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INTRODUCTION: EMAST is a poorly understood form of microsatellite instability (MSI) in colorectal cancer (CRC) for which loss of MSH3 has been proposed as the underlying mechanism, based on experimental studies. We aimed to evaluate whether MSH3 loss is associated with EMAST in CRC. METHODS: A consecutive cohort of patients with stage I-III CRC. Digital image analysis using heatmap-derived hot spots investigated MSH3 expression by immunohistochemistry. Fragment analysis of multiplex PCR was used to assess MSI and EMAST, and results cross-examined with MSH3 protein expression. RESULTS: Of 152 patients, EMAST was found in 50 (33%) and exclusively in the colon. Most EMAST-positive cancers had instability at all 5 markers, and EMAST overlapped with MSI-H in 42/50 cases (84%). The most frequently altered tetranucleotide markers were D8S321 (38.2% of tumors) and D20S82 (34.4%). Subjective evaluation of MSH3 expression by IHC in tumor found ≤10% negative tumor cells in all samples, most being ≤5% negative. Digital analysis improved the detection but showed a similar spread of MSH3 loss (range 0.1–15.7%, mean 2.2%). Hotspot MSH3 negativity ranged between 0.1 to 95.0%, (mean 8.6%) with significant correlation with the whole slide analysis (Spearman's rho = 0.677 P

Phenotypic plasticity represents the most relevant hallmark of the carcinoma cell as it bestows it with the capacity of transiently altering its morphological and functional features while en route to the metastatic site. However, the study of phenotypic plasticity is hindered by the rarity of these events within primary lesions and by the lack of experimental models. Here, we identified a subpopulation of phenotypic plastic colon cancer cells: EpCAMlo cells are motile, invasive, chemo-resistant, and highly metastatic. EpCAMlo bulk and single-cell RNAseq analysis indicated (1) enhanced Wnt/β-catenin signaling, (2) a broad spectrum of degrees of epithelial to mesenchymal transition (EMT) activation including hybrid E/M states (partial EMT) with highly plastic features, and (3) high correlation with the CMS4 subtype, accounting for colon cancer cases with poor prognosis and a pronounced stromal component. Of note, a signature of genes specifically expressed in EpCAMlo cancer cells is highly predictive of overall survival in tumors other than CMS4, thus highlighting the relevance of quasi-mesenchymal tumor cells across the spectrum of colon cancers. Enhanced Wnt and the downstream EMT activation represent key events in eliciting phenotypic plasticity along the invasive front of primary colon carcinomas. Distinct sets of epithelial and mesenchymal genes define transcriptional trajectories through which state transitions arise. pEMT cells, often earmarked by the extracellular matrix glycoprotein SPARC together with nuclear ZEB1 and β-catenin along the invasive front of primary colon carcinomas, are predicted to represent the origin of these (de)differentiation routes through biologically distinct cellular states and to underlie the phenotypic plasticity of colon cancer cells.

Abstract The tumor-node-metastasis (TNM) system fails to accurately predict disease recurrence in a considerable number of patients. Although node-negative (stage II) colon cancer is considered to have an overall good prognosis, the 5-year cancer-specific survival is reported at 81–83% in patients who did not have adjuvant chemotherapy. Thus, reliance on node status alone has led to undertreatment in a subgroup of stage II patients with an unfavorable prognosis. The search for new and better prognosticators in stage II colon cancer has suggested several proposed biomarkers of better prognostication and prediction. However, few such biomarkers have reached widespread clinical utility. For the clinician swimming in the sea of emerging biomarkers, it may be hard to recognize the true floating aid from the surrounding debris in the search for more precise decision-making. Proposed markers include microsatellite instability (MSI) and KRAS and BRAF mutations, but a number of gene panels and consensus molecular subtypes are proposed for clinical prediction and prognostication as well. Although several studies suggest such biomarkers or panels to have a prognostic role in subgroups of patients, a number of studies are reported in heterogeneous groups with in part discordant findings, which again distorts the predictive and prognostic ability of each marker. Lack of homogeneous cohorts, underpowered studies in strict subgroups and challenges in analytical and clinical validity may hamper the progress toward widespread clinical utility. The harvest of prognostic biomarkers in colon cancer has yielded a huge number of candidates for which it is now time to separate the wheat from the chaff.

