Outcome prediction for improvement of trauma care

The main aim of this thesis is to evaluate, develop and validate models for predicting fatal and non-fatal outcome after trauma in the Netherlands. The dissertation addresses the following questions: I. How can we improve and use prediction models for fatal outcome after trauma? II. To what extent can we predict non-fatal outcome after trauma

The patient's own bone marrow-derived stromal cells:disease modifiers in (neuro)degenerative disorders

The aim of this thesis was to identify a standardized stem cell product that can be used to treat secondary inflammation in neurodegenerative diseases to improve the clinical outcome. In a comprehensive literature search, the concept of the patient’s own fresh naïve stem cells was developed, tested in animal models in order to prepare for the first clinical trials in patients suffering a neurodegenerative disorder. A standardized human stem cell product (Neuro-Cells®) was developed and patented, which is produced on the Brightlands campus in the good manufacturing product (GMP) facility. In animal experiments, using human GMP processed stem cells (Neuro-Cells), the researchers were able to proof safety and efficacy in the indications spinal cord injury, amyotrophic Lateral sclerosis and Frontotemporal lobar degeneration. The stem cells act as an anti-inflammatory drug and proved to be superior to methylprednison, Celecoxib and Riluzole. They concluded that in preclinical trials, a transplantation with human stem cells might be seen as a disease modifier, acting on the secondary inflammatory mechanisms and thereby decreasing disability. With the results of the spinal cord injury experiments, they were able to start a phase I study with chronic spinal cord injured patients together with the Hospital Nacional de Parapléjicos de Toledo in Spain. All 10 patients are treated with their stem cells and so far no side effects were reported. A multi-centre Phase II/III is planned to start in June 2021

Nanobody based dual specific CARs

Recent clinical trials have shown that adoptive chimeric antigen receptor (CAR) T cell therapy is a very potent and possibly curative option in the treatment of B cell leukemias and lymphomas. However, targeting a single antigen may not be sufficient, and relapse due to the emergence of antigen negative leukemic cells may occur. A potential strategy to counter the outgrowth of antigen escape variants is to broaden the specificity of the CAR by incorporation of multiple antigen recognition domains in tandem. As a proof of concept, we here describe a bispecific CAR in which the single chain variable fragment (scFv) is replaced by a tandem of two single-antibody domains or nanobodies (nanoCAR). High membrane nanoCAR expression levels are observed in retrovirally transduced T cells. NanoCARs specific for CD20 and HER2 induce T cell activation, cytokine production and tumor lysis upon incubation with transgenic Jurkat cells expressing either antigen or both antigens simultaneously. The use of nanobody technology allows for the production of compact CARs with dual specificity and predefined affinity

Total physical activity might not be a good measure in the relationship with HDL cholesterol and triglycerides in a multi-ethnic population: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Evidence suggests that physical activity (PA) has a beneficial effect on high-density lipoprotein cholesterol (HDL) and triglycerides. However, observational studies show contrasting results for this association between different ethnic groups. It is unclear whether this is due to differences in the PA composition. The aim of this study was to assess the relationship of the total PA, along with its intensity and duration, with HDL and triglycerides in a multi-ethnic population.</p> <p>Methods</p> <p>The study population was sampled from the SUNSET study and included: 502 European- Dutch, 338 Hindustani-Surinamese, and 596 African-Surinamese participants living in Amsterdam, the Netherlands. We assessed PA with the SQUASH questionnaire. We calculated age-sex-adjusted betas, geometric mean ratios (GMRs), and prevalence ratios (PRs) to assess the relationship of PA with HDL and triglycerides.</p> <p>Results</p> <p>In the adjusted models, the highest total PA tertile compared to the lowest tertile was beneficially associated with HDL (beta: 0.08, 95% CI: 0.00, 0.16 and PR low HDL 0.59, 95% CI: 0.39, 0.88) and triglycerides (GMR: 0.93, 95% CI: 0.83, 1.03 and PR: 0.56, 95% CI: 0.29, 1.08) for the African-Surinamese. No statistically significant associations appeared for total PA among the European-Dutch and Hindustani-Surinamese. The adjusted models with the intensity score and HDL showed beneficial associations for the European-Dutch (beta: 0.06, 95% CI: 0.03, 0.10) and African-Surinamese (beta: 0.06, 0.02, 0.10), for log triglycerides for the European-Dutch (beta: -0.08, 95% CI: -0.12, 0.03), Hindustani-Surinamese (beta: -0.06, 95% CI: -0.16, 0.03), and African-Surinamese (beta: -0.04, 95% CI: -0.10, 0.01). Excepting HDL in African-Surinamese, the duration score was unrelated to HDL and triglycerides in any group.</p> <p>Conclusions</p> <p>Activity intensity related beneficially to blood lipids in almost every ethnic group. The activity duration was unrelated to blood lipids, while the total PA 'summary score' was associated only with blood lipids for African-Surinamese. The difference in total PA composition is the most probable explanation for ethnic differences in the total PA association with blood lipids. Multi-ethnic observational studies should include not only a measure of the total PA, but other measures of PA as well, particularly the intensity of activity.</p

