The Biomechanics Research and Innovation Challenge: Development, Implementation, Uptake, and Reflections on the Inaugural Program.

Biomechanics as a discipline is ideally placed to increase awareness and participation of girls and women in science, technology, engineering, and mathematics. A nationwide Biomechanics and Research Innovation Challenge (BRInC) centered on mentoring and role modeling was developed to engage high school girls (mentees) and early-mid-career women (mentors) in the field of biomechanics through the completion of a 100-day research and/or innovation project. This manuscript describes the development, implementation, and uptake of the inaugural BRInC program and synthesizes the research and innovation projects undertaken, providing a framework for adoption of this program within the global biomechanics community. Eighty-seven high school girls in years 9 and 10 (age range: 14-16 y) were mentored in teams (n = 17) by women in biomechanics (n = 24). Using a design thinking approach, teams generated solutions to biomechanics-based problem(s)/research question(s). Eight key reflections on program strengths, as well as areas for improvement and planned changes for future iterations of the BRInC program, are outlined. These key reflections highlight the innovation, impact, and scalability of the program; the importance of a program framework and effective communication tools; and implementation of strategies to sustain the program as well as the importance of diversity and building a sense of community.

Leveraging Unique Chromosomal Microarray Probes to Accurately Detect Copy Number at the Highly Homologous 15q15.3 Deafness-Infertility Syndrome Locus.

BACKGROUND: Biallelic deletions at 15q15.3, including STRC and CATSPER2, cause autosomal recessive deafness-infertility syndrome (DIS), while biallelic deletions of STRC alone cause nonsyndromic hearing loss. These deletions are among the leading genetic causes of mild-moderate hearing loss, but their detection using chromosomal microarray (CMA) is impeded by a tandem duplication containing highly homologous pseudogenes. We sought to assess copy number variant (CNV) detection in this region by a commonly-employed CMA platform. METHODS: Twenty-two specimens with known 15q15.3 CNVs, determined by droplet digital PCR (ddPCR), were analyzed by CMA. To investigate the impact of pseudogene homology on CMA performance, a probe-level analysis of homology was performed, and log2 ratios of unique and pseudogene-homologous probes compared. RESULTS: Assessment of 15q15.3 CNVs by CMA compared to ddPCR revealed 40.9% concordance, with frequent mis-assignment of zygosity by the CMA automated calling software. Probe-level analysis of pseudogene homology suggested that probes with high homology contributed to this discordance, with significant differences in log2 ratios between unique and pseudogene-homologous CMA probes. Two clusters containing several unique probes could reliably detect CNVs involving STRC and CATSPER2, despite the noise of surrounding probes, discriminating between homozygous vs heterozygous losses and complex rearrangements. CNV detection by these probe clusters showed 100% concordance with ddPCR. CONCLUSIONS: Manual analysis of clusters containing unique CMA probes without significant pseudogene homology improves CNV detection and zygosity assignment in the highly homologous DIS region. Incorporation of this method into CMA analysis and reporting processes can improve DIS diagnosis and carrier detection.

The feasibility, validity, and reliability of strain measures in the iliotibial band during isolated muscular contractions.

The iliotibial band (ITB) is a unique anatomical structure that transmits forces from two in-series muscles across the lateral knee. Little is known about how force is transmitted, via ITB strain, in response to muscle activation. We have developed a technique to measure the strain through the distal ITB during isolated contractions of the tensor fascia latae (TFL) muscle, using a Kanade-Lucas-Tomasi ultrasound image tracking algorithm. Here we report: 1) the validity of this method to track ITB tissue displacement; 2) the reliability of tracking ITB strain across multiple contractions (intra-probe placement), tracking attempts (intra-operator), data collection sessions (inter-probe placement), and tracking operators (inter-operator); and 3) the feasibility of this approach to assess differences in strain produced during different TFL contraction levels. Our method was valid for tracking ITB displacement and could be used to determine tissue strain due to isolated muscle contraction. Our method was most reliable when a single operator tracked trials without replacing the ultrasound transducer and when averaging across multiple stimulations. Our method was also able to detect changes in ITB strains resulting from differing levels of muscle activation. In the future, this method could be used to assess how factors like posture and ITB region affect the strain found in the distal ITB.

