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In addition, the numbers and percentages of patients were cross-tabulated by modal dosage (dose given on most treatment days) and years of clobazam exposure.
Very few patients (<8%) received a modal dosage below 0.375 mg/kg/day, and the majority of patients received 0.375 1.25 mg/kg/day of clobazam through Year 5.
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18 Our summary outcome of sustained therapeutic responses, as measured by numbers and percentages of patients sustaining their initial responses at Years 1, 2, and 3, as well as our analyses of mean modal dosages over time, does not exclude the possibility of the development of tolerance.
The modal clobazam dosage by duration of exposure was stable over time (Table 7).
The mean modal clobazam dosage was 0.90 mg/kg/day at Year 1 and 0.97 mg/kg/day at Year 5, suggesting that study patients did not need significant increases in dosage over time.
From Year 1 through Year 5, mean modal clobazam dosages increased by a mere 8%.
For each patient, the most common (modal) and maximum dosages of clobazam were calculated.
At Year 5, the mean modal and mean maximum dosages of clobazam in patients who received clobazam for >22 days (N = 265) were 0.97 and 1.19 mg/kg/day, respectively, and there was no substantive change over time (Table 6).
Descriptive summaries of the mean modal and mean maximum dosages were provided over 5 years for the 265 patients who received clobazam for >22 days (i.e., postdosage titration).
Selection due to dosage effects and/or stoichiometric disturbance might act more strongly to maintain a modal number of homeobox genes (and possibly transcription factors more generally) per genome, yet permit the accumulation of other (non regulatory) genes associated with these homeobox gene clusters.
Again, selection might act more strongly in bringing about the loss of interdigitated genes within cluster following a WGD to maintain a modal gene number per genome of these clustered homeobox genes in order to reduce potentially negative changes in dosage following a WGD.
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