The madness of the Black man on his own: an analysis of the silences of history, in search of herstory

The primary purpose of this thesis is to examine the autobiographical works of three Black South African women -- Mamphela Ramphele, Bessie Head, and Ellen Kuzwayo -- to see if and how they were impacted by the masculine discourse of the Black Consciousness Movement (BCM), which was articulated in terms of "the Black man" and his struggle. One of the first points I make and use as a premise throughout the thesis is that the term "man" is neither inclusive nor universal; it, instead, refers specifically to men and cannot refer to both men and women. What could have motivated the use of this masculinist language, particularly in light of the fact that the Nguni and Sotho languages of South Africa do not have a gender differentiation system for the third person pronoun? This question led me to an examination of the English language since English was the language chosen by the activists to conduct the business of the Movement. But, there was yet another factor to consider besides the language. The Black Consciousness Movement took place through the 1960s and into the late 1970s, during the latter part of an era of many other Black nationalist struggles around the world (Negritude, the U.S. Black Power Movements, liberation struggles of many of the other African countries). So, I look specifically at men's writings ' from Negritude and the Black Power Movements and compare them to a sample of writings from male writers in the Black Consciousness Movement, showing that all of these writers articulate employ this masculinist language. The significance of the timing of Black Consciousness (BC) is that it emerged into an international context with a readymade nationalist discourse of the liberation of Black people and the struggle of Black men. That discourse, however, might not have emerged if the usage of the masculine as universal were not already an acceptable practice the English language. Thus, the first chapter is an examination of the masculinity of the English language, primarily through feminist, postructuralist, psychoanalytic, and Marxist theories/theorists. The analysis begins from the premise that masculinity is a system of domination that requires femininity, a small, enclosed space designated for women. Key to the existence of masculinity and femininity is the facade that they are natural7 i.e., inherent to the male and female bodies, respectively. Thus the chapter is largely a deconstruction of that assumption, and the 18th century European assumption of a direct link between hysteria and femininity. I argue that at the base of female hysteria is a much more pervasive and normalised male hysteria, driven by the either/or binary logic of Western philosophy that shows itself in the English language. Indeed, it is masculinity, not femininity, that is irrational, illogical, and mad in its obsession for understanding and control. I move from that assertion into an analysis of how capitalism works to create femininity through Marx's structure of the non-producer, the labourer (to whom Marx consistently refers as he), and the product to examine the relationship between men and women, the masculine and the feminine. After establishing the madness of masculinity and its place in the English language, I move into how this examination of a Western context correlates to the Black Consciousness Movement. I argue that when the male BC activists entered into the English language, they simultaneously entered into its legacy of masculinity, and they adopted that masculinity. Thus their absenting of women was driven by the very same madness of masculinity. In the midst of this oppressive madness called masculinity, how, then did Black women conceive of themselves as agents? Of the three women, only one, Mamphela Ramphele, was an activist in the BCM. She is the onlywoman activist from the BCM who has written her autobiography, or who has written a sizeable body of material on her experience in the Movement. She is also the only of the three who never engages in the masculinist discourse of the Movement. I also look at Ellen Kuzwayo's autobiography, Call Me Woman7 which is dedicated to documenting the contributions of other Black women to the liberation of South Africa, despite which there are curious moments in the text when she slips into masculinist discourse in talking about the BCM and the importance of the Black man's struggle. The third is Bessie Head and her novel, A Question of Power7 which I use as an autobiographical text on the basis of her own admission that it is largely grounded in her own life experiences. Hers is an important text for the framework of madness it provides. I conclude that, true to my previous analyses, she is driven into madness by the hysteria of masculinity

Isolation of novel coregulatory protein networks associated with DNA-bound estrogen receptor alpha

