A Commentary on Ruppeiner Metrics for Black Holes

There has been some recent controversy regarding the Ruppeiner metrics that are induced by Reissner-Nordstrom (and Reissner-Nordstrom-like) black holes. Most infamously, why does this family of metrics turn out to be flat, how is this outcome to be physically understood, and can/should the formalism be suitably modified to induce curvature? In the current paper, we provide a novel interpretation of this debate. For the sake of maximal analytic clarity and tractability, some supporting calculations are carried out for the relatively simple model of a rotating BTZ black hole.Comment: 15 pages; v2, typos corrected and a few references adde

Human bone marrow mesenchymal stem cells : a systematic reappraisal via the genostem experience

Genostem (acronym for “Adult mesenchymal stem cells engineering for connective tissue disorders. From the bench to the bed side”) has been an European consortium of 30 teams working together on human bone marrow Mesenchymal Stem Cell (MSC) biological properties and repair capacity. Part of Genostem activity has been dedicated to the study of basic issues on undifferentiated MSCs properties and on signalling pathways leading to the differentiation into 3 of the connective tissue lineages, osteoblastic, chondrocytic and tenocytic. We have evidenced that native bone marrow MSCs and stromal cells, forming the niche of hematopoietic stem cells, were the same cellular entity located abluminally from marrow sinus endothelial cells. We have also shown that culture-amplified, clonogenic and highly-proliferative MSCs were bona fide stem cells, sharing with other stem cell types the major attributes of self-renewal and of multipotential priming to the lineages to which they can differentiate (osteoblasts, chondrocytes, adipocytes and vascular smooth muscle cells/pericytes). Extensive transcription profiling and in vitro and in vivo assays were applied to identify genes involved in differentiation. Thus we have described novel factors implicated in osteogenesis (FHL2, ITGA5, Fgf18), chondrogenesis (FOXO1A) and tenogenesis (Smad8). Another part of Genostem activity has been devoted to studies of the repair capacity of MSCs in animal models, a prerequisite for future clinical trials. We have developed novel scaffolds (chitosan, pharmacologically active microcarriers) useful for the repair of both bone and cartilage. Finally and most importantly, we have shown that locally implanted MSCs effectively repair bone, cartilage and tendonWork supported by the European Community (Key action 1.2.4-3 Integrated Project Genostem, contract No 503161)

Potential Impact of Mediterranean Aquaculture on the Wild Predatory Bluefish

Aquaculture impacts on wild populations of fish have been considered principally due to farm escapes. The Bluefish Pomatomus saltatrix, which exhibits two distinct genetic units in the Mediterranean Sea, is a voracious predator and is attracted to aquaculture cages to prey on farmed fish, particularly Gilthead Seabream Sparus aurata and European Sea Bass Dicentrarchus labrax. We compared the genetic diversity of adult Bluefish caught inside one aquaculture farm located in Spanish waters of the western Mediterranean Sea with reference individuals of East and West Mediterranean stocks from the open sea. Bluefish were genetically assigned to their putative origin using seven microsatellite loci and mitochondrial cytochrome oxidase subunit I as molecular markers. As expected, most of the individuals caught from inside the fish farm cages were assigned to the local genetic population. However, between 7.14% and 11.9% of individuals were assigned to the distant and different genetic unit inhabiting Turkish waters, the East Mediterranean stock. The genetic membership of those individuals revealed some degree of interbreeding between the East and West Mediterranean Bluefish stocks. All results suggest that aquaculture acts as an attractor for Bluefish and could affect genetic diversity as well as phylogeography of this fish and maybe other similar species that aggregate around marine fish farms.We are very grateful to T. Ceyhan for providing the Bluefish samples from Turkey. The study was supported by the MICINN CGL-2009-08279 Grant (Spain) and the Asturian Grant GRUPIN2014-093. Laura Miralles held a PCTI Grant from the Asturias Regional Government, referenced BP 10-004. This is a contribution from the Marine Observatory of Asturias

Geometrothermodynamics of five dimensional black holes in Einstein-Gauss-Bonnet-theory

We investigate the thermodynamic properties of 5D static and spherically symmetric black holes in (i) Einstein-Maxwell-Gauss-Bonnet theory, (ii) Einstein-Maxwell-Gauss-Bonnet theory with negative cosmological constant, and in (iii) Einstein-Yang-Mills-Gauss-Bonnet theory. To formulate the thermodynamics of these black holes we use the Bekenstein-Hawking entropy relation and, alternatively, a modified entropy formula which follows from the first law of thermodynamics of black holes. The results of both approaches are not equivalent. Using the formalism of geometrothermodynamics, we introduce in the manifold of equilibrium states a Legendre invariant metric for each black hole and for each thermodynamic approach, and show that the thermodynamic curvature diverges at those points where the temperature vanishes and the heat capacity diverges.Comment: New sections added, references adde

Patient-Specific Metrics of Invasiveness Reveal Significant Prognostic Benefit of Resection in a Predictable Subset of Gliomas

