| 1. |
- Beal, Jacob, et al.
(författare)
-
Robust estimation of bacterial cell count from optical density
- 2020
-
Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
-
Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
|
|
| 2. |
- Kanoni, Stavroula, et al.
(författare)
-
Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
-
Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
-
Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
|
|
| 3. |
- Nguyen, Thanh N, et al.
(författare)
-
Global Impact of the COVID-19 Pandemic on Stroke Volumes and Cerebrovascular Events: A 1-Year Follow-up.
- 2023
-
Ingår i: Neurology. - 1526-632X. ; 100:4
-
Tidskriftsartikel (refereegranskat)abstract
- Declines in stroke admission, IV thrombolysis (IVT), and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the effect of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), IVT, and mechanical thrombectomy over a 1-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020).We conducted a longitudinal retrospective study across 6 continents, 56 countries, and 275 stroke centers. We collected volume data for COVID-19 admissions and 4 stroke metrics: ischemic stroke admissions, ICH admissions, IVT treatments, and mechanical thrombectomy procedures. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.There were 148,895 stroke admissions in the 1 year immediately before compared with 138,453 admissions during the 1-year pandemic, representing a 7% decline (95% CI [95% CI 7.1-6.9]; p < 0.0001). ICH volumes declined from 29,585 to 28,156 (4.8% [5.1-4.6]; p < 0.0001) and IVT volume from 24,584 to 23,077 (6.1% [6.4-5.8]; p < 0.0001). Larger declines were observed at high-volume compared with low-volume centers (all p < 0.0001). There was no significant change in mechanical thrombectomy volumes (0.7% [0.6-0.9]; p = 0.49). Stroke was diagnosed in 1.3% [1.31-1.38] of 406,792 COVID-19 hospitalizations. SARS-CoV-2 infection was present in 2.9% ([2.82-2.97], 5,656/195,539) of all stroke hospitalizations.There was a global decline and shift to lower-volume centers of stroke admission volumes, ICH volumes, and IVT volumes during the 1st year of the COVID-19 pandemic compared with the prior year. Mechanical thrombectomy volumes were preserved. These results suggest preservation in the stroke care of higher severity of disease through the first pandemic year.This study is registered under NCT04934020.
|
|
| 4. |
- Menkveld, Albert J., et al.
(författare)
-
Nonstandard Errors
- 2024
-
Ingår i: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390
-
Tidskriftsartikel (refereegranskat)abstract
- In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants.
|
|
| 5. |
- Schweinsberg, Martin, et al.
(författare)
-
Same data, different conclusions : Radical dispersion in empirical results when independent analysts operationalize and test the same hypothesis
- 2021
-
Ingår i: Organizational Behavior and Human Decision Processes. - : Elsevier BV. - 0749-5978 .- 1095-9920. ; 165, s. 228-249
-
Tidskriftsartikel (refereegranskat)abstract
- In this crowdsourced initiative, independent analysts used the same dataset to test two hypotheses regarding the effects of scientists' gender and professional status on verbosity during group meetings. Not only the analytic approach but also the operationalizations of key variables were left unconstrained and up to individual analysts. For instance, analysts could choose to operationalize status as job title, institutional ranking, citation counts, or some combination. To maximize transparency regarding the process by which analytic choices are made, the analysts used a platform we developed called DataExplained to justify both preferred and rejected analytic paths in real time. Analyses lacking sufficient detail, reproducible code, or with statistical errors were excluded, resulting in 29 analyses in the final sample. Researchers reported radically different analyses and dispersed empirical outcomes, in a number of cases obtaining significant effects in opposite directions for the same research question. A Boba multiverse analysis demonstrates that decisions about how to operationalize variables explain variability in outcomes above and beyond statistical choices (e.g., covariates). Subjective researcher decisions play a critical role in driving the reported empirical results, underscoring the need for open data, systematic robustness checks, and transparency regarding both analytic paths taken and not taken. Implications for orga-nizations and leaders, whose decision making relies in part on scientific findings, consulting reports, and internal analyses by data scientists, are discussed.
|
|
| 6. |
- Guintivano, Jerry, et al.
