Establishing a high risk CKD cohort: cross-sectional analysis and early outcomes

Introduction Patients with Chronic Kidney Disease (CKD) are at increased risk of both cardiovascular disease and progression to end-stage kidney disease; our understanding of the factors that determine these poor outcomes is incomplete. The study reported in this thesis has been designed to address some of these shortfalls. Methods I established a prospective, observational cohort study of patients with high risk CKD as defined by i) declining kidney function and/or ii) proteinuria and/or iii) advanced (stage 4 and 5) CKD. Participants undergo repeated detailed bio-clinical assessment over a follow up period of ten years and are tracked for clinical outcomes. The baseline data are presented in this thesis along with some data form the six-month visit. Results I report cross-sectional data from the first 500 participants; mean age is 65 years, 60% were male and 72% white ethnicity. Mean eGFR was 27mL/min/1.73m2 and median urine ACR was 26.9 mg/mmol. Detailed analyses demonstrated important associations between i) quality of life and unemployment, male gender, deprivation, co-morbidity and inflammation ii) arterial stiffness, inflammation and renal and cardiovascular outcomes iii) periodontitis and arterial stiffness iv) mortality, inflammation and arterial stiffness. Conclusions This thesis reports important new findings from patients with CKD and establishes a resource that will provide future insights that should contribute to improving clinical outcomes

Attention skills in children with non-syndromic cleft lip and palate

Objective To describe attention skills in children with cleft lip and palate across auditory and visual domains and investigate associations with cleft subtype, biological sex, socioeconomic status, and speech and language. Design A cross-sectional observation study. Setting Participants from regional cleft lip and palate centers seen in schools and home. Participants Eighty-one children aged 5 years 0 months to 7 years 11 months with non-syndromic cleft palate +/- lip. Main outcome measure Auditory and visual attention skills including measures of distractibility, impulsivity and focus across both domains. Results Mean average scores for all measures of auditory and visual attention were below one standard deviation from the normative average (standard score <85). There was no main effect of cleft subtype. Boys had significantly lower scores for visual distractibility than girls. There was no statistically significant effect of socioeconomic status, but those from higher socioeconomic groups had scores up to 10 standard points higher in some measures than those in the middle or lower groups. Weak, significant correlations were observed between language skills and measures of attention. Conclusions A range of both auditory and visual attention skills were low in this group raising the question of potential generalised attention difficulties in children with CLP. Attention skills were correlated with language. Professionals working with children with CLP should be aware that attention difficulties are prevalent and advise families and educators accordingly. Further research including intervention studies would increase our understandin

Antimodern strategies: Ambivalence, accommodation, and protest in Willa Cather's "The Troll Garden".

In this project I argue that Willa Cather's earliest collection of stories, The Troll Garden (1905), demonstrates the antimodern ethos of the American fin de siecle period as characterized by both progressive rhetoric and resistance to modernity. This work also responds to social and economic issues examined by Cather's contemporaries Max Weber in The Protestant Ethic and the Spirit of Capitalism (1905) and Thorstein Veblen in his The Theory of the Leisure Class (1899) as well as by Walter Benjamin early in the 20th century. I argue, using historian T. J. Jackson Lears' notion of antimodernism as both "protest" and "accommodation" to modernity, that Cather figures the celebrity artist and the dandy as representations in an attempt to come to terms with her own contradictory impulses. Cather's early work confronts issues which include American individualism, consumerism, class, and aesthetic consumption in addition to gender. In addition I argue that her antimodern aesthetic is a "sensational" aesthetic, based upon Paterian and Fordian impressionism as expressed by T. E. Hulme, which is itself both a form of protest of and accommodation to the pressures of modernity upon the artist in bourgeois, modern America. Cather's early literary practices situate her within a particularly American Aestheticism traceable through European and American influences from other antimodernists such as Charles Baudelaire, Walter Pater, Candace Wheeler, and Oscar Wilde. Cather's ambivalence towards modernity as portrayed in her aesthetic is compatible with Mikhail Bakhtin's notion of art as "answerability" and the necessity of an "excess of seeing" in confronting the complexity of this period---characterized by high finance capitalism, competition for cultural capital, and the resultant competing, simultaneous rhetorics of fears for the republic and progressive belief

