Nitrous oxide versus lidocaine versus no analgesic for in-office hysteroscopy: a randomised clinical trial.

OBJECTIVE: To compare the effect of inhaled nitrous oxide (INO) on pain control during in-office hysteroscopy with 1% lidocaine paracervical infiltration and no analgesic. DESIGN: Single-blind stratified randomised clinical trial with masked assessment by a third party. SETTING: Department of Obstetrics and Gynaecology in a Spanish hospital. POPULATION: Women who underwent hysteroscopy. METHODS: Patients were stratified into three groups according to the purpose of the hysteroscopy (biopsy, polypectomy or tubal sterilisation) and then assigned to different treatment groups through a permuted-blocks randomisation within strata. Pain scale was provided by a gynaecologist totally blinded to procedures and treatments. Effects were assessed using a one-way analysis of variance following an intention-to-treat approach. MAIN OUTCOME MEASURES: Visual analogue scale (VAS) from 0 to 100 mm. RESULTS: A total of 314 women were included: 105 to INO, 104 to 1% lidocaine and 105 to no analgesic. Baseline characteristics were comparable. Mean VAS score after the procedure was 34.7 ± 25.8 mm, 36.1 ± 22.9 mm (P = 1.0) and 47.3 ± 28.2 mm (P = 0.001) for INO, 1% lidocaine and no analgesic, respectively. No adverse events were reported in 91 (86.7%) patients in the INO group compared with 79 (76%) in the 1%-lidocaine group (P = 0.04) and 85 (81%) in the no-analgesic group (P = 0.26). CONCLUSION: INO was as effective as 1% lidocaine in pain control for in-office hysteroscopy and was better tolerated. The no-analgesic group presented the poorer results, so was the least recommended clinical option.

Risk of acute myocardial infarction among new users of bisphosphonates: a nested case-control study.

OBJECTIVE: To test the hypothesis that bisphosphonates reduce AMI risk among new users and to assess whether the effect depends on the duration of treatment. METHODS: Case-control study nested in a primary cohort composed of patients aged 40 to 99 years, with at least 1-year registry in the BIFAP database throughout the study period 2002-2015. Out of this cohort, incident AMI cases were identified and five controls per case were randomly selected, matched by exact age, sex, and index date. The association of AMI with current, recent and past use of bisphosphonates was assessed by computing adjusted odds ratios (AOR) and their corresponding 95% confidence interval (CI) through an unconditional logistic regression. Only initiators of bisphosphonates were considered. RESULTS: A total of 23,590 cases of AMI and 117,612 controls were included. The mean age was 66.8 (SD 13.4) years, and 72.52% was male, in both groups. About 276 (1.17%) cases and 1458 (1.24%) controls were current users of bisphosphonates yielding an AOR of 0.98 (95% CI 0.854-1.14). Recent and past use were not associated with a reduced risk, either, nor was it found a reduction with treatment duration (AOR less than 1 year = 0.92; 95% CI 0.73-1.15; AOR more than 1 year = 1.03; 95% CI 0.86-1.23). Stratified analysis by age, sex and background cardiovascular risk did not show an effect modification by these variables. CONCLUSION: The results do not support a cardioprotective effect of bisphosphonates regardless of the duration of treatment, age, sex or background cardiovascular risk. However, a small protective effect could have been masked if patients with osteoporosis have had a background higher risk of AMI.

Holographic imaging of electromagnetic fields via electron-light quantum interference.

Holography relies on the interference between a known reference and a signal of interest to reconstruct both the amplitude and the phase of that signal. With electrons, the extension of holography to the ultrafast time domain remains a challenge, although it would yield the highest possible combined spatiotemporal resolution. Here, we show that holograms of local electromagnetic fields can be obtained with combined attosecond/nanometer resolution in an ultrafast transmission electron microscope (UEM). Unlike conventional holography, where signal and reference are spatially separated and then recombined to interfere, our method relies on electromagnetic fields to split an electron wave function in a quantum coherent superposition of different energy states. In the image plane, spatial modulation of the electron energy distribution reflects the phase relation between reference and signal fields. Beyond imaging applications, this approach allows implementing quantum measurements in parallel, providing an efficient and versatile tool for electron quantum optics.

