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This was an open-label, multicenter, phase-1 study to evaluate the drug interaction between steady-state ibrutinib and moderate (erythromycin) and strong (voriconazole) CYP3A inhibitors in patients with B-cell malignancies and to confirm dosing recommendations. During cycle 1, patients received oral ibrutinib 560 mg qd alone (Days 1-4 and 14-18), and ibrutinib 140 mg (Days 5-13; 19-27) plus erythromycin 500 mg tid (Days 5-11) and voriconazole 200 mg bid (Days 19-25). Twenty-six patients (median [range] age: 64.5 [50-88] years) were enrolled. Geometric mean ratio (90% confidence intervals) after co-administration of ibrutinib 140 mg with erythromycin and voriconazole was 74.7 (53.97-103.51) and 143.3 (107.77-190.42), respectively, versus ibrutinib 560 mg alone. The most common (≥20%) adverse events were diarrhea (27%) and neutropenia (23%). The results demonstrate that ibrutinib 140 mg with voriconazole or erythromycin provides exposure within the clinical range for patients with B-cell malignancies.

The Grupo Español de Linfomas y Trasplantes de Médula Ósea International Prognostic Index (GELTAMO-IPI) stratifies four risk groups in diffuse large B cell lymphoma (DLBCL) patients treated with immunochaemotherapy: low (LR), low-intermediate (LIR), high-intermediate (HIR), and high (HR). The present study explores the effect of GELTAMO-IPI in the DLBCL subtypes defined by the immunohistochaemistry-based Hans algorithm, Germinal Centre B (GCB) and non-GCB. A multivariate Cox regression model including GELTAMO-IPI risk groups, cell of origin (COO) subtypes and their product was developed to evaluate interaction between the two variables. The COO subtype was available in 839 patients (380 GCB; 459 non-GCB) and both the GELTAMO-IPI and the COO subtype in 780 (353 GCB; 427 non-GCB). There were no differences in 5-year overall survival (OS) between the two subtypes. The Cox model revealed interaction between the GELTAMO-IPI risk groups and the COO subtypes (P = 0·005), indicating that GELTAMO-IPI has a different effect in the two subtypes. Three risk groups were stratified in both COO subtypes: in the GCB subtype, LR, LIR and the combined HIR+HR had 5-year OS of 100%, 75% and 52%, respectively. In the non-GCB subtype, LR, the combined LIR+HIR and HR had a 5-year OS of, 97%, 82% and 35% respectively. GELTAMO-IPI identifies a genuine poor outcome group of patients in the DLBCL non-GCB subtype., (© 2018 British Society for Haematology and John Wiley & Sons Ltd.)

The means of optimally managing very elderly patients with diffuse large B-cell lymphoma (DLBCL) has not been established. We retrospectively analyzed 252 patients aged 80-100 years, diagnosed with DLBCL or grade 3B follicular lymphoma, treated in 19 hospitals from the GELTAMO group. Primary objective was to analyze the influence of the type of treatment and comorbidity scales on progression-free survival (PFS) and overall survival (OS). One hundred sixty-three patients (63%) were treated with chemotherapy that included anthracyclines and/or rituximab, whereas 15% received no chemotherapeutic treatment. With a median follow-up of 44 months, median PFS and OS were 9.5 and 12.5 months, respectively. In an analysis restricted to the 205 patients treated with any kind of chemotherapy, comorbidity scales did not influence the choice of treatment type significantly. Independent factors associated with better PFS and OS were: age < 86 years, cumulative illness rating scale (CIRS) score < 6, intermediate risk (1-2) R-IPI, and treatment with R-CHOP at full or reduced doses. We developed a prognostic model based on the multivariate analysis of the 108 patients treated with R-CHOP-like: median OS was 45 vs. 12 months (P = .001), respectively, for patients with 0-1 vs. 2-3 risk factors (age > 85 years, R-IPI 3-5 or CIRS > 5). In conclusion, treatment with R-CHOP-like is associated with good survival in a significant proportion of patients. We have developed a simple prognostic model that may aid the selection patients who could benefit from a curative treatment, although it needs to be validated in larger series., (© 2018 Wiley Periodicals, Inc.)

Novel physical properties appear when the size of a superconductor is reduced to the nanoscale, in the range of its superconducting coherence length (ξ 0 ). Such nanosuperconductors are being investigated for potential applications in nanoelectronics and quantum computing. The design of three-dimensional nanosuperconductors allows one to conceive novel schemes for such applications. Here, we report for the first time the use of a He + focused-ion-beam-microscope in combination with the W(CO) 6 precursor to grow three-dimensional superconducting hollow nanowires as small as 32 nm in diameter and with an aspect ratio (length/diameter) of as much as 200. Such extreme resolution is achieved by using a small He + beam spot of 1 nm for the growth of the nanowires. As shown by transmission electron microscopy, they display grains of large size fitting with face-centered cubic WC 1-x phase. The nanowires, which are grown vertically to the substrate, are felled on the substrate by means of a nanomanipulator for their electrical characterization. They become superconducting at 6.4 K and show large critical magnetic field and critical current density resulting from their quasi-one-dimensional superconducting character. These results pave the way for future nanoelectronic devices based on three-dimensional nanosuperconductors.

