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"Flanagan, D"
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Microenvironmental cues in cancer stemness
2018
Intra-tumour heterogeneity manifests both at the level of mutational burden, and at a functional level within genetically homogenous populations. A new modelling approach suggests stemness within colorectal tumours is defined by microenvironmental cues secreted from cancer-associated fibroblasts rather than cell-intrinsic properties.
Journal Article
Skeletal muscle adaptations to high‐intensity, low‐volume concurrent resistance and interval training in recreationally active men and women
by
Van Eck, Carola
,
Rodriguez‐Ortiz, Nathaniel
,
Wardle, Sophie L.
in
Adaptation
,
Aerobic capacity
,
Aerobics
2024
This study compared the structural and cellular skeletal muscle factors underpinning adaptations in maximal strength, power, aerobic capacity, and lean body mass to a 12‐week concurrent resistance and interval training program in men and women. Recreationally active women and men completed three training sessions per week consisting of high‐intensity, low‐volume resistance training followed by interval training performed using a variety upper and lower body exercises representative of military occupational tasks. Pre‐ and post‐training vastus lateralis muscle biopsies were analyzed for changes in muscle fiber type, cross‐sectional area, capillarization, and mitochondrial biogenesis marker content. Changes in maximal strength, aerobic capacity, and lean body mass (LBM) were also assessed. Training elicited hypertrophy of type I (12.9%; p = 0.016) and type IIa (12.7%; p = 0.007) muscle fibers in men only. In both sexes, training decreased type IIx fiber expression (1.9%; p = 0.046) and increased total PGC‐1α (29.7%, p < 0.001) and citrate synthase (11.0%; p < 0.014) content, but had no effect on COX IV content or muscle capillarization. In both sexes, training increased maximal strength and LBM but not aerobic capacity. The concurrent training program was effective at increasing strength and LBM but not at improving aerobic capacity or skeletal muscle adaptations underpinning aerobic performance.
Journal Article
Recruit-aged adults may preferentially weight task goals over deleterious cost functions during short duration loaded and imposed gait tasks
by
Anderst, William J.
,
Johnson, Camille C.
,
Krajewski, Kellen T.
in
692/698/1671
,
692/700/3160
,
Adult
2023
Optimal motor control that is stable and adaptable to perturbation is reflected in the temporal arrangement and regulation of gait variability. Load carriage and forced-marching are common military relevant perturbations to gait that have been implicated in the high incidence of musculoskeletal injuries in military populations. We investigated the interactive effects of load magnitude and locomotion pattern on motor variability, stride regulation and spatiotemporal complexity during gait in recruit-aged adults. We further investigated the influences of sex and task duration. Healthy adults executed trials of running and forced-marching with and without loads at 10% above their gait transition velocity. Spatiotemporal parameters were analyzed using a goal equivalent manifold approach. With load and forced-marching, individuals used a greater array of motor solutions to execute the task goal (maintain velocity). Stride-to-stride regulation became stricter as the task progressed. Participants exhibited optimal spatiotemporal complexity with significant but not meaningful differences between sexes. With the introduction of load carriage and forced-marching, individuals relied on a strategy that maximizes and regulates motor solutions that achieve the task goal of velocity specifically but compete with other task functions. The appended cost penalties may have deleterious effects during prolonged execution, potentially increasing the risk of musculoskeletal injuries.
Journal Article
Double-Diffusive Recipes. Part I: Large-Scale Dynamics of Thermohaline Staircases
2014
Three-dimensional dynamics of thermohaline staircases are investigated using a series of basin-scale staircase-resolving numerical simulations. The computational domain and forcing fields are chosen to reflect the size and structure of the North Atlantic subtropical thermocline. Salt-finger transport is parameterized using the flux-gradient formulation based on a suite of recent direct numerical simulations. Analysis of the spontaneous generation of thermohaline staircases suggests that thermohaline layering is a product of the gamma instability, associated with the variation of the flux ratio with the density ratio . After their formation, numerical staircases undergo a series of merging events, which systematically increase the size of layers. Ultimately, the system evolves into a steady equilibrium state with pronounced layers 20–50 m thick. The size of the region occupied by thermohaline staircases is controlled by the competition between turbulent mixing and double diffusion. Assuming, in accordance with observations, that staircases form when the density ratio is less than the critical value of , the authors arrive at an indirect estimate of the characteristic turbulent diffusivity in the subtropical thermocline.
