Comparison of pQCT parameters between ulna and radius in retired elite gymnasts : the skeletal benefits associated with long-term gymnastics are bone- and site-specific

Objectives: To compare the skeletal benefits associated with gymnastics between ulna and radius.
Methods: 19 retired artistic gymnasts, aged 18-36 years, were compared to 24 sedentary women. Bone mineral content (BMC), total and cortical bone area (ToA, CoA), trabecular and cortical volumetric density (TrD, CoD) and cortical thickness (CoTh) were measured by pQCT at the 4% and 66% forearm.
Results: At the 4% site, BMC and ToA were more than twice greater at the radius than ulna whereas at the 66% site, BMC, ToA, CoA, CoTh and SSIpol were 20 to 51% greater at the ulna than radius in both groups (p<0.0001). At the 4% site, the skeletal benefits in BMC of the retired gymnasts over the non-gymnasts were 1.9 times greater at the radius than ulna (p<0.001), with enlarged bone size at the distal radius only. In contrast, the skeletal benefits at the 66% site were twice greater at the ulna than radius for BMC and CoA (p<0.01).
Conclusion: Whereas the skeletal benefits associated with long-term gymnastics were greater at the radius than ulna in the distal forearm, the reverse was found in the proximal forearm, suggesting both bones should be analysed when investigating forearm strength.

Innervation zone shift at different levels of isometric contraction in the biceps brachii muscle

Experiments were carried out to examine whether innervation zone (IZ) location remains stable at different levels of isometric contraction in the biceps brachii muscle (BB), and to determine how the proximity of the IZ affects common surface electromyography (sEMG) parameters. Twelve subjects performed maximal (MVC) and submaximal voluntary isometric contractions at 10%, 20%, 30%, 40%, 50% and 75% of MVC. sEMG signals were recorded with a 13 rows  5 columns grid of electrodes from the short head of BB. The IZ shifted in the proximal direction by up to 2.4 cm, depending upon the subject and electrode column. The mean shift of all the columns was 0.6 ± 0.4 cm (10% vs. 100% MVC, P < 0.001). This shift biased the average values of mean frequency (+21.8 ± 9.9 Hz, P < 0.001), root mean square (0.16 ± 0.15 mV, P < 0.05) and conduction velocity (1.15 ± 0.93 m/s, P < 0.01) in the channels immediately proximal to the IZ. The shift in IZ could be explained by shortening of the muscle fibers, and thus lengthening of the (distal) tendon due to increasing force. These results underline the importance of individual investigation of IZ locations before the placement of sEMG electrodes, even in isometric contractions.

The influence of parents, siblings and peers on pre- and early-teen smoking : a multilevel model

Introduction and Aims. Despite considerable success in tobacco control, many teenagers in Australia and other industrialised countries still smoke tobacco. There is mixed evidence on the relative influence of proximal social networks (parents/siblings/peers) on pre- and early-teen smoking, and no research has examined how these influences compare after accounting for school- and community-level effects.The aim of this study was to compare the relative influences of parents, siblings and peers, after accounting for school- and community-level variation in smoking.

Design and Methods. A cross-sectional fixed and random effects model of smoking prevalence was used, with individuals (n = 7314) nested within schools (n = 231) nested within communities (n = 30). Grade 6 and 8 students (modal ages 11 and 13 years) completed an on-line survey. Key variables included parent/sibling/peer use. Controls included alcohol involvement, sensation seeking, pro-social beliefs, laws/norms about substance use and school commitment.

Results.There was significant variation in smoking at both the school and community levels, supporting the need for a multilevel model. Individual-level predictors accounted for much of the variance at higher levels. The strongest effects were for number of friends who smoke, sibling smoking and alcohol involvement. Smaller significant effects were found for parent smoking. At the community level, socioeconomic disadvantage was significant, but community-level variance in pro-social and drug-related laws/norms was not related to smoking.

