Development of a Probabilistic Chimpanzee Glenohumeral Model: Implications for Human Function

Modern human shoulder function is affected by the evolutionary adaptations that have occurred to ensure survival and prosperity of the species. Robust examination of behavioral shoulder performance and injury risk can be holistically improved through an interdisciplinary approach that integrates anthropology and biomechanics. Anthropological research methods have attempted to resolve gaps in human shoulder evolution, while biomechanics research has attempted to explain the musculoskeletal function of the modern human shoulder. Coordination of these two fields can allow different perspectives to contribute to a more complete interpretation of, not only how the modern human shoulder is susceptible to specific injuries, but also why. How the modern human shoulder arose from a, likely, weight-bearing, arboreal past to its modern form, and what this has meant for modern behaviors, is not well understood. Despite a weight-bearing, locomotor ancestral usage, the modern human upper extremity is highly fatigable in repetitive, low to moderate force tasks, such as overhead reaching. The closest living human relative, modern chimpanzees, has retained an arboreal, locomotor upper extremity. Interdisciplinary comparative research on humans and chimpanzees could lead to greater insight on modern human shoulder function. The purpose of this research was to explore the modern human capacity for ancestral, brachiating behaviors and resultant injury mechanisms through comparative experimental, computational modeling and probabilistic modeling approaches with chimpanzees. The first study experimentally explored the modern human ability to perform a horizontal bimanual arm-suspensory climbing task. EMG of 12 upper extremity muscles and motion capture of the arm and thorax were monitored in experienced and inexperienced climbers. Results were also compared to previously published or collected data on chimpanzees performing an analogous task. While all human climbers used a high proportion of their muscular reserve to perform the task, experienced climbers had moderately reduced muscle activity in most muscles, particularly during phasic shifts of the climb cycle and moderately more efficient kinematics. Climbing kinematics and muscle activity were very similar between humans and chimpanzees. However, chimpanzees appear to have a different utility of the posterior deltoid, suggesting an influence of their habitual arboreal behaviors. The second and third studies describe the development of a deterministic chimpanzee musculoskeletal glenohumeral model. Study 2 developed geometric parameters of chimpanzee shoulder rhythm and glenoid stability ratios for the construction of a chimpanzee glenohumeral model. The chimpanzee glenohumeral model of Study 3 was designed to parallel an existing human glenohumeral model, enabling comparative analyses. The chimpanzee glenohumeral model consists of three modules – an external torque module, musculoskeletal geometric module, and an internal muscle force prediction module. Together, these modules use postural kinematics, subject specific anthropometrics and hand forces to estimate joint reaction forces and moments, subacromial space dimensions, and muscle and tissue forces. Using static postural data from Study 1, predicted muscle forces and subacromial space were compared between chimpanzees and humans during an overhead, weight-bearing climbing task. Compared to chimpanzees, the human model predicted a 2mm narrower subacromial space, deltoid muscle forces that were often double those of chimpanzees and a strong reliance on infraspinatus and teres minor (60-100% maximal force) over other rotator cuff muscles. Finally, the deterministic chimpanzee and human glenohumeral models were expanded in Study 4 to a probabilistic analysis of rotator cuff function between species. Using probabilistic software and the same postural climbing inputs, both models had anthropologically relevant musculoskeletal features perturbed in a series of Monte Carlo simulations – muscle origins and insertions, glenoid inclination and glenoid stability – to determine if rotator cuff muscle force prediction distributions would converge between species. Human rotator cuff muscle behavior did not converge with chimpanzees using probabilistic simulation. The human model continued to predict strong dependence on infraspinatus and teres minor, with 99% confidence intervals of [0-100]% maximal force, over supraspinatus and subscapularis, with confidence intervals of [0-5]% maximal force. Chimpanzee rotator cuff confidence intervals were typically between [0-40]% maximal force, with median force for all four rotator cuff muscles typically 5-20% maximal force. While perturbation of muscle origins and insertions had the greatest effect on muscle force output distributions, no musculoskeletal variation notably modified human climbing performance. Structural musculoskeletal differences between species dictated differences in glenohumeral function. The results from all studies indicate susceptibility for the fatigue-induced initiation of subacromial impingement syndrome and rotator cuff pathology in modern humans during overhead and repetitive tasks. Lower muscle absolute PCSA in humans, combined with a laterally oriented glenohumeral joint and laterally projecting acromion reduced the capacity for overhead postures and weight-bearing postures. These evolutionary differences may have been vestigial consequences, concurrent with necessary adaptions for important, evolutionary human-centric behaviors such as throwing. However, they have influenced the high rates of rotator cuff pathology in humans compared to closely related primates. The present work represents an important first step toward a broad scope of future research. Interdisciplinary computational modeling offers an evolving and improving alternative to traditional methods to study human evolution and function. Computational and probabilistic simulations can be expanded to numerous other biomechanical and evolutionary queries. The results of this thesis are a promising initial step to examining the evolutionary structural connection to biomechanical human function through comparative computational modeling

