The core mission of the IceCube neutrino observatory is to study the origin and propagation of cosmic rays. IceCube, with its surface component IceTop, observes multiple signatures to accomplish this ...mission. Most important are the astrophysical neutrinos that are produced in interactions of cosmic rays, close to their sources and in interstellar space. IceCube is the first instrument that measures the properties of this astrophysical neutrino flux and constrains its origin. In addition, the spectrum, composition, and anisotropy of the local cosmic-ray flux are obtained from measurements of atmospheric muons and showers. Here we provide an overview of recent findings from the analysis of IceCube data, and their implications to our understanding of cosmic rays.
The IceCube realtime alert system Aartsen, M. G.; Anton, G.; Argüelles, C. ...
Astroparticle physics,
05/2017, Letnik:
92, Številka:
C
Journal Article
Recenzirano
Odprti dostop
Although high-energy astrophysical neutrinos were discovered in 2013, their origin is still unknown. Aiming for the identification of an electromagnetic counterpart of a rapidly fading source, we ...have implemented a realtime analysis framework for the IceCube neutrino observatory. Several analyses selecting neutrinos of astrophysical origin are now operating in realtime at the detector site in Antarctica and are producing alerts for the community to enable rapid follow-up observations. The goal of these observations is to locate the astrophysical objects responsible for these neutrino signals. This paper highlights the infrastructure in place both at the South Pole site and at IceCube facilities in the north that have enabled this fast follow-up program to be implemented. Additionally, this paper presents the first realtime analyses to be activated within this framework, highlights their sensitivities to astrophysical neutrinos and background event rates, and presents an outlook for future discoveries.
The previously published "Dose Response Multicentre International Collaborative Initiative (DoReMi)" study concluded that the high mortality of critically ill patients with acute kidney injury (AKI) ...was unlikely to be related to an inadequate dose of renal replacement therapy (RRT) and other factors were contributing. This follow-up study aimed to investigate the impact of daily fluid balance and fluid accumulation on mortality of critically ill patients without AKI (N-AKI), with AKI (AKI) and with AKI on RRT (AKI-RRT) receiving an adequate dose of RRT.
We prospectively enrolled all consecutive patients admitted to 21 intensive care units (ICUs) from nine countries and collected baseline characteristics, comorbidities, severity of illness, presence of sepsis, daily physiologic parameters and fluid intake-output, AKI stage, need for RRT and survival status. Daily fluid balance was computed and fluid overload (FO) was defined as percentage of admission body weight (BW). Maximum fluid overload (MFO) was the peak value of FO.
We analysed 1734 patients. A total of 991 (57 %) had N-AKI, 560 (32 %) had AKI but did not have RRT and 183 (11 %) had AKI-RRT. ICU mortality was 22.3 % in AKI patients and 5.6 % in those without AKI (p < 0.0001). Progressive fluid accumulation was seen in all three groups. Maximum fluid accumulation occurred on day 2 in N-AKI patients (2.8 % of BW), on day 3 in AKI patients not receiving RRT (4.3 % of BW) and on day 5 in AKI-RRT patients (7.9 % of BW). The main findings were: (1) the odds ratio (OR) for hospital mortality increased by 1.075 (95 % confidence interval 1.055-1.095) with every 1 % increase of MFO. When adjusting for severity of illness and AKI status, the OR changed to 1.044. This phenomenon was a continuum and independent of thresholds as previously reported. (2) Multivariate analysis confirmed that the speed of fluid accumulation was independently associated with ICU mortality. (3) Fluid accumulation increased significantly in the 3-day period prior to the diagnosis of AKI and peaked 3 days later.
In critically ill patients, the severity and speed of fluid accumulation are independent risk factors for ICU mortality. Fluid balance abnormality precedes and follows the diagnosis of AKI.
