Successful treatment of eosinophilic cystitis with benralizumab.

Eosinophilic cystitis is a rare form of interstitial cystitis. It can be chronic and debilitating due to urinary frequency, dysuria, incontinence, and frequent urinary tract infections. Prior attempts at treatment have included oral and intravesical steroids, antispasmodics, and antibiotics when indicated. Treatment of eosinophilic disorders has recently been improved with the use of monoclonal antibodies directed at interleukin 5. We report here a case of eosinophilic cystitis treated with the interleukin 5 antagonist, benralizumab. The patient had significant improvement in both quality of life measures and biopsy findings.

A 500-kiloton airburst over Chelyabinsk and an enhanced hazard from small impactors.

Most large (over a kilometre in diameter) near-Earth asteroids are now known, but recognition that airbursts (or fireballs resulting from nuclear-weapon-sized detonations of meteoroids in the atmosphere) have the potential to do greater damage than previously thought has shifted an increasing portion of the residual impact risk (the risk of impact from an unknown object) to smaller objects. Above the threshold size of impactor at which the atmosphere absorbs sufficient energy to prevent a ground impact, most of the damage is thought to be caused by the airburst shock wave, but owing to lack of observations this is uncertain. Here we report an analysis of the damage from the airburst of an asteroid about 19 metres (17 to 20 metres) in diameter southeast of Chelyabinsk, Russia, on 15 February 2013, estimated to have an energy equivalent of approximately 500 (±100) kilotons of trinitrotoluene (TNT, where 1 kiloton of TNT = 4.185×10(12) joules). We show that a widely referenced technique of estimating airburst damage does not reproduce the observations, and that the mathematical relations based on the effects of nuclear weapons--almost always used with this technique--overestimate blast damage. This suggests that earlier damage estimates near the threshold impactor size are too high. We performed a global survey of airbursts of a kiloton or more (including Chelyabinsk), and find that the number of impactors with diameters of tens of metres may be an order of magnitude higher than estimates based on other techniques. This suggests a non-equilibrium (if the population were in a long-term collisional steady state the size-frequency distribution would either follow a single power law or there must be a size-dependent bias in other surveys) in the near-Earth asteroid population for objects 10 to 50 metres in diameter, and shifts more of the residual impact risk to these sizes.

Human baroreflex rhythms persist during handgrip and muscle ischaemia.

AIM: To determine whether physiological, rhythmic fluctuations of vagal baroreflex gain persist during exercise, post-exercise ischaemia and recovery. METHODS: We studied responses of six supine healthy men and one woman to a stereotyped protocol comprising rest, handgrip exercise at 40% maximum capacity to exhaustion, post-exercise forearm ischaemia and recovery. We measured electrocardiographic R-R intervals, photoplethysmographic finger arterial pressures and peroneal nerve muscle sympathetic activity. We derived vagal baroreflex gains from a sliding (25-s window moved by 2-s steps) systolic pressure-R-R interval transfer function at 0.04-0.15 Hz. RESULTS: Vagal baroreflex gain oscillated at low, nearly constant frequencies throughout the protocol (at approx. 0.06 Hz - a period of about 18 s); however, during exercise, most oscillations were at low-gain levels, and during ischaemia and recovery, most oscillations were at high-gain levels. CONCLUSIONS: Vagal baroreflex rhythms are not abolished by exercise, and they are not overwhelmed after exercise during ischaemia and recovery.

The psychological challenge of genital injury.

INTRODUCTION: Injuries sustained from Improvised Explosive Devices (IEDs) can have a devastating impact on bodily integrity; physical injuries can be severe and include traumatic amputation of limbs, pelvic fracture, abdominal trauma, extremity fragmentation wounds and genital trauma. Soldiers suffering from genital trauma can experience overwhelming emotions and adjusting to their injuries is a process that occurs over time, that some find easier than others. This paper explores current practice and identifies guidelines for psychological interventions within this arena. METHODS: Relevant associated literature has been reviewed to identify the long-term consequences of genital trauma and to ascertain best practice in supporting this patient population. Current practices within the Royal Centre for Defence Medicine (RCDM) and the Defence Medical Rehabilitation Centre (DMRC) Headley Court have been explored. RESULTS: There is little published literature in this area. Therefore, in respect of guiding treatment of this patient population, related research on the psychological consequences of prostate and penile cancer, limb amputation, acquired infertility and acquired disability has been used as a base to inform interventions. Current practices at RCDM and DMRC have been found to support interventions within related areas. CONCLUSIONS: There is no published evidence base to guide psychological interventions for genital trauma. Professional multidisciplinary intervention will potentially be beneficial in establishing the long-term needs of this patient population, together with qualitative research exploring the experience of soldiers suffering genital trauma.

