A Comparison of the local Gaussian correlation and the local dependence function

Correlation is a method to measure the relation between two or more variables. In this thesis, a method of measuring correlation and a method of measuring dependence are used. These two methods, are the local Gaussian correlation and the local dependence function. The goal was to build a bridge between these two measurements. The hypothesis is that for a bivariate normal density, both methods will locally approximate the densities correlation coefficient. The local dependence function is a measure of dependence and it has to be transformed to give the function of the correlation. However, there was not a clear connection between the two methods. Instead of the local dependence function, the precision matrix was utilised. The precision matrix provides an opportunity to find the correlation coefficient locally for the bivariate normal density. Thus, a bridge between the local Gaussian correlation and the correlation estimate from the precision matrix can be built. To obtain the correlation estimate from the precision matrix, it has to be transformed to its inverse, the covariance matrix. However, while a connection was made, some details remain unclear. This is observed, with the local Gaussian correlation being defined for the range of the density. While the estimated correlation for the precision matrix has areas that are undefined for certain densities. The function of the estimated correlation from the precision matrix is discussed, to explain why some areas are undefined and why the estimate takes the form it does for different densities. The two methods also produced differing correlation estimates for given areas. In this thesis, the same set of test case densities are used, as the ones in the introductory paper for the local dependence function (Jones, 1996), and its preliminary paper (Doksum et al., 1994). As the local Gaussian correlation is an empirical method of measuring correlation, it needs data. For this thesis there is no observed data, therefore instead simulated data are used in the analyses. The correlation estimate from the precision matrix, on the other hand requires the densities to be known. To further explore the precision matrix’s correlation estimate, two novel methods are explored; the Box-Cox transformation and the Gaussian kernel estimates, but they require further work. In conclusion, while a bridge is constructed between the local Gaussian correlation and the precision matrix’s correlation estimate, more work is needed to establish a clearer connection.Masteroppgave i aktuarfagAKTUA399MAMN-AKTU

Prospects and challenges in the development of universal influenza vaccines

Current influenza vaccines offer suboptimal protection and depend on annual reformulation and yearly administration. Vaccine technology has rapidly advanced during the last decade, facilitating development of next-generation influenza vaccines that can target a broader range of influenza viruses. The development and licensure of a universal influenza vaccine could provide a game changing option for the control of influenza by protecting against all influenza A and B viruses. Here we review important findings and considerations regarding the development of universal influenza vaccines and what we can learn from this moving forward with a SARS-CoV-2 vaccine design.publishedVersio

A naval design study on a small, unmanned surface vessel

The thesis is based on a naval study of a small, unmanned surface vessel. Furthermore, the study has been conducted in accordance with the Norwegian method of procurement PRINSIX. The study has been a preliminary project and involves the three first phases of the PRINSIX method: The idea phase (IP), the concept phase (CP), and the definition phase (DP). The IP analysed three ideas of conceptual solution: Mine Counter Measurement (MCM), Intelligence Surveillance and Reconnaissance (ISR), and Force Sustainment USV’s in light of operational needs in a top-down approach. Eventually, the output of the idea phase was a recommendation to further investigate the idea of ISR USV’s. The CP analysed analysed the capabilities and mission need for chosen alternatives, and further identified the capabilities for the conceptual solutions. The output of this analysis was four potential options: Continuation of current assets, small, passive ISR USV’s in large numbers, small active and passive ISR USV’s in limited numbers, and small active and passive ISR USV’s in limited numbers with offensive capabilities. Furthermore, a trade-off analysis, risk assessment, and rought technical considerations regarding hull and propulsion was made. Consequently, the CP concludes with a recommendation to move forward with option 1, Small ISR USV’s with a towable passive sonar in conjunction with deployable sonobuoys. Furthermore, the CP recommends moving forward with a conventional hydrostatic displacement hull and a hybrid propulsion configuration. The DP started off with specifying the preliminary capabilities and requirements for the chosen conceptual solution. Furthermore, a preliminary vessel was chosen as a reference vessel. The chosen reference vessel was then subject of a trade-off analysis with respect to alternative solutions for hull, propulsor, drivetrain, energy producers, and energy storage. The preliminary design solution was then deducted through a parametric study based on the preliminary capabilities and requirements, and the parameters in the design spiral. Moreover, a set of optimized parameters and a final optimized solution was presented and further analysed with respect to a weight breakdown, cost assessment, and a risk assessment. Finally, a recommendation was made based on the findings in the points of decision and the associated risk analysis. In conclusion, the recommendation is to not move forward into a development- and completion phase, judging the current state of the vessel. Further optimization is essential to reduce the risk of procurement