Currently, Coronavirus disease (COVID-19), one of the most infectious diseases in the 21st century, is diagnosed using RT-PCR testing, CT scans and/or Chest X-Ray (CXR) images. CT (Computed ...Tomography) scanners and RT-PCR testing are not available in most medical centers and hence in many cases CXR images become the most time/cost effective tool for assisting clinicians in making decisions. Deep learning neural networks have a great potential for building COVID-19 triage systems and detecting COVID-19 patients, especially patients with low severity. Unfortunately, current databases do not allow building such systems as they are highly heterogeneous and biased towards severe cases. This article is threefold: (i) we demystify the high sensitivities achieved by most recent COVID-19 classification models, (ii) under a close collaboration with Hospital Universitario Clínico San Cecilio, Granada, Spain, we built COVIDGR-1.0, a homogeneous and balanced database that includes all levelsof severity, from normal with Positive RT-PCR, Mild, Moderate to Severe. COVIDGR-1.0 contains 426 positive and 426 negative PA (PosteroAnterior) CXR views and (iii) we propose COVID Smart Data based Network (COVID-SDNet) methodology for improving the generalization capacity of COVID-classification models. Our approach reaches good and stable results with an accuracy of 97.72% ± 0.95%, 86.90% ± 3.20%, 61.80% ± 5.49% in severe, moderate and mild COVID-19 severity levels. Our approach could help in the early detection of COVID-19. COVIDGR-1.0 along with the severity level labels are available to the scientific community through this link https://dasci.es/es/transferencia/ open-data/covidgr/.
Resveratrol (RES), a polyphenol compound with anti‑proliferative properties, has been previously evaluated for its beneficial effects against a variety of tumour cells. The current study elucidated ...the means by which RES enhances the anti‑proliferative effects of cisplatin (CIS) on MCF‑7 cells, focusing on the inhibitory effects on DNA repair of double‑strand breaks (DSBs). Chemoresistant MCF‑7 cells (MCF‑7R) were generated by continuous exposure to low concentrations of CIS (10 µM CIS‑IC40) during 5 passages, with the IC50 value increasing ~3‑fold. Using an MTT assay, we estimated the changes in IC50 for CIS in MCF‑7, T47‑D, MDA‑MB‑231 and MCF‑7R cells in the presence of RES. The relative transcript level of Nbs‑1, Mre‑11 and Rad‑50 genes was assessed using RT‑qPCR analysis. Rad51 and H2AX pSer139 protein expression was determined by western blot analysis. RES at 50 and 100 µM significantly enhanced the anti‑proliferative effects of CIS in both MCF‑7 and MCF‑7R cells, decreasing the IC50 values for CIS to one‑tenth and one‑sixth, respectively. A total of 100 µM RES decreased the relative transcript levels of homologous recombination (HR) initiation complex components and the Rad51 protein level in MCF‑7 and MCF‑7R cells. After 48 h of CIS DNA damage, the levels of Rad51 protein increased, but this effect was inhibited by 100 µM RES. RES also maintained serine 139 phosphorylation of histone H2AX, suggesting that RES prevents the repair of DSBs. It was observed that RES exerts an antagonistic effect over CIS on the activation of Rad51 and sustained phosphorylation of H2AX. The results suggest that RES in combination with DNA damage‑based therapy has potential as a strategy to overcome resistance and provide much safer and more effective treatment for breast cancer.
Plasmodium vivax is a major public health burden, responsible for the majority of malaria infections outside Africa. We explored the impact of demographic history and selective pressures on the P. ...vivax genome by sequencing 182 clinical isolates sampled from 11 countries across the globe, using hybrid selection to overcome human DNA contamination. We confirmed previous reports of high genomic diversity in P. vivax relative to the more virulent Plasmodium falciparum species; regional populations of P. vivax exhibited greater diversity than the global P. falciparum population, indicating a large and/or stable population. Signals of natural selection suggest that P. vivax is evolving in response to antimalarial drugs and is adapting to regional differences in the human host and the mosquito vector. These findings underline the variable epidemiology of this parasite species and highlight the breadth of approaches that may be required to eliminate P. vivax globally.
To describe a series of 41 patients with fresh lesions of Sweet syndrome in which the histopathologic study demonstrated an inflammatory infiltrate mostly composed of histiocytoid mononuclear cells.
...Histopathologic, immunohistochemical, and cytogenetic studies of the inflammatory infiltrate in a case series of histiocytoid Sweet syndrome.
University departments of dermatology and a private laboratory of dermatopathology.
Conventional histopathologic study as well as immunohistochemical investigations were performed using the alkaline phosphatase antialkaline phosphatase technique with a large panel of antibodies. In some cases, fluorescent in situ hybridization studies were performed to investigate the presence of the bcr/abl gene fusion.