Discrete mineralisation of the acetabular labrum: a novel marker of femoroacetabular impingement?

Femoroacetabular impingement (FAI) is increasingly thought to play a role in the development of hip osteoarthritis, but is difficult to define clinically and on imaging. This study investigates mineralisations of the acetabular labrum (MALs), which are small, discrete foci of dense radio-opacity within the region of the acetabular labrum. The study aims to characterise MALs and test the hypothesis that MALs are associated with FAI. CT images and radiographs of 106 hips in 66 individuals without known FAI were reviewed for the presence of MALs. The anatomical locations of the MALs in the acetabular labrum were measured. Three current radiographic markers of FAI were recorded in hips with MALs and in age- and gender-matched hips without MALs: centre-edge angle and acetabular version angle as measures of pincer impingement, and alpha angle as a measure of cam impingement. MALs were identified in 18% of hips (n=19). Hips with MAL had a larger mean alpha angle (p=0.013) than those without. MALs were found to be located anterosuperiorly and posterosuperiorly within the labrum, consistent with coup and contrecoup impingement lesion locations reported for FAI. No significant association was found between MAL and centre-edge angle or version angle. Our data demonstrate that MALs are associated with increased alpha angle and thus may be linked to cam-type FAI. MALs have not previously been associated with FAI. This correlation may give further insight into the disease process underlying hip osteoarthritis and might represent a future radiographic marker of cam-type FAI.

Assessment of cerebral autoregulation: the quandary of quantification.

We assessed the convergent validity of commonly applied metrics of cerebral autoregulation (CA) to determine the extent to which the metrics can be used interchangeably. To examine between-subject relationships among low-frequency (LF; 0.07-0.2 Hz) and very-low-frequency (VLF; 0.02-0.07 Hz) transfer function coherence, phase, gain, and normalized gain, we performed retrospective transfer function analysis on spontaneous blood pressure and middle cerebral artery blood velocity recordings from 105 individuals. We characterized the relationships (n = 29) among spontaneous transfer function metrics and the rate of regulation index and autoregulatory index derived from bilateral thigh-cuff deflation tests. In addition, we analyzed data from subjects (n = 29) who underwent a repeated squat-to-stand protocol to determine the relationships between transfer function metrics during forced blood pressure fluctuations. Finally, data from subjects (n = 16) who underwent step changes in end-tidal P(CO2) (P(ET)(CO2) were analyzed to determine whether transfer function metrics could reliably track the modulation of CA within individuals. CA metrics were generally unrelated or showed only weak to moderate correlations. Changes in P(ET)(CO2) were positively related to coherence [LF: ß = 0.0065 arbitrary units (AU)/mmHg and VLF: ß = 0.011 AU/mmHg, both P < 0.01] and inversely related to phase (LF: ß = -0.026 rad/mmHg and VLF: ß = -0.018 rad/mmHg, both P < 0.01) and normalized gain (LF: ß = -0.042%/mmHg(2) and VLF: ß = -0.013%/mmHg(2), both P < 0.01). However, Pet(CO(2)) was positively associated with gain (LF: ß = 0.0070 cm·s(-1)·mmHg(-2), P < 0.05; and VLF: ß = 0.014 cm·s(-1)·mmHg(-2), P < 0.01). Thus, during changes in P(ET)(CO2), LF phase was inversely related to LF gain (ß = -0.29 cm·s(-1)·mmHg(-1)·rad(-1), P < 0.01) but positively related to LF normalized gain (ß = 1.3% mmHg(-1)/rad, P < 0.01). These findings collectively suggest that only select CA metrics can be used interchangeably and that interpretation of these measures should be done cautiously.

Does trauma risk management reduce psychological distress in deployed troops?

BACKGROUND: Military personnel exposed to potentially traumatic events whilst deployed on operational duties may develop psychological problems. The Royal Marines have made extensive use of Trauma Risk Management (TRiM), a peer-support system that operates through practitioners embedded within operational units. TRiM aims to promote recognition of psychological illness and to facilitate social support. AIMS: To evaluate the effects of TRiM in two units at different stages of implementation. METHODS: Royal Marines and Army personnel were surveyed prior to, during and upon return from an operational deployment to Afghanistan. Participants completed measures of general mental health (GHQ12) and traumatic stress [PCL(C)]. RESULTS: We received responses from 180 pre-deployment, 105 during deployment and 137 post-deployment. Personnel within units with experience of TRiM reported lower levels of psychological distress than personnel in the unit who were using TRiM for the first time. Both groups reported higher psychological distress scores before and during deployment, compared with post-deployment. However, we found personnel who reported having more access to social support during deployment reported less psychological distress. CONCLUSIONS: The use of TRiM may assist in increasing the psychological resilience of military personnel through the facilitation of social support; this may have particular utility during operational deployments.