Journal Article
Load carriage changes tibiofemoral arthrokinematics during ambulatory tasks in recruit-aged women
by
Dever, Dennis E.
,
Anderst, William J.
,
Johnson, Camille C.
in
692/698/1671
,
692/700/3160
,
Adult
2024
The introduction of women into U.S. military ground close combat roles requires research into sex-specific effects of military training and operational activities. Knee osteoarthritis is prevalent among military service members; its progression has been linked to occupational tasks such as load carriage. Analyzing tibiofemoral arthrokinematics during load carriage is important to understand potentially injurious motion and osteoarthritis progression. The study purpose was to identify effects of load carriage on knee arthrokinematics during walking and running in recruit-aged women. Twelve healthy recruit-aged women walked and ran while unloaded (bodyweight [BW]) and carrying additional + 25%BW and + 45%BW. Using dynamic biplane radiography and subject-specific bone models, tibiofemoral arthrokinematics, subchondral joint space and center of closest contact location between subchondral bone surfaces were analyzed over 0–30% stance (separate one-way repeated measures analysis of variance, load by locomotion). While walking, medial compartment contact location was 5% (~ 1.6 mm) more medial for BW than + 45%BW at foot strike (p = 0.03). While running, medial compartment contact location was 4% (~ 1.3 mm) more lateral during BW than + 25%BW at 30% stance (p = 0.04). Internal rotation was greater at + 45%BW compared to + 25%BW (p < 0.01) at 30% stance. Carried load affects tibiofemoral arthrokinematics in recruit-aged women. Prolonged load carriage could increase the risk of degenerative joint injury in physically active women.
Journal Article
Wrong intraocular lens events—what lessons have we learned? A review of incidents reported to the National Reporting and Learning System: 2010–2014 versus 2003–2010
2016
Purpose
To identify the causal factors in wrong intraocular lens (IOL) events from a national data set and to compare with similar historical data (2003–2010) prior to mandatory checklist use, for the purpose of developing strategies to prevent never events.
Methods
Data from wrong IOL patient safety incidents (PSIs) submitted to the National Reporting and Learning System (2010–2014) were reviewed by thematic analysis and compared with the data previously collected by the group using the same methodology.
Results
One hundred and seventy eight wrong IOL PSIs were identified. The contributory factors included: transcription errors (
n
=26); wrong patient biometry (
n
=21); wrong IOL selection (
n
=16); changes in planned procedure (
n
=16); incorrect IOL brought into theatre (
n
=11); left/right eye selection errors (
n
=9); communication errors (
n
=9); and positive/negative IOL power errors (
n
=9). In 44 PSIs, no causal factor was reported, limiting the learning value of such reports. Compared with the data from previous years, biometry errors were much reduced but IOL transcription and documentation errors were greater, particularly if further checks did not refer to the original source documentation. IOL exchange surgery was reported in 45 cases.
Conclusions
The selection and implantation of the correct IOL is a complex process which is not adequately addressed by existing checking procedures. Despite the introduction of surgical checklists, wrong IOL incidents continue to occur and are probably under-reported. Human or behavioural factors are heavily implicated in these errors and need to be addressed by novel approaches, including simulation training. There is also scope to further improve the quality and detail of incident reporting and analysis to enhance patient safety.
Journal Article
Association of Risk-Taking Behaviors, Vestibular Provocation and Action Boundary Perception Following Sport-Related Concussion in Adolescents
by
Eagle, Shawn R.
