Labourism and the commodification of work and social life

The thesis explores concepts of alienation and commodification in relation to public and private themes of identity, in contemporary Australia. It is argued that as labour conditions have intensified and the social safety net has eroded the emphasis on private themes of identity have increased. These themes emphasise sexuality and gender, and down-grade the issue of work and labour. The Australian Labor Party helped create the conditions for postmodernist identity politics weakening their commitment to working class improvement in favour of emphasising hypercapitalism and hyperliberal gender discourses. This approach favours the inclusion of marginal groups that have been traditionally outside of labourist concerns (women, homosexuals, Aborigines) at the expense of civilising capitalism, labour alienation and commodification as the central concern for workers. In short, the abandonment of Marxism, labourism and Social democracy: and their replacement by identity issues. The backlash to a post-welfare state social democracy designed to ameliorate conditions for marginal groups, become a key feature in the election of the Howard government in 1996, with Howards battlers consisting of former Labor voters disenfranchised by political correctness. This produced an attack on welfare cheats, high taxation, and trendy concerns such as Aboriginality � and reinforced Hansonism. In this context, the Australian and American relationship and the frontier tradition is stressed as a pivotal factor in determining the role of identity in the neo-liberal political economy, with the pressures created by neo-liberalism and globalisation. Australian mythology based on Anzac symbolism and personality creates a vacuous phenomenon for genuine themes of Australian national identity to survive the homogenous nature of hyper-capitalism. The drift towards the power of American capitalism and political cosmologies can then been seen as a natural evolution of Australian political mythology. It is here that the thesis argues that hyper capitalist themes can have an implicit relationship to concepts of hyper-liberalism found in gender discourses and moreover, ironically evocative of the individualism Weber argued existed in American Protestant religious sects. Subsequently the de-construction of masculinity that has been characteristic of feminist and gay theory, that reflects a social psychological perspective rather than one based in Marxs historical materialism that places man within social history. Social theory therefore unfairly constructs the heterosexual masculine personality in relation to working class elite occupations such as coalmining or as a reflection of a corporate dominance, to create polemic avenues for marginal groups. The focus upon heterosexuality within the thesis links its relationship to the characteristics demanded by industrial capitalism such as the Fordist mode of production, and in Marxist terms, the complete enslavement and alienation that existed between social man and the capitalist mode of production. This approach emphasises the experience of wage labour, culminating with the high levels of unemployment that has risen concomitantly with de-industrialisation, globalisation and neo-liberalism. The disciplining of the unemployed in the post-welfare state exists alongside hyper-liberal themes of sexual and social identity, indicating a general shift to a social fascism, or two- tiered form of democracy that resides alongside, and is often in competition with conservative advocates for the nuclear family and heterosexuality. The development of Howards battlers reflects a conservative appropriation of the original Australian legend that was based on labourism and mateship and now exists in a nationalist paradigm evocative of frontiersmen and Anzacs rather than one based on class. A framing issue for the thesis subsequently is what role does gender and sexuality have in the function of the industrial capitalist society

LC–MS/MS Bioanalysis of Radioligand Therapeutic Drug Candidate for Preclinical Toxicokinetic Assessment

Radioligand therapy (RLT) has gained significant momentum in recent years in the diagnosis, treatment, and monitoring of cancers. In preclinical development, the safety profile of RLT drug candidate(s) is investigated at relatively low dose levels using the cold (non-radioactive, e.g., 175Lu) ligand as a surrogate of the hot (radioactive, e.g., 177Lu) one in the “ligand-linker-chelator” complex. The formulation of the test article used in preclinical safety studies contains a mixture of free ligand (i.e., ligand-linker-chelator without metal) and cold ligand (i.e., ligand-linker-chelator with non-radioactive metal) in a similar molar ratio as seen under the manufacturing conditions for the RLT drug for clinical use, where only a fraction of free ligand molecules chelate the radioactive metal to form a hot ligand. In this very first report of LC–MS/MS bioanalysis of RLT molecules in support of a regulated preclinical safety assessment study, a highly selective and sensitive LC–MS/MS bioanalytical method was developed for the simultaneous determination of free ligand (NVS001) and cold ligand (175Lu-NVS001) in rat and dog plasma. Several unexpected technical challenges in relation to LC–MS/MS of RLT molecules were successfully addressed. The challenges include poor assay sensitivity of the free ligand NVS001, formation of the free ligand (NVS001) with endogenous metal (e.g., potassium), Ga loss from the Ga-chelated internal standard during sample extraction and analysis, “instability” of the analytes at low concentrations, and inconsistent IS response in the extracted plasma samples. The methods were validated according to the current regulatory requirements in a dynamic range of 0.5–250 ng/mL for both the free and cold ligands using a 25 μL sample volume. The validated method was successfully implemented in sample analysis in support of regulated safety studies, with very good results from incurred sample reanalysis. The current LC–MS/MS workflow can be expanded to quantitative analysis of other RLTs in support of preclinical RLT drug development

