The area of a spherical region can be easily measured by considering which sampling points of a lattice are located inside or outside the region. This point-counting technique is frequently used for ...measuring the Earth coverage of satellite constellations, employing a latitude–longitude lattice. This paper analyzes the numerical errors of such measurements, and shows that they could be greatly reduced if the Fibonacci lattice were used instead. The latter is a mathematical idealization of natural patterns with optimal packing, where the area represented by each point is almost identical. Using the Fibonacci lattice would reduce the root mean squared error by at least 40%. If, as is commonly the case, around a million lattice points are used, the maximum error would be an order of magnitude smaller.
The size or energy of diverse structures or phenomena in geoscience appears to follow power law distributions. A rigorous statistical analysis of such observations is tricky, though. Observables can ...span several orders of magnitude, but the range for which the power law may be valid is typically truncated, usually because the smallest events are too tiny to be detected and the largest ones are limited by the system size. We revisit several examples of proposed power law distributions dealing with potentially damaging natural phenomena. Adequate fits of the distributions of sizes are especially important in these cases, given that they may be used to assess long‐term hazard. After reviewing the theoretical background for power law distributions, we improve an objective statistical fitting method and apply it to diverse data sets. The method is described in full detail, and it is easy to implement. Our analysis elucidates the range of validity of the power law fit and the corresponding exponent and whether a power law tail is improved by a truncated lognormal. We confirm that impact fireballs and Californian earthquakes show untruncated power law behavior, whereas global earthquakes follow a double power law. Rain precipitation over space and time and tropical cyclones show a truncated power law regime. Karst sinkholes and wildfires, in contrast, are better described by truncated lognormals, although wildfires also may show power law regimes. Our conclusions only apply to the analyzed data sets but show the potential of applying this robust statistical technique in the future.
Key Points
We reanalyze the size distribution of earthquakes, karst sinkholes, wildfires, tropical cyclones, rainfall clusters, and impact fireballs
A same, objective, statistical fitting method is improved and applied, allowing faithful comparisons between data sets
The method automatically identifies the truncations of power law distributions, crossovers between power law regimes, and the best fit in the comparison between power law and lognormal tails
The clinical benefit of sorafenib in patients with hepatocellular carcinoma (HCC) has been undervalued due to the absence of complete responses, even though patients who develop early dermatologic ...reactions have shown to have a positive outcome. In addition, sorafenib is described as an antiangiogenic drug, but it also acts on immunological cells. Thus, the goal of this study was to assess the complete response rate in a retrospective cohort of HCC patients treated with sorafenib and to describe the profile of the patients who achieve complete response for identifying factors related to this event and their connection with the immunological profile of sorafenib. Ten Spanish centers submitted cases of complete response under sorafenib. The baseline characteristics, development of early dermatologic reactions, and cause of treatment discontinuation were annotated. Radiological images taken before starting sorafenib, at first control, after starting sorafenib, at the time of complete response, and at least 1 month after treatment were centrally reviewed. Of the 1119 patients studied, 20 had been classified as complete responders by the centers, but eight of these patients were excluded after central review. Ten patients had complete disappearance of all tumor sites, and two had just a small residual fibrotic scar. Thus, 12 patients were classified as complete responders (58% HCV, median age 59.7 years, 83.4% Child‐Pugh class A, Eastern Cooperative Oncology Group performance status 0 91.7%, and Barcelona Clinic Liver Cancer stage C 83.3%). The median overall survival and treatment duration were 85.8 and 40.1 months, respectively. All but one patient developed early dermatologic reactions, and seven patients discontinued sorafenib after achieving complete response due to adverse events, patient decision, or liver decompensation. Conclusion: Complete response affects 1% of patients with HCC who are treated with sorafenib. The association of complete response with early dermatologic reactions supports the role of a specific immune/inflammatory patient profile in the improved response to sorafenib. (Hepatology 2018;67:612‐622).
•IL-8 is a chemokine frequently produced in the tumor microenvironment by human malignant cells.•IL-8 plays key roles in the immunobiology of human malignancies and resistance to ...treatments.•Circulating IL-8 concentration reflects tumor burden.•Change in serum IL-8 is a biomarker to follow immunotherapy with checkpoint inhibitors.
Interleukin-8 (CXCL8) was originally described asa chemokine whose main function is the attraction of a polymorphonuclear inflammatory leukocyte infiltrate acting on CXCR1/2. Recently, it has been found that tumors very frequently coopt the production of this chemokine, which in this malignant context exerts different pro-tumoral functions. Reportedly, these include angiogenesis, survival signaling for cancer stem cells and attraction of myeloid cells endowed with the ability to immunosuppress and locally provide growth factors. Given the fact that in cancer patients IL-8 is mainly produced by tumor cells themselves, its serum concentration has been shown to correlate with tumor burden. Thus, IL-8 serum concentrations have been shown to be useful asa pharmacodynamic biomarker to early detect response to immunotherapy. Finally, because of the roles that IL-8 plays in favoring tumor progression, several therapeutic strategies are being developed to interfere with its functions. Such interventions hold promise, especially for therapeutic combinations in the field of cancer immunotherapy.
