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.

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.

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.

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.

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.

Nosocomial Legionnaires' disease: aspiration as a primary mode of disease acquisition.

PURPOSE: Nosocomial Legionnaires' disease remains a significant problem with many unresolved questions regarding transmission of legionella organisms to patients. We performed a case-control and environmental study to identify risk factors and modes of transmission of Legionella infection during an outbreak of nosocomial Legionnaires' disease in a military medical center. PATIENTS AND METHODS: During the calendar year 1989, 14 cases of nosocomial Legionnaires' disease were identified by active surveillance following the discovery of 2 culture-proven cases among organ transplant recipients. Four control patients were matched to each case by age, sex, and date of admission. Cases and controls were compared with respect to past medical history and hospital exposure variables. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for matched variables. Environmental culturing of air and water supplies in and around the medical center was also performed. RESULTS: The case-control study revealed the following significant risk factors for the acquisition of nosocomial Legionnaires' disease: immunosuppressive therapy (OR = 32.7, CI = 4.5 to 302.6), nasogastric tube use (OR = 18.4, CI = 2.6 to 166.2), bedbathing (OR = 10.7, CI = 2.2 to 59.0), and antibiotic therapy (OR = 14.6, CI = 2.9 to 84.4). Shower use (OR = 0.1, CI = 0 to 0.4) appeared to be a negative risk factor. Water cultures revealed Legionella pneumophila serogroup 1, monoclonal antibody subtype Philadelphia (identical to all patient isolates) in the ground-water supply to the hospital, 1 hot-water tank, and 15% of 85 potable water sites tested. Air sampling of cooling towers, hospital air intakes, and medical air and oxygen supplies were negative for Legionella organisms. CONCLUSIONS: This study confirms the importance of potable water in transmitting nosocomial Legionnaires' disease and suggests that the organism gains access to the hospital via external water supplies. The risk factors identified in this case-control study provide evidence that Legionnaires' disease may act as a superinfection in a nosocomial setting and is likely acquired by aspiration, similar to other nosocomial pneumonias.

Cardiopulmonary effects of inhaled nitric oxide in normal dogs and during E. coli pneumonia and sepsis.

We investigated the effect of inhaled nitric oxide (NO) at increasing fractional inspired O2 concentrations (FIO2) on hemodynamic and pulmonary function during Escherichia coli pneumonia. Thirty-eight conscious, spontaneously breathing, tracheotomized 2-yr-old beagles had intrabronchial inoculation with either 0.75 or 1.5 x 10(10) colony-forming units/kg of E. coli 0111:B4 (infected) or 0.9% saline (noninfected) in one or four pulmonary lobes. We found that neither the severity nor distribution (lobar vs. diffuse) of bacterial pneumonia altered the effects of NO. However, in infected animals, with increasing FIO2 (0.08, 0.21, 0.50, and 0.85), NO (80 parts/million) progressively increased arterial PO2 [-0.3 +/- 0.6, 3 +/- 1, 13 +/- 4, 10 +/- 9 (mean +/- SE) Torr, respectively] and decreased the mean arterial-alveolar O2 gradient (0.5 +/- 0.3, 4 +/- 2, -8 +/- 7, -10 +/- 9 Torr, respectively). In contrast, in noninfected animals, the effect of NO was significantly different and opposite; NO progressively decreased mean PO2 with increasing FIO2 (2 +/- 1, -5 +/- 3, -2 +/- 3, and -12 +/- 5 Torr, respectively; P < 0.05 compared with infected animals) and increased mean arterial-alveolar O2 gradient (0.3 +/- 0.04, 2 +/- 2, 1 +/- 3, 11 +/- 5 Torr; P < 0.05 compared with infected animals). In normal and infected animals alike, only at FIO2 < or = 0.21 did NO significantly lower mean pulmonary artery pressure, pulmonary artery occlusion pressure, and pulmonary vascular resistance index (all P < 0.01). However, inhaled NO had no significant effect on increases in mean pulmonary artery pressure associated with bacterial pneumonia. Thus, during bacterial pneumonia, inhaled NO had only modest effects on oxygenation dependent on high FIO2 and did not affect sepsis-induced pulmonary hypertension. These data do not support a role for inhaled NO in bacterial pneumonia. Further studies are necessary to determine whether, in combination with ventilatory support, NO may have more pronounced effects.

Symptoms of anxiety disorders in normal children.

The present study examined prevalence, expression, and developmental patterns of DSM-III-R anxiety disorder symptoms in 62 never-psychiatrically-ill children. Subclinical phobias and overanxious disorder symptoms were fairly common, while symptoms of other anxiety disorders were less common. Direction of sex and age differences was generally consistent with previous literature, but few reached statistical significance. Nonanxious and subclinically anxious subsamples of never-psychiatrically-ill subjects were compared on individual and family psychopathology. Subclinically anxious children showed greater individual and family psychopathology than nonanxious children, though differences decreased at 12-month follow-up. Anxiety as a normal developmental phenomenon is discussed.

Chronic strychnine administration into the cochlea potentiates permanent threshold shift following noise exposure.

To investigate whether elimination of the medial efferent system influences permanent threshold shift following noise exposure, we developed an animal model in which strychnine was chronically delivered into the cochlea via an osmotic pump. Pigmented female guinea pigs were allocated into three groups: group I was treated with strychnine (50 microM, 0.5 microl/h, 14 days) in the left ear and exposed to noise (105 dB SPL broadband, 3 h) 3 weeks after the cessation of the strychnine perfusion; group II received strychnine in the left ear but no noise exposure; group III was treated with Ringer's solution in the left ear and exposed to noise. Animals in group II developed no hearing loss after the strychnine perfusion. The operated ears in group I demonstrated greatest hearing threshold shift 3 h after noise exposure. Hearing recovered during 2 weeks after noise exposure in both operated and non-operated ears in groups I and III. Two weeks after noise exposure, the operated ears in group I showed significantly greater threshold shift at 12, 16, and 20 kHz compared to the operated ears in group III and non-operated ears in groups I and III. These findings suggest that chronic strychnine administration into the cochlea inactivates the medial efferents without changing hearing threshold and that the medial efferents help to protect against permanent threshold shift following noise exposure.