The implementation of three-dimensional (3D) nano-objects as building blocks for the next generation of electro-mechanical, memory and sensing nano-devices is at the forefront of technology. The direct writing of functional 3D nanostructures is made feasible by using a method based on focused ion beam induced deposition (FIBID). We use this technique to grow horizontally suspended tungsten nanowires and then study their nano-mechanical properties by three-point bending method with atomic force microscopy. These measurements reveal that these nanowires exhibit a yield strength up to 12 times higher than that of the bulk tungsten, and near the theoretical value of 0.1 times the Young's modulus (E). We find a size dependence of E that is adequately described by a core-shell model, which has been confirmed by transmission electron microscopy and compositional analysis at the nanoscale. Additionally, we show that experimental resonance frequencies of suspended nanowires (in the MHz range) are in good agreement with theoretical values. These extraordinary mechanical properties are key to designing electro-mechanically robust nanodevices based on FIBID tungsten nanowires.

Aims: The aim of this systematic review and meta-analysis is to synthesize the available evidence in scientific papers of smokefree legislation effects on respiratory diseases and sensory and respiratory symptoms (cough, phlegm, red eyes, runny nose) among all populations., Materials and Methods: Systematic review and meta-analysis were carried out. A search between January 1995 and February 2015 was performed in PubMed, EMBASE, Cochrane Library, Scopus, Web of Science, and Google Scholar databases. Inclusion criteria were: 1) original scientific studies about smokefree legislation, 2) Data before and after legislation were collected, and 3) Impact on respiratory and sensory outcomes were assessed. Paired reviewers independently carried out the screening of titles and abstracts, data extraction from full-text articles, and methodological quality assessment., Results: A total number of 1606 papers were identified. 50 papers were selected, 26 were related to symptoms (23 concerned workers). Most outcomes presented significant decreases in the percentage of people suffering from them, especially in locations with comprehensive measures and during the immediate post-ban period (within the first six months). Four (50%) of the papers concerning pulmonary function reported some significant improvement in expiratory parameters. Significant decreases were described in 13 of the 17 papers evaluating asthma hospital admissions, and there were fewer significant reductions in chronic obstructive pulmonary disease admissions (range 1-36%) than for asthma (5-31%). Six studies regarding different respiratory diseases showed discrepant results, and four papers about mortality reported significant declines in subgroups. Low bias risk was present in 23 (46%) of the studies., Conclusions: Smokefree legislation appears to improve respiratory and sensory symptoms at short term in workers (the overall effect being greater in comprehensive smokefree legislation in sensory symptoms) and, to a lesser degree, rates of hospitalization for asthma.

Cutaneous manifestations of Waldenström macroglobulinemia (WM) may occur because of several mechanisms, the least common being direct skin infiltration by neoplastic cells. We report a case of patient that after 4-year history of indolent WM developed skin infiltration by lymphoplasmacytoid cells in the form of a small, mildly indurated plaque on the anterior chest. MYD88 L265P mutation was detected both in the previous bone marrow biopsy and in the cutaneous lesion. We review the impact of this new genetic tool in the diagnosis and treatment of lymphoplasmacytic proliferations., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The study included 1848 diffuse large B-cell lymphoma (DLBCL)patients treated with chemotherapy/rituximab. The aims were to validate the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) and explore the effect of adding high Beta-2 microglobulin (β2M), primary extranodal presentation and intense treatment to the NCCN-IPI variables in order to develop an improved index. Comparing survival curves, NCCN-IPI discriminated better than IPI, separating four risk groups with 5-year overall survival rates of 93%, 83%, 67% and 49%, but failing to identify a true high-risk population. For the second aim the series was split into training and validation cohorts: in the former the multivariate model identified age, lactate dehydrogenase, Eastern Cooperative Oncology Group performance status, Stage III-IV, and β2M as independently significant, whereas the NCCN-IPI-selected extranodal sites, primary extranodal presentation and intense treatments were not. These results were confirmed in the validation cohort. The Grupo Español de Linfomas/Trasplante de Médula ósea (GELTAMO)-IPI developed here, with 7 points, significantly separated four risk groups (0, 1-3, 4 or ≥5 points) with 11%, 58%, 17% and 14% of patients, and 5-year overall survival rates of 93%, 79%, 66% and 39%, respectively. In the comparison GELTAMO IPI discriminated better than the NCCN-IPI. In conclusion, GELTAMO-IPI is more accurate than the NCCN-IPI and has statistical and practical advantages in that the better discrimination identifies an authentic high-risk group and is not influenced by primary extranodal presentation or treatments of different intensity., (© 2017 John Wiley & Sons Ltd.)

