The digital Dark Ages : a retro-speculative history of possible futures

The Dark Ages are generally held to be a time of technological and intellectual stagnation in western development. But that is not necessarily the case. Indeed, from a certain perspective, nothing could be further from the truth. In this paper we draw historical comparisons, focusing especially on the thirteenth and fourteenth centuries, between the technological and intellectual ruptures in Europe during the Dark Ages, and those of our current period. Our analysis is framed in part by Harold Innis’s2 notion of "knowledge monopolies". We give an overview of how these were affected by new media, new power struggles, and new intellectual debates that emerged in thirteenth and fourteenth century Europe. The historical salience of our focus may seem elusive. Our world has changed so much, and history seems to be an increasingly far-from-favoured method for understanding our own period and its future potentials. Yet our seemingly distant historical focus provides some surprising insights into the social dynamics that are at work today: the fracturing of established knowledge and power bases; the democratisation of certain "sacred" forms of communication and knowledge, and, conversely, the "sacrosanct" appropriation of certain vernacular forms; challenges and innovations in social and scientific method and thought; the emergence of social world-shattering media practices; struggles over control of vast networks of media and knowledge monopolies; and the enclosure of public discursive and social spaces for singular, manipulative purposes. The period between the eleventh and fourteenth centuries in Europe prefigured what we now call the Enlightenment, perhaps moreso than any other period before or after; it shaped what the Enlightenment was to become. We claim no knowledge of the future here. But in the "post-everything" society, where history is as much up for sale as it is for argument, we argue that our historical perspective provides a useful analogy for grasping the wider trends in the political economy of media, and for recognising clear and actual threats to the future of the public sphere in supposedly democratic societies.

The digital Dark Ages : a retro-speculative history of possible futures

The Dark Ages are generally held to be a time of technological and intellectual stagnation in western development. But that is not necessarily the case. Indeed, from a certain perspective, nothing could be further from the truth. In this paper we draw historical comparisons, focusing especially on the thirteenth and fourteenth centuries, between the technological and intellectual ruptures in Europe during the Dark Ages, and those of our current period. Our analysis is framed in part by Harold Innis’s2 notion of "knowledge monopolies". We give an overview of how these were affected by new media, new power struggles, and new intellectual debates that emerged in thirteenth and fourteenth century Europe. The historical salience of our focus may seem elusive. Our world has changed so much, and history seems to be an increasingly far-from-favoured method for understanding our own period and its future potentials. Yet our seemingly distant historical focus provides some surprising insights into the social dynamics that are at work today: the fracturing of established knowledge and power bases; the democratisation of certain "sacred" forms of communication and knowledge, and, conversely, the "sacrosanct" appropriation of certain vernacular forms; challenges and innovations in social and scientific method and thought; the emergence of social world-shattering media practices; struggles over control of vast networks of media and knowledge monopolies; and the enclosure of public discursive and social spaces for singular, manipulative purposes. The period between the eleventh and fourteenth centuries in Europe prefigured what we now call the Enlightenment, perhaps moreso than any other period before or after; it shaped what the Enlightenment was to become. We claim no knowledge of the future here. But in the "post-everything" society, where history is as much up for sale as it is for argument, we argue that our historical perspective provides a useful analogy for grasping the wider trends in the political economy of media, and for recognising clear and actual threats to the future of the public sphere in supposedly democratic societies.

Motivations for an organisation within a developing country to report social responsibility information : evidence from Bangladesh

Purpose – The aim of the paper is to describe and explain, using a combination of interviews and content analysis, the social and environmental reporting practices of a major garment export organisation within a developing country. Design/methodology/approach – Senior executives from a major organisation in Bangladesh are interviewed to determine the pressures being exerted on them in terms of their social and environmental performance. The perceptions of pressures are then used to explain – via content analysis – changing social and environmental disclosure practices. Findings – The results show that particular stakeholder groups have, since the early 1990s, placed pressure on the Bangladeshi clothing industry in terms of its social performance. This pressure, which is also directly related to the expectations of the global community, in turn drives the industry's social policies and related disclosure practices. Research limitations/implications – The findings show that, within the context of a developing country, unless we consider the managers' perceptions about the social and environmental expectations being imposed upon them by powerful stakeholder groups then we will be unable to understand organisational disclosure practices. Originality/value – This paper is the first known paper to interview managers from a large organisation in a developing country about changing stakeholder expectations and then link these changing expectations to annual report disclosures across an extended period of analysis.

