Magneto-Optical Detection of the Spin Hall Effect in Pt and W Thin Films.

The conversion of charge currents into spin currents in nonmagnetic conductors is a hallmark manifestation of spin-orbit coupling that has important implications for spintronic devices. Here we report the measurement of the interfacial spin accumulation induced by the spin Hall effect in Pt and W thin films using magneto-optical Kerr microscopy. We show that the Kerr rotation has opposite sign in Pt and W and scales linearly with current density. By comparing the experimental results with ab initio calculations of the spin Hall and magneto-optical Kerr effects, we quantitatively determine the current-induced spin accumulation at the Pt interface as 5×10^{-12} µ_{B} A^{-1} cm^{2} per atom. From thickness-dependent measurements, we determine the spin diffusion length in a single Pt film to be 11±3 nm, which is significantly larger compared to that of Pt adjacent to a magnetic layer.

Transient ferromagnetic-like state mediating ultrafast reversal of antiferromagnetically coupled spins.

Ferromagnetic or antiferromagnetic spin ordering is governed by the exchange interaction, the strongest force in magnetism. Understanding spin dynamics in magnetic materials is an issue of crucial importance for progress in information processing and recording technology. Usually the dynamics are studied by observing the collective response of exchange-coupled spins, that is, spin resonances, after an external perturbation by a pulse of magnetic field, current or light. The periods of the corresponding resonances range from one nanosecond for ferromagnets down to one picosecond for antiferromagnets. However, virtually nothing is known about the behaviour of spins in a magnetic material after being excited on a timescale faster than that corresponding to the exchange interaction (10-100 fs), that is, in a non-adiabatic way. Here we use the element-specific technique X-ray magnetic circular dichroism to study spin reversal in GdFeCo that is optically excited on a timescale pertinent to the characteristic time of the exchange interaction between Gd and Fe spins. We unexpectedly find that the ultrafast spin reversal in this material, where spins are coupled antiferromagnetically, occurs by way of a transient ferromagnetic-like state. Following the optical excitation, the net magnetizations of the Gd and Fe sublattices rapidly collapse, switch their direction and rebuild their net magnetic moments at substantially different timescales; the net magnetic moment of the Gd sublattice is found to reverse within 1.5 picoseconds, which is substantially slower than the Fe reversal time of 300 femtoseconds. Consequently, a transient state characterized by a temporary parallel alignment of the net Gd and Fe moments emerges, despite their ground-state antiferromagnetic coupling. These surprising observations, supported by atomistic simulations, provide a concept for the possibility of manipulating magnetic order on the timescale of the exchange interaction.

Distinguishing the ultrafast dynamics of spin and orbital moments in solids.

For an isolated quantum particle, such as an electron, the orbital (L) and spin (S) magnetic moments can change provided that the total angular momentum of the particle is conserved. In condensed matter, an efficient transfer between L and S can occur owing to the spin-orbit interaction, which originates in the relativistic motion of electrons. Disentangling the absolute contributions of the orbital and spin angular momenta is challenging, however, as any transfer between the two occurs on femtosecond timescales. Here we investigate such phenomena by using ultrashort optical laser pulses to change the magnetization of a ferromagnetic film and then probe its dynamics with circularly polarized femtosecond X-ray pulses. Our measurements enable us to disentangle the spin and orbital components of the magnetic moment, revealing different dynamics for L and S. We highlight the important role played by the spin-orbit interaction in the ultrafast laser-induced demagnetization of ferromagnetic films, and show also that the magneto-crystalline anisotropy energy is an important quantity to consider in such processes. Our study provides insights into the dynamics in magnetic systems as well as perspectives for the ultrafast control of information in magnetic recording media.

[Social Law Entitlements and Compensations for Visually Impaired Patients in Germany, Focussed on Glaucoma]. / Sozialmedizinische und versorgungsrechtliche Aspekte des Glaukoms.

Although prevention of progression is the most important issue in the treatment of glaucoma patients, information on visual aids and social law entitlements is also helpful. In this article, the main aspects of compensation for visual impairment are outlined so that you can competently support your patients, without much effort, with helpful tips and appropriate instructions.

[Management of outpatient medications in care units: An audit of clinical practices]. / Traitement personnel du patient hospitalisé : audit de pratiques.

