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1.  Peak Fat Oxidation Rate During Walking in Sedentary Overweight Men and Women 
The aim of this study was to determine the relative exercise intensity that elicits maximal fat oxidation during walking in inactive and overweight men and women and evaluate any possible sex differences. Forty six healthy, sedentary, overweight men (age: 36.3 ± 1.3 years, body fat: 28.8 ± 0.8%, n = 28, mean ± SE) and women (age: 36.6 ± 1.8 years, body fat: 37.1 ± 0.8%, n = 18) participated in the study. Fat oxidation was calculated from expired air analysis using indirect calorimetry during an incremental treadmill walking test. Peak fat oxidation rate (PFO) was higher in men compared to women (0.31 ± 0.02 vs. 0.20 ± 0.02 g.min-1; p < 0.001), but this difference disappeared when PFO was scaled per kg fat-free mass (4. 36 ± 0.23 vs. 3.99 ± 0.37 mg.kg fat free mass-1.min-1). Also, the relative exercise intensity at which PFO occurred was similar for men and women and corresponded to 40.1 ± 1.8 and 39. 5 ± 2.3% of maximal oxygen uptake (VO2max) and 60.0 ± 1.4 and 57.8 ± 1.4% of maximal heart rate, respectively. The walking speed corresponding to PFO was 5.5 ± 0.2 and 5.0 ± 0.1 km·h-1 for men and women, respectively. Regression analysis showed that sex, FFM and VO2max were significant predictors of PFO expressed in g.min-1 (adjusted R2 = 0.48, p = 0.01). However when PFO was scaled per kg FFM, only a small part of the variance was explained by VO2max (adjusted R2 = 0.12, p < 0.05). In conclusion, peak fat oxidation rate and the corresponding relative exercise intensity were similar in male and female overweight and sedentary individuals, but lower compared to those reported for leaner and/or physically active persons. Walking at a moderate speed (5.0-5.5 km·h-1) may be used as a convenient way to exercise at an intensity eliciting peak fat oxidation in overweight individuals.
Key pointsPeak fat oxidation rate scaled per kg fat-free mass and the corresponding relative exercise intensity are similar in male and female overweight and sedentary individuals, but lower compared to those reported for leaner and/or physically active persons.Walking at a moderate speed (5.0-5.5 km.h-1) may be used as a convenient way to exercise at an intensity eliciting peak fat oxidation in overweight individuals.The relationship between %HRmax and %VO2max in overweight individuals is different from that reported for normal-weight adults and should be taken into account to optimize exercise intensity using heart rate in obese individuals.Due to the low intensity corresponding to peak fat oxidation in overweight and sedentary persons and the inter-individual differences, exercise intensity for health benefits should be prescribed following individual testing.
PMCID: PMC3761910  PMID: 24149961
Exercise intensity; calorimetry; substrate utilisation
2.  Gender differences in injuries among rural youth. 
Injury Prevention  1995;1(1):15-20.
GOAL: This paper presents injury data from the first year of a three year longitudinal study of risk taking behaviors among adolescents. SAMPLE: Study subjects were a cohort of 758 rural students from Maryland's Eastern Shore who were in the eighth grade in 1987. METHODS: Students completed a 45 minute, self administered survey in which they reported numbers of injuries experienced in the past year, risk taking behaviors, anger expression, delinquency, alcohol and drug use, physical exercise, work experience, and level of parental supervision. In addition, students had their height and weight measurements taken by trained research staff and completed a self rating of pubertal development using Tanner drawings. RESULTS: Slightly more than half (53.2%) of the boys and over one third (37.7%) of the girls reported experiencing one or more medically attended injuries during the last year. Poisson regression analyses were conducted to estimate the extent to which gender differences in injuries could be accounted for by adolescent behaviors. Gender effects became non-significant when adjustments were made for risk taking, school discipline problems, and exercise frequency. Gender differences in injuries were reduced but remained significant when substance use, employment, and anger were controlled. Poisson regression analyses were conducted separately for males and females to assess whether factors associated with injuries were similar across genders. For boys, risk taking, anger, and school discipline problems were significantly related to number of injuries. Boys with a low body mass index and late pubertal development (mean ratio 3.09), as well as those with high body mass index and early pubertal development (mean ratio 2.16), reported greater numbers of injuries than average boys. For girls, substance use, cruising, risk taking, anger, and exercise frequency were significantly associated with injuries. Girls with an early onset of menses reported, on average, twice the number of injuries than those who were on time. Girls with high body mass index who were late in their pubertal development reported, on average, five times more injuries than other girls. CONCLUSIONS: Although gender is a significant risk factor for injuries, certain behaviors like risk taking, school related delinquency, and physical exercise partially explain the higher number of injuries among adolescent males in this study. For both males and females, indicators of pubertal and physical development are important factors to consider in studies of injuries during early adolescence.
PMCID: PMC1067535  PMID: 9345987
3.  Cardiorespiratory Characteristics and Cholesterol Responses to a Single Session of Heavy Leg Press Exercise 
The effect of resistance exercise on blood lipids is not clear yet. The purpose of this study was to examine the cholesterol responses to a heavy resistance leg press exercise emphasizing on the eccentric movement 24 and 48 hours following exercise and to quantify the cardiorespiratory responses of the exercise bout in an attempt to clarify the exercise characteristics that may be responsible for the effects of heavy resistance exercise on blood lipids. Nine healthy, untrained male volunteers aged 27.2 ± 1.1 yrs (76.2 ± 2.5 kg, 1.79 ± 0.02 m) performed a session of heavy RE emphasizing on the eccentric movement consisting of eight sets of inclined leg presses at six repetition maximum with 3-min rest intervals. Venous blood samples were obtained at rest (control) and 24 and 48 hours following exercise. Average VO2 at rest was 4.0 ± 0.4 ml·min−1·kg−1, during exercise 19.6 ± 0.2 ml·min−1·kg−1 and during the 180 sec recovery period between sets 12.5 ± 0.2 ml·min−1·kg−1. RER values decreased with the progression of the exercise and were significantly lower during the last four sets compared with the first four sets of the exercise session. Resting heart rate was 67 ± 2 bpm, and maximum heart rate during exercise was 168 ± 1 bpm. Serum creatine kinase was significantly elevated on day 1 (1090 ± 272 U·L−1, p < 0.03) and peaked on day 2 (1230 ± 440 U·L−1 p < 0. 01). Total cholesterol, HDL cholesterol and calculated LDL cholesterol concentration did not change significantly following with exercise. This protocol of heavy resistance exercise has no effect on TC or cholesterol sub-fraction concentration 24 and 48 hours following exercise which may be due to the low energy expenditure of the exercise and/or to the gender of the participants.
Key pointsRepeated sets of heavy resistance exercise significantly increase oxygen uptake both during exercise and the following recovery period.Even though exercise was of low volume (8 sets x 6 repetitions) the elevated oxygen uptake during the rest intervals in combination with the total exercise session duration (26 min) resulted in aerobic energy expenditure that is equivalent to low to moderate intensity cycling.Leg press resistance exercise emphasizing on the eccentric movement that caused muscle damage had no effect on total cholesterol, HDL-C and LDL-C during the two days following exercise in young healthy male subjects.
PMCID: PMC3761812  PMID: 24149784
Muscle damage; energy expenditure; total cholesterol; HDL; oxygen uptake.
4.  Comparison of rehydration regimens for rehabilitation of firefighters performing heavy exercise in thermal protective clothing: A report from the Fireground Rehab Evaluation (FIRE) trial 
Background:
Fire suppression activities results in cardiovascular stress, hyperthermia, and hypohydration. Fireground rehabilitation (rehab) is recommended to blunt the deleterious effects of these conditions.
Objective:
We tested the hypothesis that three rehydration fluids provided after exercise in thermal protective clothing (TPC) would produce different heart rate or core temperature responses during a second bout of exercise in TPC.
Methods:
On three occasions, 18 euhydrated firefighters (16 males, 2 females) wearing TPC completed a standardized, 50-minute bout of upper and lower body exercise in a hot room that mimicked the National Fire Protection Association (NFPA) rehabilitation guidelines of “two cylinders before rehab” (20 min work, 10 min recovery, 20 min work). After an initial bout of exercise, subjects were randomly assigned water, sport drink, or an intravenous (IV) infusion of normal saline equal to the amount of body mass lost during exercise. After rehydration, the subject performed a second bout of exercise. Heart rate, core and skin temperature, and exercise duration were compared with a two-way ANOVA.