Clinician perspectives on reasons for, implications and management of unplanned patient returns to the Emergency Department: A descriptive study.

BACKGROUND: Unplanned return visits to the emergency department (ED) have been associated with adverse outcomes and may reflect the quality of care delivered. Several studies speculate the reasons for return and suggest clinician behaviour as potentially influencing a patient's decision to return to the ED. There is little research about this issue from the clinician's perspective, which is necessary to inform future practice improvement. METHODS: A descriptive cross sectional design was employed to ascertain perspectives on identification and management of return visits occurring within 48 hours of discharge. An electronic survey was distributed to all medical, nursing, and clerical staff at one ED. Descriptive statistics were used for quantitative data and content analysis was performed on textual data. Results were categorised as barriers or facilitators, then mapped to the Theoretical Domains Framework. RESULTS: A response rate of 59.7% (n=86/144) was achieved. Staff reported increased levels of concern for this patient group but not all staff were aware of the policy for managing return patients (40.7%). Five barriers and three facilitators were identified that mapped to eight influencers of behaviour including knowledge, memory and environmental factors. CONCLUSION: Overall, staff were aware of return patients but lacked familiarity with policy and processes to identify and commence relevant protocols. Further review of current practice as well as the patient perspective is required before any intervention to improve practice is developed.

A comparison of centre of pressure behaviour and ground reaction force magnitudes when individuals walk overground and on an instrumented treadmill.

BACKGROUND: Instrumented treadmills facilitate analysis of consecutive strides in ways that typical overground gait data collections cannot. Researchers have quantified differences between joint kinetic measures whilst walking on an instrumented treadmill compared to those walking overground. The reason for such differences has not yet been established. RESEARCH QUESTION: Can we identify the source or sources of these errors by comparing centre of pressure and ground reaction force measurements recorded on a treadmill to those collected overground? METHODS: Kinematic and kinetic data were recorded while nineteen individuals walked continuously at their self-selected walking speed overground and on a treadmill. Comparisons of the centre of pressure and ground reaction forces were made between the two conditions using 2-tailed paired t-tests and Cohen's d effect size. RESULTS: The results indicated that participants had significantly faster backwards, lateral and medial centre of pressure velocities when walking on a treadmill compared to when they were walking overground. Additionally, participants also had significantly reduced peak propulsive ground reaction forces when walking on a treadmill than walking overground. SIGNIFICANCE: These results suggest that shear forces caused by the belts sliding over the treadmill force platforms affect the centre of pressure during early stance, and the minimal acceleration of a participant's centre of mass during treadmill walking results in reduced propulsive force during late stance. Therefore, care should be taken during studies when comparing kinetic gait variables between overground and treadmill walking.

Preliminary Validation for the "BJR method"-A Possible New Mathematical Approach to Methadone Conversion.

Methadone has been effectively utilized in the palliative care setting as a second-line agent for pain management in cancer patients with refractory pain, or in those who cannot tolerate other opioid medications. The lack of reliable dosing ratios, substantial interindividual variability in methadone pharmacodynamics, the potential for extensive drug interactions, and the high potency of methadone compared with other opioids all pose significant barriers to the use of this drug in routine practice. This article describes a novel approach to methadone conversion, with case studies providing preliminary validation.

Analyzing and Reanalyzing the Genome: Findings from the MedSeq Project.

Although genome sequencing is increasingly available in clinical and research settings, many questions remain about the interpretation of sequencing data. In the MedSeq Project, we explored how much effort is required to evaluate and report on more than 4,500 genes reportedly associated with monogenic conditions, as well as pharmacogenomic (PGx) markers, blood antigen serotyping, and polygenic risk scores in 100 individuals (50 with cardiomyopathy and 50 healthy) randomized to the sequencing arm. We defined the quality thresholds for determining the need for Sanger confirmation. Finally, we examined the effort needed and new findings revealed by reanalyzing each genome (6-23 months after initial analysis; mean 13 months). Monogenic disease risk and carrier status were reported in 21% and 94% of participants, respectively. Only two participants had no monogenic disease risk or carrier status identified. For the PGx results (18 genotypes in six genes for five drugs), the identified diplotypes prompted recommendation for non-standard dosing of at least one of the analyzed drugs in 95% of participants. For blood antigen studies, we found that 31% of participants had a rare blood antigen genotype. In the cardiomyopathy cohort, an explanation for disease was identified in 48% of individuals. Over the course of the study, 14 variants were reclassified and, upon reanalysis, 18 new variants met criteria for reporting. These findings highlight the quantity of medically relevant findings from a broad analysis of genomic sequencing data as well as the need for periodic reinterpretation and reanalysis of data for both diagnostic indications and secondary findings.