Background: Trials on neoadjuvant immunotherapy in operable colon cancer with deficient mismatch repair (dMMR) reported high pathological response rates in the surgical specimen, but long-term survival is not known. Neoadjuvant immunotherapy as a stand-alone therapy without subsequent radical surgery is currently not investigated in colon cancer., Objective: The aim of this study was to model outcomes between trial data and real-world patients after surgery., Methods: We conducted a comparative modeling study between prospective trial data (NICHE-1) and a prospective, population-derived, translational cohort study (ACROBATICC) of patients with operable colon cancer and microsatellite instability (MSI) status. Comparison was performed across immune-cell infiltrates, stages, MSI, and patient demographics for adverse events, reported oncological outcomes, and modeling numbers needed to treat (NNT) to prevent recurrence., Results: Patient characteristics between the dMMR tumors in the NICHE-1 (n = 21) and ACROBATICC (n = 43) cohorts differed, with older patients and fewer hereditary dMMRs in the 'real-life' ACROBATICC cohort. Higher expression of CD8+ in dMMR tumors compared with proficient mismatch repair (pMMR) tumors was statistically significant across both cohorts. At long-term follow-up, 2/43 patients with dMMR had died from recurrent colon cancer in the ACROBATICC cohort. Assuming a curative effect of neoadjuvant immunotherapy in addition to surgery in dMMR tumors, the NNT would be >20 patients for any additional survivor., Conclusion: In unselected patients with colon cancer having dMMR, recurrence risk is very low after surgery. Assuming a curative effect of neoadjuvant immunotherapy beyond surgery alone, the NNT would be at least 20 patients to prevent one cancer death over surgery alone., Competing Interests: Disclosure: Arezo Kanani, Torhild Veen, Dordi Lea, Claudia Zaharia, Martin Watson, Marina Alexeeva, Kenneth Thorsen, and Kjetil Søreide have reported no conflicts of interest that may be relevant to the contents of this study. Ethical approval: This study was approved by the institutional Ethics Committee, and informed consent was provided by all patients., (© 2025. The Author(s).)

