Very low level viraemia and risk of virological failure in treated HIV-1-infected patients.

OBJECTIVES: The aim of the study was to investigate whether very low level viraemia (VLLV) (20-50 HIV-1 RNA copies/mL) was associated with increased risk of virological failure (VF) as compared with persistent full suppression (< 20 copies/mL). METHODS: From the VACH Cohort database, we selected those patients who started antiretroviral therapy (ART) after January 1997 and who achieved effective viral suppression [two consecutive viral loads (VLs) < 50 copies/mL] followed by full suppression (at least one VL <20 copies/mL). We carried out survival analyses to investigate whether the occurrence of VLLV rather than maintaining full suppression at < 20 copies/mL was associated with virological failure (two consecutive VLs > 200 copies/mL or one VL > 200 copies/mL followed by a change of ART regimen, administrative censoring or loss to follow-up), adjusted for nadir CD4 cell count, sex, age, ethnicity, transmission group, type of ART and time on effective suppression at < 50 copies/mL. RESULTS: Of 21 480 patients who started ART, 13 674 (63.7%) achieved effective suppression at < 50 copies/mL, of whom 4289 (31.4%) further achieved full suppression at < 20 copies/mL after May 2009. A total of 2623 patients (61.1%) remained fully suppressed thereafter, while 1666 had one or more episodes of VL detection > 20 copies/mL (excluding virological failure). A total of 824 patients had VLLV after suppression at < 20 copies/mL. VLLV was not associated with virological failure as compared with persistent full suppression [hazard ratio (HR) 0.67; 95% confidence interval (CI) 0.44-1.00], independently of the number of blips recorded (from one to 18). CONCLUSIONS: In our population of HIV-infected patients on ART who achieved viral suppression at < 20 copies/mL, the risk of virological failure was no different for patients who remained fully suppressed compared with those who experienced subsequent episodes of VLLV.

A highly transmissible tuberculosis outbreak: the importance of bars.

The transmission of tuberculosis (TB) in bars is difficult to study. The objective was to describe a large TB outbreak in a company's bar and other leisure settings. A descriptive study of a TB outbreak was carried out. Contacts were studied in the index case's workplace bar (five circles of contacts) and other recreational areas (social network of three bars in the index case's neighbourhood). Chest X-rays were recommended to contacts with positive tuberculin skin tests (TST) (⩾5 mm). The risk of latent tuberculosis infection (LTBI) was determined using an adjusted odds ratio. The dose-response relationship was determined using the chi-square test for linear trend. We studied 316 contacts at the index case's workplace and detected five new cases of TB. The prevalence of LTBI was 57·9% (183/316) and was higher in the first circle, 96·0% (24/25), and lower in the fifth, 46·5% (20/43) (P < 0·0001). Among 58 contacts in the three neighbourhood bars, two TB cases were detected and the LTBI prevalence was 51·7% (30/58). Two children of one secondary TB company patient became ill. Bars may be transmission locations for TB and, as they are popular venues for social events, should be considered as potential areas of exposure.

Untangling surface oxygen exchange effects in YBa2Cu3O6+x thin films by electrical conductivity relaxation.

The kinetics of oxygen incorporation (in-diffusion process) and excorporation (out-diffusion process), in YBa2Cu3O6+x (YBCO) epitaxial thin films prepared using the chemical solution deposition (CSD) methodology by the trifluoroacetate route, was investigated by electrical conductivity relaxation measurements. We show that the oxygenation kinetics of YBCO films is limited by the surface exchange process of oxygen molecules prior to bulk diffusion into the films. The analysis of the temperature and oxygen partial pressure influence on the oxygenation kinetics has drawn a consistent picture of the oxygen surface exchange process enabling us to define the most likely rate determining step. We have also established a strategy to accelerate the oxygenation kinetics at low temperatures based on the catalytic influence of Ag coatings thus allowing us to decrease the oxygenation temperature in the YBCO thin films.

Removal from liver transplantation list of a hepatitis C virus-HIV co-infected patient after successful treatment with sofosbuvir and daclatasvir.

We present a human immunodeficiency virus-infected patient with severe decompensated hepatitis C virus-related cirrhosis awaiting liver transplantation (LT) who received a 24-week course of interferon/ribavirin-free antiviral treatment with sofosbuvir and daclatasvir on a compassionate basis. Rapid viral suppression was associated with progressive improvement of his liver function tests. The patient achieved a sustained virological response and concomitant clinical improvement, which prompted removal from the LT list 12 weeks after the end of treatment.

Ferromagnetic 1D oxide nanostructures grown from chemical solutions in confined geometries.

