Introduction

The skin is a rather large organ comprising 16% of body weight. It contains several cell types and cell products. Three separate compartments are present and a disease may involve one or all. The topmost layer, the epidermis, is a very active metabolic area and disease involving this area is generally acute with oozing, weeping, and scaling. The dermis, which is quite large, gives support to the entire skin and body. Dermal diseases produce swelling, enlargement, and rigidity in the skin. A disease in the subcutaneous section of the skin, the third major portion, is usually nodular and edematous

Atopic Dermatitis

The term atopic, which means “strange disease,” was first used in 1925 to describe a group of diseases which include allergic rhinitis, bronchial asthma, urticarial reactions to drugs as well as food allergies or idiosyncrasies. These conditions have in common the presence of skin sensitizing homocytotropic antibodies (IgE) in the serum of the person at some point in the natural history of the disease. There is little evidence that dermatitis found in the atopic individual is produced by IgE which is present in the serum and skin of the person with atopic dermatitis

Master of Science

thesisDuring the late afternoon of 18 June 2015, ozone concentrations within a strong lake breeze arising from the Great Salt Lake in northern Utah were observed to be ~20 ppb higher than those in its advance. Ozone observations from an enhanced network were available from state air quality measurement sites, additional fixed locations, and mobile platforms, including a news helicopter. The southward progression of the well-defined lake-breeze front through the Salt Lake Valley was observed by wind, temperature, and moisture observations available at automated weather stations, as well as radial velocity scans from a nearby Terminal Doppler Weather Radar. Strong flow opposing the lake breeze increased convergent frontogenesis and delayed the onset of its passage through the Salt Lake Valley. Ozone concentrations were exceptionally high aloft in the head of the lake-breeze front. The development and progression of lake breezes on both 17 and 18 June 2015 were simulated using the Weather Research and Forecast model at 1-km horizontal resolution over northern Utah. The model was initialized at 0000 UTC 14 June 2015 using hourly analyses at 3-km resolution from the High Resolution Rapid Refresh model. The underlying surface state was improved by specifying the areal extent and surface temperature of the lake observed during June 2015. An urban canopy parameterization was added as well to better simulate urban effects on wind and heat fluxes. These modifications improved the model simulation particularly for the more typical lake breeze event on 17 June. However, on 18 June weaker than observed opposing southerly flow allowed the development of the simulated lake-breeze front to occur too early and its subsequent speed up the valley was too fast. Continuous passive tracers initialized at the surface within and ahead of the lake breeze highlight the dispersion and transport of pollutants arising from the strong lake-breeze front on 18 June. Tracers within the lake breeze are confined closer to the surface while tracers in advance of the front are lofted vertically over it

Cell-Mediated Immunity Generated in Response to a Purified Inactivated Vaccine for Dengue Virus Type 1

Dengue is the most prevalent arboviral disease afflicting humans, and a vaccine appears to be the most rational means of control. Dengue vaccine development is in a critical phase, with the first vaccine licensed in some countries where dengue is endemic but demonstrating insufficient efficacy in immunologically naive populations. Since virus-neutralizing antibodies do not invariably correlate with vaccine efficacy, other markers that may predict protection, including cell-mediated immunity, are urgently needed. Previously, the Walter Reed Army Institute of Research developed a monovalent purified inactivated virus (PIV) vaccine candidate against dengue virus serotype 1 (DENV-1) adjuvanted with alum. The PIV vaccine was safe and immunogenic in a phase I dose escalation trial in healthy, flavivirus-naive adults in the United States. From that trial, peripheral blood mononuclear cells obtained at various time points pre- and postvaccination were used to measure DENV-1-specific T cell responses. After vaccination, a predominant CD4+ T cell-mediated response to peptide pools covering the DENV-1 structural proteins was observed. Over half (13/20) of the subjects produced interleukin-2 (IL-2) in response to DENV peptides, and the majority (17/20) demonstrated peptide-specific CD4+ T cell proliferation. In addition, analysis of postvaccination cell culture supernatants demonstrated an increased rate of production of cytokines, including gamma interferon (IFN-γ), IL-5, and granulocyte-macrophage colony-stimulating factor (GM-CSF). Overall, the vaccine was found to have elicited DENV-specific CD4+ T cell responses as measured by enzyme-linked immunosorbent spot (ELISpot), intracellular cytokine staining (ICS), lymphocyte proliferation, and cytokine production assays. Thus, together with antibody readouts, the use of a multifaceted measurement of cell-mediated immune responses after vaccination is a useful strategy for more comprehensively characterizing immunity generated by dengue vaccines

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Doctor of Philosophy

dissertationThreats associated with wildland fires are exacerbated by weather conditions conducive to rapid fire spread, such as strong winds, high temperatures, and low humidity. Incident Meteorologists rely on a variety of in situ and remote observations as well as numerical weather prediction model output to assess the potential influence atmospheric conditions will have on the fires. With the accelerating accumulation of available meteorological data, efficient computational solutions are needed to process, archive, and analyze the massive datasets in ways useful to Incident Meteorologists. This work demonstrates how object-based storage technology can be used to efficiently archive multiple years of the High-Resolution Rapid Refresh (HRRR) model output-a convection-allowing operational forecast system that produces 0-18 h forecasts. The archive developed for this work now supports air quality and wildland fire research activities at the University of Utah and hundreds of other researchers. The historical HRRR model output was used to provide information on model behavior and skill that may be of great value to Incident Meteorologists. An extensive set of empirical cumulative distributions for near-surface variables based on 3 years of model analyses was efficiently computed on the Open Science Grid-a high-throughput computing resource. The cumulative distributions are used to evaluate techniques that may be appropriate to discriminate between typical and atypical atmospheric conditions in a historical context for situational awareness of hazardous weather conditions like iv strong winds. Also, the skill of HRRR model lightning forecasts-which are important to firefighting operations because of the potential for convective outflows-was evaluated by comparing forecasted lightning threat with lightning observations from the Geostationary Lightning Mapper. Based on the fractions skill score, HRRR lightning forecast skill decreases rapidly after the first 2 hours of model integration with better skill for longer lead times in the afternoon and evening hours in the western and central United States. With case studies of recent wildland fires, this dissertation illustrates how historical model data and objective evaluation of lightning forecast performance can help Incident Meteorologists identify hazardous weather conditions and interpret deterministic lightning forecasts from the HRRR model