Thermodynamic instability of rotating black holes

We show that the quasi-Euclidean sections of various rotating black holes in different dimensions possess at least one non-conformal negative mode when thermodynamic instabilities are expected. The boundary conditions of fixed induced metric correspond to the partition function of the grand-canonical ensemble. Indeed, in the asymptotically flat cases, we find that a negative mode persists even if the specific heat at constant angular momenta is positive, since the stability in this ensemble also requires the positivity of the isothermal momentum of inertia. We focus in particular on Kerr black holes, on Myers-Perry black holes in five and six dimensions, and on the Emparan-Reall black ring solution. We go on further to consider the richer case of the asymptotically AdS Kerr black hole in four dimensions, where thermodynamic stability is expected for a large enough cosmological constant. The results are consistent with previous findings in the non-rotation limit and support the use of quasi-Euclidean instantons to construct gravitational partition functions

Evolutionary dynamics of the human pseudoautosomal regions

Recombination between the X and Y human sex chromosomes is limited to the two pseudoautosomal regions (PARs) that present quite distinct evolutionary origins. Despite the crucial importance for male meiosis, genetic diversity patterns and evolutionary dynamics of these regions are poorly understood. In the present study, we analyzed and compared the genetic diversity of the PAR regions using publicly available genomic sequences encompassing both PAR1 and PAR2. Comparisons were performed through allele diversities, linkage disequilibrium status and recombination frequencies within and between X and Y chromosomes. In agreement with previous studies, we confirmed the role of PAR1 as a male-specific recombination hotspot, but also observed similar characteristic patterns of diversity in both regions although male recombination occurs at PAR2 to a much lower extent (at least one recombination event at PAR1 and in ˜1% in normal male meioses at PAR2). Furthermore, we demonstrate that both PARs harbor significantly different allele frequencies between X and Y chromosomes, which could support that recombination is not sufficient to homogenize the pseudoautosomal gene pool or is counterbalanced by other evolutionary forces. Nevertheless, the observed patterns of diversity are not entirely explainable by sexually antagonistic selection. A better understanding of such processes requires new data from intergenerational transmission studies of PARs, which would be decisive on the elucidation of PARs evolution and their role in male-driven heterosomal aneuploidies.This work was supported by: - FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 - Operacional Programme for Competitiveness and Internationalization (POCI), Portugal 2020. - Fundação para a Ciência e a Tecnologia, in the framework of the Project POCI-01–0145-FEDER-007274 to i3S. - Fundação para a Ciência e a Tecnologia, in the PhD fellowship SFRH/BD/ 135612/2018 to B.M. - Ministerio de Ciencia, Innovación y Universidades, in the Grant “Ramón y Cajal” RYC-2015-18241 to M.A. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Mercapturate Pathway in the Tubulocentric Perspective of Diabetic Kidney Disease

BACKGROUND: The recent growing evidence that the proximal tubule underlies the early pathogenesis of diabetic kidney disease (DKD) is unveiling novel and promising perspectives. This pathophysiological concept links tubulointerstitial oxidative stress, inflammation, hypoxia, and fibrosis with the progression of DKD. In this new angle for DKD, the prevailing molecular mechanisms on proximal tubular cells emerge as an innovative opportunity for prevention and management of DKD as well as to improve diabetic dysmetabolism. SUMMARY: The mercapturate pathway (MAP) is a classical metabolic detoxification route for xenobiotics that is emerging as an integrative circuitry detrimental to resolve tubular inflammation caused by endogenous electrophilic species. Herein we review why and how it might underlie DKD. Key Messages: MAP is a hallmark of proximal tubular cell function, and cysteine-S-conjugates might represent targets for early intervention in DKD. Moreover, the biomonitoring of urinary mercapturates from metabolic inflammation products might be relevant for the implementation of preventive/management strategies in DKD.info:eu-repo/semantics/publishedVersio

Lung metastases from colorectal cancer: surgical resection and prognostic factors

