Single-shot d-scan technique for ultrashort laser pulse characterization using transverse second-harmonic generation in random nonlinear crystals.

We demonstrate a novel dispersion-scan (d-scan) scheme for single-shot temporal characterization of ultrashort laser pulses. The novelty of this method relies on the use of a highly dispersive crystal featuring antiparallel nonlinear domains with a random distribution and size. This crystal, capable of generating a transverse second-harmonic signal, acts simultaneously as the dispersive element and the nonlinear medium of the d-scan device. The resulting in-line architecture makes the technique very simple and robust, allowing the acquisition of single-shot d-scan traces in real time. The retrieved pulses are in very good agreement with independent frequency-resolved optical grating measurements. We also apply the new single-shot d-scan to a terawatt-class laser equipped with a programmable pulse shaper, obtaining an excellent agreement between the applied and the d-scan retrieved dispersions.

IL17RA gene variants and anti-TNF response among psoriasis patients.

Polymorphisms at genes encoding proteins involved in the pathogenesis of psoriasis (Psor) or in the mechanism of action of biological drugs could influence the treatment response. Because the interleukin (IL)-17 family has a central role in the pathogenesis of Psor, we hypothesized that IL17RA variants could influence the response to anti-TNF drugs among Psor patients. To address this issue we performed a cross-sectional study of Psor patients who received the biological treatments for the first time, with a follow-up of at least 6 months. All of the patients were Caucasian, older than 18 years old, with chronic plaque Psor, and had completed at least 24 weeks of anti-TNF therapy (adalimumab, etanercept or infliximab). The treatment response to anti-TNF agents was evaluated according to the achievement of PASI50 and PASI75 at weeks 12 and 24. Those who achieved PASI75 at week 24 were considered good responders. All patients were genotyped for the selected single-nucleotide polymorphisms (SNPs) at IL17RA gene. A total of 238 patients were included (57% male, mean age 46 years). One hundred and five patients received adalimumab, 91 patients etanercept and 42 infliximab. The rs4819554 promoter SNP allele A was significantly more common among responders at weeks 12 (P=0.01) and 24 (P=0.04). We found a higher frequency of AA versus AG+GG among responders, but the difference was only significant at week 12 (P=0.03, odd ratio=1.86, 95% confidence of interval=1.05-3.27). Thus, in the study population, the SNP rs4819554 in the promoter region of IL17RA significantly influences the response to anti-TNF drugs at week 12.

Evaluation of new chlorhexidine- and cetylpyridinium chloride-based mouthrinse formulations adjunctive to scaling and root planing: pilot study.

OBJECTIVE: To compare the effect of two newly formulated chlorhexidine (CHX) and cetylpyridinium chloride (CPC) mouthrinses after scaling and root planing (SRP) in terms of clinical, microbiological, patient-based variables and adverse events, with a positive control with the same active components, already marketed and tested. METHODS: A pilot, randomized clinical trial, double-blind, parallel design with 1-month follow-up was conducted. Chronic periodontitis patients requiring non-surgical periodontal therapy were enrolled and randomly assigned to: (i) SRP and test-1 (new reformulation: 0.12% CHX and 0.05% CPC); (ii) SRP and test-2 (new formulation: 0.03% CHX and 0.05% CPC); or (iii) SRP and positive control (commercial product: 0.12% CHX and 0.05% CPC). All variables were evaluated at baseline and 1 month after SRP. Quantitative variables were compared by means of anova or Kruskal-Wallis test and qualitative variables by chi-square or McNemar tests. RESULTS: Thirty patients (10 per group) were included. After 1 month, there were significant differences among groups in plaque levels (P = 0.016) as test-1 showed less sites with plaque than test-2 (31.15% [standard error-SE 2.21%] versus 49.39% [SE 4.60%), respectively). No significant differences were found for global patient perception of the product or in adverse effects. Test groups showed better results in levels and proportions (P = 0.022) of Capnocytophaga spp. CONCLUSIONS: Within the limitations of this pilot study, it can be concluded that the newly formulated 0.12% CHX and 0.05% CPC mouthrinse showed larger plaque level reductions, without showing more adverse effects, when compared to the other two mouthrinses, after SRP.