Results:
Subjects were firefighters aged 28.2±11.3 years with a VO2peak of 37.4±3.4 ml/kg/min. 527±302 mL of fluid were provided during the rehabilitation period. No subject could complete either the pre- or post-rehydration 50-minute bout of exercise. Mean (SD) time to exhaustion (min) was longer (p<0.001) in bout 1 (25.9±12.9 min. water, 28.0±14.1 min. sport drink, 27.4±13.8 min. IV) compared to bout 2 (15.6±9.6 min. water, 14.7±8.6 min. sport drink, 15.7±8.0 min. IV) for all groups but did not differ by intervention. All subjects approached age predicted maximum heart rate at the end of bout 1 (180±11 bpm) and bout 2 (176±13 bpm). Core temperature rose 1.1±0.7°C during bout 1 and 0.5±0.4°C during bout 2. Core temperature, heart rate, and exercise time during bout 2 did not differ between rehydration fluids.
Conclusions:
Performance during a second bout of exercise in TPC did not differ when firefighters were rehydrated with water, sport drink, or IV normal saline when full rehydration is provided. Of concern was the inability of all subjects to complete two consecutive periods of heavy exercise in TPC suggesting the NFPA “two cylinders before rehab” guideline may not be appropriate in continuous heavy work scenarios.
doi:10.3109/10903120903524963
PMCID: PMC2867093  PMID: 20095824
Cardiovascular strain; Thermal Stress; Performance; Hydration
5.  The Effect of High Intensity Interval Exercise in High / Low Temperatures on Exercise-Induced Bronchoconstriction (EIB) in Trained Adolescent Males 
Tanaffos  2013;12(3):29-43.
Background
Exercise-induced bronchoconstriction (EIB) describes airway narrowing that occurs in association with exercise. Exercise in hot and cold environments has been reported to increase exercise-induced bronchoconstriction (EIB) in subjects with asthma. However, to our knowledge, the effect of hot and cold environment on pulmonary function and EIB in trained males has not been previously studied. The main goal of this research was to examine the influence of environmental temperature and high intensity interval exercise on pulmonary function in trained teenage males. Also, this study sought to assess the influence of exercise and environmental temperature on EIB.
Materials and Methods
Thirty trained subjects (mean age 16.56±0.89 yrs, all males) underwent high intensity interval exercise testing (22 minutes) by running on a treadmill in hot and cold environments under standardized conditions (10 °C and 45 °C with almost 50% relative humidity in random order in winter and summer). Lung function (flow volume loops) was measured before and 1, 5, 15, 30 and 60 min after the exercise by digital spirometer. Data was analyzed using SPSS software and P < 0.05 was considered significant. The diagnosis of EIB was made by 10% fall in FEV1 post-exercise.
Results
The post-exercise maximal reduction in forced expiratory volume in 1s (FEV1), peak expiratory flow (PEF) and average forced expiratory flow rate over the middle 50% of the FVC (FEF25-75) increased significantly compared to pre-exercise at 10 °C with almost 50% relative humidity (cold air). The obtained values were: -15.93(15min post-exercise), -22.53 (1 min post-exercise) and -18.25%(5min post-exercise). Post-exercise maximal reduction in FEV1, PEF and FEF25-75 increased significantly compared to pre-exercise value at 45 °C with almost 50% relative humidity (hot air). Obtained values were: -10.35 (1 min post-exercise), -9.16 (1 min post-exercise) and -7.39 (5 min post-exercise). Changes in FEV1, PEF and FEF25-75 reduction in cold air was significantly greater than in hot air (P < 0.05). Maximal prevalence of exercise-induced bronchoconstriction (EIB) in cold and hot air was 60% (18 of 30 subjects) and 40% (12 of 30 subjects), respectively.
Conclusion
This study demonstrated that pulmonary function in hot and cold air was influenced by temperature (in the same relative humidity (50%) and also high intensity interval exercise. Prevalence of EIB after high intensity exercise in hot and cold air increased in trained adolescent males; however, these changes in cold air were greater than in hot air among trained adolescent males. Therefore, results of this study suggest that adolescents (although trained) should avoid high intensity (95% maximal heart rate) exercise in winter (extremely low temperature) and summer (extremely high temperature) to prevent EIB.
PMCID: PMC4153253  PMID: 25191471
Temperature; Exercise-Induced Bronchoconstriction; Exercise
6.  Abnormal haemodynamic response to exercise in heart failure with preserved ejection fraction 
European Journal of Heart Failure  2011;13(12):1296-1304.
Aims
Peak oxygen uptake (VO2) is diminished in patients with heart failure with preserved ejection fraction (HFpEF) suggesting impaired cardiac reserve. To test this hypothesis, we assessed the haemodynamic response to exercise in HFpEF patients.
Methods and results
Eleven HFpEF patients (73 ± 7 years, 7 females/4 males) and 13 healthy controls (70 ± 4 years, 6 females/7 males) were studied during submaximal and maximal exercise. The cardiac output (Qc, acetylene rebreathing) response to exercise was determined from linear regression of Qc and VO2 (Douglas bags) at rest, ∼30% and ∼60% of peak VO2, and maximal exercise. Peak VO2 was lower in HFpEF patients than in controls (13.7 ± 3.4 vs. 21.6 ± 3.6 mL/kg/min; P < 0.001), while indices of cardiac reserve were not statistically different: peak cardiac power output [CPO = Qc × mean arterial pressure (MAP); HFpEF 1790 ± 509 vs. controls 2119 ± 581 L/mmHg/min; P = 0.20]; peak stroke work [SW = stroke volume (SV) × MAP; HFpEF 13 429 ± 2269 vs. controls 13 200 ± 3610 mL/mmHg; P = 0.80]. The ΔQc/ΔVO2 slope was abnormally elevated in HFpEF patients vs. controls (11.2 ±3.6 vs. 8.3 ± 1.5; P = 0.015).
Conclusion
Contrary to our hypothesis, cardiac reserve is not significantly impaired in well-compensated outpatients with HFpEF. The abnormal haemodynamic response to exercise (decreased peak VO2, increased ΔQc/ΔVO2 slope) is similar to that observed in patients with mitochondrial myopathies, suggesting an element of impaired skeletal muscle oxidative metabolism. This impairment may limit functional capacity by two mechanisms: (i) premature skeletal muscle fatigue and (ii) metabolic signals to increase the cardiac output response to exercise which may be poorly tolerated by a left ventricle with impaired diastolic function.
doi:10.1093/eurjhf/hfr133
PMCID: PMC3220394  PMID: 21979991
Cardiac output response to exercise; Haemodynamic response to exercise; Heart failure with preserved ejection fraction; Exercise capacity; Myocardial contractile reserve; Oxygen consumption
7.  Inspiratory Muscle Fatigue Following Moderate-Intensity Exercise in the Heat 
Heavy exercise has been shown to elicit reductions in inspiratory muscle strength in healthy subjects. Our purpose was to determine the combined effects of moderate-intensity endurance exercise and a thermal load on inspiratory muscle strength in active subjects. Eight active, non heat-acclimatized female subjects (23.5 ± 1.4 yr; VO2max = 39.8 ± 2.4 ml.kg-1.min-1) randomly performed two 40 min endurance exercise bouts (60% VO2max) in either a thermo-neutral (22°C/21% RH) or hot (37°C/33% RH) environment on separate days. Maximal sustained inspiratory mouth pressure (PImax) was obtained pre and post exercise as an index of inspiratory muscle strength. Additional variables obtained every 10 min during the endurance exercise bouts included: rectal temperature (TRE), heart rate (HR), minute ventilation (VE), oxygen uptake (VO2), tidal volume (VT), breathing frequency (Fb), and ratings of perceived exertion and dyspnea (RPE/RPD). Data were analyzed with repeated measures ANOVA. PImax was significantly reduced (p < 0.05) after exercise in the hot environment when compared to baseline and when compared to post exercise values in the thermo-neutral environment. PImax was unchanged from baseline following exercise in the thermo-neutral environment. HR and TRE were significantly higher (p < 0.05) in the hot compared to the thermo-neutral environment. VE and VO2 were not significantly different between conditions. VT was unchanged between conditions whereas Fb was higher (p < 0.05) in the hot condition compared to thermo-neutral. RPE was not significantly different between conditions. RPD was significantly higher (p < 0.05) in the hot compared to the thermo-neutral environment. We conclude that moderate-intensity endurance exercise (60% VO2max) in a hot environment elicits significant reductions in inspiratory muscle strength in unfit females. This finding is novel in that previous studies conducted in a thermo-neutral environment have shown that an exercise intensity of >80% VO2max is required to elicit reductions in inspiratory muscle strength. In addition, dyspnea perception during exercise is greater in a hot environment, compared to thermo-neutral, at a similar level of VE and VO2.
Key PointsThe combined effects of a heat load and exercise on inspiratory muscle strength were investigated in untrained female subjects.Previous studies have shown that a very high exercise intensity (> 80% VO2max) is required to elicit reductions in inspiratory muscle strength.Prolonged submaximal exercise (40-min/60% VO2max) in a hot environment significantly reduced inspiratory muscle strength in untrained females whereas the same intensity in a thermo-neutral environment had no effect on inspiratory muscle function.These reductions in inspiratory muscle strength may be related to competition for blood flow among the locomotor, inspiratory, and cutaneous circulations.
