The multiple pterygium syndromes are a heterogeneous group of conditions in which arthrogryposis (joint contractures), pterygia (webbing) and a variety of other developmental anomalies are present. It is caused by lack of fetal movement in the womb. Mutations in CHRNG, the embryonic subunit of the acetylcholine receptor (AChR), cause some of the cases. CHRNG mutation analysis was undertaken in a large patient cohort of 100 families and the mutations identified were included in a new Locus Specific Database. Genotype phenotype analysis showed that pterygia were almost invariably present in the CHRNG mutation positive patients. It was hypothesised that mutations in other genes necessary for fetal AChR function may cause fetal akinesia. Using a candidate gene approach a homozygous frameshift mutation in RAPSN was identified in one family and a homozygous splice site DOK7 mutation in second family. Mild mutations in both RAPSN and DOK7 have been previously identified in the congenital myasthenic syndromes (CMS). Thus, mild mutations in RAPSN and DOK7 cause CMS whereas severe mutations cause fetal akinesia. Finally, work was done to identify a novel cause of fetal akinesia in a consanguineous family using an autozygosity mapping approach. A region of homozygosity was located and candidate genes sequenced.

Gynaecology Teaching Associates (GTAs) are lay women trained to undergo and teach gynaecological examination giving immediate feedback to medical students. However, there are only limited data evaluating the acceptability, effectiveness and economic viability of this teaching innovation. This thesis appraises the educational impact of GTA-led teaching of female pelvic examination. An online survey showed that GTAs were used by under a third of UK medical schools. A study was conducted to establish validity and reliability of a newly developed pelvic examination assessment tool by comparing the performance of novice and experienced students and junior doctors in obstetrics and gynaecology (O&G). This study did not establish adequate psychometric properties so the tool will need further refinement. A large single blinded randomised controlled trial demonstrated an improvement in competence and confidence of medical students taught by GTAs compared with pelvic manikins at the start of their O&G placement. A parallel economic analysis showed that GTA teaching was considered cost-effective, with an investment of £640.20 needed to acquire an additionally competent student and £274.37 per student competent at merit and distinction levels. A qualitative study using semi-structured interviews found that GTA-led teaching was acceptable and considered a positive experience by stakeholders.

Obesity is associated with an increased risk of developing some gynaecological cancers, and delayed help-seeking. The thesis aims were to identify factors predictive of delayed help-seeking for women seeking help for potential symptoms of gynaecological cancers, particularly looking at the role of obesity on time to help-seeking. Qualitative and exploratory research further investigated health beliefs and help-seeking attitudes of women experiencing gynaecological cancer symptoms and built a framework for understanding women’s complex journeys toward medical help-seeking. Additionally, the research assessed for differences in time to help-seeking and cancer awareness across groups with varying body mass indexes (BMIs) and different ethnic groups. Findings suggested that women have a limited awareness of gynaecological cancers, nevertheless, low awareness of gynaecological cancers was not associated with help-seeking delay. Thesis studies showed that obese women were not more likely to delay help-seeking when compared to non-obese women, and that attendance at preventative screenings was a predictor of delayed help-seeking. In conclusion the thesis provided an understanding of the often-complex transition through the menopause and challenged assumptions in the literature about the association between obesity, help-seeking and preventative screenings. Future research should further explore the complex relationship between BMI and help-seeking for gynaecological cancer symptoms.

Restriction of fetal growth and compromise of its wellbeing remain significant causes of perinatal death and childhood disability. There is a lack of scientific consensus about the best strategies for predicting these conditions before birth and thus there is uncertainty about the best management of pregnant women who might have a growth-restricted baby. This health technology assessment thesis used state of the art methods to review 337 studies including 472,544 women. It determined : 1. The accuracy of available tests for predicting small for gestational age infants (SGA) and 2. Compromise of fetal wellbeing and 3. Summarised the effectiveness of available treatments for these conditions. To allow translation of these results into patient care, the diagnostic and therapeutic information was integrated in a model based economic evaluation. This thesis has demonstrated that the tests reviewed have a limited use in screening/diagnosis for SGA/compromise of fetal and neonatal wellbeing when used in isolation. The quality of primary research was variable with recommendations being made particularly for the use of standardised and relevant outcome measures. The decision model and economic analysis identified that an effective, affordable and safe intervention applied to all mothers without prior testing is likely to be the most cost-effective strategy in the prevention of these conditions.

