Goos-Hänchen shift for coupled vibrational modes in a semiconductor structure.

We present a theoretical investigation of the Goös-Hanchen shift (GHS) experienced by acoustic and optical vibrational modes reflected and transmitted from the surfaces of a semiconductor thin film sandwiched between two semi-infinite media. Our study focuses on the impact of the incident angle on the GHS, considering the coupling between longitudinal and transverse modes. For acoustic vibrations, our findings reveal that the GHS can reach magnitudes up to seven times larger than the thickness of the thin film and up to 20 times larger than the incident wavelength. Besides, it is shown that this significant amplification of the GHS highlights the strong influence of the incident angle and the frequency of the modes involved. In the case of optical vibrations, we observe even more pronounced GHS values, exceeding 30 times the incident wavelength. This demonstrates the potential of GHS in acoustical systems, which opens up possibilities for applications in the design of acoustic devices.

Transfer matrix in 1D Dirac-like problems.

The transfer matrix method is considered to obtain the fundamental properties of 1D Dirac-like problems. The case of 1D problems in monolayer graphene is addressed. The main characteristics of the transfer matrix are analyzed, contrasting them with the ones corresponding to 1D Schrödinger-like problems. Analytic expressions for the transmission coefficient and bound states are obtained. The continuity between bound states and states of perfect transmission is demonstrated in general, and in particular showed for the case of single electrostatic barriers. These findings in principle can be extended to 2D materials with Hamiltonian similar to monolayer graphene such as silicene and transition metal dichalcogenides.

Enhancement of the thermoelectric properties in bilayer graphene structures induced by Fano resonances.

Fano resonances of bilayer graphene could be attractive for thermoelectric devices. The special profile presented by such resonances could significantly enhance the thermoelectric properties. In this work, we study the thermoelectric properties of bilayer graphene single and double barrier structures. The barrier structures are typically supported by a substrate and encapsulated by protecting layers, reducing considerably the phonon thermal transport. So, we will focus on the electronic contribution to the thermal transport. The charge carriers are described as massive chiral particles through an effective Dirac-like Hamiltonian. The Hybrid matrix method and the Landauer-Büttiker formalism are implemented to obtain the transmission, transport and thermoelectric properties. The temperature dependence of the Seebeck coefficient, the power factor, the figure of merit and the efficiency is analyzed for gapless single and double barriers. We find that the charge neutrality point and the system resonances shape the thermoelectric response. In the case of single barriers, the low-temperature thermoelectric response is dominated by the charge neutrality point, while the high-temperature response is determined by the Fano resonances. In the case of double barriers, Breit-Wigner resonances dominate the thermoelectric properties at low temperatures, while Fano and hybrid resonances become preponderant as the temperature rises. The values for the figure of merit are close to two for single barriers and above three for double barriers. The system resonances also allows us to optimize the output power and the efficiency at low and high temperatures. By computing the density of states, we also corroborate that the improvement of the thermoelectric properties is related to the accumulation of electron states. Our findings indicate that bilayer graphene barrier structures can be used to improve the response of thermoelectric devices.

Characterization and Outcomes of SARS-CoV-2 Infection in Patients with Sarcoidosis.

To analyze the clinical characteristics and outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with sarcoidosis from a large multicenter cohort from Southern Europe and to identify the risk factors associated with a more complicated infection. We searched for patients with sarcoidosis presenting with SARS-CoV-2 infection (defined according to the European Centre for Disease Prevention and Control guidelines) among those included in the SarcoGEAS Registry, a nationwide, multicenter registry of patients fulfilling the American Thoracic Society/European Respiratory Society/World Association of Sarcoidosis and Other Granulomatous Disorders 1999 classification criteria for sarcoidosis. A 2:1 age-sex-matched subset of patients with sarcoidosis without SARS-CoV-2 infection was selected as control population. Forty-five patients with SARS-CoV-2 infection were identified (28 women, mean age 55 years). Thirty-six patients presented a symptomatic SARS-CoV-2 infection and 14 were hospitalized (12 required supplemental oxygen, 2 intensive care unit admission and 1 mechanical ventilation). Four patients died due to progressive respiratory failure. Patients who required hospital admission had an older mean age (64.9 vs. 51.0 years, p = 0.006), a higher frequency of baseline comorbidities including cardiovascular disease (64% vs. 23%, p = 0.016), diabetes mellitus (43% vs. 13%, p = 0.049) and chronic liver/kidney diseases (36% vs. 0%, p = 0.002) and presented more frequently fever (79% vs. 35%, p = 0.011) and dyspnea (50% vs. 3%, p = 0.001) in comparison with patients managed at home. Age- and sex-adjusted multivariate analysis identified the age at diagnosis of SARS-Cov-2 infection as the only independent variable associated with hospitalization (adjusted odds ratio 1.18, 95% conficence interval 1.04-1.35). A baseline moderate/severe pulmonary impairment in function tests was associated with a higher rate of hospitalization but the difference was not statistically significant (50% vs. 23%, p = 0.219). A close monitoring of SARS-CoV-2 infection in elderly patients with sarcoidosis, especially in those with baseline cardiopulmonary diseases and chronic liver or renal failure, is recommended. The low frequency of severe pulmonary involvement in patients with sarcoidosis from Southern Europe may explain the weak prognostic role of baseline lung impairment in our study, in contrast to studies from other geographical areas.