Noise-stabilized random attractor.

A two-dimensional flow model is introduced with deterministic behavior consisting of bursts that become successively larger, with longer interburst time intervals between them. The system is symmetric in one variable and there are bursts on either side of , separated by the presence of an invariant manifold at . In the presence of arbitrarily small additive noise in the direction, the successive bursts have bounded amplitudes and interburst intervals. This system with noise is proposed as a model for edge-localized modes in tokamaks. With noise, the bursts can switch from positive to negative and vice versa. The probability distribution of burst heights and interburst periods is studied, as is the dependence of the statistics on the noise variance. The modification of this behavior as the symmetry in is broken is studied, showing qualitatively similar behavior if the symmetry breaking is small enough. Experimental observations of a nonlinear circuit governed by the same equations are presented, showing good agreement.

Respiratory modulation of human autonomic rhythms.

We studied the influence of three types of breathing [spontaneous, frequency controlled (0.25 Hz), and hyperventilation with 100% oxygen] and apnea on R-R interval, photoplethysmographic arterial pressure, and muscle sympathetic rhythms in nine healthy young adults. We integrated fast Fourier transform power spectra over low (0.05-0.15 Hz) and respiratory (0.15-0.3 Hz) frequencies; estimated vagal baroreceptor-cardiac reflex gain at low frequencies with cross-spectral techniques; and used partial coherence analysis to remove the influence of breathing from the R-R interval, systolic pressure, and muscle sympathetic nerve spectra. Coherence among signals varied as functions of both frequency and time. Partialization abolished the coherence among these signals at respiratory but not at low frequencies. The mode of breathing did not influence low-frequency oscillations, and they persisted during apnea. Our study documents the independence of low-frequency rhythms from respiratory activity and suggests that the close correlations that may exist among arterial pressures, R-R intervals, and muscle sympathetic nerve activity at respiratory frequencies result from the influence of respiration on these measures rather than from arterial baroreflex physiology. Most importantly, our results indicate that correlations among autonomic and hemodynamic rhythms vary over time and frequency, and, thus, are facultative rather than fixed.

Nine months in space: effects on human autonomic cardiovascular regulation.

We studied three Russian cosmonauts to better understand how long-term exposure to microgravity affects autonomic cardiovascular control. We recorded the electrocardiogram, finger photoplethysmographic pressure, and respiratory flow before, during, and after two 9-mo missions to the Russian space station Mir. Measurements were made during four modes of breathing: 1) uncontrolled spontaneous breathing; 2) stepwise breathing at six different frequencies; 3) fixed-frequency breathing; and 4) random-frequency breathing. R wave-to-R wave (R-R) interval standard deviations decreased in all and respiratory frequency R-R interval spectral power decreased in two cosmonauts in space. Two weeks after the cosmonauts returned to Earth, R-R interval spectral power was decreased, and systolic pressure spectral power was increased in all. The transfer function between systolic pressures and R-R intervals was reduced in-flight, was reduced further the day after landing, and had not returned to preflight levels by 14 days after landing. Our results suggest that long-duration spaceflight reduces vagal-cardiac nerve traffic and decreases vagal baroreflex gain and that these changes may persist as long as 2 wk after return to Earth.

Topical anesthetic before microneurography decreases pain without affecting sympathetic traffic.

Pain associated with the microneurography procedure varies among human research volunteers, and may influence baseline sympathetic neural activity. The purpose of this study was to evaluate the efficacy and effects of applying a topical anesthetic prior to microneurography. Ten volunteers underwent microneurography twice, separated by a minimum of 4 weeks. Using a single-blind, randomized cross-over design, EMLA cream (2.5% lidocaine and 2.5% prilocaine in oil emulsion) or an aqueous placebo cream was applied 2 h prior to each session. Subjects rated pain on a scale from 0 (no pain) to 4 (extreme pain). The electrocardiogram, and efferent sympathetic nerve traffic from peroneal nerve muscle fascicles at the popliteal fossa were recorded during a 10-min supine rest period. EMLA cream significantly reduced perception of pain (P < 0.05), but did not affect burst reflex latencies from preceding R-waves or total muscle sympathetic nerve traffic (P > 0.05). These data show that use of EMLA cream prior to microneurography is innocuous, and do not support the hypothesis that baseline sympathetic traffic is increased by pain or discomfort associated with microneurography.