This review summarizes the capabilities and recent developments of nanoporous polymeric template systems directly supported on different substrates for the confined growth of epitaxial ferromagnetic complex oxide 1D nanostructures. In particular, we describe the versatility and potentiality of chemical solutions combined with track-etched polymers to synthesize (i) vertical polycrystalline La0.7Sr0.3MnO3 nanorods on top of single crystal perovskites, (ii) single crystalline manganese based octahedral molecular sieve (OMS) nanowires on silicon substrates, and (iii) the epitaxial directional single crystal OMS nanowires on top of fluorite-type substrates. The influence of the distinct growth parameters on the nanostructural evolution of the resulting nanostructures and their magnetic properties is further discussed in detail.

Chemical solution route to self-assembled epitaxial oxide nanostructures.

Self-assembly of oxides as a bottom-up approach to functional nanostructures goes beyond the conventional nanostructure formation based on lithographic techniques. Particularly, chemical solution deposition (CSD) is an ex situ growth approach very promising for high throughput nanofabrication at low cost. Whereas strain engineering as a strategy to define nanostructures with tight control of size, shape and orientation has been widely used in metals and semiconductors, it has been rarely explored in the emergent field of functional complex oxides. Here we will show that thermodynamic modeling can be very useful to understand the principles controlling the growth of oxide nanostructures by CSD, and some attractive kinetic features will also be presented. The methodology of strain engineering is applied in a high degree of detail to form different sorts of nanostructures (nanodots, nanowires) of the oxide CeO2 with fluorite structure which then is used as a model system to identify the principles controlling self-assembly and self-organization in CSD grown oxides. We also present, more briefly, the application of these ideas to other oxides such as manganites or BaZrO3. We will show that the nucleation and growth steps are essentially understood and manipulated while the kinetic phenomena underlying the evolution of the self-organized networks are still less widely explored, even if very appealing effects have been already observed. Overall, our investigation based on a CSD approach has opened a new strategy towards a general use of self-assembly and self-organization which can now be widely spread to many functional oxide materials.

Nanoscale strain-induced pair suppression as a vortex-pinning mechanism in high-temperature superconductors.

Boosting large-scale superconductor applications require nanostructured conductors with artificial pinning centres immobilizing quantized vortices at high temperature and magnetic fields. Here we demonstrate a highly effective mechanism of artificial pinning centres in solution-derived high-temperature superconductor nanocomposites through generation of nanostrained regions where Cooper pair formation is suppressed. The nanostrained regions identified from transmission electron microscopy devise a very high concentration of partial dislocations associated with intergrowths generated between the randomly oriented nanodots and the epitaxial YBa(2)Cu(3)O(7) matrix. Consequently, an outstanding vortex-pinning enhancement correlated to the nanostrain is demonstrated for four types of randomly oriented nanodot, and a unique evolution towards an isotropic vortex-pinning behaviour, even in the effective anisotropy, is achieved as the nanostrain turns isotropic. We suggest a new vortex-pinning mechanism based on the bond-contraction pairing model, where pair formation is quenched under tensile strain, forming new and effective core-pinning regions.

Soluble fatty acid synthase relates to bone biomarkers in prepubertal children.

SUMMARY: Circulating soluble fatty acid synthase (FASN, a key enzyme in de novo biosynthesis of fatty acids, expressed in both adipocytes and osteoblasts) is clinically related to a less favorable bone profile in healthy prepubertal children. Soluble FASN may participate in the reciprocal regulation between fat and bone metabolism. INTRODUCTION: Fatty acid synthase (FASN), a key enzyme in de novo biosynthesis of fatty acids, is expressed in adipocytes and osteoblasts. We hypothesized that FASN may participate in the crosstalk between fat and bone. To this aim, we studied the relation between circulating soluble FASN (an extracellular FASN that reflects previously intracellular enzymatic activity) and adipose tissue and bone biomarkers in prepubertal children. METHODS: Circulating soluble FASN, total and high molecular weight (HMW) adiponectin, bone biomarkers [osteocalcin (OC), uncarboxylated osteocalcin (ucOC), C-terminal cross-linked telopeptide of type I collagen (CTX), bone-specific alkaline phosphatase (BSAP)], and a profile of energy metabolism [body fat, insulin resistance and secretion (HOMA), serum lipids] were assessed in 84 asymptomatic prepubertal children (44 girls, 40 boys, age 6.8 ± 0.1 year). Serum 25-OH Vitamin D (Vit D) was additionally measured. RESULTS: Circulating soluble FASN increased with increasing HMW adiponectin (r = 0.29, p = 0.01) and decreasing serum Vit D (r = -0.21, p < 0.05), and was related to a less favorable bone profile, showing negative associations with bone-derived metabolic parameters [total OC (r = -0.33, p = 0.002) and ucOC (r = -0.37, p < 0.0001)] and a positive association with the CTX-to-BSAP ratio (r = 0.31, p < 0.01). These correlations were not explained by age, gender, body fat, insulin resistance or secretion or serum lipids; however, they were predominant in those subjects with Vit D levels below the population median. CONCLUSIONS: Circulating soluble FASN relates to both adipose tissue and bone biomarkers in prepubertal children, with associations that are dependent on Vit D concentrations. These findings suggest that FASN may participate in the crosstalk between fat and bone metabolism.