Ibrutinib has emerged as a promising therapy for patients with chronic lymphocytic leukemia (CLL) who are nonresponsive to standard therapies. The refractory state of monocytes and T-cell exhaustion in patients with CLL could explain the morbidity and mortality reported in these patients. We studied the effect of ibrutinib on the immune response of four relapsed patients with CLL during the first treatment cycle. We observed the ability to recover the standard response against bacterial stimulus in CD14 + cells, improving levels of phospho-Erk1/2 and antigen presentation. Meanwhile, ibrutinib drove Th1-selective pressure in T lymphocytes, thus, reducing the PD-1 and PDL-1 expression. Our data suggest the impact of BTK inhibition along with immunomodulation on the innate immune response and a switch to the specific adaptive immune response, which might help to decrease infectious complications. The potential effect of ibrutinib on CLL patient outcomes is worthy of further study, because infections could be reduced with the use of ibrutinib.

To increase the efficiency of current electronics, a specific challenge for the next generation of memory, sensing and logic devices is to find suitable strategies to move from two- to three-dimensional (3D) architectures. However, the creation of real 3D nano-objects is not trivial. Emerging non-conventional nanofabrication tools are required for this purpose. One attractive method is focused-electron-beam induced deposition (FEBID), a direct-write process of 3D nano-objects. Here, we grow 3D iron and cobalt nanopillars by FEBID using diiron nonacarbonyl Fe2(CO)9, and dicobalt octacarbonyl Co2(CO)8, respectively, as starting materials. In addition, we systematically study the composition of these nanopillars at the sub-nanometer scale by atom probe tomography, explicitly mapping the homogeneity of the radial and longitudinal composition distributions. We show a way of fabricating high-purity 3D vertical nanostructures of ∼50 nm in diameter and a few micrometers in length. Our results suggest that the purity of such 3D nanoelements (above 90 at% Fe and above 95 at% Co) is directly linked to their growth regime, in which the selected deposition conditions are crucial for the final quality of the nanostructure. Moreover, we demonstrate that FEBID and the proposed characterization technique not only allow for growth and chemical analysis of single-element structures, but also offers a new way to directly study 3D core-shell architectures. This straightforward concept could establish a promising route to the design of 3D elements for future nano-electronic devices.

NK/T-cell lymphomas are a group of clonal proliferations of NK- or, rarely, T-cell types and have peculiar clinicopathologic features. Most common site of involvement is the upper aerodigestive tract (nasal cavity, nasopharynx, paranasal sinuses, and palate). Association of autoimmune paraneoplastic disorders with NK/T-cell lymphomas is not well studied. Our patient was diagnosed with NK/T-cell lymphoma stage IV with skin involvement and treated frontline with CHOEP regimen. While he was under treatment, two immune complications presented: anterior uveitis of autoimmune origin refractory to steroids and myositis in lower limbs muscles. Autologous transplantation was rejected due to confirmed early relapse after first-line treatment, and the patient received second-line treatment according to the SMILE scheme, reaching complete response after four cycles. The patient underwent allogeneic transplantation and at the time of manuscript preparation is alive despite multiple complications. The disease should be suspected in patients with rhinitis or recurrent sinusitis, and early biopsy is recommended for all patients to avoid a delay in diagnosis. Our patient also presented symptoms of disease progression after first-line treatment, representing a paraneoplastic process, a very rare phenomenon in T-type lymphomas. This case is novel for the appearance of an inflammatory myositis, a histologically verified paraneoplastic phenomenon that responded to treatment for lymphoma.

Introduction: Higher morbidity caused by smoking-related diseases could increase health costs. We analyzed differences in the use of healthcare resources, healthcare costs and days of work absenteeism among smokers and non-smokers., Methods: Cross-sectional study in smokers and non-smokers, aged between 45 and 74 years, from one urban health area. The variables studied were: age, sex, alcohol intake, physical activity, obesity, diseases, attendance at primary care clinics and hospital emergency rooms, days of hospitalization, prescription drug consumption and work absenteeism (in days). Annual cost according to the unit cost of each service (direct costs), and indirect costs according to the number of days missed from work was calculated. Crude and adjusted risks were calculated using logistic regression., Results: Five hundred patients were included: 50% were smokers, 74% (372) men and 26% (128) women. Smokers used more healthcare resources, consumed more prescription drugs and had more days off work than non-smokers. Respective direct and indirect costs in smokers were 848.64 euros (IQ 25-75: 332.65-1517.10) and 2253.90 euros (IQ 25-75: 1024.50-13113.60), and in non-smokers were 474.71 euros (IQ 25-75: 172.88-979.59) and 1434.30 euros (IQ 25-75: 614.70-4712.70). The likelihood of generating high healthcare costs was more than double for smokers (OR=2.14; 95% CI: 1.44-3.19)., Conclusion: More investment in programs for the prevention and treatment of smoking, as a health policy priority, could help to reduce the health and social costs of smoking., (Copyright © 2015 SEPAR. Published by Elsevier Espana. All rights reserved.)

