Quantifying progressive anterior overgrowth in the thoracic vertebrae of adolescent idiopathic scoliosis patients

Study design Anterior and posterior vertebral body heights were measured from sequential MRI scans of adolescent idiopathic scoliosis (AIS) patients and healthy controls. Objective To measure changes in vertebral body height over time during scoliosis progression to assess how vertebral body height discrepancies change during growth. Summary of background data Relative anterior overgrowth has been proposed as a potential driver for AIS initiation and progression. This theory proposes that the anterior column grows faster, and the posterior column slower, in AIS patients when compared to healthy controls. There is disagreement in the literature as to whether the anterior vertebral body heights are proportionally greater than posterior vertebral body heights in AIS patients when compared to healthy controls. To some extent, these discrepancies may be attributed to methodological differences. Methods MRI scans of the major curve of 21 AIS patients (mean age 12.5 ± 1.4 years, mean Cobb 32.2 ± 12.8º) and between T4 and T12 of 21 healthy adolescents (mean age 12.1 ± 0.5 years) were captured for this study. Of the 21 AIS patients, 14 had a second scan on average 10.8 ± 4.7 months after the first. Anterior and posterior vertebral body heights were measured from the true sagittal plane of each vertebra such that anterior overgrowth could be quantified. Results The difference between anterior and posterior vertebral body height in healthy, non-scoliotic children was significantly greater than in AIS patients with mild to moderate scoliosis. However there was no significant relationship between the overall anterior-posterior vertebral body height difference in AIS and either severity of the curve or its progression over time. Conclusions Whilst AIS patients have a proportionally longer anterior column than non-scoliotic controls, the degree of anterior overgrowth was not related to the rate of progression or the severity of the scoliotic curve.

Understanding how axial loads on the spine influence segmental biomechanics for idiopathic scoliosis patients: A magnetic resonance imaging study

Background Segmental biomechanics of the scoliotic spine are important since the overall spinal deformity is comprised of the cumulative coronal and axial rotations of individual joints. This study investigates the coronal plane segmental biomechanics for adolescent idiopathic scoliosis patients in response to physiologically relevant axial compression. Methods Individual spinal joint compliance in the coronal plane was measured for a series of 15 idiopathic scoliosis patients using axially loaded magnetic resonance imaging. Each patient was first imaged in the supine position with no axial load, and then again following application of an axial compressive load. Coronal plane disc wedge angles in the unloaded and loaded configurations were measured. Joint moments exerted by the axial compressive load were used to derive estimates of individual joint compliance. Findings The mean standing major Cobb angle for this patient series was 46°. Mean intra-observer measurement error for endplate inclination was 1.6°. Following loading, initially highly wedged discs demonstrated a smaller change in wedge angle, than less wedged discs for certain spinal levels (+ 2,+1,− 2 relative to the apex, (p < 0.05)). Highly wedged discs were observed near the apex of the curve, which corresponded to lower joint compliance in the apical region. Interpretation While individual patients exhibit substantial variability in disc wedge angles and joint compliance, overall there is a pattern of increased disc wedging near the curve apex, and reduced joint compliance in this region. Approaches such as this can provide valuable biomechanical data on in vivo spinal biomechanics of the scoliotic spine, for analysis of deformity progression and surgical planning.

Inter-lamellar shear resistance confers compressive stiffness in the intervertebral disc: An image-based modelling study on the bovine caudal disc

The intervertebral disc withstands large compressive loads (up to nine times bodyweight in humans) while providing flexibility to the spinal column. At a microstructural level, the outer sheath of the disc (the annulus fibrosus) comprises 12–20 annular layers of alternately crisscrossed collagen fibres embedded in a soft ground matrix. The centre of the disc (the nucleus pulposus) consists of a hydrated gel rich in proteoglycans. The disc is the largest avascular structure in the body and is of much interest biomechanically due to the high societal burden of disc degeneration and back pain. Although the disc has been well characterized at the whole joint scale, it is not clear how the disc tissue microstructure confers its overall mechanical properties. In particular, there have been conflicting reports regarding the level of attachment between adjacent lamellae in the annulus, and the importance of these interfaces to the overall integrity of the disc is unknown. We used a polarized light micrograph of the bovine tail disc in transverse cross-section to develop an image-based finite element model incorporating sliding and separation between layers of the annulus, and subjected the model to axial compressive loading. Validation experiments were also performed on four bovine caudal discs. Interlamellar shear resistance had a strong effect on disc compressive stiffness, with a 40% drop in stiffness when the interface shear resistance was changed from fully bonded to freely sliding. By contrast, interlamellar cohesion had no appreciable effect on overall disc mechanics. We conclude that shear resistance between lamellae confers disc mechanical resistance to compression, and degradation of the interlamellar interface structure may be a precursor to macroscopic disc degeneration.