Death or Damnation: Surrogacy and Religious Beliefs.

MC is a 42-year-old female who was in a motor vehicle accident and suffered multiple contusions as well as a fracture of the left femur, pelvic ramus, and left orbit. Due to contusion of the brain, MC has been comatose for over a week and is on mechanical ventilation to protect her airway. There is no written declaration of surrogacy. During the admission, surgery to repair the left femoral fracture was performed and was complicated by severe blood loss. Currently, MC's hematocrit is 24% with a hemoglobin of 7.4. The trauma team asserts that a blood transfusion would be in MC's best interests. Since MC lacks capacity for decision making, she cannot consent to blood transfusion. Her parents are Jehovah's Witnesses and refuse to approve blood transfusion, stating that it is against their faith. MC's brother, however, states that MC is not a practicing Jehovah's Witness and wants the medical team to provide the blood transfusion. The parents insist that decision making is their right; MC's brother feels he should be making decisions. The trauma teams calls for an emergency consultation with the hospital ethics committee.

Self-Selected walking speed increases when individuals are aware of being recorded.

BACKGROUND: Typical gait data collections consist of discrete walking trials where participants are aware when data are being recorded. Anecdotally, some investigators have reported that participants often walk differently between trials or before or after data collection compared to when they know they are being recorded. In addition, walking speed, which affects a number of gait variables, is known to be different when individuals complete discrete and continuous walking trials. RESEARCH QUESTION: The purpose of this study was to determine whether changes in walking speed occurred as a result of participants being aware, versus unaware that data were being recorded, during both discrete and continuous walking trials. METHODS: Kinematic data were collected for twenty two individuals walking continuous trials or discrete trials, while they were both aware and unaware of being recorded. Comparisons of walking speeds were made between groups (continuous walking; discrete trials) and awareness of being recorded (aware; unaware) using a two way ANOVA. RESULTS: The results indicated that participants walked significantly faster during discrete trials when they were aware that data were being recorded compared to when they were unaware. However, when they walked continuously their walking speed was not affected by their awareness. SIGNIFICANCE: The results suggest that awareness of data collection, and the type of protocol used during data collection, affect an individual's walking speed during gait analysis. Therefore, care should be taken when determining gait analysis protocols where variables are sensitive to walking speeds.

A descriptive systematic review of salivary therapeutic drug monitoring in neonates and infants.

AIMS: Saliva, as a matrix, offers many benefits over blood in therapeutic drug monitoring (TDM), in particular for infantile TDM. However, the accuracy of salivary TDM in infants remains an area of debate. This review explored the accuracy, applicability and advantages of using saliva TDM in infants and neonates. METHODS: Databases were searched up to and including September 2016. Studies were included based on PICO as follows: P: infants and neonates being treated with any medication, I: salivary TDM vs. C: traditional methods and O: accuracy, advantages/disadvantages and applicability to practice. Compounds were assessed by their physicochemical and pharmacokinetic properties, as well as published quantitative saliva monitoring data. RESULTS: Twenty-four studies and their respective 13 compounds were investigated. Four neutral and two acidic compounds, oxcarbazepine, primidone, fluconazole, busulfan, theophylline and phenytoin displayed excellent/very good correlation between blood plasma and saliva. Lamotrigine was the only basic compound to show excellent correlation with morphine exhibiting no correlation between saliva and blood plasma. Any compound with an acid dissociation constant (pKa) within physiological range (pH 6-8) gave a more varied response. CONCLUSION: There is significant potential for infantile saliva testing and in particular for neutral and weakly acidic compounds. Of the properties investigated, pKa was the most influential with both logP and protein binding having little effect on this correlation. To conclude, any compound with a pKa within physiological range (pH 6-8) should be considered with extra care, with the extraction and analysis method examined and optimized on a case-by-case basis.