Iron nanostructures grown by focused electron beam induced deposition (FEBID) are promising for applications in magnetic sensing, storage and logic. Such applications require a precise design and determination of the coercive field (H C), which depends on the shape of the nanostructure. In the present work, we have used the Fe2(CO)9 precursor to grow iron nanowires by FEBID in the thickness range from 10 to 45 nm and width range from 50 to 500 nm. These nanowires exhibit an Fe content between 80 and 85%, thus giving a high ferromagnetic signal. Magneto-optical Kerr characterization indicates that H C decreases for increasing thickness and width, providing a route to control the magnetization reversal field through the modification of the nanowire dimensions. Transmission electron microscopy experiments indicate that these wires have a bell-type shape with a surface oxide layer of about 5 nm. Such features are decisive in the actual value of H C as micromagnetic simulations demonstrate. These results will help to make appropriate designs of magnetic nanowires grown by FEBID.

Infections are a significant cause of morbidity and mortality in patients with chronic lymphocytic leukemia (CLL). The pathogenesis of infections is multifactorial and includes hypogammaglobulinemia, conventional therapy with alkylating drugs, and recently, purine analogs and mAb-associated T cells. Patients without these risk factors also suffer from infections, although the mechanism remains unknown. In a cohort of 70 patients with CLL, we demonstrated that their monocytes were locked into a refractory state and were unable to mount a classic inflammatory response to pathogens. In addition, they exhibited the primary features of endotoxin tolerance, including low cytokine production, high phagocytic activity, and impaired Ag presentation. The involvement of miR-146a in this phenomenon was suspected. We found miR-146a target genes, such as IRAK1 and TRAF6, were manifestly downregulated. Our study provides a new explanation for infections in patients with CLL and describes a cross-tolerance between endotoxins and tumors., (Copyright © 2015 by The American Association of Immunologists, Inc.)

The electronic cigarette (e-cig) is a device with a conventional cigarette shape that releases a determined dose of nicotine vapour through an electronic heating process. The nicotine cartridges vary significantly in the amount of nicotine released, even within the same brand. Not all brands admit that they contain nicotine, but this is detected in the majority of units analysed. The e-cig usually contains a propellant, such as propylene glycol, which is a lung irritant. The short-term respiratory effect of the vapour of an e-cig is similar to that caused by the smoke of a cigarette, and is a cause of broncho-restriction. The majority of brands contain glycerine and at least one case of lipoid pneumonia has been detected due to this substance. Many brands contain traces of N-nitrosamines, heavy metals, and other products that are found in conventional cigarette smoke, but in a much higher proportion. There is currently no scientific evidence available that shows it is an effective device for quitting smoking, thus it should not be pro-actively recommended for this purpose, and may interfere with the use of demonstrated scientific evidence-based treatments for quitting smoking. It may have an undesirable effect on promoting the starting of smoking in adolescents or keeping adult smokers consuming nicotine and on gestural dependency. The toxicity of the vapour is not well known, but it is known that they are not innocuous, thus they should not be used in closed public spaces., (Copyright © 2014 Elsevier España, S.L. All rights reserved.)

One of the main features of any lithography technique is its resolution, generally maximized for a single isolated object. However, in most cases, functional devices call for highly dense arrays of nanostructures, the fabrication of which is generally challenging. Here, we show the growth of arrays of densely packed isolated nanowires based on the use of focused beam induced deposition plus Ar(+) milling. The growth strategy presented herein allows the creation of films showing thickness modulation with periodicity determined by the beam scan pitch. The subsequent Ar(+) milling translates such modulation into an array of isolated nanowires. This approach has been applied to grow arrays of W-based nanowires by focused ion beam induced deposition and Co nanowires by focused electron beam induced deposition, achieving linear densities up to 2.5 × 10(7) nanowires/cm (one nanowire every 40 nm). These results open the route for specific applications in nanomagnetism, nanosuperconductivity, and nanophotonics, where arrays of densely packed isolated nanowires grown by focused beam deposition are required.

Background and Aims: The fundamental mechanisms involved in the genesis and progression of heart failure are not clearly understood. The present study was conducted to analyze the cardiac mitochondrial involvement in heart failure, the possible parallelism between cardiac and skeletal muscle and if there is a link between clinical symptoms and mitochondrial damage., Methods: Left ventricle and pectoral biopsies were obtained from patients with heart failure (n: 21) and patients with inter-auricular communication as the unique diagnosis for surgery (n: 6). Mitochondria were isolated from these tissues and studied through electron microscopy, spectrophotometry to measure the activity of respiratory complex III and immunohistochemistry to determine the presence of reactive oxygen species., Results: More than 90% of cardiac and skeletal muscle mitochondria presented structural and functional alterations in relation to an increment in the reactive oxygen species production, even in patients without the presence of any clinical Framingham criteria., Conclusions: We demonstrated some parallelism between cardiac and skeletal muscle mitochondrial alterations in patients with heart failure and that these alterations begin before the major clinical Framingham criteria are installed, pointing to mitochondria as one of the possibly responsible factors for the evolution of cardiac disease., (Copyright © 2014 IMSS. Published by Elsevier Inc. All rights reserved.)

