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Article ; Online: The effects of intervention with intravenous edaravone in Study 19 on hospitalization, tracheostomy, ventilation, and death in patients with amyotrophic lateral sclerosis.

Brooks, Benjamin Rix / Pioro, Erik P / Sakata, Takeshi / Takahashi, Fumihiro / Hagan, Melissa / Apple, Stephen

2023 Volume 68, Issue 4, Page(s) 397–403

Abstract: ... in the edaravone-first vs placebo-first groups (hazard ratio = 0.47 [95% confidence interval 0.25 to 0.88], P = .02 ... versus the placebo-first group at week 24 (0.15 ± 0.05 [95% confidence interval 0.06 to 0.25], P < .01 ... and week 48 (0.11 ± 0.05 [95% confidence interval 0.02 to 0.21], P = .02).: Discussion ...

Abstract	Introduction/aims: Intravenous (IV) edaravone is a US Food and Drug Administration-approved treatment for amyotrophic lateral sclerosis (ALS), shown in clinical trials to slow physical functional decline. In this study we compared the effect of IV edaravone (edaravone-first group) versus placebo followed by IV edaravone (placebo-first group) on survival and additional milestone events. Methods: This work is a post hoc analysis of Study 19/MCI186-19, which was a randomized, placebo-controlled, phase 3 study investigating IV edaravone versus placebo. Study 19 and its 24-week extension have been described previously (NCT01492686). Edaravone-first versus placebo-first group time to events for specific milestone(s) were analyzed post hoc. Time-to-event composite endpoints were time to death; time to death, tracheostomy, or permanent assisted ventilation (PAV); and time to death, tracheostomy, PAV, or hospitalization. Results: The risk for death, tracheostomy, PAV, or hospitalization was 53% lower among patients in the edaravone-first vs placebo-first groups (hazard ratio = 0.47 [95% confidence interval 0.25 to 0.88], P = .02). The overall effect of IV edaravone on ALS progression could be seen in the significant separation of time-to-event curves for time to death, tracheostomy, PAV, or hospitalization. ALS survival composite endpoint analyses (ALS/SURV) suggested a treatment benefit (least-squares mean difference) for the edaravone-first versus the placebo-first group at week 24 (0.15 ± 0.05 [95% confidence interval 0.06 to 0.25], P < .01) and week 48 (0.11 ± 0.05 [95% confidence interval 0.02 to 0.21], P = .02). Discussion: These analyses illustrate the value of timely and continued IV edaravone treatment, as earlier initiation was associated with a lower risk of death, tracheostomy, PAV, or hospitalization in patients with ALS.
MeSH term(s)	Humans ; Edaravone/therapeutic use ; Amyotrophic Lateral Sclerosis/drug therapy ; Tracheostomy ; Proportional Hazards Models ; Survival Analysis
Chemical Substances	Edaravone (S798V6YJRP)
Language	English
Publishing date	2023-07-31
Publishing country	United States
Document type	Randomized Controlled Trial ; Clinical Trial, Phase III ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	438353-9
ISSN	1097-4598 ; 0148-639X
ISSN (online)	1097-4598
ISSN	0148-639X
DOI	10.1002/mus.27946
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Article ; Online: The extent to which soil hydraulics can explain ecohydrological separation

Catherine E. Finkenbiner / Stephen P. Good / J. Renée Brooks / Scott T. Allen / Salini Sasidharan

Nature Communications, Vol 13, Iss 1, Pp 1-

2022 Volume 8

Abstract: Soil physics simulations show water isotope ratios can differ among drainage, mobile and immobile storages due to transport processes alone, but effects were smaller than field data implying unrepresented processes underly ecohydrologic separation. ...

Abstract	Soil physics simulations show water isotope ratios can differ among drainage, mobile and immobile storages due to transport processes alone, but effects were smaller than field data implying unrepresented processes underly ecohydrologic separation.
Keywords	Science ; Q
Language	English
Publishing date	2022-10-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The extent to which soil hydraulics can explain ecohydrological separation.