[Mortality, cardiovascular risk, and health status in a male cohort initiated in 1968. The Manresa study]. / Mortalidad, riesgo cardiovascular y estado de salud actual de una cohorte de varones iniciada en el año 1968. Estudio Manresa.

OBJECTIVES: To analyse mortality and its causes in the Manresa male cohort followed over 42 years; to compare the initial risk of cardiovascular mortality with actual mortality; and to describe the health status of the participants at the end of the study. METHODS: Prospective observational study, in which an analysis of the cumulative incidence of mortality was performed. The association of cardiovascular risk factors with mortality was calculated with a logistic regression analysis of mixed effect. The risk of mortality of individuals was evaluated and compared with true cardiovascular mortality using ROC curves. At the end of the study, a descriptive analysis of CVRF and health status of participants in the last survey was performed. RESULTS: The number of deaths was 457 (43%). Cumulative incidence for cardiovascular diseases was 10.6%. Cardiovascular risk factors significantly associated with cardiovascular mortality were age, cholesterol, and smoking. The use of risk score charts for cardiovascular mortality was found to be useful, and there were no differences between tables. In the last health screening of cardiovascular risk factors levels in an elderly population, a high prevalence was found of hypertension and of regular physical activity, together with a low prevalence of smoking. CONCLUSIONS: Cardiovascular mortality remained high, although it has become the second cause after tumoural diseases. The comparison of predictions from cardiovascular mortality risk tables with actual mortality rates in our area over more than 4 decades demonstrated the importance of assessing cardiovascular risk in the adult population.

Brain metastases from lung cancer responding to erlotinib: the importance of EGFR mutation.

Median survival of patients with brain metastases from nonsmall cell lung cancer (NSCLC) is poor and more effective treatments are urgently needed. We have evaluated the efficacy of erlotinib in this setting and its association with activating mutations in the epidermal growth factor receptor (EGFR) gene. We retrospectively identified patients with NSCLC and brain metastases treated with erlotinib. EGFR mutations in exons 19 and 21 were analysed by direct sequencing. Efficacy and tolerability were compared according to EGFR mutational status. 69 NSCLC patients with brain metastases were identified, 17 of whom harboured EGFR mutations. Objective response rate in patients with EGFR mutations was 82.4%; no responses were observed in unselected patients (p<0.001). Median (95% CI) time to progression within the brain for patients harbouring EGFR mutations was 11.7 (7.9-15.5) months, compared to 5.8 (5.2-6.4) months for control patients whose EGFR mutational status had not been assessed (p<0.05). Overall survival was 12.9 (6.2-19.7) months and 3.1 (2.5-3.9) months (p<0.001), respectively. The toxicity of erlotinib was as expected and no differences between cohorts were observed. Erlotinib is active in brain metastases from NSCLC; this clinical benefit is related to the presence of activating mutations in exons 19 or 21 of the EGFR gene.

Chemical solution approaches to YBa2Cu3O7_delta-Au nanocomposite superconducting thin films.

We explore the feasibility of preparing YBa2CU3O7-Au (YBCO-Au) nanocomposite thin films by chemical solution deposition (CSD). Two approaches were used: (i) A standard in-situ methodology where Au metallorganic salts are added into the precursor solution of YBCO trifluoroacetate (TFA) salts and (ii) a novel approach where stable colloidal solutions of preformed gold nanoparticles (5-15 nm) were homogeneously mixed with TFA-YBCO solutions. A detailed analysis of the microstructure of the films showed that in both cases, there is a strong tendency of gold nanoparticles to migrate to the film surface. However the kinetics of this migration evidences important differences and in the case of preformed nanoparticles their size remains unchanged (a few nanometers) whereas for the in-situ nanocomposites gold ripening leads to large particles (hundreds of nanometers). The grown YBCO-Au films showed good superconducting characteristics (J(c) 2 MA/cm2 at 77 K) but the absence of Au inclusions inside the YBCO matrix explains the fact that no enhancement of vortex pinning was observed.

