Orientador: Lígia Maria Suppo Souza Rugolo / Resumo: A sepse neonatal tardia é importante causa de morbidade e mortalidade em recém-nascidos prematuros. Os sinais e sintomas são inespecíficos, o que dificulta o diagnóstico. As citocinas são potentes mediadores inflamatórios que desempenham importante papel na patogênese da infecção. Níveis séricos aumentados de citocinas são observados durante infecções. A Interleucina 8 (IL-8) tem função de atrair e ativar neutrófilos, mantendo o processo inflamatório. O objetivo deste estudo foi determinar os níveis séricos e urinários da IL-8 em recém-nascidos prematuros com sepse tardia confirmada por culturas (sangue, urina ou líquor) ou associada com meningite, e avaliar se os níveis urinários de IL-8 podem ser utilizados como teste diagnóstico da sepse neonatal tardia. Amostras de sangue e urina foram coletadas de 36 RN prematuros com suspeita clínica de sepse tardia e os exames foram repetidos após 48 horas do início do estudo. Os valores séricos e urinários da IL-8 foram determinados pelo método de ELISA e a IL-8 urinária foi ajustada pelo valor da creatinina urinária. Dois grupos foram constituídos: Grupo séptico: 19 RN com sepse confirmada por culturas ou associada a meningite, idade gestacional (IG) de 31 ± 2,5 semanas, peso de nascimento (PN) de 1350 ± 420g, idade pós-natal (IPN) de 9,7 ± 5,3 dias e Grupo não infectado: 17 RN nos quais o diagnóstico de sepse foi excluído, IG 31 ± 2,1 sem, PN 1510 ± 380g, IPN 6,9 ± 4,1 dias. A mediana dos níveis séricos da IL-8 não diferiu estatisticamente entre os grupos séptico e não infectado (929 x 624 pg/ml; p=0,079) mas os níveis urinários (IL-8 ur/cr) foram significativamente maiores no grupo séptico (249 x 41,7; p<0,001). O ponto de corte ótimo da IL-8 sérica foi de 304 pg/ml com sensibilidade de 84% (IC 95%: 60 a 95%) e especificidade de 47% (IC 95%: 23 a 72%)... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Late onset sepsis (LOS) is an important cause of morbidity and mortality in preterm infants. However, the diagnosis of LOS is difficult. Elevated serum levels of cytokines have been found during infections and this plays a critical role in the pathogenesis of infections. Interleukin 8 (IL-8) attracts and activates neutrophils which is crucial for the maintenance of the inflamatory process. The aim of this study was to determine serum and urine IL-8 levels in preterm infants with clinical LOS and positive culture (blood, urine ou cerebrospinal fluid) or meningitis and to evaluate if IL-8 levels can be a useful test for the diagnosis of LOS. Blood and urine were obtained from 36 premature babies with clinical signs of LOS and the collection of the samples were repeated after two days. Serum and urine IL-8 levels were determined by ELISA and the urine IL-8 concentration was corrected with the urine creatinine level. Nineteen preterm infants with sepsis (positive cultures or meningitis) - LOS Group: gestational age (GA) 31 ± 2.5wk, Birth Weight (BW) 1.35 ± 0.42 Kg, postnatal age(PNA) 9.7 ± 5.3 days and 17 noninfected - Control Group: GA 31 ± 2.1wk, BW 1.51 ± 0.38, PNA 6.9 ± 4.1 days, were studied. The medium serum IL-8 levels were not statistically different between groups (LOS vs Control, 929 x 624 pg/ml; p=0,079) but urine IL-8 levels were significantly higher in the LOS group when compared with the noninfected (249 x 41,7 p<0,001). The optimal cut-off point was 304pg/ml for serum IL8 with 84% sensitivity (95% CI: 60-95%) and 47% specificity (95% CI: 23-72%). The cut-off point for urine IL-8 was 89 with 100% sensitivity (95% CI: 82-100%) and 100% specificity (95%CI:81-100%). Two days after of clinical signs of LOS, urine IL-8 levels decreased in LOS group (p<0,001). The decrease in serum IL-8 levels in the LOS group was not statistically different (p=0,123)... (Complete abstract, click electronic address below) / Doutor

