The importance of 3D fibre architecture in cancer and implications for biomaterial model design.

The need for improved prediction of clinical response is driving the development of cancer models with enhanced physiological relevance. A new concept of 'precision biomaterials' is emerging, encompassing patient-mimetic biomaterial models that seek to accurately detect, treat and model cancer by faithfully recapitulating key microenvironmental characteristics. Despite recent advances allowing tissue-mimetic stiffness and molecular composition to be replicated in vitro, approaches for reproducing the 3D fibre architectures found in tumour extracellular matrix (ECM) remain relatively unexplored. Although the precise influences of patient-specific fibre architecture are unclear, we summarize the known roles of tumour fibre architecture, underlining their implications in cell-matrix interactions and ultimately clinical outcome. We then explore the challenges in reproducing tissue-specific 3D fibre architecture(s) in vitro, highlighting relevant biomaterial fabrication techniques and their benefits and limitations. Finally, we discuss imaging and image analysis techniques (focussing on collagen I-optimized approaches) that could hold the key to mapping tumour-specific ECM into high-fidelity biomaterial models. We anticipate that an interdisciplinary approach, combining materials science, cancer research and image analysis, will elucidate the role of 3D fibre architecture in tumour development, leading to the next generation of patient-mimetic models for mechanistic studies and drug discovery.

1†Retreatment for reactivation of ROP following initial anti-VEGF injections. A 5-year retrospective study.

To present the retreatment rates and the characteristics of ROP reactivation, as well as the differences between bevacizumab and ranibizumab injections in premature babies treated in our department over the past 5 years.A retrospective analysis of babies with treated ROP was performed. 89 babies who required treatment from 2017 to 2022 were examined. We studied the severity of their disease with regards to their gestational age, treatment time and type and the need of further treatment. We also focused on the comparison of anti-VEGF agents for ROP.22 out of 89 babies (14 boys and 8 girls) with aggressive posterior retinopathy of prematurity (APROP) and mean gestational age of 25+3w received initially anti-VEGF injections. 16 of those (11 boys and 5 girls) required retreatment with diode laser. 9 out of these 16 babies were treated with ranibizumab (Lucentis) and 7 with bevacizumab (Avastin). It is also of note that only 2 out of 67 babies who initially received laser treatment needed a complementary laser session.The majority of babies with aggressive ROP who receive anti-VEGF agents will most probably require further laser treatment. At an equal level of retinal damage, it seems that their response to ranibizumab and bevacizumab is similar.

2†Pathways to detection of non-infectious childhood uveitis in the UK: findings from the UNICORN cohort study.

INTRODUCTION: Prompt detection of childhood uveitis is key to minimising negative impact. From an internationally unique inception cohort, we report pathways to disease detection.UNICORNS is a national childhood non-infectious uveitis study with longitudinal collection of a standardised clinical dataset and patient reported outcomes. Descriptive analysis of baseline characteristics are reported.Amongst 150 recruited children (51% female, 31% non-white ethnicity) age at detection ranged from 2-18yrs (median 10). In 69%, uveitis was diagnosed following onset of symptoms: time from first symptoms to uveitis detection ranged from 0-739days (median 7days), with longer time to detection for those presenting initially to their general practitioner. Non symptomatic children were detected through JIA/other disease surveillance (16%), routine optometry review (5%) or child visual health screening (1%). Commonest underlying diagnoses at uveitis detection were JIA (17%), TINU (9%, higher than pre-pandemic reported UK disease frequency) and sarcoid (1%). 60% had no known systemic disease at uveitis detection. At disease detection, in at least one eye: 34% had structural complications (associated with greater time to detection - 17 days versus 4 days for uncomplicated presentation).The larger relative proportions of children with non-JIA uveitis reported here increase the importance of improving awareness of childhood uveitis amongst the wider clinical communities. There is scope for improvement of pathways to detection. Forthcoming analysis on the full cohort (251 recruited to date across 33 hospitals and 4 nations) will provide nationally representative data on management and the determinants of visual and broader developmental/well-being outcomes.

