Directionality of coupling from bivariate time series: how to avoid false causalities and missed connections

Causality or causation is a fundamental concept in epidemiology, vital for understanding the relationships between various factors and health outcomes. Despite its importance, there's no single, universally accepted definition of causality within the discipline. Drawing from a systematic review, causality in epidemiology encompasses several definitions, including production, necessary and sufficient, sufficient-component, counterfactual, and probabilistic models. Each has its strengths and...

Correlation and CausationStatistical tests can calculate whether there is a relationship, or correlation, between independent and dependent variables. A relationship between variables shows correlation, but it does not show cause-and-effect. A direct cause-and-effect relationship requires additional controlled experiments. If no consistent relationship exists between the variables, then there is no correlation.Correlation versus CausationIf the dependent variable increases or decreases when the...

While variables are sometimes correlated because one does cause the other, it could also be that some other factor, a confounding variable, is actually causing the systematic movement in our variables of interest. For instance, as sales in ice cream increase, so does the overall rate of crime. Is it possible that indulging in your favorite flavor of ice cream could send you on a crime spree? Or, after committing crime do you think you might decide to treat yourself to a cone?

Vicinal or three-bond coupling is commonly observed between protons attached to adjacent carbons. Here, nuclear spin information is primarily transferred via electron spin interactions between adjacent C‑H bond orbitals. This generally favors the antiparallel arrangement of spins, so 3J values are usually positive.
The extent of coupling depends on the C‑C bond length, the two H‑C‑C angles, any electron-withdrawing substituents, and the dihedral angle between the involved orbitals. The...

The coupling interactions of nuclei across four or more bonds are usually weak, with J values less than 1 Hz. While these are usually not observed in spectra, the presence of multiple bonds along the coupling pathway can result in observable long-range coupling.
In alkenes, spin information is communicated via σ–π overlap, as seen in allylic (four-bond) and homoallylic (five-bond) couplings. These coupling interactions are stronger when the σ bond is parallel to the alkene π orbitals.

Two NMR-active nuclei bonded to a central atom can be involved in geminal or two-bond coupling. Geminal coupling is commonly seen between diastereotopic protons in chiral molecules and unsymmetrical alkenes, among others.
The central atom need not be NMR-active because its electrons are affected by the electron polarization of the spin-active atoms. However, spin information is transmitted less effectively than in one-bond coupling, and 2J values are usually weaker than 1J values. The energy of...