Background/objective: Patient-derived organoids (PDOs) have emerged as essential for ex vivo modelling for pancreatic cancer (PDAC) but reports on efficacy and organoid take rate are scarce. This study aimed to assess the feasibility of establishing PDOs from resected specimens in periampullary tumors., Methods: Patients undergoing surgery for suspected periampullary cancer were included. PDO protocol amendments were tested, with organoid take rate as outcome measure. Samples from resected specimens were processed and expanded per protocol. Pooled estimate of take rates of PDOs in PDAC was derived from literature search., Results: 23 specimens were available for PDO, of which 10 were PDAC. In 15 patients other histopathology was found: neuroendocrine tumors (NET; n = 2), neuroendocrine carcinoma (NEC; n = 1), intraductal papillary mucinous neoplasm (IPMN; n = 4), distal cholangiocarcinoma (dCCA; n = 1), ampullary carcinoma (n = 1), duodenal carcinoma (n = 1), intra-ampullary papillary tubular neoplasm (IAPN; n = 1), indeterminate PDAC/ampullary carcinoma(n = 1), and one patient with chronic inflammation/fibrosis. Organoid cultures were grown from 7 of 10 (70 %) PDAC, 1 dCCA, 1 NEC, 1 duodenal carcinoma, 1 indeterminate tumor type and 1 ampullary carcinoma (i.e. 12/18; 66.7 % across periampullary cancers). Overall take rate of PDOs was 12 of 23 (52.2 %) for all tumors. A pooled mean estimate PDO take rate of 62.3 % (95 % CI:54.8-69.3 %) was reported across available studies in the literature., Conclusion: In the current study, we found that PDOs could be established from resected pancreatic tumors in over half of resected periampullary tumors, and highest in PDACs. As such, generating a pancreatic cancer PDO biobank for translational research was feasible after cryopreservation., Competing Interests: Conflict of interest None of the authors have any conflicts of interest to report., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background/aims: Contact lens-associated keratitis (CLAK) is a common sight-threatening complication of contact lens use. Current management protocols in the UK are based on historical practice and necessitate a review for every patient within 48 hours regardless of severity, increasing the treatment burden on a resource-limited healthcare service. Our study aims to identify the different risk factors associated with CLAK, categorise CLAK using a novel grading system and recommend modifications to current management protocols based on the outcomes in the individual subgroups., Methods: The retrospective cohort study identified 161 eyes from 153 patients with CLAK from the electronic patient records of a tertiary eye centre between 1 July 2021 and 28 February 2022. Patients were categorised based on epithelial defect size (grade 1: <1.0 mm, grade 2: 1.0-2.0 mm, grade 3: >2.0 mm) and their risk factors, clinical features, treatments and outcomes were analysed., Results: The most significant risk factors for CLAK include extended-wear contact lens, poor hygiene and prolonged duration of wear. Grades 1 and 2 CLAKs have excellent outcomes following an empirical treatment regime with topical moxifloxacin with 96% discharged within 48 hours and 94.1% discharged in 2 weeks, respectively. Grade 3 CLAKs require prolonged average duration of treatment., Conclusion: We recommend typical grade 1 and 2 CLAKs can be discharged with empirical fluoroquinolone treatment. Grade 3 and all CLAKs with atypical features require monitoring for resolution, further diagnostics or treatment. We provide an evidence-based approach to reduce unnecessary patient visits and optimise resource allocation in an urban setting., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Acanthamoeba keratitis (AK) is a rare but severe eye disease. A research engagement event, "The Cornea Day," in London, UK in 2013, identified the lack of credible information about AK and a need for practical day to day management strategies. Experiences of 15 AK patients attending The Cornea Day were distilled into a survey that was administered to a wider group of 76 patients, carers, researchers, and clinicians. A Patient Information Leaflet was cocreated and then represented to additional patients for final modification. The AK Patient Leaflet (revised 2019) is available in several languages and used globally., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Background: In colon cancer, the location and density of tumor-infiltrating lymphocytes (TILs) can classify patients into low and high-risk groups for prognostication. While a commercially available 'Immunoscore ® ' exists, the incurred expenses and copyrights may prevent universal use. The aim of this study was to develop a robust and objective quantification method of TILs in colon cancer., Methods: A consecutive, unselected series of specimens from patients with colon cancer were available for immunohistochemistry and assessment of TILs by automated digital pathology. CD3 + and CD8 + cells at the invasive margin and in tumor center were assessed on consecutive sections using automated digital pathology and image analysis software (Visiopharm ® ). An algorithm template for whole slide assessment, generated cell counts per square millimeters (cells/mm 2 ), from which the immune score was calculated using distribution volumes. Furthermore, immune score was compared with clinical and histopathological characteristics to confirm its relevance., Results: Based on the quantified TILs numbers by digital image analyses, patients were classified into low (n = 83, 69.7%), intermediate (n = 14, 11.8%) and high (n = 22, 18.5%) immune score groups. High immune score was associated with stage I-II tumors (p = 0.017) and a higher prevalence of microsatellite instable (MSI) tumors (p = 0.030). MSI tumors had a significantly higher numbers of CD3 + TILs in the invasive margin and CD8 + TILs in both tumor center and invasive margin, compared to microsatellite stable (MSS) tumors., Conclusion: A digital template to quantify an easy-to-use immune score corresponds with clinicopathological features and MSI in colon cancer.

Purpose: Moorfields Eye Hospital sits as a major tertiary centre for ophthalmic care in the United Kingdom and became a central hub to provide safe and effective ophthalmic care across London and surrounding regions during the COVID-19 pandemic. We explore the impact on both the acute and elective corneal services during the first wave of this pandemic., Methods: A retrospective review of the proportion of corneal transplants and anterior segment trauma repairs was performed during the period of March 23rd to July 1st 2020 compared with an identical period in 2019. Data were acquired from our in-house electronic patient records., Results: A 92% reduction in corneal elective work was observed during the lockdown period compared with an identical period in 2019, with only 10 elective cases in total being performed. In addition, 91 corneal cross-linking and 76 therapeutic lasers were cancelled. There were 15 cases of primary repair for anterior segment trauma compared with 6 cases pre-COVID-19. A similar scenario occurs with removal of foreign body (4 cases during COVID-19 period versus no cases during pre-COVID-19 era) and with traumatic lens aspirations (6 cases during COVID-19 compared with 2 pre-COVID-19). Interestingly, a statistical difference (p=0.03) was found in the time interval from presentation of symptoms to emergency corneal surgery. During the COVID-19 period, a delay of 1.5 days ± 2.29 (range 0-10 days) occurred compared with 0.8 days ± 1.54 (range 0-6 days) pre-COVID-19., Conclusion: Stringent risk stratification reduced elective corneal surgery capacity during the lockdown thereby preserving social distancing requirements. However, an apparent increase in emergency corneal surgery seen is likely attributed to centralisation of ophthalmic services during the pandemic crisis, alongside increased domestic injuries. Despite the challenges posed, successful delivery of corneal surgery occurred whilst helping to identify lessons in preparations for future pandemics and current inefficiencies in healthcare delivery., Competing Interests: None of the authors have any proprietary interests or conflicts of interest related to this paper., (© 2021 Din et al.)

