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1.
Proc Biol Sci ; 291(2014): 20232543, 2024 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-38196364

RESUMEN

The human foot is a complex structure that plays an important role in our capacity for upright locomotion. Comparisons of our feet with those of our closest extinct and extant relatives have linked shape features (e.g. the longitudinal and transverse arches, heel size and toe length) to specific mechanical functions. However, foot shape varies widely across the human population, so it remains unclear if and how specific shape variants are related to locomotor mechanics. Here we constructed a statistical shape-function model (SFM) from 100 healthy participants to directly explore the relationship between the shape and function of our feet. We also examined if we could predict the joint motion and moments occurring within a person's foot during locomotion based purely on shape features. The SFM revealed that the longitudinal and transverse arches, relative foot proportions and toe shape along with their associated joint mechanics were most variable. However, each of these only accounted for small proportions of the overall variation in shape, deformation and joint mechanics, most likely owing to the high structural complexity of the foot. Nevertheless, a leave-one-out analysis showed that the SFM can accurately predict joint mechanics of a novel foot, based on its shape and deformation.


Asunto(s)
Locomoción , Modelos Estadísticos , Humanos , Movimiento (Física)
2.
J Biomed Inform ; 154: 104641, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38642627

RESUMEN

OBJECTIVE: Clinical trials involve the collection of a wealth of data, comprising multiple diverse measurements performed at baseline and follow-up visits over the course of a trial. The most common primary analysis is restricted to a single, potentially composite endpoint at one time point. While such an analytical focus promotes simple and replicable conclusions, it does not necessarily fully capture the multi-faceted effects of a drug in a complex disease setting. Therefore, to complement existing approaches, we set out here to design a longitudinal multivariate analytical framework that accepts as input an entire clinical trial database, comprising all measurements, patients, and time points across multiple trials. METHODS: Our framework composes probabilistic principal component analysis with a longitudinal linear mixed effects model, thereby enabling clinical interpretation of multivariate results, while handling data missing at random, and incorporating covariates and covariance structure in a computationally efficient and principled way. RESULTS: We illustrate our approach by applying it to four phase III clinical trials of secukinumab in Psoriatic Arthritis (PsA) and Rheumatoid Arthritis (RA). We identify three clinically plausible latent factors that collectively explain 74.5% of empirical variation in the longitudinal patient database. We estimate longitudinal trajectories of these factors, thereby enabling joint characterisation of disease progression and drug effect. We perform benchmarking experiments demonstrating our method's competitive performance at estimating average treatment effects compared to existing statistical and machine learning methods, and showing that our modular approach leads to relatively computationally efficient model fitting. CONCLUSION: Our multivariate longitudinal framework has the potential to illuminate the properties of existing composite endpoint methods, and to enable the development of novel clinical endpoints that provide enhanced and complementary perspectives on treatment response.


Asunto(s)
Artritis Psoriásica , Artritis Reumatoide , Humanos , Artritis Reumatoide/tratamiento farmacológico , Artritis Psoriásica/tratamiento farmacológico , Estudios Longitudinales , Resultado del Tratamiento , Anticuerpos Monoclonales Humanizados/uso terapéutico , Análisis de Componente Principal , Ensayos Clínicos como Asunto , Ensayos Clínicos Fase III como Asunto , Modelos Estadísticos
3.
J Exp Biol ; 226(12)2023 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-37227005

RESUMEN

Many models have been developed to predict metabolic energy expenditure based on biomechanical proxies of muscle function. However, current models may only perform well for select forms of locomotion, not only because the models are rarely rigorously tested across subtle and broad changes in locomotor task but also because previous research has not adequately characterised different forms of locomotion to account for the potential variability in muscle function and thus metabolic energy expenditure. To help to address the latter point, the present study imposed frequency and height constraints to hopping and quantified gross metabolic power as well as the activation requirements of medial gastrocnemius (MG), lateral gastrocnemius (GL), soleus (SOL), tibialis anterior (TA), vastus lateralis (VL), rectus femoris (RF) and biceps femoris (BF), and the work requirements of GL, SOL and VL. Gross metabolic power increased with a decrease in hop frequency and increase in hop height. There was no hop frequency or hop height effect on the mean electromyography (EMG) data of ankle musculature; however, the mean EMG of VL and RF increased with a decrease in hop frequency and that of BF increased with an increase in hop height. With a reduction in hop frequency, GL, SOL and VL fascicle shortening, fascicle shortening velocity and fascicle to MTU shortening ratio increased, whereas with an increase in hop height, only SOL fascicle shortening velocity increased. Therefore, within the constraints that we imposed, decreases in hop frequency and increases in hop height resulted in increases in metabolic power that could be explained by increases in the activation requirements of knee musculature and/or increases in the work requirements of both knee and ankle musculature.


