Acute Management of Minor Head Injury

Minor head injury (MHI) is a major socioeconomic and health burden throughout the world. However, many controversies exist about the best acute management. In this thesis the extent of practice variation in acute management of MHI at the emergency department is investigated. Because CT decision rules and guidelines play a crucial role in the acute management of patients with MHI, this thesis focused on how these CT rules could be improved

Regulation of immune responses in atherosclerosis

Atherosclerose wordt veroorzaakt door een combinatie van verhoogde cholesterolniveaus en een chronische ontstekingsreactie. Deze ontstekingsreactie is het gevolg van een verstoorde balans tussen slechte, agressieve en goede, beschermende ontstekingscellen. In dit proefschrift wordt onderzocht hoe deze verstoorde balans in atherosclerose hersteld kan worden. Het onderzoek richt zich hierbij enerzijds op het remmen van de slechte ontstekingscellen en anderzijds op het stimuleren van de goede ontstekingscellen. Dit kan bereikt worden door de werking van costimulatoire en coinhibitoire eiwitten te be_nvloeden. Deze eiwitten zijn aanwezig op het celoppervlak van heel veel verschillende ontstekingscellen en bepalen of een ontstekingscel agressief of beschermend is. Costimulatoire eiwitten zorgen voor de activatie van een ontstekingscel, terwijl coinhibitoire eiwitten ontstekingscellen remmen. Blokkade van de costimulatoire eiwitten OX40L en CD30L remt atherosclerose, terwijl blokkade van het coinhibitoire eiwit Tim-3 atherosclerose verergert. Stimulatie van het coinhibitoire eiwit TIGIT vermindert de functie van T cellen. Een andere manier om de balans tussen goede en slechte ontstekingscellen te herstellen is door het aantal goede ontstekingscellen, zoals regulatoire T cellen en myeloid derived suppressor cellen, te laten toenemen. Eliminatie van regulatoire T cellen tot meer atherosclerose, terwijl een enorme expansie van regulatoire T cellen en myeloid derived suppressor cellen beschermend is.De Nederlandse Hartstichting, Universiteit Leiden, J.E.Jurriaanse Stichting, Special Diet Services (Tecnilab-BMI), Greiner Bio-One, BD BiosciencesUBL - phd migration 201

THE SOCIOLOGICAL IMAGINATION OF THE BRITISH NEW LEFT: “CULTURE” AND THE “MANAGERIAL SOCIETY,”<i>C.</i>1956–1962

Castigated as theoretically naive by Perry Anderson, or praised as culturally sensitive by later writers, the political thought of the “first New Left” has often been understood in relation to F. R. Leavis's cultural criticism. This article seeks to reframe the writings of E. P. Thompson, Stuart Hall, Charles Taylor and Alasdair Macintyre from this period as interventions in a fundamentally sociological debate about the nature of capitalism in the managed economy of postwar Britain.Writing this article was made possible by support from the Cambridge Arts and Humanities Research Council Doctoral Training Partnership

Adaptive immunity and atherosclerosis: aging at its crossroads

Adaptive immunity plays a profound role in atherosclerosis pathogenesis by regulating antigen-specific responses, inflammatory signaling and antibody production. However, as we age, our immune system undergoes a gradual functional decline, a phenomenon termed "immunosenescence". This decline is characterized by a reduction in proliferative naïve B- and T cells, decreased B- and T cell receptor repertoire and a pro-inflammatory senescence associated secretory profile. Furthermore, aging affects germinal center responses and deteriorates secondary lymphoid organ function and structure, leading to impaired T-B cell dynamics and increased autoantibody production. In this review, we will dissect the impact of aging on adaptive immunity and the role played by age-associated B- and T cells in atherosclerosis pathogenesis, emphasizing the need for interventions that target age-related immune dysfunction to reduce cardiovascular disease risk.Biopharmaceutic

