Geometry preserving numerical methods for physical systems with finite-dimensional Lie algebras

In this paper we propose a geometric integrator to numerically approximate the flow of Lie systems. The highlight of this paper is to present a novel procedure that integrates the system on a Lie group intrinsically associated to the Lie system, and then generating the discrete solution of this Lie system through a given action of the Lie group on the manifold where the system evolves. One major result from the integration on the Lie group is that one is able to solve all automorphic Lie systems at the same time, and that they can be written as first-order systems of linear homogeneous ODEs in normal form. This brings a lot of advantages, since solving a linear ODE involves less numerical cost. Specifically, we use two families of numerical schemes on the Lie group, which are designed to preserve its geometrical structure: the first one based on the Magnus expansion, whereas the second is based on RKMK methods. Moreover, since the aforementioned action relates the Lie group and the manifold where the Lie system evolves, the resulting integrator preserves any geometric structure of the latter. We compare both methods for Lie systems with geometric invariants, particularly a class on Lie systems on curved spaces. As already mentioned, the milestone of this paper is to show that the method we propose preserves all the geometric invariants very faithfully, in comparison with nongeometric numerical methods.Comment: arXiv admin note: substantial text overlap with arXiv:2204.0004

SMARCA4 deficient tumours are vulnerable to KDM6A/UTX and KDM6B/JMJD3 blockade

Cancer therapyTeràpia del càncerTerapia del cáncerDespite the genetic inactivation of SMARCA4, a core component of the SWI/SNF-complex commonly found in cancer, there are no therapies that effectively target SMARCA4-deficient tumours. Here, we show that, unlike the cells with activated MYC oncogene, cells with SMARCA4 inactivation are refractory to the histone deacetylase inhibitor, SAHA, leading to the aberrant accumulation of H3K27me3. SMARCA4-mutant cells also show an impaired transactivation and significantly reduced levels of the histone demethylases KDM6A/UTX and KDM6B/JMJD3, and a strong dependency on these histone demethylases, so that its inhibition compromises cell viability. Administering the KDM6 inhibitor GSK-J4 to mice orthotopically implanted with SMARCA4-mutant lung cancer cells or primary small cell carcinoma of the ovary, hypercalcaemic type (SCCOHT), had strong anti-tumour effects. In this work we highlight the vulnerability of KDM6 inhibitors as a characteristic that could be exploited for treating SMARCA4-mutant cancer patients

Using discrete Ricci curvatures to infer COVID-19 epidemic network fragility and systemic risk

The damage of the novel Coronavirus disease (COVID-19) is reaching unprecedented scales. There are numerous classical epidemiology models trying to quantify epidemiology metrics. Usually, to forecast epidemics, classical approaches need parameter estimations, such as the contagion rate or the basic reproduction number. Here, we propose a data-driven, parameter-free, geometric approach to access the emergence of a pandemic state by studying the Forman-Ricci and Ollivier- Ricci network curvatures. Discrete Ollivier-Ricci curvature has been used successfully to forecast risk in nancial networks and we suggest that those results can provide analogous results for COVID-19 epidemic time-series. We rst compute both curvatures in a toy-model of epidemic time-series with delays, which allows us to create epidemic networks. We also compared our results to classical network metrics. By doing so, we are able to verify that the Ollivier-Ricci and Forman-Ricci curvatures can be a parameter-free estimate for identifying a pandemic state in the simulated epidemic. On this basis, we then compute both Forman-Ricci and Ollivier-Ricci curvatures for real epidemic networks built from COVID-19 epidemic time-series available at the World Health Organization (WHO). This approach allow us to detect early warning signs of the emergence of the pandemic. The advantage of our method lies in providing an early geometrical data marker for the pandemic state, regardless of parameter estimation and stochastic modelling. This work opens the possibility of using discrete geometry to study epidemic networks. Keywords: COVID-19, SARS2, Forman-Ricci Curvature, Ollivier-Ricci curvature, Epidemiology, Topologi- cal Data Analysi

Spectral calibration of the fluorescence telescopes of the Pierre Auger Observatory