Design of a Low Micro Vibration High Precision CubeSat Reaction Wheel

Rolling element bearings are known to generate higher order harmonics. These harmonics can reach up to the 10th or higher engine order [1]. When wheels are used in a wide speed range, these higher order harmonics can pass and excite rotor eigenfrequencies and rotor modes, severely increasing the exported μ-vibrations at these frequencies. The amplification of these frequencies will then be governed by the quality factor (Q-factor) of the rotor. Single piece rotors have several advantages such as affordable tight tolerances, uniform mass and elimination of assembly errors, but such monolithic metallic structure feature high Q-factors. Material choice is a first way to address this [2], but damping will stay limited. To further increase the internal damping and reduce the Q-factor, Constrained layer damping is employed

Hip fractures in elderly people:Surgery or no surgery? A systematic review and meta-analysis

Iintroduction:  Increasing numbers of patients with hip fractures also have advanced comorbidities. A majority are treated surgically. However, a significantly increasing percentage of medically unfit patients with unacceptably high risk of perioperative death are treated nonoperatively. Important questions about patients' prefracture quality of life (QOL) and future perspectives should be asked before considering different treatment options to assess what kind of treatment is advisable in frail elderly high-risk patients with a hip fracture. Objective:  The aim of this review was to provide an overview of differences in mortality, health-related QOL [(HR)QOL], functional outcome, and costs between nonoperative management (NOM) and operative management (OM) of hip fractures in patients above 65 years. Methods:  A systematic literature search was performed in EMBASE, OvidSP, PubMed, Cochrane Central, and Web of Science for observational studies and trials. Observational studies and randomized controlled trials comparing NOM with OM in hip fracture patients were selected. The methodological quality of the selected studies was assessed according to the Methodological Index for Nonrandomized Studies (MINORS) or Furlan checklist. Results:  Seven observational studies were included with a total of 1189 patients, of whom 242 (20.3%) were treated conservatively. The methodological quality of the studies was moderate (mean: 14.7, standard deviation [SD]: 1.5). The 30-day and 1-year mortalities were higher in the nonoperative group (odds ratio [OR]: 3.95, 95% confidence interval [CI]: 1.43-10.96; OR: 3.84, 95% CI: 1.57-9.41). None of the included studies compared QOL, functional outcome, or health-care costs between the 2 groups. Conclusion:  This systematic review and meta-analysis demonstrated that only a few studies with small number of patients comparing NOM with OM were published. A significantly higher 30-day and 1-year mortality was revealed in nonoperatively treated hip fracture patients. No data were found examining (HR)QOL and costs. Further work is needed to enable shared decision-making and to initiate NOM in frail elderly patients with advanced comorbidity and limited life expectancy

Large ethnic variations in recommended physical activity according to activity domains in amsterdam, the netherlands

<p>Abstract</p> <p>Purpose</p> <p>The level of recommended physical activity (PA) is met less frequently by people from some ethnic minorities than others. We explored whether these differences in recommended PA between ethnic minority groups and the general population varied by domain and type of culturally-specific activity.</p> <p>Methods</p> <p>Participants were sampled from the population based SUNSET study and were from ethnic Dutch (n = 567), Hindustani-Surinamese (n = 370) and African-Surinamese (n = 689) descent. The validated SQUASH-questionnaire measured PA for the following domains: commuting, occupation, household, leisure time. Culturally-specific activities were added as extra question within the leisure time domain. The effect of each domain on ethnic differences in recommended PA prevalence was examined by odds-ratio (OR) analysis through recalculating recommended PA, while, in turn, excluding the contribution of each domain.</p> <p>Results</p> <p>In the ethnic Dutch population, more vigorous PA in commuting and leisure time was reported compared to the Surinamese groups. The Hindustani-Surinamese and African-Surinamese reported more walking as commuting activity, while the Dutch group reported cycling more frequently. Ethnic differences in recommended PA became smaller in both Surinamese groups compared with the Dutch after removing commuting activity, for example, in Hindustani-Surinamese men (OR = 0.92, 95%CI: 0.62-1.37 vs. OR = 1.33, 0.89-2.00) and women (OR = 1.61, 1.12-2.32 vs. OR = 2.03, 1.41-2.92). Removing occupational activity resulted in larger ethnic differences in both groups compared with the Dutch. Smaller effects were found for yoga and dancing, leisure time and household activities.</p> <p>Conclusion</p> <p>This study shows that differences in PA between ethnic minority groups and the general population vary according to the activity domain. The results indicate that including all relevant domains and activities is essential for assessment of ethnic differences in recommended PA.</p