What does “futility” mean? An empirical study of doctors’ perceptions

Objective(s) To describe how doctors define and use the terms “futility” and “futile treatment” in end-of-life care. Design, Setting, Participants A qualitative study using semi-structured interviews with 96 doctors across a range of specialties who treat adults at the end of life. Doctors were recruited from three large Australian teaching hospitals and were interviewed from May to July 2013. Results Doctors’ conceptions of futility focused on the quality and chance of patient benefit. Aspects of benefit included physiological effect, weighing benefits and burdens, and quantity and quality of life. Quality and length of life were linked, but many doctors discussed instances when benefit was determined by quality of life alone. Most doctors described the assessment of chance of success in achieving patient benefit as a subjective exercise. Despite a broad conceptual consensus about what futility means, doctors noted variability in how the concept was applied in clinical decision-making. Over half the doctors also identified treatment that is futile but nevertheless justified, such as short-term treatment as part of supporting the family of a dying person. Conclusions There is an overwhelming preference for a qualitative approach to assessing futility, which brings with it variation in clinical decision-making. “Patient benefit” is at the heart of doctors’ definitions of futility. Determining patient benefit requires discussions with patients and families about their values and goals as well as the burdens and benefits of further treatment.

The A Posteriori Aspects of Estuarine Modeling

This exercise is the application of an analytical method for systematically modeling ecosystems data to observations made on a naturally eutrophic, mesohaline planktonic microcosm. The theory and experimental design are briefly outlined and the particular steps in the acutal modeling process follow. Then there is a discussion as to how the whole endeavor can be refined to culminate in models with predictive capabilities. (PDF has 16 pages.)

Fundamental aspects of the feeding of the amphipod Gammarus (R.) balcanicus (Crustacea, Amphipoda). [Translation from: Nauchn.Dokl.vyssh.Shkoly (Biol.Nauk) 1970(7) 12-16, 1970]

The amphipods are major food items for many commercial fishes, and they are used as protein food for agricultural animals. In the present paper are presented the results of four-year observations on the feeding of Gammarus balcanicus in nature and in an aquarium. Among the studied aspects were the dependence of daily food ration on sex and physiological state (with and without eggs) and feeding on different kinds of plant food. The study concludes that Gammarus balcanicus willingly feed on soft half-decayed plant residues; into their ration also enters food of animal origin. In contrast to other amphipods, G. balcanicus eats representatives of its own species very rarely, and only dead or immobile ones.

Physiological modelling for improved reliability in silhouette-driven gradient-based hand tracking

We present a gradient-based motion capture system that robustly tracks a human hand, based on abstracted visual information - silhouettes. Despite the ambiguity in the visual data and despite the vulnerability of gradient-based methods in the face of such ambiguity, we minimise problems related to misfit by using a model of the hand's physiology, which is entirely non-visual, subject-invariant, and assumed to be known a priori. By modelling seven distinct aspects of the hand's physiology we derive prior densities which are incorporated into the tracking system within a Bayesian framework. We demonstrate how the posterior is formed, and how our formulation leads to the extraction of the maximum a posteriori estimate using a gradient-based search. Our results demonstrate an enormous improvement in tracking precision and reliability, while also achieving near real-time performance. © 2009 IEEE.

COASTAL SEA-LEVEL AND THE LARGE-SCALE CLIMATE STATE - A DOWNSCALING EXERCISE FOR THE JAPANESE ISLANDS

A major problem which is envisaged in the course of man-made climate change is sea-level rise. The global aspect of the thermal expansion of the sea water likely is reasonably well simulated by present day climate models; the variation of sea level, due to variations of the regional atmospheric forcing and of the large-scale oceanic circulation, is not adequately simulated by a global climate model because of insufficient spatial resolution. A method to infer the coastal aspects of sea level change is to use a statistical ''downscaling'' strategy: a linear statistical model is built upon a multi-year data set of local sea level data and of large-scale oceanic and/or atmospheric data such as sea-surface temperature or sea-level air-pressure. We apply this idea to sea level along the Japanese coast. The sea level is related to regional and North Pacific sea-surface temperature and sea-level air pressure. Two relevant processes are identified. One process is the local wind set-up of water due to regional low-frequency wind anomalies; the other is a planetary scale atmosphere-ocean interaction which takes place in the eastern North Pacific.

