Differences in time to heading that remain after photoperiod and vernalisation requirements have been saturated are classified as earliness per se ( Eps ) effects. It has been commonly assumed that Eps genes are purely constitutive and independent of environment, although the likely effect of temperature on Eps effects in hexaploid wheat has never been tested. We grew four near isogenic lines (NILs) for the Eps gene located in chromosome 1D ( Eps-D1 ) at 6, 9, 12, 15, 18, 21 and 24 °C. In line with expectations we found that lines carrying the Eps -late allele were always later than those with Eps -early alleles. But in addition, we reported for the first time that the magnitude of the effect increased with decreasing temperature: an Eps x temperature interaction in hexaploid wheat. Variation in heading time due to Eps x temperature was associated with an increase in sensitivity to temperature mainly during late reproductive phase. Moreover, we showed that Eps alleles exhibited differences in cardinal (base, optimum, maximum) temperatures and that the expression of ELF3 , (the likely candidate for Eps-D1 ) also interacted with temperature.

Ppd-1a reduced the number of fertile florets due largely to lowering floret survival, and the effect was not proportional to the duration of the late reproductive phase.

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Objectives The aim of the study was to assess the rates of discontinuation of integrase inhibitor regimens because of any neuropsychiatric adverse event (NPAE) and the factors associated with discontinuation. Methods A population‐based, prospective, multicentre cohort study was carried out. Treatment‐naïve subjects starting therapy with a regimen containing integrase inhibitors, or those switching to such a regimen, with plasma HIV‐1 RNA < 50 HIV‐1 RNA copies/mL in 14 hospitals in Catalonia or the Balearic Islands (Spain) were included in the study. Every discontinuation because of adverse events (AEs) was double‐checked directly with treating physicians. Multivariable Cox models identified factors correlated with discontinuation. Results A total of 4165 subjects (37% treatment‐naïve) started regimens containing dolutegravir (n = 1650; 91% with abacavir), raltegravir (n = 930) or elvitegravir/cobicistat (n = 1585). There were no significant differences among regimens in the rate of discontinuation because of any AE. Rates of discontinuation because of NPAEs were low but higher for dolutegravir/abacavir/lamivudine [2.1%; 2.9 (95% confidence interval (CI) 2.0, 4.2) discontinuations/100 patients/year] versus elvitegravir/cobicistat (0.5%; 0.8 (95% CI 0.3, 1.5) discontinuations/100 patients/year], with significant differences among centres for dolutegravir/abacavir/lamivudine and NPAEs (P = 0.003). We identified an association of female gender and lower CD4 count with increased risk of discontinuation because of any AE [Incidence ratio (IR) 2.3 (95% CI 1.4, 4.0) and 1.8 (95% CI 1.1, 2.8), respectively]. Female gender, age > 60 years and abacavir use were not associated with NPAE discontinuations. NPAEs were commonly grade 1–2, and had been present before and improved after drug withdrawal. Conclusions In this large prospective cohort study, patients receiving dolutegravir, raltegravir or elvitegravir/cobicistat did not show significant differences in the rate of discontinuation because of any toxicity. The rate of discontinuations because of NPAEs was low, but was significantly higher for dolutegravir than for elvitegravir/cobicistat, with significant differences among centres, suggesting that greater predisposition to believe that a given adverse event is caused by a given drug of some treating physicians might play a role in the discordance seen between cohorts.

Wheat Ppd-1a alleles did not affect leaf initiation but accelerated spikelet initiation, which partially compensated for the reduction in spikelet number due to a shorter period of spikelet initiation.