We describe a case of bilateral spontaneous corneal perforation secondary to pellucid marginal degeneration and present the associated swept-source anterior segment optical coherence tomography (SS-ASOCT) findings and management principles used. A 47-year-old woman presented with ocular pain, redness, foreign body sensation and clear discharge in the right eye in 2017 and with very similar symptoms in 2019 in the left eye. Clinically she had a corneal perforation at the inferior cornea with associated loss of anterior chamber volume. Corneal topography demonstrated peripheral thinning and steepening in the contralateral eye. ASOCT images revealed full-thickness perforation, iridocorneal touch and iris stranding. The patient was managed with a combination of contact bandaging and corneal gluing. SS-ASOCT is a useful adjunctive tool in the clinical assessment and evaluation of spontaneous corneal perforation. Alongside the clinical evaluation, it can be used to monitor the clinical response., (© The Author(s) 2020. Published by Oxford University Press.)

Background: Functional Strength Training (FST) could enhance recovery late after stroke. The aim of this study was to evaluate the feasibility of a subsequent fully powered, randomized controlled trial., Methods: The study was designed as a randomized, observer-blind trial. Both interventions were provided for up to one hour a day, four days a week, for six weeks. Evaluation points were before randomization (baseline), after six weeks intervention (outcome), and six weeks thereafter (follow-up). The study took place in participants' own homes. Participants (n = 52) were a mean of 24.4 months after stroke with a mean age of 68.3 years with 67.3% male. All had difficulty using their paretic upper (UL) and lower limb (LL). Participants were allocated to FST-UL or FST-LL by an independent randomization service. The outcome measures were recruitment rate, attrition rate, practicality of recruitment strategies, occurrence of adverse reactions, acceptability of FST, and estimation of sample size for a subsequent trial. Primary clinical efficacy outcomes were the Action Research Arm Test (ARAT) and the Functional Ambulation Categories (FAC). Analysis was conducted using descriptive statistics and thematic analysis of participants' views of FST. A power calculation used estimates of clinical efficacy variance to estimate sample size for a subsequent trial., Results: The screening process identified 1,127 stroke survivors of whom 52 (4.6%) were recruited. The recruitment rate was higher for referral from community therapists than for systematic identification of people discharged from an acute stroke unit. The attrition rate was 15.5% at the outcome and follow-up time-points. None of the participants experienced an adverse reaction. The participants who remained in the study at outcome had received 68% of the total possible amount of therapy. Participants reported that their experience of FST provided a sense of purpose and involvement and increased their confidence in performing activities. The power calculation provides estimation that 150 participants in each group will be required for a subsequent clinical trial., Conclusions: This study found that a subsequent clinical trial was feasible with modifications to the recruitment strategy to be used., Trial Registration: Controlled-trials.com ISCTN71632550, 30 January 2009.

In a laboratory setting where both a mechanically-braked cycling ergometer and a motion analysis (MA) system are available, flywheel angular displacement can be estimated by using MA. The purpose of this investigation was to assess the validity and reliability of a MA method for measuring maximal power output (Pmax) in comparison with a force transducer (FT) method. Eight males and eight females undertook three identical sessions, separated by 4 to 6 days; the first being a familiarization session. Individuals performed three 6-second sprints against 50% of the maximal resistance to complete two pedal revolutions with a 3-minute rest between trials. Power was determined independently using both MA and FT analyses. Validity: MA recorded significantly higher Pmax than FT (P < .05). Bland-Altman plots showed that there was a systematic bias in the difference between the measures of the two systems. This difference increased as power increased. Repeatability: Intraclass correlation coefficients were on average 0.90 ± 0.05 in males and 0.85 ± 0.08 in females. Measuring Pmax by MA, therefore, is as appropriate for use in exercise physiology research as Pmax measured by FT, provided that a bias between these measurements methods is allowed for.

