Scar massage as an intervention for post-surgical scars: A practice survey of Australian hand therapists.

Introduction: Scar massage is a commonly used treatment in hand therapy. The current empirical evidence that supports it is disparate and of variable quality, with no established effective dosage and method proposed. This study aimed to identify the current practice among Australian hand therapists using massage as an intervention for scarring following surgery to the hand and upper limb. Methods: A purposely designed self-report online survey was emailed to current members of the Australian Hand Therapy Association (n = 958). Data collected included demographics, intervention techniques, conditions treated and protocols, scar assessment and knowledge and training about scar massage as a clinical intervention. Results: A total of 116 completed questionnaires were received (a response rate of 12.1%). All respondents used scar massage as part of their clinical practice with 98% to improve soft tissue glide (n = 114), 92% for hypersensitivity (n = 107), and 84% to increase hand function (n = 97). Only 18% (n = 21) of respondents used standardised outcome measures, and most therapists had learned scar massage from a colleague (81%). Conclusions: Commonalities in how respondents implemented scar massage were found. Participants reported relying primarily on clinical experience to inform their practice. Whilst scar massage was widely used, few respondents had received formal skills training or completed outcome measures regularly to formally evaluate its clinical efficacy or impact. Replication of this study with a larger international sample of participants is warranted to determine if these findings reflect general practice.

Cortical tracking of visual rhythmic speech by 5- and 8-month-old infants: Individual differences in phase angle relate to language outcomes up to 2 years.

It is known that the rhythms of speech are visible on the face, accurately mirroring changes in the vocal tract. These low-frequency visual temporal movements are tightly correlated with speech output, and both visual speech (e.g., mouth motion) and the acoustic speech amplitude envelope entrain neural oscillations. Low-frequency visual temporal information ('visual prosody') is known from behavioural studies to be perceived by infants, but oscillatory studies are currently lacking. Here we measure cortical tracking of low-frequency visual temporal information by 5- and 8-month-old infants using a rhythmic speech paradigm (repetition of the syllable 'ta' at 2 Hz). Eye-tracking data were collected simultaneously with EEG, enabling computation of cortical tracking and phase angle during visual-only speech presentation. Significantly higher power at the stimulus frequency indicated that cortical tracking occurred across both ages. Further, individual differences in preferred phase to visual speech related to subsequent measures of language acquisition. The difference in phase between visual-only speech and the same speech presented as auditory-visual at 6- and 9-months was also examined. These neural data suggest that individual differences in early language acquisition may be related to the phase of entrainment to visual rhythmic input in infancy. RESEARCH HIGHLIGHTS: Infant preferred phase to visual rhythmic speech predicts language outcomes. Significant cortical tracking of visual speech is present at 5 and 8 months. Phase angle to visual speech at 8 months predicted greater receptive and productive vocabulary at 24 months.

Ensemble Detection of DNA Engineering Signatures.

Synthetic biology is creating genetically engineered organisms at an increasing rate for many potentially valuable applications, but this potential comes with the risk of misuse or accidental release. To begin to address this issue, we have developed a system called GUARDIAN that can automatically detect signatures of engineering in DNA sequencing data, and we have conducted a blinded test of this system using a curated Test and Evaluation (T&E) data set. GUARDIAN uses an ensemble approach based on the guiding principle that no single approach is likely to be able to detect engineering with perfect accuracy. Critically, ensembling enables GUARDIAN to detect sequence inserts in 13 target organisms with a high degree of specificity that requires no subject matter expert (SME) review.

Investigating the use of finerenone in children with chronic kidney disease and proteinuria: design of the FIONA and open-label extension studies.

