Focal cone high harmonic generation driven by a 400 TW laser.

The generation of self-focusing beams of extreme ultraviolet (XUV) radiation using the focal cone high harmonic generation (FCHHG) technique is examined for high energy lasers. The FCHHG geometry is created by passing a focusing laser beam through a gas sheet prior to reaching focus and thus creating a converging beam of high harmonic radiation. This leads to a larger interaction area that increases the total area of XUV emission while not exceeding the saturation intensity of the target atoms or increasing the density of the atoms. Such a method allows for scaling of HHG to any incident laser power. An experiment was conducted demonstrating such scaling to incident 400 TW pulses, showing both the expected spectral signature of HHG and the converging cone of XUV radiation. It was found that this technique is very sensitive to spatial non-uniformity in the driving laser, which has become more prevalent in high energy laser systems.

Guidelines for the management of coagulation disorders in patients with cirrhosis.

Coagulation management in the patient with cirrhosis has undergone a significant transformation since the beginning of this century, with the concept of a rebalancing between procoagulant and anticoagulant factors. The paradigm that patients with cirrhosis have a greater bleeding tendency has changed, as a result of this rebalancing. In addition, it has brought to light the presence of complications related to thrombotic events in this group of patients. These guidelines detail aspects related to pathophysiologic mechanisms that intervene in the maintenance of hemostasis in the patient with cirrhosis, the relevance of portal hypertension, mechanical factors for the development of bleeding, modifications in the hepatic synthesis of coagulation factors, and the changes in the reticuloendothelial system in acute hepatic decompensation and acute-on-chronic liver failure. They address new aspects related to the hemorrhagic complications in patients with cirrhosis, considering the risk for bleeding during diagnostic or therapeutic procedures, as well as the usefulness of different tools for diagnosing coagulation and recommendations on the pharmacologic treatment and blood-product transfusion in the context of hemorrhage. These guidelines also update the knowledge regarding hypercoagulability in the patient with cirrhosis, as well as the efficacy and safety of treatment with the different anticoagulation regimens. Lastly, they provide recommendations on coagulation management in the context of acute-on-chronic liver failure, acute liver decompensation, and specific aspects related to the patient undergoing liver transplantation.

Current vision on diagnosis and comprehensive care in hepatic encephalopathy.

The first clinical guidelines on hepatic encephalopathy were published in 2009. Almost 14 years since that first publication, numerous advances in the field of diagnosis, treatment, and special condition care have been made. Therefore, as an initiative of the Asociación Mexicana de Gastroenterología A.C., we present a current view of those aspects. The manuscript described herein was formulated by 24 experts that participated in six working groups, analyzing, discussing, and summarizing the following topics: Definition of hepatic encephalopathy; recommended classifications; epidemiologic panorama, worldwide and in Mexico; diagnostic tools; conditions that merit a differential diagnosis; treatment; and primary and secondary prophylaxis. Likewise, these guidelines emphasize the management of certain special conditions, such as hepatic encephalopathy in acute liver failure and acute-on-chronic liver failure, as well as specific care in patients with hepatic encephalopathy, such as the use of medications and types of sedation, describing those that are permitted or recommended, and those that are not.

Immune dysregulation and pathophysiology of alcohol consumption and alcoholic liver disease.

Alcoholic liver disease (ALD) is a clinical-pathologic entity caused by the chronic excessive consumption of alcohol. The disease includes a broad spectrum of anomalies at the cellular and tissual level that can cause acute-on-chronic (alcoholic hepatitis) or chronic (fibrosis, cirrhosis, hepatocellular cancer) injury, having a great impact on morbidity and mortality worldwide. Alcohol is metabolized mainly in the liver. During alcohol metabolism, toxic metabolites, such as acetaldehyde and oxygen reactive species, are produced. At the intestinal level, alcohol consumption can cause dysbiosis and alter intestinal permeability, promoting the translocation of bacterial products and causing the production of inflammatory cytokines in the liver, perpetuating local inflammation during the progression of ALD. Different study groups have reported systemic inflammatory response disturbances, but reports containing a compendium of the cytokines and cells involved in the pathophysiology of the disease, from the early stages, are difficult to find. In the present review article, the role of the inflammatory mediators involved in ALD progression are described, from risky patterns of alcohol consumption to advanced stages of the disease, with the aim of understanding the involvement of immune dysregulation in the pathophysiology of ALD.

