Uplifting and Inflation with D3 Branes

Back-reaction effects can modify the dynamics of mobile D3 branes moving within type IIB vacua, in a way which has recently become calculable. We identify some of the ways these effects can alter inflationary scenarios, with the following three results: (1) By examining how the forces on the brane due to moduli-stabilizing interactions modify the angular motion of D3 branes moving in Klebanov-Strassler type throats, we show how previous slow-roll analyses can remain unchanged for some brane trajectories, while being modified for other trajectories. These forces cause the D3 brane to sink to the bottom of the throat except in a narrow region close to the D7 brane, and do not ameliorate the \eta-problem of slow roll inflation in these throats; (2) We argue that a recently-proposed back-reaction on the dilaton field can be used to provide an alternative way of uplifting these compactifications to Minkowski or De Sitter vacua, without the need for a supersymmetry-breaking anti-D3 brane; and (3) by including also the D-term forces which arise when supersymmetry-breaking fluxes are included on D7 branes we identify the 4D supergravity interactions which capture the dynamics of D3 motion in D3/D7 inflationary scenarios. The form of these potentials sheds some light on recent discussions of how symmetries constrain D term interactions in the low-energy theory.Comment: JHEP.cls, 35 pages, 3 .eps figure

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden

Dans l’ombre de la prison

Cet article traite de l’intrication entre les prisons inquisitoriales et la société environnante en Languedoc à la fin du xiiie siècle et au début du xive siècle. L’expérience américaine des prisons de la fin du xxe et du début du xxie siècle le montre, les prisons peuvent avoir un impact majeur non seulement sur les détenus, mais aussi sur le reste de la société. En Languedoc, l’expérience des prisons inquisitoriales était très répandue et leur réputation était encore plus large. L’emprisonnement d’un individu avait des conséquences importantes sur ses relations demeurées à l’extérieur, notamment, pour ses héritiers, la confiscation et l’éviction des offices publics. Les inquisiteurs utilisaient les prisons comme une étape à part entière de leurs interrogatoires et de leurs stratégies pénales. L’emprisonnement d’un suspect pouvait inciter ses contacts encore libres à avouer avant d’être dénoncés. Les gens délivrés des prisons inquisitoriales entraient dans un groupe extérieur distinct et stigmatisé, ce qui les rendait sujets à manipulation par les inquisiteurs. Elles avaient aussi des conséquences non attendues par les inquisiteurs. Il semble qu’elles aient renforcé dans la société le rôle des intermédiaires, qui pouvaient entraver le travail des inquisiteurs. Elles offraient aussi le flanc le plus vulnérable aux attaques de ceux qui critiquaient les inquisiteurs et qui souhaitaient en même temps être perçus comme de bons catholiques.This essay deals with the interaction of inquisitorial prisons with their surrounding society in Languedoc in the late thirteenth- and early fourteenth-century. As the American experience with prisons in the late twentieth and early 21st centuries shows, prisons can have a major impact, not only on their inmates, but on the rest of society. In Languedoc experience of inquisitorial prisons was fairly widespread, and their reputation even more far-flung. The imprisonment of an individual had major consequences for his contacts who remained outside prison, involving, at least for his heirs, disinheritance and the barring from public office of his descendants. The inquisitors used prisons as an integral part of their interrogation and penal strategies. The imprisonment of a suspect could motivate those of his contacts who were still at large to confess before they could be denounced. People released from inquisitorial prisons entered a distinct and stigmatized outgroup, which made theme subject to manipulation by the inquisitors. Inquisitorial prisons also had consequences unintended by the inquisitors. They possibly strengthened the role of “middlemen” in society, which could hinder the work of the inquisitors. They also offered the most vulnerable flank from which the inquisitors could be attacked by their critics who wished to be perceived as good Catholics

Les inquisiteurs du Languedoc médiéval : les éléments sociétaux favorables et contraignants

This paper, drawing on the records of the inquisitors of Languedoc in the late thirteenth and early fourteenth centuries, examines the techniques the inquisitors used in their campaign against heresy. The paper also argues that the success of the inquisitors was the result not only of their own efforts, but was both facilitated and constrained by the nature of Languedocian social structures. Certain aspects of Languedocian social organizations, such as the existence of characteristic tensions and cleavages among important social groups, facilitated the work of the inquisitors; other aspects of those same social organizations, which at times made certain groups reluctant to cooperate with them, constrained their behaviour

Rnai-based treatment of chronically infected patients and chimpanzees reveals that integrated hepatitis b virus DNA is a source of hbsag

Chronic hepatitis B virus (HBV) infection is a major health concern worldwide, frequently leading to liver cirrhosis, liver failure, and hepatocellular carcinoma. Evidence suggests that high viral antigen load may play a role in chronicity. Production of viral proteins is thought to depend on transcription of viral covalently closed circular DNA (cccDNA). In a human clinical trial with an RNA interference (RNAi)-based therapeutic targeting HBV transcripts, ARC-520, HBV S antigen (HBsAg) was strongly reduced in treatment-naïve patients positive for HBV e antigen (HBeAg) but was reduced significantly less in patients who were HBeAg-negative or had received longterm therapy with nucleos(t)ide viral replication inhibitors (NUCs). HBeAg positivity is associated with greater disease risk that may be moderately reduced upon HBeAg loss. The molecular basis for this unexpected differential response was investigated in chimpanzees chronically infected with HBV. Several lines of evidence demonstrated that HBsAg was expressed not only from the episomal cccDNA minichromosome but also from transcripts arising from HBV DNA integrated into the host genome, which was the dominant source in HBeAg-negative chimpanzees. Many of the integrants detected in chimpanzees lacked target sites for the small interfering RNAs in ARC-520, explaining the reduced response in HBeAg-negative chimpanzees and, by extension, in HBeAg-negative patients. Our results uncover a heretofore underrecognized source of HBsAg that may represent a strategy adopted by HBV to maintain chronicity in the presence of host immunosurveillance. These results could alter trial design and endpoint expectations of new therapies for chronic HBV