INTRODUCTION: Proteinuria is a modifiable risk factor for chronic kidney disease (CKD) progression in children. Finerenone, a selective, non-steroidal, mineralocorticoid receptor antagonist (MRA) has been approved to treat adults with CKD associated with type 2 diabetes mellitus (T2DM) following results from the phase III clinical trials FIDELIO-DKD (NCT02540993) and FIGARO-DKD (NCT02545049). In a pre-specified pooled analysis of both studies (N = 13,026), finerenone was shown to have an acceptable safety profile and was efficacious in decreasing the risk of adverse kidney and cardiovascular outcomes and of proteinuria. OBJECTIVE: FIONA and the associated open-label extension (OLE) study aim to demonstrate that combining finerenone with an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) is safe, well-tolerated, and effective in sustainably reducing urinary protein excretion in children with CKD and proteinuria. DESIGN: FIONA (NCT05196035; Eudra-CT: 2021-002071-19) is a randomized (2:1), double-blind, placebo-controlled, multicenter, phase III study of 6 months' duration in approximately 219 pediatric patients. Patients must have a clinical diagnosis of CKD (an eGFR ≥ 30 mL/min/1.73 m2 if ≥ 1 to < 18 years or a serum creatinine level ≤ 0.40 mg/dL for infants 6 months to < 1 year) with significant proteinuria despite ACEi or ARB usage. The primary objective is to demonstrate that finerenone, added to an ACEi or ARB, is superior to placebo in reducing urinary protein excretion. FIONA OLE (NCT05457283; Eudra-CT: 2021-002905-89) is a single-arm, open-label study, enrolling participants who have completed FIONA. The primary objective of FIONA OLE is to provide long-term safety data. FIONA has two primary endpoints: urinary protein-to-creatinine ratio (UPCR) reduction of ≥ 30% from baseline to day 180 and percent change in UPCR from baseline to day 180. A sample size of 198 participants (aged 2 to < 18 years) in FIONA will provide at least 80% power to reject the null hypothesis of either of the two primary endpoints. CONCLUSION: FIONA is evaluating the use of finerenone in children with CKD and proteinuria. Should safety, tolerability, and efficacy be demonstrated, finerenone could become a useful additional therapeutic agent in managing proteinuria and improving kidney outcomes in children with CKD. TRIAL REGISTRATION: ClinicalTrials.gov NCT05196035. Registered on 19 January 2022.

Precursors to infant sensorimotor synchronization to speech and non-speech rhythms: A longitudinal study.

Impaired sensorimotor synchronization (SMS) to acoustic rhythm may be a marker of atypical language development. Here, Motion Capture was used to assess gross motor rhythmic movement at six time points between 5- and 11 months of age. Infants were recorded drumming to acoustic stimuli of varying linguistic and temporal complexity: drumbeats, repeated syllables and nursery rhymes. Here we show, for the first time, developmental change in infants' movement timing in response to auditory stimuli over the first year of life. Longitudinal analyses revealed that whilst infants could not yet reliably synchronize their movement to auditory rhythms, infant spontaneous motor tempo became faster with age, and by 11 months, a subset of infants decelerate from their spontaneous motor tempo, which better accords with the incoming tempo. Further, infants became more regular drummers with age, with marked decreases in the variability of spontaneous motor tempo and variability in response to drumbeats. This latter effect was subdued in response to linguistic stimuli. The current work lays the foundation for using individual differences in precursors of SMS in infancy to predict later language outcomes. RESEARCH HIGHLIGHT: We present the first longitudinal investigation of infant rhythmic movement over the first year of life Whilst infants generally move more quickly and with higher regularity over their first year, by 11 months infants begin to counter this pattern when hearing slower infant-directed song Infant movement is more variable to speech than non-speech stimuli In the context of the larger Cambridge UK BabyRhythm Project, we lay the foundation for rhythmic movement in infancy to predict later language outcomes.

Decoding speech information from EEG data with 4-, 7- and 11-month-old infants: Using convolutional neural network, mutual information-based and backward linear models.

BACKGROUND: Computational models that successfully decode neural activity into speech are increasing in the adult literature, with convolutional neural networks (CNNs), backward linear models, and mutual information (MI) models all being applied to neural data in relation to speech input. This is not the case in the infant literature. NEW METHOD: Three different computational models, two novel for infants, were applied to decode low-frequency speech envelope information. Previously-employed backward linear models were compared to novel CNN and MI-based models. Fifty infants provided EEG recordings when aged 4, 7, and 11 months, while listening passively to natural speech (sung or chanted nursery rhymes) presented by video with a female singer. RESULTS: Each model computed speech information for these nursery rhymes in two different low-frequency bands, delta and theta, thought to provide different types of linguistic information. All three models demonstrated significant levels of performance for delta-band neural activity from 4 months of age, with two of three models also showing significant performance for theta-band activity. All models also demonstrated higher accuracy for the delta-band neural responses. None of the models showed developmental (age-related) effects. COMPARISONS WITH EXISTING METHODS: The data demonstrate that the choice of algorithm used to decode speech envelope information from neural activity in the infant brain determines the developmental conclusions that can be drawn. CONCLUSIONS: The modelling shows that better understanding of the strengths and weaknesses of each modelling approach is fundamental to improving our understanding of how the human brain builds a language system.