Discussion and Conclusions. Cross-level interactions were generally non-significant. Early teenage smoking was best explained by sibling and peer smoking, and individual risks largely accounted for the substantial variation observed across schools and communities. In terms of future tobacco control, findings point to the utility of targeting families in disadvantaged communities.[Kelly AB, O'Flaherty M, Connor JP, Homel R, Toumbourou JW, Patton GC, Williams J. The influence of parents, siblings and peers on pre- and early-teen smoking: A multilevel model.

Do healthy cities work? A logic of method for assessing impact and outcome of healthy cities

In this article, we discuss an appropriate methodology for assessing complex urban programs such as the WHO European Healthy Cities Network. The basic tenets and parameters for this project are reviewed, and situated in the broader urban health tradition. This leads to a delineation of the types of questions researchers can address when looking at a complex urban health program. Such questions reach appropriately beyond traditional public health concepts involving proximal and distal determinants of health (and associated upstream, midstream, and downstream rhetoric). Espousing a multi-level, reciprocal pathways perspective on Healthy Cities research, we also adopt a distinction between impacts and outcomes of Healthy Cities. The former are value driven, the latter intervention-driven. These approaches lead to the acknowledgment of a logic of method that includes situational and contextual appreciation of unique Healthy City experiences in a Realist Evaluation paradigm. The article concludes with a reflection of evaluation and assessment procedures applied to Phase IV (2003-2008) of the WHO European Healthy Cities Network and an interpretation of response rates to the range of methods that have been adopted.

The angiotensin IV/AT4 receptor

The angiotensin AT4 receptor was originally defined as the specific, high-affinity binding site for the hexapeptide angiotensin IV (Ang IV). Subsequently, the peptide LVV-hemorphin 7 was also demonstrated to be a bioactive ligand of the AT4 receptor. Central administration of Ang IV, its analogues or LVV-hemorphin 7 markedly enhance learning and memory in normal rodents and reverse memory deficits observed in animal models of amnesia. The AT4 receptor has a broad distribution and is found in a range of tissues, including the adrenal gland, kidney, lung and heart. In the kidney Ang IV increases renal cortical blood flow and decreases Na+ transport in isolated renal proximal tubules. The AT4 receptor has recently been identified as the transmembrane enzyme, insulin-regulated membrane aminopeptidase (IRAP). IRAP is a type II integral membrane spanning protein belonging to the M1 family of aminopeptidases and is predominantly found in GLUT4 vesicles in insulin-responsive cells. Three hypotheses for the memory-potentiating effects of the AT4 receptor/IRAP ligands, Ang IV and LVV-hemorphin 7, are proposed: (i) acting as potent inhibitors of IRAP, they may prolong the action of endogenous promnestic peptides; (ii) they may modulate glucose uptake by modulating trafficking of GLUT4; (iii) IRAP may act as a receptor, transducing the signal initiated by ligand binding to its C-terminal domain to the intracellular domain that interacts with several cytoplasmic proteins.

Prevalence of osteoporosis in Australian women : Geelong Osteoporosis Study

To evaluate the prevalence of osteoporosis at various sites among Australian women, cross-sectional bone mineral density (BMD) data for adult females was obtained from an age-stratified population-based sample (n = 1494; 20–94 yr) drawn at random from the Barwon Statistical Division, a population characteristic of Australia. Age- and weight- (and for three sites, height) matched reference ranges for BMD at the lumbar spine, proximal femur, forearm, and total body were developed using regression techniques. The cutoff BMD level for osteoporosis at the PA spine was 0.917 g/cm² and 0.713 g/cm² at the femoral neck according to the World Health Organization (WHO) guidelines. The upper cutoff level for osteopenia was 1.128 g/cm² at the PA spine and 0.913 g/cm² for the femoral neck. The proportion of Australian women categorized as having osteoporosis at the PA spine, femoral neck, or midforearm ranged from 0.9% among those aged 40–44 yr to 87.0% for those older than 79 yr. This study provides reference data representative of the Australian female population. A large proportion of elderly Australian women has osteoporosis according to the WHO guidelines.