OBJECTIVE: To analyse our experience with excision of lung metastases from colorectal carcinoma (CRC), and to evaluate clinically relevant prognostic factors, identifying the cluster of patients who would benefit from this procedure. METHODS: Sixty-one patients, 42 men (69%), with primary CRC who underwent 94 curative resections of pulmonary metastases were retrospectively reviewed. Age was 30-80 years (mean 61.2+/-15). Population was analysed for age, sex, disease-free interval (DFI), prethoracotomy carcinoembryonic antigen (CEA) level, location and histology of primary tumour, number of lung lesions (and size of largest resected metastasis), type of lung resection, nodal involvement (hilar/mediastinal), use of adjuvant treatment, morbid-mortality and immediate and follow-up survival. RESULTS: Mean DFI was 29+/-22 months (range 5-132 months). There was no hospital mortality and significant morbidity occurred in five patients (8.2%). Mean follow-up was 39+/-4 months (range 4-173 months). Mean overall survival and disease-free survival were 67+/-16 months and 52+/-6 months, respectively. Three-, 5- and 10-year survival rates from date of primary colorectal resection were 83%, 71% and 43%, respectively. Three-, 5- and 10-year survival rates from date of lung resection were 61%, 48% and 11%, respectively. Five-year survival was 57% in patients with normal prethoracotomy CEA levels and 18% for those with high levels (>5 ng/ml) (p=0.039). CONCLUSIONS: Pulmonary metastasectomy has potential survival benefit for patients with metastatic colorectal carcinoma. Low morbidity and mortality rates, contrasting with lack of any other effective therapy, justify aggressive surgical management. Single deposits, DFI >36 months and normal prethoracotomy serum CEA were significant independent prognostic factors

Autologous fat grafting: Harvesting techniques

Autologous fat grafting is widely used for soft-tissue augmentation and replacement in reconstructive and aesthetic surgery providing a biocompatible, natural and inexpensive method. Multiple approaches have been developed in the past years, varying in the location of adipose tissue donor-sites, use of wetting solutions, harvesting, processing and placing techniques. Despite many advances in this subject, the lack of standardization in the protocols and the unpredictability of the resorption of the grafted tissue pose a significant limitation for graft retention and subsequent filling. In this review, we discuss several approaches and methods described over the last years concerning the harvesting of autologous fat grafts. We focus on contents such as the best donor-site, differences between existing harvesting techniques (namely tissue resection, hand aspiration or liposuction techniques), recommended harvesting cannula diameters, pressure application and volume of wetting solution injected prior aspiration. Results and comparisons between methods tend to vary according to the outcome measured, thus posing a limitation to pinpoint the most efficient methods to apply in fat grafting. Additionally, the lack of a standard assay to determine viability or volume augmentation of fat grafting remains another limitation to obtain universally accepted grafting procedures and protocols.This work was supported by FEDER – Fundo Europeu de Desenvolvimento Regional, through NORTE 2020 Programa Operacional Regional do Norte - NORTE-01-0145-FEDER-000012 and Instituto de Investigação e Inovação em Saúde (Projeto Estratégico UID/BIM/04293/2013 )

Left ventricular end diastolic pressure and acute coronary syndromes

BACKGROUND: Data is lacking in the literature regarding the prognostic impact of left ventricular-end diastolic pressure (LVEDP) across acute coronary syndromes (ACS). OBJECTIVE: To assess LVEDP and its prognostic implications in ACS patients. METHODS: Prospective, longitudinal and continuous study of 1329 ACS patients from a single center between 2004 and 2006. Diastolic function was determined by LVEDP. Population was divided in two groups: A - LVEDP 26.5 mmHg (n = 226). RESULTS: There were no significant differences between groups with respect to risk factors for cardiovascular disease, medical history and medical therapy during admission. In group A, patients with non-ST elevation ACS were more frequent, as well as normal coronary angiograms. In-hospital mortality was similar between groups, but one-year survival was higher in group A patients (96.9 vs 91.2%, log rank p = 0.002). On a multivariate Cox regression model, a LVEDP > 26.5 mmHg (HR 2.45, 95%CI 1.05 - 5.74) remained an independent predictor for one-year mortality, when adjusted for age, LV systolic ejection fraction, ST elevation ACS, peak troponin, admission glycemia, and diuretics at 24 hours. Also, a LVEDP > 26.5 mmHg was an independent predictor for a future readmission due to congestive HF (HR 6.65 95%CI 1.74 - 25.5). CONCLUSION: In our selected population, LVEDP had a significant prognostic influence

Identity, reputation and social interaction with an application to sequential voting

We analyze binary choices in a random utility model assuming that the agent's preferences are affected by conformism (with respect to the behavior of the society) and coherence (with respect to his identity). We apply the analysis to sequential voting when voters like to win