Reproducibility is a defining feature of science, but the extent to which it characterizes current research is unknown. We conducted replications of 100 experimental and correlational studies published in three psychology journals using high-powered designs and original materials when available. Replication effects were half the magnitude of original effects, representing a substantial decline. Ninety-seven percent of original studies had statistically significant results. Thirty-six percent of replications had statistically significant results; 47% of original effect sizes were in the 95% confidence interval of the replication effect size; 39% of effects were subjectively rated to have replicated the original result; and if no bias in original results is assumed, combining original and replication results left 68% with statistically significant effects. Correlational tests suggest that replication success was better predicted by the strength of original evidence than by characteristics of the original and replication teams.
Gilbert et al. conclude that evidence from the Open Science Collaboration’s Reproducibility Project: Psychology indicates high reproducibility, given the study methodology. Their very optimistic assessment is limited by statistical misconceptions and by causal inferences from selectively interpreted, correlational data. Using the Reproducibility Project: Psychology data, both optimistic and pessimistic conclusions about reproducibility are possible, and neither are yet warranted.
We analyze the light curve of the microlensing event OGLE-2003-BLG-175/MOA-2003-BLG-45 and show that it has two properties that, when combined with future high-resolution astrometry, could lead to a direct, accurate measurement of the lens mass. First, the light curve shows clear signs of distortion due to the Earth's accelerated motion, which yields a measurement of the projected Einstein radius (r) over tilde (E). Second, from precise astrometric measurements, we show that the blended light in the event is coincident with the microlensed source to within about 15 mas. This argues strongly that this blended light is the lens and hence opens the possibility of directly measuring the lens- source relative proper motion mu(rel) and so the mass M=(c(2)/4G)mu(rel)t(E)(r) over tilde (E), where t(E) is the measured Einstein timescale. While the light-curve-based measurement of (r) over tildeE is, by itself, severely degenerate, we show that this degeneracy can be completely resolved by measuring the direction of proper motion mu(rel)
Distinct cellular roles for PDCD10 define a gut-brain axis in cerebral cavernous malformation
(2019)
Cerebral cavernous malformation (CCM) is a genetic, cerebrovascular disease. Familial CCM is caused by genetic mutations in KRIT1, CCM2, or PDCD10. Disease onset is earlier and more severe in individuals with PDCD10 mutations. Recent studies have shown that lesions arise from excess mitogen-activated protein kinase kinase kinase 3 (MEKK3) signaling downstream of Toll-like receptor 4 (TLR4) stimulation by lipopolysaccharide derived from the gut microbiome. These findings suggest a gut-brain CCM disease axis but fail to define it or explain the poor prognosis of patients with PDCD10 mutations. Here, we demonstrate that the gut barrier is a primary determinant of CCM disease course, independent of microbiome configuration, that explains the increased severity of CCM disease associated with PDCD10 deficiency. Chemical disruption of the gut barrier with dextran sulfate sodium augments CCM formation in a mouse model, as does genetic loss of Pdcd10, but not Krit1, in gut epithelial cells. Loss of gut epithelial Pdcd10 results in disruption of the colonic mucosal barrier. Accordingly, loss of Mucin-2 or exposure to dietary emulsifiers that reduce the mucus barrier increases CCM burden analogous to loss of Pdcd10 in the gut epithelium. Last, we show that treatment with dexamethasone potently inhibits CCM formation in mice because of the combined effect of action at both brain endothelial cells and gut epithelial cells. These studies define a gut-brain disease axis in an experimental model of CCM in which a single gene is required for two critical components: gut epithelial function and brain endothelial signaling.
Water is an essential input to the majority of human activities. Often, access to sufficient water resources is limited by quality and infrastructure aspects, rather than by resource availability alone, and each activity has different requirements regarding the nature of these aspects. This paper develops an integrated approach to assess the adequacy of water resources for the three major water users: the domestic, agricultural and industrial sectors. Additionally, we include environmental water requirements. We first outline the main determinants of water adequacy for each sector. Subsequently, we present an integrated approach using fuzzy logic, which allows assessing sector-specific as well as overall water adequacy. We implement the approach in two case study settings to exemplify the main features of the approach. Using results from two climate models and two forcing RCPs (representative concentration pathways), as well as population projections, we further assess the impacts of climate change in combination with population growth on the adequacy of water resources. The results provide an important step forward in determining the most relevant factors, impeding adequate access to water, which remains an important challenge in many regions of the world. The methodology allows one to directly identify the factors that are most decisive in determining the adequacy of water in each region, pointing towards the most efficient intervention points to improve conditions. Our findings underline the fact that, in addition to water volumes, water quality is a limitation for all sectors and, especially for the environmental sector, high levels of pollution are a threat to water adequacy.