PMCID: PMC3887326  PMID: 24453527
Control of breathing; endurance; respiratory function; thermal load
8.  Ventilatory response to exercise in adolescents with cystic fibrosis and mild-to-moderate airway obstruction 
SpringerPlus  2014;3:696.
Data regarding the ventilatory response to exercise in adolescents with mild-to-moderate cystic fibrosis (CF) are equivocal. This study aimed to describe the ventilatory response during a progressive cardiopulmonary exercise test (CPET) up to maximal exertion, as well as to assess the adequacy of the ventilatory response for carbon dioxide (CO2) exhalation. Twenty-two adolescents with CF (12 boys and 10 girls; mean ± SD age: 14.3 ± 1.3 years; FEV1: 78.6 ± 17.3% of predicted) performed a maximal CPET. For each patient, data of a sex- and age matched healthy control was included (12 boys and 10 girls; mean ± SD age: 14.3 ± 1.4 years). At different relative exercise intensities of 25%, 50%, 75%, and 100% of peak oxygen uptake (VO2peak), breathing pattern, estimated ventilatory dead space ventilation (VD/VT ratio), minute ventilation (VE) to CO2 production relationship (VE/VCO2-slope), partial end-tidal CO2 tension (PETCO2), and the VE to the work rate (VE/WR) ratio were examined. VO2peak was significantly reduced in CF patients (P = 0.01). We found no differences in breathing pattern between both groups, except for a significantly higher VE at rest and a trend towards a lower VE at peak exercise in patients with CF. Significantly higher values were found for the estimated VD/VT ratio throughout the CPET in CF patients (P < 0.01). VE/VCO2-slope and PETCO2 values differed not between the two groups throughout the CPET. VE/WR ratio values were significantly higher in CF during the entire range of the CPET (P < 0.01). This study found an exaggerated ventilatory response (high VE/WR ratio values), which was adequate for CO2 exhalation (normal VE/VCO2-slope and PETCO2 values) during progressive exercise up to maximal exhaustion in CF patients with mild-to-moderate airway obstruction.
doi:10.1186/2193-1801-3-696
PMCID: PMC4254890  PMID: 25512888
Pulmonary physiology; Ventilation; Breathing pattern; Children
9.  Gender Differences in Adolescent Premarital Sexual Permissiveness in Three Asian Cities: Effects of Gender-Role Attitudes 
Purpose
Gender is an important factor in understanding premarital sexual attitudes and behaviors. Many studies indicate that males are more likely to initiate sexual intercourse and have more permissive perceptions about sex than females. Yet few studies have explored possible reasons for these gender differences. With samples of unmarried adolescents in three Asian cities influenced by Confucian cultures, this paper investigates the relationship between underlying gender norms and these differences in adolescents’ premarital sexual permissiveness.
Methods
16,554 unmarried participants aged 15–24 were recruited in the Three-City Asian Study of Adolescents and Youth, a collaborative survey conducted in 2006–2007 in urban and rural areas of Hanoi, Shanghai and Taipei, with 6204, 6023 and 4327 from each city respectively. All of the adolescents were administered face-to-face interviews, coupled with Computer Assisted Self Interview (CASI) for sensitive questions. Scales on gender-role attitudes and on premarital sexual permissiveness for both male and female respondents were developed and applied to our analysis of the data. Multi-linear regression was used to analyze the relationship between gender-role attitudes and sexual permissiveness.
Results
Male respondents in each city held more permissive attitudes towards premarital sex than did females with both boys and girls expressing greater permissiveness to male premarital sexual behaviors. Boys also expressed more traditional attitudes to gender roles (condoning greater inequality) than did girls in each city. Adolescents’ gender-role attitudes and permissiveness to premarital sex varied considerably across the three cities, with the Vietnamese the most traditional, the Taiwanese the least traditional, and the adolescents in Shanghai in the middle. A negative association between traditional gender roles and premarital sexual permissiveness was only found among girls in Shanghai and Taipei. In Shanghai, female respondents who held more traditional gender role attitudes were more likely to exercise a double standard with respect to male as opposed to female premarital sex (OR=1.18). This relationship also applied to attitudes of both girls and boys in Taipei (OR=1.20 and OR=1.22, respectively).
Conclusions
Although with variation across sites, gender differences in premarital sexual permissiveness and attitudes to gender roles among adolescents were very significant in each of the three Asian cities influenced by Confucian-based values. Traditional gender norms may still be deeply rooted in the three cities, especially among females, while it is important to advocate gender equity in adolescent reproductive health programs, the pathway of traditional gender norms in influencing adolescent reproductive health outcomes must be understood, as must differences and similarities across regions.
doi:10.1016/j.jadohealth.2011.12.001
PMCID: PMC4235609  PMID: 22340852
Gender role; Premarital sex; Attitudes; Asian; Confucian
10.  Male Circumcision at Different Ages in Rwanda: A Cost-Effectiveness Study 
PLoS Medicine  2010;7(1):e1000211.
Agnes Binagwaho and colleagues predict that circumcision of newborn boys would be effective and cost-saving as a long-term strategy to prevent HIV in Rwanda.
Background
There is strong evidence showing that male circumcision (MC) reduces HIV infection and other sexually transmitted infections (STIs). In Rwanda, where adult HIV prevalence is 3%, MC is not a traditional practice. The Rwanda National AIDS Commission modelled cost and effects of MC at different ages to inform policy and programmatic decisions in relation to introducing MC. This study was necessary because the MC debate in Southern Africa has focused primarily on MC for adults. Further, this is the first time, to our knowledge, that a cost-effectiveness study on MC has been carried out in a country where HIV prevalence is below 5%.
Methods and Findings
A cost-effectiveness model was developed and applied to three hypothetical cohorts in Rwanda: newborns, adolescents, and adult men. Effectiveness was defined as the number of HIV infections averted, and was calculated as the product of the number of people susceptible to HIV infection in the cohort, the HIV incidence rate at different ages, and the protective effect of MC; discounted back to the year of circumcision and summed over the life expectancy of the circumcised person. Direct costs were based on interviews with experienced health care providers to determine inputs involved in the procedure (from consumables to staff time) and related prices. Other costs included training, patient counselling, treatment of adverse events, and promotion campaigns, and they were adjusted for the averted lifetime cost of health care (antiretroviral therapy [ART], opportunistic infection [OI], laboratory tests). One-way sensitivity analysis was performed by varying the main inputs of the model, and thresholds were calculated at which each intervention is no longer cost-saving and at which an intervention costs more than one gross domestic product (GDP) per capita per life-year gained. Results: Neonatal MC is less expensive than adolescent and adult MC (US$15 instead of US$59 per procedure) and is cost-saving (the cost-effectiveness ratio is negative), even though savings from infant circumcision will be realized later in time. The cost per infection averted is US$3,932 for adolescent MC and US$4,949 for adult MC. Results for infant MC appear robust. Infant MC remains highly cost-effective across a reasonable range of variation in the base case scenario. Adolescent MC is highly cost-effective for the base case scenario but this high cost-effectiveness is not robust to small changes in the input variables. Adult MC is neither cost-saving nor highly cost-effective when considering only the direct benefit for the circumcised man.
Conclusions
The study suggests that Rwanda should be simultaneously scaling up circumcision across a broad range of age groups, with high priority to the very young. Infant MC can be integrated into existing health services (i.e., neonatal visits and vaccination sessions) and over time has better potential than adolescent and adult circumcision to achieve the very high coverage of the population required for maximal reduction of HIV incidence. In the presence of infant MC, adolescent and adult MC would evolve into a “catch-up” campaign that would be needed at the start of the program but would eventually become superfluous.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Acquired immunodeficiency syndrome (AIDS) has killed more than 25 million people since 1981 and more than 31 million people (22 million in sub-Saharan Africa alone) are now infected with the human immunodeficiency virus (HIV), which causes AIDS. There is no cure for HIV/AIDS and no vaccine against HIV infection. Consequently, prevention of HIV transmission is extremely important. HIV is most often spread through unprotected sex with an infected partner. Individuals can reduce their risk of HIV infection, therefore, by abstaining from sex, by having one or a few sexual partners, and by always using a male or female condom. In addition, male circumcision—the removal of the foreskin, the loose fold of skin that covers the head of penis—can halve HIV transmission rates to men resulting from sex with women. Thus, as part of its HIV prevention strategy, the World Health Organization (WHO) recommends that male circumcision programs be scaled up in countries where there is a generalized HIV epidemic and where few men are circumcised.
Why Was This Study Done?