Calculating the Fickian diffusivity for a lattice-based random walk with agents and obstacles of different shapes and sizes

Random walk models are often used to interpret experimental observations of the motion of biological cells and molecules. A key aim in applying a random walk model to mimic an in vitro experiment is to estimate the Fickian diffusivity (or Fickian diffusion coefficient),D. However, many in vivo experiments are complicated by the fact that the motion of cells and molecules is hindered by the presence of obstacles. Crowded transport processes have been modeled using repeated stochastic simulations in which a motile agent undergoes a random walk on a lattice that is populated by immobile obstacles. Early studies considered the most straightforward case in which the motile agent and the obstacles are the same size. More recent studies considered stochastic random walk simulations describing the motion of an agent through an environment populated by obstacles of different shapes and sizes. Here, we build on previous simulation studies by analyzing a general class of lattice-based random walk models with agents and obstacles of various shapes and sizes. Our analysis provides exact calculations of the Fickian diffusivity, allowing us to draw conclusions about the role of the size, shape and density of the obstacles, as well as examining the role of the size and shape of the motile agent. Since our analysis is exact, we calculateDdirectly without the need for random walk simulations. In summary, we find that the shape, size and density of obstacles has a major influence on the exact Fickian diffusivity. Furthermore, our results indicate that the difference in diffusivity for symmetric and asymmetric obstacles is significant.

Challenges to Capturing Expertise in Field Settings

This chapter proposes that to capture expertise in field settings sport scientists should base experimental designs on an inter-disciplinary theoretical foundation and utilise coach and athlete expertise to identify the key variables upon which to focus. We propose that an ecological dynamics framework may allow motor learning and performance to be examined in a more representative manner. After initially considering the problem from the view of a “new” skill acquisition scientist, we provide an overview of previous approaches, before providing theoretical and practically driven ideas to guide sport scientists’ practice going forward.

New genetic loci link adipose and insulin biology to body fat distribution

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10−8). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

Genetic studies of body mass index yield new insights for obesity biology

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10−8), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ~2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

Gravity-induced coronal plane joint moments in adolescent idiopathic scoliosis

Background Adolescent Idiopathic Scoliosis is the most common type of spinal deformity, and whilst the risk of progression appears to be biomechanically mediated (larger deformities are more likely to progress), the detailed biomechanical mechanisms driving progression are not well understood. Gravitational forces in the upright position are the primary sustained loads experienced by the spine. In scoliosis they are asymmetrical, generating moments about the spinal joints which may promote asymmetrical growth and deformity progression. Using 3D imaging modalities to estimate segmental torso masses allows the gravitational loading on the scoliotic spine to be determined. The resulting distribution of joint moments aids understanding of the mechanics of scoliosis progression. Methods Existing low-dose CT scans were used to estimate torso segment masses and joint moments for 20 female scoliosis patients. Intervertebral joint moments at each vertebral level were found by summing the moments of each of the torso segment masses above the required joint. Results The patients’ mean age was 15.3 years (SD 2.3; range 11.9 – 22.3 years); mean thoracic major Cobb angle 52° (SD 5.9°; range 42°-63°) and mean weight 57.5 kg (SD 11.5 kg; range 41 – 84.7 kg). Joint moments of up to 7 Nm were estimated at the apical level. No significant correlation was found between the patients’ major Cobb angles and apical joint moments. Conclusions Patients with larger Cobb angles do not necessarily have higher joint moments, and curve shape is an important determinant of joint moment distribution. These findings may help to explain the variations in progression between individual patients. This study suggests that substantial corrective forces are required of either internal instrumentation or orthoses to effectively counter the gravity-induced moments acting to deform the spinal joints of idiopathic scoliosis patients.

Information flow, trading activity and commodity futures volatility

Based on unique news data relating to gold and crude oil, we investigate how news volume and sentiment, shocks in trading activity, market depth and trader positions unrelated to information flow covary with realized volatility. Positive shocks to the rate of news arrival, and negative shocks to news sentiment exhibit the largest effects. After controlling for the level of news flow and cross-correlations, net trader positions play only a minor role. These findings are at odds with those of [Wang (2002a). The Journal of Futures Markets, 22, 427–450; Wang (2002b). The Financial Review, 37, 295–316], but are consistent with the previous literature which doesn't find a strong link between volatility and trader positions.