Approach to the patient with cholestasis and jaundice syndrome. Joint AMH, AMG, and AMEG scientific position statement.

The term cholestasis refers to bile acid retention, whether within the hepatocyte or in the bile ducts of any caliber. Biochemically, it is defined by a level of alkaline phosphatase that is 1.67-times higher than the upper limit of normal. Cholestatic diseases can be associated with an inflammatory process of the liver that destroys hepatocytes (hepatitis), withjaundice (yellowing of the skin and mucus membranes, associated with elevated serum bilirubin levels), or with both, albeit the three concepts should not be considered synonymous. Cholestatic diseases can be classified as intrahepatic or extrahepatic, depending on their etiology. Knowing the cause of the condition is important for choosing the adequate diagnostic studies and appropriate treatment in each case. A complete medical history, together with a thorough physical examination and basic initial studies, such as liver ultrasound and liver function tests, aid the clinician in deciding which path to follow, when managing the patient with cholestasis. In a joint effort, the Asociación Mexicana de Hepatología (AMH), the Asociación Mexicana de Gastroenterología (AMG) and the Asociación Mexicana de Endoscopia Gastrointestinal (AMEG) developed the first Mexican scientific position statement on said theme.

Sofosbuvir-velpatasvir in Mexican patients with hepatitis C: A retrospective review.

INTRODUCTION: The sofosbuvir-velpatasvir (SOF/VEL) combination is a direct-acting antiviral therapy that is authorized and available in Mexico, making the performance of a real-world multicenter study that evaluates the sustained virologic response at 12 weeks post-treatment a relevant undertaking. METHODS: A retrospective review of the case records of 241 patients seen at 20 hospitals in Mexico was conducted to assess hepatitis C treatment with the SOF/VEL combination (n = 231) and the sofosbuvir/velpatasvir/ribavirin (SOF/VEL/RBV) combination (n = 10). The primary efficacy endpoint was the percentage of patients that achieved SVR at 12 weeks after the end of treatment. RESULTS: Overall SVR was 98.8% (95% CI 97.35-100%). Only three patients did not achieve SVR, two of whom had cirrhosis and a history of previous treatment with peg-IFN. Of the subgroups analyzed, all the patients with HIV coinfection, three patients with genotype 3, and the patients treated with the SOF/VEL/RBV combination achieved SVR. The subgroups with the lower success rates were patients that were treatment-experienced (96.8%) and patients with F1 fibrosis (95.5%). The most frequent adverse events were fatigue, headache, and insomnia. No serious adverse events were reported. CONCLUSION: Treatments with SOF/VEL and SOF/VEL/RBV were highly safe and effective, results coinciding with those of other international real-world studies.

Asociación Mexicana de Hepatología A.C. Clinical guideline on hepatitis B.

Hepatitis B virus (HBV) infection continues to be a worldwide public health problem. In Mexico, at least three million adults are estimated to have acquired hepatitis B (total hepatitis B core antibody [anti-HBc]-positive), and of those, 300,000 active carriers (hepatitis B surface antigen [HBsAg]-positive) could require treatment. Because HBV is preventable through vaccination, its universal application should be emphasized. HBV infection is a major risk factor for developing hepatocellular carcinoma. Semi-annual liver ultrasound and serum alpha-fetoprotein testing favor early detection of that cancer and should be carried out in all patients with chronic HBV infection, regardless of the presence of advanced fibrosis or cirrhosis. Currently, nucleoside/nucleotide analogues that have a high barrier to resistance are the first-line therapies.

