Medieval Emergencies and the Contemporary Debate

Abstract The contemporary debate on emergencies and the state of exception often relies on historical examples. Yet, the most recent discussions on the state of exception (a legal construct that deals with emergencies) also assume its modern inception. This article shows that medieval France formulated its own state of exception, meant to deal with emergencies, based on the legal principle of necessity. This article has two purposes. First, it challenges the historical narrative inherent in the contemporary debate, which assumes the modern inception of the state of exception. Second, it reinforces the trepidation with which many scholars today view the uses and abuses of the state of exception. This article does so by showing that the French crown used and abused the medieval principle of necessity in ways similar to current uses of the state of exception; it served similar purposes. Just as some scholars fear today, the French medieval state of exception often served as a pretext meant to change the legal order, turning the exception into the ordinary. The French crown used the state of exception to enhance its power, and it was central in the long process of building the early-modern French state

Male circumcision for HIV prevention: current evidence and implementation in sub-Saharan Africa

Heterosexual exposure accounts for most HIV transmission in sub-Saharan Africa, and this mode, as a proportion of new infections, is escalating globally. The scientific evidence accumulated over more than 20 years shows that among the strategies advocated during this period for HIV prevention, male circumcision is one of, if not, the most efficacious epidemiologically, as well as cost-wise. Despite this, and recommendation of the procedure by global policy makers, national implementation has been slow. Additionally, some are not convinced of the protective effect of male circumcision and there are also reports, unsupported by evidence, that non-sex-related drivers play a major role in HIV transmission in sub-Saharan Africa. Here, we provide a critical evaluation of the state of the current evidence for male circumcision in reducing HIV infection in light of established transmission drivers, provide an update on programmes now in place in this region, and explain why policies based on established scientific evidence should be prioritized. We conclude that the evidence supports the need to accelerate the implementation of medical male circumcision programmes for HIV prevention in generalized heterosexual epidemics, as well as in countering the growing heterosexual transmission in countries where HIV prevalence is presently low

Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

Background Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. Methods In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH,non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2–F3, or F1 with at least oneaccompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpointsfor the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2–F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. Findings Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1–F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2–F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1–F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). Interpretation Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

The Invisible Safeguards of Judicial Independence in the Israeli Judiciary

The Israeli democracy regulates the operation of the judiciary through the constraints of formal rules that check the political actors, the individual judges, and the judiciary. Basic laws, laws and regulations prescribe the operation of every subject. Yet beyond these formal rules, informal institutions and practices are sometimes equally important in the operation of the judiciary, as they are in any constitutional system. In Israel, some of these informal institutions are crucial for the flourishing of democracy and the rule of law, through their protection of judicial independence from external political interference. The imminent possibility that political actors may set some of them aside is nothing less than a potential transformation in the constitutional order. Over the past few decades, judges and court administrators have introduced other internal informal institutions in the administration of the Israeli Judiciary, which qualify formal judicial accountability mechanisms in ways that may prove to be detrimental to democratic principles. This article discusses informal institutions that are important in the operation of the Israeli judiciary, separating the former external kind that are conducive to the rule of law—such as the illegitimacy of political and partisan considerations in judicial appointments—and whose disregard may signal democratic decay from the latter internal kind that may prove detrimental to the courts—such as opaquely changing who is responsible for court administration. Lastly, the political attempt to change informal institutions, detailed herein, can be seen as a harbinger of the current attempt to change formal institutions in the constitutional status of the judiciary in Israel

Sense and Sensibility in Midwestern Archaeology and the Midcontinental Journal of Archaeology, Part II

The progression of archaeology in the midcontinent over the past 40 years has moved on a series of different but overlapping fronts: regional, governmental, institutional, disciplinary, and personal. This collection of thoughts by both longtime and relatively young practitioners of our field suggests the many ways that archaeology has changed for the good ”and maybe not so good ”depending on our own experiences. Midcontinental Journal of Archaeology (MCJA) has changed along with these developments. Part I of this discussion centered on the need for, and foundation of, MCJA. Part II is more diverse, with the archaeologists who have participated in the field for the last 40 years reflecting on the shifts in archaeology within their regions ”both in terms of practice and institutional practices. The forces of national economics and academic politics and the changing sensibilities toward our public constituencies described here are themes that continue to influence us today