BackgroundPrevious studies assessing the association between body mass index (BMI) and atrial fibrillation (AF) did not account for time‐varying covariates, which may be affected by previous BMI. We illustrate how the g‐formula can account for time‐varying confounding.Methods and ResultsWe included 4392 participants from the Framingham Heart Study who were AF free at ages 45 to 55 years, and followed them for up to 20 years. We estimated hazard ratios (HRs) comparing time‐varying nonobese versus obese with Cox models. We used the g‐formula to compare nonobese versus obese and 10% annual decrease in BMI (until normal weight is reached) versus natural course. We estimated HRs and differences in restricted mean survival times, the mean difference in time alive and AF free. We adjusted for sex, age, and time‐varying risk factors. Cox models indicated that nonobese participants had a decreased rate of AF versus obese participants (HR, 0.83; 95% CI, 0.72–0.97). G‐formula analyses comparing everyone had they been nonobese versus obese yielded stronger associations (HR, 0.73; 95% CI, 0.58–0.91). The restricted mean survival time was 19.22 years had everyone been nonobese and 19.03 years had everyone been obese (difference, 2.25 months; 95% CI, −0.66 to 5.16). When assessing a 10% annual decrease in BMI, the association was weaker (HR 0.96; 95% CI, 0.86–1.08).ConclusionsDecreased BMI was associated with a lower rate of AF after accounting for time‐varying covariates that depend on previous exposure using the g‐formula, which Cox models cannot accommodate. Absolute measures like the restricted mean survival time difference offer context to relative measures of association.

Our study determines the selectivity of graphene oxide (GO) to recognize its ligands (e.g. flavonoids) in facilitating the binding with their respective cellular targets. The polyhydroxy phenolic compounds, flavonoids, have a broad spectrum of therapeutic activities with high potency and low systemic toxicity. Despite the vast medicinal importance, their bioavailability is low. In this exploratory study, GO has been used as the transporter of three flavonols fisetin (3, 7, 3′, 4′-OH flavone), quercetin (3, 5, 7, 3′, 4′-OH flavone), and morin (3, 5, 7, 2′, 4′-OH flavone) for the physiological target DNA. Calf thymus DNA is chosen as the model physiological target. Characterization of GO is performed using FTIR, Raman and dynamic light scattering (DLS) spectroscopy. The strong absorption peak at 1730 cm−1 indicated the presence of carbonyl groups (C=O) at the edges of GO. The presence of sp3 carbons due to oxidation of sp2 carbons in GO is further proved by Raman spectroscopy. DLS provided the average size of the GO particles to be ~9 μm. The dual luminescence behavior of the flavonols has been used in this study for the noninvasive sensing of the GO-flavonol and GO-flavonol-DNA interactions; as well as for the selectivity of GO for one flavonol over other in transferring the ligand to DNA. Furthermore, circular dichroism (CD) indicated that the optical activity of GO undergoes drastic change when conjugated with flavonols. Molecular modeling corroborated the findings from the binding studies. GO provides high promise as facilitators for drug delivery.