Asociación Mexicana de Hepatología A.C. Clinical guideline on hepatitis B. / Asociación Mexicana de Hepatología A.C. Guía Clínica de Hepatitis B.

Hepatitis B virus (HBV) infection continues to be a worldwide public health problem. In Mexico, at least three million adults are estimated to have acquired hepatitis B (total hepatitis B core antibody [anti-HBc]-positive), and of those, 300,000 active carriers (hepatitis B surface antigen [HBsAg]-positive) could require treatment. Because HBV is preventable through vaccination, its universal application should be emphasized. HBV infection is a major risk factor for developing hepatocellular carcinoma. Semi-annual liver ultrasound and serum alpha-fetoprotein testing favor early detection of that cancer and should be carried out in all patients with chronic HBV infection, regardless of the presence of advanced fibrosis or cirrhosis. Currently, nucleoside/nucleotide analogues that have a high barrier to resistance are the first-line therapies.

A quasi-monoenergetic short time duration compact proton source for probing high energy density states of matter.

We report on the development of a highly directional, narrow energy band, short time duration proton beam operating at high repetition rate. The protons are generated with an ultrashort-pulse laser interacting with a solid target and converted to a pencil-like narrow-band beam using a compact magnet-based energy selector. We experimentally demonstrate the production of a proton beam with an energy of 500 keV and energy spread well below 10[Formula: see text], and a pulse duration of 260 ps. The energy loss of this beam is measured in a 2 [Formula: see text]m thick solid Mylar target and found to be in good agreement with the theoretical predictions. The short time duration of the proton pulse makes it particularly well suited for applications involving the probing of highly transient plasma states produced in laser-matter interaction experiments. This proton source is particularly relevant for measurements of the proton stopping power in high energy density plasmas and warm dense matter.

Integrated quantitative PIXE analysis and EDX spectroscopy using a laser-driven particle source.

Among the existing elemental characterization techniques, particle-induced x-ray emission (PIXE) and energy-dispersive x-ray (EDX) spectroscopy are two of the most widely used in different scientific and technological fields. Here, we present the first quantitative laser-driven PIXE and laser-driven EDX experimental investigation performed at the Centro de Láseres Pulsados in Salamanca. Thanks to their potential for compactness and portability, laser-driven particle sources are very appealing for materials science applications, especially for materials analysis techniques. We demonstrate the possibility to exploit the x-ray signal produced by the co-irradiation with both electrons and protons to identify the elements in the sample. We show that, using the proton beam only, we can successfully obtain quantitative information about the sample structure through laser-driven PIXE analysis. These results pave the way toward the development of a compact and multifunctional apparatus for the elemental analysis of materials based on a laser-driven particle source.

Sofosbuvir-velpatasvir in Mexican patients with hepatitis C: A retrospective review. / Sofosbuvir-velpatasvir en pacientes mexicanos con hepatitis C: una revisión retrospectiva.

INTRODUCTION: The sofosbuvir-velpatasvir (SOF/VEL) combination is a direct-acting antiviral therapy that is authorized and available in Mexico, making the performance of a real-world multicenter study that evaluates the sustained virologic response at 12 weeks post-treatment a relevant undertaking. METHODS: A retrospective review of the case records of 241 patients seen at 20 hospitals in Mexico was conducted to assess hepatitis C treatment with the SOF/VEL combination (n = 231) and the sofosbuvir/velpatasvir/ribavirin (SOF/VEL/RBV) combination (n = 10). The primary efficacy endpoint was the percentage of patients that achieved SVR at 12 weeks after the end of treatment. RESULTS: Overall SVR was 98.8% (95% CI 97.35-100%). Only three patients did not achieve SVR, two of whom had cirrhosis and a history of previous treatment with peg-IFN. Of the subgroups analyzed, all the patients with HIV coinfection, three patients with genotype 3, and the patients treated with the SOF/VEL/RBV combination achieved SVR. The subgroups with the lower success rates were patients that were treatment-experienced (96.8%) and patients with F1 fibrosis (95.5%). The most frequent adverse events were fatigue, headache, and insomnia. No serious adverse events were reported. CONCLUSION: Treatments with SOF/VEL and SOF/VEL/RBV were highly safe and effective, results coinciding with those of other international real-world studies.