One such country is Rwanda. Here, 3% of the adult population is infected with HIV but only 15% of men are circumcised—worldwide, about 30% of men are circumcised. Demand for circumcision is increasing in Rwanda but, before policy makers introduce a country-wide male circumcision program, they need to identify the most cost-effective way to increase circumcision rates. In particular, they need to decide the age at which circumcision should be offered. Circumcision soon after birth (neonatal circumcision) is quick and simple and rarely causes any complications. Circumcision of adolescents and adults is more complex and has a higher complication rate. Although several studies have investigated the cost-effectiveness (the balance between the clinical and financial costs of a medical intervention and its benefits) of circumcision in adult men, little is known about its cost-effectiveness in newborn boys. In this study, which is one of several studies on male circumcision being organized by the National AIDS Control Commission in Rwanda, the researchers model the cost-effectiveness of circumcision at different ages.
What Did the Researchers Do and Find?
The researchers developed a simple cost-effectiveness model and applied it to three hypothetical groups of Rwandans: newborn boys, adolescent boys, and adult men. For their model, the researchers calculated the effectiveness of male circumcision (the number of HIV infections averted) by estimating the reduction in the annual number of new HIV infections over time. They obtained estimates of the costs of circumcision (including the costs of consumables, staff time, and treatment of complications) from health care providers and adjusted these costs for the money saved through not needing to treat HIV in males in whom circumcision prevented infection. Using their model, the researchers estimate that each neonatal male circumcision would cost US$15 whereas each adolescent or adult male circumcision would cost US$59. Neonatal male circumcision, they report, would be cost-saving. That is, over a lifetime, neonatal male circumcision would save more money than it costs. Finally, using the WHO definition of cost-effectiveness (for a cost-effective intervention, the additional cost incurred to gain one year of life must be less than a country's per capita gross domestic product), the researchers estimate that, although adolescent circumcision would be highly cost-effective, circumcision of adult men would only be potentially cost-effective (but would likely prove cost-effective if the additional infections that would occur from men to their partners without a circumcision program were also taken into account).
What Do These Findings Mean?
As with all modeling studies, the accuracy of these findings depends on the many assumptions included in the model. However, the findings suggest that male circumcision for infants for the prevention of HIV infection later in life is highly cost-effective and likely to be cost-saving and that circumcision for adolescents is cost-effective. The researchers suggest, therefore, that policy makers in Rwanda and in countries with similar HIV infection and circumcision rates should scale up male circumcision programs across all age groups, with high priority being given to the very young. If infants are routinely circumcised, they suggest, circumcision of adolescent and adult males would become a “catch-up” campaign that would be needed at the start of the program but that would become superfluous over time. Such an approach would represent a switch from managing the HIV epidemic as an emergency towards focusing on sustainable, long-term solutions to this major public-health problem.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000211.
This study is further discussed in a PLoS Medicine Perspective by Seth Kalichman
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
Information is available from the Joint United Nations Programme on HIV/AIDS (UNAIDS) on HIV infection and AIDS and on male circumcision in relation to HIV and AIDS
HIV InSite has comprehensive information on all aspects of HIV/AIDS
Information is available from Avert, an international AIDS charity on many aspects of HIV/AIDS, including information on HIV and AIDS in Africa, and on circumcision and HIV (some information in English and Spanish)
More information about male circumcision is available from the Clearinghouse on Male Circumcision
The National AIDS Control Commission of Rwanda provides detailed information about HIV/AIDS in Rwanda (in English and French)
doi:10.1371/journal.pmed.1000211
PMCID: PMC2808207  PMID: 20098721
11.  Continuous low- to moderate-intensity exercise training is as effective as moderate- to high-intensity exercise training at lowering blood HbA1c in obese type 2 diabetes patients 
Diabetologia  2009;52(9):1789-1797.
Aims/hypothesis
Exercise represents an effective interventional strategy to improve glycaemic control in type 2 diabetes patients. However, the impact of exercise intensity on the benefits of exercise training remains to be established. In the present study, we compared the clinical benefits of 6 months of continuous low- to moderate-intensity exercise training with those of continuous moderate- to high-intensity exercise training, matched for energy expenditure, in obese type 2 diabetes patients.
Methods
Fifty male obese type 2 diabetes patients (age 59 ± 8 years, BMI 32 ± 4 kg/m2) participated in a 6 month continuous endurance-type exercise training programme. All participants performed three supervised exercise sessions per week, either 55 min at 50% of whole body peak oxygen uptake \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$ \left( {\mathop V\limits^{ \cdot } {\text{O}}_{{2{\text{peak}}}} } \right) $$\end{document} (low to moderate intensity) or 40 min at 75% of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$ \mathop V\limits^{ \cdot } {\text{O}}_{{2{\text{peak}}}} $$\end{document} (moderate to high intensity). Oral glucose tolerance, blood glycated haemoglobin, lipid profile, body composition, maximal workload capacity, whole body and skeletal muscle oxidative capacity and skeletal muscle fibre type composition were assessed before and after 2 and 6 months of intervention.
Results
The entire 6 month intervention programme was completed by 37 participants. Continuous endurance-type exercise training reduced blood glycated haemoglobin levels, LDL-cholesterol concentrations, body weight and leg fat mass, and increased \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$ \mathop V\limits^{ \cdot } {\text{O}}_{{2{\text{peak}}}} $$\end{document}, lean muscle mass and skeletal muscle cytochrome c oxidase and citrate synthase activity (p < 0.05). No differences were observed between the groups training at low to moderate or moderate to high intensity.
Conclusions/interpretation
When matched for energy cost, prolonged continuous low- to moderate-intensity endurance-type exercise training is equally effective as continuous moderate- to high-intensity training in lowering blood glycated haemoglobin and increasing whole body and skeletal muscle oxidative capacity in obese type 2 diabetes patients.
Trial registration:
ISRCTN32206301
Funding:
None
doi:10.1007/s00125-009-1354-3
PMCID: PMC2723667  PMID: 19370339
Diabetes; Glycaemic control; Lifestyle intervention; Training modalities
12.  Effect of Intermittent Sub-Maximal Exercise on Percent Body Fat Using Leg-To-Leg Bioelectrical Impedance Analysis in Children 
The purpose of this investigation was to determine the effect of intermittent sub-maximal exercise on percent body fat (%BF) estimated by leg-to-leg bioelectrical impedance analysis (LBIA) in children. Fifty-nine children (29 girls; 30 boys) mean age 9.0 ± 1.3 years participated in this study. LBIA measured %BF values were obtained immediately before and within five minutes after completing an intermittent exercise protocol consisting of three 8-minute sub-maximal exercise bouts (2.74 km·hr-1, 0% grade; 4.03 km·hr-1, 0% grade; and 5.47 km·hr-1, 0% grade) each separated by a 5-min seated rest period. The three exercise bouts corresponded to 56%, 61% and 71% of maximal heart rate. Significant differences (p < 0.001) were observed for fat mass, fat free mass, total body water, and body weight, post-exercise in both groups. Significant reductions (p < 0.001) in %BF were observed post-exercise in the female (23.1 ± 9.9 vs. 21.8 ± 9. 9 %) and male (23.3 ± 10.5 vs. 21.8 ± 10.2 %) children when compared to pre-exercise values. However, for the majority of the subjects (females = 86%; males = 73%) the decrease in %BF post- exercise was less than 2.0 %BF. These data indicate that sub-maximal intermittent exercise, that may be representative of daily free-form activities in children, will most likely have a limited impact on %BF estimates when the assessment is performed immediately post-exercise.
Key PointsLBIA measures of body weight, percent body fat, fat mass, fat free mass and total body water were significantly lower after the intermittent sub-maximal exercise.The reductions in percent body fat for girls (1.4%) and boys (1.5%) compare favorably to previous investigations.Intermittent exercise, that may be representative of daily free-form activities in children, will most likely have a limited impact on LBIA percent body fat estimates
PMCID: PMC3842143  PMID: 24353460
Bioelectrical impedance analysis; body fat; sub-maximal exercise; children
13.  Sex differences in cardiovascular function during submaximal exercise in humans 
SpringerPlus  2014;3:445.
Differences in cardiovascular function between sexes have been documented at rest and maximal exercise. The purpose of this study was to examine the sex differences in cardiovascular function during submaximal constant-load exercise, which is not well understood.
Thirty-one male and 33 female subjects completed nine minutes moderate and nine minutes vigorous intensity submaximal exercise (40 and 75% of peak watts determined by maximal exercise test). Measurements included: intra-arterial blood pressure (SBP and DBP), cardiac index (QI), heart rate (HR), oxygen consumption (VO2) and arterial catecholamines (epinephrine = EPI and norepinephrine = NE), and blood gases. Mean arterial pressure (MAP), stroke volume index (SVI), systemic vascular resistance index (SVRI), arterial oxygen content (CaO2), arterial to venous O2 difference (AVO2) and systemic oxygen transport (SOT) were calculated.
