A B S TR A CT Calculations based on a KMnFMASH petrogenetic grid derived using an internally consistent thermodynamic dataset indicate that the principal effect of the presence of Mn in average subaluminous pelite compositions is to stabilize garnet to higher and lower pressures and temperatures over a wide range of bulk compositions. Garnet-bearing fields expand to lower temperatures and pressures with the addition of Mn, and garnet appears as an extra phase at low pressures. The addition of Mn also increases the number and extent of four AMnFM phase assemblages and stabilizes five AMnFM phases along univariant reactions. The KMnFMASH system predictions for typical subaluminous pelite bulk compositions match the sequence of isograds and assemblages observed in the Barrovian zones. The sequence of assemblages observed in the Stonehaven section can also be predicted if there is variation in bulk composition within the stratigraphic section. Mn appears to be less important in producing the sequence of isograds and garnet-absent assemblages in the low-pressure Buchan zones. The addition of Mn to the calculations does not change the sequence of isograds that are predicted to be stable in a regional metamorphic terrane, but the P-T position of these isograds does change. In particular, the predicted temperature of the garnet-in isograd is lowered by as much as 100°C by the addition of Mn to KFMASH. Mn also increases the range of metapelite bulk compositions that develop the assemblages traditionally identified as metapelite isograds.

BackgroundMediation analysis tests whether the relationship between two variables is explained by a third intermediate variable. We sought to describe the usage and reporting of mediation analysis with time-to-event outcomes in published healthcare research.MethodsA systematic search of Medline, Embase, and Web of Science was executed in December 2016 to identify applications of mediation analysis to healthcare research involving a clinically relevant time-to-event outcome. We summarized usage over time and reporting of important methodological characteristics.ResultsWe included 149 primary studies, published from 1997 to 2016. Most studies were published after 2011 (n = 110, 74%), and the annual number of studies nearly doubled in the last year (from n = 21 to n = 40). A traditional approach (causal steps or change in coefficient) was most commonly taken (n = 87, 58%), and the majority of studies (n = 114, 77%) used a Cox Proportional Hazards regression for the outcome. Few studies (n = 52, 35%) mentioned any of the assumptions or limitations fundamental to a causal interpretation of mediation analysis.ConclusionThere is increasing use of mediation analysis with time-to-event outcomes. Current usage is limited by reliance on traditional methods and the Cox Proportional Hazards model, as well as low rates of reporting of underlying assumptions. There is a need for formal criteria to aid authors, reviewers, and readers reporting or appraising such studies.Electronic supplementary materialThe online version of this article (10.1186/s12874-018-0578-7) contains supplementary material, which is available to authorized users.

BackgroundBinge drinking is a serious public health issue associated with cognitive, physiological, and anatomical differences from healthy individuals. No studies, however, have reported subcortical grey matter differences in this population. To address this, we compared the grey matter volumes of college-age binge drinkers and healthy controls, focusing on the ventral striatum, hippocampus and amygdala.MethodT1-weighted images of 19 binge drinkers and 19 healthy volunteers were analyzed using voxel-based morphometry. Structural data were also covaried with Alcohol Use Disorders Identification Test (AUDIT) scores. Cluster-extent threshold and small volume corrections were both used to analyze imaging data.ResultsBinge drinkers had significantly larger ventral striatal grey matter volumes compared to controls. There were no between group differences in hippocampal or amygdalar volume. Ventral striatal, amygdalar, and hippocampal volumes were also negatively related to AUDIT scores across groups.ConclusionsOur findings stand in contrast to the lower ventral striatal volume previously observed in more severe forms of alcohol use disorders, suggesting that college-age binge drinkers may represent a distinct population from those groups. These findings may instead represent early sequelae, compensatory effects of repeated binge and withdrawal, or an endophenotypic risk factor.