Simultaneous imaging and diffraction in the dynamic diamond anvil cell.

The ability to visualize a sample undergoing a pressure-induced phase transition allows for the determination of kinetic parameters, such as the nucleation and growth rates of the high-pressure phase. For samples that are opaque to visible light (such as metallic systems), it is necessary to rely on x-ray imaging methods for sample visualization. Here, we present an experimental platform developed at beamline P02.2 at the PETRA III synchrotron radiation source, which is capable of performing simultaneous x-ray imaging and diffraction of samples that are dynamically compressed in piezo-driven diamond anvil cells. This setup utilizes a partially coherent monochromatic x-ray beam to perform lensless phase contrast imaging, which can be carried out using either a parallel- or focused-beam configuration. The capabilities of this platform are illustrated by experiments on dynamically compressed Ga and Ar. Melting and solidification were identified based on the observation of solid/liquid phase boundaries in the x-ray images and corresponding changes in the x-ray diffraction patterns collected during the transition, with significant edge enhancement observed in the x-ray images collected using the focused-beam. These results highlight the suitability of this technique for a variety of purposes, including melt curve determination.

Novel experimental setup for megahertz X-ray diffraction in a diamond anvil cell at the High Energy Density (HED) instrument of the European X-ray Free-Electron Laser (EuXFEL).

The high-precision X-ray diffraction setup for work with diamond anvil cells (DACs) in interaction chamber 2 (IC2) of the High Energy Density instrument of the European X-ray Free-Electron Laser is described. This includes beamline optics, sample positioning and detector systems located in the multipurpose vacuum chamber. Concepts for pump-probe X-ray diffraction experiments in the DAC are described and their implementation demonstrated during the First User Community Assisted Commissioning experiment. X-ray heating and diffraction of Bi under pressure, obtained using 20 fs X-ray pulses at 17.8 keV and 2.2 MHz repetition, is illustrated through splitting of diffraction peaks, and interpreted employing finite element modeling of the sample chamber in the DAC.

New dynamic diamond anvil cells for tera-pascal per second fast compression x-ray diffraction experiments.

Fast compression experiments performed using dynamic diamond anvil cells (dDACs) employing piezoactuators offer the opportunity to study compression-rate dependent phenomena. In this paper, we describe an experimental setup which allows us to perform time-resolved x-ray diffraction during the fast compression of materials using improved dDACs. The combination of the high flux available using a 25.6 keV x-ray beam focused with a linear array of compound refractive lenses and the two fast GaAs LAMBDA detectors available at the Extreme Conditions Beamline (P02.2) at PETRA III enables the collection of x-ray diffraction patterns at an effective repetition rate of up to 4 kHz. Compression rates of up to 160 TPa/s have been achieved during the compression of gold in a 2.5 ms fast compression using improved dDAC configurations with more powerful piezoactuators. The application of this setup to low-Z compounds at lower compression rates is described, and the high temporal resolution of the setup is demonstrated. The possibility of applying finely tuned pressure profiles opens opportunities for future research, such as using oscillations of the piezoactuator to mimic propagation of seismic waves in the Earth.

Single crystal toroidal diamond anvils for high pressure experiments beyond 5 megabar.

Static compression experiments over 4 Mbar are rare, yet critical for developing accurate fundamental physics and chemistry models, relevant to a range of topics including modeling planetary interiors. Here we show that focused ion beam crafted toroidal single-crystal diamond anvils with ~9.0 µm culets are capable of producing pressures over 5 Mbar. The toroidal surface prevents gasket outflow and provides a means to stabilize the central culet. We have reached a maximum pressure of ~6.15 Mbar using Re as in situ pressure marker, a pressure regime typically accessed only by double-stage diamond anvils and dynamic compression platforms. Optimizing single-crystal diamond anvil design is key for extending the pressure range over which studies can be performed in the diamond anvil cell.

A simple and portable multi-channel pyrometer allowing temperature measurements down to 800 K on the microsecond scale.

The measurement of transient temperatures less than 1000 K for samples in laser-heated diamond anvil cells remains a challenge. Here we present the design and performance characteristics of a multi-channel pyrometer that works in the near-infrared from 1200 to 2000 nm. It has a relatively small footprint, is portable, requires only low voltage power supplies, and can report temperatures down to 800 K on the millisecond scale or faster. A single data point without averaging can be acquired in 14 µs (sampling rate of 7 kilosamples per second). In conjunction with a diamond anvil cell, the system delivers accurate and rapid measurements down to ∼830 K. The pyrometer has been successfully interfaced several times with the combined x-ray diffraction and laser heating system at the High Pressure Collaborative Access Team at the Advanced Photon Source at Argonne National Laboratories.