Cefaleas primarias con inicio en la infancia y la adolescencia: historia natural y factores pronósticos en una población portuguesa / Primary headache with onset in childhood and adolescence: natural history and prognostic factors in a Portuguese population

Introducción: Las cefaleas son el trastorno neurológico más habitual en la población pediátrica e influyen notablemente en su calidad de vida. La finalidad de este estudio es caracterizar una cohorte de pacientes en seguimiento en una unidad de neurología pediátrica entre el 1 de enero de 2013 y el 31 de diciembre de 2021. Materiales y métodos: Hemos revisado informes médicos y seleccionado a pacientes con cefaleas primarias y un seguimiento mínimo de 12 meses.Resultados: Se incluyó a un total de 226 pacientes, el 54,4% mujeres, con una media de edad al comenzar las cefaleas de 9 ± 3,5 (3,1-16,5) años; el 63,5% eran prepuberales. Se identificó un historial familiar positivo de cefalea en el 76,6% de los casos y factores desencadenantes en el 63,6%. En una primera evaluación clínica, el 45,1% se identificó como migrañas sin aura; el 10,6%, como migrañas con aura; el 3,5%, como cefalea tensional; el 8%, como de tipo mixto (cefalea tensional y migraña); el 1,3%, de otro tipo; y el 31,4% resultó inclasificable. Los pacientes se sometieron a un seguimiento promedio de 2,4 (1,8-3,3) años. El diagnóstico de cefalea tensional se mantuvo estable en el 75% de los pacientes y se solucionó en un 25%; para el 13% de los pacientes con migraña sin aura, el diagnóstico cambió a otro tipo de cefalea, y para el 17,4%, se solucionó; para el 44,4% de los pacientes sin migraña con aura, el diagnóstico cambió por el de otro tipo de cefalea, y para el 11,1%, se resolvió. De las variables estudiadas, sólo la duración del episodio de cefalea tuvo una asociación significativa con la remisión de la cefalea, con una odds ratio de 0,16 (p = 0,03; intervalo de confianza al 95%: 0,032-0,84).Conclusiones: Nuestro estudio muestra que el tipo de cefalea en la población pediátrica cambia con el paso del tiempo, especialmente en los pacientes con migraña con aura. La duración de cada uno de los episodios de cefalea se presentó como un predictor de la remisión de la cefalea con el paso del...(AU)

Introduction: Headaches are the most frequent neurological disorder in the pediatric population, with great impact on quality of life. This study aims to characterize a cohort of patients followed at a pediatric neurology unit between January 1st 2013 and December 31st, 2021. Materials and methods: We reviewed medical records and selected patients with primary headaches and a minimum follow-up of 12 months. Results: A total of 226 patients were included, 54.4% female, with an average age at headache onset of 9 ± 3.5 (3.1-16.5) years; 63.5% were prepubertal. A positive family history of headache was identified in 76.6% of cases and triggers in 63.6%. At first clinical assessment, 45.1% were classified as migraine without aura, 10.6% as migraine with aura, 3.5% tension-type, 8% mixed (tension and migraine), 1.3% other type and 31.4% were unclassifiable. The patients had a median follow-up of 2.4 (1.8-3.3) years. The diagnosis of tension-type headaches remained stable in 75% of the patients and resolved in 25%; 13% of the patients with migraine without aura changed into another type of headache and 17.4% resolved; 44.4% of the patients with migraine with aura turned into another type of headache and 11.1% resolved. Of the variables studied, only duration of headache episode had a significant association with headache remission, with odds ratio 0.16 (p = 0.03; 95% confidence interval: 0.032-0.84).Conclusions: Our study shows that headache type in pediatric population changes over time, especially in those with migraine with aura. The duration of each headache episode was presented as a predictor of headache remission over time.(AU)

Primary headache with onset in childhood and adolescence: natural history and prognostic factors in a Portuguese population. / Cefaleas primarias con inicio en la infancia y la adolescencia: historia natural y factores pronósticos en una población portuguesa.