Reformulation initiative for partial replacement of saturated with unsaturated fats in dairy foods attenuates the increase in LDL cholesterol and improves flow-mediated dilatation compared with conventional dairy: the randomized, controlled REplacement of SaturatEd fat in dairy on Total cholesterol (RESET) study

Background: Modifying dairy fat composition by increasing the MUFA content is a potential strategy to reduce dietary SFA intake for cardiovascular disease (CVD) prevention in the population.Objectives: To determine the effects of consuming SFA-reduced, MUFA-enriched (modified) dairy products, compared with conventional dairy products (control), on the fasting cholesterol profile (primary outcome), endothelial function assessed by flow-mediated dilatation (FMD; key secondary outcome), and other cardiometabolic risk markers.Methods: A double-blind, randomized, controlled crossover 12-wk intervention was conducted. Participants with a 1.5-fold higher (moderate) CVD risk than the population mean replaced habitual dairy products with study products (milk, cheese, and butter) to achieve a high-fat, high-dairy isoenergetic daily dietary exchange [38% of total energy intake (%TE) from fat: control (dietary target: 19%TE SFA; 11%TE MUFA) and modified (16%TE SFA; 14%TE MUFA) diet].Results: Fifty-four participants (57.4% men; mean ± SEM age: 52 ± 3 y; BMI: 25.8 ± 0.5 kg/m2) completed the study. The modified diet attenuated the rise in fasting LDL cholesterol observed with the control diet (0.03 ± 0.06 mmol/L and 0.19 ± 0.05 mmol/L, respectively; P = 0.03). Relative to baseline, the %FMD response increased after the modified diet (0.35% ± 0.15%), whereas a decrease was observed after the control diet (−0.51% ± 0.15%; P Conclusions: In adults at moderate CVD risk, consumption of a high-fat diet containing SFA-reduced, MUFA-enriched dairy products for 12 wk showed beneficial effects on fasting LDL cholesterol and endothelial function compared with conventional dairy products. Our findings indicate that fatty acid modification of dairy products may have potential as a public health strategy aimed at CVD risk reduction. This trial was registered at clinicaltrials.gov as NCT02089035. Am J Clin Nutr 2020;00:1–10.</div

Impact of dairy fat manipulation on endothelial function and lipid regulation in human aortic endothelial cells exposed to human plasma samples: An in vitro investigation from the RESET study

Purpose: Longer-term intake of fatty acid (FA)-modified dairy products (SFA-reduced, MUFA-enriched) was reported to attenuate postprandial endothelial function in humans, relative to conventional (control) dairy. Thus, we performed an in vitro study in human aortic endothelial cells (HAEC) to investigate mechanisms underlying the effects observed in vivo.  Methods: This sub-study was conducted within the framework of the RESET study, a 12-week randomised controlled crossover trial with FA-modified and control dairy diets. HAEC were incubated for 24 h with post-intervention plasma samples from eleven adults (age: 57.5 ± 6.0 years; BMI: 25.7 ± 2.7 kg/m2) at moderate cardiovascular disease risk following representative sequential mixed meals. Markers of endothelial function and lipid regulation were assessed.  Results: Relative to control, HAEC incubation with plasma following the FA-modified treatment increased postprandial NOx production (P-interaction = 0.019), yet up-regulated relative E-selectin mRNA gene expression (P-interaction = 0.011). There was no impact on other genes measured.  Conclusion: Incubation of HAEC with human plasma collected after longer-term dairy fat manipulation had a beneficial impact on postprandial NOx production. Further ex vivo research is needed to understand the impact of partial replacement of SFA with unsaturated fatty acids in dairy foods on pathways involved in endothelial function.</p

