Serum Calcium and the Risk of Breast Cancer: Findings from the Swedish AMORIS Study and a Meta-Analysis of Prospective Studies

To investigate the association between serum calcium and risk of breast cancer using a large cohort and a systematic review with meta-analysis. From the Swedish Apolipoprotein Mortality Risk (AMORIS) Study we included 229,674 women who had baseline measurements of serum total calcium and albumin. Multivariable Cox regression was used to assess the association between total and albumin-corrected calcium and breast cancer risk. For the systematic review, an electronic search of MEDLINE and EMBASE databases was performed to identify other prospective cohorts assessing the relationship between serum calcium and breast cancer risk. We pooled the results of our AMORIS cohort with other eligible studies in a meta-analysis using a random effects model. I² test was used to assess heterogeneity. In the AMORIS study, 10,863 women were diagnosed with breast cancer (mean follow-up: 19 years). We found an inverse association between total serum calcium and breast cancer when comparing the fourth quartile to the first quartile (HR: 0.94, 95% CI: 0.88-0.99, p value for trend 0.04) and similar results using albumin-corrected calcium. In the systematic review, we identified another two prospective cohorts evaluating pre-diagnostic serum total calcium and breast cancer. Combining these studies and our findings in AMORIS in a meta-analysis showed a protective effect of serum calcium against breast cancer, with a summary RR of 0.80 (95% CI: 0.66-0.97). No substantial heterogeneity was observed. Our findings in AMORIS and the meta-analysis support an inverse association between serum calcium and breast cancer risk, which warrants mechanistic investigations

Circulating gamma-glutamyl transferase and development of specific breast cancer subtypes: findings from the Apolipoprotein Mortality Risk (AMORIS) cohort

BACKGROUND: Different etiological pathways may precede development of specific breast cancer subtypes and impact prevention or treatment strategies. We investigated the association between gamma-glutamyl transferase (GGT) and development of specific breast cancer subtypes based on oestrogen receptor (ER), progesterone receptor (PR) and HER2 status. METHODS: We included 231,283 cancer-free women in a Swedish cohort. Associations between GGT and breast cancer subtypes were investigated with nested case-control and case-case analyses. We used logistic regression models to assess serum GGT in relation to breast cancer subtype, based on individual and combined receptor status. RESULTS: Positive associations were found between serum GGT and development of ER+, ER- and PR+ breast cancers compared to controls (odds ratio (OR) 1.14 (95% confidence interval (CI) 1.08-1.19), 1.11 (1.01-1.23) and 1.18 (1.12-1.24), respectively) and of ER+/PR+ tumours. We found inverse associations between GGT levels and PR- breast cancers compared to PR+ (OR 0.87 (0.80-0.95)), between ER+/PR- tumours compared to ER+/PR+ tumours and between ER-/PR-/HER+ compared to ER+/HER2 or PR+/HER2 tumours (OR 0.55 (95% CI 0.34-0.90). CONCLUSION: The observed associations between pre-diagnostic serum GGT and different breast cancer subtypes may indicate distinct underlying pathways and require further investigations to tease out their clinical implications

Revisiting the Users Award Programme from a Value Sensitive Design Perspective

The goal of the UsersAward (UA) programme is to develop and maintain a strategy for enhancing the quality of workplace software through on-going user-driven quality assessment. Key activities are development of sets of quality criteria, as the USER CERTIFIED 2002 and 2006 instruments, and performing large domain specific user satisfaction surveys building on these quality criteria. In 2005 we performed a first analysis of the values that inform the criteria and procedure making up the 2002 instrument, using the Value Sensitive Design methodology. This paper is a follow-up of that study. We report on new types of stakeholders having engaged with the UA programme and reflect on how the conceptual considerations and explicit values of the programme have shifted as a consequence.

Revisiting the Users Award Programme from a Value Sensitive Design Perspective

The goal of the UsersAward (UA) programme is to develop and maintain a strategy for enhancing the quality of workplace software through on-going user-driven quality assessment. Key activities are development of sets of quality criteria, as the USER CERTIFIED 2002 and 2006 instruments, and performing large domain specific user satisfaction surveys building on these quality criteria. In 2005 we performed a first analysis of the values that inform the criteria and procedure making up the 2002 instrument, using the Value Sensitive Design methodology. This paper is a follow-up of that study. We report on new types of stakeholders having engaged with the UA programme and reflect on how the conceptual considerations and explicit values of the programme have shifted as a consequence.

