Magnetic vortex nucleation and annihilation in bi-stable ultra-small ferromagnetic particles.

Vortex-mediated magnetization reversal in individual ultra-small (∼100 nm) ferromagnetic particles at low temperatures is studied by nanoSQUID magnetometry. At zero applied bias field, the flux-closure magnetic state (vortex) and the quasi uniform configuration are bi-stable. This stems from the extremely small size of the nanoparticles that lies very close to the limit of single-domain formation. The analysis of the temperature-dependent (from 0.3 to 70 K) hysteresis of the magnetization allows us to infer the nature of the ground state magnetization configuration. The latter corresponds to a vortex state as also confirmed by electron holography experiments. Based on the simultaneous analysis of the vortex nucleation and annihilation data, we estimate the magnitude of the energy barriers separating the quasi single-domain and the vortex state and their field dependence. For this purpose, we use a modified power-law scaling of the energy barriers as a function of the applied bias field. These studies are essential to test the thermal and temporal stability of flux-closure states stabilized in ultra-small ferromagnets.

Local deformation gradients in epitaxial Pb(Zr0.2Ti0.8)O3 layers investigated by transmission electron microscopy.

Lead zirconate titanate samples are used for their piezoelectric and ferroelectric properties in various types of micro-devices. Epitaxial layers of tetragonal perovskites have a tendency to relax by forming [Formula: see text] ferroelastic domains. The accommodation of the a/c/a/c polydomain structure on a flat substrate leads to nanoscale deformation gradients which locally influence the polarization by flexoelectric effect. Here, we investigated the deformation fields in epitaxial layers of Pb(Zr0.2Ti0.8)O3 grown on SrTiO3 substrates using transmission electron microscopy (TEM). We found that the deformation gradients depend on the domain walls inclination ([Formula: see text] or [Formula: see text] to the substrate interface) of the successive [Formula: see text] domains and we describe three different a/c/a domain configurations: one configuration with parallel a-domains and two configurations with perpendicular a-domains (V-shaped and hat-[Formula: see text]-shaped). In the parallel configuration, the c-domains contain horizontal and vertical gradients of out-of-plane deformation. In the V-shaped and hat-[Formula: see text]-shaped configurations, the c-domains exhibit a bending deformation field with vertical gradients of in-plane deformation. Each of these configurations is expected to have a different influence on the polarization and so the local properties of the film. The deformation gradients were measured using dark-field electron holography, a TEM technique, which offers a good sensitivity (0.1%) and a large field-of-view (hundreds of nanometers). The measurements are compared with finite element simulations.

Optimising electron microscopy experiment through electron optics simulation.

We developed a new type of electron trajectories simulation inside a complete model of a modern transmission electron microscope (TEM). Our model incorporates the precise and real design of each element constituting a TEM, i.e. the field emission (FE) cathode, the extraction optic and acceleration stages of a 300kV cold field emission gun, the illumination lenses, the objective lens, the intermediate and projection lenses. Full trajectories can be computed using magnetically saturated or non-saturated round lenses, magnetic deflectors and even non-cylindrical symmetry elements like electrostatic biprism. This multi-scale model gathers nanometer size components (FE tip) with parts of meter length (illumination and projection systems). We demonstrate that non-trivial TEM experiments requiring specific and complex optical configurations can be simulated and optimized prior to any experiment using such model. We show that all the currents set in all optical elements of the simulated column can be implemented in the real column (I2TEM in CEMES) and used as starting alignment for the requested experiment. We argue that the combination of such complete electron trajectory simulations in the whole TEM column with automatic optimization of the microscope parameters for optimal experimental data (images, diffraction, spectra) allows drastically simplifying the implementation of complex experiments in TEM and will facilitate the development of advanced use of the electron microscope in the near future.

Development of TEM and SEM high brightness electron guns using cold-field emission from a carbon nanotip.

A newly developed carbon cone nanotip (CCnT) has been used as field emission cathode both in low voltage SEM (30 kV) electron source and high voltage TEM (200 kV) electron source. The results clearly show, for both technologies, an unprecedented stability of the emission and the probe current with almost no decay during 1h, as well as a very small noise (rms less than 0.5%) compared to standard sources which use tungsten tips as emitting cathode. In addition, quantitative electric field mapping around the FE tip have been performed using in situ electron holography experiments during the emission of the new tip. These results show the advantage of the very high aspect ratio of the new CCnT which induces a strong enhancement of the electric field at the apex of the tip, leading to very small extraction voltage (some hundred of volts) for which the field emission will start. The combination of these experiments with emission current measurements has also allowed to extract an exit work function value of 4.8 eV.