INTRODUCTION: Headaches are the most frequent neurological disorder in the pediatric population, with great impact on quality of life. This study aims to characterize a cohort of patients followed at a pediatric neurology unit between January 1st 2013 and December 31st, 2021. MATERIALS AND METHODS: We reviewed medical records and selected patients with primary headaches and a minimum follow-up of 12 months. RESULTS: A total of 226 patients were included, 54.4% female, with an average age at headache onset of 9 ± 3.5 (3.1-16.5) years; 63.5% were prepubertal. A positive family history of headache was identified in 76.6% of cases and triggers in 63.6%. At first clinical assessment, 45.1% were classified as migraine without aura, 10.6% as migraine with aura, 3.5% tension-type, 8% mixed (tension and migraine), 1.3% other type and 31.4% were unclassifiable. The patients had a median follow-up of 2.4 (1.8-3.3) years. The diagnosis of tension-type headaches remained stable in 75% of the patients and resolved in 25%; 13% of the patients with migraine without aura changed into another type of headache and 17.4% resolved; 44.4% of the patients with migraine with aura turned into another type of headache and 11.1% resolved. Of the variables studied, only duration of headache episode had a significant association with headache remission, with odds ratio 0.16 (p = 0.03; 95% confidence interval: 0.032-0.84). CONCLUSIONS: Our study shows that headache type in pediatric population changes over time, especially in those with migraine with aura. The duration of each headache episode was presented as a predictor of headache remission over time.

TITLE: Cefaleas primarias con inicio en la infancia y la adolescencia: historia natural y factores pronósticos en una población portuguesa.Introducción. Las cefaleas son el trastorno neurológico más habitual en la población pediátrica e influyen notablemente en su calidad de vida. La finalidad de este estudio es caracterizar una cohorte de pacientes en seguimiento en una unidad de neurología pediátrica entre el 1 de enero de 2013 y el 31 de diciembre de 2021. Materiales y métodos. Hemos revisado informes médicos y seleccionado a pacientes con dolores de cabeza primarios y un seguimiento mínimo de 12 meses. Resultados. Se incluyó a un total de 226 pacientes, el 54,4% mujeres, con una media de edad al comenzar las cefaleas de 9 ± 3,5 (3,1-16,5) años; el 63,5% eran prepuberales. Se identificó un historial familiar positivo de cefalea en el 76,6% de los casos y factores desencadenantes en el 63,6%. En una primera evaluación clínica, el 45,1% se identificó como migrañas sin aura; el 10,6%, como migrañas con aura; el 3,5%, como cefalea tensional; el 8%, como de tipo mixto (cefalea tensional y migraña); el 1,3%, de otro tipo; y el 31,4% resultó inclasificable. Los pacientes se sometieron a un seguimiento promedio de 2,4 (1,8-3,3) años. El diagnóstico de cefalea tensional se mantuvo estable en el 75% de los pacientes y se solucionó en un 25%; para el 13% de los pacientes con migraña sin aura, el diagnóstico cambió a otro tipo de cefalea, y para el 17,4%, se solucionó; para el 44,4% de los pacientes sin migraña con aura, el diagnóstico cambió por el de otro tipo de cefalea, y para el 11,1%, se resolvió. De las variables estudiadas, sólo la duración del episodio de cefalea tuvo una asociación significativa con la remisión de la cefalea, con una odds ratio de 0,16 (p = 0,03; intervalo de confianza al 95%: 0,032-0,84). Conclusiones. Nuestro estudio muestra que el tipo de cefalea en la población pediátrica cambia con el paso del tiempo, especialmente en los pacientes con migraña con aura. La duración de cada uno de los episodios de cefalea se presentó como un predictor de la remisión de la cefalea con el paso del tiempo.

A scoping review of clinical practices and adherence to UK national guidance related to the placement and position confirmation of adult nasogastric feeding tubes.