Chemokines are secreted by monocytes following OK-432 (lyophilized Streptococcus pyogenes) stimulation

Background: OK-432, penicillin-killed Streptococcus pyogenes, is used in treating lymphangiomas and carcinomas. We have studied in vitro the role of mononuclear phagocytes (MNPs), including purified monocytes (MOs), in the immune response to OK-432. MIP-1α/β and MCP-1 secretions were assessed in whole blood (WB), peripheral blood mononuclear cells (PBMCs) and purified MOs, after in vitro stimulation with OK-432 with or without adherence for 24 hours. Results: OK-432 stimulated MNPs to secrete MCP-1 and MIP-1α/β in healthy individuals and in head and neck squamous cell carcinoma (HNSCC) patients, except for OK-432 stimulation of WB giving a minimal MIP-1α/β response. Upon culture on low-attachment wells, a spontaneous chemokine secretion was observed, with an unchanged secretion following OK-432 stimulation. Inhibition of Syk kinase and/or PI-3 kinase did not significantly change the chemokine response to OK-432, except for MIP-1α production being increased upon Syk inhibitor addition and an increased MCP-1 response upon addition of both inhibitors. Adhesion may possibly involve β1 and/ or β3 integrins, not β2, whereas β1–3 integrins may act as co-stimulatory receptors for OK-432. Based on direct blockage of CD36 or CD18 by antibodies, MCP-1 production may be mediated by CD18 while MIP-1β and MCP-1 production may occur upon binding to CD36. Conclusion: Adherent human MOs produce MCP-1 and MIP-1α/β upon stimulation with OK-432. CD36 modulates MIP-1β and MCP-1 response. Thus, to some extent OK-432 acts as a substance whereby only MOs adhered to surfaces secrete MCP-1 and MIP-1α/β, in part explaining why OK- 432 is suited as a biological response modifying drug.publishedVersio

Allergic sensitisation in tuberculosis patients at the time of diagnosis and following chemotherapy

<p>Abstract</p> <p>Background</p> <p>It is still a matter of debate whether there is an association between infection with <it>Mycobacterium tuberculosis </it>(<it>M. tuberculosis</it>) and allergy. Previously, we have shown higher levels of specific IgE to different inhalant allergens and total IgE in tuberculosis (TB) patients compared to controls. The objectives of this study were to evaluate a possible change in allergic sensitisation after successful TB treatment and to confirm the finding of our previous study of enhanced allergic sensitisation in TB patients compared to controls in a more controlled setting. Additionally, we wanted to determine the cytokine profile in the same groups and finally to evaluate the association between the presence of Bacillus Calmette-Guérin vaccination (BCG) scar and allergic sensitisation among the controls.</p> <p>Methods</p> <p>Sera were analysed for specific IgE to inhalant allergens (Phadiatop) and total IgE by the use of ImmunoCAP 1000 (Pharmacia Diagnostics). Thirteen different cytokines were also analysed in the sera by multiplex bead immunoassay (Luminex 100, Luminex Corporation), and clinical symptoms of allergy and BCG scar were reported in a questionnaire.</p> <p>Results</p> <p>A reduction in levels of specific and total IgE were observed after successful TB treatment. TB patients also had higher levels of specific and total IgE compared to healthy controls. Both interleukin (IL)-6 and interferon (IFN)γ were higher in TB patients compared to healthy controls. The levels of IL-6 were reduced after successful TB treatment. The presence of a BCG scar was associated with a reduced risk of developing allergic sensitisation.</p> <p>Conclusion</p> <p>We observed a reduced level of allergic sensitisation after successful TB treatment. TB patients seem to be more allergically sensitised than healthy controls, confirming our previous finding. Furthermore, we observed an inverse association between allergic sensitisation and visible BCG scar, which adds additional support to the hygiene hypothesis.</p