Cervical human papillomavirus (HPV) infection is a very common sexually transmitted disease which is now considered to be a necessary, but not sufficient, cause of cervical cancer. It has been suggested that the association between HPV infection and cervical neoplasia can be exploited to improve the efficiency and effectiveness of primary- and secondary-prevention programmes for cervical cancer. However, whether this aspiration can be realized in practice requires a greater understanding of the natural history of early cervical HPV infection and its role in the acquisition of epithelial abnormalities of the cervix. In this thesis, a longitudinal study of young women who had recently embarked on sexual activity has provided sequential observations on the natural history of cervical HPV infection. This thesis addresses four aspects of this natural history: the association between HPV infection and the proximity of first sexual intercourse to menarche; the association between smoking, cervical HPV infection and high-grade cervical disease; the validation of a neutralising antibody assay and its use in defining the kinetics of the humoral immune response to cervical HPV16 and HPV18 infections; and the analysis of measurements of the viral load of HPV16 and HPV18, and their association with epithelial abnormalities of the cervix

Switchable oligopeptides, able to expose of conceal biomolecules on a surface, upon the application of an electrical potential, represent a versatile tool for the development of novel devices, presenting potential biomedical applications. Recently, several studies have demonstrated the applicability of smart devices for the control of protein binding and cellular response. In this work; a detailed analysis of the steric requirements necessary to develop a mixed oligopeptide Self-Assembled Monolayer (SAM) presenting an optimum switching ability will be described. The influence of both the SAM components surface ratio and the switching unit length on the mixed SAMs switching performance will be investigated. The findings of this investigation will be used to develop, for the first time, a platform, based on electrically switchable oligopeptides, able to control the interaction between an antigen and its relative antibody. The influence of the biological medium on the oligopeptide switching ability will also be investigated. Finally, an orthogonal functionalisation strategy, will be investigated in detail, together with a new platform able to promote human sperm cells adhesion. The results of this research thesis will also represent the first building blocks towards the development of glass-gold rnicropattemed surfaces able to control the calcium signalling in human sperm cells, presenting potential applications in the improvement of in-vitro fertilisation (NF) treatments success rates.

Background: Research suggests that postnatal affective disorders such as anxiety, depression and post-traumatic stress disorder (PTSD) are associated with lower levels of maternal sensitivity. Understanding the mechanisms through which maternal affective disorders influence maternal sensitivity is important as it could lead to more tailored effective interventions to improve outcomes for women and their infants. One mechanism that is yet to be explored is the way in which mothers' process infant-related information. This thesis therefore developed a cognitive model that aimed to examine this mechanism. Aim: The aim of this thesis was to test this cognitive model of maternal sensitivity using a range of experimental, observational and questionnaire studies. The model proposed that maternal affective symptoms would be associated with maternal processing of infant-related information, which in turn would be associated with maternal sensitivity. Methods & Results: The aims were addressed through a systematic review and a study of women with (n = 23) and without (n = 47) affective symptoms and their infants (aged 2-8 months) after birth. The systematic review found that mothers with perinatal affective disorders are faster to disengage from sad infant faces and are more accurate at identifying sadness in infant faces (Article 1). To assess how mothers process infant-related information, validated pictures of infants' emotional faces were needed. Therefore, a validated set of infant emotional expressions was created and validated on student midwives and nurses and members of the general public. The images were found to have high criterion validity and good test-retest reliability (Article 2). Mothers processing of infant-related information and its relationship with maternal sensitivity was tested using a series of questionnaires, computerised and observational tasks. Results are reported in Articles 3, 4 and 5. Conclusion: Overall, the cognitive model of maternal sensitivity was only partly supported, in that maternal affective symptoms explained more of the variance of maternal sensitivity than maternal processing of infant-related information. Despite this, the work in this thesis provides a novel contribution to the literature by developing and testing a model based on previous research and by using robust measures such as eye-tracking technology and observational measures of mother-infant interaction. However, interpretation of the data is hindered due to methodological issues such as small sample sizes, homogeneous sample and demand characteristics. Therefore, more research is needed to test this model on a larger, more heterogenous sample.

