Bench-to-bedside review: The importance of the precision of the reference technique in method comparison studies - with specific reference to the measurement of cardiac output

Bland-Altman analysis is used for assessing agreement between two measurements of the same clinical variable. In the field of cardiac output monitoring, its results, in terms of bias and limits of agreement, are often difficult to interpret, leading clinicians to use a cutoff of 30% in the percentage error in order to decide whether a new technique may be considered a good alternative. This percentage error of ± 30% arises from the assumption that the commonly used reference technique, intermittent thermodilution, has a precision of ± 20% or less. The combination of two precisions of ± 20% equates to a total error of ± 28.3%, which is commonly rounded up to ± 30%. Thus, finding a percentage error of less than ± 30% should equate to the new tested technique having an error similar to the reference, which therefore should be acceptable. In a worked example in this paper, we discuss the limitations of this approach, in particular in regard to the situation in which the reference technique may be either more or less precise than would normally be expected. This can lead to inappropriate conclusions being drawn from data acquired in validation studies of new monitoring technologies. We conclude that it is not acceptable to present comparison studies quoting percentage error as an acceptability criteria without reporting the precision of the reference technique

Humans in Space: Summarizing the Medico-Biological Results of the Space Shuttle Program

As we celebrate the 50th anniversary of Gagarin's flight that opened the era of Humans in Space we also commemorate the 30th anniversary of the Space Shuttle Program (SSP) which was triumphantly completed by the flight of STS-135 on July 21, 2011. These were great milestones in the history of Human Space Exploration. Many important questions regarding the ability of humans to adapt and function in space were answered for the past 50 years and many lessons have been learned. Significant contribution to answering these questions was made by the SSP. To ensure the availability of the Shuttle Program experiences to the international space community NASA has made a decision to summarize the medico-biological results of the SSP in a fundamental edition that is scheduled to be completed by the end of 2011 beginning 2012. The goal of this edition is to define the normal responses of the major physiological systems to short-duration space flights and provide a comprehensive source of information for planning, ensuring successful operational activities and for management of potential medical problems that might arise during future long-term space missions. The book includes the following sections: 1. History of Shuttle Biomedical Research and Operations; 2. Medical Operations Overview Systems, Monitoring, and Care; 3. Biomedical Research Overview; 4. System-specific Adaptations/Responses, Issues, and Countermeasures; 5. Multisystem Issues and Countermeasures. In addition, selected operational documents will be presented in the appendices. The chapters are written by well-recognized experts in appropriate fields, peer reviewed, and edited by physicians and scientists with extensive expertise in space medical operations and space-related biomedical research. As Space Exploration continues the major question whether humans are capable of adapting to long term presence and adequate functioning in space habitats remains to be answered We expect that the comprehensive review of the medico-biological results of the SSP along with the data collected during the missions on the space stations (Mir and ISS) provides a good starting point in seeking the answer to this question

Horses discriminate between facial expressions of conspecifics

In humans, facial expressions are rich sources of social information and have an important role in regulating social interactions. However, the extent to which this is true in non-human animals, and particularly in non-primates, remains largely unknown. Therefore we tested whether domestic horses (Equus caballus) could discriminate between facial expressions of their conspecifics captured in different contexts, and whether viewing these expressions elicited functionally relevant reactions. Horses were more likely to approach photographic stimuli displaying facial expressions associated with positive attention and relaxation, and to avoid stimuli displaying an expression associated with aggression. Moreover, differing patterns of heart rate changes were observed in response to viewing the positive anticipation and agonistic facial expressions. These results indicate that horses spontaneously discriminate between photographs of unknown conspecifics portraying different facial expressions, showing appropriate behavioural and physiological responses. Thus horses, an animal far-removed from the primate lineage, also have the ability to use facial expressions as a means of gaining social information and potentially regulating social interactions

Postural Stability When Leaning from Perceived Upright

The transition between quiet stance and gait requires the volitional movement of one?s center of mass (COM) toward a limit of stability (LOS). The goal of this study was to measure the effect of leaning from perceived upright on postural stability when voluntarily maintaining fixed stance positions and during perturbations of the support surface. The COM was derived from force plate data in 12 healthy subjects while standing with feet positioned so that lateral base of support was equal to foot length. For all conditions, arms were folded and subjects were instructed to lean without bending at the hips or lifting their feet. The LOS was determined during maximal voluntary leans with eyes open and closed. The COM was then displayed on a monitor located in front of the subject. Subjects were visually guided to lean toward a target position, maintain this position for 10s, return to upright, and then repeat the same targeted lean maneuver with eyes closed. Targets were randomly presented at 2? in 8 directions and between 2-6? in these same directions according to the asymmetric LOS. Subjects were then verbally guided to lean between 2? back and 4? forward prior to a perturbation of the support surface in either a forward or backward direction. The average LOS was 5.8? forward, 2.9? back, and 4.8? in left/right directions, with no significant difference between eyes open and closed. Center of pressure (COP) velocity increased as subjects maintained fixed stance positions farther from upright, with increased variability during eyes closed conditions. The time to stability and COP path length increased as subjects leaned opposite to the direction of the support surface perturbations. We conclude that postural stability is compromised as subjects lean away from perceived upright, except for perturbations that induce sway in the direction opposite the lean. The asymmetric LOS relative to perceived upright favors postural stability for COM movements in the forward direction