The Influence of Faith on Women in Leadership Positions

Women are still underrepresented in leadership roles and still suffer from gender stereotypes and injustice. Women of faith are frequently stigmatized by both their faith and place of employment. This study is about women of faith who held leadership roles in rural communities. The objective of this study is to examine the experiences of women of faith in leadership, their qualities, and knowledge as effective leaders. The data used in this study is secondary and it was obtained from a parent study entitled, “Women Ascending to Leadership Positions in Rural Nonprofit Organizations.” This parent study used a snowball approach to interview 32 women who were serving in leadership roles in rural nonprofit organizations. The current study used a phenomenological qualitative approach to determine how their faith influenced their leadership ascension. It is necessary to investigate the journey of women’s leadership development to identify how to best develop future female leaders in nonprofit organizations in rural communities. There is limited research regarding women’s leadership experiences in rural organizations and faith

Recent Advances in the Pathogenesis and Management of Cast Nephropathy (Myeloma Kidney)

Multiple myeloma is an incurable plasma cell malignancy that is often accompanied by renal failure; there are a number of potential causes of this, of which cast nephropathy is the most important. Renal failure is highly significant in myeloma, as patient survival can be stratified by the severity of the renal impairment. Consequently, there is an ongoing focus on the pathological basis of cast nephropathy and the optimal treatment regimens in this setting, including effective chemotherapy regimens to reduce light chain production and emerging extracorporeal techniques to remove circulating light chains. This paper bridges recent advances in the pathogenesis and management of cast nephropathy in multiple myeloma

Nurse-led psychological intervention for type 2 diabetes:a cluster randomised controlled trial (Diabetes-6 study) in primary care

Background Suboptimal glycaemic control in type 2 diabetes (T2D) is common and associated with psychological barriers.Aim To investigate whether it was possible to train practice nurses in six psychological skills (Diabetes-6 [D6]) based on motivational interviewing (MI) and basic cognitive behaviour therapy (CBT), and whether integrating these with diabetes care was associated with improved glycaemic control over 18 months compared with standard care.Design and setting Two-arm, single-blind, parallel cluster randomised controlled trial in primary care.Method Adult participants (n = 334) with T2D and persistent HbA1c &gt;=69.4 mmol/mol were randomised to receive 12 sessions of either the D6 intervention or standard care over 12 months. Practice nurses were trained in the six psychological skills and their competencies were measured by standardised rating scales. Primary outcome was a change in HbA1c level at 18 months from randomisation. Secondary outcomes were changes in systolic and diastolic blood pressure, body mass index, waist circumference, depressive symptoms, harmful alcohol intake, diabetes-specific distress, and cost-effectiveness.Results Using intention-to-treat analysis, there was no significant difference between D6 intervention and standard care in HbA1c (mean difference -0.79 mmol/mol, 95% confidence interval [CI] = -5.75 to 4.18) or for any of the secondary outcomes. The competency level of D6 nurses was below the beginner proficiency level and similar to the standard-care nurses.Conclusion Training nurses in MI and basic CBT to support self-management did not lead to improvements in glycaemic control or other secondary outcomes in people with T2D at 18 months. It was also unlikely to be cost-effective. Furthermore, the increased contact with standard-care nurses did not improve glycaemic control

Impacts of the Tropical Pacific/Indian Oceans on the Seasonal Cycle of the West African Monsoon

