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Purpose: Medulloblastoma is the most common malignant brain tumor occurring in childhood and is a significant cause of morbidity and mortality in pediatric oncology. More intense treatment strategies are recommended for patients displaying high-risk factors; however, considerable variation in outcome remains, indicating a need for improved predictive markers. In this study, 1H magnetic resonance spectroscopy (MRS) was used to investigate noninvasive molecular biomarkers of survival in medulloblastoma.Experimental Design: MRS was performed on a series of 35 biopsy-confirmed medulloblastoma cases. One case was excluded because of poor quality MRS. The prognostic value of MRS detectable biomarkers was investigated using Cox regression, retrospectively (N = 15). A subsequent validation analysis (N = 19) was also performed to reduce the chance of type I errors. Where available, high-resolution ex vivo MRS of biopsy tissue was used to confirm biomarker assignments.Results: The retrospective analysis revealed that creatine, glutamate, and glycine were markers of survival (P < 0.01). The validation analysis showed that glutamate was a robust marker, with a hazard ration (HR) of 8.0 for the full dataset (P = 0.0003, N = 34). A good correlation between in vivo and ex vivo MRS glutamate/total-choline was found (P = 0.001), validating the in vivo assignment. Ex vivo glutamate/total-choline was also associated with survival (P < 0.01).Conclusion: The identification of glutamate as a predictive biomarker of survival in pediatric medulloblastoma provides a clinically viable risk factor and highlights the importance of more detailed studies into the metabolism of this disease. Noninvasive biomarker detection using MRS may offer improved disease monitoring and potential for widespread use following multicenter validation. Clin Cancer Res; 20(17); 4532–9. ©2014 AACR.

Supplementary Methods (Text 1). A description of the treatment protocols used during the study period. Supplementary Figure 1. Example medulloblastoma fits where the lowest smooth black line is the baseline; the middle black line represents the acquired spectrum following pre-processing; the red line shows the spectral fit and the top black line shows the residual between the fit and acquired spectrum. A) shows a distorted baseline leading to qc failure whereas B) is an example of an ideal smooth baseline.

Aqueduct stenosis is a recognized cause of obstructive hydrocephalus in children and can be treated effectively with endoscopic third ventriculostomy. Preoperative magnetic resonance imaging is often diagnostic of the cause of aqueduct stenosis. We describe 2 pediatric cases with obstructive hydrocephalus secondary to a working diagnosis of idiopathic aqueduct stenosis. Following successful endoscopic third ventriculostomy, repeat magnetic resonance brain imaging revealed tectal plate glioma as the primary cause of obstruction. We believe these 2 reported cases demonstrate a previously unreported phenomenon whereby concealed tectal gliomas presenting with hydrocephalus are only unmasked following relief of hydrocephalus and decompression and normalization of the ventricular system. We aim to raise awareness about this unusual phenomenon and recommend routine postoperative interval imaging following endoscopic third ventriculostomy to avoid missing underlying pathology masquerading as aqueduct stenosis.

Infiltration of the optic pathway by germ cell tumors is exceptional and can lead to confusion with glioma or inflammatory conditions. We present the case of a 14-year-old girl with an optic nerve germinoma extending to the hypothalamus and manifesting as panhypopituitarism and visual loss. The patient experienced spontaneous regression of the lesion followed by secondary deterioration requiring treatment. Four other cases of spontaneously regressing intracranial germinoma followed by regrowth have been reported in the literature. This report highlights the importance of clinical and radiologic monitoring of intracranial germinoma, even in the event of initial spontaneous improvement.

Background Bevacizumab is increasingly used in children with pediatric low-grade glioma (PLGG) despite limited evidence. A nationwide UK service evaluation was conducted to provide larger cohort “real life” safety and efficacy data including functional visual outcomes. Methods Children receiving bevacizumab-based treatments (BBT) for PLGG (2009–2020) from 11 centers were included. Standardized neuro-radiological (RANO-LGG) and visual (logMAR visual acuity) criteria were used to assess clinical–radiological correlation, survival outcomes and multivariate prognostic analysis. Results Eighty-eight children with PLGG received BBT either as 3rd line with irinotecan (85%) or alongside 1st/2nd line chemotherapies (15%). Toxicity was limited and minimal. Partial response (PR, 40%), stable disease (SD, 49%), and progressive disease (PD, 11%) were seen during BBT. However, 65% progressed at 8 months (median) from BBT cessation, leading to a radiology-based 3 yr-progression-free survival (PFS) of 29%. Diencephalic syndrome (P = .03) was associated with adverse PFS. Pre-existing visual morbidity included unilateral (25%) or bilateral (11%) blindness. Improvement (29%) or stabilization (49%) of visual acuity was achieved, more often in patients’ best eyes. Vision deteriorated during BBT in 14 (22%), with 3-year visual-PFS of 53%; more often in patients’ worst eyes. A superior visual outcome (P = .023) was seen in neurofibromatosis type 1-associated optic pathway glioma (OPG). Concordance between visual and radiological responses was 36%; optimized to 48% using only best eye responses. Conclusions BBTs provide effective short-term PLGG control and delay further progression, with a better sustained visual (best > worst eye) than radiological response. Further research could optimize the role of BBT toward a potentially sight-saving strategy in OPG.

Background Patients with localized intracranial germinoma have excellent survival. Reducing treatment burden and long‐term sequelae is a priority. Intensive inpatient chemotherapy (e.g., carboPEI = carboplatin/etoposide/ifosfamide) has been effectively employed to reduce radiotherapy treatment volume/dose. Outpatient‐based carboplatin monotherapy is associated with excellent outcomes in metastatic testicular seminoma (an identical pathology), and successful vinblastine monotherapy induction (with 77% tumor volume reduction after just two weekly vinblastine doses) has recently been reported in an intracranial germinoma patient. Methods Adapted UK guidelines for germ cell tumor management were distributed during the COVID‐19 pandemic, including nonstandard treatment options to reduce hospital visits and/or admissions. This included vinblastine monotherapy for intracranial germinoma (6 mg/m2 intravenously, or 4 mg/m2 for moderate count suppression, delivered weekly). We describe two such patients treated using this approach. Results A 30‐year‐old male with a localized pineal tumor received 12‐week vinblastine induction, with >60% volume reduction, prior to definitive radiotherapy. A 12‐year‐old female with a metastatic suprasellar tumor and progression at all sites of disease whilst awaiting proton radiotherapy received two vinblastine doses with good early response, including 36% primary tumor volume reduction. The patients tolerated vinblastine well. Conclusion Patients with intracranial germinoma have excellent outcomes, and reduction of late effects remains a priority. The description of vinblastine monotherapy in these intracranial germinoma patients warrants further exploration.