Asunto(s)
Músculo Esquelético , Músculo Cuádriceps , Humanos , Músculo Esquelético/fisiología , Electromiografía , Músculo Cuádriceps/fisiología , Extremidad Inferior , Locomoción/fisiología , Fenómenos Biomecánicos
4.
J Exp Biol ; 225(8)2022 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-35344050

RESUMEN

The central nervous system utilizes tendon compliance of the intrinsic foot muscles to aid the foot's arch spring, storing and returning energy in its tendinous tissues. Recently, the intrinsic foot muscles have been shown to adapt their energetic contributions during a variety of locomotor tasks to fulfil centre of mass work demands. However, the mechanism by which the small intrinsic foot muscles are able to make versatile energetic contributions remains unknown. Therefore, we examined the muscle-tendon dynamics of the flexor digitorum brevis during stepping, jumping and landing tasks to see whether the central nervous system regulates muscle activation magnitude and timing to enable energy storage and return to enhance energetic contributions. In step-ups and jumps, energy was stored in the tendinous tissue during arch compression; during arch recoil, the fascicles shortened at a slower rate than the tendinous tissues while the foot generated energy. In step-downs and landings, the tendinous tissues elongated more and at greater rates than the fascicles during arch compression while the foot absorbed energy. These results indicate that the central nervous system utilizes arch compression to store elastic energy in the tendinous tissues of the intrinsic foot muscles to add or remove mechanical energy when the body accelerates or decelerates. This study provides evidence for an adaptive mechanism to enable the foot's energetic versatility and further indicates the value of tendon compliance in distal lower limb muscle-tendon units in locomotion.


Asunto(s)
Pie , Músculo Esquelético , Fenómenos Biomecánicos , Pie/fisiología , Locomoción , Músculo Esquelético/fisiología , Tendones/fisiología
5.
Epilepsy Behav ; 136: 108919, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36166879

RESUMEN

OBJECTIVE: Long-term video-electroencephalographic (LTVEM) monitoring is a valuable tool in the evaluation of paroxysmal clinical events. However, vEEG itself is costly. Hence, we aimed to establish if longer duration of monitoring (DOM) is associated with higher diagnostic yield. METHOD: A retrospective review of patients admitted into the epilepsy monitoring unit (EMU) for the diagnostic evaluation of paroxysmal events was performed. Patients' demographic, clinical characteristics, and vEEG data were analyzed. In the cohort of patients with DOM > 7 days, the reasons for prolonged DOM were identified and the differences in clinical characteristics and vEEG data between conclusive and inconclusive studies were analyzed. RESULT: A total of 501 patients were included. Four hundred and thirty-six (87 %) patients had conclusive studies. Of these patients, 67.9 % patients with conclusive studies received diagnosis within the first 7 days of monitoring with the highest on day 7. The likelihood of conclusive studies decreased beyond 7 days. A total of 175 had DOM > 7 days, of which 140 (80 %) had conclusive studies. In the cohort with DOM > 7 days, patients with previous abnormal routine EEG, previous vEEG monitoring, first event recorded before day 5 of admission and ≥1 events recorded during vEEG monitoring were more likely to have conclusive studies. The most common reason for prolonging DOM beyond 7 days was to adequately record multiple semiologically distinctive events (76 %). CONCLUSION: Our study supports that longer DOM is associated with an increase in diagnostic yield. More than one-third of our cohort were monitored beyond 7 days with majority (80 %) being conclusive. Our findings may guide clinicians in planning the DOM and predicting the likelihood of conclusive vEEG studies in patients with prolonged DOM based on the clinical characteristics and vEEG data.


