Right to Counsel: Balancing the Burden of Persuasion on the Adversarial Scales of Criminal Justice

How much is society willing to pay to protect constitutional rights from government infringement? How much constitutional protection is society allowed to forfeit in exchange for more effective law enforcement? The criminal justice system\u27s allocation of the burdens of proof ultimately decides these questions. When do effective law enforcement tactics, such as undercover agent investigations, violate a defendant\u27s sixth amendment right to the effective assistance of counsel? When does the sixth amendment violation warrant judicial remedies? Only the government knows when and how improperly obtained information is ultimately utilized. The adversarial context of American criminal justice dictates allocating to the government the burden of persuasion on the issue of whether an intrusion into the defendant\u27s right to counsel was unconstitutionally prejudicial

The role of drug transporters in the kidney: lessons from tenofovir

Tenofovir disoproxil fumarate, the prodrug of nucleotide reverse transcriptase inhibitor tenofovir, shows high efficacy and relatively low toxicity in HIV patients. However, long-term kidney toxicity is now acknowledged as a modest but significant risk for tenofovir-containing regimens, and continuous use of tenofovir in HIV therapy is currently under question by practitioners and researchers. Co-morbidities (hepatitis C, diabetes), low body weight, older age, concomitant administration of potentially nephrotoxic drugs, low CD4 count, and duration of therapy are all risk factors associated with tenofovir-associated tubular dysfunction. Tenofovir is predominantly eliminated via the proximal tubules of the kidney, therefore drug transporters expressed in renal proximal tubule cells are believed to influence tenofovir plasma concentration and toxicity in the kidney. We review here the current evidence that the actions, pharmacogenetics, and drug interactions of drug transporters are relevant factors for tenofovir-associated tubular dysfunction. The use of creatinine and novel biomarkers for kidney damage, and the role that drug transporters play in biomarker disposition, are discussed. The lessons learnt from investigating the role of transporters in tenofovir kidney elimination and toxicity can be utilized for future drug development and clinical management programs

Epigenetics and the overhealing wound: the role of DNA methylation in fibrosis

Fibrosis is a progressive and potentially fatal process that can occur in numerous organ systems. Characterised by the excessive deposition of extracellular matrix proteins such as collagens and fibronectin, fibrosis affects normal tissue architecture and impedes organ function. Although a considerable amount of research has focused on the mechanisms underlying disease pathogenesis, current therapeutic options do not directly target the pro-fibrotic process. As a result, there is a clear unmet clinical need to develop new agents. Novel findings implicate a role for epigenetic modifications contributing to the progression of fibrosis by alteration of gene expression profiles. This review will focus on DNA methylation; its association with fibroblast differentiation and activation and the consequent buildup of fibrotic scar tissue. The potential use of therapies that modulate this epigenetic pathway for the treatment of fibrosis in several organ systems is also discussed

Comparing the Ancient Star Formation Histories of the Magellanic Clouds

We present preliminary results from a new HST archival program aimed at tightly constraining the ancient (>4 Gyr ago) star formation histories (SFHs) of the field populations of the SMC and LMC. We demonstrate the quality of the archival data by constructing HST/WFPC2-based color-magnitude diagrams (CMDs; M_{F555W} ~ +8) for 7 spatially diverse fields in the SMC and 8 fields in the LMC. The HST-based CMDs are >2 magnitudes deeper than any from ground based observations, and are particularly superior in high surface brightness regions, e.g., the LMC bar, which contain a significant fraction of star formation and are crowding limited from ground based observations. To minimize systematic uncertainties, we derive the SFH of each field using an identical maximum likelihood CMD fitting technique. We then compute an approximate mass weighted average SFH for each galaxy. We find that both galaxies lack a dominant burst of early star formation, which suggests either a suppression or an under-fueling of early star formation. From 10-12 Gyr ago, the LMC experienced a period of enhanced stellar mass growth relative to the SMC. Similar to some previous studies, we find two notable peaks in the SFH of the SMC at ~4.5 and 9 Gyr ago, which could be due to repeated close passages with the LMC, implying an interaction history that has persisted for at least 9 Gyr. We find little evidence for strong periodic behavior in the lifetime SFHs of both MCs, suggesting that repeated encounters with the Milky Way are unlikely. Beginning ~3.5 Gyr ago, both galaxies show increases in their SFHs, in agreement with previous studies, and thereafter, track each other remarkably well. (abridged)Comment: 9 pages, 5 Figures, Accepted for Publication in MNRA

