It is equally important to note that this also does not mean the discoveries from all 3500 of these studies are false; the effects in some studies could be so strong to be detected even despite this problem, or the findings in others could be weak but have subsequently been replicated.
These findings have subsequently been replicated in a normal volunteer sample [ 6] in which fewer perseverative errors on the WCST were made by subjects homozygous for the Met allele.
These loci including 6q23, TRAF1/C5, STAT4, IL2RB, KIF5A, PRKCQ, IL2/IL21, CD226, CCL21, CD40, CTLA4 and IL2RA, defined by single nucleotide polymorphisms (SNPs), have subsequently been replicated in large independent panels of patients and healthy controls.
Maintaining normoglycaemia through IIT significantly reduced mortality in Van den Berghe and colleagues' SICU trial [ 1] and reduced morbidity in their MICU trial [ 2], and their results have subsequently been replicated in studies using historical controls [ 26, 27].
In this regard, it is reassuring that about 90% of the associations shown in studies involving more than 150 cases and controls have subsequently been replicated, as pointed out in a recent meta-analysis [ 24].
Two additional genes, NALP1 (now NLRP1; NLR family, pyrin domain containing 1) and XBP1 (X-box binding protein 1), were first mapped by unbiased genome-wide linkage analyses and subsequently were identified by positionally targeted genetic association studies [ 7, 8]; both of these genes have subsequently been replicated by multiple studies [ 3, 6].
It has subsequently been demonstrated that these regions replicate late in S phase [ 29].
The safety of the combination has subsequently been assessed in a pooled safety analysis of two replicate phase III tiotropium + olodaterol FDC studies (Study 1237.5: NCT01431274; Study 1237.6: NCT01237.67).
"Each has subsequently been admitted".
