"cedergreen" <- function(
fixed = c(NA, NA, NA, NA, NA), names = c("b", "c", "d", "e", "f"),
method = c("1", "2", "3", "4"), ssfct = NULL,
alpha, fctName, fctText)
{
## Checking arguments
numParm <- 5
if (!is.character(names) | !(length(names)==numParm)) {stop("Not correct 'names' argument")}
if (!(length(fixed)==numParm)) {stop("Not correct 'fixed' argument")}
# if (!is.logical(useD)) {stop("Not logical useD argument")}
# if (useD) {stop("Derivatives not available")}
if (missing(alpha)) {stop("'alpha' argument must be specified")}
notFixed <- is.na(fixed)
parmVec <- rep(0, numParm)
parmVec[!notFixed] <- fixed[!notFixed]
parmVec1 <- parmVec
parmVec2 <- parmVec
## Defining the non-linear function
fct <- function(dose, parm)
{
parmMat <- matrix(parmVec, nrow(parm), numParm, byrow=TRUE)
parmMat[, notFixed] <- parm
parmMat[,2] + (parmMat[,3] - parmMat[,2] + parmMat[,5]*exp(-1/(dose^alpha)))/(1 + exp(parmMat[,1]*(log(dose) - log(parmMat[,4]))))
}
# ## Defining value for control measurements (dose=0)
# confct <- function(drcSign)
# {
# if (drcSign>0) {conPos <- 2} else {conPos <- 3}
# confct2 <- function(parm)
# {
# parmMat <- matrix(parmVec, nrow(parm), numParm, byrow=TRUE)
# parmMat[, notFixed] <- parm
# parmMat[, conPos]
# }
# return(list(pos=conPos, fct=confct2))
# }
#
#
# ## Defining flag to indicate if more general ANOVA model
## anovaYes <- TRUE
# binVar <- all(fixed[c(2, 3, 5)]==c(0, 1, 1))
# if (is.na(binVar)) {binVar <- FALSE}
# if (!binVar) {binVar <- NULL}
# anovaYes <- list(bin = binVar, cont = TRUE)
## Defining self starter function
if (FALSE)
{
ssfct <- function(dataFra)
{
dose2 <- dataFra[,1]
resp3 <- dataFra[,2]
startVal <- rep(0, numParm)
# startVal[3]<-max(resp3)+0.001 # the d parameter
# startVal[2]<-min(resp3)-0.001 # the c parameter
startVal[3] <- 1.05 * resp3[which.min(dose2)]
startVal[2] <- 0.95 * min(resp3)
# startVal[!notFixed] <- fixed[!notFixed]
if (length(unique(dose2))==1) {return((c(NA,NA,startVal[3],NA,NA))[notFixed])}
indexT2<-(dose2>0)
if (!any(indexT2)) {return((rep(NA, numParm))[notFixed])}
dose3<-dose2[indexT2]
resp3<-resp3[indexT2]
logitTrans<-log((startVal[3]-resp3)/(resp3-startVal[2] + 0.001)) # 0.001 to avoid 0 in the denominator
logitFit<-lm(logitTrans~log(dose3))
startVal[4]<-exp((-coef(logitFit)[1]/coef(logitFit)[2])) # the e parameter
startVal[1]<-coef(logitFit)[2] # the b parameter
# startVal[5] <- 0 # the f parameter
## Solving equation at x=e
startVal[5] <- (2*(median(resp3) - startVal[2]) - (startVal[3] - startVal[2]))*exp(1/(startVal[4]^alpha))
return(startVal[notFixed])
}
}
if (!is.null(ssfct))
{
ssfct <- ssfct
} else {
# ssfct <- cedergreen.ssf(method, fixed, alpha)
ssfct <- function(dframe)
{
initval <- llogistic()$ssfct(dframe)
initval[5] <- (2*(median(dframe[, 2])-initval[2])-(initval[3]-initval[2]))*exp(1/(initval[4]^alpha))
return(initval[notFixed])
}
}
## Defining names
names <- names[notFixed]