Estimation of minimally important differences in EQ-5D utility and VAS scores in cancer

We wish to correct a mistake in the abstract and conclusion of our published paper [1]. In the abstract and conclusion, the MID for EQ-VAS score should be reported as 7 rather than 0.07. EQ-VAS scores range from 0 to 100, while EQ-5D index-based scores are anchored by 0 (dead) and 1 (perfect health). The specific wording in the conclusion of the abstract should read “Important differences in EQ-5D utility and VAS scores were similar for all cancers and lung cancer, with the lower end of the range of estimates closer to the MID, i. e. 0.08 for UK-index scores, 0.06 for US-index scores, and 7 for VAS scores. Author details

Dietary transition and obesity in selected Arabic-speaking countries: a review of the current evidence

Escalating obesity rates have become a significant public health problem in the Middle East and North Africa [‎MENA]‎ region and have been associated with shifts towards a westernized diet. This integrative review aimed to examine the current dietary trends and transitions and their association with obesity in Arabic-speaking countries of the MENA region. Relevant databases were searched for studies in MENA countries between 1998 and 2014 that investigated obesity trends and changes in dietary patterns at the regional level in all age groups. A total of 39 articles fulfilled the inclusion criteria. All the articles noted that obesity was increasingly prevalent and that there was a significant dietary shift away from traditional dietary patterns; 51% reported a shift towards a westernized diet and half found that the western diet was correlated with increased obesity. Culturally relevant dietary health education and health promotion strategies are warranted to address both the dietary shifts towards the westernized diet and the increasing obesit

Uncertainty Quantification Reveals the Physical Constraints on Pumping by Peristaltic Hearts

Most biological functional systems are complex, and this complexity is a fundamental driver of diversity. Because input parameters interact in complex ways, a holistic understanding of functional systems is key to understanding how natural selection produces diversity. We present uncertainty quantification (UQ) as a quantitative analysis tool on computational models to study the interplay of complex systems and diversity. We investigate peristaltic pumping in a racetrack circulatory system using a computational model and analyse the impact of three input parameters (Womersley number, compression frequency, compression ratio) on flow and the energetic costs of circulation. We employed two models of peristalsis (one that allows elastic interactions between the heart tube and fluid and one that does not), to investigate the role of elastic interactions on model output. A computationally cheaper surrogate of the input parameter space was created with generalized polynomial chaos expansion to save computational resources. Sobol indices were then calculated based on the generalized polynomial chaos expansion and model output. We found that all flow metrics were highly sensitive to changes in compression ratio and insensitive to Womersley number and compression frequency, consistent across models of peristalsis. Elastic interactions changed the patterns of parameter sensitivity for energetic costs between the two models, revealing that elastic interactions are probably a key physical metric of peristalsis. The UQ analysis created two hypotheses regarding diversity: favouring high flow rates (where compression ratio is large and highly conserved) and minimizing energetic costs (which avoids combinations of high compression ratios, high frequencies and low Womersley numbers)

Damned if they do, damned if they don't: negotiating the tricky context of anti-social behaviour and keeping safe in disadvantaged urban neighbourhoods

Young people's relationship with anti-social behaviour (ASB) is complicated. While their behaviours are often stereotyped as anti-social (e.g. ‘hanging about’), they also experience ASB in their neighbourhood. In this study, we explore young people's own perspectives on ASB, comparing results from ‘go-along’ interviews and focus groups conducted in disadvantaged neighbourhoods in Glasgow, Scotland. This article discusses how young people's everyday experience of ASB was contextualised by social factors such as cultural stereotyping of marginalised groups, poor social connectivity and spatial marginalisation within their neighbourhood. Furthermore, we found that these social factors were mutually reinforcing and interacted in a way that appeared to leave young people in a ‘no-win’ situation regarding their association with ASB. Participation in ASB and attempts to avoid such involvement were seen to involve negative consequences: participation could entail violence and spatial restrictions linked to territoriality, but avoidance could lead to being ostracised from their peer group. Regardless of involvement, young people felt that adults stereotyped them as anti-social. Our findings therefore provide support for policies and interventions aimed at reducing ASB (perpetrated by residents of all ages); in part by better ensuring that young people have a clear incentive for avoiding such behaviours