The objective of this paper is to outline a practical approach using numerical modelling and optimization techniques for process and product developments in metal cold rolled forming industry. The optimum economic viability in manufacturing industry requires a minimization of the amount of material used while the structural performance of a cold roll formed product relies on maintaining the stiffness and strength of the section in applications. This leads to the development of new cold forming processes and alternative cold roll formed profiles searching for the optimal profile. In this paper, a Finite Element modelling approach was utilized to simulating complicated manufacturing process and products and optimization techniques including Design Of Experiments was used to optimize the shape design of the end products to obtain lighter products while maintaining the product strength. These developments were illustrated through two case studies of Hadley Industries plc which included (1) numerical modelling of a novel Ultra STEEL® cold roll forming process, and (2) optimization of cold roll forming sections.

Infiltration of the optic pathway by germ cell tumors is exceptional and can lead to confusion with glioma or inflammatory conditions. We present the case of a 14-year-old girl with an optic nerve germinoma extending to the hypothalamus and manifesting as panhypopituitarism and visual loss. The patient experienced spontaneous regression of the lesion followed by secondary deterioration requiring treatment. Four other cases of spontaneously regressing intracranial germinoma followed by regrowth have been reported in the literature. This report highlights the importance of clinical and radiologic monitoring of intracranial germinoma, even in the event of initial spontaneous improvement.

The last five years has shown advances in the molecular classification of brain tumour, molecular profiling techniques and an increased use of targeted therapies. We reviewed the molecular analysis pathways and use of targeted agents at Birmingham Children’s Hospital (BCH), a large (~55 new cases/year) neuro-oncology centre, between 2016-2021. Having previously been analysed locally by limited directed immuno-histochemical stains and referral for specific genetic tests, tissue is now referred for a range of second histopathological opinions and in depth molecular classification, via methylation array, panel sequencing, RNA fusion analysis, and whole genome sequencing. These are accessed through different evolving pathways and consent processes, including referral to other centres, national reference laboratories, clinical studies, and local genetics laboratories with links to national sequencing infrastructures. Different routes result in different reporting structures, timescales and with varying levels of interpretation, often without adequate access to clinical information and context. 21 patients were treated on five targeted agent clinical trials (Afatanib (n=6), Biomede (n=3), eSmart(n=1), PARC (n=7), Vinilo (n=5)), with one patient on both Afatanib and PARC trials. A further two patients visited other centres for trials. Eight patients received MAPK pathway inhibitors through compassionate access pathways, with benefit, including radiological response, in four. Cardiac toxicity was observed in three and retinal oedema in one. Two patients received immune checkpoint inhibition, with rapid fatal enlargement, either progression or pseudo-progression, in one case. These rapid changes in diagnostic and management options offer new opportunities for patients, but bring challenges to the delivery of neuro-oncology services, including the logistics of sample, report, clinical trial, compassionate access management and the increased multi-specialist support required for monitoring and management of toxicities. Integration of targeted agents into the appropriate part of a patient’s treatment strategy requires skilled interpretation of the benefits compared to conventional therapies.

INTRODUCTION: Bevacizumab/Irinotecan is currently 3rd-line treatment in the UK for progressive Paediatric Low-Grade Glioma (PLGG) based on limited evidence. A nationwide service evaluation was conducted to review its safety and efficacy amongst a larger cohort. METHODS: Data from children with PLGG receiving Bevacizumab-based Treatments (BBT) from 11 UK Centres (2009-2020) were reviewed. Radiological and visual outcomes were based on standardized measurements. Clinical-radiological correlation was investigated. Time to progression from BBT stop, progression free-survival (PFS) curves and multivariate analysis of prognostic factors (p 0.05) were performed. RESULTS: 88 children with PLGG (88% OPG, 24% NF1) had BBT for radiological (43%), visual (20%) or combined (27%) progression, after 40 months (median) from diagnosis. Amongst OPG cases, visual acuity (VA) per eye (better/worse) before BBT was logMAR 0.0-0.3 (23/7) 0.3 - 1.0 (27/20), > 1.0 (14/18) and LP/NLP (8/27), with 19/8 children respectively blind (LP/NLP) in one or both eyes. Bevacizumab 10 mg/kg every 14 days (median 24 doses) was given as 3rd line+ with Irinotecan (85%) or alongside 1st/2nd line chemo (15%) leading to remarkable radiological (88%) and visual (74%) responses (stable or improved) within 3-6 months, with limited toxicity. 12% progressed on treatment, and 8% died unrelated to BBT. After initial response 65% progressed at a median of 8 months (4 - 23) after BBT, resulting in 3-year-all-causes-PFS of 16% and 3-yr-visual-PFS of 45% from start of BBT. Visual concordance with MRI was poor (36%) but increases (47%) when better-eye determines visual outcome. Lack of NF1 and diencephalic syndrome (DS) at presentation were independent negative prognostic factors for PFS. CONCLUSIONS: A remarkable but transient effect of BBT has been confirmed. Visual > radiological responses can be sustained after BBT. Variations in current BBT strategies justifies further research, including the potential upfront use alongside conventional first-line chemotherapy as sight-saving strategy.

