In addition, a publicly available data set with information on gene expression from endometrial cancer patients was used for supplementary studies (NCBI GEO: GSE2109).
Other benefits include the establishment of a large cohort of patients that could be used for supplementary studies on risk factors for disease progression, the development of expertise at over 70 special multiple sclerosis treatment centres, and increased funding for specialist nurses so that now over 200 are employed compared with 75 at the start of the scheme.
Eight authors [ 1, 9, 17, 20- 23] responded to our requests for supplementary study data, and one [ 1] provided us with their original dataset and regression modeling strategy such that we could calculate an adjusted OR for a candidate risk factor that was only reported in the manuscript as an adjusted P value.
We thank Pedro Cano and Seth Myers for piloting supplementary studies of word recurrences, Roger Guimerà and Seth Myers for sharing web mining programs, Bruce Spencer for advice on the statistical analysis, Stefan Kaufmann for his assistance in developing the semantic coding scheme, and Hannah Rohde for validating it.
For the supplementary study with ambulatory measurements of BP and physical activity, for which a much smaller sample size was aimed at, 182 participants were included, indicating a response rate of 66%.
For a supplementary study with ambulatory measurements of BP and physical activity, four of the nine organizations were involved.
Supplementary studies carried out for the CO2 and N2 injection cases include that of the sensitivity to the number of available DHR loops and to the LOCA break-size.
Visual predictive check (VPC) simulations indicated good agreement between observed and simulated data for all studies (Supplementary Figures S2 and S3) and covariates (Supplementary Figure S4).
Quality scores ranged from one to five stars (out of a possible six) for cross-sectional studies (Supplementary Table 2) and from four to six stars (out of a possible eight stars) for cohort studies (Supplementary Table 3).
We used three different bioengineered constructs with the objective that at least one of them should be crystallized at a later time point for structural studies (Supplementary Figure S1): OR131-2C is the native receptor with a specific rhodopsin derived tag for affinity purification [15].
We used the compounds A22, RH02007, DSHS00884, gossypetin and a related compound, baicalein, for these studies (Supplementary Table 2).
