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Article: Closing the Gap in Global Neurosurgical Education via Online Conference: A Pre-Covid Survey.

Downes, Simon R / Lykina, Tatiana

2020 Volume 12, Issue 5, Page(s) e8015

Abstract: Introduction A reliable network for peer review and feedback can lead to an increase in knowledge and improving patient care. As opportunities to participate in online continuing medical education (CME) increase, there is a reduction in the worldwide ... ...

Abstract	Introduction A reliable network for peer review and feedback can lead to an increase in knowledge and improving patient care. As opportunities to participate in online continuing medical education (CME) increase, there is a reduction in the worldwide knowledge gap often due to a lack of resources to attend conferences and advanced training in person. Methods A total of 64 participants completed a 10-item anonymous online questionnaire to assess how their knowledge and applied practical skills improved by participating in online conferences, and whether this education modality adequately addresses challenges for countries with limited access to conferences or training. Results While an overall positive response toward this mode of neurosurgical education was expected, interesting insights were gained from the short-answer section, demonstrating a direct influence on clinical practice through online conference participation. Conclusion While limited in size, the study results support the expectation of a positive attitude toward neurosurgical e-learning, which translates directly to improving patient care and lessening the worldwide gap in neurosurgical education.
Keywords	covid19
Language	English
Publishing date	2020-05-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	2747273-5
ISSN	2168-8184
ISSN	2168-8184
DOI	10.7759/cureus.8015
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Article ; Online: Meta-analysis of health state utility values measured by EuroQol 5-dimensions (EQ5D) questionnaire in Chinese women with breast cancer.

Rautenberg, Tamlyn / Hodgkinson, Brent / Zerwes, Ute / Downes, Martin

BMC cancer

2022 Volume 22, Issue 1, Page(s) 52

Abstract: ... in State R (first year after recurrence) 0.73 (0.69, 0.76), in State S (second and following years after ... models using the inverse variance and Der Simonian-Laird methods respectively. Heterogeneity was ...

Abstract	Background: To synthesise EQ5D health state utility values in Chinese women with breast cancer for parameterising a cost utility model. Methods: Eligible studies had to report health state utility values measured by EQ-5D in Chinese women diagnosed with breast cancer. Risk of bias was assessed using the Newcastle Ottawa Scale (NOS). Data from single arm studies was pooled using meta-analysis of single proportions to provide overall point estimates and 95% confidence intervals for fixed and random effects models using the inverse variance and Der Simonian-Laird methods respectively. Heterogeneity was evaluated using the I Results: Five papers were included, when all studies were combined (n = 4,100) the mean utility (95% confidence interval) for random effects model was 0.83 (0.78, 0.89); for TNM 0-1 0.85 (0.75, 0.95); for TNM II 0.85 (0.78, 0.93); for TNM III 0.83 (0.77, 0.90) and for TNM IV 0.73 (0.63, 0.82).The utility of patients in State P (first year after primary breast cancer) 0.84 (0.80, 0.88); in State R (first year after recurrence) 0.73 (0.69, 0.76), in State S (second and following years after primary breast cancer or recurrence) 0.88 (0.83, 0.92); and in State M (metastatic disease) 0.78 (0.74, 0.82). Mean utility for duration since diagnosis 13 to 36 months was 0.88 (0.80, 0.96, I Conclusion: This study synthesises the evidence for health state utility values for Chinese women with breast cancer which is useful to inform cost utility models.
MeSH term(s)	Breast Neoplasms/epidemiology ; Breast Neoplasms/pathology ; China ; Cost-Benefit Analysis ; Female ; Health Status ; Health Surveys ; Humans ; Middle Aged ; Patient Acuity
Language	English
Publishing date	2022-01-10
Publishing country	England
Document type	Journal Article ; Meta-Analysis
ZDB-ID	2041352-X
ISSN	1471-2407 ; 1471-2407
ISSN (online)	1471-2407
ISSN	1471-2407
DOI	10.1186/s12885-021-09140-5
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Article: Seed Banks as Incidental Fungi Banks: Fungal Endophyte Diversity in Stored Seeds of Banana Wild Relatives.