(författare)
-
Meta-Analyses of Genome-Wide Association Studies for Postpartum Depression
- 2023
-
Ingår i: American Journal of Psychiatry. - : American Psychiatric Association Publishing. - 0002-953X .- 1535-7228. ; 180:12, s. 884-895
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Postpartum depression (PPD) is a common subtype of major depressive disorder (MDD) that is more heritable, yet is understudied in psychiatric genetics. The authors conducted meta-analyses of genome-wide association studies (GWASs) to investigate the genetic architecture of PPD.METHOD: Meta-analyses were conducted on 18 cohorts of European ancestry (17,339 PPD cases and 53,426 controls), one cohort of East Asian ancestry (975 cases and 3,780 controls), and one cohort of African ancestry (456 cases and 1,255 controls), totaling 18,770 PPD cases and 58,461 controls. Post-GWAS analyses included 1) single-nucleotide polymorphism (SNP)-based heritability ([Formula: see text]), 2) genetic correlations between PPD and other phenotypes, and 3) enrichment of the PPD GWAS findings in 27 human tissues and 265 cell types from the mouse central and peripheral nervous system.RESULTS: No SNP achieved genome-wide significance in the European or the trans-ancestry meta-analyses. The [Formula: see text] of PPD was 0.14 (SE=0.02). Significant genetic correlations were estimated for PPD with MDD, bipolar disorder, anxiety disorders, posttraumatic stress disorder, insomnia, age at menarche, and polycystic ovary syndrome. Cell-type enrichment analyses implicate inhibitory neurons in the thalamus and cholinergic neurons within septal nuclei of the hypothalamus, a pattern that differs from MDD.CONCLUSIONS: While more samples are needed to reach genome-wide levels of significance, the results presented confirm PPD as a polygenic and heritable phenotype. There is also evidence that despite a high correlation with MDD, PPD may have unique genetic components. Cell enrichment results suggest GABAergic neurons, which converge on a common mechanism with the only medication approved by the U.S. Food and Drug Administration for PPD (brexanolone).
|
|
| 7. |
- Abazajian, Kevork, et al.
(författare)
-
CMB-S4 : Forecasting Constraints on Primordial Gravitational Waves
- 2022
-
Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 926:1
-
Tidskriftsartikel (refereegranskat)abstract
- CMB-S4—the next-generation ground-based cosmic microwave background (CMB) experiment—is set to significantly advance the sensitivity of CMB measurements and enhance our understanding of the origin and evolution of the universe. Among the science cases pursued with CMB-S4, the quest for detecting primordial gravitational waves is a central driver of the experimental design. This work details the development of a forecasting framework that includes a power-spectrum-based semianalytic projection tool, targeted explicitly toward optimizing constraints on the tensor-to-scalar ratio, r, in the presence of Galactic foregrounds and gravitational lensing of the CMB. This framework is unique in its direct use of information from the achieved performance of current Stage 2–3 CMB experiments to robustly forecast the science reach of upcoming CMB-polarization endeavors. The methodology allows for rapid iteration over experimental configurations and offers a flexible way to optimize the design of future experiments, given a desired scientific goal. To form a closed-loop process, we couple this semianalytic tool with map-based validation studies, which allow for the injection of additional complexity and verification of our forecasts with several independent analysis methods. We document multiple rounds of forecasts for CMB-S4 using this process and the resulting establishment of the current reference design of the primordial gravitational-wave component of the Stage-4 experiment, optimized to achieve our science goals of detecting primordial gravitational waves for r > 0.003 at greater than 5σ, or in the absence of a detection, of reaching an upper limit of r < 0.001 at 95% CL.
|
|
| 8. |
- Inker, Lesley A., et al.