At rest and during submaximal exercise QI, SVI, SBP, MAP, NE, CaO2, and SOT were lower in females compared to males. VO2, AVO2, EPI were lower in females throughout exercise. When corrected for wattage, females had a higher Q, HR, SV, VO2 and AVO2 despite lower energy expenditure and higher mechanical efficiency.
This study demonstrates sex differences in the cardiovascular response to constant-load submaximal exercise. Specifically, females presented limitations in cardiac performance in which they are unable to compensate for reductions in stroke volume through increases in HR, potentially a consequence of a female’s blunted sympathetic response and higher vasodilatory state. Females demonstrated greater cardiac work needed to meet the same external work demand, and relied on increased peripheral oxygen extraction, lower energy expenditure and improvements in mechanical efficiency as compensatory mechanisms.
doi:10.1186/2193-1801-3-445
PMCID: PMC4153874  PMID: 25191635
Cardiac output; Arterial pressure; Systemic vascular resistance; Catecholamines; Energy expenditure
14.  Association between heart rate at rest and myocardial perfusion in patients with acute myocardial infarction undergoing cardiac rehabilitation – a pilot study 
Introduction
This study was conducted to determine if there was a link among heart rate at rest (rHR), muscle volume changes, and single photon emission computed tomography (SPECT) parameters after 6-month cardiac rehabilitation in patients with acute myocardial infarction (AMI).
Material and methods
Twenty-nine consecutive AMI patients (mean age: 63.0 ±9.1 years) who received appropriate percutaneous coronary intervention on admission were enrolled. 99mTc-Sestamibi myocardial SPECT images were obtained at the early (30 min) and delayed (4 h) phases after tracer injection at 2 weeks (0M) and 6 months (6M) after the onset of AMI. Within a few days of SPECT, all patients underwent cardiopulmonary exercise test for evaluation of cardiac rehabilitation effects. Before the initiation of exercise test, leg muscle volume was measured. All patients were stratified into the ≥ 70 beats per minute (bpm) (n = 15) or < 70 bpm (n = 14) group based on rHR at 6M.
Results
There were no significant differences in the recanalization time, peak cardiac enzyme, or initial left ventricular ejection fraction between the two groups. After the 6-month training, the muscle volume changes in the lower limbs (< 70 bpm, 0.23 ±0.22; ≥ 70 bpm, –0.07 ±0.26, p < 0.05) were significantly greater in the < 70 bpm group than the ≥ 70 bpm group. The decreased rate of rHR had a significant correlation with the improved global severity (r = 0.62, p = 0.001) and extent (r = 0.48, p = 0.017) of left ventricle evaluated by 99mTc-Sestamibi myocardial SPECT delayed phase.
Conclusions
The result of this preliminary study demonstrated that improved myocardial perfusion was closely related to decreased rHR after cardiac rehabilitation.
doi:10.5114/aoms.2012.30285
PMCID: PMC3460498  PMID: 23056072
cardiac rehabilitation; exercise capacity; myocardial infarction; skeletal muscle; single photon emission computed tomography
15.  Bronchial lability and skin reactivity in siblings of asthmatic children. 
Archives of Disease in Childhood  1984;59(9):871-876.
Seventy five children with asthma (42 boys and 33 girls; age range 4 years 2 months to 15 years) and 75 of their siblings (37 boys and 38 girls; age range 4 years 3 months to 17 years 8 months) were studied to elucidate the mechanisms involved in the increased prevalence of asthma in boys, a prevalence that tends to disappear after puberty. Immediate cutaneous hypersensitivity to five allergens and maximum fall in peak expiratory flow rate after six minutes of treadmill running (bronchial lability) were determined in patients and siblings. There was no significant difference between boys and girls in skin test reactivity to single or multiple allergens in the sibling group. The percentage fall in peak expiratory flow rate after exercise was significantly greater in male than in female siblings and when a positive test was defined as a fall after exercise of either 10% or 15% of the rate before exercise the number of positive tests was significantly greater in boys. The results suggest that more boys than girls in this age group have asthma because their bronchial lability is greater, and not because more boys are atopic.
PMCID: PMC1628713  PMID: 6486865
16.  Lactate Kinetics After Intermittent and Continuous Exercise Training 
The purpose of this study was to assess, the effects of continuous and intermittent exercise training on lactate kinetic parameters and maximal aerobic speed (MAS) using field tests. Twenty-four male sport students were equally divided into continuous (CT) and intermittent (IT) physically trained groups. Another six participants acted as non-trained controls (CG). The trained participants practiced 6-days per week for 6 weeks. Before and after training, all participants completed an incremental exercise test to assess their MAS, and a 30- second supra-maximal exercise followed by 30 minutes of active recovery to determine the individual blood lactate recovery curve. It was found that exercise training has significantly increased MAS (p < 0.001), the lactate exchange and removal abilities as well as the lactate concentrations at the beginning of the recovery ([La]-(0)); for both CT and IT groups; this was accompanied by a significant reduction of the time to lactate-peak. Nevertheless, the improvement in MAS was significantly higher (p < 0.001) post-intermittent (15.1 % ± 2.4) than post-continuous (10.3 % ± 3.2) training. The lactate-exchange and removal abilities were also significantly higher for IT than for CT-group (P<0.05). Moreover, IT-group showed a significantly shorter half-time of the blood lactate (t-½-[La]) than CT-group (7.2 ± 0.5 min vs 7.7 ± 0.3 min, respectively) (p < 0.05). However, no significant differences were observed in peak blood lactate concentration ([La]peak), time to reach [La]peak (t-[La]peak), and [La]-(0) between the two physically-trained groups. We conclude that both continuous and intermittent training exercises were equally effective in improving t-[La]peak and [La]peak, although intermittent training was more beneficial in elevating MAS and in raising the lactate exchange (γ1) and removal (γ2) indexes.
Key pointsCoaches and athletes need to be aware of the potentiality positive effects of exercise intensity.Improvements in physical fitness are associated with a concomitant increase in the lactate removal ability.In order to reduce lactate accumulation and increase maximal aerobic speed maximally, interval training method, with work speeds equal to 90% - 100% of MAS, may be the effective way when compared with continuous training method.
PMCID: PMC3761459  PMID: 24149461
Biexponential mathematical model; recovery; supra-maximal exercise.
17.  The oxygen delivery response to acute hypoxia during incremental knee extension exercise differs in active and trained males 
Background
It is well known that hypoxic exercise in healthy individuals increases limb blood flow, leg oxygen extraction and limb vascular conductance during knee extension exercise. However, the effect of hypoxia on cardiac output, and total vascular conductance is less clear. Furthermore, the oxygen delivery response to hypoxic exercise in well trained individuals is not well known. Therefore our aim was to determine the cardiac output (Doppler echocardiography), vascular conductance, limb blood flow (Doppler echocardiography) and muscle oxygenation response during hypoxic knee extension in normally active and endurance-trained males.
Methods
Ten normally active and nine endurance-trained males (VO2max = 46.1 and 65.5 mL/kg/min, respectively) performed 2 leg knee extension at 25, 50, 75 and 100% of their maximum intensity in both normoxic and hypoxic conditions (FIO2 = 15%; randomized order). Results were analyzed with a 2-way mixed model ANOVA (group × intensity).
Results
The main finding was that in normally active individuals hypoxic sub-maximal exercise (25 – 75% of maximum intensity) brought about a 3 fold increase in limb blood flow but decreased stroke volume compared to normoxia. In the trained group there were no significant changes in stroke volume, cardiac output and limb blood flow at sub-maximal intensities (compared to normoxia). During maximal intensity hypoxic exercise limb blood flow increased approximately 300 mL/min compared to maximal intensity normoxic exercise.
Conclusion
Cardiorespiratory fitness likely influences the oxygen delivery response to hypoxic exercise both at a systemic and limb level. The increase in limb blood flow during maximal exercise in hypoxia (both active and trained individuals) suggests a hypoxic stimulus that is not present in normoxic conditions.
doi:10.1186/1476-5918-7-11
PMCID: PMC2526084  PMID: 18700024
18.  Child Mortality Estimation: Estimating Sex Differences in Childhood Mortality since the 1970s 
PLoS Medicine  2012;9(8):e1001287.
Cheryl Sawyer uses new methods to generate estimates of sex differences in child mortality which can be used to pinpoint areas where these differences in mortality merit closer examination.
Introduction
Producing estimates of infant (under age 1 y), child (age 1–4 y), and under-five (under age 5 y) mortality rates disaggregated by sex is complicated by problems with data quality and availability. Interpretation of sex differences requires nuanced analysis: girls have a biological advantage against many causes of death that may be eroded if they are disadvantaged in access to resources. Earlier studies found that girls in some regions were not experiencing the survival advantage expected at given levels of mortality. In this paper I generate new estimates of sex differences for the 1970s to the 2000s.