Common and rare CARD14 gene variants affect the antitumour necrosis factor response among patients with psoriasis.

BACKGROUND: The CARD14 gene encodes a protein that enhances nuclear factor (NF)-κB activation and the upregulation of proinflammatory pathway genes. CARD14 is upregulated in psoriatic vs. normal skin, and rare and common CARD14 variants have been associated with the risk of developing psoriasis. Our hypothesis was that CARD14 variants could also influence the response to antitumour necrosis factor (anti-TNF) therapies among patients with psoriasis. OBJECTIVES: To determine whether CARD14 gene variants were linked to a significant positive anti-TNF response in patients with psoriasis. METHODS: DNA from 116 patients with psoriasis was subjected to next-generation sequencing of the CARD14 gene. All of the patients were nonresponders or had contraindications to conventional systemic treatments. RESULTS: A reduction of at least 75% in Psoriasis Area and Severity Index (PASI 75) at week 24 was considered a positive response to treatment. In total 116 patients (79 responders and 37 nonresponders) were next-generation sequenced, and we identified five nucleotide variants that would result in missense amino acid changes. These variants were determined in all of the patients, and allele and genotype frequencies were compared between the two groups. We found a significantly higher frequency of rs11652075 CC (p.Arg820Trp) among the group with a positive response (P = 0.01, odds ratio 3.71, 95% confidence interval 1.30-10.51). Furthermore, among responders, six patients were heterozygous carriers of the rare p.Glu422Lys variant, and two patients were heterozygous for p.Arg682Trp (P = 0.04). CONCLUSIONS: The common CARD14 p.Arg820Trp variant might have a significant effect on the response to anti-TNF therapies among patients with psoriasis. In addition, rare CARD14 missense variants could also predispose to a better response.

Carrier-envelope-phase insensitivity in high-order harmonic generation driven by few-cycle laser pulses.

We present evidence for self-stabilization of the relative spectral phase of high-order harmonic emission against intensity variations of the driving field. Our results demonstrate that, near the laser focus, phase matching of the harmonic field from a macroscopic target can compensate for the intensity dependence of the intrinsic phase of the harmonics emitted by a single radiator. As a consequence, we show experimentally and theoretically the insensitivity of the harmonic spectra produced at the laser focus against variations of the carrier-envelope phase (CEP) of a sub-two-cycle driving field. In addition, the associated attosecond pulse trains exhibit phase locking against CEP changes of the few-cycle driver.

Temporal and spectral structure of the infrared pulse during the high order harmonic generation.

We present, for the first time, the complete pulse characterization of the infrared pulse after generating harmonics. A systematic study of the high harmonic generation process, and the generating infrared pulse characterization, has been done by changing the focus-gas-jet relative position. We have concluded, supported by nonlinear propagation simulations, that there is a correlation between the spectral and temporal nonlinear evolution of the infrared generating field and the structures shown in the harmonic signal. We have identified two different pressure regimes: the low pressure regime, characterized by the effects produced by the plasma generated by the infrared pulse, and the high pressure regime where the plasma and the Kerr effect generated by the infrared field are both present. These observations highlight the important role played by the nonlinear propagation of the generating field in the high harmonic generation context.

Dose titration of intravenously administered gamma-hydroxybutyric acid for sedation in Holstein-Friesian calves.