Early Induction of Cross-Reactive CD8+ T-Cell Responses in Tonsils After Live-Attenuated Influenza Vaccination in Children

Background Live-attenuated influenza vaccine (LAIV) was licensed for prophylaxis of children 2–17 years old in Europe in 2012 and is administered as a nasal spray. Live-attenuated influenza vaccine induces both mucosal and systemic antibodies and systemic T-cell responses. Tonsils are the lymph nodes serving the upper respiratory tract, acting as both induction and effector site for mucosal immunity. Methods Here, we have studied the early tonsillar T-cell responses induced in children after LAIV. Thirty-nine children were immunized with trivalent LAIV (containing A/H1N1, A/H3N2, and B viruses) at days 3, 7, and 14 before tonsillectomy. Nonvaccinated controls were included for comparison. Tonsils and peripheral blood (pre- and postvaccination) were collected to study T-cell responses. Results Tonsillar and systemic T-cell responses differed between influenza strains, and both were found against H3N2 and B viruses, whereas only systemic responses were observed against A/H1N1. A significant increase in cross-reactive tonsillar CD8+ T cells recognizing conserved epitopes from a broad range of seasonal and pandemic viruses occurred at day 14. Tonsillar T cells showed significant cytokine responses (Th1, Th2, and granulocyte-macrophage colony-stimulating factor). Conclusions Our findings support the use of LAIV in children to elicit broadly cross-reactive T cells, which are not induced by traditional inactivated influenza vaccines and may provide protection to novel virus strains.publishedVersio

Point-of-care influenza testing impacts clinical decision, patient flow and length of stay in hospitalized adults

Background Influenza is difficult to distinguish clinically from other acute respiratory infections. Rapid laboratory diagnosis can help initiate early effective antiviral treatment and isolation. Implementing a novel point-of-care test (POCT) for influenza in the emergency department (ED) could improve treatment and isolation strategies and reduce the length of stay (LOS). Methods In a prospective, controlled observational cohort study, we enrolled patients admitted due to acute respiratory illness to 2 public hospitals in Bergen, Norway, one using a rapid POCT for influenza (n = 400), the other (n = 167) using conventional rapid laboratory-based assay. Results Prevalence of influenza was similar in the 2 hospitals (154/400, 38% vs 38%, 63/167; P = .863). Most patients in both hospitals received antiviral (83% vs 81%; P = .703) and antibiotic treatment (72% vs 62%; P = .149). Isolation was more often initiated in ED in the hospital using POCT (91% vs 80%; P = .025). Diagnosis by POCT was associated with shorter hospital stay; old age, diabetes, cancer, and use of antibiotics, particularly broad-spectrum antibiotics, were associated with prolonged stay. Conclusions POCT implementation in ED resulted in improved targeted isolation and shorter LOS. Regardless of POCT use, most influenza patients received antivirals (>80%) and antibiotics (>69%).publishedVersio

Lymphoid organisation in labial salivary gland biopsies is a possible predictor for the development of malignant lymphoma in primary Sjögren's syndrome