Disease Diplomacy

In the age of air travel and globalized trade, pathogens that once took months or even years to spread beyond their regions of origin can now circumnavigate the globe in a matter of hours. Amid growing concerns about such epidemics as Ebola, SARS, MERS, and H1N1, disease diplomacy has emerged as a key foreign and security policy concern as countries work to collectively strengthen the global systems of disease surveillance and control. The revision of the International Health Regulations (IHR), eventually adopted by the World Health Organization’s member states in 2005, was the foremost manifestation of this novel diplomacy. The new regulations heralded a profound shift in international norms surrounding global health security, significantly expanding what is expected of states in the face of public health emergencies and requiring them to improve their capacity to detect and contain outbreaks. Drawing on Martha Finnemore and Kathryn Sikkink’s "norm life cycle" framework and based on extensive documentary analysis and key informant interviews, Disease Diplomacy traces the emergence of these new norms of global health security, the extent to which they have been internalized by states, and the political and technical constraints governments confront in attempting to comply with their new international obligations. The authors also examine in detail the background, drafting, adoption, and implementation of the IHR while arguing that the very existence of these regulations reveals an important new understanding: that infectious disease outbreaks and their management are critical to national and international security. The book will be of great interest to academic researchers, postgraduate students, and advanced undergraduates in the fields of global public health, international relations, and public policy, as well as health professionals, diplomats, and practitioners with a professional interest in global health security.

Who does nutrition prevention work in Queensland? An investigation of structural and political workforce reforms

- Aim This study aimed (i) to determine the change in the number of government-funded nutrition positions following structural and political reforms and (ii) to describe the remaining workforce available to do nutrition prevention work, including student placements, in Queensland. - Methods Positions funded by the Queensland government were counted using departmental human resource data and compared with data collected 4 years earlier. Positions not funded by the government were identified using formal professional networks and governance group lists. Both groups were sent an online survey that explored their position name, funding source, employer, qualifications, years of experience, work in prevention and ability to supervise students. - Results There was a 90% reduction in the number of nutrition prevention positions funded by the government between 2009 (137 full time equivalents (FTE)) and 2013 (14 FTE). In 2013, 313 specialist (n = 92) and generalist (n = 221) practitioners were identified as potentially working in nutrition prevention throughout Queensland. A total of 30 permanent FTEs indicated over 75% of their work focused on prevention. This included the 14 FTE funded by the Queensland government and an additional 16 FTE from other sectors. Generalists did not consider themselves part of the nutrition workforce. - Conclusions Queensland experienced an extreme reduction in its nutrition prevention workforce as a result of political and structural reforms. This disinvestment by the Queensland government was not compensated for by other sectors, and has left marked deficits in public health nutrition capacity, including student placements.

Phylogenetic analysis of human Chlamydia pneumoniae strains reveals a distinct Australian indigenous clade that predates European exploration of the continent

Background The obligate intracellular bacterium Chlamydia pneumoniae is a common respiratory pathogen, which has been found in a range of hosts including humans, marsupials and amphibians. Whole genome comparisons of human C. pneumoniae have previously highlighted a highly conserved nucleotide sequence, with minor but key polymorphisms and additional coding capacity when human and animal strains are compared. Results In this study, we sequenced three Australian human C. pneumoniae strains, two of which were isolated from patients in remote indigenous communities, and compared them to all available C. pneumoniae genomes. Our study demonstrated a phylogenetically distinct human C. pneumoniae clade containing the two indigenous Australian strains, with estimates that the most recent common ancestor of these strains predates the arrival of European settlers to Australia. We describe several polymorphisms characteristic to these strains, some of which are similar in sequence to animal C. pneumoniae strains, as well as evidence to suggest that several recombination events have shaped these distinct strains. Conclusions Our study reveals a greater sequence diversity amongst both human and animal C. pneumoniae strains, and suggests that a wider range of strains may be circulating in the human population than current sampling indicates.