Asunto(s)
Epilepsia , Humanos , Estudios Retrospectivos , Epilepsia/diagnóstico , Electroencefalografía , Monitoreo Fisiológico , Estudios de Cohortes , Grabación en Video
6.
Proc Natl Acad Sci U S A ; 116(5): 1645-1650, 2019 01 29.
Artículo en Inglés | MEDLINE | ID: mdl-30655349

RESUMEN

Human feet have evolved to facilitate bipedal locomotion, losing an opposable digit that grasped branches in favor of a longitudinal arch (LA) that stiffens the foot and aids bipedal gait. Passive elastic structures are credited with supporting the LA, but recent evidence suggests that plantar intrinsic muscles (PIMs) within the foot actively contribute to foot stiffness. To test the functional significance of the PIMs, we compared foot and lower limb mechanics with and without a tibial nerve block that prevented contraction of these muscles. Comparisons were made during controlled limb loading, walking, and running in healthy humans. An inability to activate the PIMs caused slightly greater compression of the LA when controlled loads were applied to the lower limb by a linear actuator. However, when greater loads were experienced during ground contact in walking and running, the stiffness of the LA was not altered by the block, indicating that the PIMs' contribution to LA stiffness is minimal, probably because of their small size. With the PIMs blocked, the distal joints of the foot could not be stiffened sufficiently to provide normal push-off against the ground during late stance. This led to an increase in stride rate and compensatory power generated by the hip musculature, but no increase in the metabolic cost of transport. The results reveal that the PIMs have a minimal effect on the stiffness of the LA when absorbing high loads, but help stiffen the distal foot to aid push-off against the ground when walking or running bipedally.


Asunto(s)
Pie/fisiología , Marcha/fisiología , Locomoción/fisiología , Músculo Esquelético/fisiología , Carrera/fisiología , Caminata/fisiología , Adulto , Fenómenos Biomecánicos/fisiología , Femenino , Cadera/fisiología , Humanos , Masculino , Presión
7.
Proc Biol Sci ; 288(1943): 20202095, 2021 01 27.
Artículo en Inglés | MEDLINE | ID: mdl-33468002

RESUMEN

The arch of the human foot is unique among hominins as it is compliant at ground contact but sufficiently stiff to enable push-off. These behaviours are partly facilitated by the ligamentous plantar fascia whose role is central to two mechanisms. The ideal windlass mechanism assumes that the plantar fascia has a nearly constant length to directly couple toe dorsiflexion with a change in arch shape. However, the plantar fascia also stretches and then shortens throughout gait as the arch-spring stores and releases elastic energy. We aimed to understand how the extensible plantar fascia could behave as an ideal windlass when it has been shown to strain throughout gait, potentially compromising the one-to-one coupling between toe arc length and arch length. We measured foot bone motion and plantar fascia elongation using high-speed X-ray during running. We discovered that toe plantarflexion delays plantar fascia stretching at foot strike, which probably modifies the distribution of the load through other arch tissues. Through a pure windlass effect in propulsion, a quasi-isometric plantar fascia's shortening is delayed to later in stance. The plantar fascia then shortens concurrently to the windlass mechanism, likely enhancing arch recoil at push-off.


Asunto(s)
Fascia , Carrera , Fenómenos Biomecánicos , Pie , Marcha , Humanos
8.
J Exp Biol ; 224(13)2021 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-34018550

RESUMEN

The human foot is known to aid propulsion by storing and returning elastic energy during steady-state locomotion. While its function during other tasks is less clear, recent evidence suggests the foot and its intrinsic muscles can also generate or dissipate energy based on the energetic requirements of the center of mass during non-steady-state locomotion. In order to examine contributions of the foot and its muscles to non-steady-state locomotion, we compared the energetics of the foot and ankle joint while jumping and landing before and after the application of a tibial nerve block. Under normal conditions, energetic contributions of the foot rose as work demands increased, while the relative contributions of the foot to center of mass work remained constant with increasing work demands. Under the nerve block, foot contributions to both jumping and landing decreased. Additionally, ankle contributions were also decreased under the influence of the block for both tasks. Our results reinforce findings that foot and ankle function mirror the energetic requirements of the center of mass and provide novel evidence that foot contributions remain relatively constant under increasing energetic demands. Also, while the intrinsic muscles can modulate the energetic capacity of the foot, their removal accounted for only a 3% decrement in total center of mass work. Therefore, the small size of intrinsic muscles appears to limit their capacity to contribute to center of mass work. However, their role in contributing to ankle work capacity is likely important for the energetics of movement.