Functionally relevant responses to human facial expressions of emotion in the domestic horse (Equus caballus)

Whether non-human animals can recognize human signals, including emotions, has both scientific and applied importance, and is particularly relevant for domesticated species. This study presents the first evidence of horses’ abilities to spontaneously discriminate between positive (happy) and negative (angry) human facial expressions in photographs. Our results showed that the angry faces induced responses indicative of a functional understanding of the stimuli: horses displayed a left-gaze bias (a lateralization generally associated with stimuli perceived as negative) and a quicker increase in heart rate (HR) towards these photographs. Such lateralized responses towards human emotion have previously only been documented in dogs, and effects of facial expressions on HR have not been shown in any heterospecific studies. Alongside the insights that these findings provide into interspecific communication, they raise interesting questions about the generality and adaptiveness of emotional expression and perception across species

Visual Impairment/Intracranial Pressure Risk Assessment

Since 2006 there have been 6 reported cases of altered visual acuity and intracranial pressure (ICP) in long duration astronauts. In order to document this risk and develop an integrated approach to its mitigation, the NASA Space Life Sciences Directorate (SLSD) and Human Research Program (HRP) have chosen to use the Human System Risk Board (HSRB) and the risk management analysis tool (RMAT). The HSRB is the venue in which the stakeholders and customers discuss and vet the evidence and the RMAT is the tool that facilitates documentation and comparison of the evidence across mission profiles as well as identification of risk factors, and documentation of mitigation strategies. This process allows for information to be brought forward and dispositioned so that it may be properly incorporated into the RMAT and contribute to the design of the research and mitigation plans. The evidence thus far has resulted in the identification of a visual impairment/intracranial pressure (VIIP) project team, updating of both short and long duration medical requirements designed to assess visual acuity, and a research plan to characterize this issue further. In order to understand this issue more completely, a plan to develop an Accelerated Research Collaboration (ARC) has been approved by the HSRB. The ARC is a novel research model pioneered by the Myelin Repair Foundation. It is a patient centered research model that brings together researchers and clinicians, under the guidance of a scientific advisory panel, to collaborate and produce results much quickly than accomplished through traditional research models. The data and evidence from the updated medical requirements and the VIIP ARC will be reviewed at the HSRB on a regular basis. Each review package presented to the HSRB will include an assessment and recommendation with respect to continuation of research, countermeasure development, occupational surveillance modalities, selection criteria, etc. This process will determine the course of the VIIP project and ultimately how SLSD and HRP mitigate this emerging human health and performance risk

Hemodynamic optimization in severe trauma: a systematic review and meta-analysis.

OBJECTIVE: Severe trauma can be associated with significant hemorrhagic shock and impaired organ perfusion. We hypothesized that goal-directed therapy would confer morbidity and mortality benefits in major trauma. METHODS: The MedLine, Embase and Cochrane Controlled Clinical Trials Register databases were systematically searched for randomized, controlled trials of goal-directed therapy in severe trauma patients. Mortality was the primary outcome of this review. Secondary outcomes included complication rates, length of hospital and intensive care unit stay, and the volume of fluid and blood administered. Meta-analysis was performed using RevMan software, and the data presented are as odds ratios for dichotomous outcomes and as mean differences (MDs) and standard MDs for continuous outcomes. RESULTS: Four randomized, controlled trials including 419 patients were analyzed. Mortality risk was significantly reduced in goal-directed therapy-treated patients, compared to the control group(OR=0.56, 95%CI: 0.34-0.92). Intensive care (MD: 3.7 days 95%CI: 1.06-6.5)and hospital length of stay (MD: 3.5 days,95%CI: 2.75-4.25) were significantly shorter in the protocol group patients.There were no differences in reported total fluid volume or blood transfusions administered. Heterogeneity in reporting among the studies prevented quantitative analysis of complications. CONCLUSION: Following severe trauma, early goal-directed therapy was associated with lower mortality and shorter durations of intensive care unit and hospital stays. The findings of this analysis should be interpreted with caution due to the presence of significant heterogeneity and the small number of th

Exercise builds the scaffold of life: muscle extracellular matrix biomarker responses to physical activity, inactivity, and aging

Skeletal muscle extracellular matrix (ECM) is critical for muscle force production and the regulation of important physiological processes during growth, regeneration, and remodelling. ECM remodelling is a tightly orchestrated process, sensitive to multi-directional tensile and compressive stresses and damaging stimuli, and its assessment can convey important information on rehabilitation effectiveness, injury, and disease. Despite its profound importance, ECM biomarkers are underused in studies examining the effects of exercise, disuse, or aging on muscle function, growth, and structure. This review examines patterns of short- and long-term changes in the synthesis and concentrations of ECM markers in biofluids and tissues, which may be useful for describing the time course of ECM remodelling following physical activity and disuse. Forces imposed on the ECM during physical activity critically affect cell signalling while disuse causes non-optimal adaptations, including connective tissue proliferation. The goal of this review is to inform researchers, and rehabilitation, medical, and exercise practitioners better about the role of ECM biomarkers in research and clinical environments to accelerate the development of targeted physical activity treatments, improve ECM status assessment, and enhance function in aging, injury, and disease