The current consensus is that drought has developed in the Sahel during the second half of the twentieth century as a result of remote effects of oceanic anomalies amplified by local land–atmosphere interactions. This paper focuses on the impacts of oceanic anomalies upon West African climate and specifically aims to identify those from SST anomalies in the Pacific/Indian Oceans during spring and summer seasons, when they were significant. Idealized sensitivity experiments are performed with four atmospheric general circulation models (AGCMs). The prescribed SST patterns used in the AGCMs are based on the leading mode of covariability between SST anomalies over the Pacific/Indian Oceans and summer rainfall over West Africa. The results show that such oceanic anomalies in the Pacific/Indian Ocean lead to a northward shift of an anomalous dry belt from the Gulf of Guinea to the Sahel as the season advances. In the Sahel, the magnitude of rainfall anomalies is comparable to that obtained by other authors using SST anomalies confined to the proximity of the Atlantic Ocean. The mechanism connecting the Pacific/Indian SST anomalies with West African rainfall has a strong seasonal cycle. In spring (May and June), anomalous subsidence develops over both the Maritime Continent and the equatorial Atlantic in response to the enhanced equatorial heating. Precipitation increases over continental West Africa in association with stronger zonal convergence of moisture. In addition, precipitation decreases over the Gulf of Guinea. During the monsoon peak (July and August), the SST anomalies move westward over the equatorial Pacific and the two regions where subsidence occurred earlier in the seasons merge over West Africa. The monsoon weakens and rainfall decreases over the Sahel, especially in August.Peer reviewe

Severe early onset preeclampsia: short and long term clinical, psychosocial and biochemical aspects

Preeclampsia is a pregnancy specific disorder commonly defined as de novo hypertension and proteinuria after 20 weeks gestational age. It occurs in approximately 3-5% of pregnancies and it is still a major cause of both foetal and maternal morbidity and mortality worldwide1. As extensive research has not yet elucidated the aetiology of preeclampsia, there are no rational preventive or therapeutic interventions available. The only rational treatment is delivery, which benefits the mother but is not in the interest of the foetus, if remote from term. Early onset preeclampsia (<32 weeks’ gestational age) occurs in less than 1% of pregnancies. It is, however often associated with maternal morbidity as the risk of progression to severe maternal disease is inversely related with gestational age at onset2. Resulting prematurity is therefore the main cause of neonatal mortality and morbidity in patients with severe preeclampsia3. Although the discussion is ongoing, perinatal survival is suggested to be increased in patients with preterm preeclampsia by expectant, non-interventional management. This temporising treatment option to lengthen pregnancy includes the use of antihypertensive medication to control hypertension, magnesium sulphate to prevent eclampsia and corticosteroids to enhance foetal lung maturity4. With optimal maternal haemodynamic status and reassuring foetal condition this results on average in an extension of 2 weeks. Prolongation of these pregnancies is a great challenge for clinicians to balance between potential maternal risks on one the eve hand and possible foetal benefits on the other. Clinical controversies regarding prolongation of preterm preeclamptic pregnancies still exist – also taking into account that preeclampsia is the leading cause of maternal mortality in the Netherlands5 - a debate which is even more pronounced in very preterm pregnancies with questionable foetal viability6-9. Do maternal risks of prolongation of these very early pregnancies outweigh the chances of neonatal survival? Counselling of women with very early onset preeclampsia not only comprises of knowledge of the outcome of those particular pregnancies, but also knowledge of outcomes of future pregnancies of these women is of major clinical importance. This thesis opens with a review of the literature on identifiable risk factors of preeclampsia

Cost-Effectiveness of Pre-exposure HIV Prophylaxis During Pregnancy and Breastfeeding in Sub-Saharan Africa

Antiretroviral pre-exposure prophylaxis (PrEP) for the prevention of HIV acquisition is cost-effective when delivered to those at substantial risk. Despite a high incidence of HIV infection among pregnant and breastfeeding women in sub-Saharan Africa (SSA), a theoretical increased risk of preterm birth on PrEP could outweigh the HIV prevention benefit