Artificial chemical and magnetic structure at the domain walls of an epitaxial oxide.

Progress in nanotechnology requires new approaches to materials synthesis that make it possible to control material functionality down to the smallest scales. An objective of materials research is to achieve enhanced control over the physical properties of materials such as ferromagnets, ferroelectrics and superconductors. In this context, complex oxides and inorganic perovskites are attractive because slight adjustments of their atomic structures can produce large physical responses and result in multiple functionalities. In addition, these materials often contain ferroelastic domains. The intrinsic symmetry breaking that takes place at the domain walls can induce properties absent from the domains themselves, such as magnetic or ferroelectric order and other functionalities, as well as coupling between them. Moreover, large domain wall densities create intense strain gradients, which can also affect the material's properties. Here we show that, owing to large local stresses, domain walls can promote the formation of unusual phases. In this sense, the domain walls can function as nanoscale chemical reactors. We synthesize a two-dimensional ferromagnetic phase at the domain walls of the orthorhombic perovskite terbium manganite (TbMnO3), which was grown in thin layers under epitaxial strain on strontium titanate (SrTiO3) substrates. This phase is yet to be created by standard chemical routes. The density of the two-dimensional sheets can be tuned by changing the film thickness or the substrate lattice parameter (that is, the epitaxial strain), and the distance between sheets can be made as small as 5 nanometres in ultrathin films, such that the new phase at domain walls represents up to 25 per cent of the film volume. The general concept of using domain walls of epitaxial oxides to promote the formation of unusual phases may be applicable to other materials systems, thus giving access to new classes of nanoscale materials for applications in nanoelectronics and spintronics.

Knowledge and attitude of the Flemish primary care physician toward organ donation and transplantation.

PURPOSE: Primary care physicians (PCP) might play an important role in the acceptance of organ donation (OD) in the population. This would require both a positive attitude and a good basic knowledge about the organ donation and transplantation (ODT) process. Studies on this subject are very limited however. The objectives of this study are to determine the knowledge and attitude of the PCP towards OD in Flanders. METHODS: Three-hundred twenty-seven Flemish PCPs completed an electronic questionnaire, comprising 6 sections: demographic factors, practical experience, knowledge, education, attitude and potential role in the ODT process. RESULTS: Eighty-seven percent of the Flemish PCP agree with the implementation of heart-beating organ donation. Ninety-four percent would agree to donate the organs of their own child. 80% know that even without explicit consent the prelevation of the organs and tissues of each potential Belgian donor will take place. Although they are aware of the current legislation, their knowledge regarding donor criteria showed significant gaps. A minority of the PCP's know that donors can be little brain-dead children (53%) or elderly above 70 years (45%). Only 61% of PCPs know that brain dead is associated with irreversible damage to the brain and only 28% know that more than one physician is involved in making the diagnosis. A majority (91%) is willing to play a role in the ODT process. But about two-thirds (61%) of them doubt their ability to answer questions of patients on this subject. 82.5% of this group would find it useful to participate in a specific training. When they are offered different choices to play a role in the process, the most accepted (84%) one is informing the transplant centre about the donor's medical history and risk behavior. CONCLUSIONS: The Flemish PCP has a positive attitude towards ODT. He is willing to play a role in the ODT process. However, our study clearly documents deficits in the knowledge about brain death and the need for postgraduate training in the field of ODT. Correcting these deficits may be an important factor in improving the acceptance of organ donation.

High-resolution imaging of remanent state and magnetization reversal of superdomain structures in high-density cobalt antidot arrays.

