Magnetic Resonance Imaging (MRI) is the most prominent non-invasive technique used in clinical diagnosis and biomedical research. Its development as an imaging technique has been aided by contrast agents (CAs) which enhance contrast to noise ratio in the images. This dissertation deals with paramagnetic lanthanide- and superparamagnetic iron-based nanoparticles (NPs) which are potential CAs at clinical field of 3 T and a high field of 9.4 T. Chapter 1 provides a brief overview of colloidal nanoparticles, with an emphasis on their surface chemistry and magnetic properties for bio-applications. Chapter 2 employs europium as an optical probe to illustrate the contribution of inner, second and outer sphere relaxation towards longitudinal and transverse relaxivities of paramagnetic NP-based CAs. Chapter 3 investigates the positive and the negative contrast enhancement abilities and magnetization of paramagnetic NPs comprising a core of sodium dysprosium fluoride with a sodium gadolinium fluoride shell. Their surface chemistry is tuned to target prostate cancer specifically. The application of these NPs is further extended in Chapter 4 to track an intraneuronal protein called tau following mild traumatic brain injury. Chapter 5 deals with facile synthesis and long-term stability of superparamagnetic iron NPs for their potential application as CAs. Chapter 6 illustrates the concept of MRI correlation using ‘T1-only’ and ‘T2-only’ NPs. Chapter 7 investigates on the dynamics involved in the phospholipids coating the surface of NPs. Chapter 8 concludes on the work detailed in the previous chapters and outlines the future outlook. / Graduate / 2020-01-15

In the last decade, traumatic brain injuries (TBIs) and spinal cord injuries (SCIs) has become one of the most scrutinised medical challenges of our time. However, the lower quality of life experienced by the sufferer and the associated socio-economic cost of both TBI and SCI remain a huge burden for society. There is currently no reliable way to evaluate the level of functional damage caused by TBI and SCI related mechanical forces without invasive examination. The types of axonopathy involved in such injuries are the combinations of coupled mechanical-electrophysiological phenomena at multiple length and time scales, extremely challenging to approach by experimental means alone. It is therefore highly desirable to complement experimental studies with computational work to further the understanding of such multiscale problems. This thesis firstly proposes a novel 3D finite element framework coupling mechanics and electrophysiology to model cellular and subcellular phenomena, such as nerve dislocation and membrane damage by micropipette. The former study shows that 1D simulations focussing solely on the stretch component of the axonal damage are unable to capture the same electrophysiological damage that a 3D framework predicts. The latter study shows that local membrane deformation can lead to electrophysiological alterations at the axonal level solely through geometrical effects and without the need to account for ion channel activity alterations. This was demonstrated for micropipette suction in a patch clamp where the consideration of the 3D flow of current was sufficient to alter its electrophysiology, offering an alternative explanation to the damage mechanism hypothesised by published experimental work. At the axonal and tissue scale, previous models have often simplified the modelling of damage by using a single axon model. It is however unclear whether an altered axonal electrophysiology can truly be representative of the compound electrophysiology of multiple axons or fibre. Three different models: axonal, fibre and tissue level models, were evaluated and compared for their ability to model macroscale electrophysiology deficits. The results of the three models suggest that the recovery of compound action potential amplitude post-mechanical stretch can not be straightforwardly scaled from axonal level to fibre level. Furthermore, the electrophysiological recovery may not be solely dependent on mechanical recovery of the tissue. This thesis identified the need for scale specific models in the context of TBI and SCI. In particular, lipid bilayer membrane geometrical distortion following mechanical insult at the subcellular scale and functional tissue alteration at the tissue scale both require a different approach. The models proposed herein successfully identify mechanisms overlooked in previous experimental literature. In order to fully capture experimental behaviour, future models will need to account for other mechanisms such as mechanoporation, reorganisation of paranodal junctions and injury related Calcium ion imbalance.