We present a novel method to measure precisely the relative spectral response of the fluorescence telescopes of the Pierre Auger Observatory. We used a portable light source based on a xenon flasher and a monochromator to measure the relative spectral efficiencies of eight telescopes in steps of 5 nm from 280 nm to 440nm. Each point in a scan had approximately 2nm FWHM out of the monochromator. Different sets of telescopes in the observatory have different optical components, and the eight telescopes measured represent two each of the four combinations of components represented in the observatory. We made an end-to-end measurement of the response from different combinations of optical components, and the monochromator setup allowed for more precise and complete measurements than our previous multi-wavelength calibrations. We find an overall uncertainty in the calibration of the spectral response of most of the telescopes of 1.5% for all wavelengths; the six oldest telescopes have larger overall uncertainties of about 2.2%. We also report changes in physics measurables due to the change in calibration, which are generally small

Myofascial Trigger Points, Pain, Disability, and Sleep Quality in Patients with Chronic Nonspecific Low Back Pain

[EN] Objective: To investigate the difference in the presence of trigger points (TrPs) between patients with chronic nonspecific low back pain (LBP) and healthy people, and to determine the relationship of TrPs with the intensity of ongoing pain, disability, and sleep quality. Design: A cross-sectional study. Setting: The role of TrPs in LBP has not been determined. Patients: Forty-two patients with nonspecific LBP (50% women), aged 23-55 years old, and 42 age- and sex-matched controls participated. Outcome measures: TrPs were bilaterally explored within the quadratus lumborum, iliocostalis lumborum, psoas, piriformis, gluteus minimus, and gluteus medius muscles in a blinded design. TrPs were considered active if the subject recognized the local and referred pain as familiar symptoms, and TrPs were considered latent if the pain was not recognized as a familiar symptom. Pain measures were collected with a numerical pain rate scale, disability was assessed with the Roland-Morris questionnaire, and sleep quality was determined with the Pittsburgh Sleep Quality Index. Results: Patients with nonspecific LBP exhibited a greater disability and worse sleep quality than healthy controls (P < 0.001). Patients with nonspecific LBP exhibited a mean of 3.5 ± 2.3 active TrPs. Further, patients with nonspecific LBP showed a greater (P < 0.001) number of latent TrPs (mean: 2.0 ± 1.5) than healthy controls (mean: 1.0 ± 1.5). Active TrPs in the quadratus lumborum, iliocostalis lumborum, and gluteus medius muscles were the most prevalent in patients with nonspecific LBP. A greater number of active TrPs was associated with higher pain intensity (rs = 0.602; P < 0.001) and worse sleep quality (rs = 0.338; P = 0.03). Conclusions: The local and referred pain elicited by active TrPs in the back and hip muscles contributes to pain symptoms in nonspecific LBP. Patients had higher disability and worse sleep quality than controls. The number of active TrPs was associated with pain intensity and sleep quality. It is possible that a complex interaction among these factors is present in patients with nonspecific LBP

FAK induces expression of Prx1 to promote tenascin-C–dependent fibroblast migration

Fibroblast migration depends, in part, on activation of FAK and cellular interactions with tenascin-C (TN-C). Consistent with the idea that FAK regulates TN-C, migration-defective FAK-null cells expressed reduced levels of TN-C. Furthermore, expression of FAK in FAK-null fibroblasts induced TN-C, whereas inhibition of FAK activity in FAK–wild-type cells had the opposite effect. Paired-related homeobox 1 (Prx1) encodes a homeobox transcription factor that induces TN-C by interacting with a binding site within the TN-C promoter, and it also promotes fibroblast migration. Therefore, we hypothesized that FAK regulates TN-C by controlling the DNA-binding activity of Prx1 and/or by inducing Prx1 expression. Prx1–homeodomain binding site complex formation observed with FAK–wild-type fibroblasts failed to occur in FAK-null fibroblasts, yet expression of Prx1 in these cells induced TN-C promoter activity. Thus, FAK is not essential for Prx1 DNA-binding activity. However, activated FAK was essential for Prx1 expression. Functionally, Prx1 expression in FAK-null fibroblasts restored their ability to migrate toward fibronectin, in a manner that depends on TN-C. These results appear to be relevant in vivo because Prx1 and TN-C expression levels were reduced in FAK-null embryos. This paper suggests a model whereby FAK induces Prx1, and subsequently the formation of a TN-C–enriched ECM that contributes to fibroblast migration