# ## Defining parameter to be scaled
# if ( (scaleDose) && (is.na(fixed[4])) )
# {
# scaleInd <- sum(is.na(fixed[1:4]))
# } else {
# scaleInd <- NULL
# }
## Defining derivatives
# ## Constructing a helper function
# xlogx <- function(x, p)
# {
# lv <- (x < 1e-12)
# nlv <- !lv
#
# rv <- rep(0, length(x))
#
# xlv <- x[lv]
# rv[lv] <- log(xlv^(xlv^p[lv]))
#
# xnlv <- x[nlv]
# rv[nlv] <- (xnlv^p[nlv])*log(xnlv)
#
# rv
# }
## Specifying the derivatives
deriv1 <- function(dose, parm)
{
parmMat <- matrix(parmVec, nrow(parm), numParm, byrow=TRUE)
parmMat[, notFixed] <- parm
t0 <- exp(-1/(dose^alpha))
t1 <- parmMat[, 3] - parmMat[, 2] + parmMat[, 5]*t0
t2 <- exp(parmMat[, 1]*(log(dose) - log(parmMat[, 4])))
t3 <- 1 + t2
t4 <- (1 + t2)^(-2)
cbind( -t1*xlogx(dose/parmMat[, 4], parmMat[, 1])*t4,
1 - 1/t3,
1/t3,
t1*t2*(parmMat[, 1]/parmMat[, 4])*t4,
t0/t3 )[, notFixed]
}
deriv2 <- NULL
## Limits
# if (length(lowerc)==numParm) {lowerLimits <- lowerc[notFixed]} else {lowerLimits <- lowerc}
# if (length(upperc)==numParm) {upperLimits <- upperc[notFixed]} else {upperLimits <- upperc}
## Defining the ED function
# edfct <- function(parm, p, lower = 1e-4, upper = 10000, ...) # upper2=1000)
edfct <- function(parm, respl, reference, type, lower = 1e-4, upper = 10000, ...) # upper2=1000)
{
# if (is.null(upper)) {upper <- 1000}
# if (missing(upper2)) {upper2 <- 1000}
interval <- c(lower, upper)
parmVec[notFixed] <- parm
p <- EDhelper(parmVec, respl, reference, type, TRUE) # FALSE) Changed 2010-06-02 after e-mail from Claire
tempVal <- (100-p)/100
helpFct <- function(dose) {parmVec[2]+(parmVec[3]-parmVec[2]+parmVec[5]*exp(-1/(dose^alpha)))/(1+exp(parmVec[1]*(log(dose)-log(parmVec[4]))))}
# doseVec <- exp(seq(-upper2, upper2, length=1000))
doseVec <- exp(seq(log(interval[1]), log(interval[2]), length=1000))
maxAt <- doseVec[which.max(helpFct(doseVec))]
# print(maxAt)
# print(upper)
eqn <- function(dose) {tempVal*(1+exp(parmVec[1]*(log(dose)-log(parmVec[4]))))-(1+parmVec[5]*exp(-1/(dose^alpha))/(parmVec[3]-parmVec[2]))}
EDp <- uniroot(eqn, lower=maxAt, upper=upper)$root
EDdose <- EDp
tempVal1 <- exp(parmVec[1]*(log(EDdose)-log(parmVec[4])))
tempVal2 <- parmVec[3]-parmVec[2]
derParm <- c(tempVal*tempVal1*(log(EDdose)-log(parmVec[4])), -parmVec[5]*exp(-1/(EDdose^alpha))/((tempVal2)^2),
parmVec[5]*exp(-1/(EDdose^alpha))/((tempVal2)^2), -tempVal*tempVal1*parmVec[1]/parmVec[4],
-exp(-1/(EDdose^alpha))/tempVal2)
derDose <- tempVal*tempVal1*parmVec[1]/EDdose-parmVec[5]/tempVal2*exp(-1/(EDdose^alpha))/(EDdose^(1+alpha))*alpha
EDder <- derParm/derDose
return(list(EDp, EDder[notFixed]))
}
