Advances in Hepatitis C research: associated neurocognitive symptoms

Hepatitis C virus (HCV) is a major health burden in England (Public Health England, 2015). HCV treatment is a significant component in control of the disease but the neuropsychiatric side effects of the treatment have been associated with treatment interruption. We, and others, are studying how these side effects impact discontinuation rates, with particular interest in the cognitive side effects of treatment.
According to recent evidence (Monaco et al, 2015) the hepatitis C virus (HCV) associated neurocognitive disorder (HCV-AND) involves executive function, sustained attention, working memory, verbal learning and verbal recall. Several factors, such as alcohol misuse, substance abuse, interferon treatment and HCV itself have been identified as contributors to HCV-AND. Interestingly, changes in neuropsychological performance in HCV patients occurred independently of HCV genotype and stage of liver disease. The same review described results of studies looking at brain changes. These studies suggested that HCV infection is associated with brain metabolic alterations due to the presence of HCV replication in specific areas of the brain (in the frontal cortex, basal ganglia and subcortical white matter), as in agreement with previous results in HIV and HCV co-infected patients.
These findings are in line with the idea that HCV causes brain changes and activates mechanisms that increase the acceleration of cognitive impairment. Additionally, it seems that HCV and HIV are detected in the same brain areas. Despite the co-factors that contribute to cognitive dysfunction in HCV infection, the pathogenic role of the HCV virus in the brain is an issue of major importance to target treatment options.

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Reference

Monaco, S., Mariotto, S., Ferrari, S., Calabrese, M., Zanusso, G., Gajofatto, A., … & Dammacco, F. (2015). Hepatitis C virus-associated neurocognitive and neuropsychiatric disorders: Advances in 2015. World journal of gastroenterology, 21(42), 11974.

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Alzheimer’s Research UK 2016 Conference – II

Day 1

The themes of the 1st day of the main AD conference were Frontotemporal dementia, Neurovascular dysfunction, and Inflammation & Immunity. One of many fascinating presentations on this was given by Jessica Duncombe, a 3rd year PhD student from the University of Edinburgh. Jessica Duncombe hypothesised that dysfunctions in neurovascular coupling may underlie changes in AD and normal ageing. The researchers looked at TgSwDI transgenic mice and their wild type littermates, focusing on the cortex. Interestingly, both wild type and transgenic mice showed an impaired vascular response to whisker stimulation as well as increased microglial proliferation. Whilst no difference in vascular response was seen between wild-type and transgenic mice, microglial proliferation was enhanced in the transgenic mice, who also showed significantly more amyloid at 24 months (although not 6 months).

Professor Rusted presented a poster on day 1 of the conference, as shown below.

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Day 2

The themes of the 2nd day of the main conference were Models of Neurodegeneration, New Treatments for Dementia, Mechanisms of Cell Death and Tau, and AB: Two Sides of the Same Coin? Sadly, one scheduled presenter was unable to make the conference, but Dr Jack Rivers-Auty from the University of Manchester was able to step in with an interesting talk on zinc deficiency, neuroinflammation, and AD. Dr Rivers-Auty had a very engaging presentation style and set of slides; he started the talk with a countdown timer, showing the difference in rate of neuron loss in a healthy brain, and an AD brain, with an associated image of progressive atrophy – a very effective demonstration. Dr Rivers-Auty looked at IL-1b, a potential molecular mediator of the inflammatory response, the production of which is regulated by inflammasomes including NLRP3. Zinc absorption reduces in ageing, with AD patients presenting with lower plasma and serum zinc levels. Dr River-Auty hypothesised that zinc deficiency causes NLRP3 sensitivity, resulting in neuroinflammation and exacerbating AD. Evidence for this comes from APP-PS1 zinc deficient (AD zd), APP-PS1 zinc normal (AD zn), wild type zinc deficient (WT zd) and wild type zinc normal mice (WT zn). AD zinc deficient mice showed poorer Y-maze performance and a lack of morris water maze improvement (between 3-6 months) when compared with AD zn, WT zd and WT zn mice. It appears that zinc deficiency resulted in earlier impairments in the AD mice alone, therefore seemingly exacerbating the AD phenotype.