Background: Growing numbers of patients with cancer are surviving following treatment with pelvic radiotherapy. Eighty per cent will experience acute gastrointestinal (GI) toxicity during treatment and 50% will subsequently have a change in their bowel habit which will affect their quality of life. The main project in this thesis aims to determine whether delivery of a gastrointestinal bundle of care will decrease GI acute toxicity and late effects of pelvic chemoradiotherapy. Additional work in the thesis evaluated the newer technique of Volumetric Modulated Arc Therapy (VMAT) which delivers decreased dose to the organs at risk on planning scans. We aimed to determine outcomes of this technique in terms of patient-reported acute toxicity and late effects. There is no internationally accepted patient reported outcome measure to capture this toxicity data and this issue was addressed using Rasch analysis in a third project. Methods: A randomised controlled trial was performed. Patients who were scheduled to undergo potentially curative chemoradiotherapy for cervix and bladder cancers were recruited and randomised. The treatment group received dietetic input and if they developed lower GI symptoms they underwent investigations and treatment for bile acid malabsorption, small bowel bacterial overgrowth and lactose intolerance. The control group received standard care. Patients who were to undergo VMAT to treat gynaecological malignancy completed patient-reported outcomes at baseline, end of treatment and one year. The rates of patient-reported toxicity were compared with those of a historical cohort and were correlated with the volume of small bowel which was irradiated. Thirdly the technique of Rasch analysis was used to evaluate the Common Terminology Criteria for Adverse Events derived patient reported outcome to measure pelvic toxicity of gynaecological cancer treatments. Results: It was feasible and acceptable to deliver a GI care bundle to patients undergoing chemotherapy and pelvic radiotherapy. All patients' data were available for analysis for the primary outcome and 29 patients' data were available at the 1 year time point. GI toxicity at 6 weeks was predicted by the trial group, suggesting that the intervention benefited the patients in terms of GI toxicity at 6 weeks. It is not yet clear whether this benefit is maintained at the 1 year time point. The frequencies of acute and late GI toxicity reported by patients undergoing VMAT were similar to that of a historical cohort who received conformal therapy. There was not a strong association between the volume of small bowel which was irradiated and the toxicity which was reported suggesting that other factors are involved in the development of toxicity. Rasch analysis of the pelvic symptom questionnaire demonstrated the main issue to be response dependency. When this was accounted for by grouping items into sub-tests the questionnaire could be made to be unidimensional and showed high reliability in a symptomatic population. Conclusion: GI intervention holds promise as a measure to reduce the acute toxicity and late effects of pelvic radiotherapy. Although newer radiotherapy techniques appear to decrease the dose delivered to the small bowel this does not translate to a reduction in patient-reported toxicity. The measurement of toxicity is complex and patient-reported outcome measures should be developed with techniques such as Rasch analysis to ensure meaningful data is available to guide further developments to reduce GI toxicity secondary to pelvic radiotherapy.

Lithic scatters are the most abundant class of evidence relating to Late Upper Palaeolithic and Mesolithic activity in southern Britain. Many such scatters, especially those from surface and ploughsoil contexts, have long been characterised as being of low-interpretive value and have been marginalised both in academic studies of the periods and in the wider context of protecting and managing the historic environment. This vast body of evidence makes little contribution to contemporary understandings of the LUP and Mesolithic, which remains largely informed by work which privileges the investigation of well-preserved sites with in situ lithic scatters, especially those with associated faunal remains and palaeoenvironmental evidence. This has serious implications for our ability to characterise and interpret activity in locations and regions where such well preserved and intensively investigated sites are lacking, and in many areas of the country policy makers, fieldworkers and curators are not equipped with the information necessary to make informed decisions concerning the investigation, management and protection of the archaeology of these periods. This thesis explicitly address these issues through a detailed case study of the lithic scatter record from a study area in eastern England. This study is based around a comprehensive database of reported lithic scatters, assembled from a wide range of published and unpublished sources and encompassing all kinds of scatters, from well preserved and exhaustively analysed in-situ scatters to poorly provenanced collections of lithics amassed in the late 19th and early 20th century. This thesis provides the first comprehensive synthesis of the Late Upper Palaeolithic and Mesolithic of the study area and explicitly assesses the interpretative potential of the lithic scatter record, in terms of how it can be used both to develop narratives of landscape occupation and to inform future work on, and management of, lithic scatters in the study area and beyond.