Antioxidants inhibit low density lipoprotein oxidation less at lysosomal pH: a possible explanation as to why the clinical trials of antioxidants might have failed

Oxidised low density lipoprotein (LDL) was considered to be important in the pathogenesis of atherosclerosis, but the large clinical trials of antioxidants, including the first one using probucol (the PQRST Trial), failed to show benefit and have cast doubt on the importance of oxidised LDL. We have shown previously that LDL oxidation can be catalysed by iron in the lysosomes of macrophages. The aim of this study was therefore to investigate the effectiveness of antioxidants in preventing LDL oxidation at lysosomal pH and also establish the possible mechanism of oxidation. Probucol did not effectively inhibit the oxidation of LDL at lysosomal pH, as measured by conjugated dienes or oxidised cholesteryl esters or tryptophan residues in isolated LDL or by ceroid formation in the lysosomes of macrophage-like cells, in marked contrast to its highly effective inhibition of LDL oxidation at pH 7.4. LDL oxidation at lysosomal pH was inhibited very effectively for long periods by N,N'-diphenyl-1,4-phenylenediamine, which is more hydrophobic than probucol and has been shown by others to inhibit atherosclerosis in rabbits, and by cysteamine, which is a hydrophilic antioxidant that accumulates in lysosomes. Iron-induced LDL oxidation might be due to the formation of the superoxide radical, which protonates at lysosomal pH to form the much more reactive, hydrophobic hydroperoxyl radical, which can enter LDL and reach its core. Probucol resides mainly in the surface monolayer of LDL and would not effectively scavenge hydroperoxyl radicals in the core of LDL. This might explain why probucol failed to protect against atherosclerosis in various clinical trials. The oxidised LDL hypothesis of atherosclerosis now needs to be re-evaluated using different and more effective antioxidants that protect against the lysosomal oxidation of LDL

The Platform Review Alliance Board:Designing an organisational model to bring together producers and consumers in the review and commissioning of platform software

Digital networking technology has helped to bring about the platform economy, in which online networking sites mediate between individual freelance workers and their temporary employers. However, the digital platform economy undermines traditional forms of collective action, particularly trade unions. Following reflections on 15 years of trade union software quality assurance initiatives, particularly the Swedish UserAward program, we realize that there are potential benefits in combining aspects of cooperative, guild, and trade union models in the context of the platform economy. We examine the role that these models could play in enabling new forms of collective action and we bring them together in the form of a conceptual model which we have called the Platform Review Alliance Board. We articulate the Platform Review Alliance model as a set of design patterns, which we invite stakeholders to comment on, refine, and ultimately subscribe to. We then apply these design patterns in the domain of transport. In this domain, we show how software producers, users of the software, and other stakeholders, including individual transport providers, can participate in a Review Alliance Board for the commissioning, production, and review of software platforms for transport systems. The contribution we make is to propose how membership in a Review Alliance Board can be an alternative strategy for both software producers and trade union representatives in taking collective action to assure the quality of workplace software in the context of the growing platform economy

Exploring a new producer-consumer interaction model for facilitating collective action in the collaborative economy

Digital networking technology has helped to bring about the networked society, including new forms of organization and production. In what has been called the collaborative economy, online networking sites act as platforms to mediate between individual freelance workers and customers. These platforms benefit customers as they can find the lowest price for products and services worldwide, but workers do not have the job security or benefits that workers in more traditional organizations have. The collaborative economy also undermines traditional forms of collective action, particularly trade unions, who have lost members in recent years. However, these traditional forms of organization, including cooperatives and guild-like organizations as well as trade unions, are arguably more relevant than ever as growing numbers of individual freelance workers interact with their customers via online platforms. Following reflections on fifteen years of trade union software quality assurance initiatives, particularly the Swedish UserAward program, we realize that there are potential benefits in combining aspects of cooperative, guild and trade union models to promote collective action in the context of the growing collaborative economy. We examine the role that these models could play in enabling user participation and influence and bring them together in the form of a conceptual model which we have called a Software Review Alliance Board. The contribution we make is to propose how a Review Alliance Board model can be an alternative strategy for both software producers and trade unions in assuring the quality of workplace software. Through this model, union members, software programmers, workplace managers and researchers can participate in collective action through the Alliance Board. We propose that a Value Sensitive Design process that considers both direct and indirect stakeholders is appropriate to implement this model