INTRODUCTION: The administration of nutrition or medication into the lungs or pleura via a misplaced nasogastric feeding tube is considered a never event. Despite guidance from the National Patient Safety Agency and NHS Improvement this never event is regularly reported. Confirmation of correct placement and correct use of nasogastric tubes requires appropriate actions and decisions by a multidisciplinary team. METHODS: A scoping review identified 43 records that discussed and supported nasogastric tube misplacement as a Never Event. Searches were completed using Web of Science, CINAHL, Google Scholar, British Nursing Index (BNI), as well as selected journals. A further manual search revealed 22 publicly available NHS Trust policies related to nasogastric feeding tube procedures. Items generated between 2011 and 2020 were considered eligible. A thematic analysis was completed to assess adherence to guidance and the practices in place across the NHS. RESULTS: Three key themes were identified as part of the review: referral and authorisation of radiography, examination description, and visualisation of the nasogastric tube tip. Large variations in practice were identified. While there is recognition of national guidance, records showed inconsistency and lacked the required detail to ensure patient safety. CONCLUSION: Despite classification as a never event, it is apparent that there is still room for improvement and further guidance in ensuring patient safety with respect to nasogastric tube insertion. IMPLICATIONS FOR PRACTICE: Practice requires further standardisation whilst also ensuring optimisation and safety. Guidance should address in depth imaging authorisation, language and exact standards of acceptability for imaging the full length of the nasogastric tube.

MPS VII - Extending the classical phenotype.

Mucopolysaccharidosis VII (or Sly syndrome) is an autosomal recessive disorder characterised by a deficiency in the enzyme Beta-glucuronidase (GUSB). Partial degradation of glycosaminoglycans (GAGs); chondroitin sulfate (CS), dermatan sulfate (DS) and heparan sulfate (HS) results in the accumulation of these fragments in the lysosomes of many tissues, eventually leading to multisystem damage. In some cases, early diagnosis on clinical grounds alone can be difficult due to the extreme variability of the clinical presentation and disease progression. We present a case report of a 31-year-old male patient diagnosed with MPS VII at the age of 28, who multiple specialists saw without suspecting the diagnosis due to the unusual presentation. The patient presented with a history of developmental delay, scoliosis, kyphosis, corneal clouding, abnormal gait, short stature, hearing impairment, slightly coarse facial features and progressive deterioration of fine motor skills since childhood. The patient had inguinal hernia repair at around 12 months, bilateral hearing impairment with a left bone-anchored hearing aid, and spinal surgery. During spinal surveillance MPS VII was suspected by a spinal surgeon with interest in MPS, and the diagnosis confirmed with a deficiency in beta-glucuronidase in leucocytes and marginally elevated urinary GAGs. Next-generation sequencing identified two mutations in the GUSB gene (OMIM 611499), c.526C > T p.(Leu176Phe) and c.1820G > C p.(Gly607Ala). Although the patient exhibited features of the severe form of non-classical manifestations, his metabolic condition has remained reasonably stable, surviving into adulthood with only symptomatic treatment. We present the ever-expanding phenotypic spectrum of this ultra-rare disease.

Cataract management in children: a review of the literature and current practice across five large UK centres.

Congenital and childhood cataracts are uncommon but regularly seen in the clinics of most paediatric ophthalmology teams in the UK. They are often associated with profound visual loss and a large proportion have a genetic aetiology, some with significant extra-ocular comorbidities. Optimal diagnosis and treatment typically require close collaboration within multidisciplinary teams. Surgery remains the mainstay of treatment. A variety of surgical techniques, timings of intervention and options for optical correction have been advocated making management seem complex for those seeing affected children infrequently. This paper summarises the proceedings of two recent RCOphth paediatric cataract study days, provides a literature review and describes the current UK 'state of play' in the management of paediatric cataracts.

Peptide gels of fully-defined composition and mechanics for probing cell-cell and cell-matrix interactions in vitro.

Current materials used for in vitro 3D cell culture are often limited by their poor similarity to human tissue, batch-to-batch variability and complexity of composition and manufacture. Here, we present a "blank slate" culture environment based on a self-assembling peptide gel free from matrix motifs. The gel can be customised by incorporating matrix components selected to match the target tissue, with independent control of mechanical properties. Therefore the matrix components are restricted to those specifically added, or those synthesised by encapsulated cells. The flexible 3D culture platform provides full control over biochemical and physical properties, allowing the impact of biochemical composition and tissue mechanics to be separately evaluated in vitro. Here, we demonstrate that the peptide gels support the growth of a range of cells including human induced pluripotent stem cells and human cancer cell lines. Furthermore, we present proof-of-concept that the peptide gels can be used to build disease-relevant models. Controlling the peptide gelator concentration allows peptide gel stiffness to be matched to normal breast (<1 kPa) or breast tumour tissue (>1 kPa), with higher stiffness favouring the viability of breast cancer cells over normal breast cells. In parallel, the peptide gels may be modified with matrix components relevant to human breast, such as collagen I and hyaluronan. The choice and concentration of these additions affect the size, shape and organisation of breast epithelial cell structures formed in co-culture with fibroblasts. This system therefore provides a means of unravelling the individual influences of matrix, mechanical properties and cell-cell interactions in cancer and other diseases.

