v2.5.4
    - mostly based on BE/BA forums (bear feature request).
    - grouping each run with random batch# and system date marked; more outputs from this version. 
      and no more overwrite previous outputs now.
    - outlier detection analysis (ODA) is taken away from routine run; and also ODA outputs
      is separated;
    - max. data point selections for lambda_z estimation was increased to 6 (2-6);
    - single plot for point selection now (used to be 2x2 plots), old-man version?
    - fix inconsistent outputs for unbalanced dataset;
    - incomplete dataset will be blocked before being analyzed (hopefully);
    - use "file.choose()" for data file loading;
    - total lambda_z selections outputs as .csv format (sarawuto); not for demo functions;
    - pivotal and misc pk parameters output as .csv format;
    - change data() for demo functions (demodemu.r & demomenu1.r); to adapt future R (with R v3.0);
    - add "extdata" directory to store demo data files as .rda format;
    - add 'legend=FASLE' into lineplot.CI(...) (NCAplot.r) otherwise, lineplot.ci() package will 
      crash with error... [Error in rep_len(col, n.leg) : cannot replicate NULL to a non-zero 
      length] only with R v3.0.0 alpha;
    - add linear regression line plots for lambda_z estimation for manual data points selections (
      OK for R 2.15.3 and still got dev.copy() error when testing on R3.0.0beta (Helmut & sarawuto).
    - change save() and load() to saveRDS() and readRDS() for convenient scripting.
    - add mean (sd) plots on semilog scale (Helmut).
    - add alarm() and readline("...") for methods of estimation lambda_z to alert user what 
      they should know before next step.(as requested by d_labes)
    - add a section containing the means (SD) for each formulation (by time point) in NCA output 
      file (as requested by Helmut).
    - modify some output files.
    - add plots of linear regression lines for lambda_z estimation for ARS, AIC, TTT,TTT-AIC &
      TTT-ARS.
    - change all load() and save() to readRDS() and saveRDS().
    
v2.5.3
    - generalized SAS-like outputs (such as ANOVA and Type III SS) with 2x2x2 crossover;
    - added variance model into lme() and fixed random effect in lme() for replicate study
      as suggested by D. Labes posted at bebac forum (browse this thread at bebac forum);
    - the maximum data points that can be chosen to estimation of fz is set to 4, at 
      least 2 data points are required. The "Select the exact 3 data points" has been changed 
      to "Select 2-4 data point"; and
    - other minor changes.
v2.5.2
    - changed anova model back to lm(log(PK)~ seq + subj:seq + prd + drug , data) as with 
      v2.4.0; if not, this will result in error in calculation of 90% CI, as well as point
      estimates (thanks to Ji?i Hofmann, Czech Republic).
v2.5.1
    - re-compiled again to change the requirement with R v2.10.0 to enable installation in MacOSX;
      however, bear was still compiled with R v2.11.0.
v2.5.0
    - added Welch t tests (also 90% CI) for a parallel BE study (thanks to Helmut Schutz);
    - added CVintra (intra-subject CV) calculation for a replicate BE study (lme_stat.txt)
      right after classical 90% CI;
    - hide ln(PK) list in the report of ANOVA_stat.txt/lm_stat.txt/lme_stat.txt;
    - completed the function of a parallel BE study with multiple-dosed (used to be single-dosed only);
      and
    - some other bugs fixed
v2.4.4
    - fixed the output file, Statistical_summaries.txt; i.e., Table 2: remove n1, n2 list from
      nonreplicate or replicate crossover BE study; They only appear in Parallel BE study.
v2.4.3
    - changed the statitical model from linear mixed model(lme()) to linear model (lm())(similar to 
      SAS GLM) for a parallel BE study; basically, the results obtained from lme() or lm() are the same.
      However, to meet the regulatory requirements (both FDA and EU), lm() has been adopted since this
      version. Later, the Welch t-test will be added for a parallel BE study for unequal variances in
      the next release. See more discussion: Post#01 and Post#02.
    - recompiled bear under R v.2.11.0.
v2.4.2
    - fixed NCA outputs for the unbalanced parallel BE study
    - fixed TOST descriptions
    - recomplied with R v2.10.1
v2.4.1
    - add time/date stamp on the header or title page of text or pdf (plots) outputs (11.10(e) of 21 CRF 
      Part 11); more to be made for Part 11...
    - set .pdf output format as A4 paper size.
    - modify all .Rd files to fit R v2.9.2 requirements
    - change of the name "seq:subj" to "subj(seq)" in anova with the mode of "Y ~ seq + subj:seq +
      per + trt" in order to be conveniently cross validated with SAS (thanks to Elmaestro)
    - mostly minor changes with this release
v2.4.0
    - add data analysis of multiple-dose (MD) ABE data
    - add Cook's distance for outlier detection with various criteria
    - fixed y-axis scaling problem
v2.3.1
    - fixed NCA plots of  Time scale (with autoscale)
    - used the difference of lsmeans between the Ref. and the Test to calculate 90% CIs for 
      Cmax and AUCs
v2.3.0
    - add sample size estimation and lme analysis for the parallel BE study
    - add References into bear's output (such as ANOVA)
    - label outliers' subjects number for boxplot only if there is any (see crossover demo)
    - add input data summary of BA measurement (class level information, means, etc.)
    - add interpretations for some statistical tests (such as Hotelling T2 test)
    - add add Two One-Sided Tests (TOST) and Anderson-Hauck's tests (just for educational 
      purposes ONLY)
    - allow users to change BE acceptance range now (not fixed on 80%-125% any more!); different
      countries have different regulatory basis...
    - show MSResidual and MSSubject(seq) values when calculating inter- and intra-subject CV
    - change Hotelling T2 test layout