Settling sexual harassment complaints through conciliation : what complaints settle and what complaints don’t?

This paper explores why some complaints of sexual harassment lodged under Australian anti-discrimination laws might settle during the conciliation process while others do not. It draws on an analysis of data collected from files of sexual harassment complaints lodged with all state, territory and federal human rights agencies in the area of employment over a six month period. The analysis suggests that complaints that conform with the stereotypical image of sexual harassment, where a woman is physically sexually harassed by a senior man, are more likely to settle as are complaints where the complainant is in full-time, secure employment and where complainants are not legally represented. However, sustained Australian research, including by human rights agencies, is vital is to further explore these issues.

Unique X-linked familial FSGS with co-segregating heart block disorder is associated with a mutation in the NXF5 gene

Focal segmental glomerulosclerosis (FSGS) is the consequence of a disease process that attacks the kidney's filtering system, causing serious scarring. More than half of FSGS patients develop chronic kidney failure within 10 years, ultimately requiring dialysis or renal transplantation. There are currently several genes known to cause the hereditary forms of FSGS (ACTN4, TRPC6, CD2AP, INF2, MYO1E and NPHS2). This study involves a large, unique, multigenerational Australian pedigree in which FSGS co-segregates with progressive heart block with apparent X-linked recessive inheritance. Through a classical combined approach of linkage and haplotype analysis, we identified a 21.19 cM interval implicated on the X chromosome. We then used a whole exome sequencing approach to identify two mutated genes, NXF5 and ALG13, which are located within this linkage interval. The two mutations NXF5-R113W and ALG13-T141L segregated perfectly with the disease phenotype in the pedigree and were not found in a large healthy control cohort. Analysis using bioinformatics tools predicted the R113W mutation in the NXF5 gene to be deleterious and cellular studies support a role in the stability and localization of the protein suggesting a causative role of this mutation in these co-morbid disorders. Further studies are now required to determine the functional consequence of these novel mutations to development of FSGS and heart block in this pedigree and to determine whether these mutations have implications for more common forms of these diseases in the general population.

Industry policy, finance and the AIDC : Australia from the 1950s to the 1970s

This thesis, conceived within a Marxist framework, addresses key conceptual issues in the writing and theorising on industry policy in post second world- war Australia. Broadly, the thesis challenges the way that industry policy on the left of politics (reflected in the social democratic and Keynesian positions) has been constructed as a practical, progressive policy agenda. Specifically, the thesis poses a direct challenge to the primacy of the ‘national’ in interpreting the history of industry policy. The challenge is to the proposition that conflicts between national industry and international finance arose only from the mid 1980s. On the contrary, as will be seen, this is a 1960s issue and any interpretation of the debates and the agendas surrounding industry policy in the 1980s must be predicated on an understanding of how the issue was played out two decades earlier. As was the case in the 1960s, industry policy in the 1980s has been isolated from two key areas of interrogation: the role of the nation state in regulating accumulation and the role of finance in industry policy. In the 1950s and more so in the 1960s and early 1970s there was a reconfiguration of financing internationally but it is one that did not enter into industry policy analysis. The central concern therefore is to simultaneously sketch the historical political economy on industry policy from the 1950s through to the early 1970s in Australia and to analytically and empirically insert the role of finance into that history. In so doing the thesis addresses the economic and social factors that shaped the approach to industry finance in Australia during this critical period. The analysis is supported by a detailed examination of political and industry debates surrounding the proposal for, and institution of, a key national intervention in the form of the Australian Industry Development Corporation (AIDC).

