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Methods for Comparative Gait Analysis in Heterogeneous Dog Populations
No full textVertebrate locomotion is a complex process utilising both the nervous and musculoskeletal
systems. The study of gait can therefore provide significant insights concerning the health
and function of the brain, spinal cord, nerves, muscles, bones, and joints. Clinical gait
analysis can be used to understand, diagnose, monitor, rehabilitate, and design treatment
plans for a variety of musculoskeletal and neurological abnormalities.
Utilisation of gait analysis can be limited in comparisons of heterogeneous dog populations
due to the significant differences in size and shape that can exist between different
breeds and mixed-breeds of dogs. These differences create difficulties in determining what
normal parameter ranges should be for a given dog. As a result, definitively detecting the
presence and location of abnormalities in a dog’s gait is challenging, particularly in cases of
subclinical lameness or multi-limb or multi-joint involvement.
This thesis explores the use of machine learning and mechanical modelling methods to
predict expected temporospatial gait parameter ranges in a heterogeneous dog population
and identify the presence of gait abnormalities.
A preliminary study validated the use of an instrumented treadmill system to enable
rapid collection of kinetic and temporospatial gait data and improve repeatability of gait
measurements through increased gait cycle sample size and control of velocity. The effects of
various measurement qualities on the resultant parameter values were explored, and criteria
for data inclusion and processing were determined. A case study of objective kinetic and
temporospatial gait changes in a dog before and after a spinal cord injury was also found to
suggest that methods for comparison between different breeds, sizes, and conformations of
dogs in existing control group studies are not adequate.
A scalable biomechanical model consisting of non-invasive morphometric measurements
was used to inform machine learning models in the prediction of temporospatial gait parameter
ranges and identification of gait abnormalities. This approach resulted in excellent models
for prediction of expected ranges of step length, stride length, and paw contact surface area
parameters in a heterogeneous dog population. Moderately successful predictive models
for the hind reach, velocity, and cadence parameters were also developed. A preliminary classification model for identifying the presence of a gait abnormality was also successful in
identifying all clinical lameness cases in the test data.
These findings are a significant step in support of the development and implementation
of machine learning methods to enable better objectivity and abnormality detection in canine
gait studies. Further research is needed to expand and validate these models in a larger
heterogeneous dog population for clinical implementation
Genetic and Phenotypic Associations With Sustained Antidepressant Use in Major Depressive Disorder.
No full textIMPORTANCE: Antidepressant treatment remains a trial-and-error process: one-third of people with major depressive disorder (MDD) report inefficacy of first-line medications. Predictors of prescription patterns are needed to improve prescribing precision. OBJECTIVE: To investigate phenotypic and genetic heterogeneity of MDD subgroups defined by antidepressant prescription patterns. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cohort study of Australian Genetics of Depression Study (2017-2018) adult participants (aged ≥18 years) with lifetime MDD who filled 1 or more prescriptions of the 10 most commonly used antidepressants across 4.5 years (2013-2017). Data were analyzed from August 2024 to October 2025. EXPOSURES: Treatment complexity was assessed as number of different antidepressant classes in prescriptions filled in 4.5 years. Sustained-use 360 groups were defined as 360 or more cumulative days (in 4.5 years) of a single antidepressant. Participants with genome-wide genotypes were contrasted across mutually exclusive sustained-use 360 groups. MAIN OUTCOMES AND MEASURES: Associations of 44 self-reported phenotypes and polygenic scores (PGSs) for 15 traits with sustained-use 360 subgroups. Genome-wide association studies (GWASs) were conducted for selective serotonin reuptake inhibitor (SSRI) or SSRI/serotonin-norepinephrine reuptake inhibitor sustained use contrasted to other participants. RESULTS: Of 12 074 participants (9041 [75%] female with a mean [SD] age