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Carty, C.

Publications and source records attributed to Carty, C..

4 recordsLinked to original sources

Joint loading in the presence of torsional deformities is overestimated unless gait adaptations are considered: a predictive simulation approach

Lower-limb torsional deformities have been shown to alter joint loading, although the findings vary between studies perhaps due to the simulation approaches applied. This study used predictive simulations to investigate how femoral neck anteversion (FNA) and external tibial torsion (ETT) influence hip and knee joint loading. Musculoskeletal models with altered FNA (1{degrees}-48{degrees}) and ETT (12{degrees}-53{degrees}), in isolation and combination, were created from a scaled adult model, and predictive walking (speed: 1.33 m/s) simulations were generated. Predictive simulations reproduced adaptations in hip rotation and foot-progression angle reported in individuals with torsional deformities. Hip and knee compressive, shear, and resultant contact forces were estimated, and multiple linear regressions quantified the independent associations of FNA and ETT with each outcome. Regressions accounted for 23%-86% of the variance in hip loading and 5%-87% in knee loading. FNA generally made the largest relative contribution to the variance explained in joint loading across regression models, although its associations varied in direction. Each 10{degrees} increase in FNA reduced the first hip compressive and resultant peaks by 0.076 and 0.035 BW, respectively, while hip shear force showed the largest increase, averaging 0.055 BW across both peaks. Most knee loads also increased, by up to 0.131 BW for the second resultant peak. Associations with ETT were primarily observed at the second peak. Our findings suggest that considering gait adaptations due to torsional alterations is crucial for estimating lower-limb joint loading, and prescribing joint kinematics and external forces while altering lower-limb torsion might lead to overestimation.

bioengineering↗

Antigen-driven expansion of public clonal T cell populations in inflammatory bowel diseases

BackgroundInflammatory Bowel Diseases (IBDs), including Crohns disease (CD) and ulcerative colitis (UC), are known to involve shifts in the T-cell repertoires of affected individuals. These include a reduction in regulatory T cells in both diseases, increase in TNF production in CD, expansion of an unconventional T-cell population in CD, and clonal expansion of abundant T-cell populations in CD mucosal tissue. There are also differential HLA risk and protective alleles between CD and UC, implying CD- and UC-specific repertoire changes that have not yet been identified. MethodsWe performed ImmunoSequencing on blood samples from 3,853 CD cases, 1,803 UC cases, and 5,596 healthy controls. For each sample we imputed HLA type and cytomegalovirus (CMV) infection status based on public T-cell receptor {beta} (TCRB) usage and identified public TCRBs enriched in CD or UC cases. FindingsWe determine that there is more expansion across clonotypes in CD, but not UC, compared with healthy controls. We also identify novel interactive effects of HLA-DQ heterodimers with CD and UC risk. Strikingly, from blood we identify public TCRBs specifically expanded in CD or UC. These sequences are more abundant in intestinal mucosal samples, form groups of similar CDR3 sequences, and can be associated to specific HLA alleles. Although the prevalence of these sequences is higher in ileal and ileocolonic CD than colonic CD or UC, the TCRB sequences themselves are shared across CD and not between CD and UC. InterpretationThere are peptide antigens that commonly evoke immune reactions in IBD cases and rarely in non-IBD controls. These antigens differ between CD and UC. CD, particularly ileal CD, also seems to involve more substantial changes in clonal population structure than UC, compared to healthy controls.

immunology↗

Hill-type computational models of muscle-tendon actuators: a systematic review

Backed by a century of research and development, Hill-type models of skeletal muscle, often including a muscle-tendon complex and neuromechanical interface, are widely used for countless applications. Lacking recent comprehensive reviews, the field of Hill-type modelling is, however, dense and hard-to-explore, with detrimental consequences on innovation. Here we present the first systematic review of Hill-type muscle modelling. It aims to clarify the literature by detailing its contents and critically discussing the state-of-the-art by identifying the latest advances, current gaps, and potential future directions in Hill-type modelling. For this purpose, fifty-seven criteria-abiding Hill-type models were assessed according to a completeness evaluation, which identified the modelled muscle properties, and a modelling evaluation, which considered the level of validation and reusability of the models, as well as their modelling strategy and calibration. It is concluded that most models (1) do not significantly advance beyond historical gold standards, (2) neglect the importance of parameter identification, (3) lack robust validation, and (4) are not reusable in other studies. Besides providing a convenient tool supported by extensive supplementary material for navigating the literature, the results of this review highlight the need for global recommendations in Hill-type modelling to optimize inter-study consistency, knowledge transfer, and model reusability.

bioinformatics↗

State-specific gating of salient cues by midbrain dopaminergic input to basal amygdala

Basal amygdala (BA) neurons guide associative learning via acquisition of responses to stimuli that predict salient appetitive or aversive outcomes. We examined the learning- and state-dependent dynamics of BA neurons and ventral tegmental area dopamine axons that innervate BA (VTADA[->]BA) using two-photon imaging and photometry in behaving mice. BA neurons did not respond to arbitrary visual stimuli, but acquired responses to stimuli that predicted either rewards or punishments. Most VTADA[->]BA axons were activated by both rewards and punishments, and acquired responses to cues predicting these outcomes during learning. Responses to cues predicting food rewards in VTADA[->]BA axons and BA neurons in hungry mice were strongly attenuated following satiation, while responses to cues predicting unavoidable punishments persisted or increased. Therefore, VTADA[->]BA axons may provide a reinforcement signal of motivational salience that invigorates adaptive behaviors by promoting learned responses to appetitive or aversive cues in distinct, intermingled sets of BA excitatory neurons.

neuroscience↗