CT-derived measures of muscle quantity and quality predict poorer outcomes from elective colorectal surgery: a UK multicentre retrospective cohort study.

PURPOSE: To assess whether preoperative radiologically defined lean muscle measures are associated with adverse clinical outcomes in patients undergoing elective surgery for colorectal cancer. METHODS: This retrospective UK-based multicentre data collection study identified patients having had colorectal cancer resection with curative intent between January 2013 to December 2016. Preoperative computed-tomography (CT) scans were used to measure psoas muscle characteristics. Clinical records provided postoperative morbidity and mortality data. RESULTS: This study included 1122 patients. The cohort was separated into a combined group (patients with both sarcopenia and myosteatosis) and others group (either sarcopenia or myosteatosis, or neither). For the combined group, anastomotic leak was predicted on univariate (OR 4.1, 95% CI 1.43-11.79; p = 0.009) and multivariate analysis (OR 4.37, 95% CI 1.41-13.53; p = 0.01). Also for the combined group, mortality (up to 5 years postoperatively) was predicted on univariate (HR 2.41, 95% CI 1.64-3.52; p < 0.001) and multivariate analysis (HR 1.93, 95% CI 1.28-2.89; p = 0.002). A strong correlation exists between freehand-drawn region of interest-derived psoas density measurement and using the ellipse tool (R2 = 81%; p < 0.001). CONCLUSION: Measures of lean muscle quality and quantity, which predict important clinical outcomes, can be quickly and easily taken from routine preoperative imaging in patients being considered for colorectal cancer surgery. As poor muscle mass and quality are again shown to predict poorer clinical outcomes, these should be proactively targeted within prehabilitation, perioperative and rehabilitation phases to minimise negative impact of these pathological states.

Radiation, optical, power flow, and electrical diagnostics at the Z facility: Layout and techniques utilized to operate in the harsh environment.

The Z machine is a current driver producing up to 30 MA in 100 ns that utilizes a wide range of diagnostics to assess accelerator performance and target behavior conduct experiments that use the Z target as a source of radiation or high pressures. We review the existing suite of diagnostic systems, including their locations and primary configurations. The diagnostics are grouped in the following categories: pulsed power diagnostics, x-ray power and energy, x-ray spectroscopy, x-ray imaging (including backlighting, power flow, and velocimetry), and nuclear detectors (including neutron activation). We will also briefly summarize the primary imaging detectors we use at Z: image plates, x-ray and visible film, microchannel plates, and the ultrafast x-ray imager. The Z shot produces a harsh environment that interferes with diagnostic operation and data retrieval. We term these detrimental processes "threats" of which only partial quantifications and precise sources are known. We summarize the threats and describe techniques utilized in many of the systems to reduce noise and backgrounds.

Development and integration of photonic Doppler velocimetry as a diagnostic for radiation driven experiments on the Z-machine.

Plasma density measurements are key to a wide variety of high-energy-density (HED) and laboratory astrophysics experiments. We present a creative application of photonic Doppler velocimetry (PDV) from which time- and spatially resolved electron density measurements can be made. PDV has been implemented for the first time in close proximity, ∼6 cm, to the high-intensity radiation flux produced by a z-pinch dynamic hohlraum on the Z-machine. Multiple PDV probes were incorporated into the photoionized gas cell platform. Two probes, spaced 4 mm apart, were used to assess plasma density and uniformity in the central region of the gas cell during the formation of the plasma. Electron density time histories with subnanosecond resolution were extracted from PDV measurements taken from the gas cells fielded with neon at 15 Torr. As well, a null shot with no gas fill in the cell was fielded. A major achievement was the low noise high-quality measurements made in the harsh environment produced by the mega-joules of x-ray energy emitted at the collapse of the z-pinch implosion. To evaluate time dependent radiation induced effects in the fiber optic system, two PDV noise probes were included on either side of the gas cell. The success of this alternative use of PDV demonstrates that it is a reliable, precise, and affordable new electron density diagnostic for radiation driven experiments and more generally HED experiments.