A particularly interesting poster was presented by Dr Chris Henstridge from the University of Edinburgh, reporting on the first post mortem analysis of a brain from the Lothian 1936 birth cohort. Having spoken with Dr Henstridge, it seems they now have four donated brains. As this cohort had APOE status and cognitive testing from 7 years old onwards, these upcoming post mortem analyses could be of interest.

Overall impression

Whilst the conference content overall was quite molecular, it was still very good to know what is going on in the general area of AD research. I found the conference useful for improving the way in which I communicate my research to others, and for taking note of particularly effective presenting styles (through both posters and talks). Moreover, it was very helpful in deepening my level of understanding of the type of research the other PhD students in the AD Society DTC will be undertaking, especially as one conference theme centred on drug discovery (related to Lucas Kraft’s research).

 

Rebecca Atkinson

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Alzheimer’s Research UK 2016 Conference

 

This week I attended the annual ARUK conference, in Manchester. This comprised a PhD day, followed by two days of the main conference. The PhD day included a number of talks from current PhD students on their research, as well as talks on the current work of ARUK, and useful career related information.

Feedback on ARUKs current engagement work highlighted the joined up network of dementia collaborations in the UK (more so than in most, if not all, other countries). A recent ARUK survey demonstrated that only 23% of the public recognise that dementia is driven by disease processes, so a lot of their recent engagement work is aiming to increase understanding of Alzheimer’s disease, such as their very successful recent “share the orange” campaign ( #sharetheorange). The ARUK engagement feedback was useful in emphasising the reasons that we, as researchers, should be involved in public engagement – reasons as varied as ensuring the continuation of research funding; being able to offer informed input into dementia related conversations with the public, charities and policy makers; improving overall communication skills; and potentially connecting with future collaborators. Potentially of use, ARUK offer a free “researcher toolkit” to any researchers (not just those that are ARUK funded) which contains standard pathology diagrams to use in presentations, amongst other things (just email press@alzheimersresearchuk.org). Furthermore, they have a great game which involves shooting amyloid, aimed at engaging kids (http://www.alzheimersresearchuk.org/amyloids/#play-game).

 

There were a number of well presented, engaging and interesting talks and posters from PhD students. One talk that particularly caught my interest was by Claire Harwell, The Babraham Institute, Cambridge on the “Presynaptic Disruption in Organotypic Hippocampal Slice Cultures as a Model of Early and Progressive Amyloid Pathology”. In her talk, Claire Harwell presented a novel and innovative model for slice. These slice cultures combine some of the advantages of both in vivo and in vitro work, as they allow for the maintenance of cellular composition, and neuronal architecture, but with the ability to manipulate, sample and live image the slices. This is achieved through placing hippocampal slices from 7 day old mice into culture on membrane inserts – these are then able to survive for up to two months. Furthermore, this removes the problem of confounds due to inflammatory responses in acute studies. In transgenic (versus wild-type) mouse cultures, they were able to see progressive amyloid growth, associated with depletion of presynaptic proteins. No fibrillar plaques were seen, suggesting that these are not needed for synaptic disruption. This talk was especially interesting, as it relates to the work of Luca Biasetti, another 1st year PhD student in the Alzheimer’s Society Doctoral Training Centre. Luca is using the same model, but with rat brain slices.

 

In addition to the very interesting research that was presented, the most useful thing about the PhD day was probably being able to see the level that other PhD students were working at (at their respective PhD stages), speak with students in similar areas of research, and compare notes on the PhD process with those in more disparate fields. This was both confidence boosting, and reassuring. Generally, this was a very interesting and informative day.

 

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Bake-Off Win at the Life Science Impact Day

Professor Louise Serpell, co-Director of the Alzheimers Society DTC and
the Dementia Reseearch Group won second prize at the Life Sciences Impact
Day Bake-off with this wonderful Neuron Cake!

Her kids ate most of the mitochondria…

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Ageing Speciality Research Group Meeting

Four members of the lab group attended the regional meeting of the National Institute for Health Research this week. Talks covered a wide range of topics including the importance of involving patients and the general public in the design of clinical research, an introduction into health economy, and an insight into the clinical trials being ran nationally at the moment. Rebecca Atkinson, Rachel Clarke and Claire Lancaster all presented posters of their research, with many congratulations going to Rachel for winning the prize of best poster!