Orientador: José Carlos Peraçoli / Coorientador: Maria Antonieta de Barros Leite Carvalhaes / Banca: Roberto Antonio de Araújo Costa / Banca: Roseli Yamamoto Nomura / Banca: Mary Ângela Parpinelli / Banca: Maria Helena B. Benício / Resumo: Analisar possíveis associações entre resistência e reactância, avaliadas pela análise de impedância bioelétrica (BIA), no primeiro, segundo e terceiro trimestres de gestação, e ocorrência de pré-eclâmpsia; identificar qual o momento mais precoce da associação. Coorte prospectiva. Hospital das Clinicas da Faculdade de Medicina de Botucatu/Unesp. 380 gestantes acompanhadas no Serviço. As gestantes foram submetidas à BIA, no primeiro (até 14 semanas), segundo (15 a 28 semanas) e terceiro (29 a41 semanas) trimestres, para avaliação dos valores de resistência e reactância. Considerou-se o desenvolvimento de hipertensão arterial, após a 20ª semana, com ou sem proteinúria, respectivamente, Pré-eclâmpsia (PE) e Hipertensão Gestacional (HG). Foi realizada a análise estatística através teste T de student e do Odds-Ratio considerando p<0,05. No primeiro trimestre a média da resistência e reactância do grupo PE (508Ω;57Ω) foi significativamente menor que a observada no grupo normotenso (580Ω;66Ω). No segundo trimestre as médias de resistência e reactância no grupo PE, respectivamente, (502Ω e 53Ω), foram menores significativamente do que as encontradas no grupo normotenso (566Ω e 57Ω). No terceiro trimestre foram também significativamente menores quando comparadas com o grupo normotenso (452 Ω e 47 Ω). No primeiro trimestre o Odds ratio (OR) para a resistência foi de 0,99 (IC 0,98 - 1,0) com p=0,002 e reactância foi de 0,93 (IC 0,85- 1,01) com p=0,07. No Segundo trimestre o OR foi de 0,99 (IC 0,98-0,99) e p=0,001 e a reactância o OR foi de 0,95 (IC=0,9-1,00) com p=0,05. No terceiro trimestre o OR foi de foi de 0,99 (IC 0,98-0,99) e p=0,0010 para resistência e de 0,93 (IC 0,88 - 0,98) e p=0,01 para reactância. A bioimpedância mostrou associação através da resistência tanto no primeiro quanto no segundo... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: To analyze possible associations between resistance and reactance, as evaluated by electrical impedance analysis (BIA) in the first, second and third pregnancy trimesters, and preeclampsia occurrence; to identify the earliest moment of association. Prospective cohort. Botucatu School of Medicine University Hospital/Unesp. Population: 380 pregnant women attended to by the Service. The pregnant women underwent BIA in the first (up to 14 weeks), second (15 to 28 weeks) and third (29 to 41 weeks) trimesters for evaluation of resistance and reactance values. The development of arterial hypertension, after the 20th week, with or without proteinuria, respectively, Preeclampsia (PE) and Gestational Hypertension (GH) was considered. Statistical analysis by Odds-Ratio was performed considering p<0.05. In the first trimester, the resistance and reactance means in the PE group (508Ω;57Ω) were significantly lower than those observed in the healthy group (580Ω;66Ω). In the second trimester, the resistance and reactance means in the PE group, respectively (502Ω and 53Ω), were lower than those found in the healthy group (566Ω and 57Ω). In the third trimester were lower than than those found in the healthy group (452 Ω e 47 Ω). In the first trimester, the Odds ratio (OR) for resistance was 0.99 (CI 0.98 - 1.0) with p=0.002, and reactance was 0.93 (CI 0.85-1.01) with p=0.07. In the second trimester, OR was 0.99 (CI 0.98-0.99) and p=0.001, and for reactance, OR was 0.95 (CI=0.9-1.00) with p=0.05. In the third trimester, the Odds ratio (OR) for resistance was (IC 0,98-0,99) with p=0,0010 and 0,93 (IC 0,88 - 0,98) with p=0,01 for reactance. Bioimpedance showed association by means of resistance both in the first... (Complete abstract click electronic access below) / Doutor

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This thesis was focused on parent’s mental health during the perinatal period. Fear related to childbirth is common in mothers. Chapter one provides a meta-ethnographic synthesis of literature exploring mothers’ experiences of fear related to childbirth. Three meta-themes were identified which showed what it was like for women to experience fear related to childbirth, external factors than influenced their fear (e.g. the media) and internal factors (e.g. coping strategies). This study illustrated the complexity of mothers’ experiences and how fear related to childbirth can impact quality of life. The implications of these findings, and clinical recommendations, are discussed. There is increasing recognition that fathers may experience low mood in the postnatal period. Chapter two explores how fathers talk about paternal postnatal depression (PND). Six fathers who considered themselves to have had paternal PND took part in semi-structured interviews, which were analysed using discourse analysis. The results showed that PND was constructed as something that happens to women rather than men. They highlighted the difficulties men have talking about PND and how masculine identities were used to account for this difficulty. Finally, men constructed themselves as being deficient fathers when they had paternal PND. This study has significant implications for how PND is talked about with men. Chapter three presents a reflective account of conducting the research, which was written from the perspective of a parent. The focus was on the impact that the researcher may have had on the study and the effect that the study had on the researcher. It encompassed the whole process from developing ideas to potential areas of future study. The importance of terminology in mental health was discussed as well as what it is like conducting research on parents as a parent. The chapter ends with reflections on the researcher’s epistemological position.