Asunto(s)
Tobillo , Desaceleración , Aceleración , Articulación del Tobillo , Fenómenos Biomecánicos , Humanos , Músculo Esquelético , Músculos
9.
Stat Med ; 40(14): 3313-3328, 2021 06 30.
Artículo en Inglés | MEDLINE | ID: mdl-33899260

RESUMEN

Knockoffs provide a general framework for controlling the false discovery rate when performing variable selection. Much of the Knockoffs literature focuses on theoretical challenges and we recognize a need for bringing some of the current ideas into practice. In this paper we propose a sequential algorithm for generating knockoffs when underlying data consists of both continuous and categorical (factor) variables. Further, we present a heuristic multiple knockoffs approach that offers a practical assessment of how robust the knockoff selection process is for a given dataset. We conduct extensive simulations to validate performance of the proposed methodology. Finally, we demonstrate the utility of the methods on a large clinical data pool of more than 2000 patients with psoriatic arthritis evaluated in four clinical trials with an IL-17A inhibitor, secukinumab (Cosentyx), where we determine prognostic factors of a well established clinical outcome. The analyses presented in this paper could provide a wide range of applications to commonly encountered datasets in medical practice and other fields where variable selection is of particular interest.


Asunto(s)
Artritis Psoriásica , Algoritmos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Artritis Psoriásica/tratamiento farmacológico , Ensayos Clínicos como Asunto , Análisis de Datos , Humanos
10.
Ecol Appl ; 31(4): e02308, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33605500

RESUMEN

To mitigate the impact of severe wildfire on human society and the environment, prescribed fire is widely used in forest ecosystems to reduce fuel loads and limit fire spread. To avoid detrimental effects on conservation values, it is imperative to understand how prescribed fire affects taxa having a range of different adaptations to disturbance. Such studies will have greatest benefit if they extend beyond short-term impacts of burning. We used a field study to examine the effects of prescribed fire on birds and plants across a 36-yr post-fire chronosequence in a temperate dry forest ecosystem in southeastern Australia, and by making comparison with long-unburned reference sites (79 yr since wildfire). We modeled changes in the relative abundance of 22 bird species and the cover of 39 plant species, and examined how individual species, functional groups, species richness and community composition differed between sites with different fire history. For most individual bird and plant species modeled, relative abundance or cover at sites subject to prescribed fire did not change significantly with time since fire or differ from that of long-unburned vegetation. When bird species were pooled into functional groups, time since prescribed fire had strong effects on birds that forage in the lower-midstorey, facultative-resprouting shrubs and obligate-seeding shrubs. Species richness for both taxa did not differ between sites subject to prescribed fire and those in long-unburned vegetation. Bird communities varied significantly between the youngest (0-3 yr) and oldest (79 yr) post-fire age classes, driven by species associated with understorey vegetation. Plant community composition showed little evidence of a post-fire successional trajectory. The prevalence of bird species with broad habitat and dietary niches and plant regeneration through resprouting, make bird and plant communities in these forests relatively resilient to small and patchy prescribed fires they have experienced to date. Application of prescribed fire will be most compatible with maintaining biodiversity by taking a landscape approach that (1) plans for a geographic spread of stands with a range of between-prescribed-fire intervals to ensure provision of suitable habitat for all taxa, and (2) avoids burning in moist gullies to maintain their value as fire refuges.


Asunto(s)
Ecosistema , Incendios , Animales , Australia , Aves , Bosques , Humanos
11.
BMC Med Res Methodol ; 21(1): 250, 2021 11 14.
Artículo en Inglés | MEDLINE | ID: mdl-34773974

