Variational Principles for Natural Divergence-free Tensors in Metric Field Theories

Let $T^{ab}=T^{ba}=0$ be a system of differential equations for the components of a metric tensor on $R^m$. Suppose that $T^{ab}$ transforms tensorially under the action of the diffeomorphism group on metrics and that the covariant divergence of $T^{ab}$ vanishes. We then prove that $T^{ab}$ is the Euler-Lagrange expression some Lagrangian density provided that $T^{ab}$ is of third order. Our result extends the classical works of Cartan, Weyl, Vermeil, Lovelock, and Takens on identifying field equations for the metric tensor with the symmetries and conservation laws of the Einstein equations

New Faculty on the Block: Issues of Stress and Support

The research reported investigated the experiences of new faculty in their first three years of employment in higher education administration programs. New faculty face stress relative to work-life integration, issues pertaining to gender or color, teaching responsibilities, and unclear expectations. The findings of this study highlight the role of graduate school socialization and identification as a chosen student targeting a faculty position as an influence on new faculty and their acclimation during their first years. Implications include the need for intentional mentoring, inclusive support for all students seeking faculty roles, and the need for specificity on the part of hiring committees and new departments regarding expectations. Key to new faculty success is obtaining a sense of work-life integration

Factors Associated With Outcomes of Patients With Primary Sclerosing Cholangitis and Development and Validation of a Risk Scoring System.

We sought to identify factors that are predictive of liver transplantation or death in patients with primary sclerosing cholangitis (PSC), and to develop and validate a contemporaneous risk score for use in a real-world clinical setting. Analyzing data from 1,001 patients recruited to the UK-PSC research cohort, we evaluated clinical variables for their association with 2-year and 10-year outcome through Cox-proportional hazards and C-statistic analyses. We generated risk scores for short-term and long-term outcome prediction, validating their use in two independent cohorts totaling 451 patients. Thirty-six percent of the derivation cohort were transplanted or died over a cumulative follow-up of 7,904 years. Serum alkaline phosphatase of at least 2.4 × upper limit of normal at 1 year after diagnosis was predictive of 10-year outcome (hazard ratio [HR] = 3.05; C = 0.63; median transplant-free survival 63 versus 108 months; P < 0.0001), as was the presence of extrahepatic biliary disease (HR = 1.45; P = 0.01). We developed two risk scoring systems based on age, values of bilirubin, alkaline phosphatase, albumin, platelets, presence of extrahepatic biliary disease, and variceal hemorrhage, which predicted 2-year and 10-year outcomes with good discrimination (C statistic = 0.81 and 0.80, respectively). Both UK-PSC risk scores were well-validated in our external cohort and outperformed the Mayo Clinic and aspartate aminotransferase-to-platelet ratio index (APRI) scores (C statistic = 0.75 and 0.63, respectively). Although heterozygosity for the previously validated human leukocyte antigen (HLA)-DR*03:01 risk allele predicted increased risk of adverse outcome (HR = 1.33; P = 0.001), its addition did not improve the predictive accuracy of the UK-PSC risk scores. Conclusion: Our analyses, based on a detailed clinical evaluation of a large representative cohort of participants with PSC, furthers our understanding of clinical risk markers and reports the development and validation of a real-world scoring system to identify those patients most likely to die or require liver transplantation.Financial support has been received by National Institute of Health Research (RD-TRC and Birmingham Biomedical Research Centre), Isaac Newton Trust, Addenbrooke’s charitable trust, Norwegian PSC Research Center and PSC Support. GMH is supported by the Lily and Terry Horner Chair in Autoimmune Liver Disease Research, Toronto Centre for Liver Disease, Toronto

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist

Impact of direct‐acting antiviral agents on liver function in patients with chronic hepatitis C virus infection

© 2020 The Authors. Journal of Viral Hepatitis published by John Wiley & Sons Ltd Whilst the benefit of direct-acting antiviral agents (DAAs) in achieving sustained virological response (SVR) is now well-accepted, their impact on liver function, particularly in relation to achievement of SVR, has not been well documented. We studied 2394 patients with chronic HCV infection, 1276 receiving DAAs and 1118 interferon-based therapy. Liver function was assessed by the albumin-bilirubin (ALBI) score or grade. Overall survival according to SVR status and baseline ALBI grade was examined. We also studied time to first decompensation according to ALBI grade, as well as longitudinal changes in ALBI score over time according to SVR. Among the patients receiving DAAs, 89% achieved SVR (Japan=99%, UK=78%). Amongst the decompensated patients in the UK cohort, three distinct risk groups according to ALBI grade at baseline were observed. The UK patients receiving DAAs, who had predominantly decompensated disease, showed clear evidence of improvement of liver function detectable within 2years of the start of treatment, especially in those achieving SVR. These early changes in liver function were very similar to those observed in the first 2-3years after interferon-based therapy. DAAs improve liver function especially in those with decompensated disease who achieve SVR. Experience with interferon-based therapy suggests that failure to achieve SVR is associated with long-term decline in liver function and, in contrast, patients who do achieve SVR can expect long-term disease improvement and subsequent stabilization of liver function. Our initial analysis suggests that those receiving DAAs are likely, in the long term, to follow a similar course

Dear departed: writing the lifeworlds of place

This paper is concerned with the lifeworlds of place, and the significant part that the storied word might play in them. It considers the modern disciplinary history of place study, and styles of creative geographical writing presently being employed to configure place as a lived phenomenon, with a past, present and future. Across the piece, an experiment in place‐portraiture unfolds, according to a series of episodes penned in non‐fiction prose. The muse for these meditations is an arresting site reserved for burying the remains of loved ones: a seaside pet cemetery. Deep diving into the cemetery's place lore, and the life of its custodian, “The Keeper,” the essay explores the loss, love and longing felt for domestic companion animals by grieving humans, the better to understand a nexus of geographies; variously, of memory, emotion, intimacy, responsibility and creativity. The essay closes by reflecting on how a sustained fusion of site, subject and style can give voice to a language of radical parochialism and, simultaneously, reset the wider representational project by which geographers engage proprietary feelings about place, its presumed fate and possible prospects. In its avoidance of a more conventional academic mode, and adoption of descriptive geographical narratives, the paper offers an alternate literary model by which pressing environmental challenges might yet be affectively articulated and addressed