Reference ranges for bone densitometers adopted Australia-wide : Geelong Osteoporosis Study

Bone densitometry reports a measure of fracture risk in comparison with young adults (T-scores) and age-matched peers (Z-scores). To date, each manufacturer has provided its own reference range resulting in lack of uniformity. The Australia and New Zealand Bone and Mineral Society and Osteoporosis Australia have recognized the need to standardize the reference range and have recommended that data generated by the Geelong Osteoporosis Study (GOS) be used Australia-wide. The GOS recruited a random, population-based sample of adult women and measured bone mineral density (BMD) at the proximal femur and spine using a Lunar DPX-L. These data were used to establish reference ranges for Lunar machines and, using conversion equations, for Norland and Hologic machines. The new standardized Australian reference ranges for BMD will enable consistent diagnosis of osteoporosis and categorization of fracture risk across different types of densitometers.

Application of epidemiology to change health policy : defining age-related thresholds of bone mineral density for primary prevention of fracture

In Australia, benefits for antifracture therapies have been available for patients with osteoporosis and a prior fracture. No benefits were available to those with no prior fracture. We aimed to define, in women with no prior fracture, age-related thresholds of bone mineral density (BMD) associated with fracture risk equivalent to that of women with prior fracture and osteoporosis. A case-control study of women (≥50 yr) was conducted, including 291 fracture cases and 823 controls. BMD was measured at the proximal femur and posterior anterior (PA) spine. A fracture risk score (FRS) for the group with no prior fracture was calculated with discriminant analysis. The thresholds for equivalent fracture risk between those with no prior fracture and those with prior fracture were assessed using logistic regression. Increasing the FRS to +0.98 in women with no prior fracture resulted in equivalent odds of sustaining a fracture to those with prior fracture and osteoporosis. The corresponding T-score thresholds at the spine were −4.6 at 50 yr, −3.9 at 60 yr, −3.1 at 70 yr, and −2.4 at 80 yr. The femoral neck T-score thresholds were lower by 0.5 standard deviation. The high-risk individuals defined by this study should be considered for primary fracture prevention therapy.

Fracture thresholds revisited : Geelong Osteoporosis Study

Osteoporosis, in the absence of fracture, is defined as a deficit in bone mineral density (BMD) of 2.5 SD or more below the young adult reference mean in postmenopausal Caucasian populations. BMD is a measure of fracture risk but not the sole predictor. We have assessed a combination of easily accessible measures of age, height, weight, and BMD to improve fracture risk assessment. Women with low trauma fractures and a control group were recruited from south-eastern Australia. Discriminant analysis derived multivariate equations that assessed fracture risk. Age was not in the best models at the spine and forearm sites. Weight and height contributed to the relationship for the forearm sites only. At the proximal femur, the BMD level that separates fracture cases from nonfracture cases, increases with age. These separation levels of BMD were higher than the WHO's level of osteoporosis (T-score < −2.5 SD) at ages older than 62 years. This increasing BMD threshold with age suggests that other age-related risk factors assume increasing importance among the elderly.

Serum leptin levels are associated with bone mass in nonobese women

Both serum leptin and bone mineral density are positively correlated with body fat, generating the hypothesis that leptin may be a systemic and/or local regulator of bone mass. We investigated 214 healthy, nonobese Australian women aged 20-91 yr. Bone mineral content, projected bone area, and body fat mass were measured by dual energy x-ray absorptiometry and fasting serum leptin levels by RIA. Associations between bone mineral content (adjusted for age, body weight, body fat mass, and bone area) and the natural logarithm of serum leptin concentrations were analyzed by multiple regression techniques. There was a significant positive association at the lateral spine, two proximal femur sites (Ward's triangle and trochanter), and whole body (partial r² = 0.019 to 0.036; all P < 0.05). Similar trends were observed at the femoral neck and posterior-anterior-spine. With bone mineral density the dependent variable (adjusted for age, body weight, and body fat mass), the association with the natural logarithm of leptin remained significant at the lateral spine (partial r² = 0.030; P = 0.011), was of borderline significance at the proximal femur sites (partial r² = 0.012 to 0.017; P = 0.058 to 0.120), and was not significant at the other sites. Our results demonstrate an association between serum leptin levels and bone mass consistent with the hypothesis that circulating leptin may play a role in regulating bone mass.