Systemic phenotype of sarcoidosis associated with radiological stages. Analysis of 1230 patients.

BACKGROUND: To analyze the association between Scadding radiological stages of sarcoidosis at diagnosis and the disease phenotype (epidemiology, clinical presentation and extrathoracic involvement) in one of the largest cohorts of patients with sarcoidosis reported from southern Europe. METHODS: The SARCOGEAS-Study Group includes a multicenter database of consecutive patients diagnosed with sarcoidosis according to the WASOG 1999 criteria. Extrathoracic disease at diagnosis was defined according to the 2014 instrument and the clusters proposed by Schupp et al. RESULTS: We analyzed 1230 patients (712 female, mean age 47 yrs.) who showed the following Scadding radiologic stages at diagnosis: stage 0 (n = 98), stage I (n = 395), stage II (n = 500), stage III (n = 195) and stage IV (n = 42). Women were overrepresented in patients presenting with extrathoracic/extrapulmonary disease, while the diagnosis was made at younger ages in patients presenting with BHL, and at older ages in those presenting with pulmonary fibrosis (q values <0.05). Multivariable adjusted analysis showed that patients presenting with pulmonary involvement (especially those with stages II and III) had a lower frequency of concomitant systemic involvement in some specific extrathoracic clusters (cutaneous-adenopathic/musculoskeletal, ENT and neuro-ocular/OCCC) but a higher frequency for others (hepatosplenic), in comparison with patients with extrapulmonary involvement (stages 0 and I). The presence of either BHL or fibrotic lesions did not influence the systemic phenotype of patients with pulmonary involvement. CONCLUSIONS: The key determinant associated with a differentiated systemic phenotype of sarcoidosis at diagnosis was interstitial pulmonary involvement rather than the individual Scadding radiological stage.

Goos-Hänchen effect for optical vibrational modes in a semiconductor structure.

We study the tunneling of optical vibrational modes with transverse horizontal polarization that impinge, at a given angle, on a semiconductor heterostructure. We find a large influence of the Goos-Hänchen shift on tunneling times. In particular, a Goos-Hänchen shift larger than the barrier thickness is reported for the first time. The relation between Goos-Hänchen and Hartman effects is also discussed. The identity that equals the dwell time to the sum of transmission and interference times, previously derived for one-dimensional tunneling problems, is extended to the two-dimensional case. Closed-form expressions are developed for the relevant quantities. Instead of using the standard approach, the interference time is computed from the vibrational energy density. The present study could be useful for the design of semiconductor devices.

Systemic activity and mortality in primary Sjögren syndrome: predicting survival using the EULAR-SS Disease Activity Index (ESSDAI) in 1045 patients.

OBJECTIVE: To score systemic activity at diagnosis and correlate baseline activity with survival in a large cohort of patients with primary Sjögren syndrome (SS). PATIENTS AND METHODS: We include 1045 consecutive patients who fulfilled the 2002 classification criteria for primary SS. The clinical and immunological characteristics and level of activity (EULAR-SS Disease Activity Index (ESSDAI) scores) were assessed at diagnosis as predictors of death using Cox proportional hazards regression analysis adjusted for age at diagnosis. The risk of death was calculated at diagnosis according to four different predictive models. RESULTS: After a mean follow-up of 117 months, 115 (11%) patients died. The adjusted standardised mortality ratio for the total cohort was 4.66 (95% CI 3.85 to 5.60), and survival rates at 5, 10, 20 and 30 years were 96%, 90%, 81% and 60%, respectively. The main baseline factors associated with overall mortality in the multivariate analysis were male gender, cryoglobulins and low C4 levels. Baseline activity in the constitutional, pulmonary and biological domains was associated with a higher risk of death. High activity in at least one ESSDAI domain (HR 2.14), a baseline ESSDAI score ≥14 (HR 1.85) and more than one laboratory predictive marker (lymphopenia, anti-La, monoclonal gammopathy, low C3, low C4 and/or cryoglobulins) (HR 2.82) were associated with overall mortality; these HRs increased threefold to 10-fold when the analysis was restricted to mortality associated with systemic disease. CONCLUSIONS: Patients with primary SS, who present at diagnosis with high systemic activity (ESSDAI ≥14) and/or predictive immunological markers (especially those with more than one), are at higher risk of death.