Object Malignant gliomas are incurable, primary brain neoplasms noted for their potential to extensively invade brain parenchyma. Current methods of clinical imaging do not elucidate the full extent of brain invasion, making it difficult to predict which, if any, patients are likely to benefit from gross total resection. Our goal was to apply a mathematical modeling approach to estimate the overall tumor invasiveness on a patient-by-patient basis and determine whether gross total resection would improve survival in patients with relatively less invasive gliomas. Methods In 243 patients presenting with contrast-enhancing gliomas, estimates of the relative invasiveness of each patient's tumor, in terms of the ratio of net proliferation rate of the glioma cells to their net dispersal rate, were derived by applying a patient-specific mathematical model to routine pretreatment MR imaging. The effect of varying degrees of extent of resection on overall survival was assessed for cohorts of patients grouped by tumor invasiveness. Results We demonstrate that patients with more diffuse tumors showed no survival benefit (P = 0.532) from gross total resection over subtotal/biopsy, while those with nodular (less diffuse) tumors showed a significant benefit (P = 0.00142) with a striking median survival benefit of over eight months compared to sub-totally resected tumors in the same cohort (an 80% improvement in survival time for GTR only seen for nodular tumors). Conclusions These results suggest that our patient-specific, model-based estimates of tumor invasiveness have clinical utility in surgical decision making. Quantification of relative invasiveness assessed from routinely obtained pre-operative imaging provides a practical predictor of the benefit of gross total resection

Subgroup Economic Analysis for Glioblastoma in a Health Resource-Limited Setting

BACKGROUND: The aim of this research was to evaluate the economic outcomes of radiotherapy (RT), temozolomide (TMZ) and nitrosourea (NT) strategies for glioblastoma patients with different prognostic factors. METHODOLOGY/PRINCIPAL FINDINGS: A Markov model was developed to track monthly patient transitions. Transition probabilities and utilities were derived primarily from published reports. Costs were estimated from the perspective of the Chinese healthcare system. The survival data with different prognostic factors were simulated using Weibull survival models. Costs over a 5-year period and quality-adjusted life years (QALYs) were estimated. Probabilistic sensitivity and one-way analyses were performed. The baseline analysis in the overall cohort showed that the TMZ strategy increased the cost and QALY relative to the RT strategy by $25,328.4 and 0.29, respectively; and the TMZ strategy increased the cost and QALY relative to the NT strategy by$23,906.5 and 0.25, respectively. Therefore, the incremental cost effectiveness ratio (ICER) per additional QALY of the TMZ strategy, relative to the RT strategy and the NT strategy, amounts to $87,940.6 and$94,968.3, respectively. Subgroups with more favorable prognostic factors achieved more health benefits with improved ICERs. Probabilistic sensitivity analyses confirmed that the TMZ strategy was not cost-effective. In general, the results were most sensitive to the cost of TMZ, which indicates that better outcomes could be achieved by decreasing the cost of TMZ. CONCLUSIONS/SIGNIFICANCE: In health resource-limited settings, TMZ is not a cost-effective option for glioblastoma patients. Selecting patients with more favorable prognostic factors increases the likelihood of cost-effectiveness

The State of Neuro-Oncology During the COVID-19 Pandemic: A Worldwide Assessment

To assess the impact of the pandemic on the field, we performed an international web-based survey of practitioners, scientists, and trainees from 21 neuro-oncology organizations across 6 continents from April 24 through May 17. Of 582 respondents, 258 (45%) were in the US, and 314 (55%) were international. 80.4% were affiliated with academic institutions. 94% respondents reported changes in clinical practice; 95% reported conversion to telemedicine for at least some appointments. However, almost 10% practitioners felt the need to see patients in person specifically because of billing concerns and perceived institutional pressure. Over 50% believed neuro-oncology patients were at increased risk of contracting COVID-19. 67% practitioners suspended enrollment for at least one clinical trial: 53% suspended phase II and 62% suspended phase III trial enrollment. 71% clinicians feared for their or their families’ safety, specifically because of their clinical duties. 20% percent said they did not have enough PPE to work safely; about the same percentage were unhappy with their institutions’ response to the pandemic. 43% believed the pandemic would negatively affect their academic career, and 52% fellowship program directors were worried about losing funding for their training programs. While 69% respondents reported increased stress, 44% were offered no psychosocial support. 37% had their salary reduced. 36% researchers had to temporarily close their laboratories. In contrast, the pandemic created positive changes in perceived patient and family satisfaction, quality of communication, and use of technology to deliver care and interactions with other practitioners. CONCLUSIONS: The pandemic has altered standard treatment schedules and limited investigational treatment options for patients. In some cases, clinicians felt institutional pressure to continue conducting billable in-person visits when telemedicine visits would have sufficed. A lack of institutional support created anxiety among clinicians and researchers. We make specific recommendations to guide clinical and scientific infrastructure moving forward