Comparison of maternal serum CA-125 and ultrasonography findings as a prognostic marker in threatened abortion

Background: WHO defines abortion as pregnancy termination before 20 week gestation or with fetus born weighing <500 gms. Early pregnancy markers in patients with threatened abortion including biochemical marker like raised maternal serum CA-125 (cancer antigen-125, carcinoma antigen 125 or carbohydrate antigen 125) and USG parameters that is, fetal crown-rump length (CRL), the presence/absence of sub-chorionic hematoma and fetal heart rate (FHR) are good predictors of outcome.Methods: The study was conducted in the department of obstetrics and gynaecology, S.P. medical college and associated group of hospital, Bikaner, Rajasthan. This was a hospital based prospective comparative study. The study group comprise of pregnant females attending obstetrics and gynaecology OPD. A total of 200 pregnant women were examined in this study. We divided these patients into 2 groups, group A and group B. Group A consists of 100 pregnant females with threatened abortion and group B with 100 normal pregnant female.Results: Maternal serum CA-125 at cut off level 61.64 U/ml is 84.21% sensitive, 96.77% specific in predicting abortion with 94.12% positive predictive value and 90.91% negative predictive value while FHR at 115 bpm is 76.32% sensitive, 90.32% specific in predicting abortion with 82.86% PPV and 86.15% negative predictive value.Conclusions: Single raised value of maternal serum CA-125 has best predictive value followed by USG parameters (FHR, sub-chorionic hematoma and CRL ) in threatened abortion which results in loss of pregnancy

On Socially Optimal Traffic Flow in the Presence of Random Users

Traffic assignment is an integral part of urban city planning. Roads and freeways are constructed to cater to the expected demands of the commuters between different origin-destination pairs with the overall objective of minimising the travel cost. As compared to static traffic assignment problems where the traffic network is fixed over time, a dynamic traffic network is more realistic where the network's cost parameters change over time due to the presence of random congestion. In this paper, we consider a stochastic version of the traffic assignment problem where the central planner is interested in finding an optimal social flow in the presence of random users. These users are random and cannot be controlled by any central directives. We propose a Frank-Wolfe algorithm based stochastic algorithm to determine the socially optimal flow for the stochastic setting in an online manner. Further, simulation results corroborate the efficacy of the proposed algorithm

Myosin Sequestration Regulates Sarcomere Function, Cardiomyocyte Energetics, and Metabolism, Informing the Pathogenesis of Hypertrophic Cardiomyopathy

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is caused by pathogenic variants in sarcomere protein genes that evoke hypercontractility, poor relaxation, and increased energy consumption by the heart and increased patient risks for arrhythmias and heart failure. Recent studies show that pathogenic missense variants in myosin, the molecular motor of the sarcomere, are clustered in residues that participate in dynamic conformational states of sarcomere proteins. We hypothesized that these conformations are essential to adapt contractile output for energy conservation and that pathophysiology of HCM results from destabilization of these conformations. METHODS: We assayed myosin ATP binding to define the proportion of myosins in the super relaxed state (SRX) conformation or the disordered relaxed state (DRX) conformation in healthy rodent and human hearts, at baseline and in response to reduced hemodynamic demands of hibernation or pathogenic HCM variants. To determine the relationships between myosin conformations, sarcomere function, and cell biology, we assessed contractility, relaxation, and cardiomyocyte morphology and metabolism, with and without an allosteric modulator of myosin ATPase activity. We then tested whether the positions of myosin variants of unknown clinical significance that were identified in patients with HCM, predicted functional consequences and associations with heart failure and arrhythmias. RESULTS: Myosins undergo physiological shifts between the SRX conformation that maximizes energy conservation and the DRX conformation that enables cross-bridge formation with greater ATP consumption. Systemic hemodynamic requirements, pharmacological modulators of myosin, and pathogenic myosin missense mutations influenced the proportions of these conformations. Hibernation increased the proportion of myosins in the SRX conformation, whereas pathogenic variants destabilized these and increased the proportion of myosins in the DRX conformation, which enhanced cardiomyocyte contractility, but impaired relaxation and evoked hypertrophic remodeling with increased energetic stress. Using structural locations to stratify variants of unknown clinical significance, we showed that the variants that destabilized myosin conformations were associated with higher rates of heart failure and arrhythmias in patients with HCM. CONCLUSIONS: Myosin conformations establish work-energy equipoise that is essential for life-long cellular homeostasis and heart function. Destabilization of myosin energy-conserving states promotes contractile abnormalities, morphological and metabolic remodeling, and adverse clinical outcomes in patients with HCM. Therapeutic restabilization corrects cellular contractile and metabolic phenotypes and may limit these adverse clinical outcomes in patients with HCM