Thyroid hormones as potential prognostic factors in sepsis

Background: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host reaction to infection. There is an upward trend in sepsis prevalence and mortality worldwide. Sepsis causes hypoxia, which reduces the ability of cells to produce ATP. This process is also influenced by thyroid hormones. Some of the previous studies revealed association between the mortality rate in sepsis and thyroid hormone levels. We aimed to evaluate thyroid hormones’ predictive value in septic patients. Methods: Forty-nine adult patients with sepsis admitted to the Intensive Care Unit of Allergy and Immunology Department at the University Hospital in Krakow, Poland, between 2015 and 2017 were enrolled in the study. Blood samples were obtained from septic patients immediately after establishing the diagnosis, in order to measure free triiodothyronine (fT3), free thyroxine (fT4), and thyroid-stimulating hormone (TSH) levels. The primary endpoint was 30-day survival rate. The secondary endpoint was death anytime during intensive care unit (ICU) stay. Results: Patients who died within 30 days had significantly lower level of fT4 than survivors (9.8 vs. 12.7 pmol L-1; P = 0.033). There was no statistically significant difference between the groups in TSH and fT3 levels. As for the secondary endpoint, both fT3 (1.6 vs. 1.8 pmol L-1; P = 0.021) and fT4 (9.8 vs. 12.7 μIU mL-1; P = 0.019) levels were significantly lower among non-survivors compared to survivors, which was not the case for TSH. Conclusions: Thyroid hormone levels were significantly lower among patients who died during ICU stay. The results of the presented study suggest that fT3 and fT4 levels may be taken into consideration as potential new prognostic factors in sepsis

Nursing care for a patient after an ischemic stroke

Introduction and aim of the study. More than half of ischemic strokes occur above the age of 65, so a stroke is above all a disease of an old age. The problem of a stroke is crucial, because apart from a high mortality rate it also entails a disability. The aim of the study was to determine the scope of nursing care for the patient after an ischemic stroke. Methods and materials. The study was based on the case study method with the use of the following research techniques: documentation analysis, an interview, measurement and observation. Moreover, the study tools applied comprised: an individualized nursing care plan, Barthel Scale, Glasgow Scale, Dutch Scale, the authors’ own test examining the patient’s knowledge. Criteria for the care categories. Findings. After the interview, the biopsychosocial status of the patient was assessed. Nursing diagnoses were made using the empirical data for this purpose. Conclusions. The sudden occurrence of the disease, hospitalization and lack of support from relatives is a difficult and critical situation for the patient, and it disturbs normal functioning in all spheres: biological, psychological and a social one

Agonistic anti-TIGIT treatment inhibits T cell responses in LDLr deficient mice without affecting atherosclerotic lesion development

OBJECTIVE: Co-stimulatory and co-inhibitory molecules are mainly expressed on T cells and antigen presenting cells and strongly orchestrate adaptive immune responses. Whereas co-stimulatory molecules enhance immune responses, signaling via co-inhibitory molecules dampens the immune system, thereby showing great therapeutic potential to prevent cardiovascular diseases. Signaling via co-inhibitory T cell immunoglobulin and ITIM domain (TIGIT) directly inhibits T cell activation and proliferation, and therefore represents a novel therapeutic candidate to specifically dampen pro-atherogenic T cell reactivity. In the present study, we used an agonistic anti-TIGIT antibody to determine the effect of excessive TIGIT-signaling on atherosclerosis. METHODS AND RESULTS: TIGIT was upregulated on CD4(+) T cells isolated from mice fed a Western-type diet in comparison with mice fed a chow diet. Agonistic anti-TIGIT suppressed T cell activation and proliferation both in vitro and in vivo. However, agonistic anti-TIGIT treatment of LDLr(-/-) mice fed a Western-type diet for 4 or 8 weeks did not affect atherosclerotic lesion development in comparison with PBS and Armenian Hamster IgG treatment. Furthermore, elevated percentages of dendritic cells were observed in the blood and spleen of agonistic anti-TIGIT-treated mice. Additionally, these cells showed an increased activation status but decreased IL-10 production. CONCLUSIONS: Despite the inhibition of splenic T cell responses, agonistic anti-TIGIT treatment does not affect initial atherosclerosis development, possibly due to increased activity of dendritic cells

An investigation into local air quality throughout two residential communities bisected by major highways in South Auckland, New Zealand.