Remanent state and magnetization reversal processes of a series of cobalt antidot arrays with a fixed hole diameter (d ≈ 55 nm) and an array periodicity (p) ranging between 95 and 524 nm were studied by in situ Lorentz microscopy (LM) as a function of the magnetic field. At remanence, defocused LM images showed the periodicity dependence of the magnetic states inside the lattice. A remarkable transition was observed in the type of domain structures as a function of p: for the large periodicities (p > 300 nm), conventional 90° and 180° domain walls were formed, whereas in small-period antidot arrays (p â‰¦ 160 nm) magnetic superdomain walls (SDWs) were nucleated to separate regions with different average magnetization direction, the so-called magnetic superdomains. In the SDW regime, a low-frequency Fourier filtering method was implemented to allow a quantitative analysis of the LM images by the transport of intensity equation method. In situ LM experiments under applied magnetic fields were performed to study the reversal magnetization process in a particular array (p = 160 nm), and clear differences were observed as a function of the magnetic field orientation. The switching process under magnetic fields parallel to the horizontal antidot rows occurs in two stages: the system first nucleates and propagates horizontal SDWs, parallel to the field. Then, at higher magnetic fields, vertical SDWs, perpendicular to the field, appear before saturation. When the magnetic field is applied at 45° with respect to the antidot rows, both horizontal and vertical SDWs are nucleated and propagated simultaneously. All the experiments were successfully correlated with micromagnetic simulations. The current study sheds new light on the magnetization reversal processes of antidot arrays and opens new possibilities of exploiting the potential of high-resolution in situ LM and new data analysis procedures to probe magnetization processes in nanomagnetism, particularly in periodic arrays of nanomagnets.

Assessment of Maraviroc Exposure-Response Relationship at 48 Weeks in Treatment-Experienced HIV-1-Infected Patients in the MOTIVATE Studies.

Efficacy exposure-response relationships of the CCR5 antagonist maraviroc were evaluated across two phase III clinical trials. This post-hoc analysis used 48-week efficacy data from 841 treatment-experienced patients infected with CCR5-tropic human immunodeficiency virus type 1 (HIV-1), identified by the enhanced sensitivity Trofile assay. Probability of treatment success (viral RNA <50 copies/ml) was modeled using generalized additive logistic regression, testing exposure, clinical, and virologic variables. Prognostic factors for treatment success (in decreasing order of Akaike information criterion (AIC) change) were: maraviroc treatment, high-weighted overall susceptibility to background treatment, absence of an undetectable maraviroc concentration, high baseline CD4 count (BCD4), low viral load (VL), race (other than black), absence of non-R5 baseline tropism (BTRP), and absence of fosamprenavir (FPV). No concentration-response relationship was found with treatment (maraviroc vs. placebo) and presence/absence of undetectable maraviroc concentration (adherence marker) in the model. The maraviroc doses studied (300 or 150 mg with potent CYP3A4 inhibitors once (q.d.)/twice daily (b.i.d.)) deliver concentrations near the top of the concentration-response curve.CPT: Pharmacometrics & Systems Pharmacology (2013) 2, e64; doi:10.1038/psp.2013.42; published online 14 August 2013.

Quantitative in situ magnetization reversal studies in Lorentz microscopy and electron holography.

A generalized procedure for the in situ application of magnetic fields by means of the excitation of the objective lens for magnetic imaging experiments in Lorentz microscopy and electron holography is quantitatively described. A protocol for applying magnetic fields with arbitrary in-plane magnitude and orientation is presented, and a freeware script for Digital Micrograph(™) is provided to assist the operation of the microscope. Moreover, a method to accurately reconstruct hysteresis loops is detailed. We show that the out-of-plane component of the magnetic field cannot be always neglected when performing quantitative measurements of the local magnetization. Several examples are shown to demonstrate the accuracy and functionality of the methods.

Counting elementary charges on nanoparticles by electron holography.

The distribution and movement of charge is fundamental to many physical phenomena, particularly for applications involving nanoparticles, nanostructures, and electronic devices. However, there are very few ways of quantifying charge at the necessary length scale. Here, we show that aberration-corrected electron holography is capable of counting the charge on individual nanoparticles to a precision of one elementary unit of charge. We present a method that measures charges within predefined contours by directly applying Gauss's law at the nanoscale. We perform a statistical analysis to reveal the relationship between the size of the contours and the precision of the charge measurement and present strategies to optimize the spatial and signal resolution for the presented method.

Electromechanical coupling among edge dislocations, domain walls, and nanodomains in BiFeO3 revealed by unit-cell-wise strain and polarization maps.

The performance of ferroelectric devices, for example, the ferroelectric field effect transistor, is reduced by the presence of crystal defects such as edge dislocations. For example, it is well-known that edge dislocations play a crucial role in the formation of ferroelectric dead-layers at interfaces and hence finite size effects in ferroelectric thin films. The detailed lattice structure including the relevant electromechanical coupling mechanisms in close vicinity of the edge dislocations is, however, not well-understood, which hampers device optimization. Here, we investigate edge dislocations in ferroelectric BiFeO3 by means of spherical aberration-corrected scanning transmission electron microscopy, a dedicated model-based structure analysis, and phase field simulations. Unit-cell-wise resolved strain and polarization profiles around edge dislocation reveal a wealth of material states including polymorph nanodomains and multiple domain walls characteristically pinned to the dislocation. We locally determine the piezoelectric tensor and identify piezoelectric coupling as the driving force for the observed phenomena, explaining, for example, the orientation of the domain wall with respect to the edge dislocation. Furthermore, an atomic model for the dislocation core is derived.