Summary
Trace elements and heavy metals play pivotal roles in health status by regulating a myriad of vital biological functions. Abnormal metal homeostasis has been linked to a constellation of ...pathogenic complications, including oxidative stress, inflammatory processes, dyslipidemia, and impaired insulin‐mediated metabolism of carbohydrates, thereby increasing the odds of developing childhood obesity and related comorbidities. Herein, we provide a comprehensive revision of recent literature on the association between childhood obesity, trace elements, and heavy metals. Further, we emphasize on the crucial importance of addressing the influence that interindividual variability factors (e.g., sex, age, genetic determinants, concomitance of comorbidities, and environmental factors) may have in modulating the susceptibility to disease development. Altogether, this review article represents a concise guide to better understand the involvement of metals in childhood obesity pathogenesis and discusses future needs with the aim of establishing robust biomarkers in the context of precision medicine.
Glioblastoma multiforme (GBM) is the most frequent malignant brain tumor in adults, and its prognosis remains dismal despite intensive research and therapeutic advances. Diagnostic biomarkers would ...be clinically meaningful to allow for early detection of the tumor and for those cases in which surgery is contraindicated or biopsy results are inconclusive. Recent findings show that GBM cells release microvesicles that contain a select subset of cellular proteins and RNA. The aim of this hypothesis-generating study was to assess the diagnostic potential of miRNAs found in microvesicles isolated from the serum of GBM patients.
To control disease heterogeneity, we used patients with newly diagnosed GBM. In the discovery stage, PCR-based TaqMan Low Density Arrays followed by individual quantitative reverse transcriptase polymerase chain reaction were used to test the differences in the miRNA expression levels of serum microvesicles among 25 GBM patients and healthy controls paired by age and sex. The detected noncoding RNAs were then validated in another 50 GBM patients.
We found that the expression levels of 1 small noncoding RNA (RNU6-1) and 2 microRNAs (miR-320 and miR-574-3p) were significantly associated with a GBM diagnosis. In addition, RNU6-1 was consistently an independent predictor of a GBM diagnosis.
Altogether our results uncovered a small noncoding RNA signature in microvesicles isolated from GBM patient serum that could be used as a fast and reliable differential diagnostic biomarker.
Iron Metabolism in Obesity and Metabolic Syndrome González-Domínguez, Álvaro; Visiedo-García, Francisco M; Domínguez-Riscart, Jesús ...
International journal of molecular sciences,
2020-Aug-01, 2020-08-01, 20200801, Letnik:
21, Številka:
15
Journal Article
Recenzirano
Odprti dostop
Obesity is an excessive adipose tissue accumulation that may have detrimental effects on health. Particularly, childhood obesity has become one of the main public health problems in the 21st century, ...since its prevalence has widely increased in recent years. Childhood obesity is intimately related to the development of several comorbidities such as nonalcoholic fatty liver disease, dyslipidemia, type 2 diabetes mellitus, non-congenital cardiovascular disease, chronic inflammation and anemia, among others. Within this tangled interplay between these comorbidities and associated pathological conditions, obesity has been closely linked to important perturbations in iron metabolism. Iron is the second most abundant metal on Earth, but its bioavailability is hampered by its ability to form highly insoluble oxides, with iron deficiency being the most common nutritional disorder. Although every living organism requires iron, it may also cause toxic oxygen damage by generating oxygen free radicals through the Fenton reaction. Thus, iron homeostasis and metabolism must be tightly regulated in humans at every level (i.e., absorption, storage, transport, recycling). Dysregulation of any step involved in iron metabolism may lead to iron deficiencies and, eventually, to the anemic state related to obesity. In this review article, we summarize the existent evidence on the role of the most recently described components of iron metabolism and their alterations in obesity.
We show that the moduli space of metrics of nonnegative sectional curvature on every homotopy \mathbb{R} P^5 has infinitely many path components. We also show that in each dimension 4k+1 there are at ...least 2^{2k} homotopy \mathbb{R} P^{4k+1}'s of pairwise distinct oriented diffeomorphism type for which the moduli space of metrics of positive Ricci curvature has infinitely many path components. Examples of closed manifolds with finite fundamental group with these properties were known before only in dimensions 4k+3\geq 7.
El artículo estudia la aplicación de la ley catalana de transparencia, acceso a la información pública y buen gobierno a las entidades privadas que ejercen funciones públicas o potestades ...administrativas, prestan servicios públicos o perciben fondos públicos para funcionar o para llevar a cabo sus actividades por cualquier título jurídico. Se analiza la obligación que tienen estas entidades de suministrar a la administración responsable la información directamente relacionada con la actividad pública que desarrollan a la luz de la doctrina emanada por la Comisión de Garantía del Derecho de Acceso a la Información Pública de Cataluña (GAIP).
Abstract
This paper evaluates the relationship between fire occurrence (number and burned area) and climate variability (precipitation and maximum temperatures) across central and south‐central Chile ...(32°–43° S) during recent decades (1976–2013). This region sustains the largest proportion of the Chilean population, contains ecologically important remnants of endemic ecosystems, the largest extension of forest exotic plantations, and concentrates most of the fire activity in the country. Fire activity in central Chile was mainly associated with above‐average precipitation during winter of the previous year and with dry conditions during spring to summer. The later association was particularly strong in the southern, wetter part of the study region. Maximum temperature had a positive significant relationship with burned area across the study region, with stronger correlations toward the south. Fires in central Chile were significantly related to El Niño–Southern Oscillation, through rainfall anomalies during the year previous to the fire season. The Antarctic Oscillation during winter through summer was positively related to fires across the study area due to drier/warmer conditions associated with the positive polarity of this oscillation. Climate change projections for the region reveal an all‐season decrease in precipitation and increases in temperature, that may likely result in an increment of the occurrence and the area affected by fires, as it has been observed during a multi‐year drought afflicting central Chile since 2010.
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