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It is well known that in English law the indemnity insurers stand in a better position than the assureds and this is especially true when a claim is delayed: in that scenario, the insurer is neither liable for the damage caused by the late payment, nor for the compound interest. In Sprung v. Royal Insurance ([1999] 1 Lloyd's Rep IR 111) this unfair situation was justified by the Court of Appeal, naturally, it brought an opportunity for the Law Commission to reconsider the law. Recently, the new Insurance Act 2015 has been enacted and subsequently amended by the Enterprise Act 2016 in regards to the insurer’s obligation to make a timely payment; however, the legal effect of the new legislation is unknown due to the lack of binding precedents. In this work, the duty of the indemnity insurer shall be discussed in full and this work will try to make a contribution to the interpretation of the new legislation regarding to the obligation of the insurer and remedies for the assured.

The most important religious order in the later medieval and early modern kingdom of Castile was without any doubt that of the Order of Friars Minor. To date, however, historians have devoted remarkably little attention to the history of the Franciscans and the significant contributions which they made to the spiritual and social life of the period. Moreover, such studies as there are tend to concentrate on either traditional hagiographical themes or matters related to the history of ecclesiastical politics. This thesis attempts to study the growth, popularity, and spirituality of the Franciscans within the context of the social and political trends of the period. The first half is about patronage, the role played by the friars in the Durango heresy, the phenomenon of the Illuminists, and the growth of anti-semitism. The second half is particularly devoted to the female religious, who have been almost entirely ignored, or treated perfunctorily as handmaidens to the dominant males. Numerically of great importance as members of the Second and Third Orders, of the Order of the Immaculate Conception, and as beatas, this thesis analyses their financial problems and organisation, their dowries and social background, their demography, and their fascinating spiritual experiences. The chronological period covered runs from c.1640 to c.1560, and the second half tends to focus, but not exclusively, on female religious in Cordoba and Toledo.

The opium wars in China during the 1840s were followed by a surge of Christianization in the late Qing dynasty. What a kind of role played by missionaries in the modernization of the Qing China has been a long-lasting issue since the early 20th century. Due to political reasons, the contribution of the Christian mission was either underestimated in view of Cultural Invasion paradigm or overemphasized in view of Modernization paradigm. The thesis employs a less-distorted model, Liberal Theology, to analyze the influences of liberal missionaries, exemplified by Timothy Richard, on the social reform in the modernization movement of the late Qing. It describes the relevance of missionary activities to the development of Chinese history in view of the biographical records of Christian missions. The entry point of this presence is traced in the text through Richard’s activities to contribute to famine relief, literary work, reform advocacy, higher education, cross-cultural exchange, a product of the development of his ideas and strategies gained from the promotion of European models of modernization. Particularly, the thesis brings to light Richard’s symbiotic conception between religion and secularism (i.e., science, technology, education, and political reform). The main contribution of the study hinges on a couple of aspects: (1) Building a thorough portrait of Richard and of his life-long vocation by means of a number of primary and secondary sources in both English and Chinese; and (2) Interpreting the liminal role Richard played in his missionary work to answer the question: are missionaries a proxy of imperialism, or a paragon of modernization, or something in between? After pointing out the limitations of the two old paradigms, the thesis exposes that, armed with the hybrid Liberal Theology model, we can better understand the nature of the mission work done by liberal missionaries, such as Richard. Thus, though their activities happened in an era marked with colonial imperialism, the Christian mission should not be regarded as simply an imperialistic invasion in the cultural field; what is more, though missionaries introduced western civilization to Chinese people in various proselytizing approaches, they could not be considered as one of the prime movers for China’s modernization in the late Qing Dynasty, because the contributions they made subordinately promoted China’s modernization through a series of religious and cultural contacts with Chinese elites via, e.g., meetings, media, literary work, higher education.