Methods and Findings
Simple fitting methods were applied to male-to-female ratios of infant and under-five mortality rates from vital registration, surveys, and censuses. The sex ratio estimates were used to disaggregate published series of both-sexes mortality rates that were based on a larger number of sources. In many developing countries, I found that sex ratios of mortality have changed in the same direction as historically occurred in developed countries, but typically had a lower degree of female advantage for a given level of mortality. Regional average sex ratios weighted by numbers of births were found to be highly influenced by China and India, the only countries where both infant mortality and overall under-five mortality were estimated to be higher for girls than for boys in the 2000s. For the less developed regions (comprising Africa, Asia excluding Japan, Latin America/Caribbean, and Oceania excluding Australia and New Zealand), on average, boys' under-five mortality in the 2000s was about 2% higher than girls'. A number of countries were found to still experience higher mortality for girls than boys in the 1–4-y age group, with concentrations in southern Asia, northern Africa/western Asia, and western Africa. In the more developed regions (comprising Europe, northern America, Japan, Australia, and New Zealand), I found that the sex ratio of infant mortality peaked in the 1970s or 1980s and declined thereafter.
Conclusions
The methods developed here pinpoint regions and countries where sex differences in mortality merit closer examination to ensure that both sexes are sharing equally in access to health resources. Further study of the distribution of causes of death in different settings will aid the interpretation of differences in survival for boys and girls.
Please see later in the article for the Editors' Summary.
Editors' Summary
Background
In 2000, world leaders agreed to eradicate extreme poverty by 2015. To help track progress towards this global commitment, eight Millennium Development Goals (MDGs) were set. MDG 4, which aims to reduce child mortality, calls for a reduction in under-five mortality (the number of children who die before their fifth birthday) to a third of its 1990 level of 12 million by 2015. The under-five mortality rate is also denoted in the literature as U5MR and 5q0. Progress towards MDG 4 has been substantial, but with only three years left to reach it, efforts to strengthen child survival programs are intensifying. Reliable estimates of trends in childhood mortality are pivotal to these efforts. So, since 2004, the United Nations Inter-agency Group for Child Mortality Estimation (UN IGME) has used statistical regression models to produce estimates of trends in under-five mortality and infant mortality (death before age one year) from data about childbearing and child survival collected by vital registration systems (records of all births and deaths), household surveys, and censuses.
Why Was This Study Done?
In addition to estimates of overall childhood mortality trends, information about sex-specific childhood mortality trends is desirable to monitor progress towards MDG 4, although the interpretation of trends in the relative mortality of girls and boys is not straightforward. Newborn girls survive better than newborn boys because they are less vulnerable to birth complications and infections and have fewer inherited abnormalities. Thus, the ratio of infant mortality among boys to infant mortality among girls is greater than one, provided both sexes have equal access to food and medical care. Beyond early infancy, girls and boys are similarly vulnerable to infections, so the sex ratio of deaths in the 1–4-year age group is generally lower than that of infant mortality. Notably, as living conditions improve in developing countries, infectious diseases become less important as causes of death. Thus, in the absence of sex-specific differences in the treatment of children, the sex ratio of childhood mortality is expected be greater than one and to increase as overall under-five mortality rates in developing countries decrease. In this study, the researcher evaluated national and regional changes in the sex ratios of childhood mortality since the 1970s to investigate whether girls and boys have equal access to medical care and other resources.
What Did the Researcher Do and Find?
The researcher developed new statistical fitting methods to estimate trends in the sex ratio of mortality for infants and young children for individual countries and world regions. When considering individual countries, the researcher found that for 92 countries in less developed regions, the median sex ratio of under-five mortality increased between the 1970s and the 2000s, in line with the expected changes just described. However, the average sex ratio of under-five mortality for less developed regions, weighted according to the number of births in each country, did not increase between the 1970s and 2000s, at which time the average under-five mortality rate of boys was about 2% higher than that of girls. This discrepancy resulted from India and China—the two most populous developing countries—having sex ratios for both infant and under-five mortality that remained constant or declined over the study period and were below one in the 2000s, a result that indicates excess female mortality. In China, for example, infant mortality was found to be 12% higher for boys than for girls in the 1970s, but 24% lower for boys than for girls in the 2000s. Finally, although in the less developed regions (excluding India and China) girls went from having a slight survival disadvantage at ages 1–4 years in the 1970s, on average, to having a slight advantage in the 2000s, girls remained more likely to die than boys in this age group in several Asian and African countries.
What Do These Findings Mean?
Although the quality of the available data is likely to affect the accuracy of these findings, in most developing countries the ratio of male to female under-five mortality has increased since the 1970s, in parallel with the decrease in overall childhood mortality. Notably, however, in a number of developing countries—including several each in sub-Saharan Africa, northern Africa/western Asia, and southern Asia—girls have higher mortality than boys at ages 1–4 years, and in India and China girls have higher mortality in infancy. Thus, girls are benefitting less than boys from the overall decline in childhood mortality in India, China, and some other developing countries. Further studies are needed to determine the underlying reasons for this observation. Nevertheless, the methods developed here to estimate trends in sex-specific childhood mortality pinpoint countries and regions where greater efforts should be made to ensure that both sexes have equal access to health care and other important resources during early life.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001287.
This paper is part of a collection of papers on Child Mortality Estimation Methods published in PLOS Medicine
The United Nations Childrens Fund works for children's rights, survival, development, and protection around the world; it provides information on Millennium Development Goal 4, and its Childinfo website provides detailed statistics about child survival and health, including a description of the United Nations Inter-agency Group for Child Mortality Estimation; the 2011 UN IGME report Levels & Trends in Child Mortality is available
The World Health Organization also has information about Millennium Development Goal 4 and provides estimates of child mortality rates (some information in several languages)
Further information about the Millennium Development Goals is available
A 2011 report by the United Nations Department of Economic and Social Affairs entitled Sex Differentials in Childhood Mortality is available
doi:10.1371/journal.pmed.1001287
PMCID: PMC3429399  PMID: 22952433
19.  Effects of a 4-Week Eccentric Training Program on the Repeated Bout Effect in Young Active Women 
The aim of this study was to analyze the responses of women to the repeated bout effect (RBE) and to a short eccentric training program. Twenty-four young females were randomly assigned to a training group (TG, n = 14) or a control group (CG, n = 10). They performed two identical acute eccentric bouts (120 repetitions at 70% of 1RM) in a leg-press device in an 8 weeks interval. TG followed a 4-week-eccentric-training program between the bouts. Maximal isometric contraction, range of motion, peak power and quadriceps muscle soreness were compared between and within groups before and after the two acute eccentric bouts. TG and CG presented significant losses of isometric strength and peak power, and an increment in soreness after the first bout. Isometric strength and peak power were recovered faster in CG after the second bout (p < 0.05) compared with TG, which showed a similar recovery of these parameters after the second bout compared with the first one. A decrease in soreness and a faster recovery of range of motion were found in TG (p < 0.05) following the second bout compared with the first one, but not in CG. Data indicate that a 4-week eccentric training program may prevent the RBE over those adaptations related with muscle damage (e.g. strength loss), but it may increase RBE impact on inflammatory processes (e.g. soreness).
Key pointsAn acute bout of eccentric exercise induces losses of strength, peak power and range of motion, and increases muscle soreness in young active women.When the acute eccentric bout is repeated by young women, the losses of strength and power are smaller, indicating less muscle damage. However, muscle pain and range of motion do not present any difference with the results obtained after the first bout, which would indicate that the repeated bout effect does not affect inflammatory response after acute eccentric exercise.Four weeks of eccentric training is enough to increase maximal isometric strength, but not dynamic strength (1RM) or peak power. Furthermore, this training seems to prevent those adaptations provided by the repeated bout effect related with muscle damage. On the other hand, the eccentric training seems to be a positive tool to decrease muscle soreness, and thus the inflammatory response, associated to a repeated acute eccentric bout.
PMCID: PMC3761500  PMID: 24149560
Lengthening contraction; strength; peak power
20.  Alcohol Ingestion Impairs Maximal Post-Exercise Rates of Myofibrillar Protein Synthesis following a Single Bout of Concurrent Training 
PLoS ONE  2014;9(2):e88384.
Introduction
The culture in many team sports involves consumption of large amounts of alcohol after training/competition. The effect of such a practice on recovery processes underlying protein turnover in human skeletal muscle are unknown. We determined the effect of alcohol intake on rates of myofibrillar protein synthesis (MPS) following strenuous exercise with carbohydrate (CHO) or protein ingestion.