How are we treating our systemic patients with primary Sjögren syndrome? Analysis of 1120 patients.

OBJECTIVE: To describe how systemic disease is treated in a large cohort of Spanish patients with primary Sjögren syndrome (pSS) in daily practice, focusing on the adequacy of therapies for the level of systemic activity measured by ESSDAI score. PATIENTS AND METHODS: By December 2014, our database included 1120 consecutive patients who fulfilled the 2002 classification criteria for SS. Therapeutic schedules were classified into 4 categories: no systemic therapies, hydroxychloroquine (HCQ) and/or low dose glucocorticoids (GCS) (<20mg/day), high dose GCS (>20mg/day) and use of second-line therapies (immunosuppressive agents, intravenous immunoglobulins [IVIG] and/or rituximab [RTX]). RESULTS: There were 1048 (94%) women and 72 (6%) men , with a mean age at diagnosis of 54 years. The main drug-based therapeutic approaches for systemic pSS during follow-up were HCQ in 282 (25%) patients, GCS in 475 (42%, at doses >20mg/day in 255-23%), immunosuppressive agents in 148 (13%), IVIG in 25 (2%) and RTX in 35 (3%) patients. HCQ was associated with a lower risk of death (adjusted HR of 0.57, 95% 0.34-0.95). We classified 16 (7%) of the 255 patients treated with >20mg GCS and 21/148 (14%) treated with immunosuppressive agents as patients inadequately treated, mainly associated with articular involvement of low/moderate activity. CONCLUSION: The management of pSS should be organ-specific, using low dose GCS in patients with moderate systemic activity, limiting the use of high dose GCS and second-line therapies to refractory or potentially severe scenarios. The use of systemic therapies for dryness, chronic pain or fatigue is not warranted.

Undetectable HCV-RNA at treatment-week 8 results in high-sustained virological response in HCV G1 treatment-experienced patients with advanced liver disease: the International Italian/Spanish Boceprevir/Peginterferon/Ribavirin Name Patients Program.

In many countries, first-generation protease inhibitors (PIs)/peginterferon/ribavirin (P/R) still represent the only treatment option for HCV-infected patients. Subjects with advanced disease and previous failure to P/R urgently need therapy, but they are under-represented in clinical trials. All treatment-experienced F3/4 Metavir patients who received boceprevir (BOC)+P/R in the Italian-Spanish Name Patient Program have been included in this study. Multivariate logistic regression analysis (MLR) was used to identify baseline and on-treatment predictors of SVR and adverse events (AEs). Four hundred and sixteen patients, mean age 57.7 (range 25-78 years), 70% males, 69.5% (289/416) F4, 14% (41/289) Child-Pugh class A6, 24% (70/289) with varices and 42% (173/416) prior null responders to P/R, were analysed. Overall, SVR rate (all 381 patients who received one dose of BOC) was 49%, (58% in F3, 45% in F4, 61% in relapsers, 51% in partial, 38% in null responders, and 72% in subjects with undetectable HCV-RNA at treatment-week (TW)8. Among patients with TW8 HCV-RNA ≥ 1000 IU/L, SVR was 8% (negative predictive value = 92%). Death occurred in 3 (0.8%) patients, while decompensation and infections were observed in 2.9% and 11%, respectively. At MLR, SVR predictors were TW4 HCV-RNA ≥ 1log10 -decline from baseline, undetectable TW8 HCV-RNA, prior relapse, albumin levels ≥3.5 g/dL and platelet counts ≥100 000/µL. Metavir F4, Child-Pugh A6, albumin, platelets, age and female gender were associated with serious and haematological AEs. Among treatment-experienced patients with advanced liver disease eligible for IFN-based therapy, TW8 HCV-RNA characterised the subset with either high or poor likelihood of achieving SVR. Using TW8 HCV-RNA as a futility rule, BOC/P/R appears to have a favourable benefit-risk profile.

Annular erythema in primary Sjogren's syndrome: description of 43 non-Asian cases.

