A Critical Engagement with Piratical Opinion

A study of the intellectual property crime commonly known as ‘file sharing’ using the file sharing websites on which users display their activity and post comments. As a guide I will use a meta-theoretical framework first developed by Roger Sibeon and then expanded by Tim Owen to help focus the research through a post-postmodern return to sociological and criminological theory. This research also acknowledges a physical/biological component to all intangibility, internet and computer related activity and tries to build further a relationship between the physical and intangible spheres of existence. It is acknowledged here that individuals are not predetermined to commit certain actions because they are biologically programmed to do so, rather that genes can influence behaviour and behaviour can influence genes

Silenced by Free Speech: How cyberabuse affects debate and democracy

The early days of the internet promised freedom from prejudice thanks to anonymity, freedom from the gatekeepers of traditional media, and even freedom from ourselves thanks to the capacity to invent new selves. Pioneers believed this would herald true freedom of speech, but the reality has proved disappointing in terms of debate and democracy. This chapter looks at the various ways some groups, particularly women, are drowned out by organised gangs, forced out through tactics such as doxxing and swatting, or simply forced offline through repeated abuse and harassment. It pulls together research from various organisations including the Guardian, domestic abuse charities and Demos, and examines the growth of online lynchmobs and the belief systems behind them

Appalachian Research Day: Come Sit on the Porch [2016]

Rural Appalachian communities in eastern Kentucky suffer from some of the Nation’s most concerning health disparities. Community-based research can be an effective way to address health disparities by identifying problems and sharing innovative solutions. However, challenges exist in recruiting and retaining research participants in rural populations that can often be difficult to reach. Partnerships between researchers and communities are essential to the success of the research process, particularly translation of findings back into the community

Appalachian Research Day: Come Sit on the Porch

Rural Appalachian communities in eastern Kentucky suffer from some of the Nation’s most concerning health disparities. Community-based research can be an effective way to address health disparities by identifying problems and sharing innovative solutions. However, challenges exist in recruiting and retaining research participants in rural populations that can often be difficult to reach. Partnerships between researchers and communities are essential to the success of the research process, particularly translation of findings back into the communit

Tandem antifibrotic actions of L-arginine supplementation and low protein diet during the repair phase of experimental glomerulonephritis

Tandem antifibrotic actions of L-arginine supplementation and low protein diet during the repair phase of experimental glomerulonephritis.BackgroundBased upon the central role transforming growth factor-beta (TGF-β) overexpression appears to play in renal fibrotic diseases, we have recently advocated reduction of TGF-β as a therapeutic target. As part of efforts to determine the strength of this approach, we have undertaken studies to quantitate the effects of currently used and promising therapies in terms of their potential to reduce markers of disease in anti-thymocyte-serum (ATS)-glomerulonephritis in the rat. Here we assess the therapeutic effect of L-arginine supplementation, which has been shown to reduce fibrosis in a number of hypertensive models, given alone or in combination with low protein diet and started 24 hours after disease induction.MethodsGlomerulonephritis was induced by intravenous injection of OX-7 monoclonal antibody into 200g Sprague-Dawley rats. Twenty-four hours later animals were placed in groups that were either untreated, treated with 1% L-arginine in drinking water or 6% protein diets or both. On the fifth day of disease 24-hour urine specimens were collected and systemic blood pressure was measured. On the sixth day rats were anesthetized. Kidneys were perfused, tissue was taken for PAS staining and glomeruli were isolated. Aliquots of glomeruli were used for RNA preparation and for culture to determine 72-hour production of TGF-β, fibronectin and plasminogen activator-type 1 (PAI-1), which were assayed by ELISA on culture supernatants. Measures of nitrate and nitrite (NOx) production included plasma NOx, urinary NOx and glomerular production of NOx in culture.ResultsAll disease measures except proteinuria and including matrix accumulation, TGF-β, fibronectin and PAI-1 production and mRNA expression for TGF-β, fibronectin and PAI-1 were significantly and similarly reduced by about 50% in groups treated with L-arginine or with low protein diet. Proteinuria was reduced in low protein treated but not in L-arginine supplemented rats. Neither systemic blood pressure nor measures of NO synthesis showed differences between groups that could be attributed to L-arginine supplementation. In contrast, disease-related increases in glomerular production of NOx were markedly reduced by low protein. Combined therapy resulted in small, but statistically significant decreases in most measures of disease.ConclusionsL-arginine supplementation reduces fibrotic disease in ATS-induced glomerulonephritis if started after disease induction. The absence of evidence for increased NO production related to L-arginine supplementation suggests that L-arginine is acting here through different pathways from those demonstrated in hypertensive models of disease. The data support the ideas that TGF-β reduction is a valid therapeutic target and that quantitation of TGF-β reduction is a useful approach for comparing antifibrotic drug candidates

Adapting an Evidence-Based Intervention for Rural Women with Depression

Background: Prevalence of depression among rural women is nearly 4 times the national average Depression prevalence particularly high in Central Appalachia Limited services and social barriers restrict treatment acces