Gamma-hydroxybutyric acid (GHB) is a short-chain fatty acid that can potentially provide safe, prolonged sedation with minimal cardiorespiratory effects. This preliminary trial, performed in 10 three-week-old male Holstein-Friesian calves, investigated the effects of GHB administered intravenously over 5 min at a dose of 100 (G100, n=2), 150 (G150, n=4) or 200 mg/kg (G200, n=4). Once lateral recumbency was achieved, scores for sedation depth (range: 0 = no sedation to 3 = marked) and response to noxious stimulation (range: 0 = strong to 3 = absent), heart rate (HR), respiratory rate (RR), mean arterial pressure (MAP) and arterial blood gases were monitored every 15 min until sternal recumbency. Times from end of administration to lateral recumbency and return to sternal/standing positions were recorded. Dose G100 resulted in mild sedation and ataxia without decubitus. Doses G150 and G200 respectively resulted in time to lateral recumbency 8 ± 2 and 9 ± 3 min, lasting 189 ± 41 and 283 ± 29 min, while overall median (range) scores for sedation were 3 (1-3) and 3 (2-3) respectively and response to noxious stimulation 0 (0-3) and 0 (0-3) respectively. The mean ± SD for HR was 110 ± 10 and 106 ± 11 bpm respectively; for MAP 87±9 and 94±5 mmHg respectively; and for RR 28 ± 5 and 26 ± 5 bpm respectively. The mean ± SD for arterial partial pressure of oxygen (PaO2) at these two dose rates was 74 ± 6 and 74 ± 2 mmHg respectively, while the arterial partial pressure of carbon dioxide oxygen (PaCO2) was 53 ± 3 and 47 ± 0.8 mmHg respectively. Based on these preliminary results we conclude that GHB has the potential to be used as a long-acting sedative in calves. Further studies are needed to confirm this.

Tumor location on electroporation therapies by means of multi-electrode structures and machine learning.

Electroporation is a phenomenon produced in the cell membrane when it is exposed to high pulsed electric fields that increases its permeability. Among other application fields, this phenomenon can be exploited in a clinical environment for tumor ablation therapies. In this context to achieve optimum results, it is convenient to focus the treatment on the tumor tissue to minimize side effects. In this work, a pre-treatment tumor location method is developed, with the purpose of being able to precisely target the therapy. This is done by taking different impedance measurements with a multi-output electroporation generator in conjunction with a multi-electrode structure. Data are processed by means of a vector of independent artificial neural networks, trained and tested with simulation data, and validated with phantom gels. This algorithm proved to provide suitable accuracy in spite of the low electrode count compared to the number of electrodes of a standard electrical impedance tomography device.

Simulation of alpha particle emitted by 222Rn from natural spring water in Puebla, México.

A computational simulation of alpha-particle expansion, emitted by 222Rn naturally diluted in the water of a spring located in the state of Puebla Mexico, is presented. This simulation provided information on the volume of expansion of the alpha particles in the vicinity of the spring and thus awareness if there was a radiological risk for the users or the population that lived near to it. Before performing the simulation, several measurements were made to water samples with a dynamic measurement system. This in order to know the level of radon concentration and compare the results obtained with the levels recommended by the United States Environmental Protection Agency (US-EPA) and the World Health Organization (WHO). In addition, to know if there was a radiological risk due to the presence of gamma emitting radionuclides, complementary water analyses were carried out using gamma-ray spectrometry techniques. The simulation was developed using the scientific software of particle interaction with matter, Geant4. The different variables declared for the software parameters are presented in this document. The results of the radon measurements in the water and the computational simulation, determined that there was no radiological risk due to alpha radiation. Furthermore, the results from the gamma-ray spectrometer showed that there was no presence of other hazardous radionuclides in the water.

Real-life experience of hepatitis C treatment in a Spanish prison.

OBJECTIVE: Hepatitis C virus (HCV) infection is a major public health problem that causes multiple comorbidities. People in prisons who inject intravenous drugs are at increased risk of HCV infection, and HCV infection is 15-fold more prevalent among prisoners compared with the community. The objective of this study was to analyse the clinical and epidemiological characteristics of residents of a Spanish prison with HCV infection who received antiviral treatment. METHODS: An observational, descriptive and retrospective study was performed. All patients with HCV infection diagnosed or followed up in an Infectious Diseases attached to a penitentiary were included in this study. RESULTS: Of 81 patients analysed, sixty-nine (83.1%) patients were male. The mean age was 50.1 (SD8.8) years, and 70% of the inmates had a history of injection drug use. Coinfection with HIV was detected in 30%. In up to 25% of the sample, there were data on chronic liver disease in the degree of liver cirrhosis. The diagnosis of HCV infection had been made more than 15 years earlier in 28% of those studied. Decompensations from liver disease, hepatocellular carcinoma, or hospital admissions were exceptional. Most of the inmates with HCV accepted treatment, and approximately 94% of the patients who completed treatment achieved a sustained virological response without interactions or complications of interest. CONCLUSIONS: The availability of direct-acting antivirals and their exceptional side effects constitute an opportunity to reduce the burden of HCV infection in Spain, particularly in these high-risk populations.