Protecting Personhood: A Classic Grounded Theory.

The importance of perceiving and considering patients as healthcare partners has been increasingly promoted. Healthcare systems around the world are now highly interested in patient engagement, participation, collaboration, and partnership. Healthcare professionals are advised that patients, as autonomous beings, should be active in and responsible for a portion of their own care. The study presented here focused on patients' perceptions of interprofessional collaboration. It was conducted using the classic grounded theory methodology. The theory of protecting personhood emerged as the core concept of hospitalized patients, cared for by interprofessional healthcare teams. This theory encapsulates the process hospitalized patients go through to find balance in their sense of self, oscillating between personhood and patienthood in the unfamiliar hospital environment. The process consists of four stages: the stage of introspection, during which hospitalized patients become aware of their self as a person and as a patient; the stage of preservation, when patients find a balance between the sense of personhood and patienthood; the stage of rupture, wherein patients experience an imbalance between their sense of personhood and patienthood; and the stage of reconciliation, in which personhood is restored. The theory of protecting personhood offers insights into a better understanding of hospitalized patients' experiences and strategies, revealing the importance of relationships, and the driving force of empowerment. This study is about patients' perspectives of interprofessional healthcare teams. A grounded theory process allowed the emergence of patients' concerns and expectations, leading to a substantive theory grounded in the patients' data.

Neural phase angle from two months when tracking speech and non-speech rhythm linked to language performance from 12 to 24 months.

Atypical phase alignment of low-frequency neural oscillations to speech rhythm has been implicated in phonological deficits in developmental dyslexia. Atypical phase alignment to rhythm could thus also characterize infants at risk for later language difficulties. Here, we investigate phase-language mechanisms in a neurotypical infant sample. 122 two-, six- and nine-month-old infants were played speech and non-speech rhythms while EEG was recorded in a longitudinal design. The phase of infants' neural oscillations aligned consistently to the stimuli, with group-level convergence towards a common phase. Individual low-frequency phase alignment related to subsequent measures of language acquisition up to 24 months of age. Accordingly, individual differences in language acquisition are related to the phase alignment of cortical tracking of auditory and audiovisual rhythms in infancy, an automatic neural mechanism. Automatic rhythmic phase-language mechanisms could eventually serve as biomarkers, identifying at-risk infants and enabling intervention at the earliest stages of development.

AZD5438 a GSK-3a/b and CDK inhibitor is antiapoptotic modulates mitochondrial activity and protects human neurons from mitochondrial toxins.

We previously reported that kenpaullone, which inhibits GSK-3a/b and CDKs inhibited CCCP mediated mitochondrial depolarisation and augments the mitochondrial network. To investigate the actions of this class of drug further, we compared the ability of kenpaullone, alsterpaullone, 1-azakenapaullone, AZD5438, AT7519 (CDK and GSK-3a/b inhibitors) and dexpramipexole and olesoxime (mitochondrial permeability transition pore inhibitors) to prevent CCCP mediated mitochondrial depolarisation and found that AZD5438 and AT7519, were the most effective. Furthermore, treatment with AZD5438 alone increased the complexity of the mitochondrial network. We also found that AZD5438 prevented the rotenone induced decrease in PGC-1alpha and TOM20 levels and that it mediated powerful anti-apoptotic effects and promoted glycolytic respiration. Importantly, experiments in human iPSC derived cortical and midbrain neurons showed AZD5438 mediated significant protective effects, preventing the neuronal cell death, and collapse in the neurite and mitochondrial network associated with rotenone treatment. These results suggest drugs that target GSK-3a/b and CDKs should be developed and assessed further as they may have significant therapeutic potential.

Expectations about precision bias metacognition and awareness.

Bayesian models of the mind suggest that we estimate the reliability or "precision" of incoming sensory signals to guide perceptual inference and to construct feelings of confidence or uncertainty about what we are perceiving. However, accurately estimating precision is likely to be challenging for bounded systems like the brain. One way observers could overcome this challenge is to form expectations about the precision of their perceptions and use these to guide metacognition and awareness. Here we test this possibility. Participants made perceptual decisions about visual motion stimuli, while providing confidence ratings (Experiments 1 and 2) or ratings of subjective visibility (Experiment 3). In each experiment, participants acquired probabilistic expectations about the likely strength of upcoming signals. We found these expectations about precision altered metacognition and awareness-with participants feeling more confident and stimuli appearing more vivid when stronger sensory signals were expected, without concomitant changes in objective perceptual performance. Computational modeling revealed that this effect could be well explained by a predictive learning model that infers the precision (strength) of current signals as a weighted combination of incoming evidence and top-down expectation. These results support an influential but untested tenet of Bayesian models of cognition, suggesting that agents do not only "read out" the reliability of information arriving at their senses, but also take into account prior knowledge about how reliable or "precise" different sources of information are likely to be. This reveals that expectations about precision influence how the sensory world appears and how much we trust our senses. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Building the Plant SynBio Toolbox through Combinatorial Analysis of DNA Regulatory Elements.