Congenital cataracts in females caused by BCOR mutations; report of six further families demonstrating clinical variability and diverse genetic mechanisms.

BACKGROUND: Pathogenic variants in the BCOR gene have been identified in males with X-linked recessive microphthalmia and in females with X-linked dominant oculofaciocardiodental (OFCD) syndrome. This latter condition has previously been regarded as rare but the increased availability of genetic testing in recent years has led to the identification of a greater number of patients. METHODS: We report the clinical and molecular findings in a series of 10 patients with pathogenic BCOR variants from 5 families, all seen in a single institution over a two year period. RESULTS: We emphasize the phenotypic variability in this cohort and the diverse genetic mechanisms involved which included point mutations and deletions of BCOR as well as the occurrence of gonadal and somatic mosaicism. CONCLUSION: In this report we demonstrate the novel findings of four newly identified variants in BCOR associated with an OFCD phenotype, and suggest that the frequency of this condition in females presenting with congenital cataract, including unilateral cataract, is more common than anticipated. We demonstrate the utility of screening for genetic causes of congenital cataract. Although gonadal mosaicism in OFCD had previously been reported, we demonstrate the presence of somatic mosaicism where BCOR mutations may only be detected in DNA from tissues other than blood such as buccal cells.

Learning to look: Evaluating the student experience of an interactive image appraisal activity.

INTRODUCTION: Student radiographers have expressed difficulty in performing image appraisal tasks. The purpose of this study was to investigate the value of a workshop delivered to level 4 undergraduate students. All students completed an image appraisal activity, inputting their appraisal into software that displayed their response alongside an expert opinion. They were asked to identify and discuss any discrepancy. METHODS: All Level 4 students participated in an image appraisal workshop and were subsequently invited to take part in a focus group immediately after the activity. Twenty-three students took part in three focus groups (n = 7; n = 8; n = 8). A thematic analysis of transcripts was performed alongside validation from observations during the image appraisal activity. RESULTS: Findings demonstrate that despite teaching and resources being available, students had focused on learning a generic checklist for image appraisal, had not appreciated the application of projection specific criteria and felt underprepared. The use of specific criteria and repetition within the task was considered useful. They identified learning needs and misconceptions through peer discussion and via the expert opinion, highlighting the value of feedback. Students enjoyed the workshop and made suggestions for implementation into the curriculum. CONCLUSION: Educators must not assume that the provision of resources will result in students developing deep knowledge. Teaching and learning strategies that are task specific are recommended to avoid a surface approach to learning. Time, repetition and appropriate feedback are essential to enable learners to develop competence and confidence for complex visual tasks, such as image appraisal.

Trends in gabapentinoid prescribing in patients with osteoarthritis: a United Kingdom national cohort study in primary care.