Hill, Rowena / Llewellyn, Theo / Downes, Elizabeth / Oddy, Joseph / MacIntosh, Catriona / Kallow, Simon / Panis, Bart / Dickie, John B / Gaya, Ester

Frontiers in microbiology

2021 Volume 12, Page(s) 643731

Abstract: Seed banks were first established to conserve crop genetic diversity, but seed banking has more recently been extended to wild plants, particularly crop wild relatives (CWRs) (e.g., by the Millennium Seed Bank (MSB), Royal Botanic Gardens Kew). CWRs have ...

Abstract	Seed banks were first established to conserve crop genetic diversity, but seed banking has more recently been extended to wild plants, particularly crop wild relatives (CWRs) (e.g., by the Millennium Seed Bank (MSB), Royal Botanic Gardens Kew). CWRs have been recognised as potential reservoirs of beneficial traits for our domesticated crops, and with mounting evidence of the importance of the microbiome to organismal health, it follows that the microbial communities of wild relatives could also be a valuable resource for crop resilience to environmental and pathogenic threats. Endophytic fungi reside asymptomatically inside all plant tissues and have been found to confer advantages to their plant host. Preserving the natural microbial diversity of plants could therefore represent an important secondary conservation role of seed banks. At the same time, species that are reported as endophytes may also be latent pathogens. We explored the potential of the MSB as an incidental fungal endophyte bank by assessing diversity of fungi inside stored seeds. Using banana CWRs in the genus
Language	English
Publishing date	2021-03-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587354-4
ISSN	1664-302X
ISSN	1664-302X
DOI	10.3389/fmicb.2021.643731
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Article ; Online: Functional characterisation of

Simon, Claire S / Downes, Damien J / Gosden, Matthew E / Telenius, Jelena / Higgs, Douglas R / Hughes, Jim R / Costello, Ita / Bikoff, Elizabeth K / Robertson, Elizabeth J

Development (Cambridge, England)

2017 Volume 144, Issue 7, Page(s) 1249–1260

Abstract: The T-box transcription factor (TF) Eomes is a key regulator of cell fate decisions during early mouse development. ... ...

Abstract	The T-box transcription factor (TF) Eomes is a key regulator of cell fate decisions during early mouse development. The
MeSH term(s)	Animals ; Cell Differentiation/genetics ; Chromatin/metabolism ; Embryo, Mammalian/metabolism ; Endoderm/metabolism ; Enhancer Elements, Genetic ; Female ; Forkhead Transcription Factors/metabolism ; Gastrulation/genetics ; Gene Deletion ; Gene Expression Regulation, Developmental ; Gene Targeting ; Genes, Reporter ; Genotype ; Mice, Inbred C57BL ; Models, Biological ; Polycomb-Group Proteins/metabolism ; Regulatory Sequences, Nucleic Acid/genetics ; Signal Transduction/genetics ; Smad2 Protein/metabolism ; T-Box Domain Proteins/genetics ; T-Box Domain Proteins/metabolism
Chemical Substances	Chromatin ; Eomes protein, mouse ; Forkhead Transcription Factors ; Foxh1 protein, mouse ; Polycomb-Group Proteins ; Smad2 Protein ; T-Box Domain Proteins
Language	English
Publishing date	2017-02-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	90607-4
ISSN	1477-9129 ; 0950-1991
ISSN (online)	1477-9129
ISSN	0950-1991
DOI	10.1242/dev.147322
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Article ; Online: Loss-of-Function Mutations in the CFH Gene Affecting Alternatively Encoded Factor H-like 1 Protein Cause Dominant Early-Onset Macular Drusen.

