. The simplicity of his findings that challenged the Freudian theory about the Capgrass syndrome stood out for me.

Subsequently, I read 'The Emerging Mind' by the same author and got an insight into how the brain goes through a phase called the 'learned paralysis' after a paralysed arm is amputated. This phantom arm that occurs after the amputation can cause great discomfort for the patient because of the paralysis. I liked the approach Dr. Rama used to solve this problem. The simple use of a mirror can create superimposed image of the patient's intact hand. The movement of this hand can give the brain visual feedback that phantom arm is moving, and the pain is relieved.

My curiosity to learn more about stem cells motivated me to undertake an Extended Project,whereby I looked at the effects of stem cell research on stroke victims. The advancement that has led the techniques used to recover a patient from stroke has reassured me that terminal illnesses, such as cancer and AIDS will be curable in the near future. I was also made aware of the complexity of stem cells and the ability they have to track damaged tissue and encourage cell growth.

This knowledge and understanding gives me the drive to pursue my studies in biology and chemistry in particular because it gives me the fundamentals to understand more complex ideas. This project helped me gain investigative and research skills required to understand scientific theories at a more profound level and the confidence to make a presentation.

During the summer of 2011, I was able to do two weeks voluntary work at a (named)Hospital in India. I had the opportunity to observe and interact with Interns, as well as Consultants in the A&E Department wherein serious casualty cases are treated. I had first hand opportunity in testing patients for HIV, Malaria and Blood Glucose levels, besides observing the techniques of suturing and intubation. Knowing local languages, Konkani and Hindi enabled me to communicate with patients on a one to one basis. T

his was one of the most enriching experiences of my life, especially to see how Doctors work tirelessly to reach out to large number of patients. Primarily this experience taught me how important it is to remain calm in stressful situations; about team communication and quick decisions.

Taking part in the Duke of Edinburgh scheme from Bronze to Gold Award not only gave me a sense of release and adventure, but also survival and team building skills.

My other interests include sports, music and cinema. I was privileged in being chosen to captain the School cricket team and also represent my School in Football, Badminton and Rugby. I am able to read music and play the guitar.I took the opportunity to take part in a first aid program and I am a qualified first aider.

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This personal statement was written by noliveira for application in 2012.

noliveira's university choices Kingston University The University of Essex University of Lincoln University of Sunderland

Green : offer made Red : no offer made

noliveira's Comments

Feel free to comment/critique my PS. The last paragraph does seem rushed and it seems like I have listed things - I had limited characters to fit it all in.

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Tue, 20/03/2012 - 20:56

Very informative article. Cool.

some one watches a little to

Thu, 12/09/2013 - 20:15

some one watches a little to much Grey's anatomy!

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