Objective: To evaluate whether autologous conditioned plasma offers any therapeutic advantage over ultrasound-guided dry needling as a stand-alone procedure in the treatment of refractory lateral epicondylitis., Materials and Methods: Prospective, randomized pilot study of 28 patients (11 men, 17 women, mean age, 49.1  years) with refractory lateral epicondylitis (mean symptom duration, 19.1 months) who underwent either dry needling (n = 13) or dry needling combined with autologous conditioned plasma (ACP) injection (n = 15). Each patient received two separate injections (0 weeks and 1 month) and analysis of visual analogue pain scores (VAS) and Nirschl scores were performed pre-procedure, at 2 months and final evaluation at 6 months. Successful treatment was defined as more than a 25 % reduction in pain scores without re-intervention. Data was analyzed using the Mann-Whitney test and local research ethics committee approval was obtained., Results: At 2 months, the mean VAS improvement was 0.85 (12.3 %) in the dry needling group compared to 2.19 (27.1 %) in the ACP group (p = 0.76) and there was a 5.83-point and 20.3-point Nirschl score improvement respectively (p = 0.72). At the final follow-up of 6 months, the mean VAS improvement was 2.37 (34 %) in the dry needling group compared to 3.92 (48.5 %) in the ACP group (p = 0.74) and there was a 22.5-point and 40-point Nirschl score improvement, respectively (p = 0.82)., Conclusions: There is a trend to greater clinical improvement in the short term for patients treated with additional ACP, however no significant difference between the two treatment groups was demonstrated at each follow-up interval. A larger, multicenter, randomized controlled trial is required to corroborate the results of this pilot study.

Background: Clinical and radiographic diagnoses of scaphoid fractures are often challenging at the time of injury. Patients are therefore usually reassessed which has cost implications. Various investigations exist but MRI has been suggested as effective in diagnosing these injuries early., Aim: To determine whether early MRI in suspected occult scaphoid fractures is more clinically and cost effective than conventional management with immobilisation and reassessment., Methods: All patients presenting to the Emergency Department at a district general hospital with a suspected occult scaphoid fracture were randomised into two groups, MRI (early scan of the wrist, discharged if no injury) and control (reassessment in clinic)., Results: 84 patients were randomised into MRI (45) and control (39) groups. There were no baseline differences apart from greater dominant hand injuries in the MRI group (62% (26) vs 36% (14), p=0.02). There were three (6.7%) scaphoid fractures in the MRI group and four (10.3%) in the control group (p=0.7). More fractures (15.6% (7) vs 5.1% (2), p=0.9) and other injuries were detected in the MRI group who had fewer mean clinic appointments (1.1 ± 0.5 vs 2.3 ± 0.8, p=0.001) and radiographs (1.2 ± 0.8 vs 1.7 ± 1.1, p=0.03). Mean management costs were £504.13 (MRI) and £532.87 (control) (p=0.9). The MRI group had better pain and satisfaction scores (not significant) with comparable time off work and sporting activities., Conclusion: Early MRI in occult scaphoid fractures is marginally cost saving compared with conventional management and may reduce potentially large societal costs of unnecessary immobilisation. It enables early detection and appropriate treatment of scaphoid and other injuries.

Objective: The purpose of the study was to determine if the thickness of the subacromial-subdeltoid (SASD) bursa during dynamic ultrasound and on static views differs between patients with shoulder impingement syndrome and healthy volunteers., Materials and Methods: Twenty-two patients with a clinical diagnosis of shoulder impingement syndrome and 23 healthy volunteers were recruited. A subset of patients showing an immediate symptom response following intrabursal injection was identified as "injection responders". Ultrasound of the shoulder was performed on all participants using three standard static views and two dynamic views (before and after arm abduction). The thickness of both the intrabursal fluid and the superficial peribursal fat was measured on all views. The bursal thickness measurements in the two groups were compared using a t test for significance., Results: The mean increase in SASD bursal fluid thickness following arm abduction was not statistically different among all patients (0.39 ± 0.41 mm) and controls (0.35 ± 0.32 mm), p = 0.72. The same was true comparing injection responders (0.46 ± 0.49 mm) with controls, p = 0.41. On static views, greater bursal fluid thickness was found in patients (1.01 ± 0.48 mm) compared with controls (0.67 ± 0.32 mm) when using the short axis view of the supraspinatus, p = 0.006. No statistically significant difference was found between injection responders and controls when measuring peribursal fat thickness on any view., Conclusions: Gathering of the SASD bursa demonstrated during dynamic ultrasound does not necessarily indicate painful impingement of the bursa as it is found to a similar degree in patients with a clinical diagnosis of impingement and healthy volunteers.