Converting existing optical detectors into fast x-ray detectors.

The very short burn time and small size of burning plasmas created at advanced laser-fusion facilities will require high-spatial-resolution imaging diagnostics with fast time resolution. These instruments will need to function in an environment of extremely large neutron fluxes that will cause conventional diagnostics to fail because of radiation damage and induced background levels. One solution to this challenge is to perform an ultrafast conversion of the x-ray signals into the optical regime before the neutrons are able to reach the detector and then to relay image the signal out of the chamber and into a shielded bunker, protected from the effects of these neutrons. With this goal in mind, the OMEGA laser was used to demonstrate high-temporal-resolution x-ray imaging by using an x-ray snout to image an imploding backlighter capsule onto a semiconductor. The semiconductor was simultaneously probed with the existing velocity interferometry system for any surface reflector (VISAR) diagnostic, which uses an optical streak camera and provided a one-dimensional image of the phase in the semiconductor as a function of time. The phase induced in the semiconductor was linearly proportional to the x-ray emission from the backlighter capsule. This approach would then allow a sacrificial semiconductor to be attached at the end of an optical train with the VISAR and optical streak camera placed in a shielded bunker to operate in a high neutron environment and obtain time-dependent one-dimensional x-ray images or time-dependent x-ray spectra from a burning plasma.

Extreme measurements with Photonic Doppler Velocimetry (PDV).

Photonic Doppler Velocimetry (PDV) is a fiber-based diagnostic for the extreme conditions created by high-speed impact, explosive detonation, electrical pulsed power, and intense laser ablation. PDV is a conceptually simple application of the optical Doppler effect, but measurements above 1 km/s only became practical at the beginning of the twenty-first century. This review discusses the evolution of PDV, its operational details, practical analysis, and outstanding challenges.

Does prehabilitation modify muscle mass in patients with rectal cancer undergoing neoadjuvant therapy? A subanalysis from the REx randomised controlled trial.

BACKGROUND: Patients with rectal cancer who present with sarcopenia (low muscle mass) are at significantly greater risk of postoperative complications and reduction in disease-free survival. We performed a subanalysis of a randomised controlled study [the REx trial; www.isrctn.com ; 62859294] to assess the potential of prehabilitation to modify muscle mass in patients having neoadjuvant chemoradiotherapy (NACRT). METHODS: Patients scheduled for NACRT, then potentially curative surgery (August 2014-March 2016) had baseline physical assessment and psoas muscle mass measurement (total psoas index using computed tomography-based measurements). Participants were randomised to either the intervention (13-17-week telephone-guided graduated walking programme) or control group (standard care). Follow-up testing was performed 1-2 weeks before surgery. RESULTS: The 44 patients had a mean age of 66.8 years (SD 9.6) and were male (64%); white (98%); American Society of Anesthesiologists class 2 (66%); co-morbid (58%); overweight (72%) (body mass index ≥ 25 kg/m2). At baseline, 14% were sarcopenic. At follow-up, 13 (65%) of patients in the prehabilitation group had increased muscle mass versus 7 (35%) that experienced a decrease. Conversely, 16 (67%) controls experienced a decrease in muscle mass and 8 (33%) showed an increase. An adjusted linear regression model estimated a mean treatment difference in Total Psoas Index of 40.2mm2/m2 (95% CI - 3.4 to 83.7) between groups in change from baseline (p = 0.07). CONCLUSIONS: Prehabilitation improved muscle mass in patients with rectal cancer who had NACRT. These results need to be explored in a larger trial to determine if the poorer short- and long-term patient outcomes associated with low muscle mass can be minimised by prehabilitation.

Time-stretched photonic Doppler velocimetry.