Methods
In a randomized cross-over design, 8 physically active males completed three experimental trials comprising resistance exercise (8×5 reps leg extension, 80% 1 repetition maximum) followed by continuous (30 min, 63% peak power output (PPO)) and high intensity interval (10×30 s, 110% PPO) cycling. Immediately, and 4 h post-exercise, subjects consumed either 500 mL of whey protein (25 g; PRO), alcohol (1.5 g·kg body mass−1, 12±2 standard drinks) co-ingested with protein (ALC-PRO), or an energy-matched quantity of carbohydrate also with alcohol (25 g maltodextrin; ALC-CHO). Subjects also consumed a CHO meal (1.5 g CHO·kg body mass−1) 2 h post-exercise. Muscle biopsies were taken at rest, 2 and 8 h post-exercise.
Results
Blood alcohol concentration was elevated above baseline with ALC-CHO and ALC-PRO throughout recovery (P<0.05). Phosphorylation of mTORSer2448 2 h after exercise was higher with PRO compared to ALC-PRO and ALC-CHO (P<0.05), while p70S6K phosphorylation was higher 2 h post-exercise with ALC-PRO and PRO compared to ALC-CHO (P<0.05). Rates of MPS increased above rest for all conditions (∼29–109%, P<0.05). However, compared to PRO, there was a hierarchical reduction in MPS with ALC-PRO (24%, P<0.05) and with ALC-CHO (37%, P<0.05).
Conclusion
We provide novel data demonstrating that alcohol consumption reduces rates of MPS following a bout of concurrent exercise, even when co-ingested with protein. We conclude that alcohol ingestion suppresses the anabolic response in skeletal muscle and may therefore impair recovery and adaptation to training and/or subsequent performance.
doi:10.1371/journal.pone.0088384
PMCID: PMC3922864  PMID: 24533082
21.  Assessing Causality in the Association between Child Adiposity and Physical Activity Levels: A Mendelian Randomization Analysis 
PLoS Medicine  2014;11(3):e1001618.
Here, Timpson and colleagues performed a Mendelian Randomization analysis to determine whether childhood adiposity causally influences levels of physical activity. The results suggest that increased adiposity causes a reduction in physical activity in children; however, this study does not exclude lower physical activity also leading to increasing adiposity.
Please see later in the article for the Editors' Summary
Background
Cross-sectional studies have shown that objectively measured physical activity is associated with childhood adiposity, and a strong inverse dose–response association with body mass index (BMI) has been found. However, few studies have explored the extent to which this association reflects reverse causation. We aimed to determine whether childhood adiposity causally influences levels of physical activity using genetic variants reliably associated with adiposity to estimate causal effects.
Methods and Findings
The Avon Longitudinal Study of Parents and Children collected data on objectively assessed activity levels of 4,296 children at age 11 y with recorded BMI and genotypic data. We used 32 established genetic correlates of BMI combined in a weighted allelic score as an instrumental variable for adiposity to estimate the causal effect of adiposity on activity.
In observational analysis, a 3.3 kg/m2 (one standard deviation) higher BMI was associated with 22.3 (95% CI, 17.0, 27.6) movement counts/min less total physical activity (p = 1.6×10−16), 2.6 (2.1, 3.1) min/d less moderate-to-vigorous-intensity activity (p = 3.7×10−29), and 3.5 (1.5, 5.5) min/d more sedentary time (p = 5.0×10−4). In Mendelian randomization analyses, the same difference in BMI was associated with 32.4 (0.9, 63.9) movement counts/min less total physical activity (p = 0.04) (∼5.3% of the mean counts/minute), 2.8 (0.1, 5.5) min/d less moderate-to-vigorous-intensity activity (p = 0.04), and 13.2 (1.3, 25.2) min/d more sedentary time (p = 0.03). There was no strong evidence for a difference between variable estimates from observational estimates. Similar results were obtained using fat mass index. Low power and poor instrumentation of activity limited causal analysis of the influence of physical activity on BMI.
Conclusions
Our results suggest that increased adiposity causes a reduction in physical activity in children and support research into the targeting of BMI in efforts to increase childhood activity levels. Importantly, this does not exclude lower physical activity also leading to increased adiposity, i.e., bidirectional causation.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
The World Health Organization estimates that globally at least 42 million children under the age of five are obese. The World Health Organization recommends that all children undertake at least one hour of physical activity daily, on the basis that increased physical activity will reduce or prevent excessive weight gain in children and adolescents. In practice, while numerous studies have shown that body mass index (BMI) shows a strong inverse correlation with physical activity (i.e., active children are thinner than sedentary ones), exercise programs specifically targeted at obese children have had only very limited success in reducing weight. The reasons for this are not clear, although environmental factors such as watching television and lack of exercise facilities are traditionally blamed.
Why Was This Study Done?
One of the reasons why obese children do not lose weight through exercise might be that being fat in itself leads to a decrease in physical activity. This is termed reverse causation, i.e., obesity causes sedentary behavior, rather than the other way around. The potential influence of environmental factors (e.g., lack of opportunity to exercise) makes it difficult to prove this argument. Recent research has demonstrated that specific genotypes are related to obesity in children. Specific variations within the DNA of individual genes (single nucleotide polymorphisms, or SNPs) are more common in obese individuals and predispose to greater adiposity across the weight distribution. While adiposity itself can be influenced by many environmental factors that complicate the interpretation of observed associations, at the population level, genetic variation is not related to the same factors, and over the life course cannot be changed. Investigations that exploit these properties of genetic associations to inform the interpretation of observed associations are termed Mendelian randomization studies. This research technique is used to reduce the influence of confounding environmental factors on an observed clinical condition. The authors of this study use Mendelian randomization to determine whether a genetic tendency towards high BMI and fat mass is correlated with reduced levels of physical activity in a large cohort of children.
What Did the Researchers Do and Find?
The researchers looked at a cohort of children from a large long-term health research project (the Avon Longitudinal Study of Parents and Children). BMI and total body fat were recorded. Total daily activity was measured via a small movement-counting device. In addition, the participants underwent genotyping to detect the presence of several SNPs known to be linked to obesity. For each child a total BMI allelic score was determined based on the number of obesity-related genetic variants carried by that individual. The association between obesity and reduced physical activity was then studied in two ways. Direct correlation between actual BMI and physical activity was measured (observational data). Separately, the link between BMI allelic score and physical activity was also determined (Mendelian randomization or instrumental variable analysis). The observational data showed that boys were more active than girls and had lower BMI. Across both sexes, a higher-than-average BMI was associated with lower daily activity. In genetic analyses, allelic score had a positive correlation with BMI, with one particular SNP being most strongly linked to high BMI and total fat mass. A high allelic score for BMI was also correlated with lower levels of daily physical activity. The authors conclude that children who are obese and have an inherent predisposition to high BMI also have a propensity to reduced levels of physical activity, which may compound their weight gain.
What Do These Findings Mean?
This study provides evidence that being fat is in itself a risk factor for low activity levels, separately from external environmental influences. This may be an example of “reverse causation,” i.e., high BMI causes a reduction in physical activity. Alternatively, there may be a bidirectional causality, so that those with a genetic predisposition to high fat mass exercise less, leading to higher BMI, and so on, in a vicious circle. A significant limitation of the study is that validated allelic scores for physical activity are not available. Thus, it is not possible to determine whether individuals with a high allelic score for BMI also have a propensity to exercise less, or whether it is simply the circumstance of being overweight that discourages activity. This study does suggest that trying to persuade obese children to lose weight by exercising more is likely to be ineffective unless additional strategies to reduce BMI, such as strict diet control, are also implemented.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001618.
The US Centers for Disease Control and Prevention provides obesity-related statistics, details of prevention programs, and an overview on public health strategy in the United States
A more worldwide view is given by the World Health Organization
The UK National Health Service website gives information on physical activity guidelines for different age groups
The International Obesity Task Force is a network of organizations that seeks to alert the world to the growing health crisis threatened by soaring levels of obesity
MedlinePlus—which brings together authoritative information from the US National Library of Medicine, National Institutes of Health, and other government agencies and health-related organizations—has a page on obesity
Additional information on the Avon Longitudinal Study of Parents and Children is available
The British Medical Journal has an article that describes Mendelian randomization
doi:10.1371/journal.pmed.1001618
PMCID: PMC3958348  PMID: 24642734
22.  Gender differences in myocardial function and arterio-ventricular coupling in response to maximal exercise in adolescent floor-ball players 
Background
The hemodynamic and cardiac responses to exercise have been widely investigated in adults. However, little is known regarding myocardial performance in response to a short bout of maximal exercise in adolescents. We therefore sought to study alterations in myocardial function and investigate sex-influences in young athletes after maximal cardiopulmonary testing.
Methods
51 adolescent (13-19 years old) floor-ball players (24 females) were recruited. All subjects underwent a maximal exercise test to determine maximal oxygen uptake (VO2max) and cardiac output. Cardiac performance was investigated using conventional and tissue velocity imaging, as well as 2D strain echocardiography before and 30 minutes following exercise. Arterio-ventricular coupling was evaluated by means of single beat ventricular elastance and arterial elastance.