<p>Abstract</p> <p>Background</p> <p>DNA-bound transcription factors recruit an array of coregulatory proteins that influence gene expression. We previously demonstrated that DNA functions as an allosteric modulator of estrogen receptor α (ERα) conformation, alters the recruitment of regulatory proteins, and influences estrogen-responsive gene expression and reasoned that it would be useful to develop a method of isolating proteins associated with the DNA-bound ERα using full-length receptor and endogenously-expressed nuclear proteins.</p> <p>Results</p> <p>We have developed a novel approach to isolate large complexes of proteins associated with the DNA-bound ERα. Purified ERα and HeLa nuclear extracts were combined with oligos containing ERα binding sites and fractionated on agarose gels. The protein-DNA complexes were isolated and mass spectrometry analysis was used to identify proteins associated with the DNA-bound receptor. Rather than simply identifying individual proteins that interact with ERα, we identified interconnected networks of proteins with a variety of enzymatic and catalytic activities that interact not only with ERα, but also with each other. Characterization of a number of these proteins has demonstrated that, in addition to their previously identified functions, they also influence ERα activity and expression of estrogen-responsive genes.</p> <p>Conclusion</p> <p>The agarose gel fractionation method we have developed would be useful in identifying proteins that interact with DNA-bound transcription factors and should be easily adapted for use with a variety of cultured cell lines, DNA sequences, and transcription factors.</p

Association Between Cytokines and Liver Histology in Children with Nonalcoholic Fatty Liver Disease.

BackgroundReliable non-invasive markers to characterize inflammation, hepatocellular ballooning, and fibrosis in nonalcoholic fatty liver disease (NAFLD) are lacking. We investigated the relationship between plasma cytokine levels and features of NAFLD histology to gain insight into cellular pathways driving NASH and to identify potential non-invasive discriminators of NAFLD severity and pattern.MethodsCytokines were measured from plasma obtained at enrollment in pediatric participants in NASH Clinical Research Network studies with liver biopsy-proven NAFLD. Cytokines were chosen a priori as possible discriminators of NASH and its components. Minimization of Akaike Information Criterion (AIC) was used to determine cytokines retained in multivariable models.ResultsOf 235 subjects, 31% had "Definite NASH" on liver histology, 43% had "Borderline NASH", and 25% had NAFLD but not NASH. Total plasminogen activator inhibitor 1 (PAI1) and activated PAI1 levels were higher in pediatric participants with Definite NASH and with lobular inflammation. Interleukin-8 (IL-8) was higher in those with stage 3-4 fibrosis and lobular inflammation. sIL-2rα was higher in children with stage 3-4 fibrosis and portal inflammation. In multivariable analysis, PAI1 variables were discriminators of Borderline/Definite NASH, definite NASH, lobular inflammation and ballooning. IL-8 increased with steatosis and fibrosis severity; sIL-2rα increased with fibrosis severity and portal inflammation. IL-7 decreased with portal inflammation and fibrosis severity.ConclusionsPlasma cytokines associated with histology varied considerably among NASH features, suggesting promising avenues for investigation. Future, more targeted analysis is needed to identify the role of these markers in NAFLD and to evaluate their potential as non-invasive discriminators of disease severity

What are subjective cognitive difficulties and do they matter?

Background subjective cognitive difficulties (SCD) have been associated with a higher risk of developing dementia. However, there is large variation in the way SCD are assessed and in their associations with cognitive functioning. Objective to compare the agreement of different SCD measures in identifying people with SCD and to investigate whether SCD are more strongly associated with cognitive functioning, mood, subjective age or background variables. Methods this cross-sectional study included 206 community-dwelling people aged ≥65. SCD were assessed with individual domain specific questions and a multiple-item scaled measure. Performance on tests of memory, attention, and executive function, and ratings of mood, subjective age and demographic information were recorded. Results there was some classification overlap between the five measures of SCD, however of the 64 people identified as having SCD, only one person appeared in all five measures of SCD and 34 people were classified by one measure only. There were limited associations between SCD and objective cognition, with more consistent associations with mood and subjective age. Conclusions the conflicting evidence regarding whether SCD are related to objective cognition and future risk of dementia may be due to different measures of SCD being employed. Careful consideration and standardisation is recommended regarding the cognitive domains and the reference groups for comparison, the response structure and the classification criteria. Longitudinal studies of SCD that include these considerations are needed to clarify the conceptual utility of SCD