Tracking ultrafast hot-electron diffusion in space and time by ultrafast thermomodulation microscopy.

The ultrafast response of metals to light is governed by intriguing nonequilibrium dynamics involving the interplay of excited electrons and phonons. The coupling between them leads to nonlinear diffusion behavior on ultrashort time scales. Here, we use scanning ultrafast thermomodulation microscopy to image the spatiotemporal hot-electron diffusion in thin gold films. By tracking local transient reflectivity with 20-nm spatial precision and 0.25-ps temporal resolution, we reveal two distinct diffusion regimes: an initial rapid diffusion during the first few picoseconds, followed by about 100-fold slower diffusion at longer times. We find a slower initial diffusion than previously predicted for purely electronic diffusion. We develop a comprehensive three-dimensional model based on a two-temperature model and evaluation of the thermo-optical response, taking into account the delaying effect of electron-phonon coupling. Our simulations describe well the observed diffusion dynamics and let us identify the two diffusion regimes as hot-electron and phonon-limited thermal diffusion, respectively.

Ultrafast generation and control of an electron vortex beam via chiral plasmonic near fields.

Vortex-carrying matter waves, such as chiral electron beams, are of significant interest in both applied and fundamental science. Continuous-wave electron vortex beams are commonly prepared via passive phase masks imprinting a transverse phase modulation on the electron's wavefunction. Here, we show that femtosecond chiral plasmonic near fields enable the generation and dynamic control on the ultrafast timescale of an electron vortex beam. The vortex structure of the resulting electron wavepacket is probed in both real and reciprocal space using ultrafast transmission electron microscopy. This method offers a high degree of scalability to small length scales and a highly efficient manipulation of the electron vorticity with attosecond precision. Besides the direct implications in the investigation of nanoscale ultrafast processes in which chirality plays a major role, we further discuss the perspectives of using this technique to shape the wavefunction of charged composite particles, such as protons, and how it can be used to probe their internal structure.

Stimulated electron energy loss and gain in an electron microscope without a pulsed electron gun.

We report on a novel way of performing stimulated electron energy-loss and energy-gain spectroscopy (sEELS/sEEGS) experiments that does not require a pulsed gun. In this scheme, a regular scanning transmission electron microscope (STEM) equipped with a conventional continuous electron gun is fitted with a modified EELS detector and a light injector in the object chamber. The modification of the EELS detector allows one to expose the EELS camera during tunable time intervals that can be synchronized with nanosecond laser pulses hitting the sample, therefore allowing us to collect only those electrons that have interacted with the sample under light irradiation. Using  ∼ 5 ns laser pulses of  ∼ 2 eV photon energy on various plasmonic silver samples, we obtain evidence of sEELS/sEEGS through the emergence of up to two loss and gain peaks in the spectra at  ±â€¯2 and  ±â€¯4 eV. Because this approach does not involve any modification of the gun, our method retains the original performances of the microscope in terms of energy resolution and spectral imaging with and without light injection. Compared to pulsed-gun techniques, our method is mainly limited to a perturbative regime (typically no more that one gain event per incident electron), which allows us to observe resonant effects, in particular when the plasmon energy of a silver nanostructure matches the laser photon energy. In this situation, EELS and EEGS signals are enhanced in proportion to n+1 and n, respectively, where n is the average plasmon population due to the external illumination. The n term is associated with stimulated loss and gain processes, and the term of 1 corresponds to conventional (spontaneous) loss. The EELS part of the spectrum is therefore an incoherent superposition of spontaneous and stimulated EEL events. This is confirmed by a proper quantum-mechanical description of the electron/light/plasmon system incorporating light-plasmon and plasmon-electron interactions, as well as inelastic plasmon decay.

Care in patients with epidermal necrolysis in burn units. A nursing perspective.