Organizational reframing : the commercialization of a public sector organization

The purpose of this study is to elaborate shared schema change theory in the context of the radical restructuring-commercialization of an Australian public infrastructure organization. Commercialization of the case organization imposed high individual and collective cognitive processing and emotional demands as organizational members sought to develop new shared schema. Existing schema change research suggests that radical restructuring renders pre-existing shared schema irrelevant and triggers new schema development through experiential learning (Balogun and Johnson, 2004). Focus groups and semi-structured interviews were conducted at four points over a three-year period. The analysis revealed that shared schema change occurred in three broad phases: (1) radical restructuring and aftermath; (2) new CEO and new change process schema, and: (3) large-group meeting and schema change. Key findings include: (1) radical structural change does not necessarily trigger new shared schema development as indicated in prior research; (2) leadership matters, particularly in framing new means-ends schema; (3) how change leader interventions are sequenced has an important influence on shared schema change, and; (4) the creation of facilitated social processes have an important influence on shared schema change.

Depression scores predict adherence in a dietary weight loss intervention trial

Background & aims Depression has a complex association with cardiometabolic risk, both directly as an independent factor and indirectly through mediating effects on other risk factors such as BMI, diet, physical activity, and smoking. Since changes to many cardiometabolic risk factors involve behaviour change, the rise in depression prevalence as a major global health issue may present further challenges to long-term behaviour change to reduce such risk. This study investigated associations between depression scores and participation in a community-based weight management intervention trial. Methods A group of 64 overweight (BMI > 27), otherwise healthy adults, were recruited and randomised to follow either their usual diet, or an isocaloric diet in which saturated fat was replaced with monounsaturated fat (MUFA), to a target of 50% total fat, by adding macadamia nuts to the diet. Subjects were assessed for depressive symptoms at baseline and at ten weeks using the Beck Depression Inventory (BDI-II). Both control and intervention groups received advice on National Guidelines for Physical Activity and adhered to the same protocol for food diary completion and trial consultations. Anthropometric and clinical measurements (cholesterol, inflammatory mediators) also were taken at baseline and 10 weeks. Results During the recruitment phase, pre-existing diagnosed major depression was one of a range of reasons for initial exclusion of volunteers from the trial. Amongst enrolled participants, there was a significant correlation (R = −0.38, p < 0.05) between BDI-II scores at baseline and duration of participation in the trial. Subjects with a baseline BDI ≥10 (moderate to severe depression symptoms) were more likely to dropout of the trial before week 10 (p < 0.001). BDI-II scores in the intervention (MUFA) diet group decreased, but increased in the control group over the 10-week period. Univariate analysis of variance confirmed these observations (adjusted R2 = 0.257, p = 0.01). Body weight remained static over the 10-week period in the intervention group, corresponding to a relative increase in the control group (adjusted R2 = 0.097, p = 0.064). Conclusions Depression symptoms have the potential to affect enrolment in and adherence to dietbased risk reduction interventions, and may consequently influence the generalisability of such trials. Depression scores may therefore be useful for characterising, screening and allocating subjects to appropriate treatment pathways.

IL-23 is pro-proliferative, epigenetically regulated and modulated by chemotherapy in non-small cell lung cancer

Background IL-23 is a member of the IL-6 super-family and plays key roles in cancer. Very little is currently known about the role of IL-23 in non-small cell lung cancer (NSCLC). Methods RT-PCR and chromatin immunopreciptiation (ChIP) were used to examine the levels, epigenetic regulation and effects of various drugs (DNA methyltransferase inhibitors, Histone Deacetylase inhibitors and Gemcitabine) on IL-23 expression in NSCLC cells and macrophages. The effects of recombinant IL-23 protein on cellular proliferation were examined by MTT assay. Statistical analysis consisted of Student's t-test or one way analysis of variance (ANOVA) where groups in the experiment were three or more. Results In a cohort of primary non-small cell lung cancer (NSCLC) tumours, IL-23A expression was significantly elevated in patient tumour samples (p<0.05). IL-23A expression is epigenetically regulated through histone post-translational modifications and DNA CpG methylation. Gemcitabine, a chemotherapy drug indicated for first-line treatment of NSCLC also induced IL-23A expression. Recombinant IL-23 significantly increased cellular proliferation in NSCLC cell lines. Conclusions These results may therefore have important implications for treating NSCLC patients with either epigenetic targeted therapies or Gemcitabine. © 2012 Elsevier Ireland Ltd.