A Nietzschean Analysis of Cybercrime and Deviance

The intention of this thesis is to examine various types of online deviance, such as ‘trolling’ and other forms of cyber bullying with special attention paid to the deviance which occurs on social networking sites and peer-2-peer file sharing websites. The central claim of this thesis is that deviant behaviour can be influenced (encouraged, magnified) by ‘ressentiment’, which can reside within the individual. This ‘ressentiment’ forms part of a complex array of situational factors called ‘Flexible Causal Prediction’, whereby individuals may experience a particularly strong influence on behaviour but are not predetermined to act in certain ways. In this thesis the author uses Nietzsche’s philosophical notions of ‘Nihilism’, ‘Slave Morality’, ‘ressentiment’, ‘Will to Power’ and the ‘Übermensch’ to build an existential picture of deviant behaviour. The author also draws upon the criminological/sociological notions of ‘Drift’, ‘Master Status’ and the ‘Techniques of Neutralisation’ (Sykes and Matza 1957) to introduce the new concepts of ‘Flexible Causal Prediction’ (previously referred to as ‘Causal Probability’); and the idea of ‘Situational Influences’. This undertaking is done with the intention of building upon the Meta-theoretical work of Owen (2007 – 2015), which seeks to build bridges between the social and physical sciences. The theory of ‘Flexible Causal Prediction’ is also applied to the deviant activities of internet trolling and anti-social behaviours to demonstrate the influences on behaviour. Nietzsche’s philosophical notion of ‘Slave Morality’ and ‘ressentiment’ will also be extended when looking at some radical social justice movements, such as ‘AntiFa’, ‘Black LivesMatter’ and the ‘#MeToo’ movement to demonstrate the role that ‘ressentiment’ may play in behavioural choices. To assist this analysis SaulAlinksy’s 1971 book ‘Rules for Radicals’ will be referenced to demonstrate how the rules are based on a collectivist ‘herd’ mentality of slave ‘ressentiment’ and how these rules have themselves lead directly to deviant behaviour, online and offline and how a political correct ideology could be responsible for encouraging such behaviours

Glomerular matrix accumulation is linked to inhibition of the plasmin protease system

Glomerular matrix accumulation is linked to inhibition of the plasmin protease system. TGF-β plays a pivotal role in the pathological accumulation of extracellular matrix in experimental glomerulonephritis. Increased TGF-β expression leads to increased synthesis and deposition of extracellular matrix components while administration of antiserum to TGF-β suppresses the major manifestations of the disease. We hypothesized that TGF-β might also enhance matrix accumulation by decreasing matrix turnover via effects on protease/protease inhibitor balance. Plasmin is a potent protease capable of degrading a variety of matrix molecules. Plasmin generation from plasminogen is regulated by plasminogen activator(s) (PA) and plasminogen activator inhibitor(s) (PAI). In this study PA activity was markedly reduced and PAI-1 synthesis dramatically increased when TGF-β was added to normal glomeruli. Diseased glomeruli also showed decreased PA activity, increased PAI-1 synthesis and increased PAI-1 deposition into matrix. Administration of anti-TGF-β serum to glomerulonephritic rats blocked the expected increase in glomerular PAI-1 deposition. Thus changes in the PA/PAI balance favoring accumulation of matrix are induced by TGF-β in normal glomeruli and are present in nephritic glomeruli when endogenous TGF-β production is high. Our findings implicate the plasmin protease system in tissue repair following acute glomerular injury and suggest another mechanism by which TGF-β enhances the matrix accumulation characteristic of many glomerular diseases

Combining TGF-β inhibition and angiotensin II blockade results in enhanced antifibrotic effect

Combining TGF-β inhibition and angiotensin II blockade results in enhanced antifibrotic effects.BackgroundAlthough angiotensin II (Ang II) blockade is rapidly becoming standard antifibrotic therapy in renal diseases, current data suggest that Ang II blockade alone cannot stop fibrotic disease. New therapies, such as antibodies to transforming growth factor-β (TGF-β), or drug combinations will be required to further slow or halt disease progression. Here, using the anti-Thy1 model of glomerulonephritis, the maximally therapeutic dose of the TGF-β neutralizing mouse monoclonal antibody (1D11) was determined and compared with the maximally effective dose of enalapril. Then, the effect of combining both treatments at maximal doses was determined.MethodsAfter disease induction with the anti-Thy1 antibody, OX-7, increasing doses of 1D11 were given intraperitoneally (IP) on days 1, 3, and 5. Enalapril was administered in drinking water from day 1. The fibrotic response was assessed at day 6.Results1D11 dose-dependently reduced fibrosis, with the 0.5 and 5 mg/kg doses showing maximal therapeutic effects, reducing period-acid Schiff (PAS) staining by 56% and 45%, respectively. Fibronectin and collagen I staining was reduced by 32% to 36%, respectively. Glomerular mRNA and production of fibronectin, plasminogen activator inhibitor-1 (PAI-1), TGF-β1, and p-Smad2 protein were also reduced. The maximal therapeutic effects of 1D11 and enalapril alone were very similar. However, combination therapy led to further reduction in disease. Notably, matrix deposition was reduced by 80%.ConclusionWhile 1D11 or enalapril at maximal doses reduce fibrosis equally, simultaneous blockade of Ang II and TGF-β reduces fibrotic disease considerably more, offering hope that such drug combinations may confer a therapeutic advantage over angiotensin blockade alone