Femoral neck dimensions are unlikely to be associated with age at menarche

Hip axis length (HAL) has been reported as an independent risk factor for hip fracture. Later puberty may increase bone size because of delayed epiphyseal fusion. We sought to identify associations between bone size at the proximal femur with age at menarche and other indices of growth such as stature. Femoral neck dimensions were measured from dual-energy X-ray absorptiometry scans of the proximal femur in a random sample of 203 premenopausal Caucasian women (age 20–30 years). There were no associations between age at menarche and HAL, femoral axis length (FAL) or femoral neck width (FNW). Age at menarche was associated with height (r= 0.2, p= 0.02). Variations in HAL, FAL and FNW do not appear to be related to age at menarche.

Geelong Osteoporosis Study Health Database

The database contains the following clinical, questionnaire and socio-demographic data suitable for cross-sectional and longitudinal analyses:
-Body composition: dual-energy x-ray absorptiometry (DXA) measures of the lumbar spine (posterior-anterior projection), proximal femur, whole body and forearm (ultradistal forearm and distal 33%)
-Other clinical assessments: body weight, height, arm span, waist and hip circumferences, blood pressure, visual acuity, muscle strength, functional reach test and timed ‘up-&-go’ test.
-Mental health: Major axis psychiatric disorders diagnosed using a Structured Clinical Interview.
-Blood and urine collections: blood and urine collected after an overnight fast.
-Questionnaires: exposure to disease, use of medications and supplements, diet, mobility, physical activity, sleep, sun exposure, falls and fractures, alcohol and tobacco use, reproductive history, family history of fractures and disease, quality of life, pain, anxiety and depression.
-Socio-demographics: Country of birth, ethnicity, marital status, education, housing and employment status, occupation, socioeconomic Index for Areas (SEIFA) scores.

Early intervention with erythropoietin does not affect the outcome of acute kidney injury (the EARLYARF trial)

We performed a double-blind placebo-controlled trial to study whether early treatment with erythropoietin could prevent the development of acute kidney injury in patients in two general intensive care units. As a guide for choosing the patients for treatment we measured urinary levels of two biomarkers, the proximal tubular brush border enzymes γ-glutamyl transpeptidase and alkaline phosphatase. Randomization to either placebo or two doses of erythropoietin was triggered by an increase in the biomarker concentration product to levels above 46.3, with a primary outcome of relative average plasma creatinine increase from baseline over 4 to 7 days. Of 529 patients, 162 were randomized within an average of 3.5 h of a positive sample. There was no difference in the incidence of erythropoietin-specific adverse events or in the primary outcome between the placebo and treatment groups. The triggering biomarker concentration product selected patients with more severe illness and at greater risk of acute kidney injury, dialysis, or death; however, the marker elevations were transient. Early intervention with high-dose erythropoietin was safe but did not alter the outcome. Although these two urine biomarkers facilitated our early intervention, their transient increase compromised effective triaging. Further, our study showed that a composite of these two biomarkers was insufficient for risk stratification in a patient population with a heterogeneous onset of injury.

The roses of success

Sometimes success can be detrimental to learning while failure can be good. What appears as a disaster can often lay the foundations for future success.

Usually, educators and students focus on building confidence through successful completion of learning tasks, summarised by Vygotsky’s zone of proximal development. A positive feedback loop is established if learners are successful in mastering new ideas and skills. The problem is if teachers, trainers and instructors never challenge students to the fullest extent of their abilities, as this might also ensure overconfidence, slow progress and boredom.

We should not avoid the risk of failure; science is all about the possible risk of failure. Testable hypotheses have the potential to fail an experimental or computational test; ideas that are not testable are considered to be outside the realm of science. The occasional failure shows the limits and scope of an idea’s validity and enables us to advance scientific ideas.

There is a need to find the balance between challenge that extends students, and over-extension. The former results in greater and true confidence and ability, while the latter leads to catastrophic failure and crises of confidence. Education, like life and like all scientific endeavour is about taking responsible risks safely. When we cultivate the roses of success that grow from the ashes of disaster, we must not forget that roses have thorns, or that the occasional setback or failure is just as important for learning as a succession of successes.