Reconfigurable frequency multipliers based on graphene field-effect transistors.

Run-time device-level reconfigurability has the potential to boost the performance and functionality of numerous circuits beyond the limits imposed by the integration density. The key ingredient for the implementation of reconfigurable electronics lies in ambipolarity, which is easily accessible in a substantial number of two-dimensional materials, either by contact engineering or architecture device-level design. In this work, we showcase graphene as an optimal solution to implement high-frequency reconfigurable electronics. We propose and analyze a split-gate graphene field-effect transistor, demonstrating its capability to perform as a dynamically tunable frequency multiplier. The study is based on a physically based numerical simulator validated and tested against experiments. The proposed architecture is evaluated in terms of its performance as a tunable frequency multiplier, able to switch between doubler, tripler or quadrupler operation modes. Different material and device parameters are analyzed, and their impact is assessed in terms of the reconfigurable graphene frequency multiplier performance.

Multi-scale analysis of radio-frequency performance of 2D-material based field-effect transistors.

Two-dimensional materials (2DMs) are a promising alternative to complement and upgrade high-frequency electronics. However, in order to boost their adoption, the availability of numerical tools and physically-based models able to support the experimental activities and to provide them with useful guidelines becomes essential. In this context, we propose a theoretical approach that combines numerical simulations and small-signal modeling to analyze 2DM-based FETs for radio-frequency applications. This multi-scale scheme takes into account non-idealities, such as interface traps, carrier velocity saturation, or short channel effects, by means of self-consistent physics-based numerical calculations that later feed the circuit level via a small-signal model based on the dynamic intrinsic capacitances of the device. At the circuit stage, the possibilities range from the evaluation of the performance of a single device to the design of complex circuits combining multiple transistors. In this work, we validate our scheme against experimental results and exemplify its use and capability assessing the impact of the channel scaling on the performance of MoS2-based FETs targeting RF applications.

Demographic, clinical and allergological characteristics of Eosinophilic Esophagitis in a Spanish central region

BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic inflammatory emerging disease of the oesophagus with immunoallergic aetiology. The allergens involved have not been clearly defined and may depend on the exposure of the population to aeroallergens or food antigens. MATERIALS AND METHODS: Patients diagnosed with EoE between 2006 and 2011 were referred to our Allergy Section. Patch and skin prick tests (SPT) with aeroallergens and foods were performed, and total and specific IgE levels, eosinophil cationic protein levels and eosinophil count were determined. RESULTS: 43 patients were included. 36 (83.7%) were atopic. 29 patients presented choking, 19 dysphagia, 9 food impaction with urgent endoscopy, 4 chest pain, 1 isolated vomiting and 1 epigastric pain. 22 had two or more symptoms. The mean duration of symptoms was 3.73 years. Concomitant allergic diseases included rhinoconjunctivitis and/or asthma (31 patients), IgE food allergy (21 patients) and atopic dermatitis (3 patients).32 (74%) were sensitized to aeroallergens, of which 90% were sensitized to pollens; 23 (54%) showed positive tests to foods and 12 of them (52%) to lipid transfer proteins (LTP).Of the 29 pollen-allergic patients, 15 (52%) were sensitized to plant foods and 10 (34.4%) to LTP. CONCLUSIONS: Our findings support those reported in the literature: the disease is more common in men aged 30-40 years with at least a three-year history of symptoms of esophageal dysfunction, sensitized to pollens, the predominant aeroallergen in our area, but also to plant foods or panallergens. These results increase the evidence for an immunoallergic aetiology and can help us in the early diagnosis of EoE

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Demographic, clinical and allergological characteristics of Eosinophilic Esophagitis in a Spanish central region.

BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic inflammatory emerging disease of the oesophagus with immunoallergic aetiology. The allergens involved have not been clearly defined and may depend on the exposure of the population to aeroallergens or food antigens. MATERIALS AND METHODS: Patients diagnosed with EoE between 2006 and 2011 were referred to our Allergy Section. Patch and skin prick tests (SPT) with aeroallergens and foods were performed, and total and specific IgE levels, eosinophil cationic protein levels and eosinophil count were determined. RESULTS: 43 patients were included. 36 (83.7%) were atopic. 29 patients presented choking, 19 dysphagia, 9 food impaction with urgent endoscopy, 4 chest pain, 1 isolated vomiting and 1 epigastric pain. 22 had two or more symptoms. The mean duration of symptoms was 3.73 years. Concomitant allergic diseases included rhinoconjunctivitis and/or asthma (31 patients), IgE food allergy (21 patients) and atopic dermatitis (3 patients). 32 (74%) were sensitized to aeroallergens, of which 90% were sensitized to pollens; 23 (54%) showed positive tests to foods and 12 of them (52%) to lipid transfer proteins (LTP). Of the 29 pollen-allergic patients, 15 (52%) were sensitized to plant foods and 10 (34.4%) to LTP. CONCLUSIONS: Our findings support those reported in the literature: the disease is more common in men aged 30-40 years with at least a three-year history of symptoms of esophageal dysfunction, sensitized to pollens, the predominant aeroallergen in our area, but also to plant foods or panallergens. These results increase the evidence for an immunoallergic aetiology and can help us in the early diagnosis of EoE.

Diagnosis of patients with immediate hypersensitivity to beta-lactams using retest.

BACKGROUND: beta-Lactams are the drugs most frequently involved in hypersensitivity reactions mediated by immunoglobulin (Ig) E. OBJECTIVE: To evaluate a population of patients with suspected B-lactam allergy using a validated algorithm that includes specific IgE antibodies, skin testing, and/or a drug provocation test. METHODS: A total of 1032 patients with symptoms compatible with B-lactam allergy were evaluated by means of their clinical history, specific immunoglobulin (Ig) E antibody determinations (benzylpenicillin, ampicillin, and amoxicillin), and skin tests with major determinants (penicilloyl-polylysine) and minor determinants (minor determinant mixture) of benzylpenicillin, penicillin G, ampicillin, and amoxicillin-clavulanic acid. Patients whose skin test results were negative were challenged with amoxicillin-clavulanic acid. Only immediate hypersensitivity reactions were evaluated. All patients with negative study results and for whom a reaction occurred more than 1 year before were retested using the same protocol. RESULTS: A total of 170 patients (16.4%) were finally confirmed as having immediate allergic reactions to beta-lactams (62.3% by skin testing, 16.5% by specific IgE, and 21.2% by drug provocation test). The mean age of these patients was 43.3 years, and the drug most frequently involved in the reaction was amoxicillin (41.1%), followed by the combination amoxicillin-clavulanic acid (36.4%). In the remaining 22.5%, different beta-lactams were involved or the culprit drug was not known. Only mild reactions were observed after the drug provocation test. A retest was required in 23% of patients in order to confirm their hypersensitivity. CONCLUSIONS: These results indicate that a diagnostic protocol based on the combination of skin testing and in vitro determination of specific IgE antibodies plus, if required, drug provocation testing is an appropriate procedure for evaluating immediate hypersensitivity reactions to beta-lactams. Because the sensitivity of skin testing and in vitro IgE assays is not optimal and a considerable proportion of patients are tolerant, drug provocation tests are necessary to achieve the diagnosis or confirm tolerance. A large percentage of patients (23%) were diagnosed using retest.

[Immunotherapy with an oral Alternaria extract in childhood asthma. Clinical safety and efficacy and effects on in vivo and in vitro parameters]. / Inmunoterapia con un extracto oral de Alternaria en el asma infantil. Eficacia clínica, seguridad, repercusiones sobre parámetros in vivo e in vitro.