Background Despite its cardiotoxicity doxorubicin is widely used for the treatment of paediatric malignancies. Current treatment regimens appear to be suboptimal as treatment strategies vary and do not follow a clear pharmacological rationale. Standardisation of dosing strategies in particular for infants and younger children is required but is hampered by scarcely defined exposure-response relationships. The aim is to provide a rational dosing concept allowing for a reduction of variability in systemic therapy intensity and subsequently unforeseen side effects. Methods Doxorubicin plasma concentrations in paediatric cancer patients were simulated for different treatment schedules using a population pharmacokinetic model which considers age-dependent differences in doxorubicin clearance. Overall drug exposure and peak concentrations were assessed. Simulation results were used to support a three round Delphi consensus procedure with the aim to clarify the pharmacological goals of doxorubicin dosing in young children. A group of 28 experts representing paediatric trial groups and clinical centres were invited to participate in this process. Results Pharmacokinetic simulations illustrated the substantial differences in therapy intensity associated with current dosing strategies. Consensus among the panel members was obtained on a standardised a priori dose adaptation that individualises doxorubicin doses based on age and body surface area targeting uniform drug exposure across children treated with the same protocol. Further, a reduction of peak concentrations in very young children by prolonged infusion was recommended. Conclusions An approach to standardise current dose modification schemes in young children is proposed. The consented concept takes individual pharmacokinetic characteristics into account and involves adaptation of both the dose and the infusion duration potentially improving the safety of doxorubicin administration.

This article aims to explore and record the role of shadowing in preparation for a qualitative study involving children and families with sensitive health issues. The researcher was engaged for a study involving qualitative research involving paediatric patients (those under 18 years old) and their families, but was unfamiliar with a hospital environment and interviewing children and young people (CYP) with a serious health condition. The researcher &lsquo, shadowed&rsquo, healthcare professionals (HCPs) at a children&rsquo, s hospital during their day-to-day work in order to prepare for the research interviewing. From shadowing, the researcher gained: familiarity with a hospital environment, organisational processes, and medical terminology, an understanding of the appropriate ways to refer to patients, confidence and competence in talking to children with serious health conditions, and resilience to becoming upset during interviews while hearing patients&rsquo, distressing stories &ndash, they became &lsquo, desensitised&rsquo, Shadowing can therefore be highly beneficial for researchers undertaking research in unfamiliar contexts, environments, and populations prior to interviewing.

The design development of new cold roll formed sections can lead to a significant reduction in material costs if the sections are optimised for strength performance considering the effect of shapes and change of material properties by cold working during the manufacturing process. In this paper, the buckling and ultimate strengths of cold roll formed channel and zed sections with intermediate stiffeners under distortional bending were studied using experimentally validated Finite Element (FE) models. The section strength was optimised using FE modelling and optimisation based on Design Of Experiments (DOE) and response surface methodology. A nonlinear FE model was first developed for a referenced section subject to four-point bending tests and the section’s dimensions and material properties were defined as geometric parameters using the DOE technique. A response surface was then used to determine the influences of the stiffeners’ location, shape, size, and cold working at the section corners and stiffener bends during the manufacturing process. A multi-objective genetic algorithm method was deployed to obtain optimal shapes for the sections with maximum buckling and ultimate strengths while keeping the same amount of material used. The results revealed that the ultimate bending moment capacities could be enhanced up to 17% and 25% for the channel and zed sections, respectively. Including the cold working effect had considerable enhancement in the ultimate moment capacities, with a maximum increase of 5%. The results of this study clearly demonstrated an efficient and effective approach to optimise design for strength performance of cold roll formed sections.

The UltraSTEEL® forming process forms plain steel sheets into dimpled steel sheets. During the forming process both geometry and mechanical properties are considerably altered. This study aims to understand the response of the dimpled steel columns to low velocity lateral impact loads. Explicit finite element (FE) models were created and validated, including boundary conditions, element types and element sizes. Plain, dimpled columns and columns with dimpled geometry and plain material (DGPM) were analysed under lateral impact, to find out the difference between plain and dimpled columns, and the influence of the introduced dimpled geometry. Comparisons were made based mainly on the mean impact force, crush efficiency, and ability to maintain stability. A series of numerical analysis was carried out under different axial compressive loads. The dimpled columns have shown an up to 32.5% greater mean force and an up to 24.4% greater crush efficiency over the plain ones. The dimpled columns have also shown a better stability under axial compressive loads. A further investigation on the support conditions indicated that the dimpled geometry contributes to the reduction of the maximum impact force and therefore increasing the crush efficiency, where at least one end of the column is fully fixed.

New cold roll formed channel and zed sections for purlins, namely UltraBEAM™2 and UltraZED™2, have been developed by Hadley Industries plc using a combined approach of experimental testing, finite element modelling and optimisation techniques. The new sections have improved strength to weight ratio by increasing the section's strength through the use of stiffeners in the section webs. The European standard, Eurocode 3 [1], uses the traditional Effective Width Method to determine the strength of a cold formed steel member. However, the design of the new sections UltraBEAM™2 and UltraZED™2 using this method is very complicated in calculating the effective section properties as these sections contain complex folded-in stiffeners. In addition, the incorporation of competing buckling modes such as distortional buckling of these sections can be difficult to analyse. To overcome difficulties of using Eurocode 3 or such a standard with the Effective Width Method for determining the strength of these sections, the Direct Strength Method is adopted in this paper. Four-point beam bending tests were carried out to determine the buckling and ultimate bending capacities of the UltraBEAM™2 and UltraZED™2 sections. Results from both experimental testing and Finite Element analysis were initially used as validation for the design using the Direct Strength Method. The Direct Strength Method's results were then compared with the experimental test results for a broader data in which the UltraBEAM™2 and UltraZED™2 sections had a range of different width-to-thickness ratios. It showed an excellent agreement between test and Direct Strength design values suggesting that the Direct Strength Method is a powerful tool for the design and optimisation of the new cold roll formed channel and zed purlins.

