Traditional indices such as dp/dt max remain widely used in assessing ventricular contractility, yet their load-dependence limits clinical precision, particularly during dynamic hemodynamic shifts. This letter to the Editor advocates for a more physiologically grounded approach using dual pressure catheters equipped with two high-fidelity sensors, one in the left ventricle (LV) and one in the aorta, to capture real-time pressure gradients and valve events with high temporal resolution. When combined with transient inferior vena cava occlusion (IVCO), this setup enables accurate identification of the true end-systolic (ES) point, typically marked by dp/dt min or the dicrotic notch on the aortic pressure waveform. This method allows for the construction of more physiologically valid end-systolic pressure-volume relationships (ESPVR). It introduces the novel peak pressure end-systolic pressure-volume relationship (PPESPVR) model, which links peak LV pressure to the ES point within a single cardiac cycle. The resulting volume intercept (Vint) and end-systolic fraction (ESF) offer new insights into myocardial performance under varying preload and afterload conditions, without requiring extensive hemodynamic manipulation. This dual-sensor approach not only enhances diagnostic accuracy but also opens the door to real-time, patient-specific contractility assessment in both research and clinical settings.
Cellular communication network factor 2 (CCN2, formerly known as ‘connective tissue growth factor’ or ‘CTGF’) was the subject of anti-fibrotic drug development programs, largely in FibroGen, starting in the mid-1990s. This led to the development of FG-3019 (pamrevlumab) as a lead drug that was used initially to target diabetic nephropathy and subsequently pancreatic cancer, pulmonary fibrosis and Duchenne’s muscular dystrophy. All these programs failed clinically; diabetes in early development, and the others at Phase III. Could these failures have been anticipated? Is ‘CTGF’ dead as an anti-fibrotic target? What might have been done differently or could be done differently in the future? This personal commentary—based on years of experience first at FibroGen working on the ‘CTGF’ program and then as an independent academic researcher---aims to address at least some of these issues.
This commentary introduces a conceptual framework that reinterprets biodiversity assessment as a continuum, spanning from Dark diversity, representing the unobserved or uncolonized potential of species ecologically suited to a system, to Bright diversity, conceived as an aspirational, fully integrated upper bound of biodiversity knowledge. Bright diversity encompasses not only observed components and their intricate interactions, but also a profound understanding of the reasons for species' presence or absence, including the inferred insights from Dark diversity across taxonomic, functional, phylogenetic, and genetic facets. Situated in between is Grey diversity, which characterizes the predominant state of partial knowledge and inherent uncertainty in real-world ecological assessments as an epistemic gradient. By delineating this epistemological gradient, the framework offers a heuristic tool for ecologists and conservationists to critically evaluate the clarity, completeness, and uncertainty embedded in biodiversity data, and an operational basis for “epistemic cartography”, i.e., the spatial mapping of knowledge sufficiency and uncertainty. It facilitates the identification of knowledge gaps, guides research priorities, and informs conservation actions, especially under conditions of incomplete information, through a compact workflow and transparent indicators. This conceptual spectrum serves as both an epistemological reflection and a practical guide for advancing biodiversity science, while outlining a forward-looking agenda that leverages multi-faceted “bands of biodiversity knowledge” to support robust biodiversity planning.
The transition to adulthood is often marked by identity struggles, commonly conceptualised as a quarter-life crisis (QLC), leading to poorer psychological well-being. This study examined the mediating role of perceived stress in the relationship between QLC and psychological well-being, and whether this indirect effect is moderated by gender. A cross-sectional survey of 301 Nigerian university students (158 males, 141 females) completed the self-report Developmental Crisis Questionnaire, Psychological well-being Scale and Perceived Stress Scale. Data was analysed using Hayes’ PROCESS macro (Models 4 and 7). Results showed that QLC negatively predicted Psychological wellbeing (β = –0.34, p < 0.01) and positively predicted perceived stress (β = 0.21, p < 0.01). While there was no significant direct effect of QLC on PWB, there was a significant indirect effect through perceived stress (β = −0.07, 95% CI [−0.308, −0.051]), supporting evidence for mediation. Gender moderated the QLC–stress path (β = 0.10, p = 0.03). QLC predicted higher stress in females (β = 0.16, p < 0.001) but not in males (β = 0.06, p = 0.11). These findings highlight the gendered dynamics of QLC and underscore the importance of stress management, particularly among female students, in promoting psychological well-being during early adulthood.