Interaction of estrogen receptor α with proliferating cell nuclear antigen

The ability of estrogen receptor α (ERα) to modulate gene expression is influenced by the recruitment of a host of co-regulatory proteins to target genes. To further understand how estrogen-responsive genes are regulated, we have isolated and identified proteins associated with ERα when it is bound to DNA containing the consensus estrogen response element (ERE). One of the proteins identified in this complex, proliferating cell nuclear antigen (PCNA), is required for DNA replication and repair. We show that PCNA interacts with ERα in the absence and in the presence of DNA, enhances the interaction of ERα with ERE-containing DNA, and associates with endogenous estrogen-responsive genes. Interestingly, rather than altering hormone responsiveness of endogenous, estrogen-responsive genes, PCNA increases the basal expression of these genes. Our studies suggest that in addition to serving as a platform for the recruitment of DNA replication and repair proteins, PCNA may serve as a platform for transcription factors involved in regulating gene expression

SLC35A2-related congenital disorder of glycosylation : Defining the phenotype

We aim to further delineate the phenotype associated with pathogenic variants in the SLC35A2 gene, and review all published literature to-date. This gene is located on the X chromosome and encodes a UDP-galactose transporter. Pathogenic variants in SLC35A2 cause a congenital disorder of glycosylation. The condition is rare, and less than twenty patients have been reported to-date. The phenotype is complex and has not been fully defined. Here, we present a series of five patients with de novo pathogenic variants in SLC35A2. The patients' phenotype includes developmental and epileptic encephalopathy with hypsarrhythmia, facial dysmorphism, severe intellectual disability, skeletal abnormalities, congenital cardiac disease and cortical visual impairment. Developmental and epileptic encephalopathy with hypsarrhythmia is present in most patients with SLC35A2 variants, and is drug-resistant in the majority of cases. Adrenocorticotropic hormone therapy may achieve partial or complete remission of seizures, but the effect is usually temporary. Isoelectric focusing of transferrins may be normal after infancy, therefore a congenital disorder of glycosylation should still be considered as a diagnosis in the presence of a suggestive phenotype. We also provide evidence that cortical visual impairment is part of the phenotypic spectrum. (C) 2018 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.Peer reviewe

Histologic Abnormalities in Children with Nonalcoholic Fatty Liver Disease and Normal or Mildly Elevated Alanine Aminotransferase Levels.

Objectives: To investigate the histological spectrum of nonalcoholic fatty liver disease (NAFLD) in children with normal, mildly elevated (26–50 U/L boys, 23–44 U/L girls), or elevated (> 50 boys, > 44 girls) serum alanine aminotransferase (ALT) levels. Study design: The Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) enrolls children 5–18 years with NAFLD. We analyzed baseline clinical and histological data from 91 children with suspected NAFLD and normal or mildly elevated ALT and liver biopsy within 180 days of ALT, and compared them with 392 children with elevated ALT. Results: Of 91 children, 17 (19%) had normal and 74 (81%) had mildly elevated ALT levels. Overall, 45% of biopsies had ≥ 33% steatosis, lobular inflammation grade was ≥ 2 in 22%, 81% had portal inflammation, 29% had ballooned hepatocytes, 35% had “suspicious/borderline” steatohepatitis, and 8% had definite NASH, 34% had NAFLD activity score (NAS) ≥ 4. Overall, 46% had fibrosis (38% mild/moderate and 8% bridging/cirrhosis). Marked steatosis (50% vs 24%) and fibrosis (54% vs 12%) were significantly more common in mildly elevated vs normal, with no difference in ballooning, inflammation, or NAS ≥ 4. Fibrosis stage 3/4 was seen in none of the children with normal ALT, and in 9% of the mildly elevated and 15% of the elevated. Conclusions: Liver biopsies of children with NAFLD with normal or mildly elevated ALT levels show significant histologic abnormalities, including advanced fibrosis in children with mildly elevated ALT. ALT thus may underestimate liver injury in NAFLD. Appropriate ALT cut-off levels can help identify children at risk for more severe disease