Ultra-high critical current densities of superconducting YBa2Cu3O7-δ thin films in the overdoped state.

The functional properties of cuprates are strongly determined by the doping state and carrier density. We present an oxygen doping study of YBa2Cu3O7-δ (YBCO) thin films from underdoped to overdoped state, correlating the measured charge carrier density, [Formula: see text], the hole doping, p, and the critical current density, [Formula: see text]. Our results show experimental demonstration of strong increase of [Formula: see text] with [Formula: see text], up to Quantum Critical Point (QCP), due to an increase of the superconducting condensation energy. The ultra-high [Formula: see text] achieved, 90 MA cm-2 at 5 K corresponds to about a fifth of the depairing current, i.e. a value among the highest ever reported in YBCO films. The overdoped regime is confirmed by a sudden increase of [Formula: see text], associated to the reconstruction of the Fermi-surface at the QCP. Overdoping YBCO opens a promising route to extend the current carrying capabilities of rare-earth barium copper oxide (REBCO) coated conductors for applications.

Formation of stripelike flux patterns obtained by freezing kinematic vortices in a superconducting Pb film.

We demonstrate experimentally and theoretically that the dissipative state of superconducting samples with a periodic array of holes at high current densities consists of flux rivers resulting from a short-range attractive interaction between vortices. This dynamically induced vortex-vortex attraction results from the migration of quasiparticles out of the vortex core (kinematic vortices). We have directly visualized the formation of vortex chains by scanning Hall probe microscopy after freezing the dynamic state by a field cooling procedure at a constant bias current. Similar experiments carried out in a sample without holes show no hint of flux river formation. We shed light on this nonequilibrium phenomena modeled by time-dependent Ginzburg-Landau simulations.

Ultrafast transient liquid assisted growth of high current density superconducting films.

The achievement of high growth rates in YBa2Cu3O7 epitaxial high-temperature superconducting films has become strategic to enable high-throughput manufacturing of long length coated conductors for energy and large magnet applications. We report on a transient liquid assisted growth process capable of achieving ultrafast growth rates (100 nm s-1) and high critical current densities (5 MA cm-2 at 77 K). This is based on the kinetic preference of Ba-Cu-O to form transient liquids prior to crystalline thermodynamic equilibrium phases, and as such is a non-equilibrium approach. The transient liquid-assisted growth process is combined with chemical solution deposition, proposing a scalable method for superconducting tapes manufacturing. Additionally, using colloidal solutions, the growth process is extended towards fabrication of nanocomposite films for enhanced superconducting properties at high magnetic fields. Fast acquisition in situ synchrotron X-ray diffraction and high resolution scanning transmission electron microscopy (STEM) become crucial measurements in disentangling key aspects of the growth process.

Thermoelectric stack sample cooling modification of a commercial atomic force microscopy.

Enabling temperature dependent experiments in Atomic Force Microscopy is of great interest to study materials and surface properties at the nanoscale. By studying Curie temperature of multiferroic materials, temperature dependent phase transitions on crystalline structures or resistive switching phenomena are only a few examples of applications. We present an equipment capable of cooling samples using a thermoelectric cooling stage down to -61.4 °C in a 15 × 15 mm2 sample plate. The equipment uses a four-unit thermoelectric stack to achieve maximum temperature range, with low electrical and mechanical noise. The equipment is installed into a Keysight 5500LS Atomic Force Microscopy maintaining its compatibility with all Electrical and Mechanical modes of operation. We study the contribution of the liquid cooling pump vibration into the cantilever static deflection noise and the temperature dependence of the cantilever deflection. A La0.7Sr0.3MnO3-y thin film sample is used to demonstrate the performance of the equipment and its usability by analyzing the resistive switching phenomena associated with this oxide perovskite.

Prevalence of etravirine-associated mutations in clinical samples with resistance to nevirapine and efavirenz.