Background Magnetic resonance spectroscopy (MRS) aids noninvasive diagnosis of pediatric brain tumors, but use in clinical practice is not well documented. We aimed to review clinical use of MRS, establish added value in noninvasive diagnosis, and investigate potential impact on patient care. Methods Sixty-nine children with lesions imaged using MRS and reviewed by the tumor board from 2014 to 2016 met inclusion criteria. Contemporaneous MRI diagnosis, spectroscopy analysis, histopathology, and clinical information were reviewed. Final diagnosis was agreed on by the tumor board at study end. Results Five cases were excluded for lack of documented MRI diagnosis. The principal MRI diagnosis by pediatric radiologists was correct in 59%, increasing to 73% with addition of MRS. Of the 73%, 19.1% (95% CI, 9.1%-33.3%) were incorrectly diagnosed with MRI alone. MRS led to a significant improvement in correct diagnosis over all tumor types (P = .012). Of diagnoses correctly made with MRI, confidence increased by 37% when adding MRS, with no patients incorrectly re-diagnosed. Indolent lesions were diagnosed noninvasively in 85% of cases, with MRS a major contributor to 91% of these diagnoses. Of all patients, 39% were managed without histopathological diagnosis. MRS contributed to diagnosis in 68% of this group, modifying it in 12%. MRS influenced management in 33% of cases, mainly through avoiding and guiding biopsy and aiding tumor characterization. Conclusion MRS can improve accuracy and confidence in noninvasive diagnosis of pediatric brain lesions in clinical practice. There is potential to improve outcomes through avoiding biopsy of indolent lesions, aiding tumor characterization, and facilitating earlier family discussions and treatment planning.

In this paper, the effect of a dimpling process on the mechanical properties of the steel material was studied experimentally and numerically. Nano-hardness and tensile tests of steel samples prior to and after the dimpling process were conducted to evaluate the effects of the process on the mechanical properties. Numerical simulations of the dimpling process and tensile tests were done by Finite Element Analysis; they were used to quantify the amount of non-uniform plastic strains and residual stresses introduced and the manner, in which this was distributed through the sheet. The cold roll dimpling process resulted in developing the plastic strain and residual stress which could correlate to the modifications in the strength and stiffness of the dimpled steel when compared to plain steel originating from the same coil material. The simulation of the dimpling process and tensile tests of the plain and dimpled specimens predicted similar behaviour to the experimental measurements and tests.

Cold roll forming is an incremental sheet metal forming process used to supply products to numerous industries such as automotive, architecture and construction, etc. In recent years there has been an increase in the demand by customers for high value products, through the forming of high strength materials, or complex profiles. Such demands increase the challenges faced by the tooling designer to bring a successful product through from design to manufacture, on time and within specification. Finite element (FE) simulations are increasingly applied in industry due to the desired advantage of reducing design iterations by allowing the designer to investigate the effects of parameter changes, without the risk of expensive tooling costs. Some successful validation of the numerical modelling of the cold roll forming process can be found in literature, in particular when analysing the strain distribution across the material or comparing the final rolled profile geometry. However, cold roll forming is a continuous process and no one has published work on the measurement of the profile on a pass to pass basis, in particular, the three dimensional geometry of the profile. Experimental trials were carried out to obtain a 3D point cloud model of the top surface of a roll formed section. This investigation aimed to quantify how accurate FE simulation may be in relation to physical data.

BACKGROUND Treatment of medulloblastoma has evolved substantially with more chemotherapy, risk-adapted dosing of radiotherapy (RT) and new RT techniques. We present the endocrine profile for our patients treated over a 20-year period. METHODS The charts of patients treated for medulloblastoma between 1/1/00 and 31/12/19 were reviewed. 105 were available. Group 1 received chemotherapy alone, Group 2 received 23.4 Gy whole CNS RT with a posterior fossa (PF) boost to 54 Gy, Group 3 received > 35 Gy whole CNS RT with PF boost to 54–59 Gy, Group 4 received PF RT to 54 Gy. All received chemotherapy according to national guidelines or clinical trials relevant at the time. RESULTS Group 1 (M:F 11:6, 7 survivors mean age 2 years range 1–7) had no endocrinopathies. At 5 years from diagnosis Group 2 (M:F 15:13) and Group 3 (M:F 35:14) had the following % RESULTS Survival 77:61; Growth Hormone deficiency 92:100; Thyroid deficiency 75:81; ACTH deficiency 42:33. Girls were more likely to need sex hormone replacement than boys. Group 4 (M:F 7:5 mean age 2) were all treated in the first decade. 3 survivors, one GH deficiency, one thyroxine deficiency, one both. CONCLUSIONS There is a trend to earlier endocrinopathies in the group 3 vs group 2 patients, but it does not reach statistical significance. Girls are more likely to need sex hormone replacement than boys. This investigation provides a contemporary profile of endocrinopathy after treatment for medulloblastoma that can be used for future comparisons.

Dimpled steel products are produced from the combination of an innovative dimpling process and a traditional forming process such as cold-roll forming or press-braking. The wider use of cold-formed dimpled steel members has promoted considerable interest in the local instability and strength of these members. Of particular interest is their buckling behaviour and ultimate strength capacity in columns under compressive loading. However, the dimpling process produces cold-formed sections with a complex 'dimpled' surface topography and the 'dimpled' material is non-uniformly work hardened through the entire thickness. Owing to these complex issues, there are no existing analytical and design methods to calculate the buckling strength of dimpled products and validate against physical measurements. This paper presents the analysis of the compressive behaviour of cold-formed channel and lipped channel dimpled steel columns using Finite Element techniques. True stress-strain data obtained from physical tests were incorporated into nonlinear simulations of dimpled steel columns. It was found that the predicted buckling and ultimate loads correlated well with the experimental results. Based on the validated Finite Element results for different geometries, standard design formulae for determining buckling and ultimate loads of channel and lipped channel dimpled columns were developed. It is demonstrated that the Finite Element Analysis can therefore be used to analyse and design cold-formed dimpled steel columns. FE analysis is established to simulate cold-formed dimpled steel columns.Buckling and ultimate strength of dimpled steel columns were investigated.FE predicted column strength values correlated well with experimental results.Design for buckling and ultimate strength of dimpled columns was developed.