Applications based on the movement of domain walls (DWs) in magnetic nanowires (NWs) require a good DW conduit behavior, i.e. a significant difference between DW nucleation and propagation fields. In this work, we have systematically studied how this property evolves in cobalt NWs grown by focused electron beam induced deposition (FEBID) as a function of global gallium irradiation, for irradiation doses up to 1.24 × 10(17) ions cm(-2). Whereas for high doses the DW conduit is lost, below 6.42 × 10(15) ions cm(-2) the difference between the two fields increases with irradiation, becoming up to ∼9 times larger than for non-irradiated wires, due to a strong increase in the nucleation field, while the propagation field remains approximately constant. This behavior stems from two effects. The first effect is a decrease in the magnetic volume of the parasitic halo around the NW, typically present in FEBID nanostructures, leading to the disappearance of weak nucleation centers. The second effect is the formation of a 20 nm outer shell with Co crystals about twice the size of those forming the NW core, causing a net increase of the local magnetocrystalline anisotropy. The results presented here are important for the potential use of magnetic NWs grown by FEBID in DW-based devices, and might also be of interest for magnetic NWs fabricated by other techniques.

Objective: To evaluate pollution by second-hand smoke in a sample of hospitality venues before and after the implementation of smoke-free legislation., Methods: A cross sectional, before-after study was conducted in 2008 and 2011 after the total ban. A SidePack Aerosol monitor was used both inside and outside the hospitality venues to measure fine breathable particles (PM2.5). A total of 43 places with pre- and post-legislation measurements were included., Results: The median indoor pollution in hospitality venues was 204.2μg/m(3) in 2008 and 18.82μg/m(3) in 2011; the average outdoor PM2.5 concentration was 47.04μg/m(3) in 2008 and 18.82μg/m(3) in 2011. Pollution was higher in bars and cafeterias, followed by pubs and discos. Before the law was implemented, pollution was 4.34 times higher indoors than outdoors; in 2011 the average indoor PM2.5 concentration decreased by 90.88%., Conclusions: Only a complete ban is able to protect workers and customers against the health risks of second-hand smoke exposure., (Copyright © 2011 SESPAS. Published by Elsevier Espana. All rights reserved.)

A superconductor in a magnetic field acquires a finite electrical resistance caused by vortex motion. A quest to immobilize vortices and recover zero resistance at high fields made intense studies of vortex pinning one of the mainstreams of superconducting research. Yet, the decades of efforts resulted in a realization that even promising nanostructures, utilizing vortex matching, cannot withstand high vortex density at large magnetic fields. Here, we report a giant reentrance of vortex pinning induced by increasing magnetic field in a W-based nanowire and a TiN-perforated film densely populated with vortices. We find an extended range of zero resistance with vortex motion arrested by self-induced collective traps. The latter emerge due to order parameter suppression by vortices confined in narrow constrictions by surface superconductivity. Our findings show that geometric restrictions can radically change magnetic properties of superconductors and reverse detrimental effects of magnetic field.

To present the strategies used by the tobacco industry to meet government regulatory measures of its products. To demonstrate the relationship between tobacco industry and the hospitality sector. Note that the arguments and strategies used routinely by the hospitality industry have been previously provided by the tobacco industry. Location of key documents by meta-search, links to declassified documents, specific websites of the tobacco and hospitality industry, news sources and published articles in health journals. This review reveals the close relationship between tobacco industry and hospitality sector. It highlights the strategies carried out by the tobacco industry, including strategic hoarding of information, public relations, lobbying, consultation program, smoker defence groups, building partnerships, intimidation and patronage. The arguments and strategies used by the hospitality industry to match point by point that used by the tobacco industry. These arguments are refutable from the point of view of public health as it is scientifically proven that totally smoke-free environments are the only way to protect non-smokers from tobacco smoke exposure and its harmful effects on health., (Copyright © 2011 Elsevier España, S.L. All rights reserved.)