While the installation of complex genetic circuits in microorganisms is relatively routine, the synthetic biology toolbox is severely limited in plants. Of particular concern is the absence of combinatorial analysis of regulatory elements, the long design-build-test cycles associated with transgenic plant analysis, and a lack of naming standardization for cloning parts. Here, we use previously described plant regulatory elements to design, build, and test 91 transgene cassettes for relative expression strength. Constructs were transiently transfected into Nicotiana benthamiana leaves and expression of a fluorescent reporter was measured from plant canopies, leaves, and protoplasts isolated from transfected plants. As anticipated, a dynamic level of expression was achieved from the library, ranging from near undetectable for the weakest cassette to a ∼200-fold increase for the strongest. Analysis of expression levels in plant canopies, individual leaves, and protoplasts were correlated, indicating that any of the methods could be used to evaluate regulatory elements in plants. Through this effort, a well-curated 37-member part library of plant regulatory elements was characterized, providing the necessary data to standardize construct design for precision metabolic engineering in plants.

Cortical Tracking of Sung Speech in Adults vs Infants: A Developmental Analysis.

Here we duplicate a neural tracking paradigm, previously published with infants (aged 4 to 11 months), with adult participants, in order to explore potential developmental similarities and differences in entrainment. Adults listened and watched passively as nursery rhymes were sung or chanted in infant-directed speech. Whole-head EEG (128 channels) was recorded, and cortical tracking of the sung speech in the delta (0.5-4 Hz), theta (4-8 Hz) and alpha (8-12 Hz) frequency bands was computed using linear decoders (multivariate Temporal Response Function models, mTRFs). Phase-amplitude coupling (PAC) was also computed to assess whether delta and theta phases temporally organize higher-frequency amplitudes for adults in the same pattern as found in the infant brain. Similar to previous infant participants, the adults showed significant cortical tracking of the sung speech in both delta and theta bands. However, the frequencies associated with peaks in stimulus-induced spectral power (PSD) in the two populations were different. PAC was also different in the adults compared to the infants. PAC was stronger for theta- versus delta- driven coupling in adults but was equal for delta- versus theta-driven coupling in infants. Adults also showed a stimulus-induced increase in low alpha power that was absent in infants. This may suggest adult recruitment of other cognitive processes, possibly related to comprehension or attention. The comparative data suggest that while infant and adult brains utilize essentially the same cortical mechanisms to track linguistic input, the operation of and interplay between these mechanisms may change with age and language experience.

Simulation-Based Engineering of Time-Delayed Safety Switches for Safer Gene Therapies.

CRISPR-based gene editing is a powerful tool with great potential for applications in the treatment of many inherited and acquired diseases. The longer that CRISPR gene therapy is maintained within a patient, however, the higher the likelihood that it will result in problematic side effects such as off-target editing or immune response. One approach to mitigating these issues is to link the operation of the therapeutic system to a safety switch that autonomously disables its operation and removes the delivered therapeutics after some amount of time. We present here a simulation-based analysis of the potential for regulating the time delay of such a safety switch using one or two transcriptional regulators and/or recombinases. Combinatorial circuit generation identifies 30 potential architectures for such circuits, which we evaluate in simulation with respect to tunability, sensitivity to parameter values, and sensitivity to cell-to-cell variation. This modeling predicts one of these circuit architectures to have the desired dynamics and robustness, which can be further tested and applied in the context of CRISPR therapeutics.

Inhibition of Anti-Inflammatory Macrophage Phenotype Reduces Tumour Growth in Mouse Models of Brain Metastasis.