Effect of obesity on knee joint biomechanics during gait in young adults

This article is MacLean, K. F. E., Callaghan, J. P., & Maly, M. R. (2016). Effect of obesity on knee joint biomechanics during gait in young adults. Cogent Medicine, 3(1). https://doi.org/10.1080/2331205X.2016.1173778While there are many comorbidities associated with obesity, one of the more poorly understood is knee osteoarthritis through obesity. The purpose of this study was to compare the kinematics and kinetics of gait and cumulative knee adductor load, which represents the sum of repetitive exposures to medial knee loading during daily activity, between young obese adults with young, healthy-weight adults. Eight obese and eight healthy-weight young adults participated. Data from a three-dimensional motion capture system and a synchronized floor-mounted force plate were collected during gait trials. Participants wore accelerometers to determine step counts for seven consecutive days. Dependent t-tests were used to identify differences in gait kinematics, kinetics and cumulative knee adductor load between groups. Compared to the healthy-weight participants, obese young adults demonstrated a slower walking speed, greater stance duration, less knee flexion at heel contact, greater knee adduction in early stance and less knee abduction at terminal stance (p < 0.05). The obese young adults had a greater external knee extension moment (p < 0.05) and external rotation moment (p < 0.05) in early stance. The obese group had a greater cumulative knee adductor load. These results provide insight into a potential pathway by which obesity predisposes a healthy young adult for knee osteoarthritis.This research is supported by Canada Research Chairs, Canadian Institutes of Health Research, and Natural Sciences and Engineering Research Council of Canad

Comparing knee joint kinematics, kinetics and cumulative load between healthy-weight and obese young adults

One of the most poorly understood co-morbidities associated with obesity is the pathway to osteoarthritis of the knee. To implement appropriate preventative strategies, it is important to explore how obesity is a causal factor for osteoarthritis. The present research compared the kinematics and kinetics of a group of young obese, but otherwise healthy, adults to a group of young, healthy-weight adults, in an attempt to identify mechanical abnormalities at the knee during walking that may predispose the obese to osteoarthritis of the knee. Optotrak motion capture (Northern Digital Inc. Waterloo, Ontario) and a forceplate (AMTI OR6-7, Advanced Mechanical Technology Inc, Watertown, MA) were used to measure ground reaction forces and moments of 16 participants – 8 obese and 8 sex-, age- and height-matched healthy-weight – to analyze knee joint kinematics and kinetics at three walking speeds. Participants wore an accelerometer (ActiGraph GT3X, Fort Walton Beach, USA) for seven days to measure daily steps counts. Dependent t-tests were performed to determine group differences in ground reaction forces, knee angles and knee moments, as well as knee adduction moment impulse and cumulative knee adductor load (CKAL). The obese group walked at a significantly slower self-selected speed (p=0.013). While not statistically significant, the obese group did present with a more valgus mean dynamic knee alignment than the health-weight group. A significantly greater maximum abduction angle (p=0.009) and smaller minimum knee flexion angle at heel contact (p=0.001) was found in the obese group. A significant difference was found in the peak medial rotation moment in the transverse plane (p=0.003). A greater stance duration lead to a significantly greater knee adduction moment impulse (p=0.049) in the obese group. While significant group differences were not found in the steps per day, the obese group had a significantly greater CKAL (p=0.025). Obese young adults with healthy knees demonstrated a gait pattern of reduced medial knee joint compartment loading through greater knee abduction, medial knee rotation and a slower walking speed compared to matched controls. The ramifications of gait modifications on long-term musculoskeletal health remain unknown, but compensations may lead to increased risk of osteoarthritis of the knee

Three-dimensional comparison of static and dynamic scapular motion tracking techniques