OBJECTIVE: To describe how nursing care is delivered to patients with epidermal necrolysis in burn units/specialized units in Spain and a selection of countries. METHOD: Descriptive cross-sectional study. Data were collected through a structured questionnaire which was sent to nurse managers in all burn units in Spain and a selection of countries. Descriptive statistics was used to summarize the results. RESULTS: All BU/SUs in Spain (n=12) and seven BU/SUs from a selection of countries completed the questionnaire. A lack of specific nursing protocols on Epidermal Necrolysis was observed in most burn units in Spain. Skin cleansing techniques such as showering were only reported by participants from Spain. Use of antiseptics was less frequent in other countries. Conservative skin management was the most extended practice reported by all participants. The use of vaginal molds to prevent synechiae and coverage of the ocular surface with amniotic membrane to minimize sequelae were rarely reported. Pain assessment was not always documented in sedated patients and few participants reported the use of specific scales for this purpose. All nurses agreed in the need for consensus nursing care guidelines on the disease. CONCLUSIONS: Nursing care in patients with epidermal necrolysis varied between burn units in Spain. Differences and similarities were observed when compared with burn units in other countries. Genital and ocular care were outdated in all BU/SUs. Pain assessment documentation was suboptimal. Evidence-based nursing care guidelines were generally demanded by all participants to help reduce mortality and morbidity of this rare and often devastating disease.

Cardiovascular safety of noninsulin antidiabetic drugs: facts and promises. / Seguridad cardiovascular de los antidiabéticos no insulínicos: hechos y promesas.

Non insulin antidiabetic drugs are widely used in patients with type 2 diabetes. However, the drugs' effect in terms of reducing cardiovascular risk has been the subject of controversy. In 2008, based on the evidence of cardiovascular risk resulting from the use of a number of non insulin antidiabetic drugs, the US Food and Drug Administration published directives on the need to perform cardiovascular safety studies. These directives have helped obtain more evidence, such that at present there are 2 families of drugs that can reduce cardiovascular risk. These recent data have helped us add the reduction of cardiovascular morbidity and mortality to the objective of controlling blood glucose. Nevertheless, research continues with the development of new long-term studies.

Graphene-Based Active Random Metamaterials for Cavity-Free Lasing.

Manipulating and controlling the optical energy flow inside random media is a research frontier of photonics and the basis of novel laser designs. Here, we show that a metamaterial consisting of randomly dispersed graphene nanoflakes embedded within an optically pumped gain medium (rhodamine 6G) can operate as a cavity-free laser thanks to its extraordinarily low threshold for saturable absorption. The emitted light is self-organized into a well-determined spatial pattern, which depends on the graphene flake density and can be externally controlled through the optical pump. We provide different examples of tunable laser operation ranging from stable single-mode to chaoticlike behavior. Our metamaterial design holds great potential for the optical control of light amplification, as well as for the development of single-mode beam-engineered cavity-free lasers.

Self-organization of frozen light in near-zero-index media with cubic nonlinearity.

Optical beams are generally unbound in bulk media, and propagate with a velocity approximately amounting to the speed of light in free-space. Guidance and full spatial confinement of light are usually achieved by means of waveguides, mirrors, resonators, and photonic crystals. Here we theoretically demonstrate that nonlinear self-organization can be exploited to freeze optical beams in bulk near-zero-index media, thus enabling three-dimensional self-trapping of still light without the need of optical resonators. Light is stopped to a standstill owing to the divergent wavelength and the vanishing group velocity, effectively rendering, through nonlinearity, a positive-epsilon trapping cavity carved in an otherwise slightly-negative-epsilon medium. By numerically solving Maxwell's equations, we find a soliton-like family of still azimuthal doughnuts, which we further study through an adiabatic perturbative theory that describes soliton evaporation in lossy media or condensation in actively pumped materials. Our results suggest applications in optical data processing and storage, quantum optical memories, and soliton-based lasers without cavities. Additionally, near-zero-index conditions can also be found in the interplanetary medium and in the atmosphere, where we provide a complementary explanation to the rare phenomenon of ball-lightning.

Vemurafenib-induced toxic epidermal necrolysis: possible cross-reactivity with other sulfonamide compounds.