Taylor, Rachel L / Poulter, James A / Downes, Susan M / McKibbin, Martin / Khan, Kamron N / Inglehearn, Chris F / Webster, Andrew R / Hardcastle, Alison J / Michaelides, Michel / Bishop, Paul N / Clark, Simon J / Black, Graeme C

Ophthalmology

2019 Volume 126, Issue 10, Page(s) 1410–1421

Abstract: Purpose: To characterize the molecular mechanism underpinning early-onset macular drusen (EOMD), a phenotypically severe subtype of age-related macular degeneration (AMD), in a subgroup of patients.: Design: Multicenter case series, in vitro ... ...

Abstract	Purpose: To characterize the molecular mechanism underpinning early-onset macular drusen (EOMD), a phenotypically severe subtype of age-related macular degeneration (AMD), in a subgroup of patients. Design: Multicenter case series, in vitro experimentation, and retrospective analysis of previously reported variants. Participants: Seven families with apparently autosomal dominant EOMD. Methods: Patients underwent a comprehensive ophthalmic assessment. Affected individuals from families A, B, and E underwent whole exome sequencing. The probands from families C, D, F, and G underwent Sanger sequencing analysis of the complement factor H (CFH) gene. Mutant recombinant factor H like-1 (FHL-1) proteins were expressed in HEK293 cells to assess the impact on FHL-1 expression and function. Previously reported EOMD-causing variants in CFH were reviewed. Main outcome measures: Detailed clinical phenotypes, genomic findings, in vitro characterization of mutation effect on protein function, and postulation of the pathomechanism underpinning EOMD. Results: All affected participants demonstrated bilateral drusen. The earliest reported age of onset was 16 years (median, 46 years). Ultra-rare (minor allele frequency [MAF], ≤0.0001) CFH variants were identified as the cause of disease in each family: CFH c.1243del, p.(Ala415ProfsTer39) het; c.350+1G→T het; c.619+1G→A het, c.380G→A, p.(Arg127His) het; c.694C→T p.(Arg232Ter) het (identified in 2 unrelated families in this cohort); and c.1291T→A, p.(Cys431Ser). All mutations affect complement control protein domains 2 through 7, and thus are predicted to impact both FHL-1, the predominant isoform in Bruch's membrane (BrM) of the macula, and factor H (FH). In vitro analysis of recombinant proteins FHL-1 Conclusions: Early-onset macular drusen is an underrecognized, phenotypically severe subtype of AMD. We propose that haploinsufficiency of FHL-1, the main regulator of the complement pathway in BrM, where drusen develop, is an important mechanism underpinning the development of EOMD in a number of cases. Understanding the molecular basis of EOMD will shed light on AMD pathogenesis given their pathologic similarities.
MeSH term(s)	Aged ; Complement Factor H/genetics ; Female ; Genetic Variation ; Humans ; Intracellular Signaling Peptides and Proteins/metabolism ; LIM Domain Proteins/metabolism ; Male ; Middle Aged ; Muscle Proteins/metabolism ; Mutation ; Retinal Drusen/genetics ; Retinal Drusen/metabolism ; Retrospective Studies
Chemical Substances	FHL1 protein, human ; Intracellular Signaling Peptides and Proteins ; LIM Domain Proteins ; Muscle Proteins ; Complement Factor H (80295-65-4)
Language	English
Publishing date	2019-03-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	392083-5
ISSN	1549-4713 ; 0161-6420
ISSN (online)	1549-4713
ISSN	0161-6420
DOI	10.1016/j.ophtha.2019.03.013
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Article ; Online: Recommendations for clinical interpretation of variants found in non-coding regions of the genome.

Ellingford, Jamie M / Ahn, Joo Wook / Bagnall, Richard D / Baralle, Diana / Barton, Stephanie / Campbell, Chris / Downes, Kate / Ellard, Sian / Duff-Farrier, Celia / FitzPatrick, David R / Greally, John M / Ingles, Jodie / Krishnan, Neesha / Lord, Jenny / Martin, Hilary C / Newman, William G / O'Donnell-Luria, Anne / Ramsden, Simon C / Rehm, Heidi L /

Richardson, Ebony / Singer-Berk, Moriel / Taylor, Jenny C / Williams, Maggie / Wood, Jordan C / Wright, Caroline F / Harrison, Steven M / Whiffin, Nicola

Genome medicine

2022 Volume 14, Issue 1, Page(s) 73

Abstract: Background: The majority of clinical genetic testing focuses almost exclusively on regions of the genome that directly encode proteins. The important role of variants in non-coding regions in penetrant disease is, however, increasingly being ... ...