(författare)
-
New creatinine- and cystatin C-based equations to estimate GFR without race
- 2021
-
Ingår i: New England Journal of Medicine. - 0028-4793. ; 385:19, s. 1737-1749
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Current equations for estimated glomerular filtration rate (eGFR) that use serum creatinine or cystatin C incorporate age, sex, and race to estimate measured GFR. However, race in eGFR equations is a social and not a biologic construct.Methods: We developed new eGFR equations without race using data from two development data sets: 10 studies (8254 participants, 31.5% Black) for serum creatinine and 13 studies (5352 participants, 39.7% Black) for both serum creatinine and cystatin C. In a validation data set of 12 studies (4050 participants, 14.3% Black), we compared the accuracy of new eGFR equations to measured GFR. We projected the prevalence of chronic kidney disease (CKD) and GFR stages in a sample of U.S. adults, using current and new equations.Results: In the validation data set, the current creatinine equation that uses age, sex, and race overestimated measured GFR in Blacks (median, 3.7 ml per minute per 1.73 m2 of body-surface area; 95% confidence interval [CI], 1.8 to 5.4) and to a lesser degree in non-Blacks (median, 0.5 ml per minute per 1.73 m2; 95% CI, 0.0 to 0.9). When the adjustment for Black race was omitted from the current eGFR equation, measured GFR in Blacks was underestimated (median, 7.1 ml per minute per 1.73 m2; 95% CI, 5.9 to 8.8). A new equation using age and sex and omitting race underestimated measured GFR in Blacks (median, 3.6 ml per minute per 1.73 m2; 95% CI, 1.8 to 5.5) and overestimated measured GFR in non-Blacks (median, 3.9 ml per minute per 1.73 m2; 95% CI, 3.4 to 4.4). For all equations, 85% or more of the eGFRs for Blacks and non-Blacks were within 30% of measured GFR. New creatinine-cystatin C equations without race were more accurate than new creatinine equations, with smaller differences between race groups. As compared with the current creatinine equation, the new creatinine equations, but not the new creatinine-cystatin C equations, increased population estimates of CKD prevalence among Blacks and yielded similar or lower prevalence among non-Blacks.Conclusions: New eGFR equations that incorporate creatinine and cystatin C but omit race are more accurate and led to smaller differences between Black participants and non-Black participants than new equations without race with either creatinine or cystatin C alone.
|
|
| 9. |
- Bonanini, Flavio, et al.
(författare)
-
A comparison between different human hepatocyte models reveals profound differences in net glucose production, lipid composition and metabolism in vitro
- 2024
-
Ingår i: Experimental Cell Research. - : Elsevier BV. - 0014-4827 .- 1090-2422. ; 437:1
-
Tidskriftsartikel (refereegranskat)abstract
- Hepatocytes are responsible for maintaining a stable blood glucose concentration during periods of nutrient scarcity. The breakdown of glycogen and de novo synthesis of glucose are crucial metabolic pathways deeply interlinked with lipid metabolism. Alterations in these pathways are often associated with metabolic diseases with serious clinical implications. Studying energy metabolism in human cells is challenging. Primary hepatocytes are still considered the golden standard for in vitro studies and have been instrumental in elucidating key aspects of energy metabolism found in vivo. As a result of several limitations posed by using primary cells, a multitude of alternative hepatocyte cellular models emerged as potential substitutes. Yet, there remains a lack of clarity regarding the precise applications for which these models accurately reflect the metabolic competence of primary hepatocytes. In this study, we compared primary hepatocytes, stem cell-derived hepatocytes, adult donor-derived liver organoids, immortalized Upcyte-hepatocytes and the hepatoma cell line HepG2s in their response to a glucose production challenge. We observed the highest net glucose production in primary hepatocytes, followed by organoids, stem-cell derived hepatocytes, Upcyte-hepatocytes and HepG2s. Glucogenic gene induction was observed in all tested models, as indicated by an increase in G6PC and PCK1 expression. Lipidomic analysis revealed considerable differences across the models, with organoids showing the closest similarity to primary hepatocytes in the common lipidome, comprising 347 lipid species across 19 classes. Changes in lipid profiles as a result of the glucose production challenge showed a variety of, and in some cases opposite, trends when compared to primary hepatocytes.
|
|
| 10. |
|
|
| 11. |
- Jackson, Sarah S., et al.