v 2.2.0
    - add point estimate along with 90% CI in output file called 'Statistical_summaries.txt 
      (suggested by D. Labes).
    - add sample size estimation for replicate BE study, and output re-arrangement.
    - add Hotelling T2 function and boxplot for outlier detection
    - add Quantiles for intrasubject and intersubject (with boxplot)
    - add replicated study for 2*2*3, 2*2*4, 2*2*5, and 2*2*6 (using lme to analyze replicated
      BE study)
    - add sample size estimation for replicated study (using 2*2*2 sample size estimation extended 
      to 2*2*n sample size of replicate crossover design)

v.2.1.0
    - we add 'analysis of outliers detection' since this release.  These include some normality 
      tests, and some diagnostic plots for this functions, such as QQ plots and intra- and 
      inter-subject residual plots.
    - fix intra-subject CV calculation based on ref. #6. (thanks to Helmut Schutz).

v1.5.0~2.0.3
   - now fz can be estimated from three methods: manual selections of the 3 exact data points,
     computer selection based on adjusted R sq. (ARS), and the Two-Times-Tmax (TTT) Method.
   - re-structure all codes of bear since v2.0.0.
   - add R sq. in NCA output; the original one is adjusted R sq. & changed T1/2 to T1/2(z) in NCA 
     output file
   - corrected some typo errors appearing in the output files or console display
   - rearrange the output files with better styles: such as 3-decimal digits for 'power', etc.
   - built-in the data file (.RData) required for demo purposes; user doesn't need to enter/import
     /load it again
   - manual selection of the 3 exact data points can be saved now.  user does not have to redo it 
     next time.
   - displayed the method used to estimate fz in NCA output
   - changed '0.693' to ln(2) when estimating T1/2(z) (= ln(2)/fz) in NCA algorithm
   - changed LSM-ref and LSM-test to LSMEAN-ref and LSMEAN-test, respectively, in the output file 
     of 'Statistical_Summaries.txt'
   - and many more that I just cannot remember right now...

v1.1.5
   - fixed the anova (lm) calculation due to the import of a .csv file. (thanks to Ji?i Hofmann, 
     Czech Republic)
   - added Type III SS (suggested by EIMaestro)
   - changed upper bound of sample size estimation from 105% to 95% (more conservative; suggested 
     by Helmut Schutz)

v1.1.4
   - fixed the compatibility for iMac and Linux (thanks to Koji Shimamoto, Tokyo, Japan; also for 
     his testing bear on iMac)

v1.1.3-1.1.0
   - removed the function of "Sample size estimation (raw data)"; also improve the function of 
     "Sample size estimation (Log Transform)."
   - fixed the rounding error in the display of "Sample size estimation (Log transform)" (thanks
     to Helmut Schutz)
   - fixed some the format (comma, semicolon, etc.) of import data file (thanks to Helmut Schutz); users 
     now can choose their favorite formats.
   - display the PATH where bear will import from and will output the all results to.
   - display only one graphic devices (using PageDown & PageUp to change plots) (thanks to Helmut Schutz)
   - display semilog (not linear) plots when choosing data points to do linear regression for 
     fz in NCA (thanks to Helmut Schutz)
   - calculate CV_intra & CV_inter now (thanks to Helmut Schutz)
   - output both the .csv and the .RData file formats obtained from NCA; users can choose either 
     one for anova.
   - use "Tests of SUBJECT(SEQUENCE) as an error term" in ANOVA output (thanks to Helmut Schutz)
   - changed ANOVA(GLM) to ANOVA (lm) in the menu title (thanks to ElMaestro)
-----

To-do lists (July 23, 2009)
-----
- add configuration setup file (as .RData data frame) into bear.  Use can create/edit this 
  configuration file. Once data has been imported, don't need to enter anything... just sit 
  back and watch. 

-----
References
1. Hauschke D, Steinijans VW, Diletti E and Burke M. Sample size determination for bioequivalence
    assessment using a multiplicative model. J. Pharmacokin. Biopharm. 20:557-561, 1992. 
2. U.S. Dept of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and
    Research.  Guidance for industry. Statistical approaches to establishing bioequivalence, 2001.
3. Liu JP and Chow SC. Sample size determination for the twp one-sided tests procedure in bioequivalence.
    J. Pharmacokin. Biopharm. 20:101-104, 1992. 
4. Schuirmann DJ. A comparison of the two one-sided tests procedure and the power approach for assessing
    the equivalence of average bioavailability. J. Pharmacokin. Biopharm. 15:657-680, 1987. 
5. Chow SC, Liu JP. Design and Analysis of Bioavailability and Bioequivalence Studies. 2009; 3rd. ed., CRC
    Press, Chapman & Hall/CRC.
6. Hauschke D, Steinijans V, Pigeot I. Bioequivalence Studies in Drug Development: Mehtods and
    Applications, 2007; John Wiley & Sons Ltd. 