Results
Compared to baseline the early diastolic myocardial velocity (E′LV) at the basal left ventricular (LV) segments declined significantly (females: E′LV: 14.7 +/- 2.6 to 13.6 +/- 2.9 cm/s; males: 15.2 +/- 2.2 to 13.9 +/- 2.3 cm/s, p < 0.001 for both). Similarly, 2D strain decreased significantly following exercise (2D strain LV: from 21.5 +/- 2.4 to 20.2 +/- 2.7% in females, and from 20 +/- 1 to 17.9 +/- 1.5% in males, p < 0.05 for both). However, there were no significant changes in LV contractility estimated by elastance in either sex following exercise (p > 0.05). Arterial elastance) Ea) at baseline was identified as the only predictor of VO2max in males (r = 0.76, p < 0.001) but not in females (p > 0.05).
Conclusions
The present study demonstrates that vigorous exercise of short duration results in a significant decrease of longitudinal myocardial motion in both sexes. However, in view of unaltered end systolic LV elastance (Ees), these reductions most probably reflect changes in the loading conditions and not an attenuation of myocardial function per se. Importantly, we show that arterial load at rest acts as a strong predictor of VO2max in males but not in female subjects.
doi:10.1186/2052-1847-6-24
PMCID: PMC4084409  PMID: 25045524
Exercise; Echocardiography; Elastance; Tissue Doppler Imaging; Adolescent; Sex; Exercise stress test; Contractility; Peak VO2
23.  Physiological response to a breed evaluation field test in Icelandic horses 
Animal  2014;8(3):431-439.
This study examined the response in terms of heart rate (HR), respiratory rate (RR), haematocrit (Htc), rectal temperature (RT), and some plasma variables in Icelandic horses of different sexes and ages performing the riding assessment in a breed evaluation field test (BEFT). The study was conducted in Iceland on 266 horses (180 mares and 86 stallions, divided into four age groups; 4, 5, 6 and ⩾7 years old). RT and RR were recorded and blood samples were taken before the warm-up and after the riding assessment. Horse HR, velocity and distance were recorded during the warm-up, the riding assessment and a 5-min recovery period. The distance covered in the BEFT was 2.9±0.4 km (range: 1.8 to 3.8 km, n=248), the duration was 9:37±1:22 min:s (range: 5:07 to 15:32 min:s, n=260) and the average speed was 17.8±1.4 km/h (range: 13.2 to 21.3 km/h, n=248). Average HR was 184±13 b.p.m. (range: 138 to 210 b.p.m., n=102) and peak HR 224±9 b.p.m. (range: 195 to 238 b.p.m., n=102), and 36% of the BEFT was performed at HR ⩾200 b.p.m. Post-exercise plasma lactate concentration (Lac) was 18.0±6.5 mmol/l (range: 2.1 to 34.4 mmol/l, n=266), and there was an increase in total plasma protein, plasma creatine kinase and aspartate amino transferase concentration, as well as RR, RT and Htc. Stallions covered a longer total distance (in the warm-up and BEFT) (P<0.05), at a faster speed during BEFT (P<0.001) than mares and had higher Htc and lower HR and post-exercise Lac values. There were few effects of age, but the 4- and 5-year-old horses had lower Htc than older horses and 4-year-old horses had higher post-exercise RR than older horses, although they were ridden for a shorter distance, shorter duration and at lower peak velocity (P<0.1). The results showed that the riding assessment in the BEFT is a high-intensity exercise. The results also showed that aerobic fitness was higher in stallions and that age had a limited effect on the physiological response. It is suggested that these results should be used as a guide for the development of training programmes and fitness tests in Icelandic horses that would improve both performance and welfare of the horse.
doi:10.1017/S1751731113002309
PMCID: PMC3942816  PMID: 24387835
exercise physiology; hematological parameters; lactate; heart rate; Icelandic horse
24.  Baseline Differences In The HF-ACTION Trial By Sex 
American heart journal  2009;158(4 0):S16-S23.
In patients with heart failure (HF), assessment of functional capacity plays an important prognostic role. Both 6 min walk and cardiopulmonary exercise testing (CPX) have been used to determine physical function and to determine prognosis and even listing for transplantation. However, as in HF trials, the number of women reported has been small and the cutoffs for transplantation have been representative of male populations and extrapolated to women. It is also well known that peak VO2 as a determinant of fitness is inherently lower in women than in men and potentially much lower in the presence of HF. Values for a female population from which to draw for this important determination are lacking. The HF-ACTION trial randomized 2331 patients (28% women) with NYHA Class II–IV HF due to systolic dysfunction to either a formal exercise program in addition to optimal medical therapy or to optimal medical therapy alone without any formal exercise training. In order to characterize differences between men and women in the interpretation of final CPX models, the interaction of individual covariates with sex was investigated in the models of (1) VE/VCO2, (2) VO2 at VT, (3) distance on the 6 minute walk, and (4) peak VO2. The women were younger than the men and more likely to have a non-ischemic etiology and a higher EF. Dose of ACEI was lower in the women, on average. The lower ACEI dose may reflect the higher use of ARBs in women. Both the peak VO2 and the 6 min walk distance were significantly lower in the women than in the men. Perhaps the most significant finding in this dataset of baseline characteristics is that the peak VO2 for women was significantly lower than the men with similar ventricular function and health status. Therefore, in a well-medicated, stable, Class II–IV HF cohort of patients who are able to exercise, women have statistically significantly lower peak VO2 and 6 min walk distance than men with similar health status and ventricular function. These data should prompt careful thought when considering prognostic markers for women and listing for cardiac transplant.
doi:10.1016/j.ahj.2009.07.012
PMCID: PMC3748941  PMID: 19782784
25.  Effects of Low-Volume High-Intensity Interval Training (HIT) on Fitness in Adults: A Meta-Analysis of Controlled and Non-Controlled Trials 
Sports Medicine (Auckland, N.z.)  2014;44(7):1005-1017.
Background
Low-volume high-intensity interval training (HIT) appears to be an efficient and practical way to develop physical fitness.
Objective
Our objective was to estimate meta-analysed mean effects of HIT on aerobic power (maximum oxygen consumption [VO2max] in an incremental test) and sprint fitness (peak and mean power in a 30-s Wingate test).
Data Sources
Five databases (PubMed, MEDLINE, Scopus, BIOSIS and Web of Science) were searched for original research articles published up to January 2014. Search terms included ‘high intensity’, ‘HIT’, ‘sprint’, ‘fitness’ and ‘VO2max’.
Study Selection
Inclusion criteria were fitness assessed pre- and post-training; training period ≥2 weeks; repetition duration 30–60 s; work/rest ratio <1.0; exercise intensity described as maximal or near maximal; adult subjects aged >18 years.
Data Extraction
The final data set consisted of 55 estimates from 32 trials for VO2max, 23 estimates from 16 trials for peak sprint power, and 19 estimates from 12 trials for mean sprint power. Effects on fitness were analysed as percentages via log transformation. Standard errors calculated from exact p values (where reported) or imputed from errors of measurement provided appropriate weightings. Fixed effects in the meta-regression model included type of study (controlled, uncontrolled), subject characteristics (sex, training status, baseline fitness) and training parameters (number of training sessions, repetition duration, work/rest ratio). Probabilistic magnitude-based inferences for meta-analysed effects were based on standardized thresholds for small, moderate and large changes (0.2, 0.6 and 1.2, respectively) derived from between-subject standard deviations (SDs) for baseline fitness.
Results
A mean low-volume HIT protocol (13 training sessions, 0.16 work/rest ratio) in a controlled trial produced a likely moderate improvement in the VO2max of active non-athletic males (6.2 %; 90 % confidence limits ±3.1 %), when compared with control. There were possibly moderate improvements in the VO2max of sedentary males (10.0 %; ±5.1 %) and active non-athletic females (3.6 %; ±4.3 %) and a likely small increase for sedentary females (7.3 %; ±4.8 %). The effect on the VO2max of athletic males was unclear (2.7 %; ±4.6 %). A possibly moderate additional increase was likely for subjects with a 10 mL·kg−1·min−1 lower baseline VO2max (3.8 %; ±2.5 %), whereas the modifying effects of sex and difference in exercise dose were unclear. The comparison of HIT with traditional endurance training was unclear (−1.6 %; ±4.3 %). Unexplained variation between studies was 2.0 % (SD). Meta-analysed effects of HIT on Wingate peak and mean power were unclear.
Conclusions
Low-volume HIT produces moderate improvements in the aerobic power of active non-athletic and sedentary subjects. More studies are needed to resolve the unclear modifying effects of sex and HIT dose on aerobic power and the unclear effects on sprint fitness.
doi:10.1007/s40279-014-0180-z
PMCID: PMC4072920  PMID: 24743927

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