Finkenbiner, Catherine E / Good, Stephen P / Renée Brooks, J / Allen, Scott T / Sasidharan, Salini

Nature communications

2022 Volume 13, Issue 1, Page(s) 6492

Abstract: Field measurements of hydrologic tracers indicate varying magnitudes of geochemical separation between subsurface pore waters. The potential for conventional soil physics alone to explain isotopic differences between preferential flow and tightly-bound ... ...

Abstract	Field measurements of hydrologic tracers indicate varying magnitudes of geochemical separation between subsurface pore waters. The potential for conventional soil physics alone to explain isotopic differences between preferential flow and tightly-bound water remains unclear. Here, we explore physical drivers of isotopic separations using 650 different model configurations of soil, climate, and mobile/immobile soil-water domain characteristics, without confounding fractionation or plant uptake effects. We find simulations with coarser soils and less precipitation led to reduced separation between pore spaces and drainage. Amplified separations are found with larger immobile domains and, to a lesser extent, higher mobile-immobile transfer rates. Nonetheless, isotopic separations remained small (<4‰ for δ
MeSH term(s)	Soil/chemistry ; Water Movements ; Hydrology ; Water ; Plants
Chemical Substances	Soil ; Water (059QF0KO0R)
Language	English
Publishing date	2022-10-30
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-022-34215-7
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Article ; Online: Motor Assessment in Huntington's Disease Mice.

Dunnett, Stephen B / Brooks, Simon P

Methods in molecular biology (Clifton, N.J.)

2018 Volume 1780, Page(s) 121–141

Abstract: Motor deficits are a characteristic consequence of striatal damage, whether induced by experimental lesions, or in genetic models of Huntington's disease involving polyglutamine expansion in the huntingtin protein. With the growing power of genetic ... ...

Abstract	Motor deficits are a characteristic consequence of striatal damage, whether induced by experimental lesions, or in genetic models of Huntington's disease involving polyglutamine expansion in the huntingtin protein. With the growing power of genetic models and genetic tools for analysis, mice are increasingly the animal model of choice, and objective quantitative measures of motor performance are in demand for experimental analysis of disease pathophysiology, progression, and treatment. We present methodological protocols for six of the most common tests of motor function-ranging from spontaneous activity, locomotor coordination, balance, and skilled limb use-that are simple, effective, efficient, and widely used for motor assessment in Huntington's disease research in experimental mice.
MeSH term(s)	Animals ; Behavior Observation Techniques/instrumentation ; Behavior Observation Techniques/methods ; Behavior, Animal/physiology ; Corpus Striatum/physiopathology ; Disease Models, Animal ; Disease Progression ; Gait Analysis/instrumentation ; Gait Analysis/methods ; Humans ; Huntingtin Protein/genetics ; Huntingtin Protein/metabolism ; Huntington Disease/diagnosis ; Huntington Disease/genetics ; Huntington Disease/pathology ; Huntington Disease/physiopathology ; Locomotion/physiology ; Mice ; Mice, Transgenic ; Motor Activity/physiology ; Rotarod Performance Test/instrumentation ; Rotarod Performance Test/methods ; Video Recording/instrumentation ; Video Recording/methods
Chemical Substances	Htt protein, mouse ; Huntingtin Protein
Language	English
Publishing date	2018-05-31
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-4939-7825-0_7
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Article: Risk of bias in cross-sectional studies: Protocol for a scoping review of concepts and tools.

Kelly, Shannon E / Benkhedda, Karima / Brooks, Stephen P J / MacFarlane, Amanda J / Greene-Finestone, Linda S / Skidmore, Becky / Clifford, Tammy J / Wells, George A

MethodsX

2024 Volume 12, Page(s) 102610

Abstract: Cross-sectional studies are commonly used to study human health and disease, but are especially susceptible to bias. This scoping review aims to identify and describe available tools to assess the risk of bias (RoB) in cross-sectional studies and to ... ...

