The Partial Eclipse of Plotinus in the Middle Ages and his Recovery in the Renaissance

This article studies the Plotinian presence in the Middle Ages and the Renaissance. First, it accounts for the indirect transmission of the Enneads throughout Medieval times and the editions that reappears in the Renaissance. In this regard, it discusses the presence and influence of Plotinian ideas on Medieval thinkers. Secondly, it examines some main points of Plotin’s thought –the three hypostases and a single universe– and thirdly, presents the profound coincidences between Plotin and Nicholas of Cusa’s ideas, analyzing the pairings enfolding-unfolding, uncontracted-contracted. Finally, it considers the possibility of reuniting both lines in a Grand Unified Theory that goes through all the Middle Ages.Este artículo trabaja la presencia plotiniana en la Edad Media y el Renacimiento. En primer término, se presenta el movimiento de transmisión indirecta de las Enéadas a lo largo de la Edad Media y las ediciones que resurgen en el Renacimiento. En esta línea, se discute precisamente la presencia e influencia de las ideas plotinianas en pensadores medievales. En segundo término, se despliegan ciertas notas nucleares del pensamiento de Plotino –las tres hipóstasis y un solo universo– para luego, en tercer término, exponer las profundas coincidencias que pueden encontrarse en la estructura del pensamiento de Nicolás de Cusa –con el estudio del lenguaje de los binomios complicación-explicación, incontracto-contracto. Finalmente, se considera la posibilidad de incluir a ambos autores en una Gran Teoría Unificada que se despliega a lo largo de la Edad Media

Dublin's participation in the predicting media memorability task at MediaEval 2018

This paper outlines 6 approaches taken to computing video memorability, for the MediaEval media memorability task. The approaches are based on video features, an end-to-end approach, saliency, aesthetics, neural feedback, and an ensemble of all approaches

Moon Zoo: citizen science in lunar exploration

The Moon Zoo Team describe how citizen scientists can get involved and explore the Moon online

Riemannian Gauge Theory and Charge Quantization

In a traditional gauge theory, the matter fields \phi^a and the gauge fields A^c_\mu are fundamental objects of the theory. The traditional gauge field is similar to the connection coefficient in the Riemannian geometry covariant derivative, and the field-strength tensor is similar to the curvature tensor. In contrast, the connection in Riemannian geometry is derived from the metric or an embedding space. Guided by the physical principal of increasing symmetry among the four forces, we propose a different construction. Instead of defining the transformation properties of a fundamental gauge field, we derive the gauge theory from an embedding of a gauge fiber F=R^n or F=C^n into a trivial, embedding vector bundle F=R^N or F=C^N where N>n. Our new action is symmetric between the gauge theory and the Riemannian geometry. By expressing gauge-covariant fields in terms of the orthonormal gauge basis vectors, we recover a traditional, SO(n) or U(n) gauge theory. In contrast, the new theory has all matter fields on a particular fiber couple with the same coupling constant. Even the matter fields on a C^1 fiber, which have a U(1) symmetry group, couple with the same charge of +/- q. The physical origin of this unique coupling constant is a generalization of the general relativity equivalence principle. Because our action is independent of the choice of basis, its natural invariance group is GL(n,R) or GL(n,C). Last, the new action also requires a small correction to the general-relativity action proportional to the square of the curvature tensor.Comment: Improved the explanations, added references, added 3 figures and an appendix, corrected a sign error in the old figure 4 (now figure 5). Now 33 pages, 7 figures and 2 tables. E-mail Serna for annimation

Developing new health technologies for neglected diseases: a pipeline portfolio review and cost model [version 1; referees: 1 approved, 2 approved with reservations]

Background:  Funding for product development for neglected diseases fell from 2009-2015, other than a short-term injection of Ebola funding. One impediment to mobilizing resources is a lack of information on product candidates, the estimated costs to move them through the pipeline, and the likelihood of specific launches. This study aimed to help fill these information gaps. Methods: We conducted a pipeline portfolio review to identify current candidates for 35 neglected diseases. Using an adapted version of the Portfolio to Impact (P2I) financial modelling tool, we estimated the costs to move these candidates through the pipeline over the next decade and the likely launches. Since the current pipeline is unlikely to yield several critical products, we estimated the costs to develop a set of priority “missing” products. Results: We found 685 product candidates for neglected diseases as of August 31, 2017; 538 candidates met inclusion criteria for input into the model. It would cost about $16.3 billion (range$13.4-19.8B) to move these candidates through the pipeline, with three-quarters of the costs incurred in the first 5 years, resulting in about 128 (89-160) expected product launches.  Based on the current pipeline, there would be very few launches of complex new chemical entities; launches of highly efficacious vaccines for HIV, tuberculosis, or malaria would be unlikely. Estimated additional costs to launch one of each of 18 key missing products range from $13.6B-$21.8B, depending on product complexity. Over the next 5 years, total estimated costs to move current candidates through the pipeline and develop these 18 missing products would be around $4.5-5.8B/year. Conclusions: Since current annual global spending on product development is about$3B, this study suggests the annual funding gap over the next 5 years is at least $1.5-2.8B, which is probably an underestimate. The current portfolio is not balanced across health needs

Somatic evolution and global expansion of an ancient transmissible cancer lineage

The canine transmissible venereal tumour (CTVT) is a cancer lineage that arose several millennia ago and survives by ‘metastasising’ between hosts via cell transfer. The somatic mutations in this cancer record its phylogeography and evolutionary history. We constructed a time-resolved phylogeny from 546 CTVT exomes and describe the lineage’s worldwide expansion. Examining variation in mutational exposure, we identify a highly context-specific mutational process that operated early but subsequently vanished, correlate ultraviolet-light mutagenesis with tumour latitude, and describe tumours with heritable hyperactivity of an endogenous mutational process. CTVT displays little evidence of ongoing positive selection, and negative selection is detectable only in essential genes. We illustrate how long-lived clonal organisms capture changing mutagenic environments, and reveal that neutral drift is the dominant feature of long-term cancer evolution

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely