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This study investigates the familial resemblance of maximal oxygen uptake(˙VO2max) based on data from 86 nuclear families of Caucasian descent participating in the HERITAGE Family Study. In the current study,˙VO2max was measured twice on a cycle ergometer in 429 sedentary individuals (170 parents and 259 of their offspring), aged between 16 and 65 yr. The ˙VO2max was adjusted by regression procedures for the effects of 1) age and sex; 2) age, sex, and body mass; and 3) age, sex, body mass, fat mass, and fat-free mass, as determined by underwater weighing. Evidence for significant familial resemblance was observed for each of the three ˙VO2max phenotypes. Spouse, sibling, and parent-offspring correlations were significant, suggesting that both genetic and environmental factors contribute to the familial resemblance for ˙VO2max. Maximal heritability estimates were at least 50%, a value inflated to an undetermined degree by nongenetic factors. The hypothesis of maternal inheritance, with the father's contribution being environmental, was also found to fit the data with estimates of maternal heritability, potentially associated in part with mitochondrial inheritance, reaching about 30%. These results suggest that genetic and nongenetic factors as well as maternal influences contribute to the familial aggregation of ˙VO2max in sedentary individuals.

The symposium will: a) review the evidence for a role of genetic factors in fitness and performance; b) discuss strategies and technologies that can be used to investigate molecular genetic issues for complex multifactorial traits; c) identify the most important research questions to be addressed. The session will be organized around 5 presentations. The first (Bouchard) will define the key questions, the research designs that are most promising and the technologies that have the greatest chance of success in defining the molecular & genetic basis of fitness and performance. The 2nd (Perusse) will focus on candidate genes and the role that sequence variants in these genes play in these complex phenotypes in the sedentary state and in the response to regular exercise. The 3rd (Rankinen) will review the evidence from genome scans for the presence of quantitative triat loci affecting fitness and performance and their trainability. Efforts in the positional cloning of these loci will also be reviewed. The 4th (Britton) will define rodent models that can be used to investigate the genetic and molecular basis of aerobic endurance. The contributions of selective breeding designs will be emphasized. The 5th (Booth) will summarize the contributions that can be expected from gene expression studies in the context of exercise and exercise training paradigms. The role that gene expression studies play in providing new leads for candidate gene investigations will be highlighted.

Unknown

Upper body fat and abdominal visceral fat are two obesity-related phenotypes of interest because of their relationships with a variety of metabolic complications. The heritability of the amount of upper body fat or the level of upper body fat relative to lower body fat ranges from ∼30–50% of the phenotype's age, sex and total body fat adjusted variance. On the other hand, familial studies of abdominal visceral fat reveal that the familial transmission reaches >50% of the age, sex and total body fat adjusted variance. Complex segregation analysis undertaken with a panel of nuclear families indicates that major genes may account for a significant fraction of the variance in upper body fat and abdominal visceral fat. Two intervention studies conducted with pairs of male identical twins have shown that changes in upper body fat and visceral fat are more similar within pairs than between pairs, either in phenotype increments when challenged by chronic overfeeding, or in adipose tissue losses after exposure to long-term negative energy balance conditions. The evidence accumulated to date is sufficient to justify undertaking a search for the specific genes and molecular markers involved in the heterogeneity commonly observed in human fat topography.

No abstract is provided for this article.

No abstract is provided for this article.

How much physical activity is needed in adults to prevent morbidities, disabilities, and premature death? This is one of the most important questions for all those who have an interest in the topic of physical activity and health and who believe that the promotion of a physically active lifestyle should be the cornerstone of contemporary public health programs. The evolution from performance- and fitness-centered exercise prescriptions toward health-related physical activity recommendations over the last decades had a dramatic influence on this topic. This is best illustrated by the differences in the recommendations contained in the 1978 Position Statement of the ACSM on the issue (1) and in the 1996 Report of the Surgeon General of the U.S. (24). Recognizing the importance of the issue and the uncertainties concerning the amount of physical activity necessary to generate health benefits, a group of Canadians, among them those who organized the 1988 and 1992 International Conferences on exercise or physical activity and health outcomes (7,8), organized a Symposium entirely devoted to dose-response relationships. The Symposium was held from October 11 to 15, 2000, at Hockley Valley Resort, near Toronto. Participation was by invitation only and 24 experts from six countries were asked to review the evidence for a dose-response relationship between regular physical activity and health outcomes. A Consensus Committee composed of highly respected scientists from other fields was asked to evaluate the evidence and write a Consensus Statement. The Committee was chaired by Dr. Antero Kesaniemi, professor of internal medicine, University of Oulu, Finland. Ample time was set aside for discussion and for the members of the Consensus Committee to ask questions and request clarification on any relevant issues. ASSESSING THE QUALITY OF THE EVIDENCE Scientists and practitioners alike understand that the quality of the scientific evidence behind a commonly accepted view or a generalized clinical practice may vary considerably. The evidence is at times very strong but can be rather tenuous in other situations. The "gold standard," i.e., the highest level of evidence, is thought to be when a solid body of data from several randomized controlled trials (RCTs) is available. Even though it would be desirable to make recommendations based only on such a high standard level of evidence, such data are not always available. Moreover, there are situations in which RCTs cannot even be contemplated. In such cases, one has to rely on other lines of evidence and on the degree of concordance or discordance among a variety of study designs. Controlled but not randomized studies, small experimental research focusing on mechanisms, prospective observational studies, cross-sectional observational research, animal model observations, case studies, surveys of expert views, etc., are typically used to substitute or complement the evidence from RCTs. For the Dose-Response Symposium, we have elected to use a system to qualify the level of evidence that was recently developed at the National Institute of Health (see below). The topic is further addressed in the paper of David Schriger published in this Supplement. At the initiative of the National Heart, Lung, and Blood Institute (NHLBI), a group of experts from many disciplines developed evidence-based guidelines for the prevention and treatment of obesity and its comorbidities that were published in 1998 (16). The experts invited to the Dose-Response Symposium were instructed to use the four evidence categories as defined in the NHLBI report to assess the level and quality of evidence for each particular issue they were addressing and in developing a series of summary statements. Table 1 highlights the evidence categories from the NHLBI report. Evidence Category A is attained when there is a rich body of data from RCTs. The evidence is from endpoints of well-designed RCTs that provide a consistent pattern of findings. Category A therefore requires a substantial number of studies involving a substantial number of participants. Table 1: The evidence categories with the sources of evidence.Evidence Category B is reached when there is a limited body of data from RCTs. It is applicable if few randomized trials exist, they are small in size, trial results are somewhat inconsistent, or trials were undertaken in populations that differ from the target population. Category B may also be attained based on the results of meta-analysis of RCTs. Evidence Category C is granted when the data supporting the conclusion are from uncontrolled or nonrandomized trials, or from cross-sectional or prospective observational studies. Finally, Evidence CategoryD can be given when the provision of some guidance is deemed valuable but there is no compelling scientific or clinical data to justify the use of categories A to C. Category D results from the expert judgment of participants and panel members. DOSE-RESPONSE: EVOLUTION OF CONCEPTS The quantification of the amount of physical activity has been the focus of many studies in the past century. Early on the research emphasis was on the measurement and quantification of the energy costs and physiological demands of occupational tasks, personal chores, sports, and leisure-time physical activities. Subsequently, the focus shifted on the conditions under which regular exercise leads to improvement in physical fitness or optimization of physical performance. More recently, we have seen a growing interest for the assessment of physical activity level and measurement of energy expenditure in free-living individuals under a variety of circumstances. At present, a key question is how much physical activity is needed to experience health benefits and avoid premature death. The Hockley Valley Resort 2000 Symposium was designed to review and qualify the evidence bearing on the latter question. Scandinavian and German physiologists and physicians were the first to investigate the topic of the amount of training necessary to improve fitness and performance. One of the dominant research themes in the 1960s was the differential effects of intermittent and continuous exercise or exercise training (4,9,15,21,22). Another major issue was the difference in cardiovascular and metabolic adaptation to physical work performed at various intensities and durations with the goal of defining the threshold above which performance time was considerably diminished, the so-called "Ausdauerleistungsgrenze"(14). Over the years, various definitions of the concept of "intensity threshold" were proposed but were generally applied more to training and performance issues than to health-related fitness and health outcomes. During the same period, the issue of the minimal amount of regular exercise needed to generate significant health benefits with an emphasis on cardiovascular fitness began to be investigated (5). How much physical activity with comprehensive experimental manipulations of intensity, frequency, and duration of sessions was first asked in the context of training-induced changes in V̇O2max by Shephard in 1968 (23) (predicted V̇O2max) and Davies and Knibbs in 1971 (10) (measured V̇O2max). Later, Nördesjo (18) in 1974 investigated the issue in terms of short (6 min) and long (90 min) maximal performance tests. Subsequently, the attention shifted to the conditions under which submaximal working capacity (PWC at a heart rate of 170) could be improved (6). These studies were complemented by a large number of experiments in which one, or at times two, of the three dimensions of intensity, frequency, and duration of sessions were experimentally altered to assess their effects on an outcome that was generally V̇O2max. These studies up to 1972 were reviewed by Pollock (20). An important landmark in the history of the evolution of concepts on the dose-response relationships was the publication in 1978 by ACSM of the Position Statement on the Recommended Quantity and Quality of Exercise for Developing and Maintaining Fitness in Healthy Adults (1). The recommendations can be summarized as follows: intensity of 60 to 90% of maximum heart rate reserve, frequency of 3–5 d·wk-1, and duration of 15–60 min per session. Locomotor activities and other activities requiring the involvement of large muscle masses were recommended. In 1990, the Position Statement was revised (2). Although it remained essentially unchanged for the intensity, frequency, and duration recommendations, the document recognized that these exercise recommendations were designed to improve physical fitness and cardiorespiratory endurance rather than health-related fitness. It also emphasized that health benefits could be obtained from engaging in regular exercise performed under conditions that differed from those described in the ACSM Position Statement. This was followed by a series of very influential reports and pronouncements on the nature of the relationship between regular physical activity and health outcomes and public health messages. A group of about 20 experts met in 1994 at the invitation of the Centers for Disease Control and Prevention and the ACSM to review the evidence and develop a concise public health message. The results of these deliberations were summarized in JAMA in 1995 (19). The recommendation was that "every U.S. adult should accumulate 30 min or more of moderate-intensity physical activity on most, preferably all, days of the week." A year later, the very influential report of the Surgeon General of the United States on Physical Activity and Health was published (24). The same recommendation was made with the addition that it applied to people of all ages. The same public health message was adopted by the 13-member panel of the NIH Consensus Development Conference on Physical Activity and Cardiovascular Health (17). An underlying assumption made at all these gatherings of experts and behind the resulting public health message is that the relation between physical activity and health outcomes, particularly mortality rates, is not linear. The common view is that most of the benefits of a regularly active lifestyle can be obtained at low to moderate volumes of physical activity and at less than vigorous intensity (12). In 1998, ACSM published a third Position Statement on the Recommended Quantity and Quality of Exercise for Developing and Maintaining Fitness in Healthy Adults (3). In general, the recommendations were for a larger volume of activity performed at higher intensities than in the public health messages. Finally, Canada's Physical Activity Guide was published in 1998 (13). The Guide recommended that adults should accumulate 60 min of physical activity every day. In this case, the assumption was that most people interpret the public health message in terms of predominantly light intensity activities, thus the necessity to recommend a larger daily volume. KEY ISSUES CONSIDERED IN THE CONSENSUS PROCESS The emphasis of the Symposium was on level of physical activity and health outcomes. Figure 1 depicts the basic paradigm underlying the consensus effort. Two paths link physical activity to health outcomes. The first is a direct path in which variation in physical activity level is thought to have an impact on health. The second path is one in which variation in physical activity level translates into changes in health-related fitness, which in turn influence health outcomes. Obviously, references were often made to fitness in the discussion but no systematic attempt was undertaken to arrive at a consensus on the relationships between physical or health-related fitness levels and health outcomes. FIGURE 1: The basic paradigm defining the paths from physical activity levels to health outcomes.The Consensus Committee was faced with the challenge of defining the nature of the relationships between regular physical activity and a whole series of health outcomes ranging from premature mortality to quality-of-life indicators. Even though these relationships can be described in detail by a complex family of curves (11), the problem can also be approached in terms of the three curves shown in Figure 2. The first pattern (curve B) is a linear relationship. This curve seems the most appropriate for the relationship between physical activity level and mortality rates as will be evident from the research summarized in this Supplement. The other two curves (A and C) also provide good fits with specific health outcomes. Curve A best describes the dose-response pattern upon which the current physical activity recommendations are based. It specifies that most of the benefits are attained at low to moderate levels of physical activity. One of the aims of the Consensus Symposium was to examine critically the evidence commonly cited in support of this dose-response pattern. In contrast, curve C specifies that the greatest benefits are obtained only when the level of physical activity is rather high. Some of the health outcomes conform to this curve. FIGURE 2: Schematic illustration depicting the relationships between physical activity level defined in minutes of participation per week or energy expended. See text for explanation.A large number of questions are addressed in the papers prepared by the invited experts and were discussed with the Consensus Committee during the Symposium. The definitions of physical activity, exercise, and fitness were considered, as were frequency and duration of sessions. The topic of fractionation into various physical activity periods was addressed. A considerable amount of time was devoted to the topic of absolute and relative intensity, the issue of thresholds, and the monitoring of intensity. Total amount or volume of physical activity, its quantification, and monitoring also received considerable attention. The benefits resulting from an acute exposure to physical activity versus those expected with regular participation were discussed. The levels of risks versus the anticipated benefits were taken into consideration for a variety of outcomes. Whether the apparent benefits associated with a physically active lifestyle could be imputed to physical activity or energy expenditure per se or to ensuing loss of adiposity was a topic that generated much interest. The participants also discussed whether there were any differences in the dose-response relationships between men and women, young versus older people or ethnic groups. In summary, the goal of the Consensus Symposium was to critically examine the evidence for the dose-response relationships between physical activity levels and health benefits and to identify key issues for future research. The key questions were: Is there a dose-response relation? Does it vary by outcome? What is the exact nature of the relationship? Is there evidence for a threshold? These central questions provided the impetus for an evidence-based Symposium. CONTENT OF THE SUPPLEMENT The various texts published in this Supplement of Medicine and Science in Sports and Exercise deal with these major questions. After this introduction, the Consensus Statement is presented. This is followed by the papers that focused on definitions and general issues. After a series of related topics (the equivalent of half a day of meeting time), a summary of the evidence as defined by the colleague who chaired the session is presented. Thus, the Supplement includes the Preface, Introduction, Consensus Statement, 24 papers, and 6 summaries from chairpersons. Eleven of these papers deal with specific health outcomes. Address for correspondence: Claude Bouchard, Ph.D., Pennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, LA 70808; E-mail: [email protected]

A model for the calculation of secondary electron energy distributions due to bombardment of an amorphous surface by electrons is presented. It takes into account the possibilities of reflexion and tunneling at the surface potential barrier. The general shape of the energy distributions obtained are compared with some typical experimental data. The advantages of the expression obtained for the secondary electron energy distribution are its simplicity and the fact that it can fit the experimental data of a great number of different materials, thus rendering it useful in calculations relating to electron multipliers or other secondary emission devices.

This commentary is written to recommend that we consider modifying the way we express weight change in clinical trials of weight management as well as in the physician's office. In most cases, weight loss is expressed as pounds (kg in other countries) or as a percent of baseline weight. We are proposing that weight loss might be expressed as a “percentage of excess body weight loss” (%EBWL), which could complement the use of actual weight loss. %EBWL provides a better estimate of the amount of weight loss that has been achieved relative to a defined goal level; however, that may be defined. This method is typically used to express weight change after surgical treatment for obesity. Using a standard metric will facilitate comparison across behavioral, medical, and surgical trials for weight loss, and may thus be beneficial to patients, clients, health-care providers, investigators, and policy-makers. Weight loss has been expressed in many different ways over the past 150 years ((1)). In his famous pamphlet titled “Letter on Corpulence Addressed to the Public” published in 1863, William Banting expressed his own weight loss in pounds ((2)). Most others have followed his lead, using either pounds or kilograms of actual weight lost. One problem with this approach is that heavier people tend to lose more weight and thus may appear more successful over short periods of time. Expressing weight loss as a percent of initial body weight will partly correct for this, but will not provide a true assessment of the amount of excess weight a patient or client might expect to lose in relation to a floor or maximal likely weight loss. In 1835, Quetelet introduced what is now known as the BMI as a way of normalizing weight for different heights in his studies of populations ((3)). A century and a half later, the BMI was adopted, internationally, as a way of evaluating whether an individual is overweight or obese ((4),(5)). The advantage of the BMI is that it minimizes the effect of height better than other height/weight relationships, except possibly weight/height ((6)). Changes in BMI have also been used as one method of expressing weight loss. Because the height of adults does not change during weight loss, using BMI units can be confusing and provides no advantages over using weight loss alone. Moreover, reporting weight loss as change in BMI units does not reveal how much of the excess weight has been lost. In 1959, a classic article by Stunkard and McLaren-Hume ((7)) reported on a new method for evaluating weight loss in cohorts. They expressed weight loss as a percentage of patients who lost either 20 or 40 pounds. Because heavier people tend to lose more weight, Trulson ((8)) introduced a somewhat more sophisticated approach in which both initial body weight and an appropriate weight loss for the degree of overweight were included. A third criterion was developed by Jolliffe and Alpert ((9)), who proposed the performance index to measure weight loss relative to anticipated or predicted weight loss: This latter concept gets closer to the idea of expressing weight loss in terms of %EBWL, and would be synonymous if the anticipated weight loss was equivalent to the amount of excess weight. Thus its major limitation is the criterion for the anticipated weight loss. The most sophisticated approach was proposed by Feinstein ((10)), and is called the reduction index. WL = weight loss = WI − WE WI = initial weight WS = surplus weight = WI − WT WT = target weight WE = end-of-treatment weight This index considers both the degree of excess initial weight and actual weight loss. Its number ranges from 0 to 200, with higher indices reflecting a greater weight loss. It is difficult to translate this index for individual patients. When a patient begins a weight-loss program, whether at home, in a clinical environment, or as part of a research trial, there is, for all practical purposes, a floor to the amount of weight she/he can lose. Indeed some clinical trials put stopping rules in place in case too much weight is lost. The reason is obvious—we have certain amounts of lean body mass and fat mass that are essential for life. Moreover, once a person has reached what is commonly recognized as the upper limits for a normal or healthy body weight, there is no public health reason to pursue an even lower body weight. Gallagher et al. ((11)) published data showing the amount of body fat for men and women at three different levels of BMI. The data for two age groups are shown in Table 1. Although the data are curvilinear, the line for men parallels that for women. At each BMI listed, women have about 11–12% more of their total body weight as fat as a man at the same BMI. At a BMI of 25 kg/m2 the percentage body fat in women is 32–35% and in men 20–23%. Except for individuals in vigorous physical training, an increase in BMI above 30 kg/m2 is associated with an increase primarily in body fat. Between a BMI of 25 kg/m2 and 30 kg/m2 the BMI does not predict obesity, i.e., increased body fat, as well as at higher BMI values. Body fat asymptotes at about 52% in women and 56% in men ((6)). In a study of anthropometric predictors of body fat, Larson et al. ((6)) found that BMI predicted percent body fat, whereas weight/height was a better predictor of total fat. Some idea about the composition and magnitude of weight changes that might be expected with overfeeding or energy restriction has come from careful assessments of body composition during overfeeding and weight loss. During weight gain in normal individuals, lean tissue accounts for about one-third and fat for about for two-thirds of the weight gain ((12)). Weight loss on energy-deficient diets has shown a similar relationship ((13)). As noted earlier, the surgical literature already typically reports weight loss as %EBWL. This approach takes the degree of excess weight above a recognized benchmark, such as a BMI of 25 kg/m2 or some other agreed-to level, such as the upper limit of standard life insurance tables. We suggest that it makes more sense to use a BMI of 25 kg/m2 for these calculations, because this value corresponds to the upper limit of normal as recommended by the National Heart, Lung, and Blood Institute ((4)) and World Health Organization ((5)). The %EBWL calculated using a BMI of 25 kg/m2 seems a reasonable suggestion for two reasons. First, it focuses on the amount of weight that needs to be lost to reach the upper limit of normal body weight. Second, it has the effect of expressing the weight loss in larger numerical terms, which provides a better estimate for both patient and health-care provider of the true amount of weight that has been lost in any program. Table 2 shows how this approach works. A BMI of 25 kg/m2 is used as the proposed upper limit of normal, although others could be selected based on ethnicity, age, or other considerations. Excesses from this point are calculated. For example, a 95-kg (209-pound) man with a height of 178 cm (70 inches) has a BMI of 30 kg/m2. His weight at a BMI of 25 kg/m2 would be 79 kg. Thus to reach his goal, this man needs to lose 16 kg (95 − 79 kg). If he loses 8 kg or half of this target weight, he will have actually lost 50% of his excess body weight. This becomes a much more realistic description of the success of treatment than 8.4% (8/95), which is his loss from a baseline of 95 kg. After a BMI loss of 5 kg/m2, the percentage of excess body weight is about twice as large as it would be if it were expressed as a percentage of initial weight lost. This is true at any BMI. At a BMI of 50 kg/m2, a 5-BMI-unit decrease would be a 10% weight loss, but nearly a 20% loss of excess body weight. This is a more optimistic outlook for patient and health-care provider and provides a more realistic evaluation of the amount of potential weight loss that can be achieved. Patients and health-care providers are often at odds as to what constitutes meaningful weight loss ((14)). Most physicians believe that a 10% weight loss will produce improvements in metabolic and cardiac risk factors ((4)). However, a 10% weight loss does not match most patients' (clients') desires. Expressed as excess weight loss, this same 10% now becomes ∼20% and illustrates to clients that they have lost 1/5 of the weight that they might have to lose. Second, this approach has the advantage of providing practitioners with a meaningful and clearly defined target weight. We have proposed a BMI of 25 kg/m2 based on accepted standards of weight representation now widely used around the world. ((4),(5)), but other values might be acceptable for different populations. Table 3 provides a way of converting the patient/physician weight-loss goal in percent of total body weight loss into the %EBWL. For these we have used a BMI of 25 kg/m2 as the floor. Using BMI corrects for differences in height between shorter and taller individuals when expressing percent excess weight lost. It will be straightforward to make conversion tables for computers that display the percent excess weight loss for individuals with a given initial BMI, which may be helpful to the patient and provider. Different anticipated weight losses might also be used, as proposed by Jolliffe and Alpert ((9)). There is at least one drawback to using the %EBWL that needs to be acknowledged. With this approach, more obese subjects are less likely to achieve 100% reduction than less obese individuals. This is the case independent of how “normal weight” is defined. In summary, we propose that using %EBWL as a standard metric for reporting the efficacy of behavioral, medical, and surgical weight-loss treatments would unify what are now different ways of reporting results and thus be superior to the current practice. The use of %EBWL may also increase the motivation of individual patients. We believe that this approach has important benefits for patients, health-care providers, obesity researchers, and those who are consumers of the results of that research. Using %EBWL will also increase the comparability among studies of different modalities of treatment in different patient populations with differing starting weights and BMIs. The authors declared no conflict of interest.

No abstract is provided for this article.