122 - Using CRISPR/Cas9 Genome Editing to Knockout MHC Class I in Xenopus laevis

The immune system of the frog Xenopus laevis is similar to humans. MHC Class I is a vital molecule for the immune system of Xenopus laevis. It presents peptides to CD8 T-cells and the presentation of self peptide fragments is crucial for immune self recognition. When MHC Class I presents non-self peptide fragments, it triggers an immune response, causing CD8 T-cells to kill the infected cells. All cells express some level of MHC Class I because all cells can be infected. The role this molecule plays in immune function and self recognition is of particular interest in Xenopus laevis since tadpoles are immunocompetent, yet have undetectable levels of MHC Class I protein (mRNA can be detected in different tissues). MHC Class I protein levels become detectable after metamorphosis and are expressed both as mRNA and protein in adult frogs. We are interested to see if MHC Class I is critical for immune function in Xenopus laevis tadpoles and will investigate by knocking out the MHC Class I gene. To do this, we utilized the CRISPR/Cas9 gene editing tool. Cas9 creates a break in the dsDNA at the location of the gene by using specific guide RNAs, and while the cell attempts to fix its genome multiple insertions and/or deletions can occur in the sequence that inactivates the gene. We generated transgenic tadpoles that have guide RNAs targeting the MHC class I gene. Currently, we are using DNA sequencing to verify successful knockout of the MHC Class I gene

Erich Fromm and the Critical Theory of Communication

Erich Fromm (1900-1980) was a Marxist psychoanalyst, philosopher and socialist humanist. This paper asks: How can Fromm’s critical theory of communication be used and updated to provide a critical perspective in the age of digital and communicative capitalism? In order to provide an answer, the article discusses elements from Fromm’s work that allow us to better understand the human communication process. The focus is on communication (section 2), ideology (section 3), and technology (section 4). Fromm’s approach can inform a critical theory of communication in multiple respects: His notion of the social character allows to underpin such a theory with foundations from critical psychology. Fromm’s distinction between the authoritarian and the humanistic character can be used for discerning among authoritarian and humanistic communication. Fromm’s work can also inform ideology critique: The ideology of having shapes life, thought, language and social action in capitalism. In capitalism, technology (including computing) is fetishized and the logic of quantification shapes social relations. Fromm’s quest for humanist technology and participatory computing can inform contemporary debates about digital capitalism and its alternatives

Transcutanous aortic valve replacement with Medtronic CoreValve in a publicprivate partnership hospital complex

Objective: The aim of this study was to assess the initial experience of transcutaneous aortic valve implantation (TAVI) in a high risk aortic stenosis population not suitable for conventional surgical valve replacement. Background: No data exist for TAVI with Medtronic CoreValve in South Africa and especially not in a public private partnership hospital complex. Methods: Retrospective data regarding severe aortic stenosis evaluation, risk stratifi cation and management were evaluated over a 24 month period. Results: A total of 106 patients were evaluated of whom17 were accepted for surgical valve replacement (SVR) while TAVI was attempted in 25. The CoreValve was successfully implanted in 96% (24/25) of the cases. No procedural or peri-procedural deaths occurred. Threepatients required permanent pacemaker insertion in the peri-procedural period and 2 patients had vascular access complications requiring blood transfusion only. Median hospital stay was 3.7days (range: 2 - 7). Aortic valve gradient showed a signifi cant reduction after valve implantation, which was sustained during follow-up (p<0.001). NYHA class symptomatology also improved from a median of 3.3 to 1.0 (p<0.001). During follow-up there were 4 late deaths, not related to the procedure, occurring after 78 to 193 days. Average cost for private and government patients were R268 000.00 and R163 000.00 respectively. Conclusions: The CoreValve can be implanted with a high success rate. Short term mortality and morbidity are acceptable. Signifi cant symptomatic improvement is gained at follow-up. The fi nancial implications are important

Pain and analgesic use associated with skeletal-related events in patients with advanced cancer and bone metastases