Breast cancer brain metastasis is a significant clinical problem and carries a poor prognosis. Although it is well-established that macrophages are a primary component of the brain metastasis microenvironment, the role of blood-derived macrophages (BDM) and brain-resident microglia in the progression of brain metastases remains uncertain. The aim of this study, therefore, was to determine the role, specifically, of pro- and anti-inflammatory BDM and microglial phenotypes on metastasis progression. Initial in vitro studies demonstrated decreased migration of EO771 metastatic breast cancer cells in the presence of pro-inflammatory, but not anti-inflammatory, stimulated RAW 264.7 macrophages. In vivo, suppression of the anti-inflammatory BDM phenotype, specifically, via myeloid knock out of Krüppel-like Factor 4 (KLF4) significantly reduced EO771 tumour growth in the brains of C57BL/6 mice. Further, pharmacological inhibition of the anti-inflammatory BDM and/or microglial phenotypes, via either Colony Stimulating Factor 1 Receptor (CSF-1R) or STAT6 pathways, significantly decreased tumour burden in two different syngeneic mouse models of breast cancer brain metastasis. These findings suggest that switching BDM and microglia towards a more pro-inflammatory phenotype may be an effective therapeutic strategy in brain metastasis.

From outcome measurement to improving health outcomes after lower limb amputation-A narrative review exploring outcome measurement from a clinical practice perspective.

Outcome measurement is essential to understand the impact of clinical interventions and the performance of services. Despite national and professional body encouragement, and successful examples of system level outcome measurement within some health care settings, many barriers still exist preventing outcome measurement from becoming embedded in clinical practice. This paper presents a narrative review which aims to describe the state of the outcome measurement evidence base in prosthetic rehabilitation, as applied in clinical practice, with a view to identifying areas for future work aimed at making outcome measurement in prosthetic rehabilitation a meaningful reality. A literature search of four databases was undertaken, following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis principals appropriate to narrative reviews, and using the search terms outcome, measur*, tool, scale, instrument, prosthe*, amput* and limb loss. A total of 1116 papers were identified. Following screening 35 papers, focusing on four main themes, were included in the review. Themes were: 1) What outcome domains should be measured? 2) How can these outcome domains be measured? 3) What are the barriers to outcome measurement? and 4) What can be learnt from examples of ROM in prosthetic rehabilitation? Findings suggest that successful outcome measurement is multifaceted. Understanding and embedding value at every step appears to be key to success. Addressing the questions of 'what' outcome domains to measure and 'how' to measure them, may help establish consensus. Routine outcome measurement practice at the clinical level should ensure data collection is valuable to clinical practice, makes use of information technology solutions and has organisational engagement.

Is massage an effective intervention in the management of post-operative scarring? A scoping review.

BACKGROUND: Scar massage is a widely used treatment modality in hand therapy. This intervention is thoroughly discussed in the literature relating to burns rehabilitation, however, the evidence for its use in treating linear scars following surgery is limited. PURPOSE OF STUDY: To collate the empirical literature on scar massage for the treatment of postsurgical cutaneous scars. STUDY DESIGN: Scoping review. METHODS: Medline, EMBASE, CINAHL, AMED, Scopus, ProQuest Dissertations & Theses Global, and the Joanna Briggs Institute were searched from inception to December 2020. Two researchers used a data extraction tool to record key demographic, intervention and outcome data, and to apply the Oxford Levels of Evidence for each study. RESULTS: Twenty-five studies met the inclusion criteria, reporting on a combined sample of 1515 participants. Only two papers addressed hand or wrist scars (92 participants). While all studies reported favorable outcomes for scar massage, there were 45 different outcome measures used and a propensity towards non-standardized assessment. Intervention protocols varied from a single session to three treatments daily for 6 months. The results from 13 studies were confounded by the implementation of additional rehabilitation interventions. CONCLUSIONS: The overall findings suggest that while there may be benefits to scar massage in reducing pain, increasing movement and improving scar characteristics; there is a lack of consistent research methods, intervention protocols and outcome measures. This scoping review highlights the heterogenous nature of research into scar massage following surgery and supports the need for further research to substantiate its use in the clinical setting.

Neural detection of changes in amplitude rise time in infancy.

Amplitude rise times play a crucial role in the perception of rhythm in speech, and reduced perceptual sensitivity to differences in rise time is related to developmental language difficulties. Amplitude rise times also play a mechanistic role in neural entrainment to the speech amplitude envelope. Using an ERP paradigm, here we examined for the first time whether infants at the ages of seven and eleven months exhibit an auditory mismatch response to changes in the rise times of simple repeating auditory stimuli. We found that infants exhibited a mismatch response (MMR) to all of the oddball rise times used for the study. The MMR was more positive at seven than eleven months of age. At eleven months, there was a shift to a mismatch negativity (MMN) that was more pronounced over left fronto-central electrodes. The MMR over right fronto-central electrodes was sensitive to the size of the difference in rise time. The results indicate that neural processing of changes in rise time is present at seven months, supporting the possibility that early speech processing is facilitated by neural sensitivity to these important acoustic cues.