Evidence of sharp and diffuse domain walls in BiFeO3 by means of unit-cell-wise strain and polarization maps obtained with high resolution scanning transmission electron microscopy.

Domain walls (DWs) substantially influence a large number of applications involving ferroelectric materials due to their limited mobility when shifted during polarization switching. The discovery of greatly enhanced conduction at BiFeO(3) DWs has highlighted yet another role of DWs as a local material state with unique properties. However, the lack of precise information on the local atomic structure is still hampering microscopical understanding of DW properties. Here, we examine the atomic structure of BiFeO(3) 109° DWs with pm precision by a combination of high-angle annular dark-field scanning transmission electron microscopy and a dedicated structural analysis. By measuring simultaneously local polarization and strain, we provide direct experimental proof for the straight DW structure predicted by ab initio calculations as well as the recently proposed theory of diffuse DWs, thus resolving a long-standing discrepancy between experimentally measured and theoretically predicted DW mobilities.

Interface and temperature dependent magnetic properties in permalloy thin films and tunnel junction structures.

Magnetization dynamics and field dependent magnetization of different devices based on 25-30 nm thick Permalloy (Py) films: such as single Py layers (Py/MgO; Py/CoFeB/Al2O3) and Py inserted as a magnetic layer in magnetic tunnel junctions (Py/CoFe/Al2O3/CoFe; Py/CoFeB/Al2O3/CoFe; Py/MgO/Fe) have been extensively studied within a temperature range between 300 K down to 5 K. The dynamic response was investigated in the linear regime measuring the ferromagnetic resonance response of the Py layers using broadband vector network analyzer technique. Both the static and the dynamic properties suggest the possible presence of a thermally induced spin reorientation transition in the Py interface at temperatures around 60 K in all the samples investigated. It seems, however, that the details of the interface between Py and the hardening ferromagnet/insulator structure, the atomic structure of Py layers (amorphous vs. textured) as well as the presence of dipolar coupling through the insulating barrier in the magnetic tunnel junction structures could strongly influence this low temperature reorientation transition. Our conclusions are indirectly supported by structural characterization of the samples by means of X-Ray diffraction and high resolution transmission electron microscopy techniques. Micromagnetic simulations indicate the possibility of strongly enhanced surface anisotropy in thin Py films over CoFe or CoFeB underlayers. Comparison of the simulations with experimental results also shows that the thermally-induced spin reorientation transition could be influenced by the presence of strong disorder at the surface.

Flexoelectric rotation of polarization in ferroelectric thin films.

Strain engineering enables modification of the properties of thin films using the stress from the substrates on which they are grown. Strain may be relaxed, however, and this can also modify the properties thanks to the coupling between strain gradient and polarization known as flexoelectricity. Here we have studied the strain distribution inside epitaxial films of the archetypal ferroelectric PbTiO(3), where the mismatch with the substrate is relaxed through the formation of domains (twins). Synchrotron X-ray diffraction and high-resolution scanning transmission electron microscopy reveal an intricate strain distribution, with gradients in both the vertical and, unexpectedly, the horizontal direction. These gradients generate a horizontal flexoelectricity that forces the spontaneous polarization to rotate away from the normal. Polar rotations are a characteristic of compositionally engineered morphotropic phase boundary ferroelectrics with high piezoelectricity; flexoelectricity provides an alternative route for generating such rotations in standard ferroelectrics using purely physical means.

Dark-field electron holography for the measurement of geometric phase.

The genesis, theoretical basis and practical application of the new electron holographic dark-field technique for mapping strain in nanostructures are presented. The development places geometric phase within a unified theoretical framework for phase measurements by electron holography. The total phase of the transmitted and diffracted beams is described as a sum of four contributions: crystalline, electrostatic, magnetic and geometric. Each contribution is outlined briefly and leads to the proposal to measure geometric phase by dark-field electron holography (DFEH). The experimental conditions, phase reconstruction and analysis are detailed for off-axis electron holography using examples from the field of semiconductors. A method for correcting for thickness variations will be proposed and demonstrated using the phase from the corresponding bright-field electron hologram.

