Revista Jurídica Digital UANDES
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A novel physiologically based model of creatinine renal disposition to integrate current knowledge of systems parameters and clinical observations
No full textCreatinine is the most common clinical biomarker of renal function. As a substrate for renal transporters, its secretion is susceptible to inhibition by drugs, resulting in transient increase in serum creatinine and false impression of damage to kidney. Novel physiologically-based models for creatinine were developed here and (dis)qualified in a stepwise manner until consistency with clinical data. Data from a matrix of studies were integrated, including systems data (common to all models), proteomics-informed in vitro-in vivo extrapolation of all relevant transporter clearances, exogenous administration of creatinine (to estimate endogenous synthesis rate), and inhibition of different renal transporters (11 perpetrator drugs considered for qualification during creatinine model development and verification on independent datasets). The proteomics-informed bottom-up approach resulted in underprediction of creatinine renal secretion. Subsequently, creatinine-trimethoprim clinical data were used to inform key model parameters in a reverse translation manner, highlighting best-practices and challenges for middle-out optimisation of mechanistic models
The Dialogues of Lord Solomon and the Thirty-Six Rulers of Darkness (<i>T.Sol.</i> 18.1-40):A New Translation and Introduction
No full textStein's method for functions of multivariate normal random variables
No full textBy the continuous mapping theorem, if a sequence of d-dimensional random vectors (Wn)n≥1 converges in distribution to a multivariate normal random variable Σ1/2Z, then the sequence of random variables (g(Wn))n≥1 converges in distribution to g(Σ1/2Z) if g : ℝd → ℝ is continuous. In this paper, we develop Stein's method for the problem of deriving explicit bounds on the distance between g(Wn) and g(Σ1/2Z) with respect to smooth probability metrics. We obtain several bounds for the case that the j-component of Wn is given by Wn,j = 1/√n Σni=1 Xij, where the Xij are independent. In particular, provided g satisfies certain differentiability and growth rate conditions, we obtain an order n-(p-1)/2 bound, for smooth test functions, if the first p moments of the Xij agree with those of the normal distribution. If p is an even integer and g is an even function, this convergence rate can be improved further to order n-p/2. These convergence rates are shown to be of optimal order. We apply our general bounds to some examples, which include the distributional approximation of asymptotically chi-square distributed statistics; the approximation of expectations of smooth functions of binomial and Poisson random variables; rates of convergence in the delta method; and a quantitative variance-gamma approximation of the D∗2 statistic for alignment-free sequence comparison in the case of binary sequences
Revisiting Reinhart & Rogoff after the Crisis: A Time Series Perspective
No full textThis paper offers a straightforward and descriptive contribution to the recent and busy debate on fiscal discipline made popular by the seminal Reinhart and Rogoff (2010) paper, after policymakers have sought foundation and justification for a policy known as austerity measures, following on from the sovereign debt crisis of 2010. We revisit the debate on whether or not higher debt levels impede growth rates and offer a time series perspective of a corrected data set and a more recent higher frequency source. We find that with further hindsight, and from a time series perspective, there is little to no support for the view that higher levels of debt cause reductions in economic activity. In contrast to Reinhart and Rogoff (2010), we suggest that economic slumps tend to cause debt build-ups rather than vice versa
On the effect of ITZ thickness in meso-scale models of concrete
No full textThis work addresses a knowledge gap in meso-scale modelling of concrete – the effect of selected computational ITZ thickness on predicted macroscopic behaviour. A novel approach for models’ generation with arbitrarily ITZ thickness is developed, offering lower computational cost with accurate ITZ representation. Models are validated by comparison with published experimental results and verified by comparison with published simulation results. Systematic parametric study is performed to clarify the effect of ITZ thickness selection in combination with other meso-structure parameters on the predicted concrete behaviour. Results indicate that tensile strength is increasingly underestimated, up to 25%, as the ITZ thickness increases from its average physical value of 0.05 mm to the commonly used 1 mm. Correlations between selected ITZ thickness and aggregate shape, maximum aggregate size, aggregate volume fraction and ITZ tensile strength are also studied, providing guidance for future research with meso-scale models
John Taylor Coleridge and English criminal law
No full textThis chapter examines how the networks and connections of John Taylor Coleridge, Justice of the King’s Bench (1835-1858), shaped his approach to criminal law. Coleridge’s career coincided with a period of significant reform: the ‘bloody code’ collapsed and a sustained attempt was made to rationalize the criminal law. Judges’ resistance to these reforms prompted contemporaries to criticize the judiciary for being insular and narrowly reactionary in approach. Coleridge was cited as an exemplar of the severe and illiberal judge. This chapter draws upon his extensive private papers to offer a more nuanced view, which accommodates a range of influences. These included the conservative philosophy of his uncle, Samuel Taylor Coleridge, and a network of connections to leading figures in contemporary religious, political and literary debates. In tracing these seams of influence into Coleridge’s work, the chapter aims to illuminate a judicial perspective on a transformative period in criminal law history