OBJECTIVES: To assess the outpatient medication management in care units two years after the release of an institutional procedure. To assess the patients' satisfaction with their treatment and with the information transmitted by healthcare professionals. METHODS: An audit of clinical practices was conducted in 23 units of our universitary hospital - general, surgery, emergency departments. Questionnaires were developed and validated by an institutional working group and were composed of three themes: management of the outpatient medication at the admission, awareness of tools and information transmission. Two physicians (a senior and a resident), a registered nurse, a head nurse and a patient were interviewed. RESULTS: Eighty-one medical and paramedical team members and 21 patients were interviewed for the study. According to statements collected, the procedure was unknown by 100% of the interviewed surgeons and 69% of the interviewed physicians. The practices being used by the medical units were more in line with recommendations than the surgery units. Among the patients interviewed, 19 (86%) were satisfied with the information they received during their hospitalization and 4 (19%) managed their own medication treatment with the help of a nurse in only 36% of the cases according to their statements. CONCLUSIONS: The management of outpatient medications during hospitalization is representative of the difficulties to master the continuity of pharmaceutical care at the various transition points. Coordination and cooperation between the different healthcare professionals and patients are the major key success to ensure an optimized healthcare procedure.

Ultrafast spin transport as key to femtosecond demagnetization.

Irradiating a ferromagnet with a femtosecond laser pulse is known to induce an ultrafast demagnetization within a few hundred femtoseconds. Here we demonstrate that direct laser irradiation is in fact not essential for ultrafast demagnetization, and that electron cascades caused by hot electron currents accomplish it very efficiently. We optically excite a Au/Ni layered structure in which the 30 nm Au capping layer absorbs the incident laser pump pulse and subsequently use the X-ray magnetic circular dichroism technique to probe the femtosecond demagnetization of the adjacent 15 nm Ni layer. A demagnetization effect corresponding to the scenario in which the laser directly excites the Ni film is observed, but with a slight temporal delay. We explain this unexpected observation by means of the demagnetizing effect of a superdiffusive current of non-equilibrium, non-spin-polarized electrons generated in the Au layer.

Challenges of spatially extrapolating aquatic pesticide pollution for policy evaluation.

Aquatic pesticide pollution is an important issue worldwide. Countries rely on monitoring programs to observe water bodies quality and on models to evaluate pesticide risks for entire stream networks. Measurements are typically sparse and discontinuous which lead to issues in quantifying pesticide transport at the catchment scale. Therefore, it is essential to assess the performance of extrapolation approaches and provide guidance on how to extend monitoring programs to improve predictions. Here we present a feasibility study to predict pesticide levels in a spatially explicit manner in the Swiss stream network based on the national monitoring program quantifying organic micropollutants at 33 sites and spatially distributed explanatory variables. Firstly, we focused on a limited set of herbicides used on corn crops. We observed a significant relationship between herbicide concentrations and the areal fraction of hydrologically connected cornfields. Neglecting connectivity revealed no influence of areal corn coverage on the herbicide levels. Considering chemical properties of the compounds slightly improved the correlation. Secondly, we analysed a set of 18 pesticides widely used on different crops and monitored across the country. In this case, the areal fractions of arable or crop lands showed significant correlations with average pesticide concentrations. Similar results were found with average annual discharge or precipitation if two outlier sites were neglected. The correlations found in this paper explained only about 30 % of the observed variance leaving most of the variability unexplained. Accordingly, extrapolating the results from the existing monitoring sites to the Swiss river network comes with substantial uncertainty. Our study highlights possible reasons for weak matches, such as missing pesticide application data, limited set of compounds in the monitoring program, or a limited understanding of factors differentiating the loss rates from different catchments. Improving the data on pesticide applications will be essential to progress in this regard.

Methods comparison for detecting trends in herbicide monitoring time-series in streams.