DNA damage modeled with Geant4-DNA: effects of plasmid DNA conformation and experimental conditions.

The chemical stage of the Monte Carlo track-structure (MCTS) code Geant4-DNA was extended for its use in DNA strand break (SB) simulations and compared against published experimental data. Geant4-DNA simulations were performed using pUC19 plasmids (2686 base pairs) in a buffered solution of DMSO irradiated by60Co or137Csγ-rays. A comprehensive evaluation of SSB yields was performed considering DMSO, DNA concentration, dose and plasmid supercoiling. The latter was measured using the super helix density value used in a Brownian dynamics plasmid generation algorithm. The Geant4-DNA implementation of the independent reaction times method (IRT), developed to simulate the reaction kinetics of radiochemical species, allowed to score the fraction of supercoiled, relaxed and linearized plasmid fractions as a function of the absorbed dose. The percentage of the number of SB after •OH + DNA and H• + DNA reactions, referred as SSB efficiency, obtained using MCTS were 13.77% and 0.74% respectively. This is in reasonable agreement with published values of 12% and 0.8%. The SSB yields as a function of DMSO concentration, DNA concentration and super helix density recreated the expected published experimental behaviors within 5%, one standard deviation. The dose response of SSB and DSB yields agreed with published measurements within 5%, one standard deviation. We demonstrated that the developed extension of IRT in Geant4-DNA, facilitated the reproduction of experimental conditions. Furthermore, its calculations were strongly in agreement with experimental data. These two facts will facilitate the use of this extension in future radiobiological applications, aiding the study of DNA damage mechanisms with a high level of detail.

Self-compression controlled by the chirp of the input pulse.

Self-compressed (SC) pulses have been achieved through the filamentation process in air without any additional dispersion compensation, using the input pulse chirp as the control parameter. For any studied input pulse energy (3-5 mJ), we have found two opposite sign input group-delay dispersion values for which SC pulses can be achieved systematically. In addition, we have observed that the energy coupled into the inner core of the filament is always of the order of 20% of the total input pulse energy, which opens the way to a scalable technique to obtain intense short pulses directly from the filamentation process.

Hypocarotenemia after bariatric surgery: a preliminary study.

BACKGROUND: Dietary carotenoids have attracted a great deal of attention due to their potential clinical relevance in conditions such as age-related maculopathy, osteoporosis, cardiovascular disease, and cancer. Surgical procedures have become the primary treatment of severe obesity, although nutrient deficiencies are common and long-term metabolic sequelae remain unknown. Thus, our aim was to assess the carotenoid status in serum of subjects after obesity surgery. METHODS: We evaluated the status of lutein, zeaxanthin, alpha- and beta-cryptoxanthin, lycopene, alpha- and beta-carotene, and fat-soluble vitamins by a quality-controlled high-performance liquid chromatography method in serum of 53 patients. Subjects were consecutively included as they were monitored for nutritional status after Roux-en-Y gastric bypass (RYGBP) or biliopancreatic diversion (BPD). Average follow-up time was 18 and 14 months for each protocol, respectively. RESULTS: After obesity surgery, a consistent and continuous decline in all carotenoids to almost undetectable levels occurs, especially in those who underwent BPD diversion who, on average, displayed serum levels about one half to one third of those found in RYGBP patients. CONCLUSION: The hypocarotenemia observed after bariatric surgery may compromise the availability of carotenoids to tissues and the vitamin A status, reducing the fat-soluble antioxidant capacity and constituting an additional risk factor for several clinical conditions. Given the emerging role of carotenoids in disease prevention, dietary advice on carotenoid-rich and fortified foods or the use of supplements in these patients should be considered.

Bioavailability of carotenoids and alpha-tocopherol from fruit juices in the presence of absorption modifiers: in vitro and in vivo assessment.