To view the posters, please click the links below.

Attention changes in the early stages of memory change- Claire Lancaster

Cognitive advantages in young e4-carriers-The when, why and when: Rebecca Atkinson

Work and life balance among working family carers of a person with dementia-Rachel Clarke

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Rachel Clarke on Beginning my PhD…

I have been lucky enough to secure a studentship which started at The University of Sussex in September. It is linked to my previous role on the IDEAL study – Improving the Experience of Dementia and Enhancing Active Lifeliving well with dementia (http://www.idealproject.org.uk/). The IDEAL study is a five year study which began in early 2014 and is recruiting a sample of 1500 participants with dementia and 1000 caregivers to explore what it means to live well with dementia from the perspective both of thes person with dementia and the carer, collecting data over three time points. The IDEAL study is analysing quality of life, well being and satisfaction with life through a series of quantitative assessments. My PhD will be using a mixed methods data analyses to explore the work-life balance of employed caregivers from the IDEAL study. In addition to analysing data that has already been collected, fieldwork will principally consist of a single interview with a sample of around 50 participants, and will explore the challenging and positive aspects of combining caring with employment, how employers are facilitating this process and what employment legislation can do to improve this process. This study will enhance the dataset by adding a new component which assesses the effect of work life balance outcomes on carers’ cognitive function, including memory and attention. Findings from this study will also inform policy makers who develop programs to assist caregivers who are juggling multiple roles.

I am very excited to be part of an absolutely fascinating, topical area of research and a major project generally which will contribute to dementia research for a long time. I’m also looking forward to the process of completing the PhD which will give me the chance to stretch my skill-set by integrating psychological, cognitive and sociological perspectives, and the opportunities this PhD will present following completion. And so it begins…..

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Dan Goodwin: Junior Research Associate

Before applying for the JRA award I knew that becoming a researcher in Psychology was what I wanted to do, but deciding what I wanted to study seemed almost impossible given the sheer number of options available. When I saw that Sussex was offering JRA awards focusing on the causes and cures for Alzheimer’s I jumped at the opportunity, as I felt this would give me a good opportunity to explore a more neuroscience-based research project which greatly interested me. Professor Jenny Rusted was advertising JRAs in the newly established Alzheimer’s Society Doctoral Training Centre and it was with her I worked closely on my application; Prof Rusted was incredibly approachable and supportive throughout the application process, assisting me right from the start.

During the summer I got involved in an ongoing research project aimed at investigating the neural and behavioural consequences of a gene, APOE-E4, widely accepted to be the strongest genetic risk factor for Alzheimer’s disease. I assisted Dr Simon Evans, a postdoctoral fellow in Prof Rusted’s lab, in analysing data and writing a literature review on the use of the subsequent memory paradigm in research examining the neural consequences of ageing and APOE-E4. The subsequent memory paradigm involves participants being incidentally (unintentionally) exposed to words whilst completing an ongoing task in an MRI scanner, followed by a surprise recognition test in which participants indicate whether they had seen the words previously or not. This task is designed to induce episodic memory and activation in the hippocampus, an area implicated in the premature neural ageing seen in carriers of APOE-E4.

The analysis of the data itself proved to be a rewarding experience as it allowed me to gain extremely valuable knowledge with MRI data analysis software such as MATLAB and SPM. Immersing myself in the data for several weeks increased my personal investment in the project and the data itself, this gave me a hunger and excitement that was certainly lacking in my first and second years at university, as I felt I was genuinely contributing to something that would make a difference. Happily, the results of the analysis also proved very interesting; results from the MRI analysis indicated that APOE-E4 carriers were consistently underactivating several regions in the brain, relative to non-carriers, throughout the task. APOE-E4 carriers demonstrated significantly less activation in frontal, temporal, and parietal regions in the brain; these areas have been reported many times before in the literature to exhibit genotype differences with APOE-E4 in a number of cognitive domains. Surprisingly, we were unable to extract any genotype differences in hippocampal activation; this is not unusual – the hippocampus is such a small area in the brain, and so it can be difficult to pull out reliable data. Taken as a whole, the results suggest that APOE-E4 carriers may be more efficiently processing memories and information, as they retained equal memory performance to non-carriers in the face of lesser neural activation.