Paediatric Ependymoma is the second most common malignant brain tumour of childhood with approximately 50% of cases recurring. It has been described as a “surgical” disease since patients who have undergone a gross total surgical resection (GTR) have a better prognosis than those who have a subtotal resection (STR). Analysis of the UKCCSG/SIOP 1992 04 clinical trial has shown that only 49% of cases had a GTR, with 5-year survival rates for STR of 22–47% and GTR of 67–80%. As part of the SIOP II Ependymoma trial the UK established a panel of experts in the treatment of Ependymoma from Neuro-oncology, Neuro-radiology and Neuro-surgery. Meeting weekly, cases are discussed to provide a consensus on radiological review, ensuring central pathological review, trial stratification and whether further surgery should be advocated on any particular case. Evaluation of the first 68 UK patients has shown a GTR in 47/68 (69%) of patients and STR in 21/68 (31%) of patients. Following discussion at EMAG it was felt that 9/21 (43%) STR patients could be offered early second look surgery. Following this 2nd look surgery the number of cases with a GTR increased to 56/68 (82%). There has been a clear increase in the number of patients for whom a GTR has been achieved following discussion at EMAG and prior to them moving forwards with their oncological treatment. This can only have beneficial effects in decreasing their risk of tumour recurrence or CSF dissemination and also in reducing the target volume for radiotherapy.

In 2006 we reported the youngest case of a large clival chordoma, a 15-week old baby, the second case to present without skull base involvement and the fourth case of chordoma in a patient with tuberous sclerosis. This unusually rare case (surgically un-resect able) underwent endoscopic skull-base diagnostic biopsy and a novel chemotherapy regime that aimed to control his disease[i]. Initial tumour control was achieved with chemotherapy (Ifosfamide, doxorubicin with dexrazonane, intrathecal hydrocortisone, methotrexate, cytarabine). Carboplatin and etoposide were later given for a further year. Following this, Sirolimus and imatinib were used for another twelve months due to primary tumour regrowth and three new skull-vault lesions. Sirolimus alone was continued for an additional year, but stopped due to optic neuritis. Imatinib was given until further progression two years later, leading to a change to everolimus. Surgery for the ventral foramen magnum was performed a year later. The patient received further surgery and radiotherapy for tumour recurrence. Sadly the tumour metastasised and he succumbed at age 13. Chordomas are aggressive and recur frequently. Complete primary resection followed by radiotherapy/proton beam therapy offers the best chance of cure but is not an option in infants with giant lesions, as in our case. We inform on alternative targeted treatment strategies and review the literature on these rare lesions. [i] Kambogiorgas D, St George EJ, Chapman S, English M, Solanki G: Infantile Clivus chordoma without clivus involvement: Case report and review of the literature, Childs Nerv System (2006) 22:1369–1374

Optimal design of a structural member is a design process of selecting alternative forms to obtain its maximum strength while maintaining the same weight, leading to the most economical and efficient structure. Amongst steel structures, cold rolled steel ones can effectively gain this requirement as they are thin-walled structures that offer the high ratio of strength over weight. However, the design is very challenging as these members are prone to buckling and failure at low loads. In this paper, the buckling and ultimate strength of cold rolled channel sections was studied using numerical modelling. In order to improve the section strength, the development of various alternative cold rolled formed sections included additional bends such as intermediate stiffeners. The section strength was optimised through a practical approach which altered the stiffener's position and shape and searched for maximum buckling and ultimate strength under bending. In this approach, a nonlinear Finite Element model was first developed for an industrial channel beam subjected to four-point bending tests and this model was validated against experimental test data. The verified model was then used to conduct a parametric study in which the effects of a stiffener's properties on the section strength including its position, shape, size and material properties by the cold work at bends were investigated in detail. Several different cold rolled channel sections having intermediate stiffeners at web and flanges with and without the cold work effect on material properties at the stiffener's bends were considered for this investigation. In addition, a design method, the Direct Strength Method (DSM), was utilised to take into account the effects of a stiffener's properties on the section strength and results were compared with the Finite Element modelling results. It was found that some significant improvements were obtained for the section strength of the optimised sections in comparison to the original sections. An optimal shape for the channel section with maximum ultimate strength in distortional buckling could be obtained with both the stiffeners' position, shape, size and quantity, and the cold work effect. The cold work effect was found most significant in the cases of changing the width of the web stiffeners and the position of the flange stiffeners. It also revealed that, the currently available DSM beam design curve for distortional buckling provided good agreement in predicting buckling load and ultimate strength capacity for most of the considered sections with and without the cold work effect included; however, the DSM provided overestimate results compared to the Finite Element model results in the sections with web intermediate stiffeners, in particular, when the tip of web intermediate stiffener moved away from the web-flange junction in the horizontal direction.

Cold roll forming is a highly productive sheet metal forming process capable of producing an exceptional range of profile geometries. Over the last few years customers have increased the demand for high value components, through the specification of complex profiles, tighter tolerances and/or use of high strength materials. In particular, there has been a high interest by the automotive industry in utilising ultra-high strength steels (UHSSs) within the roll forming process. These steels are ideal for the forming of lightweight products, which possess increased material performance when compared to traditional low strength steels. The industry’s attraction towards the roll forming process may be due to the increased deformation capabilities it can provide and due to the formability limitations of UHSS when using traditional stamping or press braking processes. This investigation aimed to determine an appropriate approach to simulating the cold roll forming process using UHSSs for future industrial applications. Currently a large volume of research can be found on the material characterisation and formability of UHSS using traditional processes. While the interest in roll forming is rapidly increasing over time, there remains a large research gap in this field. Hence, a dual phase steel (DP1000) and complex phase steel (CP1000) provided by TATA Steel were analysed using a five pass roll forming assembly to form the following two profiles: (a) V-section; and (b) flat strip with rib feature. The principal strains along the outer radius of each specimen were analysed using a GOM Argus photogrammetry system. A circle grid analysis was the method used to complete these measurements. The strain analyses were compared with corresponding strains along the surface of the finite element (FE) analysis model results. The non-linear FE simulations were carried out using COPRA® FEA RF 2017. Correlations in the results were achieved, setting a foundation for further investigations on the formability of UHSSs.

