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Article ; Online: Robotic-assisted total hip arthroplasty: an economic analysis.

Pierce, James / Needham, Keith / Adams, Chris / Coppolecchia, Andrea / Lavernia, Carlos

Journal of comparative effectiveness research

2021 Volume 10, Issue 16, Page(s) 1225–1234

Abstract: Aim: ...

Abstract	Aim:
MeSH term(s)	Aged ; Arthroplasty, Replacement, Hip ; Episode of Care ; Hospitalization ; Humans ; Length of Stay ; Medicare ; Retrospective Studies ; Robotic Surgical Procedures ; United States
Language	English
Publishing date	2021-09-28
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2669725-7
ISSN	2042-6313 ; 2042-6305
ISSN (online)	2042-6313
ISSN	2042-6305
DOI	10.2217/cer-2020-0255
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Article ; Online: Clinical associations of patients with anti-3-hydroxy-3-methylglutaryl CoA reductase antibody-associated immune-mediated necrotising myopathy.

Tan, Elina / Knight, Jacinta / Khonasti, Steffi / Nolan, David / McGettigan, Benjamin / Bundell, Chris / Needham, Merrilee / Brusch, Anna

Internal medicine journal

2023 Volume 53, Issue 10, Page(s) 1846–1853

Abstract: Background: Anti-3-hydroxy-3-methylglutaryl CoA reductase (HMGCR) antibodies are associated with a subtype of immune-mediated necrotising myopathy (IMNM).: Aims: To determine clinical associations of anti-HMGCR antibodies for anti-HMGCR-associated ... ...

Abstract	Background: Anti-3-hydroxy-3-methylglutaryl CoA reductase (HMGCR) antibodies are associated with a subtype of immune-mediated necrotising myopathy (IMNM). Aims: To determine clinical associations of anti-HMGCR antibodies for anti-HMGCR-associated IMNM (HMGCR-IMNM) among a cohort of patients in Western Australia and to determine whether serial HMGCR antibody levels parallel disease activity. Methods: Adult patients with positive anti-HMGCR antibodies detected by enzyme-linked immunosorbent assay between January 2015 and November 2019 were included. Symptoms, examination findings, imaging findings and blood test results were reviewed retrospectively using patient records and laboratory database results. Results: Among 26 patients with positive anti-HMGCR antibodies, 23 were diagnosed with HMGCR-IMNM representing a positive predictive value (PPV) of 88%. Myopathy was frequently severe at diagnosis with limb weakness graded as Medical Research Council score 3 or below in 78% of patients, bulbar muscle weakness in 39% and an average creatine kinase (CK) at diagnosis of 7986 U/L. The majority (83%) required at least two therapies to maintain remission, 48% had at least one flare of disease and 57% did not achieve CK normalisation. Correlation between CK and anti-HMGCR antibody level at diagnosis was low (r = 0.04). Anti-HMGCR antibodies fell with treatment in 10 of 12 patients, but remained persistently positive in 83% of patients. Conclusions: The PPV of anti-HMGCR antibodies for HMGCR-IMNM in this Western Australian cohort is 88%. Patients typically present with proximal limb weakness, dysphagia and markedly elevated CK, and, despite multiagent immunosuppression, a significant number of patients have evidence of persistent biochemical myositis. Anti-HMGCR antibodies did not correlate with CK levels at diagnosis.
MeSH term(s)	Adult ; Humans ; Australia ; Autoantibodies ; Autoimmune Diseases/diagnosis ; Creatine Kinase ; Hydroxymethylglutaryl CoA Reductases ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects ; Muscle, Skeletal ; Muscular Diseases/diagnosis ; Myositis/diagnosis ; Myositis/drug therapy ; Retrospective Studies
Chemical Substances	Autoantibodies ; Creatine Kinase (EC 2.7.3.2) ; Hydroxymethylglutaryl CoA Reductases (EC 1.1.1.-) ; Hydroxymethylglutaryl-CoA Reductase Inhibitors
Language	English
Publishing date	2023-01-27
Publishing country	Australia
Document type	Journal Article
ZDB-ID	2045436-3
ISSN	1445-5994 ; 1444-0903
ISSN (online)	1445-5994
ISSN	1444-0903
DOI	10.1111/imj.16004
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Zs.A 792: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 424: Show issues

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Article ; Online: Faster detection of asymptomatic COVID-19 cases among care home staff in England through the combination of SARS-CoV-2 testing technologies.