Inertial confinement fusion facilities generate implosions at speeds greater than 100 km/s, and measuring the material velocities is important and challenging. We have developed a new velocimetry technique that uses time-stretched spectral interferometry to increase the measurable velocity range normally limited by the detector bandwidth. In this approach, the signal is encoded on a chirped laser pulse that is stretched in time to reduce the beat frequency before detection. We demonstrate the technique on an imploding liner experiment at the Sandia National Laboratories' Z machine, where beat frequencies in excess of 50 GHz were measured with 20 GHz bandwidth detection.

The relationship between sarcopenia and survival at 1 year in patients having elective colorectal cancer surgery.

BACKGROUND: Colorectal cancer remains a common cause of cancer death in the UK, with surgery being the mainstay of treatment. An objective measurement of the suitability of each patient for surgery, and their risk-benefit calculation, would be of great utility. We postulate that sarcopenia (low muscle mass) could fulfil this role as a prognostic indicator. The aim of this study was to determine the relationship between sarcopenia and long-term outcomes in patients undergoing elective bowel resection for colorectal cancer. METHODS: One hundred and sixty-three consecutive patients who had elective curative colorectal resection for cancer were eligible for inclusion in the study. Psoas muscle mass was assessed on preoperative computed tomography scan at the level of the L3 vertebra and standardised for patient height (total psoas index, TPI). Sarcopenia (low muscle mass) was defined as < 524 mm2/m2 in males and 385 mm2/m2 in females. In addition to clinical-pathological parameters, postoperative complications were recorded and patients were followed up for mortality for 1 year after surgery. RESULTS: Sarcopenia was present in 19.6% of the study participants and was significantly related to body mass index (p = 0.007), 30-day mortality (p = 0.042) and 1-year mortality (p = 0.046). In univariate analysis, American Society of Anesthesiologists grade (p = 0.016), tumour stage (p = 0.018) and sarcopenia (p = 0.043) were found to be significant independent predictors of 1-year mortality. CONCLUSIONS: This study has found sarcopenia to be prevalent in patients with colorectal cancer having elective surgery. Independent of age, sarcopenia was associated with poorer 30-day mortality and survival at 1 year. Measurement of muscle mass preoperatively could be used to stratify a patient's risk, allowing targeted strategies such as prehabilitation, to be implemented to modify sarcopenia and improve long-term outcomes for patients.

Compression Freezing Kinetics of Water to Ice VII.

Time-resolved x-ray diffraction (XRD) of compressed liquid water shows transformation to ice VII in 6 nsec, revealing crystallization rather than amorphous solidification during compression freezing. Application of classical nucleation theory indicates heterogeneous nucleation and one-dimensional (e.g., needlelike) growth. These first XRD data demonstrate rapid growth kinetics of ice VII with implications for fundamental physics of diffusion-mediated crystallization and thermodynamic modeling of collision or impact events on ice-rich planetary bodies.

Age-related changes in auditory nerve-inner hair cell connections, hair cell numbers, auditory brain stem response and gap detection in UM-HET4 mice.

This study compared the timing of appearance of three components of age-related hearing loss that determine the pattern and severity of presbycusis: the functional and structural pathologies of sensory cells and neurons and changes in gap detection (GD), the latter as an indicator of auditory temporal processing. Using UM-HET4 mice, genetically heterogeneous mice derived from four inbred strains, we studied the integrity of inner and outer hair cells by position along the cochlear spiral, inner hair cell-auditory nerve connections, spiral ganglion neurons (SGN), and determined auditory thresholds, as well as pre-pulse and gap inhibition of the acoustic startle reflex (ASR). Comparisons were made between mice of 5-7, 22-24 and 27-29 months of age. There was individual variability among mice in the onset and extent of age-related auditory pathology. At 22-24 months of age a moderate to large loss of outer hair cells was restricted to the apical third of the cochlea and threshold shifts in the auditory brain stem response were minimal. There was also a large and significant loss of inner hair cell-auditory nerve connections and a significant reduction in GD. The expression of Ntf3 in the cochlea was significantly reduced. At 27-29 months of age there was no further change in the mean number of synaptic connections per inner hair cell or in GD, but a moderate to large loss of outer hair cells was found across all cochlear turns as well as significantly increased ABR threshold shifts at 4, 12, 24 and 48 kHz. A statistical analysis of correlations on an individual animal basis revealed that neither the hair cell loss nor the ABR threshold shifts correlated with loss of GD or with the loss of connections, consistent with independent pathological mechanisms.