The Mexican consensus on alcoholic hepatitis. / Consenso Mexicano de hepatitis alcohólica.

Alcoholic hepatitis is a frequent condition in the Mexican population. It is characterized by acute-on-chronic liver failure, important systemic inflammatory response, and multiple organ failure. The severe variant of the disease implies elevated mortality. Therefore, the Asociación Mexicana de Gastroenterología and the Asociación Mexicana de Hepatología brought together a multidisciplinary team of health professionals to formulate the first Mexican consensus on alcoholic hepatitis, carried out utilizing the Delphi method and resulting in 37 recommendations. Alcohol-related liver disease covers a broad spectrum of pathologies that includes steatosis, steatohepatitis, different grades of fibrosis, and cirrhosis and its complications. Severe alcoholic hepatitis is defined by a modified Maddrey's discriminant function score ≥ 32 or by a Model for End-Stage Liver Disease (MELD) score equal to or above 21. There is currently no specific biomarker for its diagnosis. Leukocytosis with neutrophilia, hyperbilirubinemia (> 3 mg/dL), AST > 50 U/l (< 400 U/l), and an AST/ALT ratio > 1.5-2 can guide the diagnosis. Abstinence from alcohol, together with nutritional support, is the cornerstone of treatment. Steroids are indicated for severe disease and have been effective in reducing the 28-day mortality rate. At present, liver transplantation is the only life-saving option for patients that are nonresponders to steroids. Certain drugs, such as N-acetylcysteine, granulocyte-colony stimulating factor, and metadoxine, can be adjuvant therapies with a positive impact on patient survival.

Production of insulin-like growth factor-binding proteins during the development of hepatic fibrosis due to chronic hepatitis C. / Producción de las proteínas de unión al factor de crecimiento insulinoide durante el desarrollo de la fibrosis hepática por hepatitis C crónica.

INTRODUCTION AND AIMS: Insulin-like growth factor 1 is modulated by the insulin-like growth factor-binding proteins (IGFBPs) that are synthesized in the liver. The aim of the present study was to evaluate the concentrations of IGFBPs 1-7 in patients with chronic hepatitis C and study their association with fibrosis stage. PATIENTS AND METHODS: A prospective, cross-sectional study was conducted that included patients with chronic hepatitis C. The stages of fibrosis were determined through FibroTest and FibroScan and the patients were compared with a control group. Serum levels of IGFBPs 1-7 were quantified through multiple suspension arrays. The Kruskal-Wallis test, Mann-Whitney U test, Spearman's correlation, and ROC curves were used for the statistical analysis. RESULTS: Upon comparing the patients and controls, the highest concentrations were found in IGFBPs 1, 2, 4, and 7 (p=0.02, p=0.002, p=0.008, and p<0.001, respectively). IGFBP-3 levels had a tendency to be lower in the patients (p=0.066), whereas values were similar between patients and controls for IGFBP-5 and 6 (p=0.786 and p=0.244, respectively). Of the seven IGFBPs, IGFBP-3 concentrations were the highest. There were significant differences between fibrosis stages for IGFBP-5 and IGFBP-7. CONCLUSION: IGFBPs play a relevant role in the fibrotic process in liver damage. IGFBP-7, in particular, differentiates fibrosis stages, making it a potential serum biomarker.

Towards an in situ, full-power gauge of the focal-volume intensity of petawatt-class lasers.