Abstract	Background: The majority of clinical genetic testing focuses almost exclusively on regions of the genome that directly encode proteins. The important role of variants in non-coding regions in penetrant disease is, however, increasingly being demonstrated, and the use of whole genome sequencing in clinical diagnostic settings is rising across a large range of genetic disorders. Despite this, there is no existing guidance on how current guidelines designed primarily for variants in protein-coding regions should be adapted for variants identified in other genomic contexts. Methods: We convened a panel of nine clinical and research scientists with wide-ranging expertise in clinical variant interpretation, with specific experience in variants within non-coding regions. This panel discussed and refined an initial draft of the guidelines which were then extensively tested and reviewed by external groups. Results: We discuss considerations specifically for variants in non-coding regions of the genome. We outline how to define candidate regulatory elements, highlight examples of mechanisms through which non-coding region variants can lead to penetrant monogenic disease, and outline how existing guidelines can be adapted for the interpretation of these variants. Conclusions: These recommendations aim to increase the number and range of non-coding region variants that can be clinically interpreted, which, together with a compatible phenotype, can lead to new diagnoses and catalyse the discovery of novel disease mechanisms.
MeSH term(s)	Genetic Variation ; Genome ; Genome-Wide Association Study ; Open Reading Frames ; Regulatory Sequences, Nucleic Acid
Language	English
Publishing date	2022-07-19
Publishing country	England
Document type	Letter ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2484394-5
ISSN	1756-994X ; 1756-994X
ISSN (online)	1756-994X
ISSN	1756-994X
DOI	10.1186/s13073-022-01073-3
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Article ; Online: Pre-treatment and real-time image guidance for a fixed-beam radiotherapy system.

Liu, Paul Z Y / Gardner, Mark / Heng, Soo Min / Shieh, Chun-Chen / Nguyen, Doan Trang / Debrot, Emily / O'Brien, Ricky / Downes, Simon / Jackson, Michael / Keall, Paul J

Physics in medicine and biology

2021 Volume 66, Issue 6, Page(s) 64003

Abstract: Purpose: A radiotherapy system with a fixed treatment beam and a rotating patient positioning system could be smaller, more robust and more cost effective compared to conventional rotating gantry systems. However, patient rotation could cause anatomical ...

Abstract	Purpose: A radiotherapy system with a fixed treatment beam and a rotating patient positioning system could be smaller, more robust and more cost effective compared to conventional rotating gantry systems. However, patient rotation could cause anatomical deformation and compromise treatment delivery. In this work, we demonstrate an image-guided treatment workflow with a fixed beam prototype system that accounts for deformation during rotation to maintain dosimetric accuracy. Methods: The prototype system consists of an Elekta Synergy linac with the therapy beam orientated downward and a custom-built patient rotation system (PRS). A phantom that deforms with rotation was constructed and rotated within the PRS to quantify the performance of two image guidance techniques: motion compensated cone-beam CT (CBCT) for pre-treatment volumetric imaging and kilovoltage infraction monitoring (KIM) for real-time image guidance. The phantom was irradiated with a 3D conformal beam to evaluate the dosimetric accuracy of the workflow. Results: The motion compensated CBCT was used to verify pre-treatment position and the average calculated position was within -0.3 ± 1.1 mm of the phantom's ground truth position at 0°. KIM tracked the position of the target in real-time as the phantom was rotated and the average calculated position was within -0.2 ± 0.8 mm of the phantom's ground truth position. A 3D conformal treatment delivered on the prototype system with image guidance had a 3%/2 mm gamma pass rate of 96.3% compared to 98.6% delivered using a conventional rotating gantry linac. Conclusions: In this work, we have shown that image guidance can be used with fixed-beam treatment systems to measure and account for changes in target position in order to maintain dosimetric coverage during horizontal rotation. This treatment modality could provide a viable treatment option when there insufficient space for a conventional linear accelerator or where the cost is prohibitive.
MeSH term(s)	Algorithms ; Cone-Beam Computed Tomography/methods ; Humans ; Imaging, Three-Dimensional/methods ; Materials Testing ; Motion ; Particle Accelerators ; Phantoms, Imaging ; Radiometry ; Radiotherapy Planning, Computer-Assisted ; Radiotherapy, Image-Guided/methods ; Reproducibility of Results ; Rotation
Language	English
Publishing date	2021-03-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	208857-5
ISSN	1361-6560 ; 0031-9155
ISSN (online)	1361-6560
ISSN	0031-9155
DOI	10.1088/1361-6560/abdc12
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Article ; Online: Seed banks as incidental fungi banks