Canadian Stroke Best Practice Recommendations: Mood, Cognition and Fatigue Following Stroke practice guidelines, update 2015

Every year, approximately 62 000 people with stroke and transient ischemic attack are treated in Canadian hospitals, and the evidence suggests one-third or more will experience vascular-cognitive impairment, and/or intractable fatigue, either alone or in combination. The 2015 update of the Canadian Stroke Best Practice Recommendations: Mood, Cognition and Fatigue Module guideline is a comprehensive summary of current evidence-based recommendations for clinicians in a range of settings, who provide care to patients following stroke. The three consequences of stroke that are the focus of the this guideline (poststroke depression, vascular cognitive impairment, and fatigue) have high incidence rates and significant impact on the lives of people who have had a stroke, impede recovery, and result in worse long-term outcomes. Significant practice variations and gaps in the research evidence have been reported for initial screening and in-depth assessment of stroke patients for these conditions. Also of concern, an increased number of family members and informal caregivers may also experience depressive symptoms in the poststroke recovery phase which further impact patient recovery. These factors emphasize the need for a system of care that ensures screening occurs as a standard and consistent component of clinical practice across settings as stroke patients transition from acute care to active rehabilitation and reintegration into their community. Additionally, building system capacity to ensure access to appropriate specialists for treatment and ongoing management of stroke survivors with these conditions is another great challenge.

Prediction of individual genetic risk to prostate cancer using a polygenic score

BACKGROUND Polygenic risk scores comprising established susceptibility variants have shown to be informative classifiers for several complex diseases including prostate cancer. For prostate cancer it is unknown if inclusion of genetic markers that have so far not been associated with prostate cancer risk at a genome-wide significant level will improve disease prediction. METHODS We built polygenic risk scores in a large training set comprising over 25,000 individuals. Initially 65 established prostate cancer susceptibility variants were selected. After LD pruning additional variants were prioritized based on their association with prostate cancer. Six-fold cross validation was performed to assess genetic risk scores and optimize the number of additional variants to be included. The final model was evaluated in an independent study population including 1,370 cases and 1,239 controls. RESULTS The polygenic risk score with 65 established susceptibility variants provided an area under the curve (AUC) of 0.67. Adding an additional 68 novel variants significantly increased the AUC to 0.68 (P = 0.0012) and the net reclassification index with 0.21 (P = 8.5E-08). All novel variants were located in genomic regions established as associated with prostate cancer risk. CONCLUSIONS Inclusion of additional genetic variants from established prostate cancer susceptibility regions improves disease prediction. Prostate 75:1467–1474, 2015. © 2015 Wiley Periodicals, Inc.

The effects of height and BMI on prostate cancer incidence and mortality: A Mendelian randomization study in 20,848 cases and 20,214 controls from the PRACTICAL consortium

Background Epidemiological studies suggest a potential role for obesity and determinants of adult stature in prostate cancer risk and mortality, but the relationships described in the literature are complex. To address uncertainty over the causal nature of previous observational findings, we investigated associations of height- and adiposity-related genetic variants with prostate cancer risk and mortality. Methods We conducted a case–control study based on 20,848 prostate cancers and 20,214 controls of European ancestry from 22 studies in the PRACTICAL consortium. We constructed genetic risk scores that summed each man’s number of height and BMI increasing alleles across multiple single nucleotide polymorphisms robustly associated with each phenotype from published genome-wide association studies. Results The genetic risk scores explained 6.31 and 1.46 % of the variability in height and BMI, respectively. There was only weak evidence that genetic variants previously associated with increased BMI were associated with a lower prostate cancer risk (odds ratio per standard deviation increase in BMI genetic score 0.98; 95 % CI 0.96, 1.00; p = 0.07). Genetic variants associated with increased height were not associated with prostate cancer incidence (OR 0.99; 95 % CI 0.97, 1.01; p = 0.23), but were associated with an increase (OR 1.13; 95 % CI 1.08, 1.20) in prostate cancer mortality among low-grade disease (p heterogeneity, low vs. high grade <0.001). Genetic variants associated with increased BMI were associated with an increase (OR 1.08; 95 % CI 1.03, 1.14) in all-cause mortality among men with low-grade disease (p heterogeneity = 0.03). Conclusions We found little evidence of a substantial effect of genetically elevated height or BMI on prostate cancer risk, suggesting that previously reported observational associations may reflect common environmental determinants of height or BMI and prostate cancer risk. Genetically elevated height and BMI were associated with increased mortality (prostate cancer-specific and all-cause, respectively) in men with low-grade disease, a potentially informative but novel finding that requires replication.