Population exposure to traffic pollution is a rapidly developing, multi-disciplinary scientific field. While the link between long-term exposure and respiratory issues is well-established, there are probable links to a number of more serious health effects, which are still not fully understood. In the interests of protecting human health, it is prudent that we take a cautionary approach and actively seek to reduce exposure levels, especially in the home environment where people spend a significant portion of their time. In many large cities, a substantial number of homes are situated on land immediately adjacent to busy freeways and other heavily-trafficked roads. Characterising exposures of local residents is incredibly challenging but necessary for advancing epidemiological understandings. While existing studies are plentiful, the results are mixed and generally not transferable to other urban areas due to the localised nature of the built environment and meteorological influences. This thesis aimed to employ a variety of methods to develop a holistic understanding of the influence of traffic emissions on near-highway residents' exposure in two communities of South Auckland, New Zealand, where Annual Average Daily Traffic (AADT) is as high as 122,000 vehicles. First, ultrafine particles (UFPs), nitrogen oxides (NOx), carbon monoxide (CO) and particulate matter ≤ 10 μm (PM₁₀) were continuously monitored using a series of fixed stations at different distances from the highways, over several months during the winters of 2010 and 2011. Emissions modelling output (based on traffic composition), was used within a dispersion model to compare modelled concentrations with monitored levels. In addition, community census meshblock units were mapped by level of social deprivation in order to assess potential inequities in highway emissions exposure. The second layer of local air quality investigation involved using a bicycle platform to systematically measure concentrations of UFPs, CO and PM₁₀ using the entire street-grid network throughout each community. This was done forty times - five times at four times of day (07:00, 12:00, 17:00 and 22:00), for each study area, with the aim of mapping the diurnal fluctuation of microspatial variation in concentrations. Using global positioning system (GPS) data and geographical information system (GIS) software, spatially-resolved pollutant levels were pooled by time of day and the median values mapped, providing a visualisation of the spatial extent of the influence of emissions from the highways compared to minor roads. The third layer involved using data from multiple ambient monitors, both within the local areas and around the city, to simulate fifty-four residents' personal exposure for the month of June, 2010. This required collecting timeactivity information which was carried out by door-to-door surveying. The time-activity data were transformed into microenvironment and activity codes reflecting residents movements across a typical week, which were then run through the US-EPA's Air Pollution Exposure Model (APEX). APEX is a probabilistic population exposure model for which the user sets numerous microenvironmental parameters such as Air Exchange Rates (AERs) and infiltration factors, which are used in combination with air pollutant concentrations, meteorological, and geospatial data, to calculate individuals' exposures. Simulated exposure outputs were grouped by residents' occupations and their home addresses were artificially placed at varying distances from the highways. The effects of residential proximity to the highway, occupation, work destination and commute distance were explored using a Generalised Linear Model (GLM). Surveyed residents were also asked a series of Likert-type, ordered response questions relating to their perceptions and understandings of the potential impacts of living near a significant emissions source. Their response scores were explored as a function of proximity to the highway using multivariate linear regression. This formed the final layer of this investigation into air quality throughout these South Auckland communities of Otahuhu and Mangere Bridge. Results show that concentrations of primary traffic pollutants (UFPs, NOx, CO) are elevated by 41 - 64% within the roadside corridor compared to setback distances approximately 150 m away and that the spatial extent of UFPs can reach up to 650 m downwind early in the morning and late in the evening. Further, social deprivation mapping revealed that 100% of all census meshblocks within 150 m either side of both highways are at the extreme end of the deprivation index (NZDep levels 8 - 10). Simulations for residents dispersed across the community of Otahuhu estimated daily NOx and CO exposure would increase by 32 and 37% (p<0.001) if they lived immediately downwind of the highway. If they were to shift 100 m further downwind, daily exposure would decline by 56 - 70% (p<0.001). The difference in individuals' exposure levels by occupation varied across the same distance by a factor of eight (p<0.05), with unemployed or retired persons the most exposed due to having more free time to spend outdoors at home (recreation, gardening, etc.). Those working in ventilated offices were the least exposed, even though ambient concentrations - likely due to a strong urban street canyon effect - were higher than the nearest highway monitor (5 m downwind) by 25 - 30% for NOx and CO, respectively. Inverse linear relationships were identified for distance from highway and measures of concern for health impacts, as well as for noise (p<0.05). Positive linear relationships were identified for distance from highway and ratings of both outdoor and indoor air quality (p0.05). The main findings within this thesis demonstrate that those living within the highway corridor are disproportionately exposed to elevated long-term average concentrations of toxic air pollutants which may impact on physical health. While the socioeconomic characteristics could also heighten susceptibility to potential health impacts in these areas, certain activity patterns can help mitigate exposure. This thesis has also shown that there may be quantifiable psychological benefits of a separation buffer of at least 100 m alongside major highways. These results enhance a very limited knowledge base on the impacts of near-roadway pollution in New Zealand. Furthermore, the results lend additional support to the international literature which is working to reduce residential exposures and population exposure disparities through better policies and improved environmental planning. Where possible, the placement of sensitive population groups within highway corridors, e.g. retirement homes, social housing complexes, schools and childcare centres, should be avoided