The medial cochlear efferent system does not appear to contribute to the development of acquired resistance to acoustic trauma.

Noise-induced hearing loss (NIHL) was compared between sound conditioned and unconditioned guinea pigs, in which the left ear in both groups had been perfused with strychnine. Animals in the conditioned group were subjected to moderate sound (85 dB SPL broadband, 5 h/day, 10 days) and then exposed to intense sound (110 dB SPL broadband, 5 h). Unconditioned animals were exposed only to the intense sound. Following intense sound exposure, strychnine-treated ears showed greater NIHL than untreated ears in both unconditioned and conditioned animals, demonstrating the role of the medial efferents to reduce NIHL. Conditioned animals, however, showed smaller hearing loss and cochlear damage in both strychnine-treated and untreated ears compared to unconditioned animals; the protective effects given by conditioning were equivalent between the strychnine-treated and untreated ears. These results suggest that, although the medial efferent system acts to attenuate NIHL, it may not be necessary for the acquired resistance to NIHL provided by conditioning.

Cochlear microphonic enhancement in two tone interactions.

Two tone interaction functions of the cochlear microphonic (CM) were obtained from pigmented guinea pigs. First (basal) cochlear turn recording locations show optimally enhanced levels of CM when the interfering tone (F2) was positioned about 4 kHz above probe tones (F1) of 12 kHz and 20 kHz. Maximum enhancement occurred for equal level tones. No enhancement was seen for a probe tone of 4 kHz. When basal turn cochlear sensitivity was compromised, CM enhancement caused by the interfering tone was altered and only CM reduction was then seen. The CM reduction was the typical characteristic described by many earlier studies. Guinea pigs with various changes in cochlear sensitivity were studied, providing evidence in support of earlier reports that CM interference (both reductions and enhancements) depends on far field vector summation of the outputs of hair cells from a restricted area of the basilar membrane. No CM enhancement was seen in micropipette recordings from within the organ of Corti.

The effects of efferent activation on the acoustically and electrically evoked otoacoustic emission.

The effects of efferent activation on the otoacoustic emission were measured in anesthetized guinea pigs. The otoacoustic emission (2F(1)-F(2)) was evoked by the conventional method of presenting either two continuous tones or a sinusoidal current to the round window (RW) of the cochlea. The efferent effects on the acoustically evoked emission are greatest at low stimulus levels and least for high levels. The efferent effects on the electrically evoked emission (EEOAE) are relatively constant across current levels. In each case, efferent activation resulted in an initial large reduction in the emission amplitude followed by a smaller and more constant reduction. Strychnine eliminated the efferent effects independent of the method of emission activation. Strychnine had no effect on the EEOAE, suggesting that the RW current did not evoke a local efferent effect. Slow versus fast efferent effects were observed in the recovery of the emission amplitude at the termination of efferent activation. Only a fast recovery in the emission amplitude was observed for stimuli below 10 kHz while the amplitude recovery had fast and slow components for stimuli presented above 10 kHz.

Laser Doppler velocimetry of basilar membrane vibration.

A method is described for the measurement of basilar membrane (BM) vibration velocimeter (LDV). The instrumentation was coupled to a compound microscope which served to visualize reflective glass microbeads placed on the BM. The laser beam of the LDV was focused in the microscope object plane and positioned over the reflective bead. We show examples of frequency tuning curves and displacement input/output intensity functions obtained with the technique.

Acquired resistance to acoustic trauma by sound conditioning is primarily mediated by changes restricted to the cochlea, not by systemic responses.

Hearing loss caused by intense sound exposure can be significantly reduced by pre-exposing subjects to moderate-level acoustic stimuli. This phenomenon occurs in a variety of mammals. We investigated whether sound conditioning provides acquired resistance to acoustic trauma through local mechanisms selectively in the conditioned ears or if systemic mechanisms are involved that would yield contralateral protection in unconditioned ears. Guinea pigs (group I) in which one external ear canal was occluded were exposed to conditioning sound (2-20 kHz, 85 dB SPL, 5 h/day, 10 days). After removing the occlusion, the animals were then subjected bilaterally to intense noise (2-20 kHz, 110 dB SPL, 5 h) 5 days after the last conditioning exposure. Animals without ear canal occlusion were also exposed to the intense sound without conditioning (group II) or following the same conditioning exposure (group III). Intense sound exposure caused significantly greater permanent ABR threshold shifts at all frequencies tested (4, 8, 12, 16 and 20 kHz) in group II than in group III. In group I, the occluded ears showed significantly greater threshold shifts at all frequencies compared to the unoccluded ears. The threshold shifts in the occluded ears in group I were identical to those observed in group II; and the shifts in unoccluded ears in group I were identical to those in group III. Protective effects provided by sound conditioning were almost the same in group III and in the unoccluded ears in group I. The extent of hair cell damage supported the physiological findings. These results indicate that acquired resistance to acoustic trauma provided by sound conditioning is restricted to the cochlea exposed to conditioning sound, suggesting that conditioning protection is mediated primarily by the changes that occur locally within the conditioned cochlea. This animal model, with unilateral external ear canal occlusion during sound conditioning, is useful for studies of the mechanisms of conditioning protection.