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Diary of a Sussex University Junior Research Associate: Research using PARO – a robotic seal – with people with dementia

26/06/2015

My first day. Visited the Dementia unit in Sussex Partnership NHS Foundation Trust to see PARO for the first time. Really exciting – I was instantly drawn to it’s eye movements and the way it reacted to me when I stroked it. I believe it had a therapeutic effect on me because I felt relaxed and watching it put a smile on my face! It was also nice seeing how the other members of staff acted around it. It was like having a pet in the room everyone was smiling and saying how cute it is.

Observed a ward round where different members of the multidisciplinary team (psychiatrist, specialist pharmacist, nurse, occupational therapist and assistant manager) worked together as a team. They decide the best plan for different patients starting from their medication to whether it’s okay to discharge them. This ward round was different to ones I had seen before because it didn’t involve going around the ward to talk to patients. In addition, as we went through the list of individual patients in all of them it was either the family member, nurse or social worker that was there to represent the patient and not the patient themselves. This to me was an invaluable insight into how things work in a dementia care setting.

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29/06/2015

Attended a meeting with the Care Home in Reach team. The team’s role is to provide advice, information and training for care homes that provide care to older people.

Shadowed a specialist pharmacist. Patients with severe dementia often are given drugs to manage their behaviour like agitation and aggression. Therapeutic measures that involve activities like music and colouring would be better because these drugs come with side effects leading to more drugs being prescribed in order to treat these side effects. I thought – this is where PARO could come in: a non-pharmacological intervention, no unpleasant side effects to it, some people may not be into colouring or music so PARO could be a good alternative to that.

Visited a nursing home and I had the chance to listen to some training that was going on about how to communicate to people with dementia.

Observed the pharmacist do a medication review of the patients in the home. I was amazed by the vast amount of medication all the patients were on.

Day 2(26/06/2015) at Dementia unit.

Met with the research team (Dr Dodds, a clinical psychologist, two occupational therapists (OTs) and a Masters student). We discussed who I would interview and how.

Observed one of the OT interact with a resident using PARO. I could see an immediate positive reaction as the resident stroked PARO and talked to him. This lady was once a health visitor and was gentle with PARO. She sometimes had a doll to care for. Another lady was quite restless but happy to have PARO on her lap. Another lady was asleep but woke up and was happy to receive PARO with her arm outstretched. She talked about her cat being “cat with colours” but found PARO heavy so she gave him back.

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29/06/2014Monday

Met with my supervisor Prof Rusted and my mentor Molly discussed how I would achieve my thematic analysis. Later that day, attended JRA launch where I had the opportunity to meet and talk other JRA students and learn about the projects they were doing.

03/07/2015

Went to a second Dementia Unit with OT to have a PARO session with the residents there. Interviewed OT for my PARO project. Observed PARO session. The first patient was visually impaired but could hear the sounds that PARO made. She talked about pets and joked that with Paro there was no mess to clear up. Another patient seem very relaxed when holding PARO and she talked to PARO and the other members of the group.

Interviewed 3 more people: the nursing assistant, another OT and a psychology graduate interning at the unit.

10/07/2015.

Met the OT at Dementia unit for a group session with PARO. We had two patients one male and another female that both showed interest in PARO but none of them were willing to interact with him. Another Patient that was male responded very well to PARO he stroked him and kissed him. It was very touching watching the gentleman interact with PARO you could see the emotion when he was engaging with PARO. He treated him as though PARO was real and he kept say “he’s beautiful”. I was moved to see how happy he was with PARO. It just shows the impact that PARO has on the emotional states of people. Had a one to one session with a patient who had hearing loss. This lady is usually alone in her room and doesn’t go out that much. We communicated to her through writing and signs. She responded very positively stroking PARO and we had conversation about pets. She was very happy that we came to see her. The next patient used to be a and was more interested in the technology side of PARO. He kept asking questions about how and where it’s made. Even though he passed on holding PARO he still found him intriguing. This shows you don’t need to interact directly with PARO in order for it to have its effect on increasing social interactions. I noticed that when PARO was brought to the lounge it became a common topic of conversation between both staff and residents. The lounge became a bit livelier with more people talking to each other; it was nice to see that.