Quality of life and survival in patients treated with radical chemoradiation alone for oesophageal cancer

Aims: To report cancer-specific and health-related quality-of-life outcomes in patients undergoing radical chemoradiation (CRT) alone for oesophageal cancer. Materials and methods: Between 1998 and 2005, 56 patients with oesophageal cancer received definitive radical CRT, due to local disease extent, poor general health, or patient choice. Data from European Organization for Research and Treatment of Cancer quality-of-life questionnaires QLQ-30 and QLQ-OES24 were collected prospectively. Questionnaires were completed at diagnosis, and at 3, 6 and 12 months after CRT where applicable. Results: The median follow-up was 18 months. The median overall survival was 14 months, with a 51, 26 and 13% 1-, 3- and 5-year survival, respectively. At 12 months after treatment there was a significant improvement compared with before treatment with respect to dysphagia and pain. Global health scores were not significantly affected. Conclusions: Considering the relatively short long-term survival for this cohort of patients, maximising the quality of those final months should be very carefully borne in mind from the outset. The health-related quality-of-life data reported herein helps to establish benchmarks for larger evaluation within randomised clinical trials. © 2007 The Royal College of Radiologists.

Single-agent versus combination chemotherapy in patients with advanced non-small cell lung cancer and a performance status of 2 : prognostic factors and treatment selection based on two large randomized clinical trials

Purpose: Data from two randomized phase III trials were analyzed to evaluate prognostic factors and treatment selection in the first-line management of advanced non-small cell lung cancer patients with performance status (PS) 2. Patients and Methods: Patients randomized to combination chemotherapy (carboplatin and paclitaxel) in one trial and single-agent therapy (gemcitabine or vinorelbine) in the second were included in these analyses. Both studies had identical eligibility criteria and were conducted simultaneously. Comparison of efficacy and safety was performed between the two cohorts. A regression analysis identified prognostic factors and subgroups of patients that may benefit from combination or single-agent therapy. Results: Two hundred one patients were treated with combination and 190 with single-agent therapy. Objective responses were 37 and 15%, respectively. Median time to progression was 4.6 months in the combination arm and 3.5 months in the single-agent arm (p < 0.001). Median survival imes were 8.0 and 6.6 months, and 1-year survival rates were 31 and 26%, respectively. Albumin <3.5 g, extrathoracic metastases, lactate dehydrogenase ≥200 IU, and 2 comorbid conditions predicted outcome. Patients with 0-2 risk factors had similar outcomes independent of treatment, whereas patients with 3-4 factors had a nonsignificant improvement in median survival with combination chemotherapy. Conclusion: Our results show that PS2 non-small cell lung cancer patients are a heterogeneous group who have significantly different outcomes. Patients treated with first-line combination chemotherapy had a higher response and longer time to progression, whereas overall survival did not appear significantly different. A prognostic model may be helpful in selecting PS 2 patients for either treatment strategy. © 2009 by the International Association for the Study of Lung Cancer.

RanGTPase : a candidate for myc-mediated cancer progression

Background Ras-related nuclear protein (Ran) is required for cancer cell survival in vitro and human cancer progression, but the molecular mechanisms are largely unknown. Methods We investigated the effect of the v-myc myelocytomatosis viral oncogene homolog (Myc) on Ran expression by Western blot, chromatin immunoprecipitation, and luciferase reporter assays and the effects of Myc and Ran expression in cancer cells by soft-agar, cell adhesion, and invasion assays. The correlation between Myc and Ran and the association with patient survival were investigated in 14 independent patient cohorts (n = 2430) and analyzed with Spearman's rank correlation and Kaplan-Meier plots coupled with Wilcoxon-Gehan tests, respectively. All statistical tests were two-sided. Results Myc binds to the upstream sequence of Ran and transactivates Ran promoter activity. Overexpression of Myc upregulates Ran expression, whereas knockdown of Myc downregulates Ran expression. Myc or Ran overexpression in breast cancer cells is associated with cancer progression and metastasis. Knockdown of Ran reverses the effect induced by Myc overexpression in breast cancer cells. In clinical data, a positive association between Myc and Ran expression was revealed in 288 breast cancer and 102 lung cancer specimens. Moreover, Ran expression levels differentiate better or poorer survival in Myc overexpressing breast (χ2 = 24.1; relative risk [RR] = 9.1, 95% confidence interval [CI] = 3.3 to 24.7, P <. 001) and lung (χ2 = 6.04; RR = 2.8, 95% CI = 1.2 to 6.3; P =. 01) cancer cohorts. Conclusions Our results suggest that Ran is required for and is a potential therapeutic target of Myc-driven cancer progression in both breast and lung cancers. © 2013 The Author.