An inadvertent consequence of pesticide use is aquatic pesticide pollution, which has prompted the implementation of mitigation measures in many countries. Water quality monitoring programs are an important tool to evaluate the efficacy of these mitigation measures. However, large interannual variability of pesticide losses makes it challenging to detect significant improvements in water quality and to attribute these improvements to the application of specific mitigation measures. Thus, there is a gap in the literature that informs researchers and authorities regarding the number of years of aquatic pesticide monitoring or the effect size (e.g., loss reduction) that is required to detect significant trends in water quality. Our research addresses this issue by combining two exceptional empirical data sets with modelling to explore the relationships between the achieved pesticide reduction levels due to mitigation measures and the length of the observation period for establishing statistically significant trends. Our study includes both a large (Rhine at Basel, ∼36,300 km2) and small catchment (Eschibach, 1.2 km2), which represent spatial scales at either end of the spectrum that would be realistic for monitoring programs designed to assess water quality. Our results highlight several requirements in a monitoring program to allow for trend detection. Firstly, sufficient baseline monitoring is required before implementing mitigation measures. Secondly, the availability of pesticide use data helps account for the interannual variability and temporal trends, but such data are usually lacking. Finally, the timing and magnitude of hydrological events relative to pesticide application can obscure the observable effects of mitigation measures (especially in small catchments). Our results indicate that a strong reduction (i.e., 70-90 %) is needed to detect a change within 10 years of monitoring data. The trade-off in applying a more sensitive method for change detection is that it may be more prone to false-positives. Our results suggest that it is important to consider the trade-off between the sensitivity of trend detection and the risk of false positives when selecting an appropriate method and that applying more than one method can provide more confidence in trend detection.

Seasonal drivers and risks of aquatic pesticide pollution in drought and post-drought conditions in three Mediterranean watersheds.

The Western Cape in South Africa has a Mediterranean climate, which has in part led to an abundance of agriculturally productive land supporting the wheat, deciduous fruit, wine, and citrus industries. South Africa is the leading pesticide user in Sub-Saharan Africa. There is limited data on the pesticide pollution of surface water over different seasons in low- and middle-income countries. We evaluated the seasonal drivers of aquatic pesticide pollution in three river catchments (Berg, Krom, and Hex Rivers) from July 2017 to June 2018 and April to July 2019, using 48 passive samplers. Our sampling followed the most severe drought (2015-2018) since recordings in 1960. Thus, our analyses focus on how drought and post-drought conditions may affect in-stream pesticide concentrations and loads. Samples were analyzed for 101 pesticide compounds using liquid chromatography - high-resolution mass spectrometry. Environmental Quality Standards (EQS) were used to assess the risks. We detected 60 pesticide compounds across the sampling periods. Our results indicate that all samples across all three catchments contained at least three pesticides and that the majority (83%) contained five or more pesticides. Approximately half the number of pesticides were detected after the drought in 2018. High concentration sums of pesticides (>1 µg/L) were detected over long time periods in the Hex River Valley (22 weeks) and in Piketberg (four weeks). Terbuthylazine, imidacloprid, and metsulfuron-methyl were detected in the highest concentrations, making up most of the detected mass, and were frequently above EQS. The occurrence of some pesticides in water generally correlated with their application and rainfall events. However, those of imidacloprid and terbuthylazine did not, suggesting that non-rainfall-driven transport processes are important drivers of aquatic pesticide pollution. The implementation of specific, scientifically sound, mitigation measures against aquatic pesticide pollution would require comprehensive pesticide application data as well as a targeted study identifying sources and transport processes for environmentally persistent pesticides.

Moving targets, long-lived infrastructure, and increasing needs for integration and adaptation in water management: an illustration from Switzerland.

Switzerland provides an example of successful management of water infrastructure and water resources that was accomplished largely without integration across sectors. Limitations in this approach have become apparent; decisions that were formerly based only on technical and economic feasibility must now incorporate broader objectives such as ecological impact. In addition, current and emerging challenges relate to increasingly complex problems that are likely to demand more integrated approaches. If such integration is to be of benefit, it must be possible to redirect resources across sectors, and the synergies derived from integration must outweigh the additional cost of increased complexity.

[Diabetes and end stage renal disease. Eight year progression in the Canton de Vaud, Switzerland]. / Diabète et insuffisance rénate terminate. Evolution en huit ans dans le canton de Vaud.

Diabetic nephropathy is the first cause of endstage renal disease. The demographic expansion, the increase in the incidence of diabetes and the prolonged survival rates explain the steep increase observed these last 30 years. In the United States, improved treatment has brought to a decline in the incidence of end-stage renal disease in the diabetic population since the mid nineties. We examined the change in prevalence of diabetics on dialysis from 2001 and 2009 in the Canton de Vaud, Switzerland. The prevalence of diabetics on dialysis increased from 18% to 31% in dialysis centers and increased from 1.1/1000 to 1.9/1000 in the diabetic population. These are strong indicators that efforts are needed to improve the renal outcome of patients with diabetic nephropathy.