Ryan, Finola / Cole-Hamilton, Joanna / Dandamudi, Niharika / Futschik, Matthias E / Needham, Alexander / Saquib, Rida / Kulasegaran-Shylini, Raghavendran / Blandford, Edward / Kidd, Michael / O'Moore, Éamonn / Hall, Ian / Sudhanva, Malur / Klapper, Paul / Dodgson, Andrew / Moore, Adam / Duke, Madeleine / Tunkel, Sarah / Kenny, Chris / Fowler, Tom

Scientific reports

2024 Volume 14, Issue 1, Page(s) 7475

Abstract: To detect SARS-CoV-2 amongst asymptomatic care home staff in England, a dual-technology weekly testing regime was introduced on 23 December 2020. A lateral flow device (LFD) and quantitative reverse transcription polymerase chain reaction (qRT-PCR) test ... ...

Abstract	To detect SARS-CoV-2 amongst asymptomatic care home staff in England, a dual-technology weekly testing regime was introduced on 23 December 2020. A lateral flow device (LFD) and quantitative reverse transcription polymerase chain reaction (qRT-PCR) test were taken on the same day (day 0) and a midweek LFD test was taken three to four days later. We evaluated the effectiveness of using dual-technology to detect SARS-CoV-2 between December 2020 to April 2021. Viral concentrations derived from qRT-PCR were used to determine the probable stage of infection and likely level of infectiousness. Day 0 PCR detected 1,493 cases of COVID-19, of which 53% were in the early stages of infection with little to no risk of transmission. Day 0 LFD detected 83% of cases that were highly likely to be infectious. On average, LFD results were received 46.3 h earlier than PCR, enabling removal of likely infectious staff from the workplace quicker than by weekly PCR alone. Demonstrating the rapidity of LFDs to detect highly infectious cases could be combined with the ability of PCR to detect cases in the very early stages of infection. In practice, asymptomatic care home staff were removed from the workplace earlier, breaking potential chains of transmission.
MeSH term(s)	Humans ; SARS-CoV-2/genetics ; COVID-19/diagnosis ; COVID-19/epidemiology ; COVID-19 Testing ; England/epidemiology
Language	English
Publishing date	2024-03-29
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-57817-1
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Article ; Online: Polymer Microparticles with Defined Surface Chemistry and Topography Mediate the Formation of Stem Cell Aggregates and Cardiomyocyte Function.

Alvarez-Paino, Marta / Amer, Mahetab H / Nasir, Aishah / Cuzzucoli Crucitti, Valentina / Thorpe, Jordan / Burroughs, Laurence / Needham, David / Denning, Chris / Alexander, Morgan R / Alexander, Cameron / Rose, Felicity R A J

ACS applied materials & interfaces

2019 Volume 11, Issue 38, Page(s) 34560–34574

Abstract: Surface-functionalized microparticles are relevant to fields spanning engineering and biomedicine, with uses ranging from cell culture to advanced cell delivery. Varying topographies of biomaterial surfaces are also being investigated as mediators of ... ...

Abstract	Surface-functionalized microparticles are relevant to fields spanning engineering and biomedicine, with uses ranging from cell culture to advanced cell delivery. Varying topographies of biomaterial surfaces are also being investigated as mediators of cell-material interactions and subsequent cell fate. To investigate competing or synergistic effects of chemistry and topography in three-dimensional cell cultures, methods are required to introduce these onto microparticles without modification of their underlying morphology or bulk properties. In this study, a new approach for surface functionalization of poly(lactic acid) (PLA) microparticles is reported that allows decoration of the outer shell of the polyesters with additional polymers via aqueous atom transfer radical polymerization routes. PLA microparticles with smooth or dimpled surfaces were functionalized with poly(poly(ethylene glycol) methacrylate) and poly[
MeSH term(s)	Cell Aggregation/drug effects ; Cell Differentiation ; Cell Line, Transformed ; Humans ; Induced Pluripotent Stem Cells/cytology ; Induced Pluripotent Stem Cells/metabolism ; Mesenchymal Stem Cells/cytology ; Mesenchymal Stem Cells/metabolism ; Microplastics/chemistry ; Microplastics/pharmacology ; Myocytes, Cardiac/cytology ; Myocytes, Cardiac/metabolism ; Polyesters/chemistry ; Polyesters/pharmacology
Chemical Substances	Microplastics ; Polyesters
Language	English
Publishing date	2019-09-10
Publishing country	United States
Document type	Journal Article
ISSN	1944-8252
ISSN (online)	1944-8252
DOI	10.1021/acsami.9b04769
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Article ; Online: Functional characterisation of the amyotrophic lateral sclerosis risk locus GPX3/TNIP1.