Anomalous elastic properties across the γ to α volume collapse in cerium.

The behavior of the f-electrons in the lanthanides and actinides governs important macroscopic properties but their pressure and temperature dependence is not fully explored. Cerium with nominally just one 4f electron offers a case study with its iso-structural volume collapse from the γ-phase to the α-phase ending in a critical point (p C, V C, T C), unique among the elements, whose mechanism remains controversial. Here, we present longitudinal (c L) and transverse sound speeds (c T) versus pressure from higher than room temperature to T C for the first time. While c L experiences a non-linear dip at the volume collapse, c T shows a step-like change. This produces very peculiar macroscopic properties: the minimum in the bulk modulus becomes more pronounced, the step-like increase of the shear modulus diminishes and the Poisson's ratio becomes negative-meaning that cerium becomes auxetic. At the critical point itself cerium lacks any compressive strength but offers resistance to shear.

A versatile medium-resolution x-ray emission spectrometer for diamond anvil cell applications.

We present design and performance details for a polycapillary-coupled x-ray spectrometer that provides very high collection efficiency at a moderate energy resolution suitable for many studies of nonresonant x-ray emission spectroscopy, especially for samples of heavy elements under high pressures. Using a single Bragg analyzer operating close to backscattering geometry so as to minimize the effect of the weak divergence of the quasicollimated exit beam from the polycapillary optic, this instrument can maintain a typical energy resolution of 5 eV over photon energies from 5 keV to 10 keV. We find dramatically improved count rates as compared to a traditional higher-resolution instrument based on a single spherically bent crystal analyzer.

Strength and Debye temperature measurements of cerium across the γ → α volume collapse: the lattice contribution.

The longitudinal and transverse sound speeds, cL and cT, of polycrystalline cerium were measured under pressure across the iso-structural γ-α phase transition at 0.75 GPa to beyond 3 GPa. In contrast to previous methods all quantities were directly obtained and no assumptions were made about the size of the volume collapse. Up to the transition our values for cL are in excellent agreement with previous ones, while our values for cT are significantly lower. We deduce values for the adiabatic bulk modulus BS, the shear modulus [Formula: see text], and the pressure dependent Debye temperature, ΘD(p). ΘD(p) is in good agreement with recent results derived from phonon dispersion measurements on single crystals. The ratio of the Debye temperature values bracketing the transition indicates a lattice contribution to the entropy change across the volume collapse, ΔSvib(γ â†’ α) ≈ (0.68 ± 0.06)kB, consistent with previous results obtained by neutron scattering, but significantly larger than other previously determined values.

Age attenuates leucine oxidation after eccentric exercise.

Aging may alter protein metabolism during periods of metabolic and physiologic challenge. The purpose of this study was to assess the effects of age on whole-body amino acid turnover in response to eccentric exercise and hyperglycemia-induced hyperinsulinemia. 16 healthy men were divided into young (N=8) and older (N=8) groups. Protein metabolism was assessed using a [1-13C]-leucine isotopic tracer approach. Measures were obtained under fasted basal conditions and during 3-h hyperglycemic clamps that were performed without (control) and 48 h after eccentric exercise. Exercise reduced leucine oxidation in the younger men (P<0.05), but not in older men. Insulin sensitivity was inversely correlated with leucine oxidation (P<0.05), and was lower in older men (P<0.05). Healthy aging is associated with an impaired capacity to adjust protein oxidation in response to eccentric exercise. The decreased efficiency of protein utilization in older men may contribute to impaired maintenance, growth, and repair of body tissues with advancing age.

X-ray emission spectroscopy of cerium across the γ-α volume collapse transition.

High-pressure x-ray emission measurements are used to provide crucial evidence in the longstanding debate over the nature of the isostructural (α, γ) volume collapse in elemental cerium. Extended local atomic model calculations show that the satellite of the Lγ emission line offers direct access to the total angular momentum observable (J(2)). This satellite experiences a 30% steplike decrease across the volume collapse, validating the Kondo model in conjunction with previous measurements. Direct comparisons are made with previous predictions by dynamical mean field theory. A general experimental methodology is demonstrated for analogous work on a wide range of strongly correlated f-electron systems.

Discovering pathways of sarcopenia in older adults: a role for insulin resistance on mitochondria dysfunction.

