The prevalence of potential CYP-mediated DDIs is high in geriatric patients with polypharmacy. The risk of DDIs increases as a function of the number of medications dispensed. Pharmacists' decision to intervene for potential CYP-mediated DDIs depends on clinical judgment in addition to the output from drug alert software programs, but may be facilitated by a single multicomponent, multidrug potential CYP-mediated DDI assessment.

Brokers are fundamental for maintaining flexibility in the networks that embed criminal activities. Our study aims at offering more precision on this key issue by examining the impact that brokers may have on crime‐commission processes. To do so, we analyze two stolen‐vehicle exportation (or ringing) operations within a framework that merges crime‐script analysis and social‐network analysis. We assess how diverse degrees of brokerage are distributed across the ringing operations and how the removal of key brokers would have had a disruptive impact by reducing the scope of alternatives for crime‐script permutation and flexibility.

Hypertension, the most frequently diagnosed clinical condition world-wide, predisposes individuals to morbidity and mortality, yet its underlying pathological etiologies are poorly understood. So far, a large number of quantitative trait loci (QTLs) have been identified in both humans and animal models, but how they function together in determining overall blood pressure (BP) in physiological settings is unknown. Here, we systematically and comprehensively performed pair-wise comparisons of individual QTLs to create a global picture of their functionality in an inbred rat model. Rather than each of numerous QTLs contributing to infinitesimal BP increments, a modularized pattern arises: two epistatic 'blocks' constitute basic functional 'units' for nearly all QTLs, designated as epistatic module 1 (EM1) and EM2. This modularization dictates the magnitude and scope of BP effects. Any EM1 member can contribute to BP additively to that of EM2, but not to those of the same module. Members of each EM display epistatic hierarchy, which seems to reflect a related functional pathway. Rat homologues of 11 human BP QTLs belong to either EM1 or EM2. Unique insights emerge into the novel genetic mechanism and hierarchy determining BP in the Dahl salt-sensitive SS/Jr (DSS) rat model that implicate a portion of human QTLs. Elucidating the pathways underlying EM1 and EM2 may reveal the genetic regulation of BP.

Essential hypertension is a complex trait influenced by multiple genes known as quantitative trait loci (QTLs) for blood pressure (BP). It is not clear, however, what roles these QTLs play in maintaining normotension. Insights gained toward the maintenance of normotension will shed light on how hypertension can result from a deficiency or malfunctioning of this maintenance. Currently, congenic strains were systematically constructed using Dahl salt-sensitive (DSS) and Lewis (LEW) rats not only to define QTLs (i.e. in DSS background), but also to ascertain effects of the same QTLs in preserving normotension (i.e. in LEW background), a first such study. Results showed that although LEW alleles for two QTLs on Chromosome (Chr) 18 lowered BP on the DSS background, their BP-increasing DSS alleles failed to influence BP in the LEW background. To further prove that the LEW background is resistant and the DSS background is susceptible to the effects of QTLs, BP-increasing alleles of a QTL on Chr 2 were introgressed into the DSS background, and its BP-decreasing alleles into the LEW background. Indeed, there was no BP-decreasing effect on the LEW background while demonstrating a BP-increasing effect on the DSS background. Thus, a genetic regulation of BP QTLs in the LEW genome inhibits BP changes by nullifying the effects of BP-altering QTLs. In comparison, the DSS genome must have lost the buffering capacity for stabilizing BP. The current work presents good evidence that a lack of regulation for functions of BP QTLs is a potential underlying cause of hypertension.