Kairos

The first major public presentation of Kairos by artist and musician Anat Ben-David, an ambitious new theatrical song-cycle commissioned by the Stanley Picker Gallery at Kingston University, incorporating fashion, opera, dance, experimental music and multi-media. Inspired by Sadie Plant’s seminal book Zeroes and Ones (1997), Kairos brings together performers from the worlds of opera, and electronic and experimental composition, in a futuristic staging by avant-garde fashion studio Boudicca, providing a journey through the new spaces with a series of choreographed sequences. The event took place in July 2017. The Ancient Greeks had two distinct concepts relating to notions of time. The word Chronos referred to chronological time, whilst Kairos signified a time lapse, an indeterminate time in which everything happens at once. The human instinct of marking the present with an improvised yet intense act of creativity, is the moment when controlled and measured chronological time (Chronos) gives way to the intensity of the supreme moment of the now (Kairos) and the urgent, demonstrative act of self-expression; the holler, the gesture, the strike, the cut, the dash, the mark. 2017 will mark 20 years of the Stanley Picker Gallery at Kingston University; two decades commissioning ambitious new work by some of today’s most significant creative practitioners across artistic disciplines including Oreet Ashery, David Austen, Mark Beasley, Marloes ten Bhömer, BOUDICCA,Fabien Cappello, Daniel Eatock, Andy Holden, Shelley Fox, Juneau Projects, Onkar Kular, Laura Oldfield Ford, Elizabeth Price, Ab Rogers, Nicole Wermers and others. Chronos & Kairos will evolve through a series of collaborative workshops during 2016/17. The project’s intentionally flexible structure will remain changeable, generating tensions between its formal and improvised elements, with a diverse troupe of collaborators, and ultimately allowing each individual staging of the work to evolve and adapt to its given context. This event took place in January 201

Embodiment and social distancing: Practices

A collection of five video essays on embodiment and social distancing, with a focus on practices. RAFFAELE RUFO, “Dancing Together Alone: What Can Be Learnt About Connection When Touch is Forbidden?” (00:10): This video essay reengages the experience of leading a dance improvisation practice on Zoom during the Coronavirus lockdown. As a tango and contact improvisation dancer confined at home, I felt urged to ask: what can be learnt about embodied connection when we are not allowed to physically touch each other? ANAT BEN-DAVID AND CATHARINE ANNE CARY, “What’s the Matter?” (05:54): Performers, scenographers, musicians and wordsmiths Anat Ben-David and Catharine Cary improvised via ZOOM every Tuesday from March to May 2020. Embracing latency, zoom’s affordances, limitations and distortions, they show here excerpts of a transformed body of work. Separated by 5218 km, given the Covid-19 situation, it could have been 200 meters. DEANNA BORLAND-SENTINELLA, LOUISE GWENNETH PHILLIPS, AND ALICE OWEN, “Virtually Embodied: Remembering the Sensations of Connection” (12:04): This film is an exploration of the body: Being present to place and time; being aware of connection with others, whether that be in reality or through virtual connection and sensorial memory. NATHALIE S. FARI, “Notes from a zoom 5Rhythms® session” (17:10): By using a three-hour 5Rhythms® online workshop as basis, this video sheds light into the ways in which the practitioner interacts and engages with both one’s own bodily awareness and the new technology of zoom. AMBERBECKYCREATIVE, “Sheltering in Spacetimematterings: Audiovisual Considerations of Social Distancing” (22:42): Two socially distant authors glitch audiovisual intra-actions through embodied (dis)orientations of space, time, and matter in past/present/future collapsed to (re)present what it’s like to shelter in place during the COVID-19 pandemic

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

Effect of natalizumab on disease progression in secondary progressive multiple sclerosis (ASCEND). a phase 3, randomised, double-blind, placebo-controlled trial with an open-label extension