OBJECTIVE: To investigate trends in gabapentinoid prescribing in patients with osteoarthritis (OA). METHODS: Patients aged 40 years and over with a new OA diagnosis recorded between 1995 and 2015 were identified in the Clinical Practice Research Datalink (CPRD) and followed to first prescription of gabapentin or pregabalin, or other censoring event. We estimated the crude and age-standardised annual incidence rates of gabapentinoid prescribing, stratified by patient age, sex, geographical region, and time since OA diagnosis, and the proportion of prescriptions attributable to OA, or to other conditions representing licensed and unlicensed indications for a gabapentinoid prescription. RESULTS: Of 383,680 newly diagnosed OA cases, 35,031 were prescribed at least one gabapentinoid. Irrespective of indication, the annual age-standardised incidence rate of first gabapentinoid prescriptions rose from 1.6 [95% confidence interval (CI): 1.3, 2.0] per 1000 person-years in 2000, to 27.6 (26.7, 28.4) in 2015, a trend seen across all ages and not explained by length of follow-up. Rates were higher among women, younger patients, and in Northern Ireland, Scotland and the North of England. Approximately 9% of first prescriptions could be attributed to OA, a further 13% to comorbid licensed or unlicensed indications. CONCLUSION: Gabapentinoid prescribing in patients with OA increased dramatically between 1995 and 2015. In most cases, diagnostic codes for licensed or unlicensed indications were absent. Gabapentinoid prescribing may be attributable to OA in a significant proportion but evidence for their effectiveness in OA is lacking. Further research to investigate clinical decision making around prescribing these expensive and potentially harmful medicines is recommended.

Potential roles of nitrate and live yeast culture in suppressing methane emission and influencing ruminal fermentation, digestibility, and milk production in lactating Jersey cows.

Concern over the carbon footprint of the dairy industry has led to various dietary approaches to mitigate enteric CH4 production. One approach is feeding the electron acceptor NO3-, thus outcompeting methanogens for aqueous H2. We hypothesized that a live yeast culture (LYC; Saccharomyces cerevisiae from Yea-Sacc 1026, Alltech Inc., Nicholasville, KY) would stimulate the complete reduction of NO3- to NH3 by selenomonads, thus decreasing the quantity of CH4 emissions per unit of energy-corrected milk production while decreasing blood methemoglobin concentration resulting from the absorbed intermediate, NO2-. Twelve lactating Jersey cows (8 multiparous and noncannulated; 4 primiparous and ruminally cannulated) were used in a replicated 4 × 4 Latin square design with a 2 × 2 factorial arrangement of treatments. Cattle were fed diets containing 1.5% NO3- (from calcium ammonium nitrate) or an isonitrogenous control diet (containing additional urea) and given a top-dress of ground corn without or with LYC, with the fourth week used for data collection. Noncannulated cows were spot measured for CH4 emission by mouth using GreenFeed (C-Lock Inc., Rapid City, SD). The main effect of NO3- decreased CH4 by 17% but decreased dry matter intake by 10% (from 19.8 to 17.8 kg/d) such that CH4:dry matter intake numerically decreased by 8% and CH4:milk net energy for lactation production was unaffected by treatment. Milk and milk fat production were not affected, but NO3- decreased milk protein from 758 to 689 g/d. Ruminal pH decreased more sharply after feeding for cows fed diets without NO3-. Acetate:propionate was greater for cows fed NO3-, particularly when combined with LYC (interaction effect). Blood methemoglobin was higher for cattle fed NO3- than for those fed the control diet but was low for both treatments (1.5 vs. 0.5%, respectively; only one measurement exceeded 5%), indicating minimal risk for NO2- accumulation at our feeding level of NO3-. Although neither apparent organic matter nor neutral detergent fiber digestibilities were affected, apparent N digestibility had an interaction for NO3- × LYC such that apparent N digestibility was numerically lowest for diets containing both NO3- and LYC compared with the other 3 diets. Under the conditions of this study, NO3- mitigated ruminal methanogenesis but also depressed dry matter intake and milk protein yield. Based on the fact that few interactions were detected, LYC had a minimal role in attenuating negative cow responses to NO3- supplementation.

Lathosterolosis: A Relatively Mild Case with Cataracts and Learning Difficulties.

Lathosterolosis is a rare defect of cholesterol synthesis. Only four previous cases have been reported, two of whom were siblings. We report a fifth patient, with a relatively mild phenotype. He presented at 5 years of age with bilateral posterior cataracts, which were managed with lensectomies and intraocular lens implants. He also had learning difficulties, with a full-scale IQ of 64 at 11 years of age. His head circumference is between the 0.4th and 2nd centiles, and he has mild hypotonia and subtle dysmorphism (a high-arched palate, anteverted nostrils, long philtrum and clinodactyly of toes). The diagnosis was established after sequencing a panel of genes associated with cataracts, which revealed compound heterozygous SC5D mutations: c.479C>G p.(Pro160Arg) and c.630C>A p.(Asp210Glu). The plasma lathosterol concentration was markedly raised at 219.8 µmol/L (control range 0.53-16.0), confirming the diagnosis. The c.630C>A p.(Asp210Glu) mutation has been reported in one previous patient, who also had a relatively mild phenotype (Ho et al., JIMD Rep 12:129-134, 2014). The mutation leads to a relatively conservative amino acid substitution, consistent with some residual enzyme activity. Our patient's family did not notice any benefit from treatment with simvastatin. In summary, milder patients with lathosterolosis may present with learning difficulties, cataracts and very subtle dysmorphism. The diagnosis will be missed unless plasma sterols are analysed or relevant genes sequenced.

A qualitative analysis of patient-identified adaptive behaviour changes following interdisciplinary Acceptance and Commitment Therapy for chronic pain.

BACKGROUND: Interdisciplinary treatment programmes for chronic pain have strong evidence of treatment effect both immediately after treatment and at follow-up. However, despite strong outcome evidence, it is less clear which specific changes in behaviour are most relevant to patients or to outcomes. Indeed, it is not unknown for clinicians and patients to have different views with regard to goals of treatment. This study sought to evaluate the patients' perspective regarding important behavioural changes that occurred while they were enrolled in a 4-week interdisciplinary programme of Acceptance and Commitment Therapy (ACT) for chronic pain. METHODS: Qualitative data were collected during a treatment session towards the end of treatment. In total, 104 completers from 16 consecutive treatment groups contributed to a data set consisting of 315 unique qualitative comments. RESULTS: Thematic analysis resulted in a theme hierarchy including overarching themes, midlevel themes and subthemes. Three overarching themes were identified as follows: (1) interacting with self - describing an interplay between various aspects of the individual, (2) activity - concerning how individuals practically and sustainably undertook activities and (3) interacting with others - exploring relationships with other people. The results section further describes the midlevel and subthemes that cluster under the overarching themes. CONCLUSIONS: These data provide initial insights into the patient's perspective of adaptive behavioural changes gained as part of an interdisciplinary programme of chronic pain rehabilitation. Overall, the data suggest the importance of a mix of both ACT-specific and more universal coping/pain rehabilitation elements. Future research may examine how these processes relate more directly to treatment outcome. SIGNIFICANCE: This study provides new qualitative insights into the patient's perspective of adaptive behavioural changes gained as part of interdisciplinary pain rehabilitation. This and future work may help provide a more detailed understanding of the processes and behaviours that result in successful rehabilitation outcomes.

The permeability of fractured rocks in pressurised volcanic and geothermal systems.

The connectivity of rocks' porous structure and the presence of fractures influence the transfer of fluids in the Earth's crust. Here, we employed laboratory experiments to measure the influence of macro-fractures and effective pressure on the permeability of volcanic rocks with a wide range of initial porosities (1-41 vol. %) comprised of both vesicles and micro-cracks. We used a hand-held permeameter and hydrostatic cell to measure the permeability of intact rock cores at effective pressures up to 30 MPa; we then induced a macro-fracture to each sample using Brazilian tensile tests and measured the permeability of these macro-fractured rocks again. We show that intact rock permeability increases non-linearly with increasing porosity and decreases with increasing effective pressure due to compactional closure of micro-fractures. Imparting a macro-fracture both increases the permeability of rocks and their sensitivity to effective pressure. The magnitude of permeability increase induced by the macro-fracture is more significant for dense rocks. We finally provide a general equation to estimate the permeability of intact and fractured rocks, forming a basis to constrain fluid flow in volcanic and geothermal systems.

Structural determinants of hydration, mechanics and fluid flow in freeze-dried collagen scaffolds.