OBJECTIVES: To evaluate the expected activity of etravirine in clinical samples, according to mutational patterns associated with decreased virological response (VR). METHODS: We identified 1586 routine clinical samples with resistance-associated mutations (RAMs) to nevirapine and efavirenz (K103N 60%, Y181C 37%, G190A 27%, V108I 13%). Concerning in vitro identified etravirine mutations, samples with F227C, Y181I, M230L or L100I plus K103N plus Y181C were considered highly resistant. Samples with two RAMs plus Y181C or V179D or K101E or Y188L were considered intermediate. The prevalence of 13 RAMs recently associated with decreased VR to etravirine in the DUET clinical trials was also investigated. RESULTS: Most samples (69%) harboured more than one IAS-USA RAM to first-generation non-nucleoside reverse transcriptase inhibitors (NNRTIs): 42% harboured two RAMs, 21% three RAMs and 6% four or more RAMs. The prevalence of 13 specific etravirine RAMs was V179F 0.12%, G190S 3.9%, Y181V 0.1%, V106I 2.6%, V179D 1.6%, K101P 2.0%, K101E 10.1%, Y181C 36.9%, A98G 5.9%, V90I 6.9%, Y181I 3.6%, G190A 27% and L100I 9.1%. The five RAMs with the most impact on VR (V179F/D, G190S, Y181V and V106I) occurred less often. Overall, 8.2% of the samples had three or more etravirine RAMs and only 1.1% had four or more. In addition, patterns of RAMs previously associated with intermediate etravirine resistance were present in 26.2% of the samples, whereas 4.85% displayed patterns of high-degree resistance. CONCLUSIONS: For RAMs associated with decreased VR, etravirine resistance in routine clinical samples was lower than previously reported. High-degree resistance was uncommon, even in patients with resistance to first-generation NNRTIs, whereas low-to-intermediate etravirine resistance was more common.

Angular flux creep contributions in YBa2Cu3O7-δ nanocomposites from electrical transport measurements.

The shape of the electric-field-current-density (E-J) curve is determined by flux pinning and also by dynamics of vortices. Here, we propose a novel methodology to study the normalized flux creep rate S in YBa2Cu3O7-δ measured from E-J curves obtained by electrical transport measurements that provides a fast and versatile way to foresee the flux magnetic relaxation in films and disentangle angular flux creep contributions by the scaling of the isotropic contribution of S. After a detailed comparison of various pristine and nanocomposite films with differentiated nanostructures, we focus on the roles that intrinsic pinning and stacking faults (YBa2Cu4O8-intergrowths) play when the magnetic field is applied parallel to the superconducting CuO2 planes. This study reveals that the emerging intergrowths provide advanced pinning properties that additionally reduce the thermal activated flux magnetic relaxation. For this purpose, creep analysis becomes a very appropriate tool to elucidate the dominance of the different pinning sites at different regions of the magnetic-field-temperature diagram.

Author Correction: Angular flux creep contributions in YBa2Cu3O7-δ nanocomposites from electrical transport measurements.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Synergistic arsenic(v) and lead(ii) retention on synthetic jarosite. I. Simultaneous structural incorporation behaviour and mechanism.

Jarosite [KFe3(SO4)2(OH)6] minerals are effective scavengers of potentially toxic elements (PTEs) and are abundant, for example, in acid rock/mine drainage scenarios. The retention process is highly relevant for environmental attenuation of heavy metals and metalloids since these are usually highly soluble and thus mobile under acidic conditions. We investigated both macroscopically and at the molecular scale the extent and the effects of concomitant incorporation of As(v) and Pb(ii) into synthetic jarosite at different As/Pb starting molar ratios, using XRD-Rietveld, SEM, ATR-FTIR spectroscopy and wet chemistry. The amount of arsenate substituted in the jarosite structure was larger when Pb(ii) was also incorporated, the former filling up to approximately 33% of the tetrahedral sites normally occupied by SO42-, as compared to 21% when Pb(ii) was absent. Similarly, the amount of Pb(ii) incorporated in the structure was larger when As(v) was also taken up. The jarosite unit cell volume increased as higher amounts of As(v) incorporated into its structure, but simultaneous Pb(ii) incorporation seemed to limit this increase due to its smaller size as compared to K+. The extent to which As and Pb can accommodate in the jarosite structure was found to be limited by concentration maxima under the imposed synthesis conditions. At As/Pb ratios up to 1, Pb-As-jarosites were the only crystalline products. Above this ratio, a mixture of Pb-As-jarosite, anglesite (PbSO4) and poorly-crystalline ferric arsenate (AFA) phases was observed. At the highest As/Pb ratio investigated of 1.80 Pb-As-jarosite was no longer formed. Infrared spectroscopy analysis was applied for the first time here to substituted jarosites with both cations and anions, showing spectral changes in the solids as the As/Pb ratio increased: a characteristic As-O doublet at ∼810 and ∼855 cm-1 was observed upon Pb incorporation, showing an indirect effect of Pb(ii) on the As-O bonds in the jarosite structure. Thus, structural incorporation of Pb plays a pivotal role in the unit cell environment of jarosite to balance the distortion caused by AsO4-for-SO4 substitution. The retention processes found in this work have important environmental implications and impacts: through the synergistic incorporation encountered, remediation enhancement of cationic pollutants such as Pb(ii) is possible in a concomitant fashion with As(v) attenuation in acidic mining and metallurgical environments.