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Article ; Online: Theory of general balance applied to step wedge designs.

Bond, Simon

2018 Volume 38, Issue 2, Page(s) 184–191

Abstract: A standard idealized step-wedge design satisfies the requirements, in terms of the structure of the observation units, to be considered a balanced design and can be labeled as a criss-cross design (time crossed with cluster) with replication. As such, ... ...

Abstract	A standard idealized step-wedge design satisfies the requirements, in terms of the structure of the observation units, to be considered a balanced design and can be labeled as a criss-cross design (time crossed with cluster) with replication. As such, Nelder's theory of general balance can be used to decompose the analysis of variance into independent strata (grand mean, cluster, time, cluster:time, residuals). If time is considered as a fixed effect, then the treatment effect of interest is estimated solely within the cluster and time:cluster strata; the time effects are estimated solely within the time stratum. This separation leads directly to scalar, rather than matrix, algebraic manipulations to provide closed-form expressions for standard errors of the treatment effect estimate. We use the tools provided by the theory of general balance to obtain an expression for the standard error of the estimated treatment effect in a general case where the assumed covariance structure includes random-effects at the time and time:cluster levels. This provides insights that are helpful for experimental design regarding the assumed correlation within clusters over time, sample size in terms of numbers of clusters and replication within cluster, and components of the standard error for estimated treatment effect.
MeSH term(s)	Cluster Analysis ; Data Interpretation, Statistical ; Humans ; Models, Statistical ; Observational Studies as Topic/methods ; Statistics as Topic ; Time Factors
Language	English
Publishing date	2018-09-12
Publishing country	England
Document type	Journal Article
ZDB-ID	843037-8
ISSN	1097-0258 ; 0277-6715
ISSN (online)	1097-0258
ISSN	0277-6715
DOI	10.1002/sim.7960
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Article: Adipose-Derived Extracellular Vesicles: Systemic Messengers and Metabolic Regulators in Health and Disease.

Bond, Simon T / Calkin, Anna C / Drew, Brian G

Frontiers in physiology

2022 Volume 13, Page(s) 837001

Abstract: Adipose tissue is comprised of a heterogeneous population of cells that co-operate to perform diverse physiological roles including endocrine-related functions. The endocrine role of adipose tissue enables it to communicate nutritional and health cues to ...

Abstract	Adipose tissue is comprised of a heterogeneous population of cells that co-operate to perform diverse physiological roles including endocrine-related functions. The endocrine role of adipose tissue enables it to communicate nutritional and health cues to other organs, such as the liver, muscle, and brain, in order to regulate appetite and whole body metabolism. Adipose tissue dysfunction, which is often observed in obesity, is associated with changes in the adipose secretome, which can subsequently contribute to disease pathology. Indeed, secreted bioactive factors released from adipose tissue contribute to metabolic homeostasis and likely play a causal role in disease; however, what constitutes the entirety of the adipose tissue secretome is still poorly understood. Recent advances in nanotechnology have advanced this field substantially and have led to the identification of small, secreted particles known as extracellular vesicles (EVs). These small nano-sized lipid envelopes are released by most cell types and are capable of systemically delivering bioactive molecules, such as nucleic acids, proteins, and lipids. EVs interact with target cells to deliver specific cargo that can then elicit effects in various tissues throughout the body. Adipose tissue has recently been shown to secrete EVs that can communicate with the periphery to maintain metabolic homeostasis, or under certain pathological conditions, drive disease. In this review, we discuss the current landscape of adipose tissue-derived EVs, with a focus on their role in the regulation of metabolic homeostasis and disease pathology.
Language	English
Publishing date	2022-02-23
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2022.837001
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Article ; Online: Sex differences in white adipose tissue expansion: emerging molecular mechanisms.

Bond, Simon T / Calkin, Anna C / Drew, Brian G

Clinical science (London, England : 1979)

2022 Volume 135, Issue 24, Page(s) 2691–2708

Abstract: The escalating prevalence of individuals becoming overweight and obese is a rapidly rising global health problem, placing an enormous burden on health and economic systems worldwide. Whilst obesity has well described lifestyle drivers, there is also a ... ...

Abstract	The escalating prevalence of individuals becoming overweight and obese is a rapidly rising global health problem, placing an enormous burden on health and economic systems worldwide. Whilst obesity has well described lifestyle drivers, there is also a significant and poorly understood component that is regulated by genetics. Furthermore, there is clear evidence for sexual dimorphism in obesity, where overall risk, degree, subtype and potential complications arising from obesity all differ between males and females. The molecular mechanisms that dictate these sex differences remain mostly uncharacterised. Many studies have demonstrated that this dimorphism is unable to be solely explained by changes in hormones and their nuclear receptors alone, and instead manifests from coordinated and highly regulated gene networks, both during development and throughout life. As we acquire more knowledge in this area from approaches such as large-scale genomic association studies, the more we appreciate the true complexity and heterogeneity of obesity. Nevertheless, over the past two decades, researchers have made enormous progress in this field, and some consistent and robust mechanisms continue to be established. In this review, we will discuss some of the proposed mechanisms underlying sexual dimorphism in obesity, and discuss some of the key regulators that influence this phenomenon.
MeSH term(s)	Adipose Tissue, White/metabolism ; Adipose Tissue, White/physiopathology ; Female ; Humans ; Male ; Obesity/genetics ; Obesity/physiopathology ; Sex Characteristics
Language	English
Publishing date	2022-01-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	206835-7
ISSN	1470-8736 ; 0301-0538 ; 0009-0360 ; 0143-5221
ISSN (online)	1470-8736
ISSN	0301-0538 ; 0009-0360 ; 0143-5221
DOI	10.1042/CS20210086
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Article ; Online: Acetabular Fractures in older patients Intervention Trial (AceFIT): a feasibility triple-arm randomized controlled study.

Carrothers, Andrew / O'Leary, Ronan / Hull, Peter / Chou, Daud / Alsousou, Joseph / Queally, Joseph / Bond, Simon J / Costa, Matthew L

The bone & joint journal

2024 Volume 106-B, Issue 4, Page(s) 401–411

Abstract: Aims: To assess the feasibility of a randomized controlled trial (RCT) that compares three treatments for acetabular fractures in older patients: surgical fixation, surgical fixation and hip arthroplasty (fix-and-replace), and non-surgical treatment.: ...

Abstract	Aims: To assess the feasibility of a randomized controlled trial (RCT) that compares three treatments for acetabular fractures in older patients: surgical fixation, surgical fixation and hip arthroplasty (fix-and-replace), and non-surgical treatment. Methods: Patients were recruited from seven UK NHS centres and randomized to a three-arm pilot trial if aged older than 60 years and had a displaced acetabular fracture. Feasibility outcomes included patients' willingness to participate, clinicians' capability to recruit, and dropout rates. The primary clinical outcome measure was the EuroQol five-dimension questionnaire (EQ-5D) at six months. Secondary outcomes were Oxford Hip Score, Disability Rating Index, blood loss, and radiological and mobility assessments. Results: Between December 2017 and December 2019, 60 patients were recruited (median age 77.4 years, range 63.3 to 88.5) (39/21 M/F ratio). At final nine-month follow-up, 4/60 (7%) had withdrawn, 4/60 (7%) had died, and one had been lost to follow-up; a 98% response rate (50/51) was achieved for the EQ-5D questionnaire. Four deaths were recorded during the three-year trial period: three in the non-surgical treatment group and one in the fix-and-replace group. Conclusion: This study has shown a full-scale RCT to be feasible, but will need international recruitment. The Acetabular Fractures in older patients Intervention Trial (AceFIT) has informed the design of a multinational RCT sample size of 1,474 or 1,974 patients for a minimal clinically important difference of 0.06 on EQ-5D, with a power of 0.8 or 0.9, and loss to follow-up of 20%. This observed patient cohort comprises a medically complex group requiring multidisciplinary care; surgeon, anaesthetist, and ortho-geriatrician input is needed to optimize recovery and rehabilitation.
MeSH term(s)	Humans ; Aged ; Middle Aged ; Aged, 80 and over ; Feasibility Studies ; Hip Fractures ; Spinal Fractures ; Research Design ; Arthroplasty, Replacement ; Treatment Outcome
Language	English
Publishing date	2024-04-01
Publishing country	England
Document type	Randomized Controlled Trial ; Journal Article
ZDB-ID	2697156-2
ISSN	2049-4408 ; 2049-4394
ISSN (online)	2049-4408
ISSN	2049-4394
DOI	10.1302/0301-620X.106B4.BJJ-2023-1080.R1
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Article ; Online: Cost-effectiveness of real time continuous glucose monitoring to target glucose control in preterm infants.

Petrou, Stavros / Kim, Sungwook / Bond, Simon / Allison, Annabel / Beardsall, Kathryn

Seminars in perinatology

2021 Volume 45, Issue 3, Page(s) 151392

Abstract: The optimal management of glucose levels in critical care remains an area for research due to the problems of balancing the risks of hyperglycemia versus hypoglycemia. This paper reports the first economic evaluation of real time continuous glucose ... ...

Abstract	The optimal management of glucose levels in critical care remains an area for research due to the problems of balancing the risks of hyperglycemia versus hypoglycemia. This paper reports the first economic evaluation of real time continuous glucose monitoring to guide the clinical management of preterm infants, based on evidence from the REACT trial. Bivariate regression of costs (£, 2016-17 prices) and cases of adequate glucose control, with multiple imputation of missing data, was conducted. When the economic evaluation was restricted to the first week of life, real time continuous glucose monitoring was associated with increased costs and a statistically significant increase in adequate glucose control. When the assessment was performed over a time horizon extending to 36 weeks' corrected gestational age, real time CGM was dominant in health economic terms, i.e. associated with lower costs and better outcomes. These results largely remained robust to a range of sensitivity analyses and sub-group analyses designed to address uncertainty and heterogeneity surrounding the cost-effectiveness outcomes. This study suggests that the use of real time continuous glucose monitoring in preterm infants is associated with a high probability of cost-effectiveness.
MeSH term(s)	Blood Glucose ; Blood Glucose Self-Monitoring ; Cost-Benefit Analysis ; Humans ; Hypoglycemia/prevention & control ; Infant, Newborn ; Infant, Premature
Chemical Substances	Blood Glucose
Language	English
Publishing date	2021-01-27
Publishing country	United States
Document type	Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	752403-1
ISSN	1558-075X ; 0146-0005
ISSN (online)	1558-075X
ISSN	0146-0005
DOI	10.1016/j.semperi.2021.151392
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Article: Editorial: Adipose Tissue in Obesity and Metabolic Disease.

Keshvari, Sahar / Ceddia, Ryan P / Rajbhandari, Prashant / Chaurasia, Bhagirath / Bond, Simon T

Frontiers in physiology

2022 Volume 13, Page(s) 898861

Language	English
Publishing date	2022-04-19
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2022.898861
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Article ; Online: Loss of Trim28 in muscle alters mitochondrial signalling but not systemic metabolism.

King, Emily J / Bond, Simon T / Yang, Christine / Liu, Yingying / Calkin, Anna C / Henstridge, Darren C / Drew, Brian G

The Journal of endocrinology

2023 Volume 259, Issue 2

Abstract: Type 2 diabetes mellitus (T2DM), a condition characterised by insulin resistance (IR) and skeletal muscle mitochondrial abnormalities, is a leading cause of death in developed societies. Much work has postulated that improving pathways linked to ... ...

Abstract	Type 2 diabetes mellitus (T2DM), a condition characterised by insulin resistance (IR) and skeletal muscle mitochondrial abnormalities, is a leading cause of death in developed societies. Much work has postulated that improving pathways linked to mitochondrial health, including autophagy, may be a potential avenue to prevent or treat T2DM. Given the recent data indicating a role for tripartite motif-containing 28 (TRIM28) in autophagy and mitochondrial pathways, we investigated whether muscle-specific deletion of TRIM28 might impact on obesity, glucose tolerance, and IR in mice. We studied two different muscle-specific (MCK-cre and ACTA1-cre-ERT2) TRIM28 knockout models, which were phenotyped during and after being fed a chow or high-fat diet (HFD). Whilst muscle-specific deletion of TRIM28 in both models demonstrated alterations in markers of mitochondrial activity and autophagy in skeletal muscle, we did not observe major impacts on the majority of metabolic measures in these mice. Specifically, we demonstrate that deletion of TRIM28 in skeletal muscle of mice during (MCK-cre) or post-development (ACTA1-cre-ERT2) does not prevent HFD-induced obesity or glucose intolerance. These findings are consistent with those reported previously in relation to autophagy and mitochondria in other cell types, and thus warrant further study into the biological role TRIM28 has in relation to mitochondrial function.
MeSH term(s)	Mice ; Animals ; Diabetes Mellitus, Type 2/metabolism ; Insulin Resistance/genetics ; Muscle, Skeletal/metabolism ; Glucose Intolerance/metabolism ; Obesity/metabolism ; Diet, High-Fat/adverse effects ; Mice, Inbred C57BL ; Mitochondria, Muscle/metabolism ; Tripartite Motif-Containing Protein 28/metabolism
Chemical Substances	Trim28 protein, mouse (EC 2.3.2.27) ; Tripartite Motif-Containing Protein 28 (EC 2.3.2.27)
Language	English
Publishing date	2023-10-09
Publishing country	England
Document type	Journal Article
ZDB-ID	3028-4
ISSN	1479-6805 ; 0022-0795
ISSN (online)	1479-6805
ISSN	0022-0795
DOI	10.1530/JOE-23-0210
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Article ; Online: Deletion of the muscle enriched lncRNA Oip5os1 induces atrial dysfunction in male mice with diabetes.

Zhuang, Aowen / Tan, Yanie / Liu, Yingying / Yang, Christine / Kiriazis, Helen / Grigolon, Kyah / Walker, Shannen / Bond, Simon T / McMullen, Julie R / Calkin, Anna C / Drew, Brian G

Physiological reports

2024 Volume 11, Issue 23, Page(s) e15869

Abstract: Long ncRNAs (lncRNAs) have been shown to play a biological and physiological role in various tissues including the heart. We and others have previously established that the lncRNA Oip5os1 (1700020I14Rik, OIP5-AS1, Cyrano) is enriched in striated muscles, ...

Abstract	Long ncRNAs (lncRNAs) have been shown to play a biological and physiological role in various tissues including the heart. We and others have previously established that the lncRNA Oip5os1 (1700020I14Rik, OIP5-AS1, Cyrano) is enriched in striated muscles, and its deletion in mice leads to defects in both skeletal and cardiac muscle function. In the present study, we investigated the impact of global Oip5os1 deletion on cardiac function in the setting of streptozotocin (STZ)-induced diabetes. Specifically, we studied male WT and KO mice with or without diabetes for 24 weeks, and phenotyped animals for metabolic and cardiac endpoints. Independent of genotype, diabetes was associated with left ventricular diastolic dysfunction based on a fall in E'/A' ratio. Deletion of Oip5os1 in a setting of diabetes had no significant impact on ventricular function or ventricular weight, but was associated with left atrial dysfunction (reduced fractional shortening) and myopathy which was associated with anesthesia intolerance and premature death in the majority of KO mice tested during cardiac functional assessment. This atrial phenotype was not observed in WT diabetic mice. The most striking molecular difference was a reduction in the metabolic regulator ERRalpha in the atria of KO mice compared with WT mice. There was also a trend for a reduction in Serca2a. These findings highlight Oip5os1 as a gene of interest in aspects of atrial function in the setting of diabetes, highlighting an additional functional role for this lncRNA in cardiac pathological settings.
MeSH term(s)	Animals ; Male ; Mice ; Atrial Fibrillation/complications ; Atrial Fibrillation/genetics ; Diabetes Mellitus, Experimental/complications ; Diabetes Mellitus, Experimental/pathology ; Heart Atria/metabolism ; Heart Atria/pathology ; Myocardium/pathology ; RNA, Long Noncoding/genetics
Chemical Substances	RNA, Long Noncoding
Language	English
Publishing date	2024-04-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	2724325-4
ISSN	2051-817X ; 2051-817X
ISSN (online)	2051-817X
ISSN	2051-817X
DOI	10.14814/phy2.15869
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Article: rpsftm: An R Package for Rank Preserving Structural Failure Time Models.

Allison, Annabel / White, Ian R / Bond, Simon

The R journal

2018 Volume 9, Issue 2, Page(s) 342–353

Abstract: Treatment switching in a randomised controlled trial occurs when participants change from their randomised treatment to the other trial treatment during the study. Failure to account for treatment switching in the analysis (i.e. by performing a standard ... ...

Abstract	Treatment switching in a randomised controlled trial occurs when participants change from their randomised treatment to the other trial treatment during the study. Failure to account for treatment switching in the analysis (i.e. by performing a standard intention-to-treat analysis) can lead to biased estimates of treatment efficacy. The rank preserving structural failure time model (RPSFTM) is a method used to adjust for treatment switching in trials with survival outcomes. The RPSFTM is due to Robins and Tsiatis (1991) and has been developed by White et al. (1997, 1999). The method is randomisation based and uses only the randomised treatment group, observed event times, and treatment history in order to estimate a causal treatment effect. The treatment effect,
Language	English
Publishing date	2018-01-31
Publishing country	United States
Document type	Journal Article
ISSN	2073-4859
ISSN	2073-4859
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Article: The Antioxidant Moiety of MitoQ Imparts Minimal Metabolic Effects in Adipose Tissue of High Fat Fed Mice.

Bond, Simon T / Kim, Jisu / Calkin, Anna C / Drew, Brian G

Frontiers in physiology

2019 Volume 10, Page(s) 543

Abstract: Mitochondrial dysfunction is associated with a diverse array of diseases ranging from dystrophy and heart failure to obesity and hepatosteatosis. One of the major biochemical consequences of impaired mitochondrial function is an accumulation of ... ...

Abstract	Mitochondrial dysfunction is associated with a diverse array of diseases ranging from dystrophy and heart failure to obesity and hepatosteatosis. One of the major biochemical consequences of impaired mitochondrial function is an accumulation of mitochondrial superoxide, or reactive oxygen species (ROS). Excessive ROS can be detrimental to cellular health and is proposed to underpin many mitochondrial diseases. Accordingly, much research has been committed to understanding ways to therapeutically prevent and reduce ROS accumulation. In white adipose tissue (WAT), ROS is associated with obesity and its subsequent complications, and thus reducing mitochondrial ROS may represent a novel strategy for treating obesity related disorders. One therapeutic approach employed to reduce ROS abundance is the mitochondrial-targeted coenzyme Q (MitoQ), which enables mitochondrial specific delivery of a CoQ10 antioxidant via its triphenylphosphonium bromide (TPP+) cation. Indeed, MitoQ has been successfully shown to accumulate at the outer mitochondrial membrane and prevent ROS accumulation in several tissues
Language	English
Publishing date	2019-05-08
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2019.00543
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