Immunohistochemical studies demonstrated that most cells of the infiltrate showed immunoreactivity for CD15, CD43, CD45, CD68, MAC-386, HAM56, and lysozyme, which is consistent with a monocytic-histiocytic immunoprofile. However, intense myeloperoxidase reactivity was detected in most of the cells with histiocytic appearance, which raised the possibility of specific cutaneous involvement by myelogenous leukemia. Nevertheless, cytologic peripheral blood examinations, fluorescent in situ hybridization studies to investigate the bcr/abl gene fusion, and follow-up of the patients, taken all together, ruled out this possibility.
This case series demonstrates that some fresh cutaneous lesions of Sweet syndrome are histopathologically characterized by an infiltrate mostly composed of cells that may be misinterpreted as histiocytes, when in fact they are immature myeloid cells. We named this histopathologic variant histiocytoid Sweet syndrome, which should not be mistaken with leukemia cutis or other inflammatory dermatoses that are histopathologically characterized by histiocytes interstitially arranged between collagen bundles of the dermis.
Cell physiology parameters are essential aspects of biological processes; however, they are difficult to determine on-line. Dielectric spectroscopy allows the on-line estimation of viable cells and ...can provide important information about cell physiology during culture. In this study, we investigated the dielectric property variations in
Kluyveromyces marxianus
SLP1 and
Saccharomyces cerevisiae
ERD yeasts stressed by 5-hydroxymethyl-2-furaldehyde and 2-furaldehyde during aerobic growth. The dielectric properties of cell permittivity, specific membrane capacitance (
Cm
), and intracellular conductivity (
σ
In
) were considerably affected by furan aldehydes in the same way that the cell population, viability, cell size, substrate consumption, organic acid production, and respiratory parameters were. The yeasts stressed with furan aldehydes exhibited three physiological states (
φ
): adaptation, replicating, and nonreplicating states. During the adaptation state, there were small and stable signs of permittivity,
Cm
, and
σ
In
; additionally, no cell growth was observed. During the replicating state, cell growth was restored, and the cell viability increased; in addition, the permittivity and
σ
In
increased rapidly and reached their maximum values, while the
Cm
decreased. In the nonreplicating state, the permittivity and
σ
In
were stable, and
Cm
decreased to its minimum value. Our results demonstrated that knowing dielectric properties allowed us to obtain information about the physiological state of the cells under control and stressed conditions. Since the permittivity,
Cm
, and
σ
In
are directly associated with the physiological state of the yeast, these results should contribute to a better understanding of the stress response of yeasts and open the possibility to on-line monitor and control the physiological state of the cell in the near future.
Establishing affordable, efficient, accessible, innovative, and multidisciplinary methodologies to the diagnosis of the conservation state of an artwork is key to carry out appropriate strategies of ...conservation and consequently to the creation of modern public policies on cultural heritage. Limited access to large-format paintings is a challenge to restoration scientists seeking to obtain information quickly, in a non-destructive and non-invasive manner, and identify regions of interest. Therefore, we put forward two unique software tools based on multispectral imaging techniques, with the long-term aim to assess the artist's intentions, creative process, and colour palette. This development paves the way for a comprehensive and multidisciplinary understanding of the mysteries encompassed in each pictorial layer, through the study of their physical and chemical characteristics. We conducted the first ever study on Musas I and Musas II, two large-format paintings by Italian artist Carlo Ferrario, located in the National Theatre of Costa Rica. In this study, we used our novel imaging techniques to choose regions of interest in order to study sample layers; while also assessing the works' state of conservation and possible biodeterioration. We explored the applications of our two versatile software tools, RegionOfInterest and CrystalDistribution, and confirmed paint stratigraphies by means of microscopy and spectroscopy analyses (OM, SEM-EDX, Fluorescent microscopy, FTIR-ATR and micro-Raman). In a pilot study, we identified the artist's main colour palette: zinc white, lead white, chrome yellow, lead read, viridian, along with artificial vermilion and ultramarine pigments. We were able to identify artificial vermilion and ultramarine and distinguish them from the natural pigments using CrystalDistribution to map the average size and diameter of the pigment crystals within the paint layers. This study demonstrated that software-based multidisciplinary imaging techniques are novel in establishing preventive and non-invasive methods for historical painting conservation studies, in addition, this study provides tools with great potential to be used in the future in applications such as virtual restoration.