LC determination of amino acids in rat plasma with fluorescence detection: Application to exercise physiology

An LC method for the determination of 20 amino acids (AAs), using 1,2-Benzo-3,4-dihydrocarbazole-9-ethyl chloroformate (BCEOC) as fluorescent labeling reagent, has been validated and applied for the analysis of AAs in rat plasma at three different states concerning exercise physiology. Identification of AA derivatives was carried out by LC-MS with electrospray ion (ESI), and the MS-MS cleavage mode of the representative tyrosine (Tyr) derivative was analyzed. Gradient elution on a Hypersil BDS C-18 column gave good separation of the derivatives. Excellent linear responses were observed and good compositional data could be obtained from as little as 50-200 mu L of plasma samples. The contents of 20 AAs in rat plasma of three groups (24 rats, group A: quiet state, group B: at exercising exhaust, group C: 12 h after exercising exhaust) exhibited evident difference corresponding to the physiological states. Facile BCEOC derivatization coupled with LC-FLD-ESI-MS analysis allowed the development of a highly sensitive method for the quantitative analysis of trace level of AAs from plasma or other biochemical samples.

Rodent models for resolving extremes of exercise and health

The extremes of exercise capacity and health are considered a complex interplay between genes and the environment. In general, the study of animal models has proven critical for deep mechanistic exploration that provides guidance for focused and hypothesis driven discovery in humans. Hypotheses underlying molecular mechanisms of disease, and gene/tissue function can be tested in rodents in order to generate sufficient evidence to resolve and progress our understanding of human biology. Here we provide examples of three alternative uses of rodent models that have been applied successfully to advance knowledge that bridges our understanding of the connection between exercise capacity and health status. Firstly we review the strong association between exercise capacity and all-cause morbidity and mortality in humans through artificial selection on low and high exercise performance in the rat and the consequent generation of the "energy transfer hypothesis". Secondly we review specific transgenic and knock-out mouse models that replicate the human disease condition and performance. This includes human glycogen storage diseases (McArdle and Pompe) and α-actinin-3 deficiency. Together these rodent models provide an overview of the advancements of molecular knowledge required for clinical translation. Continued study of these models in conjunction with human association studies will be critical to resolving the complex gene-environment interplay linking exercise capacity, health, and disease.

The effects of ageing and exercise on skeletal muscle structure and function

Musculoskeletal ageing is associated with profound morphological and functional changes that increase fall risk and disease incidence and is characterised by age-related reductions in motor unit number and atrophy of muscle fibres, particularly type II fibres. Decrements in functional strength and power are relatively modest until the 6th decade, after which the rate of loss exponentially accelerates, particularly beyond the 8th decade of life. Physical activity is a therapeutic modality that can significantly attenuate age-related decline. The underlying signature of ageing, as manifested by perturbed redox homeostasis, leads to a blunting of acute and chronic redox regulated exercise adaptations. Impaired redox regulated exercise adaptations are mechanistically related to altered exercise-induced reactive oxygen and nitrogen species generation and a resultant failure to properly activate redox regulated signaling cascades. Despite the aforementioned specific impairment in redox signaling, exercise induces a plethora of beneficial effects, irrespective of age. There is, therefore, strong evidence for promoting regular physical exercise, especially progressive resistance training as a lifelong habitual practice.

Sedentariness and physical inactivity in diabetes: a case for home-based exercise prescription

Increasing proportions of the global population are being diagnosed with diabetes. It is anticipated that by 2030, 10% of the adult population worldwide will be living with this condition. Lifestyle factors can impact on the development, management and progression of diabetes. Obesity and sedentary living are contributory factors to the increased volume of diabetes. Physical activity offers those living with diabetes the opportunities to keep well and attain potentially more stable blood glucose control reducing the level of medical intervention required and delaying or preventing some of the life-changing complications that can derive from a diabetes diagnosis. Exercise interventions are effective in preventing and treating type-II diabetes. However, maintaining regular exercise routines, especially home-based exercises may provide a key for sustaining the health benefits.