RESUMEN

BACKGROUND: Novartis and the University of Oxford's Big Data Institute (BDI) have established a research alliance with the aim to improve health care and drug development by making it more efficient and targeted. Using a combination of the latest statistical machine learning technology with an innovative IT platform developed to manage large volumes of anonymised data from numerous data sources and types we plan to identify novel patterns with clinical relevance which cannot be detected by humans alone to identify phenotypes and early predictors of patient disease activity and progression. METHOD: The collaboration focuses on highly complex autoimmune diseases and develops a computational framework to assemble a research-ready dataset across numerous modalities. For the Multiple Sclerosis (MS) project, the collaboration has anonymised and integrated phase II to phase IV clinical and imaging trial data from ≈35,000 patients across all clinical phenotypes and collected in more than 2200 centres worldwide. For the "IL-17" project, the collaboration has anonymised and integrated clinical and imaging data from over 30 phase II and III Cosentyx clinical trials including more than 15,000 patients, suffering from four autoimmune disorders (Psoriasis, Axial Spondyloarthritis, Psoriatic arthritis (PsA) and Rheumatoid arthritis (RA)). RESULTS: A fundamental component of successful data analysis and the collaborative development of novel machine learning methods on these rich data sets has been the construction of a research informatics framework that can capture the data at regular intervals where images could be anonymised and integrated with the de-identified clinical data, quality controlled and compiled into a research-ready relational database which would then be available to multi-disciplinary analysts. The collaborative development from a group of software developers, data wranglers, statisticians, clinicians, and domain scientists across both organisations has been key. This framework is innovative, as it facilitates collaborative data management and makes a complicated clinical trial data set from a pharmaceutical company available to academic researchers who become associated with the project. CONCLUSIONS: An informatics framework has been developed to capture clinical trial data into a pipeline of anonymisation, quality control, data exploration, and subsequent integration into a database. Establishing this framework has been integral to the development of analytical tools.


Asunto(s)
Ciencia de los Datos , Difusión de la Información , Bases de Datos Factuales , Desarrollo de Medicamentos , Humanos , Proyectos de Investigación
12.
Conserv Biol ; 35(2): 492-501, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-32557849

RESUMEN

Global biodiversity indices are used to measure environmental change and progress toward conservation goals, yet few indices have been evaluated comprehensively for their capacity to detect trends of interest, such as declines in threatened species or ecosystem function. Using a structured approach based on decision science, we qualitatively evaluated 9 indices commonly used to track biodiversity at global and regional scales against 5 criteria relating to objectives, design, behavior, incorporation of uncertainty, and constraints (e.g., costs and data availability). Evaluation was based on reference literature for indices available at the time of assessment. We identified 4 key gaps in indices assessed: pathways to achieving goals (means objectives) were not always clear or relevant to desired outcomes (fundamental objectives); index testing and understanding of expected behavior was often lacking; uncertainty was seldom acknowledged or accounted for; and costs of implementation were seldom considered. These gaps may render indices inadequate in certain decision-making contexts and are problematic for indices linked with biodiversity targets and sustainability goals. Ensuring that index objectives are clear and their design is underpinned by a model of relevant processes are crucial in addressing the gaps identified by our assessment. Uptake and productive use of indices will be improved if index performance is tested rigorously and assumptions and uncertainties are clearly communicated to end users. This will increase index accuracy and value in tracking biodiversity change and supporting national and global policy decisions, such as the post-2020 global biodiversity framework of the Convention on Biological Diversity.


Uso de las Ciencias de la Decisión para Evaluar los Índices Globales de Biodiversidad Resumen Los índices globales de biodiversidad se usan para medir el cambio ambiental y el avance hacia los objetivos de conservación, aunque pocos han sido evaluados completamente en cuanto a su capacidad para detectar las tendencias de interés como las declinaciones de especies amenazadas o la función del ecosistema. Evaluamos cualitativamente nueve índices de uso común para dar seguimiento a la biodiversidad a escala global y regional contra cinco criterios relacionados con los objetivos, diseño, comportamiento, incorporación de la incertidumbre y restricciones (p. ej.: costos y disponibilidad de datos) mediante una estrategia estructurada basada en las ciencias de la decisión. La evaluación se basó en la literatura de referencia para los índices disponibles al momento del análisis. Identificamos cuatro vacíos importantes en los índices estudiados: las vías para lograr los objetivos (objetivos medios) no fueron siempre claras o relevantes para los resultados deseados (objetivos fundamentales); el análisis del índice y el entendimiento del comportamiento esperado casi siempre fueron escasos; pocas veces se consideró o explicó la incertidumbre; y casi nunca se consideraron los costos de la implementación. Estos vacíos pueden hacer que los índices sean inadecuados en ciertos contextos de toma de decisiones y son problemáticos para los índices vinculados a los objetivos de biodiversidad y las metas de sustentabilidad. Es de suma importancia asegurarse que los objetivos del índice sean claros y que su diseño esté respaldado por un modelo de procesos relevantes para tratar con los vacíos identificados en nuestro estudio. La aceptación y el uso productivo de los índices mejorarán si el desempeño del índice es evaluado rigurosamente y las suposiciones e incertidumbres se les comunican claramente a los usuarios finales. Lo anterior aumentará la precisión y valor del índice en el seguimiento de los cambios de la biodiversidad y en el apoyo a las decisiones políticas nacionales y mundiales, como el marco de trabajo para la biodiversidad post-2020 establecido por la Convención sobre la Diversidad Biológica.