of 41.8 [14.6] years; 3022 [25%] male with a mean [SD] age of 47.7 [14.6] years) with 1 or more prescriptions and lifetime MDD, 8898 had genotyping data. High treatment complexity was significantly associated with 37 of 44 self-reported phenotypes (eg, higher rates of smoking, recurrent MDD, suicidal ideation, chronic pain, and circadian and atypical depression subtypes) and higher PGSs for psychiatric traits (MDD PGS: β, 0.04; 95% CI, 0.03-0.06; P = 1.2 × 10-8; ADHD PGS: β, 0.03; 95% CI, 0.02-0.05; P = 2.1 × 10-5 ; bipolar disorder PGS: β, 0.03; 95% CI, 0.01-0.04. P = 1.2 × 10-4 ; neuroticism PGS: β, 0.02; 95% CI, 0.01-0.04; P = 1.3 × 10-3). A total of 5453 (61%) met criteria for an exclusive antidepressant sustained-use 360 group. These groups had distinct phenotypic profiles, including associations with body mass index, suicidal ideation, and co-occurring conditions. GWASs identified novel loci, including an immune-related gene SLAMF3/LY9, for which single-nucleotide variant rs4656934 was associated with reduced odds of sustained SSRI use (G allele; odds ratio, 0.81; 95% CI, 0.75-0.87; P = 3.5 × 10-8). CONCLUSIONS AND RELEVANCE: This study found that phenotypic factors were associated with sustained antidepressant use and treatment complexity. PGSs for traits studied were associated with treatment complexity but showed little association with sustained-use 360 groups. These findings support further research to guide treatment selection and to identify patients at risk of difficult-to-treat depression, informing precision psychiatry and early intervention in MDD
Beyond the ESG Facade: Measuring and Addressing Corporate ‘Lip Service’
No full textAmid growing global attention to Environmental, Social, and Governance (ESG), this study examines the misalignment between ESG disclosures and actual practices—termed ‘lip service’ —using data from Chinese firms from 2006 to 2022, constructing an index to quantify it. The findings indicate that such behaviour is more common in high-emission and capital-dependent industries, significantly undermining firm value. External oversight mechanisms (media, analysts, and institutional investors) and CEO compensation incentives help mitigate its impact, whereas traditional governance tools, such as managerial ownership and CEO duality, are largely ineffective. The severity of this behaviour is influenced by pollution levels, ownership structure, business risk, and the tone of annual reports. Further analysis reveals that ‘lip service’ also weakens financial performance, including earnings per share, net profit, and corporate reputation. These findings highlight the economic risks of ESG inconsistencies and underscore the need for stronger regulatory enforcement and active stakeholder supervision to promote genuine ESG engagement
EXPRESS: Up, down, and all around? Deciphering the boundary conditions for training induced transfer effects within a set of hierarchically nested tasks.
No full textConvergent evidence suggests that the transfer effects engendered by training studies are tied to specific task features. The present study examined transfer in a set of three hierarchically nested change detection tasks (CDTs) using a tightly controlled adaptive training paradigm. These CDT paradigms all required participants to remember arrays of stimuli, and then report the change (in colour, orientation or both) of a probed item. The three tasks were identical except for the response judgment requirements: colour, orientation, or dual (both colour and orientation). We also included a retro-cue - a spatial cue within the retention period - allowing us to test whether training impacts the allocation of attention during maintenance. Each training group made significantly greater on-task gains relative to the active control group (digit-span training). Between-task transfer patterns were present but limited and largely feature-specific. Training gains on the orientation task did not transfer to the colour variant and vice versa; in fact, there was some evidence of negative transfer. However, those trained on the colour variant did show benefits to both variants within the dual task context. The dual CDT trainees also showed transfer to the simple orientation and colour variants. Finally, we found no compelling evidence to distinguish whether training gains and transfer effects are due to improved capacity or the improved precision with which representations are held. In short, participants learn to better represent and report specific features, but it is not clear if this is driven by changes in capacity or precision.