Objectives: To assess the impact of the Law 42/2010, on the health measures on smoking, on the prevalence of the exposure to environmental tobacco smoke (ETS), the repercussions in frequently visited places, and support of the new legislation., Design: A before-after evaluation by comparing two cross-sectional studies the comparison of two transverse surveys., Place: Primary Care, Delicias district (115,446 inhabitants) of Zaragoza city, including the Delicias Sur, Delicias Norte, Bombarda and Univérsitas basic health districts., Participants: A total of 387 users in 2009, and 400 in 2011 with ages between 20 and 79 years old assigned to the participating Primary Care Centres., Main Measurements: Prevalences and mean exposure times, with their confidence intervals (CI). The differences were then calculated using the Chi-squared test and Analysis of Variance (ANOVA)., Results: The exposure prevalence to the ETS in 2011 was shown to be lower and statistically significant than that found before the implementation of the new legislative measure, falling from the 61.9% to the 40.5% (CI 95%=35.8-45.4%), with 61.5% of those polled being in favour of the new law (CI 95%=59.2-68.75), and 80.5% (79,08-86.44) mentioned still going to the same places with the same frequency., Conclusions: The impact has been favourable, decreasing the exposure by more than 20%, with this fall being more marked in the population that currently define themselves as non-smokers. There is population support for the new legislation. Finally, there has been no observed fall in the frequency of visits to the same places., (Copyright © 2011 Elsevier España, S.L. All rights reserved.)

Monocyte exposure to tumor cells induces a transient state in which these cells are refractory to further exposure to cancer. This phenomenon, termed "tumor tolerance", is characterized by a decreased production of proinflammatory cytokines in response to tumors. In the past, we found that this effect comprises IRAK-M up regulation and TLR4 and CD44 activation. Herein we have established a human model of tumor tolerance and have observed a marked down-regulation of MHCII molecules as well as the MHCII master regulator, CIITA, in monocytes/macrophages. These cells combine an impaired capability for antigen presentation with potent phagocytic activity and exhibit an M2-like phenotype. In addition circulating monocytes isolated from Chronic Lymphocytic Leukemia patients exhibited the same profile as tumor tolerant cells after tumor ex vivo exposition., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Extended-release (ER) paliperidone is an innovative atypical antipsychotic that allows minimal peak-to-through fluctuations with once-daily dosing., Objective: To evaluate effectiveness, safety and tolerability of flexible, once-daily doses of paliperidone ER (3-12 mg/day) in patients with schizophrenia from Argentina and Colombia who had previously failed treatment with other antipsychotic agents., Methods: The authors conducted a 6-month, open-label, prospective and multicentric study. Effectiveness was assessed with Positive and Negative Syndrome Scale (PANSS) and Personal and Social Performance scale (PSP). Other measures of effectiveness, safety and tolerability, were also conducted., Results: Paliperidone ER 3-12 mg/day improved Positive and Negative Syndrome Scale (PANSS) total scores (primary endpoint) from baseline to study end (p < 0,001). In the PANSS total score, the mean change from baseline (83, 9 units) to end point (53,7 units) was significant (p < 0,001). Flexible doses of paliperidone ER demonstrated a ≥20% reduction in the PANSS total score (p<0.001) in almost two-thirds of patients. PSP mean change from baseline (52 units) to end point (85 units) was significant (p < 0,001). Secondary effectiveness assessments, as well as safety and tolerability measures, demonstrated favourable results throughout the study., Conclusions: Flexible doses of paliperidone ER over 6 months were effective, safe and well tolerated in patients with schizophrenia from Argentina and Colombia., (Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.)

Scanning transmission x-ray microscopy (STXM) and magnetoresistance (MR) measurements are used to investigate the magnetic behavior of a nanoconstriction joining two micrometric electrodes (a pad and a wire). The reversal of the magnetization under variable external static magnetic fields is imaged. By means of a detailed analysis of the STXM images at the nanocontact area, the MR is calculated, based on diffusive anisotropic-MR. This MR agrees well with that obtained from electrical transport measurements, allowing a direct correlation between the MR signal and the magnetic reversal of the system. The magnetization behavior depends on the sample thickness and constriction dimensions. In 40 nm-thick samples, with 20 × 175 nm(2) contact areas, the magnetization at the two sides of the constriction forms a net angle of 90°, with a progressive evolution of the magnetization structure between the electrodes during switching. The MR in those cases has a more peaked shape than with 20 nm-thick electrodes and 10 × 80 nm(2) contact areas, where the magnetization forms 180° between them, with a wide domain wall pinned at the constriction. As a consequence of this configuration, a plateau in the MR is observed for about 20 Oe.

Nanolithography techniques in a scanning electron microscope/focused ion beam are very attractive tools for a number of synthetic processes, including the fabrication of ferromagnetic nano-objects, with potential applications in magnetic storage or magnetic sensing. One of the most versatile techniques is the focused electron beam induced deposition, an efficient method for the production of magnetic structures highly resolved at the nanometric scale. In this work, this method has been applied to the controlled growth of magnetic nanostructures using Co2(CO)8. The chemical and structural properties of these deposits have been studied by electron energy loss spectroscopy and high-resolution transmission electron microscopy at the nanometric scale. The obtained results allow us to correlate the chemical and structural properties with the functionality of these magnetic nanostructures.

We have successfully grown ultrasmall cobalt nanostructures (lateral size below 30 nm) by optimization of the growth conditions using focused electron-beam-induced deposition techniques. This direct-write nanolithography technique is thus shown to produce unprecedented resolution in the growth of magnetic nanostructures. The challenging magnetic characterization of such small structures is here carried out by means of electron holography techniques. Apart from growing ultranarrow nanowires, very small Hall sensors have been created and their large response has been unveiled.