Studies of immunotherapy with oral Alternaria extracts are scarce. We decided to perform a clinical trial of the clinical safety and efficacy of this extract as well as of its effects on in vivo and in vitro parameters in 39 patients with Alternaria allergy, aged between 7 and 17 years, who are also sensitized extract was used. Allergic activity was determined through RAST inhibition and skin prick test. Quantification of the principal allerten (Alt a 1) was performed through the 2-site binding assay, with a mean content of 34.2 ng Alt a 1/micro g protein. The parameters analyzed were the symptom-medication score, skin prick using the end-point technique, specific bronchial challenge test, peak flow, total and specific IgE and IgG4. Nineteen patiens received active treatment with oral immunotherapy and another 19 received symptomatic treatment. The initial phase of immunotherapy lasted 3 months until the maximum dose was reached. This was maintained for 12 months; the mean accumulated dos was 280,000 PNU. Significant differences were found in reduction in the symptom-medication score in the treated group after 12 months of immunotherapy. No differences were found in the control group. Immunotherapy was well tolerated with 0.42 adverse reactions per 100 doses administered. All adverse reactions were mild-to-moderate. In the treated group, papule size was significantly reduced. Values for the specific bronchial challenge test, expressed through PD20, were significantly higher in the immunotherapy group. Peak flow showed no changes in either group. Values of IgG4 were significantly higher in the immunotherapy group. Total and specific IgE levels showed no significant changes in either group. In conclusion, oral immunotherapy with Alternaria extract is clinically effective in pediatric patients. In general, the therapy was well tolerated. It modified specific cutaneous and bronchial reactivity in our sample and increased levels of specific IgG4, wich are implicated in humoral response.

La rinitis a la luz de los consensos internacionales / Rhinitis in the light of international consensuses

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Inmunoterapia con un extracto oral del Alternaria en el asma infantil. Eficacia clínica, seguridad, repercusines sobre parámetros in vivo e in vitro / Immunotherapy with an oral Alternaria extract in chilhood asthma. Clinical safety and efficacy and effects on in vivo and in vitro

Ante la escasez de trabajos con inmunoterapia oral de Alternaria, planteamos la realización de un ensayo clínico en 39 pacientes, con edades comprendidas entre 7 y 17 años, alérgicos a Alternaria, y sensibilizados también a pólenes y epitelios para evaluar su eficacia clínica y seguridad, así como las repercusiones sobre parámetros in vivo e in vitro. Se empleó un extracto estandarizado, determinando la actividad alérgica mediante RAST inhibición y prick test cutáneo. La cuantificación del alergeno principal (Alt a 1) se llevó a cabo mediante la técnica de fijación en dos lugares, siendo el contenido medio de 34,2 ng Alt a 1/ g de proteína. Los parámetros analizados fueron la puntuación de síntomas-medicación, prick test cutáneo a punto final (TC), test de bronco provocación específico (TBPE), pico de flujo (PF), IgE total y específica e IgG4.Diecinueve pacientes recibieron tratamiento activo con inmunoterapia oral (ITO) y otros diecinueve recibieron tratamiento sintomático. La fase de inicio de la inmunoterapia duró 3 meses, hasta llegar a dosis máxima, que se mantuvo durante 12 meses, alcanzando una dosis acumulada media de 280.000 PNU. Se hallaron diferencias significativas en la disminución de la puntuación de síntomas-medicación en el grupo tratado, tras los 12 meses de inmunoterapia (ITO). No se encontraron diferencias en el grupo control. La inmunoterapia fue bien tolerada, presentando 0,42 reacciones adversas (RA) por 100 dosis administradas, siendo de carácter leve-moderado exclusivamente. Se encontró disminución significativa del tamaño de pápula en el grupo tratado. El TBPE expresado mediante la PD20 mostró cifras significativamente más altas en el grupo con ITO. El pico de flujo no mostró cambios en ninguno de los dos grupos. Los valores de la IgG4 fueron significativamente más altos en el grupo con inmunoterapia. Los niveles de IgE total y específica no mostraron cambios significativos en ambos grupos. En conclusión, la Inmunoterapia Oral con extracto de Alternaria ha demostrado eficacia clínica en pacientes pediátricos, siendo en general bien tolerada, modificando la reactividad específica cutánea y bronquial con incremento de los niveles de IgG4 específica implicados en la respuesta humoral (AU)

Studies of immunotherapy with oral Alternaria extracts are scarce. We decided to perform a clinical trial of the clinical safety and efficacy of this extract as well as of its effects on in vivo and in vitro parameters in 39 patients with Alternaria allergy, aged between 7 and 17 years, who are also sensitized extract was used. Allergic activity was determined through RAST inhibition and skin prick test. Quantification of the principal allerten (Alt a 1) was performed through the 2-site binding assay, with a mean content of 34.2 ng Alt a 1/μg protein. The parameters analyzed were the symptom-medication score, skin prick using the end-point technique, specific bronchial challenge test, peak flow, total and specific IgE and IgG4. Nineteen patiens received active treatment with oral immunotherapy and another 19 received symptomatic treatment. The initial phase of immunotherapy lasted 3 months until the maximum dose was reached. This was maintained for 12 months; the mean accumulated dos was 280,000 PNU. Significant differences were found in reduction in the symptom-medication score in the treated group after 12 months of immunotherapy. No differences were found in the control group. Immunotherapy was well tolerated with 0.42 adverse reactions per 100 doses administered. All adverse reactions were mild-to-moderate. In the treated group, papule size was significantly reduced. Values for the specific bronchial challenge test, expressed through PD20, were significantly higher in the immunotherapy group. Peak flow showed no changes in either group. Values of IgG4 were significantly higher in the immunotherapy group. Total and specific IgE levels showed no significant changes in either group. In conclusion, oral immunotherapy with Alternaria extract is clinically effective in pediatric patients. In general, the therapy was well tolerated. It modified specific cutaneous and bronchial reactivity in our sample and increased levels of specific IgG4, wich are implicated in humoral response (AU)

Spring pollen and related allergies in southern Spain.

Over the last 10 years, there has been an increase in pollen allergies throughout Europe; this trend is clearly reflected in this study carried out in Córdoba (southern Spain) over 7 consecutive years, which recorded important increases in the concentrations of certain pollen types of particular interest in this city, together with an increase in the number of patients with pollinosis visiting the Allergy Unit at Córdoba's Reina Sofía University Hospital. The purpose of this study was to ascertain whether these two trends were related. Sampling was carried out from 1984 to 1990, using a Burkard spore trap placed at a height of approximately 15 m on a building situated in the city center. The trend towards an annual increase in the concentration of pollen grains was positive in all cases, although very slight for Quercus and very marked for Olea europaea. However, a different pattern of behavior was recorded with respect to the correlation between pollen concentration and cases of pollinosis, a correlation which varied according to taxa.

Variations in the concentrations of airborne Olea pollen and associated pollinosis in Córdoba (Spain): a study of the 10-year period 1982-1991.

The amount and the seasonal and daily changes in the concentrations of Olea pollen grains in the atmosphere of Córdoba (Spain) have been studied over a 10-year period. The year by year seasonal variation pattern and the theoretical intradiurnal variation model are presented. The data show a high annual variability, median concentrations varying from 75 g/m3/h in 1983 to 1413 g/m3/h in 1986. A steady increase in the total amount of pollen is attributed to the climatological characteristics of the period studied. On the other hand, the clinical data show that the number of cases of Olea allergy has increased considerably during this period, probably more because of changes in the quality of the atmosphere than because of the increase in the amount of antigen present in the air.

Monitoring of various types of immunotherapy with gramineal pollens. I. Variation of clinical and biochemical parameters.

We assessed the clinical effectiveness and adverse effect of various types of immunotherapy on 42 pollinotic patients by monitoring their evolution on administration of Perennial lolium specific extract standardized in protein nitrogen units to 14 of them, the same extract but standardized in biological units (BUs) to another 13, and an extract containing four different pollens standardized in BUs to the remaining 15. For this purpose we measured clinical and medicinal scores, liver and kidney biochemical parameters, skin reactions and circulating immunocomplexes (CICs), both before immunotherapy was started (basal levels) and after 3, 6 and 12 month's treatment. We found no significant differences in clinical effectiveness or the occurrence of any adverse effects on administration of the different immunotherapies after one year's monitoring. We did found gradually decreased reactions to the skin tests, which thus provide a reliable means of monitoring allergen-specific immunotherapy.