#
# ## Defining the SI function
# sifct <- function(parm1, parm2, pair, upper = 10000, interval = c(1e-4, 10000))
# {
## if (is.null(upper)) {upper <- 1000}
## if (missing(upper2)) {upper2 <- 1000}
#
# parmVec1[notFixed] <- parm1
# parmVec2[notFixed] <- parm2
#
# tempVal1 <- (100-pair[1])/100
# tempVal2 <- (100-pair[2])/100
#
## doseVec <- exp(seq(-upper2, upper2, length=max(c(1000, upper2))))
# doseVec <- exp(seq(log(interval[1]), log(interval[2]), length=1000))
# helpFct1 <- function(dose)
# {
# parmVec1[2]+(parmVec1[3]-parmVec1[2]+parmVec1[5]*exp(-1/(dose^alpha)))/(1+exp(parmVec1[1]*(log(dose)-log(parmVec1[4]))))
# }
# maxAt1 <- doseVec[which.max(helpFct1(doseVec))]
#
# helpFct2 <- function(dose)
# {
# parmVec2[2]+(parmVec2[3]-parmVec2[2]+parmVec2[5]*exp(-1/(dose^alpha)))/(1+exp(parmVec2[1]*(log(dose)-log(parmVec2[4]))))
# }
# maxAt2 <- doseVec[which.max(helpFct2(doseVec))]
#
# eqn1 <- function(dose) {tempVal1*(1+exp(parmVec1[1]*(log(dose)-log(parmVec1[4]))))-(1+parmVec1[5]*exp(-1/(dose^alpha))/(parmVec1[3]-parmVec1[2]))}
# EDp1 <- uniroot(eqn1, lower=maxAt1, upper=upper)$root
# eqn2 <- function(dose) {tempVal2*(1+exp(parmVec2[1]*(log(dose)-log(parmVec2[4]))))-(1+parmVec2[5]*exp(-1/(dose^alpha))/(parmVec2[3]-parmVec2[2]))}
# EDp2 <- uniroot(eqn2, lower=maxAt2, upper=upper)$root
#
# SIpair <- EDp1/EDp2
#
# EDdose1 <- EDp1
# EDdose2 <- EDp2
# tempVal11 <- exp(parmVec1[1]*(log(EDdose1)-log(parmVec1[4])))
# tempVal12 <- parmVec1[3]-parmVec1[2]
# derParm1 <- c(tempVal1*tempVal11*(log(EDdose1)-log(parmVec1[4])), -parmVec1[5]*exp(-1/(EDdose1^alpha))/((tempVal12)^2),
# parmVec1[5]*exp(-1/(EDdose1^alpha))/((tempVal12)^2), -tempVal1*tempVal11*parmVec1[1]/parmVec1[4],
# -exp(-1/(EDdose1^alpha))/tempVal12)
# derDose1 <- tempVal1*tempVal11*parmVec1[1]/EDdose1-parmVec1[5]/tempVal12*exp(-1/(EDdose1^alpha))/(EDdose1^(1+alpha))*alpha
#
# SIder1 <- (derParm1/derDose1)/EDp2
#
# tempVal21 <- exp(parmVec2[1]*(log(EDdose2)-log(parmVec2[4])))
# tempVal22 <- parmVec2[3]-parmVec2[2]
# derParm2 <- c(tempVal2*tempVal21*(log(EDdose2)-log(parmVec2[4])), -parmVec2[5]*exp(-1/(EDdose2^alpha))/((tempVal22)^2),
# parmVec2[5]*exp(-1/(EDdose2^alpha))/((tempVal22)^2), -tempVal2*tempVal21*parmVec2[1]/parmVec2[4],
# -exp(-1/(EDdose2^alpha))/tempVal22)
# derDose2 <- tempVal2*tempVal21*parmVec2[1]/EDdose2-parmVec2[5]/tempVal22*exp(-1/(EDdose2^alpha))/(EDdose2^(1+alpha))*alpha
#
# SIder2 <- (derParm2/derDose2)*(-EDp1/(EDp2*EDp2))
#
# return(list(SIpair, SIder1[notFixed], SIder2[notFixed]))
# }
## Finding the maximal hormesis
maxfct <- function(parm, lower = 1e-3, upper = 1000)
{
# if (is.null(upper)) {upper <- 1000}
# if (is.null(interval)) {interval <- c(1e-3, 1000)}
# alpha <- 0.5
parmVec[notFixed] <- parm
optfct <- function(t)
{
expTerm1 <- parmVec[5]*exp(-1/(t^alpha))
expTerm2 <- exp(parmVec[1]*(log(t)-log(parmVec[4])))
return(expTerm1*alpha/(t^(alpha+1))*(1+expTerm2)-(parmVec[3]-parmVec[2]+expTerm1)*expTerm2*parmVec[1]/t)
}
ED1 <- edfct(parm, 1, lower, upper)[[1]]
doseVec <- exp(seq(log(1e-6), log(ED1), length = 100))
# print((doseVec[optfct(doseVec)>0])[1])
maxDose <- uniroot(optfct, c((doseVec[optfct(doseVec)>0])[1], ED1))$root