Wearable assistive robotics have the potential to address an unmet medical need of reducing disability in individuals with chronic hand impairments due to neurological trauma. Despite myriad prior works, few patients have seen the benefits of such devices. Following application experience with tendon-actuated soft robotic gloves and a collaborator's orthosis with novel flat-spring actuators, we identified two common assumptions regarding hand orthosis design. The first was reliance on incomplete studies of grasping forces during activities of daily living as a basis for design criteria, leading to poor optimization. The second was a neglect of increases in muscle tone following neurological trauma, rendering most devices non-applicable to a large subset of the population. To address these gaps, we measured joint torques during activities of daily living with able-bodied subjects using dexterity representative of orthosis-aided motion. Next, we measured assistive torques needed to extend the fingers of individuals with increased flexor tone following TBI. Finally, we applied this knowledge to design a cable actuated orthosis for assisting finger extension, providing a basis for future work focused on an under-represented subgroup of patients.

BACKGROUND: Although concussion and sport-related traumatic brain injury is being acknowledged as a major public issue, especially in professional football players, current study is mostly limited to retrospective studies and post-mortem autopsies. The purpose of this study is to identify a potential association between concussion and neurodegenerative disease in athletes, and propose a prospective approach of studying concussion and its effect. METHODS: A total of 26 studies related to concussion in athletes and published after January 2000 were collected from PubMed and Google Scholar. More recent papers with higher citation counts were given the priority. RESULTS: Retired professional football players showed five times greater risk for mild cognitive impairment, three times greater risk for memory loss, and four times greater risk for amyotrophic lateral sclerosis and Alzheimer disease. Autopsy results from football players also revealed findings consistent with chronic traumatic encephalopathy. Population with the Apolipoprotein E (APOE) promoter G-219T TT (Thymine-Thymine) genotype showed increased susceptibility for concussion. CONCLUSION: This study revealed that a history of concussion has statistically significant associations with high incidence of neurodegenerative diseases in professional athletes. In addition, the results suggest the 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitril(FDDNP)-positron emission tomography tau binding patterns and the APOE promoter G-219T TT genotype provide a new approach to study and monitor the progression of neurodegenerative conditions in athletes.

Consolidated memories can become reactivated in order to permit the integration of new information into the memory trace. Blockade of the resultant process, reconsolidation, with NMDA receptor antagonists or protein synthesis inhibition can lead to a decrease in subsequent memory expression. This may offer a potential tool for the treatment of psychiatric disorders characterised by maladaptive memories, including drug addiction and post-traumatic disorder. Given the importance of instrumental associations in supporting drug addiction experiments in Chapters 3 & 4 aimed to disrupt reconsolidation of these memories. Treatment with an NMDA receptor antagonist prior to retrieval sessions of various durations was not able to consistently prevent reconsolidation of these associations. Drug addiction is characterised by memories that have been formed not over days or weeks, but months or years. Experiments in Chapters 5 & 6 therefore investigated how the extent of training affects the propensity of an appetitive pavlovian memory to reconsolidate. Experiments in Chapter 5 were not able disrupt reconsolidation of these memories after a relatively short period of training. In Chapter 6 attempts to disrupt reconsolidation of a cocaine-seeking memory having undergone extensive training (>1 month, designed to promote the formation of drug-seeking habits) were also unsuccessful. However, when animals were trained in a similar fashion to respond for a food reinforcer treatment with a NMDA receptor antagonist prior to a reactivation session resulted in a decrease in food-seeking behaviour the following day. However, this deficit was only found in the first test session; drug treatment had no effect on responding following reminder of the memory. If data from preclinical studies are to inform future psychiatric treatments the findings from these works must be robust and replicable. Experiments in previous chapters encountered several issues in this regard, namely the repeated inability to prevent reconsolidation with NMDA receptor antagonism. Given that reconsolidation of auditory fear memories is well characterised a final series of experiments in Chapter 7 used this procedure to explore the possible reasons for the fleeting or absent effects of disrupted memory reconsolidation in previous chapters. Despite the use of similar methods as published reports showing decreases in memory expression as a result of blockade of reconsolidation it was not possible to disrupt this process with NMDA receptor antagonism or protein synthesis inhibition. Results suggested that the failure to observe reactivation-dependent amnesia was due to the amnestic agent used not being able to prevent reconsolidation, should it be taking place, and a failure of the given retrieval trial to result in memory reactivation. On numerous occasions throughout this thesis it was not possible to disrupt memory reconsolidation. One difficulty in interpreting null data of this nature is that it is often unclear whether the results are due to insufficient retrieval conditions to result in memory reconsolidation, or an inability of the pharmacological agent to disrupt this process. The final experiments of this thesis raised the possibility both of these issues may have contributed in tandem towards this inability to prevent memory reconsolidation.