Asunto(s)
Conservación de los Recursos Naturales , Ecosistema , Animales , Biodiversidad , Especies en Peligro de Extinción , Incertidumbre
13.
Nature ; 579(7797): 31-32, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-32123361
14.
Radiology ; 297(1): 225-234, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32780006

RESUMEN

Background Intermediate stage hepatocellular carcinomas (HCCs) are treated by inducing ischemic cell death with transarterial embolization (TAE) or transarterial chemoembolization (TACE). A subset of HCCs harbor nuclear factor E2-related factor 2 (NRF2), a major regulator of the oxidative stress response implicated in cell survival after ischemia. NRF2-mutated HCC response to TAE and/or TACE is unknown. Purpose To test whether ischemia resistance is present in individuals with NRF2-mutated HCC and if this resistance can be overcome by means of NRF2 inhibition in HCC cell lines. Materials and Methods This was a combined retrospective review of an institutional database (from January 2011 to December 2018) and prospective study (from January 2014 to December 2018) of participants with HCC who underwent TAE and a laboratory investigation of HCC cell lines. Imaging follow-up included liver CT or MRI at 1 month after the procedure followed by 3-month interval scans. Tumor radiologic response was assessed on the basis of follow-up imaging. The time to local progression after TAE for individuals with and individuals without NRF2 pathway alterations was estimated by using competing risk analysis (Gray test). The in vitro response to ischemia in four HCC cell lines with and without NRF2 overexpression was evaluated, and the combination of ischemia with NRF2 knockdown by means of short hairpin RNA or an NRF2 inhibitor was tested. Doubling time estimates, dose response curve regression, and comparison analyses were performed. Results Sixty-five individuals (median age, 69 years [range, 19-84 years]; 53 men) were evaluated. HCCs with NRF2 pathway mutation had a shorter time to local progression after TAE compared to those without mutation (6-month cumulative incidence of local progression, 56% [range, 19%-91%] vs 22% [range, 12%-34%], respectively; P < .001) and confirmed ischemia resistance in NRF2-overexpressing HCC cell lines. However, ischemia and NRF2 knock-down worked synergistically to decrease proliferation of NRF2-overexpressing HCC cell lines. Dose response curves of ML385, an NRF2 inhibitor, showed that ischemia induces addiction to NRF2 in cells with NRF2 alterations. Conclusion Hepatocellular carcinoma with nuclear factor E2-related factor 2 (NRF2) alterations showed resistance to ischemia, but ischemia simultaneously induced sensitivity to NRF2 inhibition. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Weiss and Nezami in this issue.


Asunto(s)
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Factor 2 Relacionado con NF-E2/genética , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/terapia , Línea Celular Tumoral , Progresión de la Enfermedad , Embolización Terapéutica , Femenino , Humanos , Isquemia/genética , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/terapia , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Mutación , Factor 2 Relacionado con NF-E2/antagonistas & inhibidores , Estudios Prospectivos , Estudios Retrospectivos , Medición de Riesgo , Tomografía Computarizada por Rayos X
15.
Ecol Appl ; 26(8): 2412-2421, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27907257