About 50 years ago, Sarachick and Schappert [Phys. Rev. D. 1, 2738-2752 (1970)] showed that relativistic Thomson scattering leads to wavelength shifts that are proportional to the laser intensity. About 28 years later, Chen et al. [Nature 396, 653-655 (1998)] used these shifts to estimate their laser intensity near 1018 W/cm 2. More recently, there have been several theoretical studies aimed at exploiting nonlinear Thomson scattering as a tool for direct measurement of intensities well into the relativistic regime. We present the first quantitative study of this approach for intensities between 1018 and 1019 W/cm 2. We show that the spectral shifts are in reasonable agreement with estimates of the peak intensity extracted from images of the focal area obtained at reduced power. Finally, we discuss the viability of the approach, its range of usefulness and how it might be extended to gauge intensities well in excess of 1019 W/cm 2.

Development of an adjustable Kirkpatrick-Baez microscope for laser driven x-ray sources.

A prototype of a highly adjustable Kirkpatrick-Baez (KB) microscope has been designed, built, and tested in a number of laser driven x-ray experiments using the high power (200 TW) VEGA-2 laser system of the Spanish Centre for Pulsed Lasers (CLPU). The presented KB version consists of two, perpendicularly mounted, 500 µm thick silicon wafers, coated with a layer of platinum, a few tens of nanometers thick. Unlike the usual millimeter thick glass substrate, this design allows for a larger bending flexibility and large adjustment range. According to simulations, this KB microscope offers broadband multikiloelectron volt reflection spectra (1 eV-20 keV), allowing more spectral tunability than conventional Bragg crystals. In addition to be vacuum compatible, this prototype is characterized by a relatively small size (21 cm × 31 cm × 27 cm) and permits remote control and modification both of the radii of curvature (down to 10 m) and of the grazing incidence angle (up to 60 mrad). A few examples of focusing performance tests and experimental results are discussed.

Effect of silver diamine fluoride on adhesion and microleakage of a pit and fissure sealant to tooth enamel: in vitro trial.

AIM: To identify the effect of silver diamine fluoride in adhesion and microleakage of a pit and fissure sealant to tooth enamel. METHODS: An in vitro study including 120 human molars without caries, and caries grade 1 was performed. Molars were randomly divided into four groups. Occlusal surfaces of groups 2 and 4 were sealed. In groups 1 and 3 silver diamine fluoride (SDF) was placed in the occlusal surface and then molars were sealed according to manufacturer's instructions. Afterwards, all groups were submitted to the adhesion test. Groups 1 and 2 were placed in a forming cylinder and their roots were submerged in polymethyl methacrylate after that they were stored in deionised water (37 °C ± 1). Subsequently, they were tested by applying a tractional load (Instron machine, speed cross of 1 mm/min). Sealant adhesion was evaluated through: Resistance to the detachment (MPa), residues of sealant area (mm2) and adhesive remaining index (ARI) (0-3 interval). Microleakage test: Groups 3 and 4 were placed in a plastic container and subjected to 2000 cycles at different temperatures one at 6 °C ± 1 and the other at 60 °C ± 1. Later the occlusal surface was immersed for 24 h in 1% toluidine blue. Microleakage was observed by optical microscopy (10×) and was interpreted in micrometres. RESULTS: Of the samples without SDF 18.1 and 23.0% of the sealant remaining and of the samples with SDF present 100% of sealant remaining on enamel. Samples with SDF obtained an average in the test of detachment of 6.89 ± 3.09 MPa, whereas in the group without SDF the average obtained was 6.42 ± 3.35 MPa. Differences were not statistically significant (p = 0.579). Most of the samples not treated with SDF (81.6%) showed microleakage than those treated with SDF in which 47% presented microleakage. CONCLUSIONS: There is an improvement in the retention properties of a fissure sealant applied after treatment with silver diamine fluoride. The application of fissure sealant to improve the aesthetics of teeth treated with SDF is recommended.

Emergence of a Higher Energy Structure in Strong Field Ionization with Inhomogeneous Electric Fields.