Abstract	Cross-sectional studies are commonly used to study human health and disease, but are especially susceptible to bias. This scoping review aims to identify and describe available tools to assess the risk of bias (RoB) in cross-sectional studies and to compile the key bias concepts relevant to cross-sectional studies into an item bank. Using the JBI scoping review methodology, the strategy to locate relevant RoB concepts and tools is a combination of database searches, prospective review of PROSPERO registry records; and consultation with knowledge users and content experts. English language records will be included if they describe tools, checklists, or instruments which describe or permit assessment of RoB for cross-sectional studies. Systematic reviews will be included if they consider eligible RoB tools or use RoB tools for RoB of cross-sectional studies. All records will be independently screened, selected, and extracted by one researcher and checked by a second. An analytic framework will be used to structure the extraction of data. Results for the scoping review are pending. Results from this scoping review will be used to inform future selection of RoB tools and to consider whether development of a new RoB tool for cross-sectional studies is needed.
Language	English
Publishing date	2024-02-12
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2830212-6
ISSN	2215-0161
ISSN	2215-0161
DOI	10.1016/j.mex.2024.102610
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Article ; Online: A Bayesian method for identifying associations between response variables and bacterial community composition.

Verster, Adrian / Petronella, Nicholas / Green, Judy / Matias, Fernando / Brooks, Stephen P J

PLoS computational biology

2022 Volume 18, Issue 7, Page(s) e1010108

Abstract: Determining associations between intestinal bacteria and continuously measured physiological outcomes is important for understanding the bacteria-host relationship but is not straightforward since abundance data (compositional data) are not normally ... ...

Abstract	Determining associations between intestinal bacteria and continuously measured physiological outcomes is important for understanding the bacteria-host relationship but is not straightforward since abundance data (compositional data) are not normally distributed. To address this issue, we developed a fully Bayesian linear regression model (BRACoD; Bayesian Regression Analysis of Compositional Data) with physiological measurements (continuous data) as a function of a matrix of relative bacterial abundances. Bacteria can be classified as operational taxonomic units or by taxonomy (genus, family, etc.). Bacteria associated with the physiological measurement were identified using a Bayesian variable selection method: Stochastic Search Variable Selection. The output is a list of inclusion probabilities ([Formula: see text]) and coefficients that indicate the strength of the association ([Formula: see text]) for each bacterial taxa. Tests with simulated communities showed that adopting a cut point value of [Formula: see text] ≥ 0.3 for identifying included bacteria optimized the true positive rate (TPR) while maintaining a false positive rate (FPR) of ≤ 5%. At this point, the chances of identifying non-contributing bacteria were low and all well-established contributors were included. Comparison with other methods showed that BRACoD (at [Formula: see text] ≥ 0.3) had higher precision and a higher TPR than a commonly used center log transformed LASSO procedure (clr-LASSO) as well as higher TPR than an off-the-shelf Spike and Slab method after center log transformation (clr-SS). BRACoD was also less likely to include non-contributing bacteria that merely correlate with contributing bacteria. Analysis of a rat microbiome experiment identified 47 operational taxonomic units that contributed to fecal butyrate levels. Of these, 31 were positively and 16 negatively associated with butyrate. Consistent with their known role in butyrate metabolism, most of these fell within the Lachnospiraceae and Ruminococcaceae. We conclude that BRACoD provides a more precise and accurate method for determining bacteria associated with a continuous physiological outcome compared to clr-LASSO. It is more sensitive than a generalized clr-SS algorithm, although it has a higher FPR. Its ability to distinguish genuine contributors from correlated bacteria makes it better suited to discriminating bacteria that directly contribute to an outcome. The algorithm corrects for the distortions arising from compositional data making it appropriate for analysis of microbiome data.
MeSH term(s)	Animals ; Bacteria ; Bayes Theorem ; Butyrates ; Clostridiales ; Linear Models ; Microbiota ; Rats
Chemical Substances	Butyrates
Language	English
Publishing date	2022-07-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	2193340-6
ISSN	1553-7358 ; 1553-734X
ISSN (online)	1553-7358
ISSN	1553-734X
DOI	10.1371/journal.pcbi.1010108
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Article: Behavioral plasticity mitigates the effect of warming on white-tailed deer.