Impact of dairy fat manipulation on endothelial function and lipid regulation in human aortic endothelial cells exposed to human plasma samples: An in vitro investigation from the RESET study

Purpose: Longer-term intake of fatty acid (FA)-modified dairy products (SFA-reduced, MUFA-enriched) was reported to attenuate postprandial endothelial function in humans, relative to conventional (control) dairy. Thus, we performed an in vitro study in human aortic endothelial cells (HAEC) to investigate mechanisms underlying the effects observed in vivo.  Methods: This sub-study was conducted within the framework of the RESET study, a 12-week randomised controlled crossover trial with FA-modified and control dairy diets. HAEC were incubated for 24 h with post-intervention plasma samples from eleven adults (age: 57.5 ± 6.0 years; BMI: 25.7 ± 2.7 kg/m2) at moderate cardiovascular disease risk following representative sequential mixed meals. Markers of endothelial function and lipid regulation were assessed.  Results: Relative to control, HAEC incubation with plasma following the FA-modified treatment increased postprandial NOx production (P-interaction = 0.019), yet up-regulated relative E-selectin mRNA gene expression (P-interaction = 0.011). There was no impact on other genes measured.  Conclusion: Incubation of HAEC with human plasma collected after longer-term dairy fat manipulation had a beneficial impact on postprandial NOx production. Further ex vivo research is needed to understand the impact of partial replacement of SFA with unsaturated fatty acids in dairy foods on pathways involved in endothelial function.</p

Postprandial fatty acid profile, but not cardiometabolic risk markers, is modulated by dairy fat manipulation in adults with moderate cardiovascular disease risk: the randomized, controlled RESET study

Background: Chronic consumption of dairy products with a saturated fatty acid (SFA)- reduced, monounsaturated fatty acid (MUFA)-enriched content was shown to impact favourably on brachial artery flow-mediated dilatation (FMD). However, their acute effect on postprandial cardiometabolic risk biomarkers requires investigation. Objective: The effects of sequential high-fat mixed meals rich in fatty acid (FA)-modified or conventional (control) dairy products on postprandial FMD (primary outcome) and systemic cardiometabolic biomarkers in adults with moderate cardiovascular risk (≥50% above population mean) were compared. Methods: In a randomized cross-over trial, fifty-two participants (mean ± SEM age 53 ± 2 y; BMI 25.9 ± 0.5 kg/m2 ) consumed high-dairy fat breakfast (0 min; ~50 g total fat: Modified: 25 g SFAs, 20 g MUFAs; Control: 32 g SFAs, 12 g MUFAs) and lunch (330 min; ~30 g total fat; Modified: 15 g SFAs, 12 g MUFAs; Control: 19 g SFAs, 7 g MUFAs). Blood samples were obtained before and until 480 min after breakfast, with FMD assessed at 0, 180, 300 and 420 min. Data were analysed by linear mixed models. Results: Postprandial changes in cardiometabolic biomarkers were comparable between the different dairy meals, with the exception of a tendency for a 4% higher area under the curve (AUC) for the %FMD response following the modified dairy fat meals (P = 0.075). Plasma total lipid FA analysis revealed that incremental AUC responses were 53% lower for total SFAs, 214% and 258% higher for total cis-MUFAs (predominantly cis-9 18:1), and trans 18:1 respectively following the modified, relative to control dairy meals (all P Conclusions: In adults at moderate cardiovascular risk, acute consumption of sequential high fat meals containing FA-modified dairy products had little impact on postprandial endothelial function or systemic cardiometabolic biomarkers, but a differential effect on the plasma total lipid FA profile, relative to conventional dairy fat meals

Effect of fat-reformulated dairy food consumption on postprandial flow-mediated dilatation and cardiometabolic risk biomarkers compared with conventional dairy: a randomized controlled trial