,
Flanagan, Shawn D.
,
Kontos, Anthony P.
in
Accuracy
,
Adolescents
,
Balloon treatment
2025
Background/Objectives: The purpose of this study was to evaluate the association between risk-taking behaviors, vestibular symptoms/impairment and perception–action coupling behavior in recently concussed adolescents. Methods: This study utilized a cross-sectional design to evaluate the early effects of concussion on 12–18-year-old adolescents (n = 47) recruited from a concussion specialty clinic at their presenting clinical appointment. The Perception–Action Coupling Task (PACT) was used to assess action boundary perception by evaluating the participant’s ability to quickly and accurately determine whether a virtual “ball” fits in a virtual “hole”. Accuracy, response time and inverse efficiency were evaluated at the 0.8 and 1.2 ratios of ball–hole pairings, where 0.8 indicates the ball was slightly smaller than the hole and 1.2 indicates the ball was slightly larger than the hole. The Balloon Analog Risk Task (BART) is a computerized test which measures risk-taking behavior by “pumping” up a balloon. Each pump provides a small amount of virtual money into their bank; the goal is to make as much money as possible without popping the virtual balloon. The Vestibular Ocular Motor Screening (VOMS) tool is a brief screening tool designed to identify ocular or vestibular dysfunction following sport-related concussion, where horizontal/vertical vestibular ocular reflex (VOR) and visual motion sensitivity (VMS) are the primary vestibular outcomes. Pearson correlation matrices were developed to evaluate the association between BART, VOMS and PACT outcomes within the study cohort of concussed adolescents. Results: PACT inverse efficiency at the 1.2 ball–hole ratio was significantly correlated with all three VOMS outcomes (r = 0.33–0.37). The standard deviation of pump reaction time during BART was significantly correlated with accuracy (r = −0.47) and inverse efficiency (r = 0.42) at the 1.2 ratio. The standard deviation of the total number of pumps during BART was significantly correlated with PACT response time at the 1.2 ratio (r = 0.34). Horizontal VOR correlated with balloons collected (r = −0.30) and balloons popped (r = −0.30). Conclusions: The results of this study suggest that risk-taking behaviors and vestibular symptoms/impairment are associated with worse action boundary perception in adolescents following concussion. This relationship is more pronounced in male adolescents than females.
Journal Article
Orthopaedic surgery residents report little subjective or objective familiarity with healthcare costs
by
Joseph, Noah M
,
Flanagan, Christopher D
,
Sinkler, Margaret A
in
Medical residencies
,
Orthopedics
,
Surgery
2023
PurposeResidents have limited education regarding the cost of orthopaedic interventions. Orthopaedic residents’ knowledge was surveyed in three scenarios involving an intertrochanteric femur fracture: 1) uncomplicated course with 2-day hospital stay; 2) complicated course necessitating ICU admission; and 3) readmission for pulmonary embolism management.MethodsFrom 2018 to 2020, 69 orthopaedic surgery residents were surveyed. Respondents estimated hospital charges and collections; professional charges and collections; implant cost; and level of knowledge depending on the scenario.ResultsMost residents (83.6%) reported feeling “not knowledgeable”. Respondents reporting “somewhat knowledgeable” did not perform better than those who reported “not knowledgeable”. In the uncomplicated scenario, residents underestimated hospital charges and collections (p < 0.01; p = 0.87), and overestimated hospital charges and collections and professional collections (all p < 0.01) with an average percent error of 57.2%. Most residents (88.4%) were aware the sliding hip screw construct costs less than a cephalomedullary nail. In the complex scenario, while residents underestimated the hospital charges (p < 0.01), the estimated collections were closer to the actual figure (p = 0.16). In the third scenario, residents overestimated the charges and collections (p = 0.04; p = 0.04).ConclusionsOrthopaedic surgery residents receive little education regarding healthcare economics and feel unknowledgeable therefore a role for formal economic education during orthopaedic residency may exist.
Journal Article