OBJECTIVE: The objective of this paper is to evaluate the prevalence and characterize the main epidemiological, clinical and immunological features of annular erythema (AE) in non-Asian patients with primary Sjögren's syndrome (SS). METHODS: We carried out a retrospective study searching for AE in 377 Spanish patients with primary SS fulfilling the 2002 American-European criteria. In addition, we searched PubMed (1994-2012) using the MeSH terms "annular erythema" and "primary Sjögren's syndrome" for additional cases. All cases with AE reported in patients with SS associated with systemic lupus erythematosus were excluded. RESULTS: In our Spanish cohort, we found 35 (9%) patients diagnosed with AE. All were white females, with a mean age of 47 years at diagnosis of AE. AE preceded diagnosis of SS in 27 (77%) patients. Cutaneous AE lesions involved principally the face and upper extremities. All patients reported photosensitivity, with cutaneous flares being reported during the warmest months in 93% of patients. Immunological markers consisted of anti-Ro/La antibodies in 31 (89%) patients. In the literature search, we identified eight additional non-Asian patients with primary SS diagnosed with AE. In comparison with 52 Asian patients, the 43 non-Asian patients with AE related to primary SS were more frequently women (100% vs 78%, p=0.008), and cutaneous lesions were less frequently reported in the face (55% vs 81%, p=0.045) and more frequently in the neck (40% vs 14%, p=0.041). Immunologically, non-Asian patients had a lower frequency of anti-Ro antibodies and a higher frequency of negative Ro/La antibodies, although the differences were not statistically significant. CONCLUSION: AE is not an exclusive cutaneous feature of Asian patients with primary SS. In addition to the characteristic cutaneous expression, AE has a very specific clinical and immunological profile: often presenting before the fulfillment of SS criteria, overwhelmingly associated with anti-Ro antibodies but weakly associated with other immunological markers and the main systemic SS-related features.

White matter abnormalities in primary Sjögren syndrome.

OBJECTIVE: To describe the main characteristics of patients with primary Sjögren syndrome (SS) and white matter abnormalities (WMA) seen by a specialist SS unit. METHODS: The study cohort included 321 consecutive patients fulfilling the 2002 classification criteria for primary SS. We retrospectively analyzed the results of neuroimaging studies performed in patients who presented with neurological symptoms. Patients were further evaluated by three neurologists to determine fulfillment of the McDonald criteria for the diagnosis of multiple sclerosis (MS). RESULTS: Fifty-one (16%) patients had at least one neuroimaging study, and 25 of these had WMA. WMA were classified as vascular pathological changes in 21 patients: 10 had multiple small focal lesions, 7 had beginning confluence of lesions and 4 had diffuse involvement of the entire region. WMA were classified as inflammatory/demyelinating lesions (MS-like) in 4 patients who fulfilled the MRI Barkhof criteria. Patients with inflammatory/demyelinating lesions were younger (53.7 vs. 73.5 years, P = 0.001) and had a lower frequency of hypertension (25% vs. 86%, P = 0.031) and altered glomerular filtration rate (0% vs. 70%, P = 0.047) in comparison with patients with vascular lesions. The multivariate age-sex adjusted model including the seven variables which were statistically significant in the univariate analysis (antimalarial therapy, leukopenia, anti-La/SSB antibodies, diabetes, hypertension, metabolic syndrome and HDL-c levels) identified hypertension (P = 0.019) and HDL-c levels (P = 0.032) as independent predictors of WMA in primary SS patients. CONCLUSION: Neuroimaging studies disclosed WMA in 49% of patients with primary SS and suspected neurological involvement. WMA were identified as vascular pathological changes in 80% of the patients, and hypertension and HDL-c levels as predictive factors for this association.

[Pegylated interferon and ribavirin associated retinopathy in patients with hepatitis C]. / Retinopatía asociada a interferón pegilado y ribavirina en pacientes con hepatitis C.

CASE REPORT: We describe two patients with chronic hepatitis C, treated with pegylated interferon and ribavirin, who developed multiple cotton-wool spots in the retina of both eyes. The ocular findings were identified as pegylated interferon associated retinopathy, and in one case spontaneously resolved and in the other after the treatment was withdrawn. DISCUSSION: Interferon is an immunomodulating cytokine used as a first line treatment of hepatitis C. Numerous adverse effects have been reported, but ocular ones are less known. We believe that periodic ophthalmological examinations during this treatment are required in order to detect these complications, which can be serious.