BACKGROUND: Surveillance magnetic resonance imaging (MRI) is routinely used to detect recurrence in children with high-grade central nervous system (CNS) tumors, although no consensus has been reached regarding its effectiveness and whether earlier detection is associated with improved patient outcomes. This review aimed to evaluate this practice and any associated benefits and harms. METHODS: Systematic searches for relevant studies were undertaken in a number of databases, including MEDLINE and EMBASE, from 1985 to August 2018. Study selection and data extraction was undertaken independently by two reviewers. Due to heterogeneity between studies, no pooling of data was undertaken. Reporting followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: No comparative studies were identified. Three retrospective observational studies involving 306 patients were reviewed. All had high risk of bias by virtue of study design. Two studies reported outcomes by symptomatic status-both recurrence rates and overall survival for asymptomatic patients were comparable with those for clinically symptomatic patients. No quality-of-life outcomes were reported. CONCLUSION: There is a paucity of evidence to guide clinical practice as to the effectiveness of MRI surveillance in pediatric patients with high-grade CNS tumors. These studies do not clearly demonstrate benefit or harm for the practice. With more research needed, there is a role for researchers to build into future trials data collection on surveillance imaging to give more information for the assessment of imaging frequency and duration in asymptomatic patients. This is an important question not only to clinicians and patients and their families but also from a health service resource perspective.

OBJECTIVE: Paediatric low-grade glioma can progress or recur following primary surgical/non-surgical treatment and require further therapy. Studies have identified clinical characteristics predictive of disease progression. This study aims to determine whether size of residual disease following primary treatment is a prognostic indicator for predicting progression. METHODS: A retrospective analysis of 61 children with histopathologically confirmed low-grade glioma treated at Birmingham Children’s Hospital between 2004 and 2015 was performed. Residual tumour size following primary treatment was measured from MR imaging and analysed in context of clinical characteristics. RESULTS: 47.5% (29/61) children progressed during the follow-up period. A residual tumour size of ≤1cm(3) was predictive of better progression free survival for the entire cohort (p2cm(3)) progressed earlier (minimum 0.36 years) than those with smaller residuals (

Magnetic resonance imaging (MRI) is routinely used as a surveillance tool to detect early asymptomatic tumour recurrence with a view to improving patient outcomes. This systematic review aimed to assess its utility in children with low-grade CNS tumours. Using standard systematic review methods, twelve databases were searched up to January 2017. Seven retrospective case series studies (n = 370 patients) were included, with average follow-up ranging from 5.6 to 7 years. No randomised controlled trials (RCTs) were identified. Due to study heterogeneity only a descriptive synthesis could be undertaken. Imaging was most frequent in the first year post-surgery (with 2–4 scans) reducing to around half this frequency in year two and annually thereafter for the duration of follow-up. Diagnostic yield ranged from 0.25 to 2%. Recurrence rates ranged from 5 to 41%, with most recurrences asymptomatic (range 65–100%). Collectively, 56% of recurrences had occurred within the first year post-treatment (46% in the first 6-months), 68% by year two and 90% by year five. Following recurrence, 90% of patients underwent treatment changes, mainly repeat surgery (72%). Five-year OS ranged from 96 to 100%, while five-year recurrence-free survival ranged from 67 to 100%. None of the studies reported quality of life measures. This systematic review highlights the paucity of evidence currently available to assess the utility of MRI surveillance despite it being routine clinical practice and costly to patients, their families and healthcare systems. This needs to be evaluated within the context of an RCT.

Architects, designers, and engineers are making great efforts to design acoustically-efficient metal-framed walls, minimizing acoustic bridging. Therefore, efficient simulation models to predict the acoustic insulation complying with ISO 10140 are needed at a design stage. In order to achieve this, a numerical model consisting of two fluid-filled reverberation chambers, partitioned using a metal-framed wall, is to be simulated at one-third-octaves. This produces a large simulation model consisting of several millions of nodes and elements. Therefore, efficient meshing procedures are necessary to obtain better solution times and to effectively utilise computational resources. Such models should also demonstrate effective Fluid-Structure Interaction (FSI) along with acoustic-fluid coupling to simulate a realistic scenario. In this contribution, the development of a finite element frequency-dependent mesh model that can characterize the sound insulation of metal-framed walls is presented. Preliminary results on the application of the proposed model to study the geometric contribution of stud frames on the overall acoustic performance of metal-framed walls are also presented. It is considered that the presented numerical model can be used to effectively visualize the noise behaviour of advanced materials and multi-material structures.

Cold-formed steel studs are often used in lightweight partition walls to provide structural stability but in the same time they change the acoustic performance of the whole system. The overall design of such lightweight structures for acoustic sound insulation becomes very complicated as the sound passing through stud needs to be quantified. One of the greatest challenges is to characterize the stud's geometric effects on the sound transmission of the partition walls. This paper presents a 2-D Finite Element modelling approach and results into the vibro-acoustic performance of different studs in double-leaf walls which are placed in between a reverberant source room and a receiving room. The acoustic medium inside rooms was modelled using fluid elements and the structure was modelled with plane strain elements. The interaction between the acoustic medium and the structure was modelled in a coupled structural-acoustic analysis. An FE modelling setup which includes appropriate model parameters to be used in the structural-acoustic analysis was presented. The FE sound reduction of double-leaf walls using two different stud profiles was then calculated. Experimental tests complying with standards ISO 717-1:1997 and 140-3:1995 were also carried out to evaluate the FE results. It has shown that the stud's shape have significant effects on the sound reduction of the double-leaf walls, and the FE results have similar trends are in fair agreement with the experimental results. A parametric study was conducted and the effects of the stud's shapes on the sound reduction were presented and discussed.

© 2017 The Authors. Published by Elsevier Ltd. The UltraSTEEL dimpling forming process forms plain steel sheets into dimpled steel sheets, which have higher energy absorption performance. The energy absorption performance of dimpled products can be further improved through optimizing the forming depth in the UltraSTEEL process. In this paper, forming depths have been optimized through numerical simulations. Explicit dynamics finite element simulations were carried out to analyze the effect of forming depth on material properties as well as the effect of geometry on energy absorption separately. It has been found that yield strengths are maximized when the forming depth is approximately 1mm, and the energy absorption performance is optimized when the forming depth is approximately 0.9 times of the gauge thickness.