Este trabalho apresenta pesquisa que busca, por meio da produção de autobiografias por alunos de sexto ano, possibilitar reflexões sobre trajetórias de vida, bem como desenvolver noções do trabalho do historiador, em especial o uso de fontes históricas. Para atingir este objetivo, promoveram-se encontros com os alunos nos quais se desenvolveu a caracterização das escritas de si, principalmente as autobiografias. Posteriormente o trabalho apresentou aos alunos informações sobre fontes históricas e buscou-se instrumentalizá-los para o uso de memórias, fotografias e relatos orais para a confecção de seus escritos. Autores como Gomes, Lejeune, Ricoeur, Freud, Selligmann-Silva, entre outros, foram essenciais para orientar e analisar as produções feitas. No relato destas vidas, imaginava-se o encontro de recordações traumáticas, em um número elevado, o que não se concretizou quando se iniciou a leitura das produções. A riqueza de situações apresentadas pelos trabalhos justifica o uso das autobiografias para percepção de trajetórias de vida e para o ensino de fontes históricas. / The present work introduces research that aims, using the production of autobiographies by students of the sixth year, to enable reflections on trajectory of lives, as well as develop notions of the work of the historian, specially the usage of historical sources. To reach this objective, meetings with the students were promoted in which the characterization of the self writings were developed, mainly the autobiographies. Then the work presented to the students information about historical sources and, aimed to give them instruments to the usage of memories, photography, and oral reports to the making of their writings. Authors such as Gomes, Lejeune, Ricoeur, Freud, Selligmann-Silva and others were essential to guide and analyze the productions that were made. In the report of these lives, it was thought to find many traumatic memories, which was not confirmed once the reading of the productions began. The richness of situations presented by the works justifies the usage of autobiographies to realize the trajectory of life and to the teaching of historical sources.

I och med den utvecklade tekniska utrustningen överlever allt fler patienter som drabbats av trauma. Därför är det stor sannolikhet att vårdpersonal under sitt arbete kommer i kontakt med dessa patienter. När vårdpersonalen är i kontakt med patienter som drabbats av trauma är det många gånger omöjligt att själv bli påverkad. Detta kan leda till att vårdpersonalen själva får liknande symptom som patienten. För att undvika framtida obehag är det av överordnad betydelse att vårdpersonalen har kunskap om att omhändertagande av traumatiska patientfall på arbetsplatsen kan komma att påverka vårdpersonalens egen kropp och psyke samt hur vårdpersonalen kan lära sig uppmärksamma dessa symptom. Syftet med uppsatsen är att med hjälp av Evans (2003) metod för att analysera kvalitativa artiklar beskriva vårdpersonalens upplevelser av att utsättas för traumatiska händelser på arbetet. Resultatet består av tre huvudteman. Den första behandlar upplevelser av att vara i kaos, med underteman: upplevelser av triggers som utlöser stress, upplevelser av att känna moralisk plikt, upplevelser av övergivenhet samt upplevelser av att inte räcka till. Tema två berör att reagera på den traumatiska händelsen och behandlar att märka av somatiska och psykiska symptom, upplevelser av att bli alltför personligt involverad, upplevelser av skam och skuld samt att distansera sig. Tredje temat berör att bemästra den traumatiska händelsen och handlar om strävan att upprätthålla balans i livet. Resultatet visar att vårdpersonalens upplevelser stämde bra överens med aktuell forskning, att det finns ett stort behov av att bearbeta traumatiska händelser samt arbetsgivarens möjlighet att fånga upp vårdpersonalen innan de mår alltför dåligt. / <p>Program: Sjuksköterskeutbildning</p><p>Uppsatsnivå: C</p>