RESUMEN

Fire plays an important role in structuring vegetation in fire-prone regions worldwide. Progress has been made towards documenting the effects of individual fire events and fire regimes on vegetation structure; less is known of how different fire history attributes (e.g., time since fire, fire frequency) interact to affect vegetation. Using the temperate eucalypt foothill forests of southeastern Australia as a case study system, we examine two hypotheses about such interactions: (1) post-fire vegetation succession (e.g., time-since-fire effects) is influenced by other fire regime attributes and (2) the severity of the most recent fire overrides the effect of preceding fires on vegetation structure. Empirical data on vegetation structure were collected from 540 sites distributed across central and eastern Victoria, Australia. Linear mixed models were used to examine these hypotheses and determine the relative influence of fire and environmental attributes on vegetation structure. Fire history measures, particularly time since fire, affected several vegetation attributes including ground and canopy strata; others such as low and sub-canopy vegetation were more strongly influenced by environmental characteristics like rainfall. There was little support for the hypothesis that post-fire succession is influenced by fire history attributes other than time since fire; only canopy regeneration was influenced by another variable (fire type, representing severity). Our capacity to detect an overriding effect of the severity of the most recent fire was limited by a consistently weak effect of preceding fires on vegetation structure. Overall, results suggest the primary way that fire affects vegetation structure in foothill forests is via attributes of the most recent fire, both its severity and time since its occurrence; other attributes of fire regimes (e.g., fire interval, frequency) have less influence. The strong effect of environmental drivers, such as rainfall and topography, on many structural features show that foothill forest vegetation is also influenced by factors outside human control. While fire is amenable to human management, results suggest that at broad scales, structural attributes of these forests are relatively resilient to the effects of current fire regimes. Nonetheless, the potential for more frequent severe fires at short intervals, associated with a changing climate and/or fire management, warrant further consideration.


Asunto(s)
Incendios , Bosques , Australia , Clima , Ecosistema
16.
Conserv Biol ; 29(2): 473-81, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25163611

RESUMEN

Fire is used as a management tool for biodiversity conservation worldwide. A common objective is to avoid population extinctions due to inappropriate fire regimes. However, in many ecosystems, it is unclear what mix of fire histories will achieve this goal. We determined the optimal fire history of a given area for biological conservation with a method that links tools from 3 fields of research: species distribution modeling, composite indices of biodiversity, and decision science. We based our case study on extensive field surveys of birds, reptiles, and mammals in fire-prone semi-arid Australia. First, we developed statistical models of species' responses to fire history. Second, we determined the optimal allocation of successional states in a given area, based on the geometric mean of species relative abundance. Finally, we showed how conservation targets based on this index can be incorporated into a decision-making framework for fire management. Pyrodiversity per se did not necessarily promote vertebrate biodiversity. Maximizing pyrodiversity by having an even allocation of successional states did not maximize the geometric mean abundance of bird species. Older vegetation was disproportionately important for the conservation of birds, reptiles, and small mammals. Because our method defines fire management objectives based on the habitat requirements of multiple species in the community, it could be used widely to maximize biodiversity in fire-prone ecosystems.


Asunto(s)
Biodiversidad , Conservación de los Recursos Naturales/métodos , Incendios , Animales , Australia , Aves/fisiología , Ecosistema , Mamíferos/fisiología , Modelos Biológicos , Reptiles/fisiología
17.
Future Oncol ; 11(2 Suppl): 35-6, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25662326

RESUMEN

Pulmonary metastasectomy has become an established mode of therapy in the management of certain patients with metastatic colorectal cancer. All patients undergoing pulmonary resection for metastatic colorectal cancer between March 2008 and February 2014 were studied. 190 patients were identified. Most had a single metastasis (83%); 17% had multiple lesions (maximum: 4). The approach was thoracotomy in 92 and VATS in 98. 67% underwent wedge resection and 33% lobectomy. The size of the resected lesions was 8-110 mm (median: 24). 13% of patients underwent more than one procedure (maximum: 4); 8% had prior hepatic metastasectomy. There was no operative mortality. The 1-, 3- and 5-year survival was 92, 87 and 82%, respectively. Guidelines for referral and follow-up of these patients should be developed.


Asunto(s)
Neoplasias Colorrectales/patología , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/cirugía , Metastasectomía/métodos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Estudios Retrospectivos , Tasa de Supervivencia , Cirugía Torácica Asistida por Video , Toracotomía , Reino Unido/epidemiología
18.
J R Soc Interface ; 21(214): 20240074, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38807524

RESUMEN

The interaction among joints of the midtarsal complex and subtalar joint is important for locomotor function; however, its complexity poses substantial challenges in quantifying the joints' motions. We determine the mobility of these joints across locomotion tasks and investigate the influence of individual talus morphology on their motion. Using highly accurate biplanar videoradiography, three-dimensional bone kinematics were captured during walking, running and hopping. We calculated the axis of rotation of the midtarsal complex and subtalar joint for the landing and push-off phases. A comparison was made between these rotation axes and the morphological subtalar axis. Measurement included total rotation about and the orientation of the rotation axes in the direction of the subtalar joint and its deviation via spatial angles for both phases. The rotation axes of all three bones relative to the talus closely align with the morphological subtalar axis. This suggests that the midtarsal and subtalar joints' motions might be described by one commonly oriented axis. Despite having such an axis, the location of the axes and ranges of motion differed among the bones. Our results provide a novel perspective of healthy foot function across different sagittal plane-dominant locomotion tasks underscoring the importance of quantifying midtarsal complex and subtalar motion while accounting for an individual's talus morphology.