Operator Bias Errors Are Reduced Using Standing Marker Alignment Device for Repeated Visit Studies.

When optical motion capture is used for motion analysis, reflective markers or a digitizer are typically used to record the location of anatomical landmarks identified through palpation. The landmarks are then used to construct anatomical coordinate systems. Failure to consistently identify landmarks through palpation over repeat tests creates artifacts in the kinematic waveforms. The purpose of this work was to improve intra- and inter-rater reliability in determining lower limb anatomical landmarks and the associated anatomical coordinate systems using a marker alignment device (MAD). The device aids the subject in recreating the same standing posture over multiple tests, and recreates the anatomical landmarks from previous static calibration trials. We tested three different raters who identified landmarks on eleven subjects. The subjects performed walking trials and their gait kinematics were analyzed with and without the device. Ankle kinematics were not improved by the device suggesting manual palpation over repeat visits is just as effective as the MAD. Intra-class correlation coefficients between gait kinematics registered to the reference static trial and registered to follow-up static trials with and without the device were improved between 1% and 33% when the device was used. Importantly, out-of-plane hip and knee kinematics showed the greatest improvements in repeatability. These results suggest that the device is well suited to reducing palpation artifact during repeat visits to the gait lab.

A Comparison of Self-Selected Walking Speeds and Walking Speed Variability When Data Are Collected During Repeated Discrete Trials and During Continuous Walking.

A typical gait analysis data collection consists of a series of discrete trials, where a participant initiates gait, walks through a motion capture volume, and then terminates gait. This is not a normal 'everyday' gait pattern, yet measurements are considered representative of normal walking. However, walking speed, a global descriptor of gait quality that can affect joint kinematics and kinetics, may be different during discrete trials, compared to continuous walking. Therefore, the purpose of this study was to investigate the effect of continuous walking versus discrete trials on walking speed and walking speed variability. Data were collected for 25 healthy young adults performing 2 walking tasks. The first task represented a typical gait data collection session, where subjects completed repeated trials, beginning from a standstill and walking along a 12-m walkway. The second task was continuous walking along a "figure-of-8" circuit, with 1 section containing the same 12-m walkway. Walking speed was significantly higher during the discrete trials compared to the continuous trials (p < .001), but there were no significant differences in walking speed variability between the conditions. The results suggest that choice of gait protocol may affect results where variables are sensitive to walking speed.

Healthcare students' experiences of an interprofessional, student-led neuro-rehabilitation community-based clinic.

Student-led clinics are becoming more prominent as educators seek alternate models of clinical education for health professionals. The purpose of this study was to evaluate healthcare students' experiences of an interprofessional student-led clinic for clients with neurological conditions. Thirteen students representing occupational therapy, physiotherapy, and speech pathology were recruited for the study. A sequential mixed-methods evaluation was employed and the results from the Interprofessional Education Scale and focus group revealed that the students experienced positive perceptions of working collaboratively with other professions, forming good relationships with others, as well as an increased respect for the roles of other professions. The findings suggest that providing a capstone opportunity, where students can work as part of an interprofessional team with a real client, in a format they may come across in future clinical practice, may be beneficial in providing them with essential interprofessional skills as new graduate health professionals.

The impact of non-aggressive behaviour early in aggressive interactions: Sex differences in direct and indirect aggression in response to provocation.

Using an adapted form of the Taylor competitive reaction time task (TCRT: Taylor, 1967), we examined the effect of initially non-aggressive behaviour during aggressive encounters. Specifically, if a person is initially non-aggressive, but becomes more aggressive later, does an opponent respond more or less aggressively in response? Participants (N = 148) played a competitive reaction time task against a bogus partner, who was either initially non-aggressive, or initially moderately aggressive, and then delivered increasingly loud noise blasts to participants on trials when the participant lost. Both direct (noise blasts delivered to the partner) and indirect aggression (damage to partner's reputation) were assessed. The impact of whether or not participants expected to meet the partner on direct and indirect aggression was also examined. All participants reduced their direct aggression towards an initially non-aggressive partner and a partner they expected to meet. However, for females, the switch from initial non-aggression to later aggression generated a negative evaluation of the partner, exhibited by indirect but not direct aggression.