Power spectral analysis imperfectly informs changes in sympathetic traffic during acute simulated microgravity.

The purpose of this study was to investigate the value of frequency-domain analysis of autonomic rhythms as a simple, non-invasive technique for the study of immediate neural adjustments to simulated microgravity. We continuously recorded the electrocardiogram, non-invasive beat-by-beat arterial pressure, and muscle sympathetic nerve activity (MSNA) during 5-min periods of controlled frequency breathing (15 breaths.min-1) with subjects (n = 10) in supine, and 10 degrees head-down tilt positions. We estimated changes in fluid volume with lower leg circumference measurements. We analyzed data in the frequency domain with fast Fourier-based power spectral analysis, and calculated the ratio of normalized low-to-respiratory frequency RR-interval spectral power as an index of sympathetic activity. Head-down tilt significantly reduced lower leg volume, MSNA, and MSNA oscillations at the respiratory frequency (p < 0.05). Head-down tilt did not change RR-interval, arterial pressure, or their power spectra (p > 0.05). We conclude that non-invasive frequency-domain estimates do not adequately reveal subtle changes in sympathetic traffic during acute, simulated microgravity.

Human responses to upright tilt: a window on central autonomic integration.

1. We examined interactions between haemodynamic and autonomic neural oscillations during passive upright tilt, to gain better insight into human autonomic regulatory mechanisms. 2. We recorded the electrocardiogram, finger photoplethysmographic arterial pressure, respiration and peroneal nerve muscle sympathetic activity in nine healthy young adults. Subjects breathed in time with a metronome at 12 breaths min-1 (0.2 Hz) for 5 min each, in supine, and 20, 40, 60, 70 and 80 deg head-up positions. We performed fast Fourier transform (and autoregressive) power spectral analyses and integrated low-frequency (0.05-0.15 Hz) and respiratory-frequency (0. 15-0.5 Hz) spectral powers. 3. Integrated areas of muscle sympathetic bursts and their low- and respiratory-frequency spectral powers increased directly and significantly with the tilt angle. The centre frequency of low-frequency sympathetic oscillations was constant before and during tilt. Sympathetic bursts occurred more commonly during expiration than inspiration at low tilt angles, but occurred equally in expiration and inspiration at high tilt angles. 4. Systolic and diastolic pressures and their low- and respiratory-frequency spectral powers increased, and R-R intervals and their respiratory-frequency spectral power decreased progressively with the tilt angle. Low-frequency R-R interval spectral power did not change. 5. The cross-spectral phase angle between systolic pressures and R-R intervals remained constant and consistently negative at the low frequency, but shifted progressively from positive to negative at the respiratory frequency during tilt. The arterial baroreflex modulus, calculated from low-frequency cross-spectra, decreased at high tilt angles. 6. Our results document changes of baroreflex responses during upright tilt, which may reflect leftward movement of subjects on their arterial pressure sympathetic and vagal response relations. The intensity, but not the centre frequency of low-frequency cardiovascular rhythms, is modulated by the level of arterial baroreceptor input. Tilt reduces respiratory gating of sympathetic and vagal motoneurone responsiveness to stimulatory inputs for different reasons; during tilt, sympathetic stimulation increases to a level that overwhelms the respiratory gate, and vagal stimulation decreases to a level below that necessary for maximal respiratory gating to occur.

Controlled breathing protocols probe human autonomic cardiovascular rhythms.