Influence of polymorphisms of the human glutathione transferases and cytochrome P450 2E1 enzyme on the metabolism and toxicity of ethylene oxide and acrylonitrile

A cohort of 59 persons with industrial handling of low levels of acrylonitrile is being studied as part of a medical surveillance programme. Previously, an extended haemoglobin adduct monitoring (N-(cyanoethyl)valine and N-(hydroxyethyl)-valine) was performed regarding the glutathione transferases hGSTM1 and hGSTT1 polymorphisms but no influence of hGSTM1 or hGSTT1 polymorphisms on specific adduct levels was found. A compilation of case reports of human accidental poisonings had pointed to significant individual differences in human acrylonitrile metabolism and toxicity. Therefore, a re-evaluation of the industrial cohort included known polymorphisms of the glutathione transferases hGSTM3 and hGSTP1 as well as of the cytochrome P450 CYP2E1. A detailed statistical analysis revealed that exposed carriers of the allelic variants of hGSTP1, hGSTP1*B/hGSTP1*C, characterized by a single nucleotide polymorphism at nucleotide 313 which results in a change from Ile to Val at codon 104, had higher levels of the acrylonitrile-specific haemoglobin adduct N-(cyanoethyl)valine compared to the carriers of the codon 113 alleles hGSTP1*A and hGSTP1*D. The single nucleotide polymorphism at codon 113 of hGSTP1 (hGSTP1*A/hGSTP1*B versus hGSTP1*C/hGSTP1*D) did not show an effect, and also no influence was seen on specific haemoglobin adduct levels of the polymorphisms of hGSTM3 or CYP2E1. The data, therefore, point to a possible influence of a human enzyme polymorphism of the GSTP1 gene at codon 104 on the detoxication of acrylonitrile which calls for experimental toxicological investigation. The study also confirmed the impact of GSTT1 polymorphism on background N-(hydroxyethyl)-valine adduct levels in haemoglobin which are caused by endogenous ethylene oxide.

Biological monitoring in workers in a nitrobenzene reduction plant : Haemoglobin versus serum albumin adducts

The high priority of monitoring workers exposed to nitrobenzene is a consequence of clear findings of experimental carcinogenicity of nitrobenzene and the associated evaluations by the International Agency for Research on Cancer. Eighty male employees of a nitrobenzene reduction plant, with potential skin contact with nitrobenzene and aniline, participated in a current medical surveillance programme. Blood samples were routinely taken and analysed for aniline, 4-aminodiphenyl (4-ADP) and benzidine adducts of haemoglobin (Hb) and human serum albumin (HSA). Also, levels of methaemoglobin (Met-Hb) and of carbon monoxide haemoglobin (CO-Hb) were monitored. Effects of smoking were straightforward. Using the rank sum test of Wilcoxon, we found that very clear-cut and statistically significant smoking effects (about 3-fold increases) were apparent on CO-Hb (P = 0.00085) and on the Hb adduct of 4-ADP (P = 0.0006). The mean aniline-Hb adduct level in smokers was 1.5 times higher than in non-smokers; the significance (P = 0.05375) was close to the 5% level. The strongest correlation was evident between the Hb and HSA adducts of aniline (rs = 0.846). Less pronounced correlations (but with P values < 0.02) appeared between aniline-Hb and 4-ADP-Hb adducts (rs = 0.388), between 4-ADP and 4-ADP-HSA adducts (rs = 0.373), and between 4-ADP-Hb and aniline-HSA adducts (rs = 0.275). In view of the proposal for additional use of the aniline-HSA adduct for biological monitoring, particularly in cases of acute overexposures or poisonings, the strong correlation of the Hb and HSA conjugates is noteworthy; the ratio aniline-HSA:aniline-Hb was 1:42 for the entire cohort.