Restuadi, Restuadi / Steyn, Frederik J / Kabashi, Edor / Ngo, Shyuan T / Cheng, Fei-Fei / Nabais, Marta F / Thompson, Mike J / Qi, Ting / Wu, Yang / Henders, Anjali K / Wallace, Leanne / Bye, Chris R / Turner, Bradley J / Ziser, Laura / Mathers, Susan / McCombe, Pamela A / Needham, Merrilee / Schultz, David / Kiernan, Matthew C /

van Rheenen, Wouter / van den Berg, Leonard H / Veldink, Jan H / Ophoff, Roel / Gusev, Alexander / Zaitlen, Noah / McRae, Allan F / Henderson, Robert D / Wray, Naomi R / Giacomotto, Jean / Garton, Fleur C

Genome medicine

2022 Volume 14, Issue 1, Page(s) 7

Abstract: Background: Amyotrophic lateral sclerosis (ALS) is a complex, late-onset, neurodegenerative disease with a genetic contribution to disease liability. Genome-wide association studies (GWAS) have identified ten risk loci to date, including the TNIP1/GPX3 ... ...

Abstract	Background: Amyotrophic lateral sclerosis (ALS) is a complex, late-onset, neurodegenerative disease with a genetic contribution to disease liability. Genome-wide association studies (GWAS) have identified ten risk loci to date, including the TNIP1/GPX3 locus on chromosome five. Given association analysis data alone cannot determine the most plausible risk gene for this locus, we undertook a comprehensive suite of in silico, in vivo and in vitro studies to address this. Methods: The Functional Mapping and Annotation (FUMA) pipeline and five tools (conditional and joint analysis (GCTA-COJO), Stratified Linkage Disequilibrium Score Regression (S-LDSC), Polygenic Priority Scoring (PoPS), Summary-based Mendelian Randomisation (SMR-HEIDI) and transcriptome-wide association study (TWAS) analyses) were used to perform bioinformatic integration of GWAS data (N Results: SMR analyses implicated both TNIP1 and GPX3 (p < 1.15 × 10 Conclusions: These results support GPX3 as a lead ALS risk gene in this locus, with more data needed to confirm/reject a role for TNIP1. This has implications for understanding disease mechanisms (GPX3 acts in the same pathway as SOD1, a well-established ALS-associated gene) and identifying new therapeutic approaches. Few previous examples of in-depth investigations of risk loci in ALS exist and a similar approach could be applied to investigate future expected GWAS findings.
MeSH term(s)	Amyotrophic Lateral Sclerosis/genetics ; Animals ; Genetic Predisposition to Disease ; Genome-Wide Association Study/methods ; Humans ; Neurodegenerative Diseases ; Polymorphism, Single Nucleotide ; Zebrafish/genetics
Language	English
Publishing date	2022-01-19
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2484394-5
ISSN	1756-994X ; 1756-994X
ISSN (online)	1756-994X
ISSN	1756-994X
DOI	10.1186/s13073-021-01006-6
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Article ; Online: Functional characterisation of the amyotrophic lateral sclerosis risk locus GPX3/TNIP1

Restuadi Restuadi / Frederik J. Steyn / Edor Kabashi / Shyuan T. Ngo / Fei-Fei Cheng / Marta F. Nabais / Mike J. Thompson / Ting Qi / Yang Wu / Anjali K. Henders / Leanne Wallace / Chris R. Bye / Bradley J. Turner / Laura Ziser / Susan Mathers / Pamela A. McCombe / Merrilee Needham / David Schultz / Matthew C. Kiernan /

Wouter van Rheenen / Leonard H. van den Berg / Jan H. Veldink / Roel Ophoff / Alexander Gusev / Noah Zaitlen / Allan F. McRae / Robert D. Henderson / Naomi R. Wray / Jean Giacomotto / Fleur C. Garton

Genome Medicine, Vol 14, Iss 1, Pp 1-

2022 Volume 22

Abstract: Abstract Background Amyotrophic lateral sclerosis (ALS) is a complex, late-onset, neurodegenerative disease with a genetic contribution to disease liability. Genome-wide association studies (GWAS) have identified ten risk loci to date, including the ... ...

Abstract	Abstract Background Amyotrophic lateral sclerosis (ALS) is a complex, late-onset, neurodegenerative disease with a genetic contribution to disease liability. Genome-wide association studies (GWAS) have identified ten risk loci to date, including the TNIP1/GPX3 locus on chromosome five. Given association analysis data alone cannot determine the most plausible risk gene for this locus, we undertook a comprehensive suite of in silico, in vivo and in vitro studies to address this. Methods The Functional Mapping and Annotation (FUMA) pipeline and five tools (conditional and joint analysis (GCTA-COJO), Stratified Linkage Disequilibrium Score Regression (S-LDSC), Polygenic Priority Scoring (PoPS), Summary-based Mendelian Randomisation (SMR-HEIDI) and transcriptome-wide association study (TWAS) analyses) were used to perform bioinformatic integration of GWAS data (N cases = 20,806, N controls = 59,804) with ‘omics reference datasets including the blood (eQTLgen consortium N = 31,684) and brain (N = 2581). This was followed up by specific expression studies in ALS case-control cohorts (microarray N total = 942, protein N total = 300) and gene knockdown (KD) studies of human neuronal iPSC cells and zebrafish-morpholinos (MO). Results SMR analyses implicated both TNIP1 and GPX3 (p < 1.15 × 10−6), but there was no simple SNP/expression relationship. Integrating multiple datasets using PoPS supported GPX3 but not TNIP1. In vivo expression analyses from blood in ALS cases identified that lower GPX3 expression correlated with a more progressed disease (ALS functional rating score, p = 5.5 × 10−3, adjusted R 2 = 0.042, B effect = 27.4 ± 13.3 ng/ml/ALSFRS unit) with microarray and protein data suggesting lower expression with risk allele (recessive model p = 0.06, p = 0.02 respectively). Validation in vivo indicated gpx3 KD caused significant motor deficits in zebrafish-MO (mean difference vs. control ± 95% CI, vs. control, swim distance = 112 ± 28 mm, time = 1.29 ± 0.59 s, speed = 32.0 ± 2.53 mm/s, respectively, p for all ...
Keywords	Motor neurone disease ; MND ; Genome-wide association study ; Computational biology ; Zebrafish ; Neurodegenerative diseases ; Medicine ; R ; Genetics ; QH426-470
Subject code	610
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Provisional practice recommendation for the management of myopathy in VCP-associated multisystem proteinopathy.

Annals of clinical and translational neurology

2023 Volume 10, Issue 5, Page(s) 686–695

Abstract: Valosin-containing protein (VCP)-associated multisystem proteinopathy (MSP) is a rare genetic disorder with abnormalities in the autophagy pathway leading to various combinations of myopathy, bone diseases, and neurodegeneration. Ninety percent of ... ...

Abstract	Valosin-containing protein (VCP)-associated multisystem proteinopathy (MSP) is a rare genetic disorder with abnormalities in the autophagy pathway leading to various combinations of myopathy, bone diseases, and neurodegeneration. Ninety percent of patients with VCP-associated MSP have myopathy, but there is no consensus-based guideline. The goal of this working group was to develop a best practice set of provisional recommendations for VCP myopathy which can be easily implemented across the globe. As an initiative by Cure VCP Disease Inc., a patient advocacy organization, an online survey was initially conducted to identify the practice gaps in VCP myopathy. All prior published literature on VCP myopathy was reviewed to better understand the different aspects of management of VCP myopathy, and several working group sessions were conducted involving international experts to develop this provisional recommendation. VCP myopathy has a heterogeneous clinical phenotype and should be considered in patients with limb-girdle muscular dystrophy phenotype, or any myopathy with an autosomal dominant pattern of inheritance. Genetic testing is the only definitive way to diagnose VCP myopathy, and single-variant testing in the case of a known familial VCP variant, or multi-gene panel sequencing in undifferentiated cases can be considered. Muscle biopsy is important in cases of diagnostic uncertainty or lack of a definitive pathogenic genetic variant since rimmed vacuoles (present in ~40% cases) are considered a hallmark of VCP myopathy. Electrodiagnostic studies and magnetic resonance imaging can also help rule out disease mimics. Standardized management of VCP myopathy will optimize patient care and help future research initiatives.
MeSH term(s)	Humans ; Valosin Containing Protein/genetics ; Muscular Diseases/diagnosis ; Muscular Diseases/genetics ; Muscular Diseases/therapy ; Muscular Dystrophies, Limb-Girdle/diagnosis ; Muscular Dystrophies, Limb-Girdle/genetics ; Muscular Dystrophies, Limb-Girdle/therapy ; Phenotype ; Proteostasis Deficiencies
Chemical Substances	Valosin Containing Protein (EC 3.6.4.6) ; VCP protein, human (EC 3.6.4.6)
Language	English
Publishing date	2023-04-07
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2740696-9
ISSN	2328-9503 ; 2328-9503
ISSN (online)	2328-9503
ISSN	2328-9503
DOI	10.1002/acn3.51760
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Article ; Online: A primer on learning in Bayesian networks for computational biology.

Needham, Chris J / Bradford, James R / Bulpitt, Andrew J / Westhead, David R

PLoS computational biology

2007 Volume 3, Issue 8, Page(s) e129

MeSH term(s)	Algorithms ; Artificial Intelligence ; Bayes Theorem ; Computational Biology/methods ; Computer Simulation ; Models, Biological ; Models, Statistical ; Pattern Recognition, Automated/methods
Language	English
Publishing date	2007-09-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2193340-6
ISSN	1553-7358 ; 1553-734X
ISSN (online)	1553-7358
ISSN	1553-734X
DOI	10.1371/journal.pcbi.0030129
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Article: Polymer Microparticles with Defined Surface Chemistry and Topography Mediate the Formation of Stem Cell Aggregates and Cardiomyocyte Function

ACS applied materials & interfaces. 2019 June 20, v. 11, no. 38

2019

Abstract	Surface-functionalized microparticles are relevant to fields spanning engineering and biomedicine, with uses ranging from cell culture to advanced cell delivery. Varying topographies of biomaterial surfaces are also being investigated as mediators of cell–material interactions and subsequent cell fate. To investigate competing or synergistic effects of chemistry and topography in three-dimensional cell cultures, methods are required to introduce these onto microparticles without modification of their underlying morphology or bulk properties. In this study, a new approach for surface functionalization of poly(lactic acid) (PLA) microparticles is reported that allows decoration of the outer shell of the polyesters with additional polymers via aqueous atom transfer radical polymerization routes. PLA microparticles with smooth or dimpled surfaces were functionalized with poly(poly(ethylene glycol) methacrylate) and poly[N-(3-aminopropyl)methacrylamide] brushes, chosen for their potential abilities to mediate cell adhesion. X-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectrometry analysis indicated homogeneous coverage of the microparticles with polymer brushes while maintaining the original topographies. These materials were used to investigate the relative importance of surface chemistry and topography both on the formation of human immortalized mesenchymal stem cell (hiMSCs) particle–cell aggregates and on the enhanced contractility of cardiomyocytes derived from human-induced pluripotent stem cells (hiPSC-CMs). The influence of surface chemistry was found to be more important on the size of particle–cell aggregates than topographies. In addition, surface chemistries that best promoted hiMSC attachment also improved hiPSC-CM attachment and contractility. These studies demonstrated a new route to obtain topo-chemical combinations on polyester-based biomaterials and provided clear evidence for the predominant effect of surface functionality over micron-scale dimpled topography in cell–microparticle interactions. These findings, thus, provide new guiding principles for the design of biomaterial interfaces to direct cell function.
Keywords	X-ray photoelectron spectroscopy ; biocompatible materials ; cardiomyocytes ; cell adhesion ; cell aggregates ; cell culture ; humans ; induced pluripotent stem cells ; mass spectrometry ; medicine ; mesenchymal stromal cells ; microparticles ; polyesters ; polyethylene glycol ; polylactic acid ; polymerization ; synergism
Language	English
Dates of publication	2019-0620
Size	p. 34560-34574.
Publishing place	American Chemical Society
Document type	Article
ISSN	1944-8252
DOI	10.1021/acsami.9b04769
Database	NAL-Catalogue (AGRICOLA)

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Article: Inference in Bayesian networks.

Needham, Chris J / Bradford, James R / Bulpitt, Andrew J / Westhead, David R

Nature biotechnology

2006 Volume 24, Issue 1, Page(s) 51–53

MeSH term(s)	Animals ; Bayes Theorem ; Cell Physiological Phenomena ; Computer Simulation ; Gene Expression Regulation/physiology ; Humans ; Models, Biological ; Models, Statistical ; Proteome/metabolism ; Signal Transduction/physiology
Chemical Substances	Proteome
Language	English
Publishing date	2006-01-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	1311932-1
ISSN	1546-1696 ; 1087-0156
ISSN (online)	1546-1696
ISSN	1087-0156
DOI	10.1038/nbt0106-51
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Zs.A 2167: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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