Wolff, Carter L / Demarais, Stephen / Brooks, Christopher P / Barton, Brandon T

Ecology and evolution

2020 Volume 10, Issue 5, Page(s) 2579–2587

Abstract: Climate change is expected to create novel environments in which extant species cannot persist, therefore leading to the loss of them and their associated ecological functions within the ecosystem. However, animals may employ behavioral mechanisms in ... ...

Abstract	Climate change is expected to create novel environments in which extant species cannot persist, therefore leading to the loss of them and their associated ecological functions within the ecosystem. However, animals may employ behavioral mechanisms in response to warming that could allow them to maintain their functional roles in an ecosystem despite changed temperatures. Specifically, animals may shift their activity in space or time to make use of thermal heterogeneity on the landscape. However, few studies consider the role of behavioral plasticity and spatial or temporal heterogeneity in mitigating the effects of climate change. We conducted experiments to evaluate the potential importance of behavior in mediating the net effects of warming on white-tailed deer (
Language	English
Publishing date	2020-02-11
Publishing country	England
Document type	Journal Article
ZDB-ID	2635675-2
ISSN	2045-7758
ISSN	2045-7758
DOI	10.1002/ece3.6087
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Article ; Online: A Bayesian method for identifying associations between response variables and bacterial community composition.

Adrian Verster / Nicholas Petronella / Judy Green / Fernando Matias / Stephen P J Brooks

PLoS Computational Biology, Vol 18, Iss 7, p e

2022 Volume 1010108

Abstract	Determining associations between intestinal bacteria and continuously measured physiological outcomes is important for understanding the bacteria-host relationship but is not straightforward since abundance data (compositional data) are not normally distributed. To address this issue, we developed a fully Bayesian linear regression model (BRACoD; Bayesian Regression Analysis of Compositional Data) with physiological measurements (continuous data) as a function of a matrix of relative bacterial abundances. Bacteria can be classified as operational taxonomic units or by taxonomy (genus, family, etc.). Bacteria associated with the physiological measurement were identified using a Bayesian variable selection method: Stochastic Search Variable Selection. The output is a list of inclusion probabilities ([Formula: see text]) and coefficients that indicate the strength of the association ([Formula: see text]) for each bacterial taxa. Tests with simulated communities showed that adopting a cut point value of [Formula: see text] ≥ 0.3 for identifying included bacteria optimized the true positive rate (TPR) while maintaining a false positive rate (FPR) of ≤ 5%. At this point, the chances of identifying non-contributing bacteria were low and all well-established contributors were included. Comparison with other methods showed that BRACoD (at [Formula: see text] ≥ 0.3) had higher precision and a higher TPR than a commonly used center log transformed LASSO procedure (clr-LASSO) as well as higher TPR than an off-the-shelf Spike and Slab method after center log transformation (clr-SS). BRACoD was also less likely to include non-contributing bacteria that merely correlate with contributing bacteria. Analysis of a rat microbiome experiment identified 47 operational taxonomic units that contributed to fecal butyrate levels. Of these, 31 were positively and 16 negatively associated with butyrate. Consistent with their known role in butyrate metabolism, most of these fell within the Lachnospiraceae and Ruminococcaceae. We conclude ...
Keywords	Biology (General) ; QH301-705.5
Subject code	310
Language	English
Publishing date	2022-07-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Practice Consolidation Among US Medical Oncologists, 2015-2022.

Milligan, Michael / Erfani, Parsa / Orav, E John / Schleicher, Stephen / Brooks, Gabriel A / Lam, Miranda B

JCO oncology practice

2024 , Page(s) OP2300748

Abstract: Purpose: Health care consolidation has significantly affected cancer care delivery, with oncology practices undergoing substantial consolidation over the past two decades. This study investigates practice consolidation trends among medical oncologists ( ... ...