return(c(maxDose, fct(maxDose, matrix(parm, 1, length(names)))))
}
returnList <-
list(fct=fct, ssfct=ssfct, names=names, deriv1=deriv1, deriv2=deriv2, # lowerc=lowerLimits, upperc=upperLimits,
edfct=edfct, maxfct=maxfct,
# scaleInd=scaleInd, anovaYes=anovaYes, confct=confct,
# name = "cedergreen",
# text = "Cedergreen-Ritz-Streibig",
name = ifelse(missing(fctName), as.character(match.call()[[1]]), fctName),
text = ifelse(missing(fctText), "Cedergreen-Ritz-Streibig", fctText),
noParm = sum(is.na(fixed)))
class(returnList) <- "mllogistic"
invisible(returnList)
}
"CRS.4a" <-
function(names = c("b", "d", "e", "f"), ...)
{
## Checking arguments
if (!is.character(names) | !(length(names)==4)) {stop("Not correct 'names' argument")}
return(cedergreen(fixed = c(NA, 0, NA, NA, NA), names = c(names[1], "c", names[2:4]), alpha = 1,
fctName = as.character(match.call()[[1]]),
fctText = "Cedergreen-Ritz-Streibig with lower limit 0 (alpha=1)",
...))
}
ml3a <- CRS.4a
"CRS.4b" <-
function(names = c("b", "d", "e", "f"), ...)
{
## Checking arguments
if (!is.character(names) | !(length(names)==4)) {stop("Not correct 'names' argument")}
return(cedergreen(fixed = c(NA, 0, NA, NA, NA), names = c(names[1], "c", names[2:4]), alpha = 0.5,
fctName = as.character(match.call()[[1]]),
fctText = "Cedergreen-Ritz-Streibig with lower limit 0 (alpha=.5)",
...))
}
ml3b <- CRS.4b
"CRS.4c" <-
function(names = c("b", "d", "e", "f"), ...)
{
## Checking arguments
if (!is.character(names) | !(length(names)==4)) {stop("Not correct 'names' argument")}
return(cedergreen(fixed = c(NA, 0, NA, NA, NA), names = c(names[1], "c", names[2:4]), alpha = 0.25,
fctName = as.character(match.call()[[1]]),
fctText = "Cedergreen-Ritz-Streibig with lower limit 0 (alpha=.25)",
...))
}
ml3c <- CRS.4c
"CRS.5a" <-
function(names = c("b", "c", "d", "e", "f"), ...)
{
## Checking arguments
if (!is.character(names) | !(length(names)==5)) {stop("Not correct 'names' argument")}
return(cedergreen(fixed = c(NA, NA, NA, NA, NA), names = names, alpha = 1,
fctName = as.character(match.call()[[1]]),
fctText = "Cedergreen-Ritz-Streibig (alpha=1)",
...))
}
ml4a <- CRS.5a
"CRS.5b" <-
function(names = c("b", "c", "d", "e", "f"), ...)
{
## Checking arguments
if (!is.character(names) | !(length(names)==5)) {stop("Not correct 'names' argument")}
return(cedergreen(fixed = c(NA, NA, NA, NA, NA), names = names, alpha = 0.5,
fctName = as.character(match.call()[[1]]),
fctText = "Cedergreen-Ritz-Streibig (alpha=.5)",
...))
}
ml4b <- CRS.5b
"CRS.5c" <-
function(names = c("b", "c", "d", "e", "f"), ...)
{
## Checking arguments
if (!is.character(names) | !(length(names)==5)) {stop("Not correct 'names' argument")}
return(cedergreen(fixed = c(NA, NA, NA, NA, NA), names = names, alpha = 0.25,
fctName = as.character(match.call()[[1]]),
fctText = "Cedergreen-Ritz-Streibig (alpha=.25)",
...))
}
ml4c <- CRS.5c
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