Long-term results of a prospective study on laparoscopic adjustable gastric banding for morbid obesity.

BACKGROUND: The objective of this study was to study the long-term outcome of adjustable gastric banding in the treatment of morbid obesity. In Europe, the preference for gastric band has declined in favor of Roux-Y-gastric bypass. METHODS: This is a follow-up of a prospective study on a large cohort of patients after laparoscopic gastric banding (LAGB) for morbid obesity. RESULTS: Complete data were collected on 656 patients (88%) from a cohort of 745 patients. After a median follow-up of 95 months (range 60-155), the mean BMI dropped from 41.0 ± 7.3 to 33.2 ± 7.1 kg/m², with a 46.2 ± 36.5% excess weight loss (EWL). A more than 50% EWL was achieved in 44% of patients. The band was still in place in 77.1% of patients; conversion to gastric bypass after band removal was carried out in 98 (14.9%) patients, while a simple removal was done in only 52 (7.9%) patients. Band removal was more likely in women and patients with a higher BMI. CONCLUSIONS: After LAGB, band removal was necessary for complications or insufficient weight loss in 24% of patients. Nearly half of the patients achieved a more than 50% EWL, but in 88%, a more than 10% EWL was observed. LAGB can achieve an acceptable weight loss in some patients, but the failure in one out of four patients does not allow proposing it as a first-line option for the treatment of obesity.

Pharmacokinetics and pharmacodynamics of the non-nucleoside reverse-transcriptase inhibitor etravirine in treatment-experienced HIV-1-infected patients.

The pharmacokinetics and pharmacodynamics of the antiretroviral agent etravirine were evaluated in two phase III clinical trials. Pharmacokinetic data were available in 577 patients randomized to receive etravirine. The mean (SD) population-pharmacokinetics-derived area under the concentration-time curve at 12 h (AUC(12 h)) and concentration at 0 h (C(0 h)) were 5,501 (4,544) ng·h/ml and 393 (378) ng/ml, respectively. Hepatitis C coinfection raised etravarine exposure, and concomitant use of tenofovir disoproxil fumarate lowered etravirine exposure, but these changes were not considered clinically relevant. Etravirine apparent oral clearance was not affected by age, weight, sex, race, hepatitis B coinfection status, creatinine clearance, or concomitant use of enfuvirtide. Virologic response (<50 copies/ml) at week 24 was 59% in patients randomized to etravirine vs. 41% in those receiving placebo (P < 0.0001). There was no apparent relationship between etravirine pharmacokinetics and either efficacy or safety. Factors other than the pharmacokinetics of etravirine such as the characteristics of the patients and the disease, as well as characteristics of the treatment regimen, predict virologic response.

A comprehensive hepatitis C viral kinetic model explaining cure.

We propose a model that characterizes and links the complexity and diversity of clinically observed hepatitis C viral kinetics to sustained virologic response (SVR)-the primary clinical end point of hepatitis C treatment, defined as an undetectable viral load at 24 weeks after completion of treatment)-in patients with chronic hepatitis C (CHC) who have received treatment with peginterferon alpha-2a +/- ribavirin. The new attributes of our hepatitis C viral kinetic model are (i) the implementation of a cure/viral eradication boundary, (ii) employment of all hepatitis C virus (HCV) RNA measurements, including those below the lower limit of quantification (LLOQ), and (iii) implementation of a population modeling approach. The model demonstrated excellent positive (99.3%) and negative (97.1%) predictive values for SVR as well as high sensitivity (96.6%) and specificity (99.4%). The proposed viral kinetic model provides a framework for mechanistic exploration of treatment outcome and permits evaluation of alternative CHC treatment options with the ultimate aim of developing and testing hypotheses for personalizing treatments in this disease.

Unexpected resonant response in [Fe(001)/Cr(001)]10/MgO(001) multilayers in a magnetic field.

We observed unexpected resonant response in [Fe/Cr]10 multilayers epitaxially grown on MgO(100) substrates which exists only when both ac current and dc magnetic field are simultaneously applied. The magnitude of the resonances is determined by the multilayer magnetization proving their intrinsic character. The reduction of interface epitaxy leads to nonlinear dependence of the magnitude of resonances on the alternating current density. We speculate that the existence of the interface transition zone could facilitate the subatomic vibrations in thin metallic films and multilayers grown on bulk insulating substrates.