Retinopatía asociada a interferón pegilado y ribavirina en pacientes con hepatitis C / Pegylated interferon and ribavirin associated retinopathy in patients with hepatitis C

Caso clínicoSe describen dos pacientes portadores de hepatitis C y tratados con interferón pegilado y ribavirina que desarrollaron múltiples exudados algodonosos en la retina de ambos ojos. El cuadro oftalmológico fue etiquetado de retinopatía asociada a interferón pegilado y en un caso cedió espontáneamente y en otro tras su retirada.DiscusiónEl interferón es una citocina inmunomoduladora utilizada como primera línea de tratamiento de la hepatitis C. Numerosos efectos adversos han sido descritos, pero los oculares son menos conocidos. Consideramos necesario el seguimiento oftalmológico sistemático durante el tratamiento con interferón por la posibilidad de detectar dichas complicaciones, algunas graves(AU)

Case reportWe describe two patients with chronic hepatitis C, treated with pegylated interferon and ribavirin, who developed multiple cotton-wool spots in the retina of both eyes. The ocular findings were identified as pegylated interferon associated retinopathy, and in one case spontaneously resolved and in the other after the treatment was withdrawn.DiscussionInterferon is an immunomodulating cytokine used as a first line treatment of hepatitis C. Numerous adverse effects have been reported, but ocular ones are less known. We believe that periodic ophthalmological examinations during this treatment are required in order to detect these complications, which can be serious(AU)

Cardiovascular risk factors in primary Sjögren's syndrome: a case-control study in 624 patients.

We evaluated the prevalence and clinical significance of cardiovascular risk factors in a large series of patients with primary Sjögren's syndrome (SS), focusing on the possible association with clinical and immunological SS features, the therapies administered, and the impact on cardiovascular disease. The study cohort included 312 patients fulfilling the 2002 classification criteria for primary SS, consecutively evaluated and followed in our department between 1984 and 2009. The control group consisted of 312 age- and sex-matched patients without systemic autoimmune diseases followed during the study period in a primary care centre. In comparison with the age- and sex-matched control group, patients with primary SS showed a higher frequency of diabetes mellitus (27% versus 13%, p < 0.001) and hypertriglyceridaemia (22% versus 15%, p = 0.023), and a lower frequency of hypertension (30% versus 46%, p < 0.001) and smoking (19% versus 31%, p < 0.001). The adjusted, multivariate analysis showed that SS patients with at least three cardiovascular risk factors had a higher mean age at SS diagnosis (p < 0.001), a higher frequency of liver involvement (p = 0.01) and central nervous system involvement (p = 0.001), higher mean levels of C-reactive protein (CRP, p = 0.001), a lower percentage of circulating gamma globulins (p = 0.001), and had received corticosteroids more frequently (p = 0.003) in comparison with patients without cardiovascular risk factors. Patients who had received corticosteroids showed a higher frequency of hypertension (37% versus 25%, p = 0.032), diabetes mellitus (37% versus 21%, p = 0.002), and hypertriglyceridaemia (33% versus 15%, p < 0.001). Patients with primary SS showed a twofold higher prevalence of diabetes mellitus and a 1.5-fold higher prevalence of hypertriglyceridaemia in comparison with primary care patients. Corticosteroid use was closely associated with cardiovascular risk factors. These results suggest that cardiovascular risk factors should be taken into account in the management of patients with primary SS and show the importance of recognizing and controlling both traditional and SS-related modifiable risk factors.

Off-label use of rituximab in 196 patients with severe, refractory systemic autoimmune diseases.

OBJECTIVES: To analyse the safety and efficacy of the off-label use of rituximab in patients with severe, refractory systemic autoimmune diseases. METHODS: In 2006, the Study Group on Autoimmune Diseases of the Spanish Society of Internal Medicine created the BIOGEAS project, a multicenter study devoted to collecting data on the use of biological agents in adult patients with systemic autoimmune diseases refractory to standard therapies (failure of at least two immunosuppressive agents). RESULTS: One hundred and ninety-six patients with systemic autoimmune diseases treated with rituximab have been included in the Registry (158 women and 38 men, mean age 43 years). Systemic autoimmune diseases included systemic lupus erythematosus (107 cases), inflammatory myopathies (20 cases), ANCA-related vasculitides (19 cases), Sjögren's syndrome (15 cases) and other diseases (35 cases). A therapeutic response was evaluable in 194 cases: 99 (51%) achieved a complete response, 51 (26%) a partial response and 44 (23%) were classified as non-responders. After a mean follow-up of 27.56+/-1.32 months, 44 (29%) out of the 150 responders patients relapsed. There were 40 adverse events reported in 33 (16%) of the 196 patients. The most frequent adverse events were infections, with 24 episodes being described in 19 patients. Thirteen (7%) patients died, mainly due to disease progression (7 cases) and infection (3 cases). CONCLUSIONS: Although not yet licensed for this use, rituximab is currently used to treat severe, refractory systemic autoimmune diseases, with the most favourable results being observed in Sjögren's syndrome, inflammatory myopathies, systemic lupus erythematosus and cryoglobulinemia.