The dimpling process is a novel cold-roll forming process that involves dimpling of a rolled flat strip prior to the roll forming operation. This is a process undertaken to enhance the material properties and subsequent products’ structural performance while maintaining a minimum strip thickness. In order to understand the complex and interrelated nonlinear changes in contact, geometry and material properties that occur in the process, it is necessary to accurately simulate the process and validate through physical tests. In this paper, 3D non-linear finite element analysis was employed to simulate the dimpling process and mechanical testing of the subsequent dimpled sheets, in which the dimple geometry and material properties data were directly transferred from the dimpling process. Physical measurements, tensile and bending tests on dimpled sheet steel were conducted to evaluate the simulation results. Simulation of the dimpling process identified the amount of non-uniform plastic strain introduced and the manner in which this was distributed through the sheet. The plastic strain resulted in strain hardening which could correlate to the increase in the strength of the dimpled steel when compared to plain steel originating from the same coil material. A parametric study revealed that the amount of plastic strain depends upon on the process parameters such as friction and overlapping gap between the two forming rolls. The results derived from simulations of the tensile and bending tests were in good agreement with the experimental ones. The validation indicates that the finite element analysis was able to successfully simulate the dimpling process and mechanical properties of the subsequent dimpled steel products.

BackgroundMRI is essential to the clinical management of children and young people with brain tumours. Advances in technology have made images more complicated to interpret, yet more easily available digitally. It is common practice to show these to patients and families, but how they emotionally respond to, understand and value, seeing brain tumour MRIs has not been formally studied.MethodsQualitative semi-structured interviews were undertaken with 14 families (8 patients, 15 parents) purposively sampled from paediatric patients (0 to 18 years) attending a large UK children’s hospital for treatment or monitoring of a brain tumour. Transcripts were analysed thematically using the Framework Method.ResultsFour themes were identified: Receiving results (waiting for results, getting results back, preferences to see images), Emotional responses to MRIs, Understanding of images (what they can show, what they cannot show, confusion) and Value of MRIs (aesthetics, aiding understanding, contextualised knowledge/emotional benefits, enhanced control, enhanced working relationships, no value). All families found value in seeing MRIs, including reassurance, hope, improved understanding and enhanced feeling of control over the condition. However emotional responses varied enormously.ConclusionsClinical teams should always explain MRIs after ‘framing’ the information. This should minimise participant confusion around meaning, periodically evident even after many years. Patient and parent preferences for being shown MRIs varied, and often changed over time, therefore clinicians should identify, record and update these preferences. Time between scanning and receiving the result was stressful causing ‘scanxiety’, but most prioritised accuracy over speed of receiving results.

Optimum acoustic performance of building components is a fundamental factor towards sustainable building design. Accordingly, it is essential that designers have the capability to effectively predict the acoustic performance to achieve sustainable designs. This paper introduces a 2-D Harmonic Acoustic Finite Element Analysis to predict the sound insulation of stud based double-leaf walls. This research was motivated by the necessity to develop acoustically efficient light weight building structures, which are both affordable and sustainable. Prediction of the Sound Reduction Index (R) of plasterboard partitions with structural links is a challenging problem due to the fluid-structure interaction (FSI) between the structural and fluid systems. Several finite element models to predict the sound reduction index of double-leaf walls were developed in compliance with BSENISO 717 and 140. The validity of the finite element predictions were assessed by comparison with experimental test results carried out in a certified laboratory. The effect of using different mesh sizes, fixing mechanisms and sound source locations on the predicted sound reduction index were looked into. The effects of air humidity and temperature on the experimental measurements of R values were also investigated. The FEA model presented in this work is capable of predicting the weighted sound reduction index (Rw) along with A-weighted pink noise (C) and A-weighted urban noise (Ctr) to within an accuracy of ±1 dB. Furthermore, the finite element modelling procedure reported can be extended to efficiently predict the acoustic behaviour of other building components undergoing FSI.

The dimpling process is a novel cold-roll forming process that can enhance the steel material and structural performance by plastically deforming the material surface prior to the section forming operation [1]. Owing to the complex and interrelated nonlinear changes in contact, geometry and material properties that occur in the process and section forming, there have been no existing methods to simulate the process and resultant dimpled products and validate through physical measurements. This paper describes a numerical modelling approach and results into the mechanical properties and structural behaviour of cold-formed dimpled steel. A series of mechanical tests including tensile, plate bending and column compression tests on cold-formed plain and dimpled steel material were conducted for evaluation of numerical results. A finite element approach to practically simulate the dimpling process and experimental tests was presented. True stress–strain data obtained from tests were incorporated into nonlinear simulations of dimpled steel sheets and sections. The simulation of the dimpling process revealed that during the process, various levels of plastic strain are developed throughout the thickness of the steel sheet; this could correlate to the increase in the strength of the dimpled steel as observed in experimental tests and simulations. The simulation of the mechanical tests of dimpled specimens predicted similar results to the experiments, in terms of mechanical properties and structural behaviour. Since the finite element approach was able to successfully represent mechanical properties and structural behaviour of dimpled steel, it can be a powerful method in analysis and design of dimpled steel material and completed sections.

The UltraSTEEL® forming process forms plain steel sheets into dimpled steel sheets and this process increases the sheet material's strengths by generating plastic deformation on the material during the process. This paper presented experimental testing and developed a finite element (FE) model to predict the energy absorption characteristics of dimpled thin-walled structures under axial impact loads, and compared the energy absorption efficiencies (specific energy absorption) of plain and dimpled columns. Dynamic experimental tests were conducted using the drop tower at two different impact velocities. Explicit FE analysis were then carried out to simulate the experiments. The FE method was validated by comparing the numerical and experimental failure modes, crushing force response and specific energy absorptions. The validated FE method was then applied in an optimization study on the parameter of forming depth. The effects of forming depth on both geometry and material properties have been taken into account in the optimization study. It has been found that the specific energy absorption of dimpled columns is up to 16.3% higher than the comparable plain columns.