Asunto(s)
Carrera , Articulación Talocalcánea , Caminata , Humanos , Masculino , Articulación Talocalcánea/fisiología , Articulación Talocalcánea/anatomía & histología , Fenómenos Biomecánicos , Carrera/fisiología , Adulto , Caminata/fisiología , Femenino , Rango del Movimiento Articular/fisiología
19.
J Biomech ; 166: 112051, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38503062

RESUMEN

Measuring or estimating the forces acting on the human body during movement is critical for determining the biomechanical aspects relating to injury, disease and healthy ageing. In this study we examined whether quantifying whole-body motion (segmental accelerations) using a commercial markerless motion capture system could accurately predict three-dimensional ground reaction force during a diverse range of human movements: walking, running, jumping and cutting. We synchronously recorded 3D ground reaction forces (force instrumented treadmill or in-ground plates) with high-resolution video from eight cameras that were spatially calibrated relative to a common coordinate system. We used a commercially available software to reconstruct whole body motion, along with a geometric skeletal model to calculate the acceleration of each segment and hence the whole-body centre of mass and ground reaction force across each movement task. The average root mean square difference (RMSD) across all three dimensions and all tasks was 0.75 N/kg, with the maximum average RMSD being 1.85 N/kg for running vertical force (7.89 % of maximum). There was very strong agreement between peak forces across tasks, with R2 values indicating that the markerless prediction algorithm was able to predict approximately 95-99 % of the variance in peak force across all axes and movements. The results were comparable to previous reports using whole-body marker-based approaches and hence this provides strong proof-of-principle evidence that markerless motion capture can be used to predict ground reaction forces and therefore potentially assess movement kinetics with limited requirements for participant preparation.


Asunto(s)
Captura de Movimiento , Carrera , Humanos , Fenómenos Biomecánicos , Fenómenos Mecánicos , Movimiento
20.
J Neurophysiol ; 110(4): 891-8, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23678020

RESUMEN

Abductor hallucis is the largest muscle in the arch of the human foot and comprises few motor units relative to its physiological cross-sectional area. It has been described as a postural muscle, aiding in the stabilization of the longitudinal arch during stance and gait. The purpose of this study was to describe the discharge properties of abductor hallucis motor units during ramp and hold isometric contractions, as well as its discharge characteristics during fatigue. Intramuscular electromyographic recordings from abductor hallucis were made in 5 subjects; from those recordings, 42 single motor units were decomposed. Data were recorded during isometric ramp contractions at 60% maximum voluntary contraction (MVC), performed before and after a submaximal isometric contraction to failure (mean force 41.3 ± 15.3% MVC, mean duration 233 ± 116 s). Motor unit recruitment thresholds ranged from 10.3 to 54.2% MVC. No significant difference was observed between recruitment and derecruitment thresholds or their respective discharge rates for both the initial and postfatigue ramp contractions (all P > 0.25). Recruitment threshold was positively correlated with recruitment discharge rate (r = 0.47, P < 0.03). All motor units attained similar peak discharge rates (14.0 ± 0.25 pulses/s) and were not correlated with recruitment threshold. Thirteen motor units could be followed during the isometric fatigue task, with a decline in discharge rate and increase in discharge rate variability occurring in the final 25% of the task (both P < 0.05). We have shown that abductor hallucis motor units discharge relatively slowly and are considerably resistant to fatigue. These characteristics may be effective for generating and sustaining the substantial level of force that is required to stabilize the longitudinal arch during weight bearing.


Asunto(s)
Pie/fisiología , Contracción Isométrica , Neuronas Motoras/fisiología , Fatiga Muscular , Músculo Esquelético/inervación , Adulto , Electromiografía , Humanos , Masculino , Músculo Esquelético/fisiología
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