The food industry is playing an increasing role in the development and marketing of new products although little is known regarding the bioavailability of the phytochemicals they contain. Our aim was to assess the effect of the presence of absorption modifiers (milk and iron) on the in vitro bioaccessibility and the serum response in vivo of carotenoids and alpha-tocopherol from fruit juices. Thirty-two young women participated in a three-period (21 d each) supplementation study with a 2-week wash-out in between. Subjects consumed consecutively 2 x 250 ml/d vitamin C-fortified juices supplied as fruit juice, fruit juice containing milk and fruit juice containing milk and iron. Fasting blood samples were collected before and after each supplementation period. In vitro bioaccessibility of carotenoids and alpha-tocopherol was assessed by a static digestion model. Vitamin E and carotenoids from both studies were determined by HPLC. In vitro, xanthophyll ester hydrolysis and transference of free xanthophylls and alpha-tocopherol into the micellar phase were higher in the presence of absorption modifiers. In vivo, consumption of the fruit juices provoked significant increments (within-subject) of alpha-tocopherol and some carotenoids in serum. Dose-adjusted increments in serum of some carotenoids were higher when subjects consumed juices with milk and milk plus iron, although differences did not reach statistical significance. In conclusion, the presence of milk and milk plus iron do not influence the bioavailability of carotenoids and alpha-tocopherol from fruit juices in vivo. Our results support the use of in vitro models to assess food-related factors affecting bioavailability of carotenoids and tocopherols from foods.

Fagerstrom test for nicotine dependence vs heavy smoking index in a general population survey.

BACKGROUND: The Fagerström Test for Nicotine Dependence (FTND) is used for assessing nicotine dependence. A shorter test derived from the FTND used for the general population is the Heavy Smoking Index (HSI) (six questions vs. two). The objective of this study is to compare the validity of the HSI versus the FTND. METHODS: A survey of tobacco use in the general population was carried out in the northern Spanish region of Galicia using both the FTND and the HSI to study a representative sample of 1655 daily smokers. The HSI was compared with the FTND, considered the gold standard. Measures of sensitivity, specificity and predictive values were calculated. Concordance between the tests was also established (Cohen's kappa). RESULTS: Cohen's kappa showed good agreement between measures (Kappa = 0.7); specificity values were also high (Sp = 96.2%). Sensitivity analysis in females (Se = 62.3%) did not show good agreement. CONCLUSIONS: The HSI can be used as a reasonably good screening test in order to identify daily smokers with high nicotine dependence. Nevertheless, for populations or subpopulations having low nicotine dependence, such as women, the FTND is more reliable.

Effects of 2 physiotherapy programs on pain perception, muscular flexibility, and illness impact in women with fibromyalgia: a pilot study.

OBJECTIVE: This study assessed the effect of 2 physiotherapy programs designed to improve flexibility and to reduce the impact of the illness and pain perception in women with the fibromyalgia syndrome (FMS), and compared the effects of the 2 programs in the short and intermediate term. METHODS: Twenty FMS patients were randomly assigned to 2 training groups, one following a program of kinesiotherapy and active muscular stretching and one using techniques of Global Myofascial Physiotherapy, according to the Mézières method. Both groups met twice a week for 12 weeks, for a total of 150 minutes each week. Flexibility and illness impact were measured by means of a standard test, whereas pain was assessed by means of thumb palpation. Measurements were taken at the beginning and end of the program and 24 weeks after its end. RESULTS: Patients had achieved a statistically significant reduction in the severity of the disease and improved their flexibility level by the end of the program, but had returned to initial values after follow-up. Significant differences were not observed between the 2 treatment groups in the initial values or in the results at the end of the program or after the follow-up, so neither program proved better than the other. CONCLUSION: The FMS patients in this study improved their flexibility level and general well-being using both kinesiotherapy and stretching exercises techniques.

Histopathological and Ultrastructural Changes after Electroporation in Pig Liver Using Parallel-Plate Electrodes and High-Performance Generator.

