Sepsis inflammation accelerates myeloid cell generation to compensate for rapid mobilization of the myeloid progenitors from bone marrow. This inflammation-driven myelopoiesis, however, generates myeloid progenitors with immunosuppressive functions that are unable to differentiate into mature, innate immune cells. The myeloid-derived suppressor cells (MDSCs) expand markedly in the later phases of sepsis, suppress both innate and adaptive immunity, and thus, elevate mortality. Using a murine model with myeloid-restricted deletion of the C/EBPβ transcription factor, we show that sepsis-induced generation of MDSCs depends on C/EBPβ. C/EBPβ myeloid cell–deficient mice did not generate MDSCs or develop immunosuppression and survived sepsis. However, septic mice still generated Gr1+ CD11b+ myeloid progenitors at the steady-state levels similar to the control sham mice, suggesting that C/EBPβ is not involved in healthy, steady-state myelopoiesis. C/EBPβ-deficient Gr1+ CD11b+ cells generated fewer monocyte- and granulocyte-like colonies than control mice did, indicating reduced proliferation potential, but differentiated normally in response to growth factors. Adoptive transfer of C/EBPβ-deficient Gr1+ CD11b+ cells from late septic mice exacerbated inflammation in control mice undergoing early sepsis, confirming they were not immunosuppressive. These results show that C/EBPβ directs a switch from proinflammatory to repressor myeloid cells and identifies a novel treatment target.

In sub-Saharan Africa, women are disproportionately affected by HIV. Sustained adherence to lifelong antiretroviral therapy (ART) is needed to ensure their own health and prevent transmission of HIV to their partners and their children. However, non-adherence to ART remains a substantial challenge with many associated risk factors. Travel is often reported in the qualitative literature as a barrier to ART adherence among women living with HIV, but few quantitative studies have explored this association. This research aimed to describe travel in the past year among mothers living with HIV in the Long-term Adherence and Care Engagement (LACE) study, to explore factors associated with travel, and to investigate the associations between travel and i) self-reported adherence, and ii) HIV viral load. Part A of this dissertation is the study protocol that introduces the need for this research and presents how the research will be carried out. Part B is a narrative literature review. The review summarises and synthesises existing research relating to HIV treatment and travel in sub-Saharan Africa, giving context to the dissertation. Part C is the journal “ready” manuscript. This section presents an analysis of data from the LACE study, a cross-sectional survey of women living with HIV approximately four years after they had started ART during pregnancy in Gugulethu, Cape Town. At the LACE study visit, data on short-term travel patterns (stayed away from home for 3 or more nights) in the past year and self-reported adherence in the past 30 days (using a validated three-item scale) were collected through structured questionnaires, and a blood specimen was tested for HIV viral load. Poisson regression models with robust standard errors were used to explore factors associated with travel (any versus none), self-reported adherence (100% versus <100%), and viral suppression (≤50 copies/mL). Results were reported as crude risk ratios (RR) and adjusted risk ratios (aRR) with 95% confidence intervals (CI). The results showed that among 353 women enrolled in the LACE study (mean age 32.6 years, 48% employed, 38% married/cohabiting, median 44 months postpartum) 23% (n=81) reported travelling in the past year. Of the women who travelled, most went to the Eastern Cape (90%) and travelled 1-2 times during the year (93%). Women who travelled were more likely to be married/cohabiting than women who had not travelled (aRR = 1.45; 95% Cl: 0.97 - 2.16). Only 9% of women who travelled (7 of 81) reported difficulty with ART adherence due to travel. Overall, 59% of women reported 100% adherence in the past 30 days: 52% of women who had travelled in the past year versus 61% of those who had not travelled (aRR = 0.83; 95% Cl: 0.66-1.04). Only 56% of the cohort were virally suppressed: 60% and 55% of those who had and had not travelled in the past year, respectively (aRR = 1.10; 95% Cl: 0.89-1.36). Travel in the past year was not significantly associated with self-reported adherence or viral suppression in crude or adjusted analyses. These results highlight that poor adherence and viremia were very common in this cohort of women, four years after starting ART in pregnancy. Almost a quarter of women reported travel in the past year but only a v few reported difficulties with adherence related to travel and we found no association between travel in the past year, self-reported adherence in the past 30 days or viremia. Further research is needed to understand adherence patterns during periods of travel and interventions are clearly needed to support women's long-term adherence to ART.

This thesis work presents a new harmonic suppression technique for microstrip patch antennas. Harmonic suppression in active integrated antennas is known as an effective method to improve the efficiency of amplifiers in transmitter side. In the proposed design, the antenna works as the radiating element and, at the same time, as the tuning load for the amplifier circuit that is directly matched to the antenna. The proposed active antenna architecture is easy to fabricate and is symmetric, so it can be conveniently mass-produced and designed to have circular polarization, which is preferred in many applications such as satellite communications. The antenna simulations were performed using Ansoft High Frequency System Simulator (HFSS) and all amplifier design steps were simulated by Advanced Design System (ADS). The final prototypes of the linearly polarized active integrated antenna and the circularly polarized active integrated antenna were fabricated using a circuit board milling machine. The antenna radiation pattern was measured inside Utah State University's anechoic chamber and the results were satisfactory. Power measurements for the amplifiers' performance were carried out inside the chamber and calculated by using the Friis transmission equation. It is seen that a significant improvement in the efficiency is achieved compared to the reference antenna without harmonic suppression. Based on the success in the single element active antenna design, the thesis also presents a feasibility of applying the active integrated antenna in array configuration, in particular, in scanning array design to yield a low-profile, low-cost alternative to the parabolic antenna transmitter of satellite communication systems.