Vemurafenib is a newly licensed target-directed medication. It has been proven to improve the survival of patients with metastatic melanoma and the BRAF(V600E) mutation; however, adverse cutaneous reactions are frequent. Few cases of life-threatening severe cutaneous adverse reactions (SCARs) induced by vemurafenib have been reported. Dabrafenib, another selective BRAF inhibitor, has been licensed recently as an alternative drug with the same indications. From a molecular point of view, both vemurafenib and dabrafenib contain a sulfonamide group; cross-reactivity to sulfonamide compounds has been reported in allergic patients. We report on a patient with vemurafenib-induced toxic epidermal necrolysis (TEN). In vitro analysis of lymphocyte reactivity to vemurafenib showed positive results, confirming drug causality. In addition, lymphocytes from the patient reacted to dabrafenib and to the antibiotic sulfonamide drug sulfamethoxazole. Moreover, lymphocytes from two patients with cutaneous adverse reactions to sulfamethoxazole also reacted to vemurafenib and dabrafenib in vitro. These data strongly suggest that there might be clinical cross-reactivity between BRAF inhibitors and sulfonamides in some patients. Thus, precautions should be taken to avoid sulfonamide drugs as much as possible in patients showing serious hypersensitivity reactions to vemurafenib and vice versa.

Risk of ischemic stroke associated with non-steroidal anti-inflammatory drugs and paracetamol: a population-based case-control study.

OBJECTIVE: To assess the risk of non-fatal ischemic stroke associated with non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol. The effects of dose, duration of treatment, background cardiovascular (CV) risk and use of concomitant aspirin were studied. METHODS: We performed a population-based case-control study. Patients were considered exposed if they were on treatment within a 30-day window before the index date. We estimated adjusted odds ratios (ORs) and their 95% confidence intervals (CIs) using logistic regression. RESULTS: Two thousand eight hundred and eighty-eight cases and 20 000 controls were included. No increased risk was observed with traditional NSAIDs as a group (OR = 1.03; 95% CI, 0.90-1.19), but results varied across individual agents and conditions of use. An increased risk was found with diclofenac (OR = 1.53; 95% CI, 1.19-1.97), in particular when used at high doses (OR = 1.62; 1.06-2.46), over long-term periods (> 365 days; OR = 2.39; 1.52-3.76) and in patients with a high background CV risk (OR = 1.78; 1.23-2.58), as well as with aceclofenac when used at high doses (OR = 1.67; 1.05-2.67), in long-term treatments (OR = 2.00; 1.14-3.53) and in patients with CV risk factors (OR = 2.33; 1.40-3.87). No association was found with ibuprofen (OR = 0.94; 0.76-1.17) or naproxen (OR = 0.68; 0.36-1.29). The concomitant use of aspirin did not show a significant effect modification. Paracetamol did not increase the risk overall (OR = 0.97; 0.85-1.10) or in patients at high CV risk (OR = 0.94; 0.78-1.14). CONCLUSIONS: Diclofenac and aceclofenac increase the risk of ischemic stroke while ibuprofen and naproxen do not. Dose, duration and baseline CV risk, but not aspirin use, appear to modulate the risk. Paracetamol does not increase the risk, even in patients with a high background CV risk.

Phonon-mediated mid-infrared photoresponse of graphene.

The photoresponse of graphene at mid-infrared frequencies is of high technological interest and is governed by fundamentally different underlying physics than the photoresponse at visible frequencies, as the energy of the photons and substrate phonons involved have comparable energies. Here, we perform a spectrally resolved study of the graphene photoresponse for mid-infrared light by measuring spatially resolved photocurrent over a broad frequency range (1000-1600 cm(-1)). We unveil the different mechanisms that give rise to photocurrent generation in graphene on a polar substrate. In particular, we find an enhancement of the photoresponse when the light excites bulk or surface phonons of the SiO2 substrate. This work paves the way for the development of graphene-based mid-infrared thermal sensing technology.

Dichroism in the interaction between vortex electron beams, plasmons, and molecules.

We study the transfer of orbital angular momentum between vortex electron beams and chiral samples, such as staircase plasmonic nanostructures and biomolecules. Inelastic electron scattering from these samples produces large dichroism in the momentum-resolved electron energy-loss spectra. We illustrate this phenomenon with calculations for chiral and nonchiral clusters of silver spheres using both focused and extended electron beams, which exhibit ∼10% difference between channels of opposite angular momentum. In addition to its fundamental interest, this remarkably high dichroism suggests a way of spatially resolving chiral optical excitations, including dark plasmons. We also predict a dichroic response when probing a chiral biomolecule, which suggests the use of these electron beams for resolving different enantiomers.

Incidence rates and trends of hip/femur fractures in five European countries: comparison using e-healthcare records databases.