Objective: This study assessed the treatment preferences among Latin-American psychiatrists for their bipolar disorder patients and if these preferences reflect the current guidelines., Methods: We designed a survey comprised of fourteen questions. All the questions were aimed at the treatment of bipolar I patients only. We distributed the survey by hand or e-mail to psychiatrists in eight different countries: Argentina, Brasil, Colombia, Costa Rica, Ecuador, México, Perú and Venezuela. Between May 2008 and June 2009, we were able to gather 1143 surveys., Results: As the initial choice of treatment for a bipolar patient who debuts with mania, 61.3% choose a combination of an atypical antipsychotic and a mood stabilizer. Lithium Carbonate (50%) was the first choice for a mood stabilizer in a manic episode. Olanzapine (55.4%) was the initial antipsychotic of choice for the treatment of acute mania. For the treatment of acute bipolar depression, 27% choose Lamotrigineas their first choice. Most of the psychiatrists (74.8%) prescribe antidepressants for the treatment of bipolar depression. For maintenance treatment of bipolar depression most psychiatrists first choice would be Lamotrigine (50.3%). Most of the psychiatrists (89.1%) prescribed two or more psychotropic drugs for the maintenance treatment of their bipolar patients., Conclusions: There were some similarities with the studies previously done in the US. It seems that for the most part the Latin-American psychiatrists don't strictly follow the literature guidelines that are published, but rather adapt the treatment to the specific case. More longitudinal studies of prescribing patterns in bipolar disorder are needed to corroborate these findings., (Copyright © 2011 SEP y SEPB. Published by Elsevier Espana. All rights reserved.)

Titanium is a relevant technological material due to its extraordinary mechanical and biocompatible properties, its nanopatterning being an increasingly important requirement in many applications. We report the successful nanopatterning of titanium by means of focused electron beam induced etching using XeF(2) as a precursor gas. Etch rates up to 1.25 × 10(-3) µm(3) s(-1) and minimum pattern sizes of 80 nm were obtained. Different etching parameters such as beam current, beam energy, dwell time and pixel spacing are systematically investigated, the etching process being optimized by decreasing both the beam current and the beam energy. The etching mechanism is investigated by transmission electron microscopy. Potential applications in nanotechnology are discussed.

Objective: To estimate the levels of small breathable suspended particles (PM(2.5)) as atmospheric markers of environmental tobacco smoke in catering establishments in Zaragoza, Spain., Material and Method: An observational study was conducted between October 2006 and April 2008 in various catering establishments in Zaragoza. A SidePack Aerosol Monitor (AM510 model) was used to sample and record the levels of breathable suspended particles (PM(2.5)) indoors and outdoors, and the following variables were collected: smoking policy (smoking allowed, completely banned, or partially banned with non-smoking sections, physically separated or not); percentage of smokers and presence of cigarette ends, ashtrays or smokers in non-smoking sections., Results: A total of 111 venues were sampled. The level of PM(2.5) was eight times higher in smoking venues than in non-smoking ones and also higher than outdoors. The correlation between the level of particles and percentage of smokers was 0.61 (P<.01). In the non-smoking sections without physical separation the level of particles was twice as much as outdoors and similar to physically separated smokers sections., Conclusion: Only a complete ban on smoking in all workplaces, including leisure venues, has been shown to have a positive effect on workers and customers health. The measurement of PM(2.5) can be a simple method to assess the presence of environmental tobacco smoke., (Copyright © 2010 SEPAR. Published by Elsevier Espana. All rights reserved.)

Objective: The aim of this study was to investigate the impact of self-rated stigma and functioning in patients with bipolar disorder in Latin-America., Methods: Two-hundred and forty-one participants with bipolar disorder were recruited from three Latin American countries (Argentina, Brazil, and Colombia). Functional impairment was assessed with the Functioning Assessment Short Test (FAST) and experiences with and impact of perceived stigma was evaluated using the Inventory of Stigmatizing Experiences (ISE)., Results: Higher scores of self-perceived stigma were correlated with lower scores of functioning. After multiple regression analysis, being on disability benefit, current mood symptoms and functioning were associated with self-perceived stigma., Conclusions: This is the first study to demonstrate an association between stigma and poor functioning in bipolar disorder. Possible implications of such findings for practitioners are discussed., Limitations: The main limitation of this study is that the Inventory of Stigmatizing Experiences has not yet been validated in a population of bipolar patients in our countries. The sample size and heterogeneous clinical subjects from different countries and cultures limit the generalization of the present findings., (Copyright © 2010 Elsevier B.V. All rights reserved.)

We study the behavior of bundles of superconducting vortices when increasing the magnetic field using scanning tunneling microscopy and spectroscopy at 100 mK. Pinning centers are given by features on the surface corrugation. We find strong net vortex motion in a bundle towards a well-defined direction. We observe continuous changes of the vortex arrangements, and identify small displacements, which stress and deform the vortex bundle, separated by larger rearrangements or avalanches, which release accumulated stress.