(författare)
-
Associations between reproductive factors and biliary tract cancers in women from the Biliary Tract Cancers Pooling Project
- 2020
-
Ingår i: Journal of Hepatology. - : ELSEVIER. - 0168-8278 .- 1600-0641. ; 73, s. 863-872
-
Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Gallbladder cancer (GBC) is known to have a female predominance while other biliary tract cancers (BTCs) have a male predominance. However, the role of female reproductive factors in BTC etiology remains unclear. Methods: We pooled data from 19 studies of >1.5 million women participating in the Biliary Tract Cancers Pooling Project to examine the associations of parity, age at menarche, reproductive years, and age at menopause with BTC. Associations for age at menarche and reproductive years with BTC were analyzed separately for Asian and non-Asian women. Hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards models, stratified by study. Results: During 21,681,798 person-years of follow-up, 875 cases of GBC, 379 of intrahepatic bile duct cancer (IHBDC), 450 of extrahepatic bile duct cancer (EHBDC), and 261 of ampulla of Vater cancer (AVC) occurred. High parity was associated with risk of GBC (HR >= 5 vs. 0 births 1.72; 95% CI 1.25-2.38). Age at menarche (HR per year increase 1.15; 95% CI 1.06-1.24) was associated with GBC risk in Asian women while reproductive years were associated with GBC risk (HR per 5 years 1.13; 95% CI 1.04-1.22) in non-Asian women. Later age at menarche was associated with IHBDC (HR 1.19; 95% CI 1.09-1.31) and EHBDC (HR 1.11; 95% CI 1.01-1.22) in Asian women only. Conclusion: We observed an increased risk of GBC with increasing parity. Among Asian women, older age at menarche was associated with increased risk for GBC, IHBDC, and EHBDC, while increasing reproductive years was associated with GBC in non-Asian women. These results suggest that sex hormones have distinct effects on cancers across the biliary tract that vary by geography. Lay summary: Our findings show that the risk of gallbladder cancer is increased among women who have given birth (especially women with 5 or more children). In women from Asian countries, later age at menarche increases the risk of gallbladder cancer, intrahepatic bile duct cancer and extrahepatic bile duct cancer. We did not see this same association in women from Western countries. Age at menopause was not associated with the risk of any biliary tract cancers. Published by Elsevier B.V. on behalf of European Association for the Study of the Liver.
|
|
| 12. |
- Leite, Melina de Souza, et al.
(författare)
-
Major axes of variation in tree demography across global forests
- 2024
-
Ingår i: Ecography. - 0906-7590 .- 1600-0587.
-
Tidskriftsartikel (refereegranskat)abstract
- The future trajectory of global forests is closely intertwined with tree demography, and a major fundamental goal in ecology is to understand the key mechanisms governing spatio-temporal patterns in tree population dynamics. While previous research has made substantial progress in identifying the mechanisms individually, their relative importance among forests remains unclear mainly due to practical limitations. One approach to overcome these limitations is to group mechanisms according to their shared effects on the variability of tree vital rates and quantify patterns therein. We developed a conceptual and statistical framework (variance partitioning of Bayesian multilevel models) that attributes the variability in tree growth, mortality, and recruitment to variation in species, space, and time, and their interactions – categories we refer to as organising principles (OPs). We applied the framework to data from 21 forest plots covering more than 2.9 million trees of approximately 6500 species. We found that differences among species, the species OP, proved a major source of variability in tree vital rates, explaining 28–33% of demographic variance alone, and 14–17% in interaction with space, totalling 40–43%. Our results support the hypothesis that the range of vital rates is similar across global forests. However, the average variability among species declined with species richness, indicating that diverse forests featured smaller interspecific differences in vital rates. Moreover, decomposing the variance in vital rates into the proposed OPs showed the importance of unexplained variability, which includes individual variation, in tree demography. A focus on how demographic variance is organized in forests can facilitate the construction of more targeted models with clearer expectations of which covariates might drive a vital rate. This study therefore highlights the most promising avenues for future research, both in terms of understanding the relative contributions of groups of mechanisms to forest demography and diversity, and for improving projections of forest ecosystems.
|
|
| 13. |
- Piponiot, Camille, et al.
(författare)
-
Distribution of biomass dynamics in relation to tree size in forests across the world
- 2022
-
Ingår i: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 234, s. 1664-1677
-
Tidskriftsartikel (refereegranskat)abstract
- Tree size shapes forest carbon dynamics and determines how trees interact with their environment, including a changing climate. Here, we conduct the first global analysis of among-site differences in how aboveground biomass stocks and fluxes are distributed with tree size. We analyzed repeat tree censuses from 25 large-scale (4–52 ha) forest plots spanning a broad climatic range over five continents to characterize how aboveground biomass, woody productivity, and woody mortality vary with tree diameter. We examined how the median, dispersion, and skewness of these size-related distributions vary with mean annual temperature and precipitation. In warmer forests, aboveground biomass, woody productivity, and woody mortality were more broadly distributed with respect to tree size. In warmer and wetter forests, aboveground biomass and woody productivity were more right skewed, with a long tail towards large trees. Small trees (1–10 cm diameter) contributed more to productivity and mortality than to biomass, highlighting the importance of including these trees in analyses of forest dynamics. Our findings provide an improved characterization of climate-driven forest differences in the size structure of aboveground biomass and dynamics of that biomass, as well as refined benchmarks for capturing climate influences in vegetation demographic models.
|
|
| 14. |
- Sun, Vivian Z., et al.