Note: Heated flyer-plate impact system.

A technique for launching heated flyer plates was developed on a single-stage gas gun. This type of impact creates a well-posed mechanical state and a tunable thermal state, which is useful for calibrating dynamic temperature measurements. Proof-of-principle thermoreflectance measurements were performed using this technique. Since the target remains at room temperature until the moment of impact, heated flyers avoid differential expansion and annealing issues, allowing novel impact experiments to be performed.

Impaired sensorimotor gating in Fmr1 knock out and Fragile X premutation model mice.

Fragile X syndrome (FXS) is a common inherited cause of intellectual disability that results from a CGG repeat expansion in the FMR1 gene. Large repeat expansions trigger both transcriptional and translational suppression of Fragile X protein (FMRP) production. Fragile X-associated Tremor/Ataxia Syndrome (FXTAS) is an allelic neurodegenerative disease caused by smaller "pre-mutation" CGG repeat expansions that enhance FMR1 transcription but lead to translational inefficiency and reduced FMRP expression in animal models. Sensorimotor gating as measured by pre-pulse inhibition (PPI) is altered in both FXS patients and Fmr1 knock out (KO) mice. Similarly, FXTAS patients have demonstrated PPI deficits. Recent work suggests there may be overlapping synaptic defects between Fmr1 KO and CGG knock-in premutation mouse models (CGG KI). We therefore sought to interrogate PPI in CGG KI mice. Using a quiet PPI protocol more akin to human testing conditions, we find that Fmr1 KO animals have significantly impaired PPI. Using this same protocol, we find CGG KI mice demonstrate an age-dependent impairment in PPI compared to wild type (WT) controls. This study describes a novel phenotype in CGG KI mice that can be used in future therapeutic development targeting premutation associated symptoms.

Note: visible reflectivity system for high-pressure studies.

A near-normal visible reflectivity system was constructed for investigating the optical properties of materials at high pressure and temperatures. The system consists of focusing optics, spectrometers, and imaging cameras for use with a resistively-heated membrane-controlled diamond anvil cell (DAC). The DAC allows optical access on two sides: one dedicated to pressure measurement via fluorescence, the other side dedicated to absolute reflectance measurements. With this configuration, pressure and temperature may be controlled and measured without disturbing the sample position, permitting quantitative reflectivity measurements as a function of thermodynamic state variables. The system was tested on gold at high pressure conditions, and compared to data obtained on a commercial ellipsometer system at 1 bar.

Tracking an imploding cylinder with photonic Doppler velocimetry.

Cylindrical implosion offers a path to extreme material states, reaching considerably higher pressures than planar geometry. However, diagnosing compressed material in cylindrical geometry is challenging. Time-resolved velocimetry, a standard technique in planar compression, is difficult to incorporate into cylindrical experiments. This paper describes the use of photonic Doppler velocimetry (PDV) in magnetically driven cylindrical compression experiments at the Sandia Z machine. With this diagnostic, it is possible to track the interior of an imploding cylinder beyond 20 km/s. A "leapfrog" implementation is described to support velocities well above the bandwidth limits of standard PDV measurements.

Note: Frequency-conversion photonic Doppler velocimetry with an inverted circulator.

Photonic Doppler velocimetry (PDV) is a fiber-based interferometer used in dynamic compression research. Conventional PDV systems are simple to construct but do not perform well in all measurement conditions, while universal PDV systems that support many different configurations are complex and expensive. A simpler approach is the use of external, inverted circulators which can be added and removed in a modular fashion. This technique permits frequency-conversion measurements with a conventional PDV system. Using a correction to remove baseline effects, frequency conversion systems can resolve low velocity transients that conventional PDV cannot.