Continuous high-frequency pesticide monitoring to observe the unexpected and the overlooked.

Synthetic Plant Protection Products (PPPs) are a key element for a large part of today's global food systems. However, the transport of PPPs and their transformation products (TPs) to water bodies has serious negative effects on aquatic ecosystems. Small streams in agricultural catchments may experience pronounced concentration peaks given the proximity to fields and poor dilution capacity. Traditional sampling approaches often prevent a comprehensive understanding of PPPs and TPs concentration patterns being limited by trade-offs between temporal resolution and duration of the observation period. These limitations result in a knowledge gap for accurate ecotoxicological risk assessment and the achievement of optimal monitoring strategies for risk mitigation. We present here high-frequency PPPs and TPs concentration time-series measured with the autonomous MS2Field platform that combines continuous sampling and on-site measurements with a high-resolution mass spectrometer, which allows for overcoming temporal trade-offs. In a small agricultural catchment, we continuously measured 60 compounds at 20 minutes resolution for 41 days during the growing season. This observation period included 8 large and 15 small rain events and provided 2560 concentration values per compound. To identify similarities and differences among the compound-specific concentration time-series, we analysed the entire dataset with positive matrix factorisation. Six factors sufficiently captured the overall complexity in concentration dynamics. While one factor reflected dilution during rainfall, five factors identified PPPs groups that seemed to share a common history of recent applications. The investigation per event of the concentration time-series revealed a surprising complexity of dynamic patterns; physico-chemical properties of the compounds did not influence the (dis)similarity of chemographs. Some PPPs concentration peaks led while others lagged by several hours the water level peaks during large events. During small events, water level peaks always preceded concentration peaks, which were generally only observed when the water levels had almost receded to pre-event levels. Thus, monitoring schemes relying on rainfall or water level as proxies for triggering sampling may lead to systematic biases. The high temporal resolution revealed that the Swiss national monitoring integrating over 3.5 days underestimated critical concentration peaks by a factor of eight to more than 32, captured 3 out of 11 exceedances of legal acute quality standards (the relevant values in the Swiss Water Protection Law) and recorded 1 out of 9 exceedances of regulatory acceptable concentrations (the relevant values for the PPPs registration process). MS2Field allowed for observing unexpected and overlooked pesticide dynamics with consequences for further research but also for monitoring. The large variability in timing of concentration peaks relative to water level calls for more in-depth analyses regarding the respective transport mechanisms. To perform these analyses, spatially distributed sampling and time-series of geo-referenced PPPs application data are needed.

The ultimate speed of magnetic switching in granular recording media.

In magnetic memory devices, logical bits are recorded by selectively setting the magnetization vector of individual magnetic domains either 'up' or 'down'. In such devices, the fastest and most efficient recording method involves precessional switching: when a magnetic field B(p) is applied as a write pulse over a period tau, the magnetization vector precesses about the field until B(p)tau reaches the threshold value at which switching occurs. Increasing the amplitude of the write pulse B(p) might therefore substantially shorten the required switching time tau and allow for faster magnetic recording. Here we use very short pulses of a very high magnetic field to show that under these extreme conditions, precessional switching in magnetic media supporting high bit densities no longer takes place at well-defined field strengths; instead, switching occurs randomly within a wide range of magnetic fields. We attribute this behaviour to a momentary collapse of the ferromagnetic order of the spins under the load of the short and high-field pulse, thus establishing an ultimate limit to the speed of deterministic switching and magnetic recording.

[Best practice agreement: implementation of best practice guidelines in HCL hospitals in Lyon, France]. / Contrat de bon usage : mise en oeuvre opérationnelle des référentiels de bon usage aux hospices civils de Lyon.