Delta- and theta-band cortical tracking and phase-amplitude coupling to sung speech by infants.

The amplitude envelope of speech carries crucial low-frequency acoustic information that assists linguistic decoding at multiple time scales. Neurophysiological signals are known to track the amplitude envelope of adult-directed speech (ADS), particularly in the theta-band. Acoustic analysis of infant-directed speech (IDS) has revealed significantly greater modulation energy than ADS in an amplitude-modulation (AM) band centred on ∼2 Hz. Accordingly, cortical tracking of IDS by delta-band neural signals may be key to language acquisition. Speech also contains acoustic information within its higher-frequency bands (beta, gamma). Adult EEG and MEG studies reveal an oscillatory hierarchy, whereby low-frequency (delta, theta) neural phase dynamics temporally organize the amplitude of high-frequency signals (phase amplitude coupling, PAC). Whilst consensus is growing around the role of PAC in the matured adult brain, its role in the development of speech processing is unexplored. Here, we examined the presence and maturation of low-frequency (<12 Hz) cortical speech tracking in infants by recording EEG longitudinally from 60 participants when aged 4-, 7- and 11- months as they listened to nursery rhymes. After establishing stimulus-related neural signals in delta and theta, cortical tracking at each age was assessed in the delta, theta and alpha [control] bands using a multivariate temporal response function (mTRF) method. Delta-beta, delta-gamma, theta-beta and theta-gamma phase-amplitude coupling (PAC) was also assessed. Significant delta and theta but not alpha tracking was found. Significant PAC was present at all ages, with both delta and theta -driven coupling observed.

Machine learning accurately classifies neural responses to rhythmic speech vs. non-speech from 8-week-old infant EEG.

Currently there are no reliable means of identifying infants at-risk for later language disorders. Infant neural responses to rhythmic stimuli may offer a solution, as neural tracking of rhythm is atypical in children with developmental language disorders. However, infant brain recordings are noisy. As a first step to developing accurate neural biomarkers, we investigate whether infant brain responses to rhythmic stimuli can be classified reliably using EEG from 95 eight-week-old infants listening to natural stimuli (repeated syllables or drumbeats). Both Convolutional Neural Network (CNN) and Support Vector Machine (SVM) approaches were employed. Applied to one infant at a time, the CNN discriminated syllables from drumbeats with a mean AUC of 0.87, against two levels of noise. The SVM classified with AUC 0.95 and 0.86 respectively, showing reduced performance as noise increased. Our proof-of-concept modelling opens the way to the development of clinical biomarkers for language disorders related to rhythmic entrainment.

Minimal clinically important difference in walking velocity, gait profile score and two minute walk test for individuals with lower limb amputation.

BACKGROUND: Individuals with lower limb amputation are routinely assessed with a variety outcome measures, however there is a lack of published data to indicate minimal clinically important differences (MCID) for many of these outcome measures. Three such important gait-specific outcome measures include walking velocity, gait profile score (GPS) and the two minute walk test (2MWT). RESEARCH QUESTION: Determine the MCIDs for walking velocity, GPS and 2MWT for individuals with lower limb amputation. METHODS: Walking velocity and GPS (n = 60), and 2MWT (n = 119) data for individuals with unilateral transfemoral or knee disarticulation were identified retrospectively from a database held at the study centre. An anchor-based method was used with Medicare functional classification level (MFCL) acting as the impairment-related criterion, and a least-squares linear regression approach was used to calculate the gradient required for a change between MFCL levels. RESULTS: An increase of 0.21 m/s (95 % CI: 0.13,0.29) for walking velocity, a reduction of 1.7° (95 % CI: -2.449,-1.097) for GPS and an increase of 37.2 m (95 % CI: 28.8,45.5) for 2MWT were found to correspond to an increase in MFCL of one level. Walking velocity, GPS and 2MWT correlated with MFCL with R2 values of 0.333, 0.322 and 0.398 respectively (p < 0.00001). The authors propose that 0.21 m/s for walking velocity, 1.7° for GPS and 37.2 m for 2MWT be used as MCID values for individuals with lower limb amputation. SIGNIFICANCE: The results of this study can be used to help both researchers and clinicians to objectively evaluate if interventions for individuals with lower limb amputation are effective.