PURPOSE: Bone metastases secondary to solid tumors increase the risk of skeletal-related events (SREs), including the occurrence of pathological fracture (PF), radiation to bone (RB), surgery to bone (SB), and spinal cord compression (SCC). The aim of this study was to evaluate the impact of SREs on patients' pain, analgesic use, and pain interference with daily functioning. METHODS: Data were combined from patients with solid tumors and bone metastases who received denosumab or zoledronic acid across three identically designed phase 3 trials (N = 5543). Pain severity (worst pain) and pain interference were assessed using the Brief Pain Inventory at baseline and each monthly visit. Analgesic use was quantified using the Analgesic Quantification Algorithm. RESULTS: The proportion of patients with moderate/severe pain and strong opioid use generally increased in the 6 months preceding an SRE and remained elevated, while they remained relatively consistent over time in patients without an SRE. Regression analysis indicated that all SRE types were significantly associated with an increased risk of progression to moderate/severe pain and strong opioid use. PF, RB, and SCC were associated with significantly greater risk of pain interference overall. Results were similar for pain interference with emotional well-being. All SRE types were associated with significantly greater risk of pain interference with physical function. CONCLUSIONS: SREs are associated with increased pain and analgesic use in patients with bone metastases. Treatments that prevent SREs may decrease pain and the need for opioid analgesics and reduce the impact of pain on daily functioning

Pain and analgesic use associated with skeletal-related events in patients with advanced cancer and bone metastases

PURPOSE: Bone metastases secondary to solid tumors increase the risk of skeletal-related events (SREs), including the occurrence of pathological fracture (PF), radiation to bone (RB), surgery to bone (SB), and spinal cord compression (SCC). The aim of this study was to evaluate the impact of SREs on patients' pain, analgesic use, and pain interference with daily functioning. METHODS: Data were combined from patients with solid tumors and bone metastases who received denosumab or zoledronic acid across three identically designed phase 3 trials (N = 5543). Pain severity (worst pain) and pain interference were assessed using the Brief Pain Inventory at baseline and each monthly visit. Analgesic use was quantified using the Analgesic Quantification Algorithm. RESULTS: The proportion of patients with moderate/severe pain and strong opioid use generally increased in the 6 months preceding an SRE and remained elevated, while they remained relatively consistent over time in patients without an SRE. Regression analysis indicated that all SRE types were significantly associated with an increased risk of progression to moderate/severe pain and strong opioid use. PF, RB, and SCC were associated with significantly greater risk of pain interference overall. Results were similar for pain interference with emotional well-being. All SRE types were associated with significantly greater risk of pain interference with physical function. CONCLUSIONS: SREs are associated with increased pain and analgesic use in patients with bone metastases. Treatments that prevent SREs may decrease pain and the need for opioid analgesics and reduce the impact of pain on daily functioning

The New ‘Hidden Abode’: Reflections on Value and Labour in the New Economy

In a pivotal section of Capital, volume 1, Marx (1976: 279) notes that, in order to understand the capitalist production of value, we must descend into the ‘hidden abode of production’: the site of the labour process conducted within an employment relationship. In this paper we argue that by remaining wedded to an analysis of labour that is confined to the employment relationship, Labour Process Theory (LPT) has missed a fundamental shift in the location of value production in contemporary capitalism. We examine this shift through the work of Autonomist Marxists like Hardt and Negri, Lazaratto and Arvidsson, who offer theoretical leverage to prize open a new ‘hidden abode’ outside employment, for example in the ‘production of organization’ and in consumption. Although they can open up this new ‘hidden abode’, without LPT's fine-grained analysis of control/resistance, indeterminacy and structured antagonism, these theorists risk succumbing to empirically naive claims about the ‘new economy’. Through developing an expanded conception of a ‘new hidden abode’ of production, the paper demarcates an analytical space in which both LPT and Autonomist Marxism can expand and develop their understanding of labour and value production in today's economy. </jats:p