17/07/2015

Went to Dementia unit and spent the day with masters student and we worked on thematic analysis of the interviews that I had transcribed and the reflection forms written by the nurse and OTs from each PARO session they did. I initially didn’t have any experience of doing a thematic analysis so working with her make made it easy because I was learning from practising it with her. We worked on coding the transcripts and using the codes to develop themes.

20/07/2015.

Met with Dr.Penny Dodds at Brighton University and I told what I have been doing that week and some interesting themes that were coming out of the thematic analysis. We started the process of creating a mind map and a spread sheet from the codes I had extracted from the interviews and the reflections form done by the OT.

24/7/2015

Went to Dementia Unit for another PARO session with patients. Most of the patients who interacted with PARO stroked him. PARO got staff members to talk about him. SO again, the seal helped communication for both patents and care staff in different ways.

30/07/2015

We had a JRA get together which involved a speed date, barbecue and quiz. The speed dating isn’t actually dating but more about finding out about what other people’s projects are about. There was lots of drinks and my team lost on the quiz but it was great fun. It was a good opportunity to meet new people and I learnt quite a bit from the quiz.

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31/07/2015

More thematic analysis work and another group PARO session to observe. Our last patient was deaf so we went to her room and did a one to one session. We wrote down everything for her. She seemed happy to see PARO but didn’t want to hold him saying she doesn’t like to cuddle. We did a lot of laughing and she talked about her love for art and crafts.

04/08/2015.

Workshop day: It was an early start. Helped Dr Dodds (Penny) to arrange the place for the workshop. Went to Dementia unit to do my last interview on the OT. The workshop was for a group of practitioners involved in dementia care – people from Derbyshire and Coventry NHS care who were interested in learning more about PARO’s use and wanted to introduce PARO into their care homes. The people from Derbyshire were interested on how they could use PARO to decrease their falls rate at their care home. There was discussions about one of the biggest challenges at the moment of introducing PARO in NHS setting which is Infection Control. And one of the ladies from Derbyshire mentioned how they have lambs and farm animals come in their ward in Derbyshire because the residents there were farmers. At the end of the day the group came up with ideas on how they can move forward and gave their thoughts on what they have learnt and suggestions on how to improve.

7/08/2015

Went to Dementia unit but it was busy that day and the OT had to sort out fencing around the facility. I talked with the administrator for a short while. The OT came back and we began the PARO session. At the end of the session I talked to the OT while she filled in a PARO reflection form. She told me what her day is like and what her job involves.

13/08/2015.

Attend an Alzheimer Society Doctoral Training Centre tea party at Sussex University. I had the chance to meet other students researching on dementia and learn about their projects, and also people who were caring for family members with dementia. Penny brought PARO over and everyone was excited to see it. I got asked lots of questions about it which was good because I knew quite a lot about PARO because I had spent the past weeks living and breathing PARO.

17/08/2015

I did a presentation at my supervisor Jenny’s lab meeting. I was so nervous but it went well. I spoke about what PARO is, the research behind it and the process of thematic analysis, how I came up with the codes and the themes that emerged from it. I was given ideas on how I should go about making my poster. This is my last challenge after a summer research experience that gave me a taste of what a career in research is like.

 

 

 

 

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Reflections of a research assistant: Getting to Grips with Prospective Memory

I am a third-year medical student, currently visiting the Rusted lab group from Brazil to complete a summer research assistantship. As my goals are to become a clinical physician, working in the field of behavioural research is an area I never expected to participate in. For the past 3 years I have been busy studying the physiology of the human body, disease pathology and how best to treat the sick.. This summer, I have adopted a completely different psychological perspective through which to study the ageing brain and dementia.

 

During my summer internship I have been involved with an ongoing research project investigating how a genetic risk factor for Alzheimer’s disease alters cognition earlier on in the lifespan. I have been working with Claire Lancaster, a PhD student in the Rusted lab, from who I have learnt a lot. In particular, I have had a opportunity to dip into a behavioural genetics study and explore how our genetic make-up can influence cognition, in particular focusing on the APOE gene, a risk factor for dementia.