The precise cause of sarcopenia, skeletal muscle loss and strength, in older persons is unknown. However, there is a strong evidence for muscle loss due to insulin resistance as well as mitochondrial dysfunction over aging. Considering that epidemiological studies have underlined that insulin resistance may have a specific role on skeletal muscle fibre atrophy and mitochondrial dysfunction has also been extensively shown to have a pivotal role on muscle loss in older persons, a combined pathway may not be ruled out. Considering that there is growing evidence for an insulin-related pathway on mitochondrial signaling, we hypothesize that a high degree of insulin resistance will be associated with the development of sarcopenia through specific alterations on mitochondrial functioning. This paper will highlight recent reviews regarding the link between skeletal muscle mitochondrial dysfunction and insulin resistance. We will specifically emphasize possible steps involved in sarcopenia over aging, including potential biomolecular mechanisms of insulin resistance on mitochondrial functioning.

Sarcopenia: designing phase IIB trials.

Sarcopenia is the age-related involuntary loss of skeletal muscle mass and functionality that can lead to the development of disability, frailty and increased health care costs. The development of interventions aimed at preventing and/or treating sarcopenia is complex, requiring the adoption of assumptions and standards that are not well established scientifically or clinically. A number of investigators and clinicians (both from academia and industry) met in Rome (Italy) in 2009 to develop a consensus definition of sarcopenia. Subsequently, in Albuquerque (New Mexico, USA) in 2010, the same group met again to consider the complex issues necessary for designing Phase II clinical trials for sarcopenia. Current clinical trial data indicate that fat-free mass (FFM) parameters are responsive to physical activity/nutritional treatment modalities over short time periods, but pharmacological trials of sarcopenia have yet to show significant efficacy. In order to conduct a clinical trial within a reasonable time frame, groups that model or display accelerated aging and loss of FFM are necessary. Few studies have used acceptable designs for testing treatment effects, sample sizes or primary outcomes that could provide interpretable findings or effects across studies. Dual energy x-ray absorptiometry (DXA) is the measure of choice for assessing FFM, but sufficient time is needed for changes to be detected accurately and reliably. A tool set that would allow clinical, basic and epidemiological research on sarcopenia to advance rapidly toward diagnosis and treatment phases should be those reflecting function and strength.

Randomised controlled clinical trial for the use of deracoxib during intense rehabilitation exercises after tibial plateau levelling osteotomy.

During intense physical exercise, the cyclo-oxygenase-2 (COX-2) pathway is upregulated which contributes to soreness. The aim of this study was to determine if there was a clinical affect of deracoxib (COX-2 selective antagonist) on dogs engaged in intense rehabilitation following tibial plateau levelling osteotomy for cranial cruciate ligament rupture. Our hypothesis was that dogs receiving deracoxib would demonstrate less lameness, better range-of-motion (ROM), and faster muscle mass recovery than the control dogs. Thirty dogs were randomised to the treatment (deracoxib at 1-2 mg/kg once daily by mouth) or control (no treatment) group. Outcomes including gait analysis, thigh circumference, and goniometry, were measured by one investigator, who was masked to group preoperatively, and at the end of each intense rehabilitation week (3, 5, and 7 weeks postoperatively). The only difference between groups for any outcome measure at any time point was a greater preoperative stifle ROM in the group receiving deracoxib (p = 0.04). This study showed that treatment with deracoxib did not provide better outcomes when dogs were subjected to intense rehabilitation after tibial plateau levelling osteotomy. Each patient should be evaluated individually to determine if administration of deracoxib is appropriate.

Frailty and muscle metabolism dysregulation in the elderly.

The frailty syndrome is increasingly recognized by geriatricians to identify elders at an extreme risk of adverse health outcomes. The physiological changes that result in frailty are complex and up to now have been extremely difficult to characterize due to the frequent coexistence of acute and chronic illness. Frailty is characterized by an decline in the functional reserve with several alterations in diverse physiological systems, including lower energy metabolism, decreased skeletal muscle mass and quality, altered hormonal and inflammatory functions. This altered network leads to an extreme vulnerability for disease, functional dependency, hospitalization and death. One of the most important core components of the frailty syndrome is a decreased reserve in skeletal muscle functioning which is clinically characterized by a loss in muscle mass and strength (sarcopenia), in walking performance and in endurance associated with a perception of exhaustion and fatigue. There are a number of physiological changes that occur in senescent muscle tissues that have a critical effect on body metabolism. The causes of sarcopenia are multi-factorial and can include disuse, changing hormonal function, chronic diseases, inflammation, insulin resistance, and nutritional deficiencies. In this review, we will explore the dysregulation of some biological mechanisms that may contribute to the pathophysiology of the frailty syndrome through age-related changes in skeletal muscle mass and function.