Irreversible electroporation (IRE) has gained attention as a new non-thermal therapy for ablation with important benefits in terms of homogeneous treatment and fast recovery. In this study, a new concept of high voltage generator is used, enabling irreversible electroporation treatment in large tissue volume using parallel plates. Unlike currently available generators, the proposed versatile structure enables delivering high-voltage high-current pulses. To obtain homogeneous results, 3-cm parallel-plates electrodes have also been designed and implemented. IRE ablation was performed on six female pigs at 2000 V/cm electric field, and the results were analysed after sacrifice three hours, three days and seven days after ablation. Histopathological and ultrastructural studies, including transmission and scanning electron microscopy, were carried out. The developed high-voltage generator has proved to be effective for homogeneous IRE treatment using parallel plates. The destruction of the membrane of the hepatocytes and the alterations of the membranes of the cellular organelles seem incompatible with cell death by apoptosis. Although endothelial cells also die with electroporation, the maintenance of vascular scaffold allows repairing processes to begin from the third day after IRE as long as the blood flow has not been interrupted. This study has opened new direction for IRE using high performance generators and highlighted the importance of taking into account ultrastructural changes after IRE by using electron microscopy analysis.

Consumption of restructured meat products with added walnuts has a cholesterol-lowering effect in subjects at high cardiovascular risk: a randomised, crossover, placebo-controlled study.

BACKGROUND: Diet and lifestyle are modifiable factors involved in the development and prevention of non-communicable diseases, including cardiovascular disease. Nut consumption, particularly walnut intake, has been inversely related to incident coronary heart disease (CHD) in observational studies and to improved lipid profiles in short-term feeding trials. OBJECTIVE: To assess the potential functional effect associated with the regular consumption of walnut-enriched restructured meat products in subjects at risk for cardiovascular disease (CVD). DESIGN: A crossover single-dose bioavailability study (n = 3) using gamma-tocopherol as exposure marker and a crossover unblinded dietary intervention study (5 weeks) in subjects at risk (n = 25). Dietary intervention consisted of regular consumption of the meat product, with or without walnuts, five times per week for five weeks with a 1-month washout in between. Overnight fasting blood samples were collected on days 0, 12, 21, 28 and 35, coinciding with blood pressure and body weight recordings. Participants were asked to complete a diet record throughout the study. The functional effects were assessed using clinically relevant and related biomarkers of CHD: serum total, HDL and LDL cholesterol, triacylglycerols, homocysteine, vitamins B(6) and B(12), folic acid, alpha-tocopherol and platelet function test (obturation time). RESULTS: The regular consumption of walnut-enriched meat products compared with that of the restructured meat products without added walnuts provokes a decrease in total cholesterol of 6.8 mg/dl (CI(95%): -12.8, -0.85). Compared to baseline (mixed diet), meat products with walnuts decreased total cholesterol (-10.7 mg/dl, CI(95%): -17.1, -4.2), LDL cholesterol (-7.6 mg/dl, CI(95%): -2.2, -13.0) and body weight (-0.5 kg, CI(95%): -0.1, -0.9) and increased gamma-tocopherol (8.9 mg/dl, CI(95%): 1.0, 16.8). CONCLUSIONS: The restructured meat products with added walnuts supplied in this study can be considered functional foods for subjects at high risk for CVD, as their regular consumption provokes a reduction in total cholesterol of 4.5% with respect to baseline values (mixed diet) and 3% with respect to the restructured meat without walnuts.

Low level radioactivity measurements with phoswich detectors using coincident techniques and digital pulse processing analysis.

A new system has been developed for the detection of low radioactivity levels of fission products and actinides using coincidence techniques. The device combines a phoswich detector for alpha/beta/gamma-ray recognition with a fast digital card for electronic pulse analysis. The phoswich can be used in a coincident mode by identifying the composed signal produced by the simultaneous detection of alpha/beta particles and X-rays/gamma particles. The technique of coincidences with phoswich detectors was proposed recently to verify the Nuclear Test Ban Treaty (NTBT) which established the necessity of monitoring low levels of gaseous fission products produced by underground nuclear explosions. With the device proposed here it is possible to identify the coincidence events and determine the energy and type of coincident particles. The sensitivity of the system has been improved by employing liquid scintillators and a high resolution low energy germanium detector. In this case it is possible to identify simultaneously by alpha/gamma coincidence transuranic nuclides present in environmental samples without necessity of performing radiochemical separation. The minimum detectable activity was estimated to be 0.01 Bq kg(-1) for 0.1 kg of soil and 1000 min counting.