Hill, Rowena / Llewellyn, Theo / Downes, Elizabeth / Oddy, Joseph / MacIntosh, Catrona / Kallow, Simon / Panis, Bartholomeus / Dickie, John B. / Gaya, Ester

Frontiers in Microbiology

Fungal endophyte diversity in stored seeds of banana wild relatives

2021

Abstract	Seed banks were first established to conserve crop genetic diversity, but seed banking has more recently been extended to wild plants, particularly crop wild relatives (CWRs) (e.g., by the Millennium Seed Bank (MSB), Royal Botanic Gardens Kew). CWRs have been recognised as potential reservoirs of beneficial traits for our domesticated crops, and with mounting evidence of the importance of the microbiome to organismal health, it follows that the microbial communities of wild relatives could also be a valuable resource for crop resilience to environmental and pathogenic threats. Endophytic fungi reside asymptomatically inside all plant tissues and have been found to confer advantages to their plant host. Preserving the natural microbial diversity of plants could therefore represent an important secondary conservation role of seed banks. At the same time, species that are reported as endophytes may also be latent pathogens. We explored the potential of the MSB as an incidental fungal endophyte bank by assessing diversity of fungi inside stored seeds. Using banana CWRs in the genus Musa as a case-study, we sequenced an extended ITS-LSU fragment in order to delimit operational taxonomic units (OTUs) and used a similarity and phylogenetics approach for classification. Fungi were successfully detected inside just under one third of the seeds, with a few genera accounting for most of the OTUs–primarily Lasiodiplodia, Fusarium, and Aspergillus–while a large variety of rare OTUs from across the Ascomycota were isolated only once. Fusarium species were notably abundant–of significance in light of Fusarium wilt, a disease threatening global banana crops–and so were targeted for additional sequencing with the marker EF1α in order to delimit species and place them in a phylogeny of the genus. Endophyte community composition, diversity and abundance was significantly different across habitats, and we explored the relationship between community differences and seed germination/viability. Our results show that there is a ...
Keywords	musa ; endophytes ; fungi ; gene banks ; crop wild relatives ; endofitas ; hongos ; banco de genes
Language	English
Publishing date	2021-03-25T09:22:43Z
Publisher	Frontiers Media
Publishing country	fr
Document type	Article ; Online
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Article ; Online: Morphological and functional parameters in X-linked retinoschisis patients–A multicentre retrospective cohort study

Peter Kiraly / Immanuel P. Seitz / Maram E. A. Abdalla Elsayed / Susan M. Downes / Chetan K. Patel / Peter Charbel Issa / Johannes Birtel / Luca Mautone / Simon Dulz / Yevgeniya Atiskova / Philipp Herrmann / Nika Vrabič / Martina Jarc-Vidmar / Marko Hawlina / M. Dominik Fischer

Frontiers in Medicine, Vol

2024 Volume 10

Abstract: ... carbonic anhydrase inhibitors (CAI).ResultsInter-eye symmetry revealed strong correlation in CRT (r = 0.77; p < 0.0001) and ... moderate correlations in MV (r = 0.51, p < 0.0001) and BCVA (r = 0.49; p < 0.0001). Weak or no correlations ...