Effect of window reflections on photonic Doppler velocimetry measurements.

Photonic Doppler velocimetry (PDV) has rapidly become a standard diagnostic for measuring velocities in dynamic compression research. While free surface velocity measurements are fairly straightforward, complications occur when PDV is used to measure a dynamically loaded sample through a window. Fresnel reflections can severely affect the velocity and time resolution of PDV measurements, especially for low-velocity transients. Shock experiments of quartz compressed between two sapphire plates demonstrate how optical window reflections cause ringing in the extracted PDV velocity profile. Velocity ringing is significantly reduced by using either a wedge window or an antireflective coating.

Accuracy and precision in photonic Doppler velocimetry.

While photonic Doppler velocimetry (PDV) is becoming a common diagnostic in dynamic compression research, its limiting accuracy and precision are not well understood. Velocity resolution is known to be inversely proportional to the time resolution, but resolution estimates differ by one to two orders of magnitude. Furthermore, resolution varies with the number of recorded signals and how these signals are analyzed. Numerical simulations reveal factors that affect accuracy and precision in PDV, and the results may be extended to a broad class of measurements. After systematic effects are eliminated, the limiting velocity uncertainty in a PDV measurement is governed by the sampling rate, the signal noise fraction, and the analysis time duration.

Shock-wave exploration of the high-pressure phases of carbon.

The high-energy density behavior of carbon, particularly in the vicinity of the melt boundary, is of broad scientific interest and of particular interest to those studying planetary astrophysics and inertial confinement fusion. Previous experimental data in the several hundred gigapascal pressure range, particularly near the melt boundary, have only been able to provide data with accuracy capable of qualitative comparison with theory. Here we present shock-wave experiments on carbon (using a magnetically driven flyer-plate technique with an order of magnitude improvement in accuracy) that enable quantitative comparison with theory. This work provides evidence for the existence of a diamond-bc8-liquid triple point on the melt boundary.

Push-pull analysis of photonic Doppler velocimetry measurements.

A robust analysis method is presented for multiple-phase heterodyne velocimetry measurements. By combining information from three phase-shifted signals, it is possible to eliminate coherent intensity variations and incoherent light from the measurement. The three data signals are reduced to a pair of quadrature signals, allowing unambiguous calculation of target displacement. The analysis relies on a minimum number of adjustable parameters, and these parameters can be precisely determined from simple interferometer characterization.

Nanosecond freezing of water under multiple shock wave compression: continuum modeling and wave profile measurements.

Using real time optical transmission and imaging measurements in multiple shock wave compression experiments, water was shown to solidify on nanosecond time scales [D. H. Dolan and Y. M. Gupta, J. Chem. Phys. 121, 9050 (2004)]. Continuum modeling and wave profile measurements, presented here, provide a complementary approach to examine the freezing of shocked water. The water model consisted of thermodynamically consistent descriptions of liquid and solid (ice VII) water, relationships for phase coexistence, and a time-dependent transition description to simulate freezing dynamics. Continuum calculations using the water model demonstrate that, unlike single shock compression, multiple shock compression results in pressure-temperature conditions where the ice VIII phase is thermodynamically favored over the liquid phase. Wave profile measurements, using laser interferometry, were obtained with quartz and sapphire windows at a peak pressure of 5 GPa. For water confined between sapphire windows, numerical simulations corresponding to a purely liquid response are in excellent agreement with the measured wave profile. For water confined between quartz windows (to provide a nucleating surface), wave profile measurements demonstrate a pure liquid response for an incubation time of approximately 100 ns followed by a time-dependent transformation. Analysis of the wave profiles after the onset of transformation suggests that water changes from a metastable liquid to a denser phase, consistent with the formation of a high-pressure ice phase. Continuum analyses and simulations underscore the need for multiple time scales to model the freezing transition. Findings from the present continuum work are extremely consistent with optical results reported previously. These studies constitute the first comprehensive investigation reported for freezing of a liquid at very short time scales.