Magister Public Health - MPH / In 2018, it was estimated that 33,000 adolescent girls and 4,200 adolescent boys were HIV-positive in South Africa. The Free State province reports that 89% of people living with HIV are diagnosed; 72% of those diagnosed are receiving antiretroviral therapy (ART); of which 93% have achieved viral suppression (< 1000 RNA copies/mL). Thabo Mofutsanyane District has the highest HIV prevalence in the Free State province. A retrospective, quantitative cross-sectional study was conducted to determine the predictors of viral suppression among adolescents on ART in Thabo Mofutsanyane District Municipality, Free State province, South Africa. Data for all adolescents, aged 10–19 years, receiving ART in 2019 (N = 6 300) was extracted from Tier.net electronic database into an Excel spread sheet and exported into Statistical Package for the Social Sciences – Version 26 (SPSS v 26) for analysis.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20253号 / 医博第4212号 / 新制||医||1020(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 河本 宏, 教授 戸井 雅和, 教授 小川 誠司 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Syfte: I denna litteraturstudie var syftet att undersöka potentiella amblyopibehandlingar samt deras effektivitet utifrån kliniska studier. Metod: Avancerade sökningar gjordes i PubMed mellan 16 och 19 april 2023. Inklusionskraven för denna litteraturstudie var att det var en klinisk studie, studien fanns i fulltext, språket var svenska eller engelska samt att de publicerades mellan årtalen 2000 och 2023. Kraven för relevant innehåll var att det handlade om behandlingsalternativ för amblyopi som inte vanligtvis används i vården idag. Studier som inte uppfyllde kraven om relevant innehåll exkluderades. Resultat: 42 studier granskades med sex identifierade kategorier av behandlingsalternativ: dichoptic binocular training, akupunktur, farmakologi, perceptuell inlärning, aktiv monokulär terapi och low-level laser therapy. Effektiviteten av behandlingarna varierar starkt mellan kategorierna. Av de granskade är dichoptic binocular training mest sannolik att användas som komplement till vedertagen behandling. Slutsats: Inga av dessa amblyopi behandlingar kan ersätta vedertagen behandling. Det är mer sannolikt att vissa av dem kan användas som komplement efter att fler kliniska prövningar utförts och metodiken fastställts. / Aim: The aim of this literature study was to investigate novel amblyopia treatments and their effectiveness based on clinical studies. Method: The literature study is based on PubMed searches made between the 16th and 19th of April 2023. The inclusion criteria of the reviewed studies were as follows: it was a clinical trial, available in full text, in Swedish or English, published between 2000 and 2023, and had relevant content. To be included as relevant content, the study had to be discussing treatment options not used in healthcare as a treatment option outside of clinical trials. Studies that did not fulfil the criteria of relevance were excluded.   Result: Forty-two studies were reviewed with six identified categories of non-conventional treatment options: dichoptic binocular training, acupuncture, pharmacological, perceptual learning, active monocular therapy, and low-level laser therapy. The effectiveness of the treatments varies greatly between the categories. Of the reviewed studies, dichoptic binocular training is most likely to be used as an adjunct to treatments that are already established. Conclusion: Despite the fact that many trials have shown positive results in terms of improvement in visual acuity, none of them seem promising enough to replace current treatments such as occlusion due to mixed results with respect to amblyopia resolution and long-term maintenance of the improved acuity. Some of these solutions are more likely to be available and used as a complement or in situations where established treatments are no longer working. Before they may be regarded as having potential for use in treatment, more clinical trials and studies are required in each area examined.

Commercial concealed weapon detection systems are large and expensive and are not suitable to be used as a portable system. Currently, new methods of concealed weapon detection are being developed to build small and compact systems. One such method is based upon the natural resonances of objects; however, no such system has made it to the market due to the low quality of the signals used in the detection algorithms. In this thesis, a prototype concealed weapon detection system is developed and tested for operation in a cluttered environment. This system utilizes the late-time portion of a radar return to extract the resonance information of an unknown target. After proper signal processing and clutter suppression, the signals are classified to determine if the object is a threat. Multiple measurements with frequency-sweep and time-domain systems are used to verify the algorithm. Microwave tissue imaging techniques aim to reconstruct the internal dielectric distribution of the tissue and rely on the dielectric contrast between healthy and malignant tissues. This contrast has been shown to be weak, and therefore, the signals are easily susceptible to noise. This thesis proposes and validates a method for signal-to-noise ratio analysis of complex S-parameter data sets that are used for microwave imaging. A study of de-noising and artifact reduction techniques for microwave holographic imaging is also presented. / Thesis / Master of Applied Science (MASc)