The purpose of this study was to determine how breathing protocols requiring varying degrees of control affect cardiovascular dynamics. We measured inspiratory volume, end-tidal CO2, R-R interval, and arterial pressure spectral power in 10 volunteers who followed the following 5 breathing protocols: 1) uncontrolled breathing for 5 min; 2) stepwise frequency breathing (at 0.3, 0.25, 0.2, 0.15, 0.1, and 0.05 Hz for 2 min each); 3) stepwise frequency breathing as above, but with prescribed tidal volumes; 4) random-frequency breathing (approximately 0.5-0.05 Hz) for 6 min; and 5) fixed-frequency breathing (0.25 Hz) for 5 min. During stepwise breathing, R-R interval and arterial pressure spectral power increased as breathing frequency decreased. Control of inspired volume reduced R-R interval spectral power during 0.1 Hz breathing (P < 0.05). Stepwise and random-breathing protocols yielded comparable coherence and transfer functions between respiration and R-R intervals and systolic pressure and R-R intervals. Random- and fixed-frequency breathing reduced end-tidal CO2 modestly (P < 0.05). Our data suggest that stringent tidal volume control attenuates low-frequency R-R interval oscillations and that fixed- and random-rate breathing may decrease CO2 chemoreceptor stimulation. We conclude that autonomic rhythms measured during different breathing protocols have much in common but that a stepwise protocol without stringent control of inspired volume may allow for the most efficient assessment of short-term respiratory-mediated autonomic oscillations.

The influence of recovery duration on high-intensity exercise performance after oral creatine supplementation.

The purpose of this study was to determine the effects of creatine supplementation on the ability to reproduce and maintain a high percentage of peak power output during the second of two bouts of high-intensity cycle sprinting following four different recovery intervals. Eighty healthy, active male subjects were randomly assigned to one of two groups (creatine or placebo) and one of four recovery intervals (30, 60, 90, or 120 s). Two maximal cycle ergometer sprints, separated by the assigned recovery interval were performed before and after a 5-day supplementation protocol in which 20 g/day of creatine (plus 4 g/day glucose) or 24 g/day glucose placebo were ingested by subjects from creatine and placebo groups, respectively. Maximal peak power output (PP) and the absolute time to fatigue (TTF) were compared pre- versus postsupplementation. No significant group interactions were noted in this study. Specifically, creatine supplementation had no effect on subjects' ability to reproduce or maintain a high percentage of PP during the second bout of exercise.

Measuring fatigue relative to peak power output during high-intensity cycle sprinting.

The purpose of this report was to introduce and validate a method to account for variable fatigue rates during cycle sprinting by incorporating decline from peak power (30%) as a test termination criterion. Fifteen healthy men performed three maximal sprint tests separated by 20 min (Bouts 1 and 2) and 48 hours (Bout 3). Power curves were analyzed for peak power, time to peak, time to fatigue (decline of 30% from peak), total work, total test time, fatigue rate, and the fatigue index. High test-retest reliability was demonstrated for all variables (R = 0.85-0.98). No significant differences were detected between variables (Bouts 1, 2 and 3; p > 0.01). Fatigue rates varied widely among participants (range = 24.7-65.4 W.s-1), but the fatigue index was consistent (31.1 +/- 0.16; mean +/- standard error of measurement, range = 30.1-32.5%). Our data show that variable fatigue responses among participants are normalized to the percentage of decline from peak power by incorporating a relative fatigue cutoff criterion. This approach might inform mechanisms relating to short-term fatigue and recovery during consecutive sprint bouts.

Understanding and countering racism with first nations children in out-of-home care.

Although First Nations communities in Canada are increasingly taking control of their own child welfare services, their children are still overrepresented in out-of-home care. First Nations children are frequently placed in non-Native environments where they encounter racist attitudes and behaviors. This situation originated in assimilation policies in which governments removed First Nations children from their families, placing them in residential schools, and later, in non-Native foster or adoptive homes. This article suggests ways for social workers and foster carers to combat racism, both individually and by supporting the initiatives of First Nations people to regain control of their own children.

Effect of oral creatine supplementation on power output and fatigue during bicycle ergometry.

Our purpose was to determine the effect of oral creatine supplementation on exercise performance during high-intensity short-duration bicycle sprinting. Power output was recorded for 12 healthy untrained males (age 24.08 +/- 0.53 yr, weight 81.22 +/- 1.32 kg) before and after 5 days of creatine (n = 6) or placebo (n = 6) supplementation. A double-blind research design was employed. Subjects performed maximal sprints against a constant load (111.8 N) for 15 s. Each one-half pedal revolution was magnetically counted, and subsequent measurements of peak power, time to peak power, total work, and the fatigue index were digitized and stored on disk. Mean values for peak power, time to peak power, total work, and fatigue index were 958.01 +/- 40.66 W, 4.09 +/- 0.82 s, 11.28 +/- 0.46 kJ, and 32.1 +/- 1.58% decline from peak power, respectively. No significant differences were observed within or between groups before or after supplementation for any of the mechanical parameters measured (P > 0.05). These findings suggest that oral creatine supplementation does not positively affect power output or fatigue during continuous high-intensity bicycle exercise in untrained men.