Purpose: Acute knee injury is common, and MRI is often only used when non-operative management fails because of limited availability. We investigated whether early MRI in acute knee injury is more clinically and cost-effective compared to conventional physiotherapy and reassessment., Methods: All patients with acute indirect soft tissue knee injury referred to fracture clinic were approached. Recruited patients were randomised to either the MRI group: early MRI within 2 weeks or the control group: conventional management with physiotherapy. Patients were assessed in clinic initially, at 2 weeks and 3 months post-injury. Management costs were calculated for all patients until surgical treatment or discharge., Results: Forty-six patients were recruited: 23 in the MRI and 23 in the control group. Male sex and mean age were similar in the two groups. The total management cost of the MRI group was £16,127 and control group was £16,170, with a similar mean cost per patient (NS). The MRI group had less mean physiotherapy (2.5 ± 1.9 vs. 5.1 ± 3.5, p < 0.01) and outpatient appointments (NS). Median time to surgery and time off work was less in the MRI group (NS). The MRI group had less pain (p < 0.05), less activity limitation (p = 0.04) and better satisfaction (p = 0.04)., Conclusions: Early MRI in acute knee injury facilitates faster diagnosis and management of internal derangement at a cost comparable to conventional treatment. Moreover, patients had significantly less time off work with improved pain, activity limitation and satisfaction scores., Level of Evidence: II.

Poly(ADP-ribose) glycohydrolase (PARG) is the only enzyme known to catalyse hydrolysis of the O-glycosidic linkages of ADP-ribose polymers, thereby reversing the effects of poly(ADP-ribose) polymerases. PARG deficiency leads to cell death whilst PARG depletion causes sensitisation to certain DNA damaging agents, implicating PARG as a potential therapeutic target in several disease areas. Efforts to develop small molecule inhibitors of PARG activity have until recently been hampered by a lack of structural information on PARG. We have used a combination of bio-informatic and experimental approaches to engineer a crystallisable, catalytically active fragment of human PARG (hPARG). Here, we present high-resolution structures of the catalytic domain of hPARG in unliganded form and in complex with three inhibitors: ADP-ribose (ADPR), adenosine 5'-diphosphate (hydroxymethyl)pyrrolidinediol (ADP-HPD) and 8-n-octyl-amino-ADP-HPD. Our structures confirm conservation of overall fold amongst mammalian PARG glycohydrolase domains, whilst revealing additional flexible regions in the catalytic site. These new structures rationalise a body of published mutational data and the reported structure-activity relationship for ADP-HPD based PARG inhibitors. In addition, we have developed and used biochemical, isothermal titration calorimetry and surface plasmon resonance assays to characterise the binding of inhibitors to our PARG protein, thus providing a starting point for the design of new inhibitors.

This phase 1 exploratory study aimed to establish proof of concept of the effects of dynamic elastomeric fabric orthoses (DEFOs) on the gait of children with spastic diplegic cerebral palsy. Replicated single case experiments employing an ABA methodology were carried out on eight subjects (median age 5.5 years, range 3-13 years; 4 girls/boys) utilizing quantitative/qualitative data collection. Outcome measures were: Ten metre walking test (10MWT); physiological cost index (PCI); visual analogue scale (VAS) scoring of perceived gait changes; functional mobility changes using Patient Specific Functional Scale (PSFS); subject/carer perceptions recorded in daily diaries. Results identified following analysis of quantitative data indicated a treatment effect from the orthoses which could be corroborated by participant subjective impressions and comments. Statistically significant (p < 0.05) intervention-related improvements in gait velocity and gait consistency were identified respectively in 5/8 and 4/8 subjects. Power calculations support the feasibility of a larger controlled study to further investigate this orthotic intervention. This study indicates that DEFO leggings can confer beneficial effects on the gait of some children with spastic diplegia resulting from CP. These findings have implications for orthotic intervention with this subject group.

Building block methodology from trifluoroethanol and ring-closing metathesis using a Fürstner modification of Grubbs' conditions allows the rapid synthesis of novel difluorinated cyclooctenones.