With the steadily increase in demand for roll formed products due to their application for fields such as automotive, construction, architecture, etc., roll forming companies are challenge with rising customer demands. Companies are struggling to bring a product through from design to manufacture at improved rates, whilst achieving tighter tolerances. The roll forming process may also induce undesirable forming defects such as twist, distortion and straightness problems.Traditionally these issues would be resolved through an empirical approach which heavily relies on the designer's expertise and intuition. This approach can increase undesired development costs due to materials wasted and time delayed. Over the years, numerical simulations have been deployed to try and geometrically validate these defects and ultimately reduce the development phase of a product. The designer has the capability to virtually investigate changes in specific parameters without the risk of expensive tooling costs. The industry partner of this project, Hadley Group, Birmingham, implement Belleville washers into the roll tool configuration. The purpose of these washers is to apply pressure to the strip during roll forming in order to drive material through each forming station. They are also used to adjust the gap between the top and bottom forming rolls, since the incoming material gauge can vary by the nominal tolerance values from coil to coil. For the purpose of this paper, an investigation is carried out focusing on an individual parameter within the finite element analysis (FEA) of the cold roll forming process, i.e. the 'unknown' spring acting on the top roll during the forming process due to the implementation of Belleville washers in the pillar set up. The work explained in this paper shows the eects of the pressure applied to the forming process on the geometric attributes of the section being formed. The outcome will determine the viability of this parameter, which may ultimately require the numerical design methodology of roll formed products to be amended accordingly.

HG-54. THE ROLE OF HIGH-DOSE MYELOABLATIVE CHEMOTHERAPY (HDCT) WITH HAEMATOPOIETIC STEM CELL TRANSPLANTATION (HSCT) IN CHILDREN WITH HIGH GRADE GLIOMAS (HGG) OR DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG): RESULTS OF A SYSTEMATIC REVIEW Caroline Main1, Madeline Adams2, Katherine Cooper3, Sophie Wilne4, Bob Phillips5, Martin English6, Pamela R. Kearns1,6, Barry Pizer3, Simon P. Stevens1, Keith Wheatley1, and Jayne S. Wilson1; Cancer Research UK Clinical Trials Unit; University of Birmingham, Birmingham, UK; Bristol Children’s Hospital, Bristol, UK; Alder Hey Children’s NHS Foundation Trust, Liverpool, UK; Nottingham University Hospitals’ NHS Trust, Nottingham, UK; UK Centre for Reviews and Dissemination, University of York, UK; Birmingham Children’s Hospital NHS Foundation Trust, Birmingham, UK OBJECTIVES: To assess the impact of HDCT/HSCT in children with HGG or DIPG. METHODS: Ten electronic databases were searched from 1985 to Oct 2015 for studies assessing HDCT/HSCT in HGG and DIPG. Outcomes included overall survival (OS), response rates (RR), adverse events and treatment related mortality (TRM). Standard systematic review methods were used to minimise bias. RESULTS: For HGG, 167 patients were included, 56% newly diagnosed and 44% relapsed. Mean age was 8.7 years. Mean follow-up was 2.8-years (range: 0.2-5.4). HDCT mainly consisted of one cycle, with preor post radiotherapy (RT) used in 59% of patients. Median OS for newly diagnosed HGG was between 9-14 months (range: 1-65) (n 1⁄4 27), with one and four year OS 73%+13% (n 1⁄4 11) and 43% (n 1⁄4 21) respectively. Overall RR was 30% (n 1⁄4 26). For relapsed HGG median OS was 12.7months (n 1⁄4 18). Across the studies nine TRM occurred. Sixty-two patients with DIPG were included, 68% newly diagnosed and 32% relapsed. Mean age was 6.8-years. Median follow-up was 1.5 years (range: 0.1-7). HDCT consisted of one cycle, with 77% patients receiving prior RT. For newly diagnosed patients with DIPG, median OS was 10-11.4 months (range: 6.4-17.1) (n 1⁄4 42), and for relapsed patients 4.8 months (0.1-18.7) (n 1⁄4 16). Across the studies five toxicity related deaths occurred (8%). CONCLUSIONS: The limited evidence on HDCT/HSCT in children with HGG or DIPG does not allow reliable conclusions to be drawn. However, use of HDCT/HSCT in these patient groups is associated with a significant toxicity profile and TRM. Neuro-Oncology 18:iii48–iii77, 2016. doi:10.1093/neuonc/now073.50 #The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Background The aim of this study is to assess the impact of routine MRI surveillance to detect tumour recurrence in children with no new neurological signs or symptoms compared with alternative follow-up practices, including periodic clinical and physical examinations and the use of non-routine imaging upon presentation with disease signs or symptoms. Methods Standard systematic review methods aimed at minimising bias will be employed for study identification, selection and data extraction. Ten electronic databases have been searched, and further citation searching and reference checking will be employed. Randomised and non-randomised controlled trials assessing the impact of routine surveillance MRI to detect tumour recurrence in children with no new neurological signs or symptoms compared to alternative follow-up schedules including imaging upon presentation with disease signs or symptoms will be included. The primary outcome is time to change in therapeutic intervention. Secondary outcomes include overall survival, surrogate survival outcomes, response rates, diagnostic yield per set of images, adverse events, quality of survival and validated measures of family psychological functioning and anxiety. Two reviewers will independently screen and select studies for inclusion. Quality assessment will be undertaken using the Cochrane Collaboration’s tools for assessing risk of bias. Where possible, data will be summarised using combined estimates of effect for time to treatment change, survival outcomes and response rates using assumption-free methods. Further sub-group analyses and meta-regression models will be specified and undertaken to explore potential sources of heterogeneity between studies within each tumour type if necessary. Discussion Assessment of the impact of surveillance imaging in children with CNS tumours is methodologically complex. The evidence base is likely to be heterogeneous in terms of imaging protocols, definitions of radiological response and diagnostic accuracy of tumour recurrence due to changes in imaging technology over time. Furthermore, the delineation of tumour recurrence from either pseudo-progression or radiation necrosis after radiotherapy is potentially problematic and linked to the timing of follow-up assessments. However, given the current routine practice of MRI surveillance in the follow-up of children with CNS tumours in the UK and the resource implications, it is important to evaluate the cost-benefit profile of this practice. Systematic review registration PROSPERO CRD42016036802 Electronic supplementary material The online version of this article (doi:10.1186/s13643-016-0318-1) contains supplementary material, which is available to authorized users.