Abstract	Purpose: Health care consolidation has significantly affected cancer care delivery, with oncology practices undergoing substantial consolidation over the past two decades. This study investigates practice consolidation trends among medical oncologists (MOs), factors associated with consolidation, and changes in MO geographic distribution. Methods: Medicare data from 2015 to 2022 were used to assess MO practice consolidation in hospital referral regions (HRRs), linked with regional health care market data and physician demographics. The Herfindahl-Hirschman Index (HHI) was used to measure consolidation, and the Gini coefficient was used to measure MO distribution across counties. Multivariable linear regression explored factors associated with MO practice consolidation. Results: Between 2015 and 2022, the number of MOs increased by 14.5% (11,727-13,433), whereas the number of MO practices decreased by 18.0% (2,774-2,276). The mean number of MOs per practice increased by 40% (4.26-5.95; Conclusion: On the basis of Federal Trade Commission classifications, MO practices were highly concentrated in 2015 and consolidated even further by 2022. While distribution of MOs at the county level remained stable, further research is needed to assess the effects of rapid consolidation on cancer care cost, quality, and access. These data have important implications for policymakers and payers as they design programs that ensure high-quality, affordable cancer care.
Language	English
Publishing date	2024-02-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	3028198-2
ISSN	2688-1535 ; 2688-1527
ISSN (online)	2688-1535
ISSN	2688-1527
DOI	10.1200/OP.23.00748
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Article: Inadequate vitamin D status is associated with lower food plus supplemental intake of vitamin D in children of South Asian ethnicity living in the National Capital Region of Canada

Brooks, Stephen P.J. / Ratnayake, W.M. Nimal / Rondeau, Isabelle / Swist, Eleonora / Sarafin, Kurtis / Weiler, Hope A.

Applied physiology, nutrition and metabolism. 2022, v. 47, no. 1

2022

Abstract: ... A greater proportion of South Asian children had serum 25OHD <40 nmol/L (56.9 vs. 8.6%, P < 0.0001) and ... fewer took supplements (31 vs. 50%, P = 0.0389). In a multi-factorial model (r² = 0.54), lower vitamin D ...

Abstract	Vitamin D status, measured in a Vitamin D Standardization Program certified laboratory, was assessed among children of South Asian and European ethnicity living in the national capital region of Canada to explore factors that may account for inadequate status. Demographic information, dietary and supplemental vitamin D over 30 d prior to measurement of serum 25-hydroxyvitamin D (25OHD), and anthropometry were measured (age 6.0–18.9 y; n = 58/group; February–March 2015). No group related differences in age, height and body mass index (BMI) Z-scores or in food vitamin D intakes were observed. Standardized serum 25OHD was lower in South Asian children (mean ± SD: 39.0 ± 16.8 nmol/L vs. European: 58.4 ± 15.8 nmol/L). A greater proportion of South Asian children had serum 25OHD <40 nmol/L (56.9 vs. 8.6%, P < 0.0001) and fewer took supplements (31 vs. 50%, P = 0.0389). In a multi-factorial model (r² = 0.54), lower vitamin D status was associated with overweight/obese BMI and older age (14–18 y); no interaction with ethnicity was observed. Lower vitamin D status was associated with lower total vitamin D intake only in South Asian children. This study reinforces the importance of public health actions towards meeting vitamin D intake recommendations among those of high-risk deficiency. Novelty: A higher proportion of South Asian vs. European children had inadequate vitamin D status. Lower vitamin D status was associated with a BMI in the overweight/obese range. Lower vitamin D status was associated with lower total vitamin D intake in South Asian but not European children.
Keywords	blood serum ; body mass index ; metabolism ; models ; overweight ; public health ; vitamin supplements ; Canada
Language	English
Size	p. 91-98.
Publishing place	NRC Research Press
Document type	Article
ZDB-ID	2236708-1
ISSN	1715-5320 ; 1715-5312
ISSN (online)	1715-5320
ISSN	1715-5312
DOI	10.1139/apnm-2021-0203
Database	NAL-Catalogue (AGRICOLA)

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