Researchers have categorized emotion regulation strategies generally as adaptive or maladaptive, depending on impacts of the strategy on psychophysiological, cognitive, and emotional outcomes. A strategy that is widely considered to be maladaptive is expressive suppression, which refers to inhibiting one’s facial expression, to appear neutral. Another emotion regulation strategy that is commonly used but infrequently studied is expressive dissonance, which refers to showing the opposite of how one feels. There is limited research on expressive dissonance, but the longstanding facial feedback hypothesis suggests that facial expressions can further enhance or lower one’s mood; if this is the case, then smiling, even when feeling anxious, may be more adaptive than showing no emotion at all. The objective of my thesis was to examine whether using expressive dissonance was more adaptive than expressive suppression, for regulating negative emotions. To determine adaptiveness, I examined the effect of these two strategies on both intrapersonal factors (i.e., impacts of the strategy on one’s own psychophysiology, memory accuracy, and affect) and interpersonal factors (i.e., impacts of the strategy on social qualities like friendliness and likeability). In the first study, I tested the intrapersonal impacts of expressive suppression and expressive dissonance, compared to a control condition, while women participants (n = 144) viewed negatively arousing images. In the second study, I expanded on the first study by examining intrapersonal and interpersonal qualities (e.g., friendliness, likeability, warmth), in an ecologically valid context (i.e., a conversation with an unacquainted opposite gender confederate). Across both studies, I found no effect of strategy on intrapersonal factors; however, there were effects on interpersonal factors in Study 2. Participants engaging in expressive dissonance were rated more positively, and people in the expressive suppression condition were rated more negatively on interpersonal qualities, relative to the control condition. Taken together, our findings suggest that neither strategy impacted the participant intrapersonally, but both strategies influenced the observer’s impression of the participant. Based on the findings, I encourage a shift from conceptualizing strategies as overall maladaptive or adaptive, to considering specific strategies as helpful or unhelpful based on the regulation’s goal.

This thesis includes three studies. The first study examined how reductions in light availability and changes in soil chemistry that occur as conifers establish in aspen stands, differentially affects the regeneration success of aspen and conifers. We found that aspen were more sensitive to changes in light and soil then subalpine fir. For aspen, reduced light and conifer influenced soils significantly reduced height, biomass, photosynthesis and the production of secondary defense compounds. Subalpine fir seedlings were significantly reduced in photosynthesis, biomass and R:S under lower light conditions but showed no differences in physiology or growth when grown on the contrasting soil types. Subalpine fir seedlings were significantly reduced in photosynthesis, biomass and root:shoot ratio under lower light conditions but showed no differences in physiology or growth when grown on the contrasting soil types. Results from this study suggest that reduction in light and changes in soil chemistry associated with conifer succession place constraints on aspen growth and defense capacity, which may contribute to losses in aspen cover under longer disturbance return intervals. The second study looked at regeneration dynamics of aspen and conifers as forest stands transition from canopy gaps to aspen dominated canopies to conifer dominated canopies. We found that as overstory conifer density increases, aspen decrease in density, basal area, and seedling establishment. Conifers were shown to establish closer to aspen as the canopy increased in conifer density. As this proximity relationship extended into the canopy there is increased mortality in both aspen and subalpine fir, suggesting both facilitation and competition. Our third study looked at the physiological effects of smoke exposure on growth and primary and secondary metabolic responses of deciduous and conifer tree species. Twenty minutes of smoke exposure resulted in a greater than 50% reduction in photosynthetic capacity in five of the six species we examined. Impairment of photosynthesis in response to smoke was a function of reductions in stomatal conductance and biochemical limitations. In general, deciduous species showed greater sensitivity than conifer species. Smoke had no significant affect on growth or secondary defense compound production in any of the tree species examined.

In the past decade, considerable attention has been paid to examination of the impact of amblyopia, and strabismus, upon the lives of the individuals. Although an extensive amount of literature exists regarding amblyopia and its associated visual defects, little is known about the contribution of the amblyopic eye in the habitual viewing condition (i.e. both eyes viewing). The purpose of these studies was to determine whether amblyopes are disadvantaged in the performance of tasks under habitual viewing conditions, highlighting any functional differences which may exist as a consequence of amblyopia. Secondly, the work aimed to investigate whether the amblyopic eye contributes to the habitual performance of these tasks. A simple light detection task, in a dichoptic arrangement based upon blue/yellow stimuli viewed through yellow filters, was used to investigate the above two aims and investigate the degree of interocular suppression in amblyopic participants. Using a 3D motion analysis system performance was assessed for an obstacle crossing task (adaptive gait) and a task of reaching for and grasping of an isolated object and in a ¿cluttered¿ environment. Fine motor skills were assessed in a threading a needle task. On the whole it was found that amblyopes are not disadvantaged under habitual viewing conditions, and in cases where differences were found to exist this appeared to be in tasks requiring speed and accuracy. Consistently across all studies it was found that the amblyopic eye contributed in a positive manner, thus, as in visual normals, two eyes are better than one.