Uncertainties in exposure predictions arising from point measurements of carbon dioxide in classroom environments
No full textPredictions of airborne infection risk can be made based on the fraction of rebreathed air inferred from point measurements of carbon dioxide (CO2). We investigate the extent to which environmental factors, particularly spatial variations due to the ventilation provision, affect the uncertainty in these predictions. Spatial variations are expected to be especially problematic in naturally ventilated spaces, which include the majority of classrooms in the UK. An idealized classroom, broadly representative of the physics of (buoyancy-driven) displacement ventilation, is examined using computational fluid dynamics, with different ventilation configurations. Passive tracers are used to model both the CO2 generated by all 32 occupants and the breath of a single infectious individual (located in nine different regions). The distribution of infected breath is shown to depend strongly on the distance from the release location but is also affected by the pattern of the ventilating flow, including the presence of stagnating regions. However, far-field exposure predictions based on single point measurements of CO2 within the breathing zone are shown to rarely differ from the actual exposure to infected breath by more than a factor of two—we argue this uncertainty is small compared with other uncertainties inherent in modelling airborne infection risk
Intralabyrinthine MRI FLAIR as a predictive marker for hearing loss in vestibular schwannomas in Neurofibromatosis Type 2
No full textBackground and objectives: The onset of hearing loss due to vestibular schwannomas (VS) is inevitable but does not correlate with the size of the tumor. In patients with Neurofibromatosis Type 2 (NF2) and VS, we previously found an association between pre-contrast fluid-attenuated inversion recovery magnetic resonance imaging (FLAIR MRI) signal in the labyrinth and hearing loss. Here, we asked whether FLAIR hyper-intensity could serve as a predictive biomarker for hearing loss in NF2 patients with VS. Methods: A prospective longitudinal study (NCT00598351) of NF2 enrolled 168 subjects between 2008 and 2013. This study included 34 patients with small VS (total volume ≤ 500mm3). Middle fossa decompression surgery (n = 4 patients) was provided via a standard-of-care trial (NCT00060541). Results: From 34 eligible subjects (mean age 26.8y) with NF2 and small VS, 53 ears met inclusion criteria. Abnormal hearing was recorded in 18 ears at study entry; all 18 ears had FLAIR hyper-intensity. Of the 35 ears with normal hearing, 16 had FLAIR hyper-intensity at study entry, 6 (37.5%) of which developed new hearing loss (median time to hearing loss of 4.45 years). Conversion to FLAIR hyper-intensity occurred in 11 ears, 3 of which proceeded to hearing loss. No hearing loss developed in the eight ears that remained FLAIR negative. FLAIR conversion has high sensitivity (1·00, 95% CI 0·39–1) and negative predictive value (1·00, 95% CI 0·63–1) for new-onset hearing loss. In 4 patients undergoing middle fossa decompression surgery, we found that surgery stabilized hearing but did not reverse FLAIR hyperintensity. Conclusions: Our findings suggest that intralabyrinthine FLAIR hyper-intensity is a sensitive, non-invasive biomarker for hearing loss related to VS. Hearing decline followed FLAIR hyper-intensity by approximately 4 years but was absent in ears with normal FLAIR signal. Trial registration: Registry: ClinicalTrials.gov, TRN: NCT00060541, Registration date: 4 June 2003
Circulating saturated fatty acids and incident chronic kidney disease: a meta-analysis of de-novo prospective cohort investigations
No full textBackground Chronic kidney disease (CKD) is a global health problem which is associated with poor outcomes, and its prevalence is expected to increase. Identifying novel risk factors for CKD may lead to improved outcomes. Circulating saturated fatty acids (SFAs) have been posited as contributors to CKD risk. Objectives We aimed to evaluate associations between circulating SFAs (measured in phospholipids in 7 cohorts, serum or plasma total in 5 cohorts, and cholesterol esters in 1 cohort) and incident CKD in 13 cohorts, and to pool results by meta-analysis across the studies. Methods SFAs were measured in 13 cohorts in the Fatty Acids Outcomes Research Consortium, including 18,193 participants with estimated glomerular filtration rate >60 mL/min/1.73 m2 across 9 countries. Associations between each SFA [palmitic acid (16:0), stearic acid (18:0), arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0)] and incident CKD (defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2 and ≥25% decrease from baseline) were assessed by Cox or Poisson regressions. Results were pooled using inverse variance weighted meta-analysis. Results In total, 2554 participants developed CKD over a weighted median follow-up of 7.6 y. After adjustment, higher concentrations of 18:0 were associated with a lower risk of CKD with minimal heterogeneity (relative risk per interquintile range: 0.87; 95% confidence interval: 0.80, 0.95, P = 0.003, I2 = 14.7%). These associations remained consistent in secondary and sensitivity analyses. We did not observe significant associations of other SFAs with CKD. Conclusions In a meta-analysis of 18,193 participants across 9 countries, we observed no indication that SFA increased CKD risk, whereas higher 18:0 concentrations were associated with a lower risk of CKD. Future research is needed to assess mechanisms by which SFA 18:0 may exert kidney-protective effects, and how circulating SFA 18:0 concentrations may be altered
Instruction as orchestration: multimodal connection building with the interactive whiteboard
No full textThe interactive whiteboard (IWB), the first ICT tool primarily designed for whole-class interaction, is now in regular use in most British primary schools. In this paper, we explore its distinctive potential for enabling the teacher to plan and orchestrate activities and lessons using a wide range of multimodal resources, to engage students' cognitive and imaginative capacities. We show how teachers use combinations of ‘matched resources’ to support the bridging of pupils' understanding from the known to the new, and from everyday to academic understandings. We demonstrate how teachers can use the IWB to resource the development of ideas and themes over time while maintaining spontaneous responsiveness to situations as they arise, effectively enacting Sawyer's notion of teaching as ‘disciplined improvisational performance’
Absolute Quantification of Brain Deuterium Metabolic Imaging in Healthy Volunteers and Glioblastoma Patients at 7T.