Abstract	IntroductionX-linked retinoschisis (XLRS) is a potential target for gene supplementation approaches. To establish potential structural and functional endpoints for clinical trials, a comprehensive understanding of the inter-eye symmetry, relationship between structural and functional parameters, and disease progression is vital.MethodsIn this retrospective multicentre study, 118 eyes of 59 XLRS patients with RS1 mutations were assessed. Information from center databases included: RS1 variant; age at presentation; best-corrected visual acuity (BCVA), central retinal thickness (CRT), macular volume (MV) at presentation and at the last follow up; full-field electroretinogram (ERG) findings; presence of peripheral retinoschisis and complications (vitreous hemorrhage, retinal detachment); treatment with systemic or topical carbonic anhydrase inhibitors (CAI).ResultsInter-eye symmetry revealed strong correlation in CRT (r = 0.77; p < 0.0001) and moderate correlations in MV (r = 0.51, p < 0.0001) and BCVA (r = 0.49; p < 0.0001). Weak or no correlations were observed between BCVA and structural parameters (CRT, MV). Peripheral retinoschisis was observed in 40 (68%), retinal detachment in 9 (15%), and vitreous hemorrhage in 5 (8%) patients, respectively. Longitudinal examinations (mean, 4.3 years) showed no BCVA changes; however, a reduction of the CRT (p = 0.02), and MV (p = 0.01) was observed. Oral and/or topical CAI treatment did not significantly alter the CRT (p = 0.34).DiscussionThe XLRS phenotype demonstrates a strong CRT symmetry between the eyes within individual patients and stable BCVA over several years. BCVA exhibits a weak correlation with the morphological parameters of retinal thickness (CRT MV). In our cohort, longitudinal functional changes were not significant, likely attributed to the short average follow-up period. Furthermore, CAI treatment didn’t influence both morphological and functional outcomes.
Keywords	X-linked retinoschisis ; XLRS ; morphological parameters ; functional parameters ; symmetry between eyes ; carbonic anhydrase inhibitors ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2024-01-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
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Article ; Online: Characterization of small-field stereotactic radiosurgery beams with modern detectors.

Tyler, Madelaine / Liu, Paul Z Y / Chan, Kin Wa / Ralston, Anna / McKenzie, David R / Downes, Simon / Suchowerska, Natalka

Physics in medicine and biology

2013 Volume 58, Issue 21, Page(s) 7595–7608

Abstract: To derive accurate beam models for stereotactic radiosurgery (SRS) planning it is necessary to characterize the beam with dosimetric measurements. The aim of this study is to identify the best detectors for each task in the characterization process. ... ...

Abstract	To derive accurate beam models for stereotactic radiosurgery (SRS) planning it is necessary to characterize the beam with dosimetric measurements. The aim of this study is to identify the best detectors for each task in the characterization process. Output ratios, beam profiles and percentage depth doses were measured for SRS cone diameters of 5-45 mm. Commercially available and emerging detectors were used: Gafchromic EBT2 film, an air-core fibre optic dosimeter (FOD) (developed at Royal Prince Alfred Hospital, Sydney), an IBA stereotactic field diode, a PTW 60012 electron diode and an IBA cc01 small volume thimble ion chamber. Analysis of the measured data supported by baseline Monte Carlo simulation data, led to the following recommendations: (1) water-equivalent detectors (Gafchromic EBT2 film or FOD) are the preferred choice for SRS dosimetry, (2) ion chambers (including small volume chambers with high-density central electrodes) should be avoided due to volume averaging effects and energy dependence, (3) if diodes are used, corrections must be made to account for their over-response in small fields.
MeSH term(s)	Monte Carlo Method ; Radiometry ; Radiosurgery/instrumentation
Language	English
Publishing date	2013-11-07
Publishing country	England
Document type	Journal Article
ZDB-ID	208857-5
ISSN	1361-6560 ; 0031-9155
ISSN (online)	1361-6560
ISSN	0031-9155
DOI	10.1088/0031-9155/58/21/7595
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