Objective The development of non-Hodgkin's lymphoma (NHL) confers a high risk of mortality in primary Sjogren's syndrome (pSS) patients, but the sensitivity and specificity of proposed lymphoma predictors are insufficient for practical use. The performance of lymphoid organisation in the form of germinal centre (GC)-like lesions was evaluated in labial salivary gland biopsies taken at pSS diagnosis as a potential lymphoma-predicting biomarker. Methods Labial salivary gland tissue biopsies available from two Swedish pSS research cohorts (n = 175) were re-evaluated by light microscopy in a blind study in order to identify GC-like structures as a sign of ectopic lymphoid tissue formation and organisation. A linkage study was performed with the Swedish Cancer Registry for lymphoma identification. The risk of developing NHL in GC-positive patients in comparison with GC-negative patients was evaluated using Kaplan-Meier statistics and log-rank test. Associations between GC-like structures and clinical and/or laboratory disease markers were also determined using. 2 or Fisher's exact tests. Results At diagnosis, 25% of pSS patients had GC-like structures in their salivary glands. Seven of the 175 patients studied (14% GC+ and 0.8% GC-) developed NHL during 1855 patient-years at risk, with a median onset of 7 years following the initial diagnostic salivary gland biopsy. Six of the seven patients had GC-like structures at diagnosis; the remaining patient was GC negative at the time of diagnosis (p=0.001). Conclusions The detection of GC-like structures by light microscopy in pSS diagnostic salivary biopsies is proposed as a highly predictive and easy-to-obtain marker for NHL development. This allows for risk stratification of patients and the possibility to initiate preventive B-cell-directed therapy

A randomized, double-blind, placebo-controlled clinical study to investigate the efficacy of herring roe oil for treatment of psoriasis

The effect of omega-3 polyunsaturated fatty acid supplements in patients with psoriasis vulgaris has previously been investigated, but interventions varied in source, composition, dose, administration route and duration of treatment. The observed beneficial effects in patients with psoriasis vulgaris using herring roe oil as a dietary supplement prompted this investigation. This randomised, double-blind and placebo-controlled study was designed and performed to explore the efficacy and safety of herring roe oil supplementation in 64 patients with plaque psoriasis (ClinicalTrials.gov: NCT03359577). The primary end-point was comparing the change in mean Psoriasis Area Severity Index (PASI) scores in the herring roe oil treatment group and the placebo group from baseline to week 26. In the intention-to-treat population, a statistically significant improvement in the mean PASI score was observed with herring roe oil compared to placebo at 26 weeks. In the recruited patient group, the measured improvement was greatest in patients with a PASI score from 5.5–9.9 at baseline.publishedVersio

Comparative analysis of influenza A(H3N2) virus hemagglutinin specific IgG subclass and IgA responses in children and adults after influenza vaccination

AbstractTwo different influenza vaccines are generally used in many countries; trivalent live attenuated influenza vaccine (LAIV3) and trivalent inactivated influenza vaccine (IIV3). Studies comparing the antibody response to IIV3 and LAIV3 commonly investigate the seroprotective response by hemagglutination-inhibition (HI) assay. However, there is limited data regarding comparative analysis of IgG subclass and IgA responses induced by LAIV3 and IIV3.Fifteen children <5years received 2 doses of LAIV3 while 14 children aged 10–17years received one dose. In addition, 15 adults were vaccinated with either intranasal LAIV3 or intramuscular IIV3. We analyzed the H3N2 humoral responses by HI assay and the hemagglutinin (HA) specific IgG1, IgG2, IgG3, IgG4 and IgA1 responses by ELISA. Furthermore, we investigated the avidity of induced IgG antibodies.Pre-existing seroprotective HI antibodies were present in adults (73%) previously vaccinated with IIV3. Vaccination resulted in a significant increase in HI titers in all groups, except LAIV3 vaccinated adults. Furthermore, a negative correlation between age and HI titers in LAIV3 vaccinated subjects was observed post-vaccination. LAIV3 in children and IIV3 in adults induced HA-specific IgG1, low IgG3 but no IgG2 or IgG4. Moreover, significant IgA1 responses were only induced in children. Interestingly, IIV3 and LAIV3 induced IgG antibodies with comparable and significantly augmented avidity post-vaccination in children and adults.Our results suggest that age and/or exposure history play a significant role in determining the antibody response.Clinical trial registry: ClinicalTrials.gov NCT01003288 and NCT0186654