Since 2004, the Hospices Civils de Lyon (HCL) hospitals are committed to comply with best practice guidelines for healthcare products that are reimbursed in addition to diagnosis related groups' (DRGs) tariffs in France, and that, even before the publication of the law concerning best practice agreement. It has been necessary to adapt national drugs best practice guidelines to every-day practice. A working group, COPIL RBU, has been created in HCL hospitals to manage the best practice guidelines locally. This group has two main activities: it conducts a scientific and regulatory information watch and follows up emerging indications at HCL. The group's best practice guidelines contain a classification of indications into three categories: approved indications (market authorization and temporary protocol of treatment), currently-assessed indications and contra-indications. Our best practice guidelines are more than a rewriting of national guidelines since they include emerging indications validated by prescribing physicians at HCL hospitals. A scientific argumentation is made for each emerging indication that is classified in our guidelines, based on the level of scientific evidence available. The practical use of our best practice guidelines is made through a best practice prescription that enables the traceability of drugs from the prescription to the administration to the patient. These prescriptions are accompanied with best practice guidelines made by medical and pharmaceutical professional groups. Audits will then be conducted to assess the indications' conformity to our guidelines and to have a better knowledge of current medical practice.

A review of long-term pesticide monitoring studies to assess surface water quality trends.

Aquatic pesticide pollution from both agricultural and urban pest control is a concern in many parts of the world. Making an accurate assessment of pesticide exposure is the starting point to protecting aquatic ecosystems. This in turn requires the design of an effective monitoring program. Monitoring is also essential to evaluate the efficacy of mitigation measures aimed to curb pesticide pollution. However, empirical evidence for their efficacy can be confounded by additional influencing factors, most prominently variable weather conditions. This review summarizes the experiences gained from long-term (>5 years) pesticide monitoring studies for detecting trends and provides recommendations for their improvement. We reviewed articles published in the scientific literature, with a few complements from selected grey literature, for a total of 20 studies which fulfill our search criteria. Overall, temporal trends of pesticide use and hydrological conditions were the two most common factors influencing aquatic pesticide pollution. Eighteen studies demonstrated observable effects to surface water concentrations from changes in pesticide application rates (e.g., use restriction) and sixteen studies from interannual variability in hydrological conditions during the application period. Accounting for seasonal- and streamflow-related variability in trend analysis is important because the two factors can obscure trends caused by changes in pesticide use or management practices. Other mitigation measures (e.g., buffer strips) were only detectable in four studies where concentrations or loads were reduced by > 45%. Collecting additional agricultural (e.g., pesticide use, mitigation measures) and environmental (e.g., precipitation, stream flow) data, as well as establishing a baseline before the implementation of mitigation measures have been consistently reported as prerequisites to interpret water quality trends from long-term monitoring studies, but have rarely been implemented in the past.

Agriculture versus wastewater pollution as drivers of macroinvertebrate community structure in streams.

Water pollution is ubiquitous globally, yet how the effects of pollutants propagate through natural ecosystems remains poorly understood. This is because the interactive effects of multiple stressors are generally hard to predict. Agriculture and municipal wastewater treatment plants (WWTPs) are often major sources of contaminants for streams, but their relative importance and the role of different pollutants (e.g. nutrients or pesticides) are largely unknown. Using a 'real world experiment' with sampling locations up- and downstream of WWTPs, we studied how effluent discharges affected water quality and macroinvertebrate communities in 23 Swiss streams across a broad land-use gradient. Variation partitioning of community composition revealed that overall water quality explained approximately 30% of community variability, whereby nutrients and pesticides each independently explained 10% and 2%, respectively. Excluding oligochaetes (which were highly abundant downstream of the WWTPs) from the analyses, resulted in a relatively stronger influence (3%) of pesticides on the macroinvertebrate community composition, whereas nutrients had no influence. Generally, the macroinvertebrate community composition downstream of the WWTPs strongly reflected the upstream conditions, likely due to a combination of efficient treatment processes, environmental filtering and organismal dispersal. Wastewater impacts were most prominently by the Saprobic index, whereas the SPEAR index (a trait-based macroinvertebrate metrics reflecting sensitivity to pesticides) revealed a strong impact of arable cropping but only a weak impact of wastewater. Overall, our results indicate that agriculture can have a stronger impact on headwater stream macroinvertebrate communities than discharges from WWTP. Yet, effects of wastewater-born micropollutants were clearly quantifiable among all other influence factors. Improving our ability to further quantify the impacts of micropollutants requires highly-resolved water quality and taxonomic data with adequate spatial and temporal sampling. These improvements would help to better account for the underlying causal pathways that drive observed biological responses, such as episodic contaminant peaks and dispersal-related processes.