The final publication is available at Elsevier via http://dx.doi.org/10.1016/j.jelekin.2013.09.011. © 2014. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/The shoulder is complex and comprised of many moving parts. Accurately measuring shoulder rhythm is difficult. To classify shoulder rhythm and identify pathological movement, static measures have been the preferred method. However, dynamic measures are also used and can be less burdensome to obtain. The purpose of this paper was to determine how closely dynamic measures represent static measures using the same acromion marker cluster scapular tracking technique. Five shoulder angles were assessed for 24 participants using dynamic and static tracking techniques during humeral elevation in three planes (frontal, scapular, sagittal). ANOVAs were used to identify where significant differences existed for the factors of plane, elevation angle, and tracking technique (static, dynamic raising, dynamic lowering). All factors were significantly different for all shoulder angles (p<0.001), except for elevation plane in scapulothoracic protraction/retraction (p=0.955). Tracking techniques were influential (p<0.001), but the grouped mean differences fell below a clinically relevant 5° benchmark. There was large variation in mean differences of the techniques across individuals. While population averages are similar, individual static and dynamic shoulder assessments may be different. Caution should be taken when dynamic shoulder assessments are performed on individuals, as they may not reflect those obtained in static scapular motion tracking.Natural Sciences and Engineering Research Council || Canada Foundation for Innovatio

Bioavailability of Macro and Micronutrients Across Global Topsoils: Main Drivers and Global Change Impacts

Understanding the chemical composition of our planet\u27s crust was one of the biggest questions of the 20th century. More than 100 years later, we are still far from understanding the global patterns in the bioavailability and spatial coupling of elements in topsoils worldwide, despite their importance for the productivity and functioning of terrestrial ecosystems. Here, we measured the bioavailability and coupling of thirteen macro- and micronutrients and phytotoxic elements in topsoils (3–8 cm) from a range of terrestrial ecosystems across all continents (∼10,000 observations) and in response to global change manipulations (∼5,000 observations). For this, we incubated between 1 and 4 pairs of anionic and cationic exchange membranes per site for a mean period of 53 days. The most bioavailable elements (Ca, Mg, and K) were also amongst the most abundant in the crust. Patterns of bioavailability were biome-dependent and controlled by soil properties such as pH, organic matter content and texture, plant cover, and climate. However, global change simulations resulted in important alterations in the bioavailability of elements. Elements were highly coupled, and coupling was predictable by the atomic properties of elements, particularly mass, mass to charge ratio, and second ionization energy. Deviations from the predictable coupling-atomic mass relationship were attributed to global change and agriculture. Our work illustrates the tight links between the bioavailability and coupling of topsoil elements and environmental context, human activities, and atomic properties of elements, thus deeply enhancing our integrated understanding of the biogeochemical connections that underlie the productivity and functioning of terrestrial ecosystems in a changing world

Barcoding a Quantified Food Web: Crypsis, Concepts, Ecology and Hypotheses

The efficient and effective monitoring of individuals and populations is critically dependent on correct species identification. While this point may seem obvious, identifying the majority of the more than 100 natural enemies involved in the spruce budworm (Choristoneura fumiferana – SBW) food web remains a non-trivial endeavor. Insect parasitoids play a major role in the processes governing the population dynamics of SBW throughout eastern North America. However, these species are at the leading edge of the taxonomic impediment and integrating standardized identification capacity into existing field programs would provide clear benefits. We asked to what extent DNA barcoding the SBW food web would alter our understanding of the diversity and connectence of the food web and the frequency of generalists vs. specialists in different forest habitats. We DNA barcoded over 10% of the insects collected from the SBW food web in three New Brunswick forest plots from 1983 to 1993. For 30% of these specimens, we amplified at least one additional nuclear region. When the nodes of the food web were estimated based on barcode divergences (using molecular operational taxonomic units (MOTU) or phylogenetic diversity (PD) – the food web became much more diverse and connectence was reduced. We tested one measure of food web structure (the “bird feeder effect”) and found no difference compared to the morphologically based predictions. Many, but not all, of the presumably polyphagous parasitoids now appear to be morphologically-cryptic host-specialists. To our knowledge, this project is the first to barcode a food web in which interactions have already been well-documented and described in space, time and abundance. It is poised to be a system in which field-based methods permit the identification capacity required by forestry scientists. Food web barcoding provided an effective tool for the accurate identification of all species involved in the cascading effects of future budworm outbreaks. Integrating standardized barcodes within food webs may ultimately change the face of community ecology. This will be most poignantly felt in food webs that have not yet been quantified. Here, more accurate and precise connections will be within the grasp of any researcher for the first time

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p&lt;0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (&lt;1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (&lt;1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead