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Article ; Online: Microalgae: potential novel protein for sustainable human nutrition.

Williamson, Ellen / Ross, Ian L / Wall, Benjamin T / Hankamer, Benjamin

2023 Volume 29, Issue 3, Page(s) 370–382

Abstract: To support a global population of ~10 billion people in 2050, dietary protein demand is forecast to increase 32-78% compared to 2017, requiring significantly higher planetary resources. Microalgae are an attractive sustainable protein source compared ... ...

Abstract	To support a global population of ~10 billion people in 2050, dietary protein demand is forecast to increase 32-78% compared to 2017, requiring significantly higher planetary resources. Microalgae are an attractive sustainable protein source compared with current plant and animal sources. Benefits include mass scalability, low CO
MeSH term(s)	Animals ; Humans ; Microalgae
Language	English
Publishing date	2023-09-08
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1305448-x
ISSN	1878-4372 ; 1360-1385
ISSN (online)	1878-4372
ISSN	1360-1385
DOI	10.1016/j.tplants.2023.08.006
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Article ; Online: Integrated survey methodologies provide process-driven framework for marine renewable energy environmental impact assessment.

Chapman, James / Williamson, Benjamin J / Couto, Ana / Zampollo, Arianna / Davies, Ian M / Scott, Beth E

Marine environmental research

2024 Volume 198, Page(s) 106532

Abstract: Environmental interactions of marine renewable energy developments vary from fine-scale direct (e.g. potential collision) to indirect wide-scale hydrodynamic changes altering oceanographic features. Current UK Environmental Impact Assessment (EIA) and ... ...

Abstract	Environmental interactions of marine renewable energy developments vary from fine-scale direct (e.g. potential collision) to indirect wide-scale hydrodynamic changes altering oceanographic features. Current UK Environmental Impact Assessment (EIA) and associated Habitats Regulations Appraisal (HRA) guidelines have limited focus on underlying processes affecting distribution and movements (hence vulnerability) of top predators. This study integrates multi-trophic ship survey (active acoustics and observer data) with an upward-facing seabed platform and 3-dimensional hydrodynamic model as a process-driven framework to investigate predator-prey linkages between seabirds and fish schools. Observer-only data highlighted the need to measure physical drivers of variance in species abundances and distributions. Active acoustics indicated that in situ (preferable to modelled) data were needed to identify temporal changes in hydrodynamics to predict prey and consequently top predator presence. Revising methods to identify key habitats and environmental covariates within current regulatory frameworks will enable more robust and transferable EIA and HRA processes and outputs, and at larger scales for cumulative and strategic-level assessments, enabling future modelling of ecosystem impacts from both climate change and renewable energy extraction.
Language	English
Publishing date	2024-05-03
Publishing country	England
Document type	Journal Article
ZDB-ID	1502505-6
ISSN	1879-0291 ; 0141-1136
ISSN (online)	1879-0291
ISSN	0141-1136
DOI	10.1016/j.marenvres.2024.106532
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Article: Assembly of the Bacterial Ribosome with Circularly Permuted rRNA.

Dong, Xiyu / Sheng, Kai / Gebert, Luca F R / Aiyer, Sriram / MacRae, Ian J / Lyumkis, Dmitry / Williamson, James R

bioRxiv : the preprint server for biology

2024

Abstract: Co-transcriptional assembly is an integral feature of the formation of RNA-protein complexes that mediate translation. For ribosome synthesis, prior studies have indicated that the strict order of transcription of rRNA domains may not be obligatory ... ...

Abstract	Co-transcriptional assembly is an integral feature of the formation of RNA-protein complexes that mediate translation. For ribosome synthesis, prior studies have indicated that the strict order of transcription of rRNA domains may not be obligatory during bacterial ribosome biogenesis, since a series of circularly permuted rRNAs are viable. In this work, we report the insights into assembly of the bacterial ribosome large subunit (LSU) based on cryo-EM density maps of intermediates that accumulate during
Language	English
Publishing date	2024-04-10
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.04.10.588894
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Article ; Online: A comparison of covariate adjustment approaches under model misspecification in individually randomized trials.

Tackney, Mia S / Morris, Tim / White, Ian / Leyrat, Clemence / Diaz-Ordaz, Karla / Williamson, Elizabeth

Trials

2023 Volume 24, Issue 1, Page(s) 14

Abstract: Adjustment for baseline covariates in randomized trials has been shown to lead to gains in power and can protect against chance imbalances in covariates. For continuous covariates, there is a risk that the the form of the relationship between the ... ...

Abstract	Adjustment for baseline covariates in randomized trials has been shown to lead to gains in power and can protect against chance imbalances in covariates. For continuous covariates, there is a risk that the the form of the relationship between the covariate and outcome is misspecified when taking an adjusted approach. Using a simulation study focusing on individually randomized trials with small sample sizes, we explore whether a range of adjustment methods are robust to misspecification, either in the covariate-outcome relationship or through an omitted covariate-treatment interaction. Specifically, we aim to identify potential settings where G-computation, inverse probability of treatment weighting (IPTW), augmented inverse probability of treatment weighting (AIPTW) and targeted maximum likelihood estimation (TMLE) offer improvement over the commonly used analysis of covariance (ANCOVA). Our simulations show that all adjustment methods are generally robust to model misspecification if adjusting for a few covariates, sample size is 100 or larger, and there are no covariate-treatment interactions. When there is a non-linear interaction of treatment with a skewed covariate and sample size is small, all adjustment methods can suffer from bias; however, methods that allow for interactions (such as G-computation with interaction and IPTW) show improved results compared to ANCOVA. When there are a high number of covariates to adjust for, ANCOVA retains good properties while other methods suffer from under- or over-coverage. An outstanding issue for G-computation, IPTW and AIPTW in small samples is that standard errors are underestimated; they should be used with caution without the availability of small-sample corrections, development of which is needed. These findings are relevant for covariate adjustment in interim analyses of larger trials.
MeSH term(s)	Humans ; Randomized Controlled Trials as Topic ; Computer Simulation ; Probability ; Sample Size
Language	English
Publishing date	2023-01-06
Publishing country	England
Document type	Journal Article
ZDB-ID	2040523-6
ISSN	1745-6215 ; 1468-6694 ; 1745-6215
ISSN (online)	1745-6215
ISSN	1468-6694 ; 1745-6215
DOI	10.1186/s13063-022-06967-6
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Article ; Online: Study found increasing use of core outcome sets in Cochrane systematic reviews and identified facilitators and barriers.

Saldanha, Ian J / Hughes, Karen L / Dodd, Susanna / Lasserson, Toby / Kirkham, Jamie J / Wu, Yuhui / Lucas, Samuel W / Williamson, Paula R

Journal of clinical epidemiology

2024 Volume 169, Page(s) 111277

Abstract: Objectives: In 2019, only 7% of Cochrane systematic reviews (SRs) cited a core outcome set (COS) in relation to choosing outcomes, even though a relevant COS existed but was not mentioned (or cited) for a further 29% of SRs. Our objectives for the ... ...

Abstract	Objectives: In 2019, only 7% of Cochrane systematic reviews (SRs) cited a core outcome set (COS) in relation to choosing outcomes, even though a relevant COS existed but was not mentioned (or cited) for a further 29% of SRs. Our objectives for the current work were to (1) examine the extent to which authors are currently considering COS to inform outcome choice in Cochrane protocols and completed SRs, and (2) understand author facilitators and barriers to using COS. Study design and setting: We examined all completed Cochrane SRs published in the last 3 months of 2022 and all Cochrane protocols published in 2022 for the extent to which they: (a) cited a COS, (b) searched for COS, (c) used outcomes from existing COS, and (d) reported outcome inconsistency among included studies and/or noted the need for COS. One investigator extracted information; a second extractor verified all information, discussing discrepancies to achieve consensus. We then conducted an online survey of authors of the included SRs to assess awareness of COS and identify facilitators and barriers to using COS to inform outcome choice. Results: Objective 1: We included 294 SRs of interventions (84 completed SRs and 210 published SR protocols), of which 13% cited specific COS and 5% did not cite but mentioned searching for COS. A median of 83% of core outcomes from cited COS (interquartile range [IQR] 57%-100%) were included in the corresponding SR. We identified a relevant COS for 39% of SRs that did not cite a COS. A median of 50% of core outcomes from noncited COS (IQR 35%-72%) were included in the corresponding SR. Objective 2: Authors of 236 (80%) of the 294 eligible SRs completed our survey. Seventy-seven percent of authors noted being aware of COS before the survey. Fifty-five percent of authors who did not cite COS but were aware of them reported searching for a COS. The most reported facilitators of using COS were author awareness of the existence of COS (59%), author positive perceptions of COS (52%), and recommendation in the Cochrane Handbook regarding COS use (48%). The most reported barriers related to matching of the scope of the COS and the SR: the COS target population was too narrow/broad relative to the SR population (29%) or the COS target intervention was too narrow/broad relative to the SR intervention (21%). Most authors (87%) mentioned that they would consider incorporating missing core outcomes in the SR/update. Conclusion: Since 2019, there is increasing consideration and awareness of COS when choosing outcomes for Cochrane SRs of interventions, but uptake remains low and can be improved further. Use of COS in SRs is important to improve outcome standardization, reduce research waste, and improve evidence syntheses of the relevant effects of interventions across health research.
Language	English
Publishing date	2024-02-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	639306-8
ISSN	1878-5921 ; 0895-4356
ISSN (online)	1878-5921
ISSN	0895-4356
DOI	10.1016/j.jclinepi.2024.111277
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Article ; Online: Planning a method for covariate adjustment in individually randomised trials: a practical guide.

Morris, Tim P / Walker, A Sarah / Williamson, Elizabeth J / White, Ian R

Trials

2022 Volume 23, Issue 1, Page(s) 328

Abstract: Background: It has long been advised to account for baseline covariates in the analysis of confirmatory randomised trials, with the main statistical justifications being that this increases power and, when a randomisation scheme balanced covariates, ... ...

Abstract	Background: It has long been advised to account for baseline covariates in the analysis of confirmatory randomised trials, with the main statistical justifications being that this increases power and, when a randomisation scheme balanced covariates, permits a valid estimate of experimental error. There are various methods available to account for covariates but it is not clear how to choose among them. Methods: Taking the perspective of writing a statistical analysis plan, we consider how to choose between the three most promising broad approaches: direct adjustment, standardisation and inverse-probability-of-treatment weighting. Results: The three approaches are similar in being asymptotically efficient, in losing efficiency with mis-specified covariate functions and in handling designed balance. If a marginal estimand is targeted (for example, a risk difference or survival difference), then direct adjustment should be avoided because it involves fitting non-standard models that are subject to convergence issues. Convergence is most likely with IPTW. Robust standard errors used by IPTW are anti-conservative at small sample sizes. All approaches can use similar methods to handle missing covariate data. With missing outcome data, each method has its own way to estimate a treatment effect in the all-randomised population. We illustrate some issues in a reanalysis of GetTested, a randomised trial designed to assess the effectiveness of an electonic sexually transmitted infection testing and results service. Conclusions: No single approach is always best: the choice will depend on the trial context. We encourage trialists to consider all three methods more routinely.
MeSH term(s)	Humans ; Probability ; Research Design ; Sample Size
Language	English
Publishing date	2022-04-18
Publishing country	England
Document type	Journal Article ; Randomized Controlled Trial
ZDB-ID	2040523-6
ISSN	1745-6215 ; 1468-6694 ; 1745-6215
ISSN (online)	1745-6215
ISSN	1468-6694 ; 1745-6215
DOI	10.1186/s13063-022-06097-z
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Article ; Online: Authors' note.

Todd, Victoria L G / Williamson, Laura D / Jiang, Jian / Cox, Sophie E / Todd, Ian B / Ruffert, Maximilian

Marine pollution bulletin

2022 Volume 174, Page(s) 113108

Language	English
Publishing date	2022-01-14
Publishing country	England
Document type	Published Erratum
ZDB-ID	2001296-2
ISSN	1879-3363 ; 0025-326X
ISSN (online)	1879-3363
ISSN	0025-326X
DOI	10.1016/j.marpolbul.2021.113108
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Article ; Online: More than half of systematic reviews have relevant core outcome sets.

Saldanha, Ian J / Dodd, Susanna / Gorst, Sarah L / Williamson, Paula R

Journal of clinical epidemiology

2021 Volume 136, Page(s) 168–179

Abstract: Objectives: Using recent systematic reviews (SRs), our objectives were to: (1) develop a framework to assess whether a given COS is relevant to the scope of a SR; (2) examine the proportion of SRs for which relevant COS exist; and (3) for SRs for which ... ...

Abstract	Objectives: Using recent systematic reviews (SRs), our objectives were to: (1) develop a framework to assess whether a given COS is relevant to the scope of a SR; (2) examine the proportion of SRs for which relevant COS exist; and (3) for SRs for which COS exist, examine the extent to which outcomes in the COS and outcomes in the SR match. Study design and setting: We included a sample of SRs published by the Agency for Healthcare Research and Quality Evidence-based Practice Center Program between January 1, 2018 and October 12, 2020. We searched for potentially relevant COS from the Core Outcome Measures for Effectiveness Trials (COMET) database. We assessed the matching between outcomes recommended by COS and those included in corresponding SRs. When outcomes were matched, we considered matches to be specific (i.e., exact) or general (i.e., non-specific). Results: Sixty-seven SRs met criteria. We found relevant COS for 36 of 67 SRs (54%). Our framework for comparing the scope of a SR and a COS describes 16 scenarios arising when the breadth of the populations and the interventions are considered. The framework guides systematic reviewers to determine whether a COS is very likely to be relevant, may be relevant, or unlikely to be relevant. Sixty-two percent of outcomes in COS (interquartile range, 40% - 80%) were either specific or general matches to outcomes in SRs. Conclusion: We found a COS with relevant scope for more than half of the SRs in our sample, with almost two-thirds of the recommended core outcomes matched to outcomes chosen for the SRs. Consideration of COS appears relevant for SR planning and our framework for assessing relevance of a given COS may help with this process.
MeSH term(s)	Data Management/statistics & numerical data ; Epidemiologic Research Design ; Humans ; Outcome Assessment, Health Care/statistics & numerical data ; Publications/statistics & numerical data ; Systematic Reviews as Topic
Language	English
Publishing date	2021-05-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	639306-8
ISSN	1878-5921 ; 0895-4356
ISSN (online)	1878-5921
ISSN	0895-4356
DOI	10.1016/j.jclinepi.2021.04.019
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Article ; Online: A Randomized Trial Of Letters To Encourage Prescription Monitoring Program Use And Safe Opioid Prescribing.