Monitoring of various types of immunotherapy with gramineal pollens. II. Variation of humoral immunochemical parameters.

We monitored the total and Perennial lolium-specific IgE, IgG, IgM and IgA serum levels of pollinotic patients under three different immunotherapeutic treatments with gramineal pollens over a one-year period. We found statistically significant (p < 0.05) decreases in the total serum IgE levels in successive controls performed after 3, 6 and 12 month's treatment with respect to the basal control levels. The specific IgE levels also decreased gradually throughout the study, while the total serum IgG and IgM levels increased significantly over the first 3 months, and those of IgG continued to increase up to the sixth month. Finally, the total serum IgA levels did not change significantly during the first year of treatment of our pollinotic patients.

[Clinical performance of the basophil degranulation test. Correlation with other diagnostic technics in allergy (II)]. / Rentabilidad clínica del test de degranulación de basófilos. Correlación con otras técnicas diagnósticas en alergia (II).

Although the clinical history is the fundamental method for the diagnosis of reaginic diseases, the use of complementary techniques that gears on the detection of the humoral and cellular effector cells intervening in such affectation is necessary. Thus, we can detect the existence of specific IgE. It can be joined to the basophil membrane by means of techniques "in vivo" as in cutaneous tests, or by means of techniques "in vitro" through cellular techniques in which we apply a biochemical pattern (release of histamine) or a morphological one (HBDT). It can also be free in serum by means of the P-K test or "in vitro" by means of techniques of double antibody. We can also determine, by this last technique, the quantity of the total IgE in serum. In the present work, we review the human basophil degranulation test (HBDT) and its correlation with the prick test, the peripheral blood eosinophilia, the total serum IgE quantification by enzymatic technique and the specific IgE detection by isotope method. In our technique the test was considered positive when the degranulation index with known allergen concentration was greater than 30% for pollens and greater than 25% for D. pteronyssinus with a p less than 0.001. As reported in a previous work, we explain that the normal limits are slightly inferior to those used by some other authors, because in our series, the degranulation average of healthy controls is inferior to that reported by those authors which makes us consider the convenience that the normal limits of degranulation index should be established in a particular way by each technique and allergen.(ABSTRACT TRUNCATED AT 250 WORDS)

[Human basophil degranulation test. Results of a modified technic (I)]. / Test de degranulación de basófilos humanos. Variantes técnicas aportadas (I).

The degranulation of human basophils towards antigenic substances, to which they must be previously sensitized as a result of the antigen-antibody union at the membrane level, is a phenomenon that has an important application complementing diagnosis of diseases mediated by the Gell and Coombs classification of Type I Hypersensitivity, on which the principle of Human Basophils Degranulation Test (HBDT) was based. An essential requirement is to be able to collect an adequate quantity of basophils, as well as the visualization by means of a technique of convenient stain. In this work, we show a modified HBDT technique for basophil granulocytes staining. A total of 33 HBDT was carried out on patients sensitive to grass pollen and/or Olea europea pollen and/or D. pteronyssinus, and as controls, HBDT was done on healthy individuals with negative clinical history. Basophil enrichemnt from the circulating blood sample was done by means of centrifugation in Percoll density gradients of 1072, 1076, 1080 and 1082, and we obtained a higher number of basophils with a density of 1080 at 400 Xg for 30 minutes. The cellular bottom was resuspended in 600 microliters of PBS. We employed lyophilized antigenic extracts from grass pollen, Olea europea and D. pteronyssinus, employing weight/volume concentration of 10(-4), 10(-5), 10(-6) and 10(-7). The optimum dilutions were 10(-5) for grass pollen and D. pteronyssinus.