Hip fractures represent a major public health challenge worldwide. Multinational studies using a common methodology are scarce. We aimed to estimate the incidence rates (IRs) and trends of hip/femur fractures over the period 2003-2009 in five European countries. The study was performed using seven electronic health-care records databases (DBs) from Denmark, The Netherlands, Germany, Spain, and the United Kingdom, based on the same protocol. Yearly IRs of hip/femur fractures were calculated for the general population and for those aged ≥50 years. Trends over time were evaluated using linear regression analysis for both crude and standardized IRs. Sex- and age-standardized IRs for the UK, Netherlands, and Spanish DBs varied from 9 to 11 per 10,000 person-years for the general population and from 22 to 26 for those ≥50 years old; the German DB showed slightly higher IRs (about 13 and 30, respectively), whereas the Danish DB yielded IRs twofold higher (19 and 52, respectively). IRs increased exponentially with age in both sexes. The ratio of females to males was ≥2 for patients aged ≥70-79 years in most DBs. Statistically significant trends over time were only shown for the UK DB (CPRD) (+0.7% per year, P < 0.01) and the Danish DB (-1.4% per year, P < 0.01). IRs of hip/femur fractures varied greatly across European countries. With the exception of Denmark, no decreasing trend was observed over the study period.

Extraordinary absorption of sound in porous lamella-crystals.

We present the design of a structured material supporting complete absorption of sound with a broadband response and functional for any direction of incident radiation. The structure which is fabricated out of porous lamellas is arranged into a low-density crystal and backed by a reflecting support. Experimental measurements show that strong all-angle sound absorption with almost zero reflectance takes place for a frequency range exceeding two octaves. We demonstrate that lowering the crystal filling fraction increases the wave interaction time and is responsible for the enhancement of intrinsic material dissipation, making the system more absorptive with less material.

Tunable plasmons in atomically thin gold nanodisks.

The ability to modulate light at high speeds is of paramount importance for telecommunications, information processing and medical imaging technologies. This has stimulated intense efforts to master optoelectronic switching at visible and near-infrared frequencies, although coping with current computer speeds in integrated architectures still remains a major challenge. As a partial success, mid-infrared light modulation has been recently achieved through gating patterned graphene. Here we show that atomically thin noble metal nanoislands can extend optical modulation to the visible and near-infrared spectral range. We find plasmons in thin metal nanodisks to produce similar absorption cross-sections as spherical particles of the same diameter. Using realistic levels of electrical doping, plasmons are shifted by about half their width, thus leading to a factor-of-two change in light absorption. These results, which we substantiate on microscopic quantum theory of the optical response, hold great potential for the development of electrical visible and near-infrared light modulation in integrable, nanoscale devices.

Controlled interaction of surface quantum-well electronic states.

We report on the construction of well-defined surface quantum well arrangements by combining self-assembly protocols and molecular manipulation procedures. After the controlled removal of individual porphyrin molecules from dense-packed arrays on Ag(111), the surface state electrons are confined at the bare silver patches. These act as quantum wells that show well-defined unoccupied bound surface states. Scanning tunneling spectroscopy and complementary boundary element method calculations are performed to characterize the interaction between the bound states of adjacent quantum wells and reveal a hybridization of wave functions resulting in bonding and antibonding states. The interwell coupling can be tuned by the deliberate choice of the molecules acting as potential barriers. The fabrication method is shown to be ideally suited to engineer specific configurations as one-dimensional chains or two-dimensional artificial molecules.

Universal distance-scaling of nonradiative energy transfer to graphene.

The near-field interaction between fluorescent emitters and graphene exhibits rich physics associated with local dipole-induced electromagnetic fields that are strongly enhanced due to the unique properties of graphene. Here, we measure emitter lifetimes as a function of emitter-graphene distance d, and find agreement with a universal scaling law, governed by the fine-structure constant. The observed energy transfer rate is in agreement with a 1/d(4) dependence that is characteristic of two-dimensional lossy media. The emitter decay rate is enhanced 90 times (energy transfer efficiency of ~99%) with respect to the decay in vacuum at distances d ≈ 5 nm. This high energy transfer rate is mainly due to the two-dimensionality and gapless character of the monatomic carbon layer. Graphene is thus shown to be an extraordinary energy sink, holding great potential for photodetection, energy harvesting, and nanophotonics.