Background: Longer-term consumption of saturated fatty acid (SFA)-reduced, monounsaturated fatty acid (MUFA)-enriched dairy products have been reported to improve fasting flow-mediated vasodilation (FMD). Yet, their impact on endothelial function in the postprandial state warrants investigation. Objective: To compare the impact of a fatty acid (FA)-modified with a conventional (control) dairy diet on the postprandial %FMD (primary outcome) and systemic cardiometabolic responses to representative meals, and retrospectively explore whether treatment effects differ by apolipoprotein (APO)E or endothelial nitric oxide synthase (eNOS) Glu298Asp gene polymorphisms. Methods: In a crossover-design randomized controlled study, 52 adults with moderate cardiovascular disease risk consumed dairy products [38% total energy intake (%TE) from fat: FA-modified (target: 16%TE SFAs; 14%TE MUFAs) or control (19%TE SFAs; 11%TE MUFAs)] for 12-wk, separated by an 8-wk washout. Blood sampling and FMD measurements (0-480 min) were performed pre- and post-intervention after sequential mixed meals that were representative of the assigned dairy diets (0 min; ~50 g fat; 330 min; ~30 g fat). Results: Relative to pre-intervention (∆), the FA-modified dairy diet and meals (treatment) attenuated the increase in the incremental AUC (iAUC), but not AUC, for the %FMD response observed with the conventional treatment (-135 ± 69 vs +199 ± 82 % x min; P = 0.005). The ∆ iAUC, but not AUC, for the apoB response decreased after FA-modified yet increased after the conventional treatment (-4 ± 3 vs +3 ± 3 mg/mL x min; P = 0.004). The ∆ iAUC decreased for total plasma SFAs (P = 0.003) and trans 18:1 (P < 0.0001) and increased for cis-MUFAs (P < 0.0001) following conventional, relative to the FA-modified treatment. No treatment x APOE- or eNOS-genotype interactions were evident for any outcome. Conclusions: This study provides novel insights into the longer-term effects of FA-modified dairy food consumption on postprandial cardiometabolic responses. This study was registered at clinicaltrials.gov as NCT02089035

Effect of fat-reformulated dairy food consumption on postprandial flow-mediated dilatation and cardiometabolic risk biomarkers compared with conventional dairy: a randomized controlled trial

Background: Longer-term consumption of saturated fatty acid (SFA)-reduced, monounsaturated fatty acid (MUFA)-enriched dairy products have been reported to improve fasting flow-mediated vasodilation (FMD). Yet, their impact on endothelial function in the postprandial state warrants investigation. Objective: To compare the impact of a fatty acid (FA)-modified with a conventional (control) dairy diet on the postprandial %FMD (primary outcome) and systemic cardiometabolic responses to representative meals, and retrospectively explore whether treatment effects differ by apolipoprotein (APO)E or endothelial nitric oxide synthase (eNOS) Glu298Asp gene polymorphisms. Methods: In a crossover-design randomized controlled study, 52 adults with moderate cardiovascular disease risk consumed dairy products [38% total energy intake (%TE) from fat: FA-modified (target: 16%TE SFAs; 14%TE MUFAs) or control (19%TE SFAs; 11%TE MUFAs)] for 12-wk, separated by an 8-wk washout. Blood sampling and FMD measurements (0-480 min) were performed pre- and post-intervention after sequential mixed meals that were representative of the assigned dairy diets (0 min; ~50 g fat; 330 min; ~30 g fat). Results: Relative to pre-intervention (∆), the FA-modified dairy diet and meals (treatment) attenuated the increase in the incremental AUC (iAUC), but not AUC, for the %FMD response observed with the conventional treatment (-135 ± 69 vs +199 ± 82 % x min; P = 0.005). The ∆ iAUC, but not AUC, for the apoB response decreased after FA-modified yet increased after the conventional treatment (-4 ± 3 vs +3 ± 3 mg/mL x min; P = 0.004). The ∆ iAUC decreased for total plasma SFAs (P = 0.003) and trans 18:1 (P < 0.0001) and increased for cis-MUFAs (P < 0.0001) following conventional, relative to the FA-modified treatment. No treatment x APOE- or eNOS-genotype interactions were evident for any outcome. Conclusions: This study provides novel insights into the longer-term effects of FA-modified dairy food consumption on postprandial cardiometabolic responses. This study was registered at clinicaltrials.gov as NCT02089035