Studies of strong field ionization have historically relied on the strong field approximation, which neglects all spatial dependence in the forces experienced by the electron after ionization. More recently, the small spatial inhomogeneity introduced by the long-range Coulomb potential has been linked to a number of important features in the photoelectron spectrum, such as Coulomb asymmetry, Coulomb focusing, and the low energy structure. Here, we demonstrate using midinfrared laser wavelength that a time-varying spatial dependence in the laser electric field, such as that produced in the vicinity of a nanostructure, creates a prominent higher energy peak. This higher energy structure (HES) originates from direct electrons ionized near the peak of a single half-cycle of the laser pulse. The HES is separated from all other ionization events, with its location and width highly dependent on the strength of spatial inhomogeneity. Hence, the HES can be used as a sensitive tool for near-field characterization in the "intermediate regime," where the electron's quiver amplitude is comparable to the field decay length. Moreover, the large accumulation of electrons with tuneable energy suggests a promising method for creating a localized source of electron pulses of attosecond duration using tabletop laser technology.

Attosecond physics at the nanoscale.

Recently two emerging areas of research, attosecond and nanoscale physics, have started to come together. Attosecond physics deals with phenomena occurring when ultrashort laser pulses, with duration on the femto- and sub-femtosecond time scales, interact with atoms, molecules or solids. The laser-induced electron dynamics occurs natively on a timescale down to a few hundred or even tens of attoseconds (1 attosecond = 1 as = 10-18 s), which is comparable with the optical field. For comparison, the revolution of an electron on a 1s orbital of a hydrogen atom is ∼152 as. On the other hand, the second branch involves the manipulation and engineering of mesoscopic systems, such as solids, metals and dielectrics, with nanometric precision. Although nano-engineering is a vast and well-established research field on its own, the merger with intense laser physics is relatively recent. In this report on progress we present a comprehensive experimental and theoretical overview of physics that takes place when short and intense laser pulses interact with nanosystems, such as metallic and dielectric nanostructures. In particular we elucidate how the spatially inhomogeneous laser induced fields at a nanometer scale modify the laser-driven electron dynamics. Consequently, this has important impact on pivotal processes such as above-threshold ionization and high-order harmonic generation. The deep understanding of the coupled dynamics between these spatially inhomogeneous fields and matter configures a promising way to new avenues of research and applications. Thanks to the maturity that attosecond physics has reached, together with the tremendous advance in material engineering and manipulation techniques, the age of atto-nanophysics has begun, but it is in the initial stage. We present thus some of the open questions, challenges and prospects for experimental confirmation of theoretical predictions, as well as experiments aimed at characterizing the induced fields and the unique electron dynamics initiated by them with high temporal and spatial resolution.

Carrier-wave Rabi-flopping signatures in high-order harmonic generation for alkali atoms.

We present a theoretical investigation of carrier-wave Rabi flopping in real atoms by employing numerical simulations of high-order harmonic generation (HHG) in alkali species. Given the short HHG cutoff, related to the low saturation intensity, we concentrate on the features of the third harmonic of sodium (Na) and potassium (K) atoms. For pulse areas of 2π and Na atoms, a characteristic unique peak appears, which, after analyzing the ground state population, we correlate with the conventional Rabi flopping. On the other hand, for larger pulse areas, carrier-wave Rabi flopping occurs, and is associated with a more complex structure in the third harmonic. These characteristics observed in K atoms indicate the breakdown of the area theorem, as was already demonstrated under similar circumstances in narrow band gap semiconductors.

Strong-field plasmonic photoemission in the mid-IR at <1†GW/cm² intensity.

We investigated nonlinear photoemission from plasmonic films with femtosecond, mid-infrared pulses at 3.1 µm wavelength. Transition between regimes of multi-photon-induced and tunneling emission is demonstrated at an unprecedentedly low intensity of <1 GW/cm(2). Thereby, strong-field nanophysics can be accessed at extremely low intensities by exploiting nanoscale plasmonic field confinement, enhancement and ponderomotive wavelength scaling at the same time. Results agree well with quantum mechanical modelling. Our scheme demonstrates an alternative paradigm and regime in strong-field physics.