Background and Objective: This study estimates smoking-attributable mortality in Spain in 2006., Population and Method: Source data included 1) smoking prevalence in Spain; 2) deaths occurred in Spain; and 3) relative risks of mortality by tobacco-caused diseases drawn from the Cancer Prevention Study II. All data corresponded to individuals aged 35 years and older., Results: In 2006, 53,155 smoking-attributable deaths were estimated (14.7% of all deaths occurred in individuals≥35 years; 25.1% in men and 3.4% in women). Almost 90% (47,174) of these attributable deaths corresponded to men, and 11.3% (5,981) to women. The most frequent attributable deaths were: cancer (24,058), specially lung cancer (16,482), cardiovascular disease (17,560), specially ischemic heart disease (6,263) and stroke (4,283), and respiratory disease (11,537), specially chronic obstructive lung disease (9,886). Since 2001, a decrease in smoking-attributable mortality was observed in men and an increase in women., Conclusions: About one out of 7 deaths occurring annually in individuals≥35 years in Spain is attributable to smoking (one in 4 in men and one in 29 in women). Despite a decreasing trend in the number of smoking-attributable deaths over time (except in women, where they increase), the toll of estimated attributable deaths is still very high., (Copyright © 2010. Published by Elsevier Espana.)

We systematically study the effect of oxygen content on the magneto-transport and microstructure of Fe:O:C nanowires deposited by focused-electron-beam-induced (FEBID) deposition. The Fe/O ratio can be varied with an Fe content varying between ∼ 50 and 80 at.% with overall low C content (≈16 ± 3 at.%) by adding H(2)O during the deposition while keeping the beam parameters constant as measured by energy dispersive x-ray (EDX) spectroscopy. The room-temperature magnetic properties for deposits with an Fe content of 66-71 at.% are investigated using the magneto-optical Kerr effect (MOKE) and electric magneto-transport measurements. The nanostructure of the deposits is investigated through cross-sectional high-resolution transmission electron microscopy (HRTEM) imaging, allowing us to link the observed magneto-resistance and resistivity to the transport mechanism in the deposits. These results demonstrate that functional magnetic nanostructures can be created, paving the way for new magnetic or even spintronics devices.

Background: Risperidone long-acting injection (RLAI) has been shown to be efficacious, improve compliance, and increase long-term retention rate on therapy. The aim of this work was to determine the effect of RLAI on clinical outcome and hospitalization rate in patients with schizophrenia or schizoaffective disorder enrolled in the electronic Schizophrenia Treatment Adherence Registry in Latin America., Methods: Data were collected at baseline, retrospectively for the 12 months prior to baseline, and prospectively every three months for 24 months. Hospitalization prior to therapy was assessed by a retrospective chart review. Efficacy and functioning were evaluated using Clinical Global Impression of Illness Severity (CGI-S), Personal and Social Performance (PSP), and Global Assessment of Functioning (GAF) scores. Relapse and treatment were also registered., Results: Patients were recruited in Mexico (n = 53), Brazil (n = 11), and Colombia (n = 15). Sixty-five percent (n = 52) were male, and mean age was 32.9 years. Patients were classified as having schizophrenia (n = 73) or schizoaffective disorder (n = 6). The mean dose of RLAI at six months was 34.1 mg (standard deviation = 10.2 mg). The percentage of hospitalized patients before treatment was 28.2% and 5.1% at six months after initiating RLAI (P < 0.001). Significant changes were registered on CGI-S, GAF, and PSP scores., Conclusions: RLAI was associated with an improvement in clinical symptoms and functioning, and a greater reduction in hospitalization.

The silver-copper mixed oxide AgCuO(2) (also formulated as Ag(2)Cu(2)O(4)) possesses a peculiar electronic structure in which both Ag and Cu are partially oxidized, with the charge being delocalized among the three elements in the oxide. Accordingly, a quasi-metallic behavior should be expected for this oxide, and indeed bulk transport measurements show conductivity values that are orders of magnitude higher than for other members of this novel oxide family. The presence of silver makes thermal sintering an inadequate method to evaluate true conductivity, and thus such measurements were performed on low density pellets, giving an underestimated value for the conductivity. In the present work we present a new synthetic route for AgCuO(2) based on mild hydrothermal reactions that has yielded unprecedented large AgCuO(2) single-crystals well over 1 μm in size using temperatures as low as 88 °C. We have used a dual beam instrument to apply nanocontacts to those crystals, allowing the in situ measurement of transport properties of AgCuO(2) single crystals. The results show a linear relationship between applied current and measured voltage. The conductivity values obtained are 50 to 300 times higher than those obtained for bulk low density AgCuO(2) pellets, thus confirming the high conductivity of this oxide and therefore supporting the delocalized charge observed by spectroscopic techniques.