An experimental model of chronic severe mitral regurgitation

OBJECTIVE: To develop a minimally invasive, reproducible model of chronic severe mitral regurgitation (MR) that replicates the clinical phenotype of left atrial (LA) and left ventricular dilation and susceptibility to atrial fibrillation. METHODS: Under transesophageal echocardiographic guidance, chordae tendinae were avulsed using endovascular forceps until the ratio of regurgitant jet area to LA area was ≥70%. Animals survived for an average of 8.6 ± 1.6 months (standard deviation) and imaged with monthly transthoracic echocardiography (TTE). Animals underwent baseline and preterminal magnetic resonance imaging. Terminal studies included TTE, transesophageal echocardiography, and rapid atrial pacing to test inducibility of atrial tachyarrhythmias. RESULTS: Eight dogs underwent creation of severe MR and interval monitoring. Two were excluded-one died from acute heart failure, and the other had resolution of MR. Six dogs underwent the full experimental protocol; only one required medical management of clinical heart failure. MR remained severe over time, with a mean terminal regurgitant jet area to LA area of 71 ± 14% (standard deviation) and regurgitant fraction of 52 ± 11%. Mean LA volume increased over 130% (TTE: 163 ± 147%, CONCLUSIONS: Within the 6 dogs that successfully completed the full experimental protocol, this model replicated the clinical phenotype of severe MR, which led to marked structural and electrophysiologic cardiac remodeling. This model allowed for precise measurements at repeated time points and will facilitate future studies to elucidate the mechanisms of atrial and ventricular remodeling secondary to MR and the pathophysiology of valvular atrial fibrillation

Clinical and economic outcomes of nurse-led services in the ambulatory care setting: a systematic review

With the increasing burden of chronic and age-related diseases, and the rapidly increasing number of patients receiving ambulatory or outpatient-based care, nurse-led services have been suggested as one solution to manage increasing demand on the health system as they aim to reduce waiting times, resources, and costs while maintaining patient safety and enhancing satisfaction.The aims of this review were to assess the clinical effectiveness, economic outcomes and key implementation characteristics of nurse-led services in the ambulatory care setting.A systematic review was conducted using the standard Cochrane Collaboration methodology and was prepared in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.We searched the Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library, MEDLINE EBSCO, CINAHL EBSCO, and PsycINFO Ovid (from inception to April 2016).Data were extracted and appraisal undertaken. We included randomised controlled trials; quasi-randomised controlled trials; controlled and non-controlled before-and-after studies that compared the effects of nurse-led services in the ambulatory or community care setting with an alternative model of care or standard care.Twenty-five studies of 180,308 participants were included in this review. Of the 16 studies that measured and reported on health-related quality of life outcomes, the majority of studies (n = 13) reported equivocal outcomes; with three studies demonstrating superior outcomes and one demonstrating inferior outcomes in comparison with physician-led and standard care. Nurse-led care demonstrated either equivalent or better outcomes for a number of outcomes including symptom burden, self-management and behavioural outcomes, disease-specific indicators, satisfaction and perception of quality of life, and health service use. Benefits of nurse-led services remain inconclusive in terms of economic outcomes.Nurse-led care is a safe and feasible model of care for consideration across a number of ambulatory care settings. With appropriate training and support provided, nurse-led care is able to produce at least equivocal outcomes or at times better outcomes in terms of health-related quality of life compared to physician-led care or standard care for managing chronic conditions. There is a lack of high quality economic evaluations for nurse-led services, which is essential for guiding the decision making of health policy makers. Key factors such as education and qualification of the nurse; self-management support; resources available for the nurse; prescribing capabilities; and evaluation using appropriate outcome should be carefully considered for future planning of nurse-led services