Adult mental health practitioner beliefs about psychosis, parenting and the role of the practitioner:a Q methodological investigation
No full textObjectives: There is a lack of research into parenting interventions for families which include a parent experiencing psychosis or other serious mental illness (SMI). Preliminary findings highlight the potential benefits of adult mental health practitioners supporting parents experiencing SMI by using self-directed parenting interventions. This study explored beliefs relating to parenting and psychosis held by practitioners working in adult mental health settings, specifically examining their beliefs about the parenting needs of adults experiencing psychosis who have dependent children, as well as their role as adult mental health practitioners.Design: This study used Q methodology to explore the beliefs of mental health practitioners on psychosis and parenting.Methods: Twenty-one adult mental health practitioners ranked 58 items according to how much they agreed with the belief statement presented. Participants also provided additional written information and interviews to contextualise the Q methodology data.Results: Three factors emerged representing three groups of practitioners with similar beliefs around psychosis and parenting. Factors were labelled: ‘Parenting interventions are worthwhile, and I’d deliver them’, ‘Parenting interventions are worthwhile, but I’m not confident to deliver them’, and ‘Parenting interventions might be worthwhile, but it’s not my responsibility’.Conclusion: Using parenting interventions as part of their clinical work was acceptable to most practitioners; however, some lacked confidence in their ability to work in a family-focused way. Efforts now need to focus on enhancing practitioners’ skill, knowledge and confidence in family-focused approaches to provide increased and improved support to families which include a parent experiencing psychosis or other SMI
Hypoxia and hyperglycaemia determine why some endometrial tumours fail to respond to metformin
No full textBackground: High expression of Ki67, a proliferation marker, is associated with reduced endometrial cancer-specific survival. Pre-surgical metformin reduces tumour Ki-67 expression in some women with endometrial cancer. Metformin’s anti-cancer activity may relate to effects on cellular energy metabolism. Since tumour hypoxia and glucose availability are major cellular redox determinants, we evaluated their role in endometrial cancer response to metformin. Methods: Endometrial cancer biopsies from women treated with pre-surgical metformin were tested for the hypoxia markers, HIF-1α and CA-9. Endometrial cancer cell lines were treated with metformin in variable glucose concentrations in normoxia or hypoxia and cell viability, mitochondrial biogenesis, function and energy metabolism were assessed.Results: In women treated with metformin (n=28), Ki-67 response was lower in hypoxic tumours. Metformin showed minimal cytostatic effects towards Ishikawa and HEC1A cells in conventional medium (25mM glucose). In low glucose (5.5mM), a dose-dependent cytostatic effect was observed in normoxia, but attenuated in hypoxia. Tumours treated with metformin showed increased mitochondrial mass (n=25), while in cultured cells metformin decreased mitochondrial function. Metformin targets mitochondrial respiration, however, in hypoxic, high glucose conditions, there was a switch to glycolytic metabolism and decreased metformin response.Conclusions: Understanding the metabolic adaptations of endometrial tumours may identify patients likely to derive clinical benefit from metformin
La prueba del hecho contrario en la presunción legal contemplada en el artículo 23 de la Ley Orgánica de la Dirección del Trabajo (Comentario a la sentencia de la Corte Suprema Rol 18865-2018)
No full textThe present commentary critically assesses the judgement delivered on 9 July 2019 by the Supreme Court on the occasion of the knowledge of a Unification of Jurisprudence Appeal. The purpose of the latter was to determine the probative value of the findings of the Labour Inspectorate reports. To this end, and after summarizing the procedural history of the case, we will set out the arguments outlined by the Court and analyze them critically, giving special relevance to the concept of legal presumption. In doing so, we aim to achieve an adequate understanding of the legal consequences of the presumption referred to in article 23 of the Organic Law on the Directorate of Labour: its probative value and the possibility of proof contrary to the requirement proportionality enshrined in article 493 of the Labour Code.El presente comentario evalúa, críticamente, la sentencia dictada el 9 de julio de 2019 por la Excelentísima Corte Suprema con ocasión del conocimiento de un recurso de unificación de jurisprudencia. Este tuvo como objetivo determinar el valor probatorio que revisten las constataciones de los informes de la Inspección del Trabajo. Para ello, y luego de resumir sucintamente la historia procesal del caso, expondremos los argumentos esbozados por la Corte y los analizaremos críticamente, otorgando especial relevancia al concepto de presunción legal. Con ello pretendemos lograr una adecuada comprensión de las consecuencias jurídicas que conlleva la presunción contemplada en el artículo 23 de la Ley Orgánica de la Dirección del Trabajo: su valor probatorio y la posibilidad de prueba en contrario a la luz del requisito de proporcionalidad consagrado en el artículo 493 del Código del Trabajo