Cachexia and aging: an update based on the Fourth International Cachexia Meeting.

This manuscript highlights the new developments in the pathophysiology of anorexia, cachexia and sarcopenia, based on presentations given at the Fourth International Cachexia Meeting. It stresses the importance of these conditions in older persons.

Double-blind placebo-controlled trial of adjuvant pamidronate with palliative radiotherapy and intravenous doxorubicin for canine appendicular osteosarcoma bone pain.

BACKGROUND: Canine osteosarcoma (OSA) causes focal malignant osteolysis leading to severe pain. Despite the documented efficacy of radiotherapy or IV aminobisphosphonates for managing cancer bone pain, their potential combined therapeutic value has not been reported in OSA-bearing dogs. HYPOTHESIS: Pamidronate combined with standardized palliative therapy will improve pain control and bone biologic effects in OSA-bearing dogs. ANIMALS: Fifty dogs with appendicular OSA treated with standardized palliative therapy and either pamidronate or sterile saline. METHODS: Randomized, prospective, double-blinded, placebo-controlled study. Treatment responses for dogs receiving standardized palliative therapy with (n = 26) or without (n = 24) adjuvant pamidronate were serially evaluated for changes in subjective pain scores, urine N-telopeptide (NTx) excretion, primary tumor relative bone mineral density (rBMD), and computerized pressure platform gait analysis. RESULTS: Median duration of subjective pain relief for dogs treated with adjuvant pamidronate or placebo was 76 and 75 days, respectively (P= .39). Forty percent (20/50; pamidronate [11/26] and placebo [9/24]) of dogs experienced durable analgesia, defined by pain alleviation > or =112 days. For patients achieving durable pain control, dogs treated with pamidronate achieved greater reductions in NTx excretion and larger increases in rBMD compared with placebo controls. Changes in peak vertical force assessed by computerized pressure platform gait analysis correlated with pain alleviation in OSA-bearing dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: Combining pamidronate with standardized palliative therapy is safe, but does not clearly improve pain alleviation. However, in dogs achieving durable pain control, adjuvant pamidronate appears to decrease focal bone resorption in the local tumor microenvironment.

Thermal signatures of the Kondo volume collapse in cerium.

X-ray diffraction measurements of cerium in the vicinity of the isostructural gamma-alpha transition have been performed with high precision and accuracy from room temperature to almost 800 K. The disputed location of the critical point has been found to occur at 1.5+/-0.1 GPa and 480+/-10 K. The data are well fit by the Kondo volume collapse model plus a quasiharmonic representation of the phonons. The resultant free energy is validated against data for the thermodynamic Grüneisen parameter and, beyond the dominant spin-fluctuation contribution, indicates a dramatic change in the lattice Grüneisen parameter across the transition.

Comparison of three methods for the management of fragmented medial coronoid process in the dog. A systematic review and meta-analysis.

The objective of this review and analysis was to compare arthroscopy, medial arthrotomy and medical management for treating fragmented coronoid process in the dog. The data come from manuscripts published in peer-reviewed veterinary journals, and the study design is a systematic review followed by meta-analysis. The meta-analysis combines data from a set of studies so that surgical techniques and medial management can be compared in a single analysis. Several literature databases and veterinary texts were thoroughly searched to provide a list of over 400 candidate manuscripts. Inclusion criteria were used to filter the candidate manuscripts to a final set of four manuscripts that directly pertained to the clinical question. They were scored for their evidentiary value using a semi-objective measure. The results were that arthroscopy was superior to medial arthrotomy and medical management, but medial arthrotomy was not superior to medical management. Only one manuscript was a randomized controlled trial, hence the results must be tempered by the evidentiary value of the data.

New cubic phase of Li3N: stability of the N3- ion to 200 GPa.

Diamond-anvil cell experiments augmented by first-principles calculations have found a remarkable stability of the N(3-) ion in Li3N to a sixfold volume reduction. A new (gamma) phase is discovered above 40(+/-5) GPa, with an 8% volume collapse and a band gap quadrupling at the transition determined by synchrotron x-ray diffraction and inelastic x-ray scattering. gamma-Li(3)N (Fm3m, Li(3)Bi-like structure) remains stable up to 200 GPa, and calculations do not predict metallization until approximately 8 TPa. The high structural stability, wide band gap, and simple electronic structure make this N(3-) based system analogous to lower valency compounds (MgO, NaCl, Ne), meriting its use as an internal pressure standard.