To whom does the law speak? Canvassing a neglected picture of law’s interpretive field

Among the most common strategies underlying the so-called indeterminacy thesis is the following two-step argument: (1) that law is an interpretive practice, and that evidently legal actors more generally hold different (and competing) theories of meaning, which lead to disagreements as to what the law says (that is, as to what the law is); (2) and that, as there is no way to establish the prevalence of one particular theory of meaning over the other, indeterminacy is pervasive in law. In this paper I offer some reflections to resist this trend. In particular I claim that a proper understanding of law as an authoritative communicative enterprise sheds new light on the relation between the functioning of the law and our theories of interpretation, leading to what can be considered a neglected conclusion: the centrality of the linguistic criterion of meaning in our juridical interpretive practices. In the first part of the chapter I discuss speech-act theory in the study of law, assessing its relevance between alternative options. Then I tackle the ‘to whom does the law speak?’ question, highlighting the centrality of lay-people for our juridical practices. Lastly, I examine the consequences of this neglected fact for our interpretive theories

Poly[ADP-Ribose] Polymerase-1 Expression Is Related To Cold Ischemia, Acute Tubular Necrosis, and Delayed Renal Function In Kidney Transplantation

Cold ischemia time especially impacts on outcomes of expanded-criteria donor (ECD) transplantation. Ischemia-reperfusion (IR) injury produces excessive poly[ADP-Ribose] Polymerase-1 (PARP-1) activation. The present study explored the hypothesis that increased tubular expression of PARP-1 contributes to delayed renal function in suboptimal ECD kidney allografts and in non-ECD allografts that develop posttransplant acute tubular necrosis (ATN)

Balancing, Proportionality, and Constitutional Rights

In the theory and practice of constitutional adjudication, proportionality review plays a crucial role. At a theoretical level, it lies at core of the debate on rights adjudication; in judicial practice, it is a widespread decision-making model characterizing the action of constitutional, supra-national and international courts. Despite its circulation and centrality in contemporary legal discourse, proportionality in rights-adjudication is still extremely controversial. It raises normative questions—concerning its justification and limits—and descriptive questions—regarding its nature and distinctive features. The chapter addresses both orders of questions. Part I centres on the justification of proportionality review, the connection between proportionality, balancing and theories of rights and the critical aspects of this connection. Part II identifies and analyses the different forms of proportionality both in review, as a template for rights-adjudication, and of review, as a way of defining the scope and limits of adjudication

Clinical variables according to nuclear immunohistochemical expression of PARP-1 in human kidney biopsies.

<p>Values are expressed as mean ± standard deviation; NS: Non-significant.</p>*<p>Student's <i><u>t</u>-</i> test.</p

Kidney transplant from controlled donors following circulatory death: Results from the GEODAS-3 multicentre study

INTRODUCTION: Many European countries have transplant programmes with controlled donors after cardiac death (cDCD). Twenty-two centres are part of GEODAS group. We analysed clinical results from a nephrological perspective. METHODS: Observational, retrospective and multicentre study with systematic inclusion of all kidney transplant recipients from cDCD, following local protocols regarding extraction and immunosuppression. RESULTS: A total of 335 cDCD donors (mean age 57.2 years) whose deaths were mainly due to cardiovascular events were included. Finally, 566 recipients (mean age 56.5 years; 91.9% first kidney transplant) were analysed with a median of follow-up of 1.9 years. Induction therapy was almost universal (thymoglobulin 67.4%; simulect 32.8%) with maintenance with prednisone-MMF-tacrolimus (91.3%) or combinations with mTOR (6.5%). Mean cold ischaemia time (CIT) was 12.3h. Approximately 3.4% (n=19) of recipients experienced primary non-function, essentially associated with CIT (only CIT ≥ 14 h was associated with primary non-function). Delayed graft function (DGF) was 48.8%. DGF risk factors were CIT ≥ 14 h OR 1.6, previous haemodialysis (vs. peritoneal dialysis) OR 2.1 and donor age OR 1.01 (per year). Twenty-one patients (3.7%) died with a functioning graft, with a recipient and death-censored graft survival at 2-years of 95% and 95.1%, respectively. The estimated glomerular filtration rate at one year of follow-up was 60.9 ml/min. CONCLUSIONS: CIT is a modifiable factor for improving the incidence of primary non-function in kidney transplant arising from cDCD. cDCD kidney transplant recipients have higher delayed graft function rate, but the same patient and graft survival compared to brain-dead donation in historical references. These results are convincing enough to continue fostering this type of donation

Representation of ROC curves using PARP-1 expression as state variable.

<p>Representation of ROC curves using PARP-1 expression as state variable.</p

PARP-1 expression in human kidneys using polymer peroxidase-based method.

<p>A) Absence of PARP-1 expression in tubular cell nuclei in transplant protocol biopsy of kidney with stable renal function and without ATN (×100). B) Moderate PARP-1 expression in tubular cells of ECD kidney biopsy with ATN (×200). C) Moderate PARP-1 expression in necrotic tubuli of posttransplant kidney biopsy with ATN (×200). D, E, F): Intense PARP-1 expression in various biopsies with severe ATN (D x200, and E, F ×400). G) Glomerular immunostaining in a case of severe ATN. Note nuclear immunostaining in capillary and Bowman's capsule (×400). H) Negative isotype control (x200).</p

Western-blot analysis of PARP-1 expression in kidney of C57BL/6 mice.

<p>A) Presence of PARP-1 expression in kidney of C57BL/6 Parp1^+/+ mice absence of PARP-1 in knockout mice; and evident increase in PARP-1 expression at 48 h of reperfusion. Note partial inhibition of PARP-1 after inoculation with 3-ABA at 6 h of reperfusion. B) Induction of protein poly(ADP-ribosyl)ation after renal IR and its total inhibition by PARP-1 with 3-ABA. +/+: C57BL/6 wild-type mouse; −/−: C57BL/6 Parp-1 knockout mouse; 3-ABA: 3-aminobenzamide; C: Control; IR: Ischemia-Reperfusion; R: Reperfusion.</p

Comparative data among control kidneys (from expanded-criteria donors [ECD] and patients with stable renal function), preimplant kidneys from ECDs, and transplanted kidneys from patients with ATN.

<p>ECD: Expanded-criteria donor with ATN; ATN: Acute tubular necrosis. Values are expressed as mean ± standard deviation.</p>*<p>P = 0.0001 one-way ANOVA test and <i>post hoc</i> with Bonferroni test.</p>†<p>Transplant protocol biopsies with stable renal function; NS: Non-significant.</p

Area under the ROC curve, statistical significance and p-values using dichotomous PARP-1 expression in human kidney biopsies as state variable.

*<p>95% Confidence Interval.</p