Endothelial nitric oxide synthase mediates protective effects of hypoxic preconditioning in lungs.

To elucidate the protective mechanism of whole-body hypoxic preconditioning (WHPC) on pulmonary ischemia-reperfusion injury focussing on nitric oxide synthases (NOS), mice were placed in a hypoxic chamber (FIO(2)=0.1) for 4h followed by 12h of normoxia. Then, pulmonary ischemia for 1h followed by 5h of reperfusion was performed by clamping the left hilum in vivo (I/R). WHPC protected WT mice from pulmonary leukocyte infiltration as assessed by myeloperoxidase (MPO) activity, associated with a mild further increase in endothelial permeability (Evans Blue extravasation). When all NOS isoforms were inhibited during WHPC by L-NAME, mortality and MPO activity after I/R markedly increased. To determine the responsible NOS isoform, quantitative RT-PCR was performed for eNOS and iNOS mRNA, showing that only eNOS was upregulated in response to WHPC. While eNOS total protein expression remained unchanged, the amount of phosphorylated eNOS also increased. The WHPC/IR experiments were then repeated with eNOS knockout mice. Here, we found that the protective effect of WHPC on pulmonary leukocyte sequestration was abrogated, and endothelial leakage was further exacerbated. We conclude that WHPC limits neutrophil sequestration via an eNOS-dependent mechanism, and that eNOS helps preserve endothelial permeability during hypoxia and I/R.

Spin currents during ultrafast demagnetization of ferromagnetic bilayers.

Ultrafast spin currents induced by femtosecond laser excitation of ferromagnetic metals have been found to contribute to sub-picosecond demagnetization, and to cause a transient enhancement of the magnetization of the bottom Fe layer in a Ni/Ru/Fe layered structure. We analyze the ultrafast magnetization dynamics in such layered structures by element- and femtosecond time-resolved x-ray magnetic circular dichroism, for different Ni and Fe layer thicknesses, Ru and Ta interlayers, and by varying the pump laser fluence. While we do not observe the transient enhancement of the magnetization in Ni/Ru/Fe discovered previously, we do find a reduced demagnetization of the Fe layer compared to a Ni/Ta/Fe layered structure. In the latter, the spin-scattering Ta layer suppresses spin currents from the Ni layer into Fe, consistent with previous results. Any spin current arriving in the lower Fe layer will counteract other, local demagnetization mechanisms such as phonon-mediated spin-flip scattering. We find by increasing the Ni and Fe layer thicknesses in Ni/Ru/Fe a decreasing effect of spin currents on the buried Fe layer, consistent with a mean free path of the laser-induced spin currents of just a few nm. Our results suggest that in order to utilize ultrafast spin currents in an efficient manner, the sample design has to be optimized with these considerations in mind, and further studies clarifying the role of interfaces in the employed layered structures are needed.

Lipopolysaccharide internalization activates endotoxin-dependent signal transduction in cardiomyocytes.

We tested the hypothesis that bacterial lipopolysaccharide (LPS) must be internalized to facilitate endotoxin-dependent signal activation in cardiac myocytes. Fluorescently labeled LPS was used to treat primary cardiomyocyte cultures, perfused heart preparations, and the RAW264.7 macrophage cell line. Using confocal microscopy and spectrofluorometry, we found that LPS was rapidly internalized in cardiomyocyte cultures and Langendorff-perfused hearts. Although LPS uptake was also observed in macrophages, only a fraction of these cells were found to internalize endotoxin to the extent seen in cardiomyocytes. Colocalization experiments with organelle or structure-specific fluorophores showed that LPS was concentrated in the Golgi apparatus, lysosomes, and sarcomeres. Similar intracellular localization was demonstrated in cardiomyocytes by transmission electron microscopy using gold-labeled LPS. The internalization of LPS was dependent on endosomal trafficking, because an inhibitor of microfilament reorganization prevented uptake in both cardiomyocytes and whole hearts. Inhibition of endocytosis specifically restricted early activation of extracellular signal-regulated kinase proteins and nuclear factor-kappaB as well as later tumor necrosis factor-alpha production and inducible nitric oxide synthase expression. In conclusion, we have demonstrated that bacterial endotoxin is internalized and transported to specific intracellular sites in heart cells and that these events are obligatory for activation of LPS-dependent signal transduction.