Gender differences in variables associated with sleep quality in chronic tension type headache

We aimed to evaluate gender differences in the relationships between headache features, sleep quality, anxiety, depressive symptoms, and burden of headache in 193 patients (73 percent women) with chronic tension type headache (CTTH). Sleep quality was assessed with the Pittsburgh Sleep Quality Index. Headache features were collected with a four-week diary. The Hospital Anxiety and Depression Scale was used to assess anxiety/depressive symptoms. Headache Disability Inventory was used to evaluate the burden of headache. In men with CTTH, sleep quality was positive correlated with headache frequency (r = 0.310; p = .018), emotional (r = 0.518; p < .001) and physical (r = 0.468; p < .001) burden of headache, and depressive symptoms (r = 0.564; p < .001). In women, positive correlations were observed between sleep quality and headache intensity (r = 0.282; p < .001), headache frequency (r = 0.195; p = .021), emotional burden (r = 0.249; p = .004), and depressive symptoms (r = 0.382; p < .001). The results of stepwise regression analyses revealed that depressive symptoms and emotional burden of headache explained 37.2 percent of the variance in sleep quality in men (p < .001), whereas depressive symptoms and headache intensity explained 17.4 percent of the variance in sleep quality in women (p < .001) with CTTH. Gender differences associated with poor sleep should be considered for proper management of individuals with CTTH

Cuidados enfermeros en cuidados paliativos: análisis, consensos y retos

La creciente complejidad de los cuidados que requieren las personas en situación de enfermedad avanzada y al final de vida, y la variabilidad de profesionales sanitarios que intervienen en el proceso asistencial, nos conduce a clarificar el rol profesional enfermero en el equipo multidisciplinar de Cuidados Paliativos (CP). Objetivo: reflexionar sobre la práctica enfermera en CP. Metodología: Técnica del grupo nominal. Se seleccionaron 10 enfermeras con más de 10 años de experiencia profesional en CP. Categorías elegidas para la atención enfermera: Evolución de los cuidados, de la profesión enfermera, funciones y actividades de enfermería, historia de los cuidados paliativos. Conclusiones: Necesidad de definir las competencias enfermeras en CP; Necesidad de contemplar la práctica profesional en el marco de un modelo conceptual y la aplicación del método científico enfermero; Necesidad de avanzar en prácticas reflexivas basadas en evidencias científicas; Iniciar una línea de investigación en competencias enfermeras en CP

Identification of coherent flood regions across Europe by using the longest streamflow records

This study compiles a new dataset, consisting of the longest available flow series from across Europe, and uses it to study the spatial and temporal clustering of flood events across the continent. Hydrological series at 102 gauging stations were collected from 25 European countries. Five geographically distinct large-scale homogeneous regions are identified: (i) an Atlantic region, (ii) a Continental region, (iii) a Scandinavian region, (iv) an Alpine region, and (v) a Mediterranean region. The months with a higher likelihood of flooding were identified in each region. The analysis of the clustering of annual counts of floods revealed an over-dispersion in the Atlantic and Continental regions, forming flood-rich and flood-poor periods, as well as an under-dispersion in the Scandinavian region that points to a regular pattern of flood occurrences at the inter-annual scale. The detection of trends in flood series is attempted by basing it on the identified regions, interpreting the results at a regional scale and for various time periods: 1900-1999; 1920-1999; 1939-1998 and 1956-1995. The results indicate that a decreasing trend in the magnitude of floods was observed mainly in the Continental region in the period 1920-1999 with 22% of the catchments revealing such a trend, as well as a decreasing trend in the timing of floods in the Alpine region in the period 1900-1999 with 75% of the catchments revealing this trend. A mixed pattern of changes in the frequency of floods over a threshold and few significant changes in the timing of floods were detected