På många intensivvårdsavdelningar skrivs det dagbok för patienten. Dagboksskrivande på intensivvårdsavdelning är dokumentation av vårdtiden skrivet till patienten av sjuksköterskor och annan vårdpersonal och i vissa fall närstående. Intensivvårdsavdelningen är en tekniktät miljö som kan upplevas skrämmande och stressig för patienten, vård på intensivvårdsavdelning kan orsaka posttraumatisk stress syndrom efter vårdtiden. Forskning visar att dagboken tillsammans med uppföljningsverksamhet efter vårdtiden på intensivvårdsavdelningen kan minska risken för utveckling av post traumatisk stress syndrom. Syftet med studien var att beskriva innehållet i patientens dagbok från vårdtiden på intensivvårdsavdelningen. Den vetenskapliga ansatsen är kvalitativ där datainsamling har skett genom insamling av totalt sju patientdagböcker från fyra olika sjukhus i Sverige. Analysmetoden kvalitativ innehållsanalys användes. Resultatet presenteras i 16 underkategorier och fem kategorier. Resultatet visar att innehållet i dagboken handlar om orsak till patientens sjukdomstillstånd och behandling, förändringar i andningen, patientens kommunikation, hälsofrämjande aktiviteter och beskrivningar av omvärlden. Kategorierna har sammanförts till ett tema där dagbokens innehåll ses som en verklighetsbeskrivning genom dialog grundad på uppmuntran och hopp. / Program: Specialistsjuksköterskeutbildning med inriktning mot intensivvård

This study compared the Children’s Depression Inventory (CDI) scores of traumatized youth with or without PTSD to the scores of a nonclinical comparison group. Diagnostic interviews identified children with PTSD (28), traumatized PTSD negatives (64), and a nonclinical comparison group (41). In the absence of major comorbid disorders, the CDI scores of children and adolescents with PTSD significantly exceeded the CDI scores of traumatized PTSD negatives and controls on the CDI Total, Negative Mood, Ineffectiveness, and Anehdonia scales. The PTSD group also had significantly higher scores than the traumatized PTSD negatives on the Negative Self Esteem scale. Furthermore, as hypothesized, the CDI scores of the traumatized PTSD negatives and controls were not significantly different on any of the six subscales measured. On the other hand, there were three unexpected nonsignificant findings. First, the PTSD group mean CDI Interpersonal Problems score did not significantly differ from the traumatized PTSD negative group. Second, the PTSD group mean CDI Interpersonal Problems score also did not significantly differ from the control group. Finally, the PTSD group mean CDI Negative Self Esteem score did not significantly differ from the control group. Overall, PTSD was associated with increased depression across the majority of the CDI scales and trauma exposure without PTSD was not. Implications for research and practice are considered.

The present study was conducted to help understand the impact of living with multiple sclerosis (MS), an unpredictable, chronic illness that is widely known to have a large influence on psychosocial functioning, mental health, and life satisfaction (Motl & Gosney, 2007; Weiner, 2004). Recent research has begun to position certain chronic illnesses, such as MS, as traumatic events that influence mental health in both beneficial and detrimental ways. Thus, the present study investigated the positive and negative consequences of centralizing one’s identity within their MS experiences as related to trauma, growth, and psychosocial influences via a path model with 616 individuals with MS. The results indicate strong support for the hypothesized paths between the variables of interest—centrality of MS, posttraumatic stress, posttraumatic growth, social support, personal mastery, depression, and life satisfaction. Specifically, results indicate that posttraumatic stress and posttraumatic growth partially mediated the relations between centrality of MS with depression and life satisfaction. Moderation analyses indicated that social support and personal mastery did not moderate any relations between centrality of MS with depression and life satisfaction. Rather, additional analyses suggest social support and personal mastery may be viewed as additional mediators between centrality and posttraumatic stress and posttraumatic growth. The results of the present study is the first known study to extend trauma literature to the population of MS in order to provide an approach to help understand the high rates of depression and inconsistent findings on quality of life for this population. Implications for practice, theory and research are discussed.