Workplace sedentary health risks and exercise interventions

Sedentary lifestyle and physical inactivity are causes of major health risks including cardiovascular disease (CVD), diabetes and cancer. Workplace is an ideal setting to understand both the prevalence of these risks and for devising and implementing effective intervention strategies. It is now possible to perform direct workplace assessments to identify the sedentary prevalence and assess the sedentary related health risks, which can include assessing the risks of atherosclerosis, hypertension, hypercholesterolemia, hyperglyaemia and reduced cardiorespiratory capacity. Based on evaluating the workplace health risks, it is possible to identify individuals who may be at higher CVD risk so they can be targeted with a risk-reduction intervention that can also be tailored towards improving healthy behaviours, especially towards physical activity activity and exercise. This chapter explains workplace sedentary risks, and provides examples of CVD risk prevalence, particularly within the university campus workplace, and presents examples of an exercise based targeted interventions aimed at reducing CVD risks amongst high risk sedentary employees.

Characteristics of preferred gait patterns: considerations for exercise prescription

Gait patterns have been widely studied in different fields of science for their particular characteristics. A dynamic approach of human locomotion considers walking and running as two stable behaviors adopted spontaneously under certain levels and natures of constraints. When no constraints are imposed, people naturally prefer to walk at the typical speed (i.e., around 4.5 km.h-1) that minimizes metabolic energy cost. The preferred walking speed (PWS) is also known to be an indicator of mobility and an important clinical factor in tracking impairements in motor behaviors. When constrained to move at higher speeds (e.g., being late), people naturally switch their preference to running for similar optimization reasons (e.g., physiological, biomechanical, perceptual, attentionnal costs). Indeed, the preferred transition speed (PTS) marks the natural seperation between walking and running and consistently falls within a speed range around 7.5 km.h-1. This chapter describes the constraint-dependant spontaneous organisation of the locomotor system, specifically on the walk-to-run speed continuum. We provide examples of the possibility of long-term adaptations of preferred behaviors to specific constraints such as factors related to traditional clothing or practice. We use knowledge from studies on preferred behaviors and on the relationship between affect and exercise adherence as a backdrop to prescribing a walk exercise program with an emphasis on populations with overweight or obesity.

The lung cancer exercise training study: a randomized trial of aerobic training, resistance training, or both in postsurgical lung cancer patients: rationale and design.

BACKGROUND: The Lung Cancer Exercise Training Study (LUNGEVITY) is a randomized trial to investigate the efficacy of different types of exercise training on cardiorespiratory fitness (VO2peak), patient-reported outcomes, and the organ components that govern VO2peak in post-operative non-small cell lung cancer (NSCLC) patients. METHODS/DESIGN: Using a single-center, randomized design, 160 subjects (40 patients/study arm) with histologically confirmed stage I-IIIA NSCLC following curative-intent complete surgical resection at Duke University Medical Center (DUMC) will be potentially eligible for this trial. Following baseline assessments, eligible participants will be randomly assigned to one of four conditions: (1) aerobic training alone, (2) resistance training alone, (3) the combination of aerobic and resistance training, or (4) attention-control (progressive stretching). The ultimate goal for all exercise training groups will be 3 supervised exercise sessions per week an intensity above 70% of the individually determined VO2peak for aerobic training and an intensity between 60 and 80% of one-repetition maximum for resistance training, for 30-45 minutes/session. Progressive stretching will be matched to the exercise groups in terms of program length (i.e., 16 weeks), social interaction (participants will receive one-on-one instruction), and duration (30-45 mins/session). The primary study endpoint is VO2peak. Secondary endpoints include: patient-reported outcomes (PROs) (e.g., quality of life, fatigue, depression, etc.) and organ components of the oxygen cascade (i.e., pulmonary function, cardiac function, skeletal muscle function). All endpoints will be assessed at baseline and postintervention (16 weeks). Substudies will include genetic studies regarding individual responses to an exercise stimulus, theoretical determinants of exercise adherence, examination of the psychological mediators of the exercise - PRO relationship, and exercise-induced changes in gene expression. DISCUSSION: VO2peak is becoming increasingly recognized as an outcome of major importance in NSCLC. LUNGEVITY will identify the optimal form of exercise training for NSCLC survivors as well as provide insight into the physiological mechanisms underlying this effect. Overall, this study will contribute to the establishment of clinical exercise therapy rehabilitation guidelines for patients across the entire NSCLC continuum. TRIAL REGISTRATION: NCT00018255.

Irisin - a myth rather than an exercise-inducible myokine.

The myokine irisin is supposed to be cleaved from a transmembrane precursor, FNDC5 (fibronectin type III domain containing 5), and to mediate beneficial effects of exercise on human metabolism. However, evidence for irisin circulating in blood is largely based on commercial ELISA kits which are based on polyclonal antibodies (pAbs) not previously tested for cross-reacting serum proteins. We have analyzed four commercial pAbs by Western blotting, which revealed prominent cross-reactivity with non-specific proteins in human and animal sera. Using recombinant glycosylated and non-glycosylated irisin as positive controls, we found no immune-reactive bands of the expected size in any biological samples. A FNDC5 signature was identified at ~20 kDa by mass spectrometry in human serum but was not detected by the commercial pAbs tested. Our results call into question all previous data obtained with commercial ELISA kits for irisin, and provide evidence against a physiological role for irisin in humans and other species.

The effects of cadence and power output upon physiological and biomechanical responses to incremental arm-crank ergometry

The aim of this study was to examine the effects of cadence and power output on physiological and biomechanical responses to incremental arm-crank ergometry (ACE). Ten male subjects (mean +/- SD age, 30.4 +/-5.4 y; height, 1.78 +/-0.07 m; mass, 86.1 +/-14.2 kg) undertook 3 incremental ACE protocols to determine peak oxygen uptake (VO2 peak; mean of 3 tests: 3.07 +/- 0.17 L.min-1) at randomly assigned cadences of 50, 70, or 90 r.min-1. Heart rate and expired air were continually monitored. Central (RPE-C) and local (RPE-L) ratings of perceived exertion were recorded at volitional exhaustion. Joint angles and trunk rotation were analysed during each exercise stage. During submaximal power outputs of 50, 70, and 90 W, oxygen consumption (VO2) was lowest for 50 r.min-1 and highest for 90 r.min-1 (p < 0.01). VO2 peak was lowest during 50 r.min-1 (2.79 +/-0.45 L.min-1; p < 0.05) when compared with both 70 r.min-1 and 90 r.min-1 (3.16 +/-0.58, 3.24 +/-0.49 L.min-1, respectively; p > 0.05). The difference between RPE-L and RPE-C at volitional exhaustion was greatest during 50 r.min-1 (2.9 +/- 1.6) when compared with 90 r.min-1 (0.9 +/- 1.9, p < 0.05). At VO2 peak, shoulder range of motion (ROM) and trunk rotation were greater for 50 and 70 r.min-1 when compared with 90 r.min-1 (p < 0.05). During submaximal power outputs, shoulder angle and trunk rotation were greatest at 50 r.min-1 when compared with 90 r.min-1 (p < 0.05). VO2 was inversely related to both trunk rotation and shoulder ROM during submaximal power outputs. The results of this study suggest that the greater forces required at lower cadences to produce a given power output resulted in greater joint angles and range of shoulder and trunk movement. Greater isometric contractions for torso stabilization and increased cost of breathing possibly from respiratory-locomotor coupling may have contributed increased oxygen consumption at higher cadences.

Parameterisation of bivalve functional traits for mechanistic eco-physiological dynamic energy budget (DEB) models

Mechanistic models such as those based on dynamic energy budget (DEB) theory are emergent ecomechanics tools to investigate the extent of fitness in organisms through changes in life history traits as explained by bioenergetic principles. The rapid growth in interest around this approach originates from the mechanistic characteristics of DEB, which are based on a number of rules dictating the use of mass and energy flow through organisms. One apparent bottleneck in DEB applications comes from the estimations of DEB parameters which are based on mathematical and statistical methods (covariation method). The parameterisation process begins with the knowledge of some functional traits of a target organism (e. g. embryo, sexual maturity and ultimate body size, feeding and assimilation rates, maintenance costs), identified from the literature or laboratory experiments. However, considering the prominent role of the mechanistic approach in ecology, the reduction of possible uncertainties is an important objective. We propose a revaluation of the laboratory procedures commonly used in ecological studies to estimate DEB parameters in marine bivalves. Our experimental organism was Brachidontes pharaonis. We supported our proposal with a validation exercise which compared life history traits as obtained by DEBs (implemented with parameters obtained using classical laboratory methods) with the actual set of species traits obtained in the field. Correspondence between the 2 approaches was very high (>95%) with respect to estimating both size and fitness. Our results demonstrate a good agreement between field data and model output for the effect of temperature and food density on age-size curve, maximum body size and total gamete production per life span. The mechanistic approach is a promising method of providing accurate predictions in a world that is under in creasing anthropogenic pressure.