There has been an increased interest in Romeʼs connections with the Far East over the course of the last 20 years. This has resulted in the publication of many articles and monographs about the Roman involvement in the Red Sea which was the key maritime region linking the Far East with the West. This thesis synthesizes the recent scholarship on the Red Sea trade in Late Antiquity by merging all of the most up to date information into a concise narrative. In order to accomplish this, three major sources of information have been analyzed. Firstly, the historical time frame of all of the major regions of the Red Sea including Egypt, Aksum, and Himyar have been laid out in a straight forward narrative. This offers the most pertinent background information for the development of Red Sea trade. Secondly, the most up to date archaeological evidence has been incorporated into a description of the ancient maritime trade infrastructure of the Red Sea and Indian Ocean. The archaeological evidence broadens our knowledge of the roads through the Eastern Desert of Egypt, the ports of the Red Sea, and the development of the Indian subcontinent more generally. Thirdly, this thesis builds on all of the historical as well as archaeological data and attempts to quantify the impact of Red Sea trade on the Late Antique Roman Empire both economically and culturally. This synthesis helps to elucidate the growing conception among Late Antique scholars that the Roman Empire was far more interconnected with its eastern neighbours. This further nuances the role which outside forces had on the evolution of the Late Antique world.

This thesis investigates the dual roles that women played in the cult of the martyrs in Christianity in Late Antiquity: as martyrs worthy of admiration and as venerators engaged in acts of celebration. The investigation is driven by questions regarding the identity, agency, and power of women in the cult of martyrs, focusing on late antique (second- to fifth-century) North Africa. Late antique Christians expressed their veneration of the martyrs in a variety of ways, including (but not limited to) special church services, praying for the martyrs, visiting martyrs’ shrines to ask for miracles (often healing in nature), and partaking in commemorative feasts at the martyrs’ graves on the anniversaries of their deaths. In all of these modes of veneration, women took on various roles that were analogous with other roles outside of the cult of the martyrs, such as wife, mother, patron, or client. Female martyrs are also identified using these roles, and thus this provides a useful area of comparison. By exploring these roles, this thesis arrives at a more nuanced understanding of women’s agency and power in traditional contexts and how such agency and power were transferred, continued, and challenged within the cult of the martyrs. The thesis engages in textual and discourse analysis of the relevant primary sources, particularly the martyr texts, sermons, letters, and treatises by North African writers. In the secondary literature, this study engages with the diverse works of classicists, historians, archaeologists, religious studies scholars, and feminist theorists. The interdisciplinary approach of the thesis is further nuanced by an examination of the concepts of identity, agency, and power. Applying these analyses to the context of women’s participation in the cult of the martyrs provides new insights into how we can uncover women’s experiences in ancient sources, where women’s voices are almost always obscured by male discourses.

How can we approach the surviving evidence on Paliochora in order for it to become a site of cultural consciousness in a wider medieval context? Its architectural and iconographic identity is hidden in its thirty-four Late and Post Byzantine churches. This thesis constitutes the first complete interdisciplinary approach to this settlement accompanied by a detailed appendix in the second volume. The two parts of this study examine Paliochora through different perspectives which reveal different aspects of its character. Urban planning and individual architectural specificities are examined through the prism of four construction periods associated with political and economic factors. Structural variety and multiplicity raises questions concerning religious functions. The iconography, on the other hand, relies on the general Late Byzantine canons and influences, but demonstrates provincial tendencies and promotes a distinct style of fresco painting. Furthermore, the possible interference of the continuous Western presence creates new aspects for conceptual discussion in both fields. Consequently the three parameters of this comparative approach are underlined, either on an architectural or iconographic level: • Between the different examples in Paliochora • Within the vast array of Greek and Mediterranean ecclesiastical examples • In contrast to Western practices and models. Throughout the text problems of archaeological evidence and archival information are raised. However, this first effort to place and contextualise Paliochora on the map of existing late medieval cities of the Mediterranean is a call for further research in multiple disciplines. It is a survey which will be used as the basic material for any future actions related both to academic knowledge and restoration processes.