Sacarny, Adam / Avilova, Tatyana / Powell, David / Williamson, Ian / Merrick, Weston / Jacobson, Mireille

Health affairs (Project Hope)

2022 Volume 42, Issue 1, Page(s) 140–149

Abstract: To facilitate safer prescribing of opioids and other drugs, nearly all states operate prescription monitoring programs (PMPs), which collect and share data on controlled substance dispensing. Policy makers have sought to raise clinicians' engagement with ...

Abstract	To facilitate safer prescribing of opioids and other drugs, nearly all states operate prescription monitoring programs (PMPs), which collect and share data on controlled substance dispensing. Policy makers have sought to raise clinicians' engagement with these programs but lack evidence on effective interventions. Working with the Minnesota Prescription Monitoring Program, we conducted a randomized trial to assess whether letters to clinicians increased program use and decreased risky coprescribing of opioids with benzodiazepines or gabapentinoids. In March 2021 we randomly assigned 12,000 coprescribers to either a control arm or one of three study arms sent differing letters. The respective letters highlighted a new mandate to check the PMP before prescribing, provided information about coprescribing risks with a list of coprescribed patients, or contained both messages combined. Letters highlighting the mandate alone or along with coprescribing information increased PMP search rates by 4.5 and 4.0 percentage points, respectively, with no significant effect on coprescribing. These letters also increased PMP account-holding rates among clinicians. Effects persisted for at least eight months. The letter with only coprescribing information had no detected effects on key outcomes. Our results support the use of simple letter interventions as evidence-based tools to increase PMP engagement and potentially facilitate better-informed prescribing.
MeSH term(s)	Humans ; Analgesics, Opioid/adverse effects ; Prescription Drug Monitoring Programs ; Practice Patterns, Physicians' ; Drug Prescriptions ; Minnesota
Chemical Substances	Analgesics, Opioid
Language	English
Publishing date	2022-12-30
Publishing country	United States
Document type	Randomized Controlled Trial ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	632712-6
ISSN	1544-5208 ; 0278-2715
ISSN (online)	1544-5208
ISSN	0278-2715
DOI	10.1377/hlthaff.2022.00859
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Article ; Online: Investigating the effects of chronic low-dose radiation exposure in the liver of a hypothermic zebrafish model.

Cahill, Thomas / da Silveira, Willian Abraham / Renaud, Ludivine / Wang, Hao / Williamson, Tucker / Chung, Dongjun / Chan, Sherine / Overton, Ian / Hardiman, Gary

Scientific reports

2023 Volume 13, Issue 1, Page(s) 918

Abstract: Mankind's quest for a manned mission to Mars is placing increased emphasis on the development of innovative radio-protective countermeasures for long-term space travel. Hibernation confers radio-protective effects in hibernating animals, and this has led ...

Abstract	Mankind's quest for a manned mission to Mars is placing increased emphasis on the development of innovative radio-protective countermeasures for long-term space travel. Hibernation confers radio-protective effects in hibernating animals, and this has led to the investigation of synthetic torpor to mitigate the deleterious effects of chronic low-dose-rate radiation exposure. Here we describe an induced torpor model we developed using the zebrafish. We explored the effects of radiation exposure on this model with a focus on the liver. Transcriptomic and behavioural analyses were performed. Radiation exposure resulted in transcriptomic perturbations in lipid metabolism and absorption, wound healing, immune response, and fibrogenic pathways. Induced torpor reduced metabolism and increased pro-survival, anti-apoptotic, and DNA repair pathways. Coupled with radiation exposure, induced torpor led to a stress response but also revealed maintenance of DNA repair mechanisms, pro-survival and anti-apoptotic signals. To further characterise our model of induced torpor, the zebrafish model was compared with hepatic transcriptomic data from hibernating grizzly bears (Ursus arctos horribilis) and active controls revealing conserved responses in gene expression associated with anti-apoptotic processes, DNA damage repair, cell survival, proliferation, and antioxidant response. Similarly, the radiation group was compared with space-flown mice revealing shared changes in lipid metabolism.
MeSH term(s)	Animals ; Mice ; Zebrafish/genetics ; Liver ; Hibernation/physiology ; Torpor/physiology ; Radiation Exposure
Language	English
Publishing date	2023-01-17
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-26976-4
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