No full textPURPOSE: We present a method for absolute quantification of deuterated metabolites in vivo at 7T. We describe acquisition protocols and an analysis pipeline compatible with 7T Terra MRIs. We apply them using a 2H/1H receive array in healthy volunteers and glioblastoma patients. METHODS: B1 +/B1 - maps from multiple CSI scans in a uniform phantom were used to derive calibrated coil weights for absolute quantification. We validated this in phantoms with known deuterated compounds. 2H MRSI was performed in twelve healthy volunteers (two post-[6,6-2H2]-glucose) and five treatment-naive glioblastoma patients (all post-[6,6-2H2]-glucose). Spectra were fitted with OXSA. We compared Glx/Lac between tumor and normal-appearing brain using linear mixed-effects models. RESULTS: Measured B1 + maps were 0.82 ± 0.19 μT/√W across the whole phantom. Natural abundance deuterium in water was 8.96 ± 0.7 mmol/L. Absolute maps of HDO, Glc, Glx, and Lac were acquired following [6,6-2H2]glucose. Rate maps showed higher Lac production in tumors (2.3 μmol/L/min, SE = 0.87) compared with normal-appearing regions (1.0 μmol/L/min, SE = 0.36; p < 0.01) and healthy brain (0.5 μmol/L/min, SE = 0.17; p < 0.01). Glx production was lower in tumors (3.8 μmol/L/min, SE = 0.44) relative to normal-appearing contralateral regions (6.0 μmol/L/min, SE = 0.36; p < 0.001) and healthy brain (9.2 μmol/L/min, SE = 0.61; p < 0.001). CONCLUSION: We demonstrate robust absolute quantification for human 7T DMI. Glioblastoma tumors showed elevated Lac and reduced Glx labeling relative to normal brain, with inter-patient heterogeneity consistent with an existence of different metabolic subtypes
The stability of the Autism Diagnostic Observation Schedule-2 in children aged 14-36 months with elevated likelihood for autism.
Get PDFBACKGROUND: This study investigated the stability of Autism Diagnostic Observation Schedule, Second Edition (ADOS-2) classifications in a cohort of 304 siblings at elevated likelihood for autism (EL-siblings). METHODS: ADOS-2 assessments were conducted at 14, 24 and 36 months, with Clinical Best Estimate (CBE) autism diagnoses determined at 36 months. RESULTS: Our findings indicate that while some children have stable ADOS-2 classifications from early on, a significant proportion of the children show inconsistent classifications over time. The overall stability of ADOS-2 autism spectrum classifications increased from 14 to 36 months and agreement with CBE autism clinical diagnosis was moderate and increased with age. CONCLUSIONS: Caution is warranted when interpreting individual ADOS-2 results, as they should always complement, and can never replace, a comprehensive clinical evaluation. These findings highlight the importance of continued follow-up beyond 14 months in young EL-children, a group for whom early assessment may be both feasible and beneficial and emphasises the need to integrate multiple assessment measures and multiple informants for accurate early autism identification