(författare)
-
Overview and Results From the Mars 2020 Perseverance Rover's First Science Campaign on the Jezero Crater Floor
- 2023
-
Ingår i: Journal of Geophysical Research: Planets. - : John Wiley and Sons Inc. - 2169-9097 .- 2169-9100. ; 128:6
-
Tidskriftsartikel (refereegranskat)abstract
- The Mars 2020 Perseverance rover landed in Jezero crater on 18 February 2021. After a 100-sol period of commissioning and the Ingenuity Helicopter technology demonstration, Perseverance began its first science campaign to explore the enigmatic Jezero crater floor, whose igneous or sedimentary origins have been much debated in the scientific community. This paper describes the campaign plan developed to explore the crater floor's Máaz and Séítah formations and summarizes the results of the campaign between sols 100–379. By the end of the campaign, Perseverance had traversed more than 5 km, created seven abrasion patches, and sealed nine samples and a witness tube. Analysis of remote and proximity science observations show that the Máaz and Séítah formations are igneous in origin and composed of five and two geologic members, respectively. The Séítah formation represents the olivine-rich cumulate formed from differentiation of a slowly cooling melt or magma body, and the Máaz formation likely represents a separate series of lava flows emplaced after Séítah. The Máaz and Séítah rocks also preserve evidence of multiple episodes of aqueous alteration in secondary minerals like carbonate, Fe/Mg phyllosilicates, sulfates, and perchlorate, and surficial coatings. Post-emplacement processes tilted the rocks near the Máaz-Séítah contact and substantial erosion modified the crater floor rocks to their present-day expressions. Results from this crater floor campaign, including those obtained upon return of the collected samples, will help to build the geologic history of events that occurred in Jezero crater and provide time constraints on the formation of the Jezero delta.
|
|
| 15. |
- Yuan, Shuai, et al.
(författare)
-
Genetic Liability to Rheumatoid Arthritis in Relation to Coronary Artery Disease and Stroke Risk
- 2022
-
Ingår i: Arthritis & Rheumatology. - : John Wiley & Sons. - 2326-5191 .- 2326-5205. ; 74:10, s. 1638-1647
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To assess the causality of the associations of rheumatoid arthritis (RA) with coronary artery disease (CAD) and stroke using the Mendelian randomization approach.METHODS: Independent single-nucleotide polymorphisms strongly associated with RA (n = 70) were selected as instrumental variables from a genome-wide association meta-analysis including 14,361 RA patients and 43,923 controls of European ancestry. Summary-level data for CAD, all stroke, any ischemic stroke and its subtypes, intracerebral hemorrhage (ICH), and subarachnoid hemorrhage were obtained from meta-analyses of genetic studies, international genetic consortia, the UK Biobank, and the FinnGen consortium. We obtained summary-level data for common cardiovascular risk factors and related inflammatory biomarkers to assess possible mechanisms.RESULTS: Genetic liability to RA was associated with an increased risk of CAD and ICH. For a 1-unit increase in log odds of RA, the combined odds ratios were 1.02 (95% confidence interval [1.01, 1.03]; P = 0.003) for CAD and 1.05 (95% confidence interval [1.02, 1.08]; P = 0.001) for ICH. Genetic liability to RA was associated with increased levels of tumor necrosis factor and C-reactive protein (CRP). The association with CAD was attenuated after adjustment for genetically predicted CRP levels. There were no associations of genetic liability to RA with the other studied outcomes.CONCLUSION: This study found that genetic liability to RA was associated with an increased risk of CAD and ICH and that the association with CAD might be mediated by CRP. The heightened cardiovascular risk should be actively monitored and managed in RA patients, and this may include dampening systemic inflammation.
|
|