Background: Although several disease-modifying treatments are available for relapsing multiple sclerosis, treatment effects have been more modest in progressive multiple sclerosis and have been observed particularly in actively relapsing subgroups or those with lesion activity on imaging. We sought to assess whether natalizumab slows disease progression in secondary progressive multiple sclerosis, independent of relapses. Methods: ASCEND was a phase 3, randomised, double-blind, placebo-controlled trial (part 1) with an optional 2 year open-label extension (part 2). Enrolled patients aged 18–58 years were natalizumab-naive and had secondary progressive multiple sclerosis for 2 years or more, disability progression unrelated to relapses in the previous year, and Expanded Disability Status Scale (EDSS) scores of 3·0–6·5. In part 1, patients from 163 sites in 17 countries were randomly assigned (1:1) to receive 300 mg intravenous natalizumab or placebo every 4 weeks for 2 years. Patients were stratified by site and by EDSS score (3·0–5·5 vs 6·0–6·5). Patients completing part 1 could enrol in part 2, in which all patients received natalizumab every 4 weeks until the end of the study. Throughout both parts, patients and staff were masked to the treatment received in part 1. The primary outcome in part 1 was the proportion of patients with sustained disability progression, assessed by one or more of three measures: the EDSS, Timed 25-Foot Walk (T25FW), and 9-Hole Peg Test (9HPT). The primary outcome in part 2 was the incidence of adverse events and serious adverse events. Efficacy and safety analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01416181. Findings: Between Sept 13, 2011, and July 16, 2015, 889 patients were randomly assigned (n=440 to the natalizumab group, n=449 to the placebo group). In part 1, 195 (44%) of 439 natalizumab-treated patients and 214 (48%) of 448 placebo-treated patients had confirmed disability progression (odds ratio [OR] 0·86; 95% CI 0·66–1·13; p=0·287). No treatment effect was observed on the EDSS (OR 1·06, 95% CI 0·74–1·53; nominal p=0·753) or the T25FW (0·98, 0·74–1·30; nominal p=0·914) components of the primary outcome. However, natalizumab treatment reduced 9HPT progression (OR 0·56, 95% CI 0·40–0·80; nominal p=0·001). In part 1, 100 (22%) placebo-treated and 90 (20%) natalizumab-treated patients had serious adverse events. In part 2, 291 natalizumab-continuing patients and 274 natalizumab-naive patients received natalizumab (median follow-up 160 weeks [range 108–221]). Serious adverse events occurred in 39 (13%) patients continuing natalizumab and in 24 (9%) patients initiating natalizumab. Two deaths occurred in part 1, neither of which was considered related to study treatment. No progressive multifocal leukoencephalopathy occurred. Interpretation: Natalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component. Longer-term trials are needed to assess whether treatment of secondary progressive multiple sclerosis might produce benefits on additional disability components. Funding: Biogen

Multidisciplinary management of acromegaly: A consensus.

The 13th Acromegaly Consensus Conference was held in November 2019 in Fort Lauderdale, Florida, and comprised acromegaly experts including endocrinologists and neurosurgeons who considered optimal approaches for multidisciplinary acromegaly management. Focused discussions reviewed techniques, results, and side effects of surgery, radiotherapy, and medical therapy, and how advances in technology and novel techniques have changed the way these modalities are used alone or in combination. Effects of treatment on patient outcomes were considered, along with strategies for optimizing and personalizing therapeutic approaches. Expert consensus recommendations emphasize how best to implement available treatment options as part of a multidisciplinary approach at Pituitary Tumor Centers of Excellence

SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids

Kidney failure is frequently observed during and after COVID-19, but it remains elusive whether this is a direct effect of the virus. Here, we report that SARS-CoV-2 directly infects kidney cells and is associated with increased tubule-interstitial kidney fibrosis in patient autopsy samples. To study direct effects of the virus on the kidney independent of systemic effects of COVID-19, we infected human induced pluripotent stem cell-derived kidney organoids with SARS-CoV-2. Single cell RNA-sequencing indicated injury and dedifferentiation of infected cells with activation of pro-fibrotic signaling pathways. Importantly, SARS-CoV-2 infection also led to increased collagen 1 protein expression in organoids. A SARS-CoV-2 protease inhibitor was able to ameliorate the infection of kidney cells by SARS-CoV-2. Our results suggest that SARS-CoV-2 can directly infect kidney cells and induce cell injury with subsequent fibrosis. These data could explain both acute kidney injury in COVID-19 patients and the development of chronic kidney disease in Long-COVID

The NlpD Lipoprotein Is a Novel Yersinia pestis Virulence Factor Essential for the Development of Plague

Yersinia pestis is the causative agent of plague. Previously we have isolated an attenuated Y. pestis transposon insertion mutant in which the pcm gene was disrupted. In the present study, we investigated the expression and the role of pcm locus genes in Y. pestis pathogenesis using a set of isogenic surE, pcm, nlpD and rpoS mutants of the fully virulent Kimberley53 strain. We show that in Y. pestis, nlpD expression is controlled from elements residing within the upstream genes surE and pcm. The NlpD lipoprotein is the only factor encoded from the pcm locus that is essential for Y. pestis virulence. A chromosomal deletion of the nlpD gene sequence resulted in a drastic reduction in virulence to an LD50 of at least 107 cfu for subcutaneous and airway routes of infection. The mutant was unable to colonize mouse organs following infection. The filamented morphology of the nlpD mutant indicates that NlpD is involved in cell separation; however, deletion of nlpD did not affect in vitro growth rate. Trans-complementation experiments with the Y. pestis nlpD gene restored virulence and all other phenotypic defects. Finally, we demonstrated that subcutaneous administration of the nlpD mutant could protect animals against bubonic and primary pneumonic plague. Taken together, these results demonstrate that Y. pestis NlpD is a novel virulence factor essential for the development of bubonic and pneumonic plague. Further, the nlpD mutant is superior to the EV76 prototype live vaccine strain in immunogenicity and in conferring effective protective immunity. Thus it could serve as a basis for a very potent live vaccine against bubonic and pneumonic plague