UNLABELLED: Freeze-dried scaffolds provide regeneration templates for a wide range of tissues, due to their flexibility in physical and biological properties. Control of structure is crucial for tuning such properties, and therefore scaffold functionality. However, the common approach of modeling these scaffolds as open-cell foams does not fully account for their structural complexity. Here, the validity of the open-cell model is examined across a range of physical characteristics, rigorously linking morphology to hydration and mechanical properties. Collagen scaffolds with systematic changes in relative density were characterized using Scanning Electron Microscopy, X-ray Micro-Computed Tomography and spherical indentation analyzed in a time-dependent poroelastic framework. Morphologically, all scaffolds were mid-way between the open- and closed-cell models, approaching the closed-cell model as relative density increased. Although pore size remained constant, transport pathway diameter decreased. Larger collagen fractions also produced greater volume swelling on hydration, although the change in pore diameter was constant, and relatively small at ∼6%. Mechanically, the dry and hydrated scaffold moduli varied quadratically with relative density, as expected of open-cell materials. However, the increasing pore wall closure was found to determine the time-dependent nature of the hydrated scaffold response, with a decrease in permeability producing increasingly elastic rather than viscoelastic behavior. These results demonstrate that characterizing the deviation from the open-cell model is vital to gain a full understanding of scaffold biophysical properties, and provide a template for structural studies of other freeze-dried biomaterials. STATEMENT OF SIGNIFICANCE: Freeze-dried collagen sponges are three-dimensional microporous scaffolds that have been used for a number of exploratory tissue engineering applications. The characterization of the structure-properties relationships of these scaffolds is necessary to understand their biophysical behavior in vivo. In this work, the relationship between morphology and physical properties in the dry and hydrated states was investigated across a range of solid concentrations in the scaffolds. The quantitative results provided can aid the design of scaffolds with a target trade-off between mechanical properties and structural features important for their biological activity.

Diagnosing the cause of bilateral paediatric cataracts: comparison of standard testing with a next-generation sequencing approach.

PurposeIn addition to environmental causes such as TORCH infection, trauma and drug or chemical exposure, childhood cataracts (CC) frequently have a genetic basis. They may be isolated or syndromic and have been associated with mutations in over 110 genes. We have recently demonstrated that next-generation sequencing (NGS), a high throughput sequencing technique that enables the parallel sequencing of multiple genes, is ideally suited to the investigation of bilateral CC. This study assesses the diagnostic outcomes of traditional routine investigations and compares this with outcomes of NGS testing.MethodsA retrospective review of the medical records of 27 consecutive patients with bilateral CC presenting in 2010-2012 was undertaken. The outcomes of routine investigations in these patients, including TORCH screen, urinalysis, karyotyping, and urinary and plasma organic amino acids, were collated. The success of routine genetic investigations undertaken over 10 years (2000-2010) was also assessed.ResultsBy April 2014, the underlying cause of bilateral CC had been identified in just one of 27 patients despite 44% (n=12) receiving a full 'standard' investigative work-up and 22% (n=6) investigations in addition to the standard work-up. Fifteen of these patients underwent NGS testing and nine (60%) of these received a diagnosis for their CC.ConclusionThe frequency of patients receiving a diagnosis for their CC after standard care and the time taken to diagnosis was disappointing. NGS testing improved diagnostic rates and time to diagnosis, as well as changing clinical management. These data serve as a baseline for future evaluation of novel diagnostic modalities.

CHILDSPLA: a collaboration between children and researchers to design and animate health states.

AIM: The children's health state preferences learnt from animation (CHILDSPLA) project developed an interactive application presented on a touch screen device using an animated character to collect information from children about their health. BACKGROUND: The underlying hypothesis was that health information could be directly collected from children as young as 4 years old by the use of animated characters. This paper describes in detail how children were involved in the development of the application, and recounts both the challenges and benefits of that process. A child psychologist and an animation filmmaker worked closely with children to design a character and to animate it to represent different health states. Children were recruited from a local primary school (n = 38) and a paediatric specialist hospital (n = 36). Diverse interactive activities were organized to help children give feedback and guide the design process. The activities for each session were adjusted to the children's needs, based on the experience of previous sessions. RESULTS: The character and the animations were modified according to the feedback provided by the children. CONCLUSIONS: Developing the CHILDSPLA app in collaboration with children was a worthwhile and enriching experience, despite the required iteration and extension of the design process, as it enabled us to adjust the tool to the children's needs.