 

As part of my assistantship, I have analysed a subset of data collected from 31 healthy volunteers, aged 45-55 years old. Performance on a measure of prospective memory, meaning the ability to remember to act on an earlier formed intention, was compared across participants divided according to their genetic status. Specifically, this task asked individuals to remember to perform a certain action when presented with a specific card, while they were busily engaged in a response time card-sort challenge.

 

It was a challenge for me to extract the accuracy and response time data onto a spreadsheet and analyze it using SPSS, a software package I had never opened before nor had expected to use before my fifth year graduation. Performing the analysis was exciting as I sought to uncover how storing an intention in mind altered task performance, and whether carrying the risk variant of the APOE gene altered performance. As expected, holding the prospective intention in mind reduced response times across the board in the card sort task, suggesting the experimental manipulation worked. Disappointingly, however, no difference in accuracy or response times was found across the three groups of genotypes. My work was a pre-analysis with a smaller sample than the 80 volunteers expected to take part, and so perhaps more exciting results will emerge by the end of the summer. By looking at the data, it appears volunteers carrying the genetic risk variant trended towards being quicker but less accurate in their responses, which would certainly be a point for discussion!

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Recruitment day at the Jubilee library , Brighton

I cannot describe all the knowledge that I, as an undergraduate student, can absorb from this opportunity. Weekly lab meetings with Jenny Rusted and post graduate students keep me interested and open-minded to new avenues for learning. I have also been busy recruiting volunteers, running experimental sessions and reading classical and up to date papers in the field of behavioural genetics. And all that after having moved from a completely different culture, away from my friends and family, into a very distinct teaching method… and all in a non-native language for me! I still have one month of the assistantship before I return to Brazil, my home country. I mean, I only have 4 weeks of learning with these extraordinary people, and I really want to make the most of this opportunity.

 

By Juliana Burgardt

 

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Reflections of a Research Assistant

Screen shot 2015-07-01 at 14.19.21It is the best of times, it is the worst of times. For six years the University of Sussex has been my home, but now I must leave and start a new chapter in my life. This bittersweet new beginning would not be possible without my time as a research assistant in Jenny Rusted’s lab.

I first met Jenny as a third year undergraduate; a student in her Psychobiology of Ageing and Dementia course. She was instantly approachable and friendly. Throughout this year and my masters degree she was very supportive and encouraging with my aspirations for a career in research. When I finished my masters and I failed to get accepted onto a PhD, Jenny offered me a position as an RA within her lab to help boost my CV and give me experience I desperately needed.

The year and a half I spent in the lab was the best work experience of my life. Not only did it develop my skills as a researcher, but helped me grow as a person. I remember my first lab meeting, being introduced to everyone who would one day become my friends. Their names and area of research were forgotten the moment I heard them. I thought I had no place there. I thought a mere RA has no valuable input in a room of PhD students and postdocs. As the weeks went by however, I learned I did in fact have something worthwhile to add. My courage grew and I would occasionally contribute an astute point.

My time in this lab prepared me for PhD life in ways I didn’t know I needed preparation. From talking to and overserving my colleagues I got a better idea of what PhD life was like. I had my dissertations and some previous research experience under my belt, but the average undergraduate experience does prepare anyone for everything else that comes with the academic lifestyle. One of the most exciting aspects of the RA position was the weekly meetings. It prevented my wits from dulling. Listening to the scintillating discussion of a variety of topics kept my critical analysing skills in use during my time out of education.

Unfortunately now my time in the lab and at the university has come to an end. It is time to say “Goodbye Sussex” and “Hello Southampton” as I start my own PhD studentship in a couple of months. Everyone in the lab (and a lot of people at Sussex in general) has either directly or indirectly played a small or large part in getting me into my position today. The experience and skills I acquired as a RA has been instrumental in getting onto my own studentship. I would therefore like to take this opportunity to thank everyone for their involvement.

As Aeneas left his beloved Ilium after it was sacked by the Achaeans only to go on and be the catalyst for the foundations of Rome, I too am leaving my beloved Sussex for greater and better things.

 

By Carl Buckfield

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