The nature of economic development and the economic development of nature

Contemporary models of growth and development are founded on a category error: they ignore nature as a form of productive capital. Using as backdrop two recent books on the Indian economy that are representative of the prevailing orthodoxy, I review and in part extend an emerging literature that integrates development and environmental thinking. Contributors to the literature have reworked the economics of the household, communities, and other non-market institutions, reframed national accounting, reconstructed the theory of macro-economic development and public and trade policy, and revised the theory of collective action. In this paper I focus on a small part of the literature: economic evaluation. I develop the notion of sustainable development and construct a unified language for sustainability and policy analyses. I show that by economic growth we should mean growth in wealth - which is the social worth of an economy's entire set of capital assets - not growth in GDP nor the many ad hoc indicators of human development that have been proposed in recent years. The concept of wealth invites us to extend the notion of capital assets and the idea of investment well beyond conventional usage. I also show that by sustainable development we should mean development in which wealth (per head) adjusted for its distribution does not decline. This has radical implications for the way national accounts are prepared and interpreted. I then provide an account of a recent publication that has put the theory to work by studying the composition of wealth accumulation in contemporary India. Although much attention was given by the study's authors to the measurement of natural capital, due to a paucity of data the value of natural capital is acknowledged by them to be under-estimated, in all probability by a large margin. The study reveals that the entire architecture of contemporary development thinking is stacked against nature. These are still early days in the measurement of the wealth of nations, but both theory and the few empirical studies we now have at our disposal should substantially alter the way we interpret the progress and regress of nations

Intercellular and extracellular adhesion signals control cardiac myocyte structural and functional remodeling: mechanosensing mediated by cadherin and hyaluronan receptors

Heart failure is a major clinical and public health problem worldwide. During development and in many forms of progressive heart failure, a mechanical substrate may be the causative mediator whereby changes in myocyte shape are largely responsible for cardiac remodeling. The long-term preservation or enhancement of cardiac function depends on structural adaptation. The extracellular matrix (ECM) of the heart provides biochemical and mechanical cues, involved in morphogenesis and pathogenesis. What remains unclear is how these mechanical cues influence cardiomyocyte maturation during both development and disease progression. The central objective of this thesis is to examine the effect of cell-cell (N-cadherin) mediated mechanical forces and the combined effect of cell-matrix biochemical and mechanical cues directing myocyte structure and function.Cardiac myocytes were cultured on either N-cadherin or matrix ligands conjugated to inert polyacrylamide gels of defined elastic modulus. Myocyte shape, cytoskeletal architecture, mechanical properties and force generating profiles were analyzed. Our results indicate a remarkable structural and functional adaptation to perceived forces that are mediated by N-cadherin and matrix adhesions. Engineering cardiac myocytes using micropatterned geometries were used to map the distribution of mechnosensory proteins associated with the N-cadherin complex, demonstrating that -catenin is a key adaptor protein.Relating the results of in vitro studies in which cells are cultured on inert synthetic materials to the function of cells within biologically relevant gels is not obvious. Hyaluronan, a glycosaminoglycan expressed during cardiac development and disease, was used to engineer a physiologically relevant cardiac biosynthetic gel. Remarkably, myocytes cultured on much lower stiffnesses than normal cardiac tissue exhibited a developmental hypertrophic response with well assembled sarcomeric architecture, compared to inert gels inducing atrophy. Furthermore, hyaluronan receptors (CD44 and RHAMM) can modulate integrin-mediated signaling, effectively reprogramming the myocyte structure-function response. This mechanism and gain of function response was previously unknown in field of cardiac biology.The results from this thesis form the basis and rationale for engineering a new class of injectable hydrogels that can be used as part of a surgical and therapeutic strategy to reverse the remodeling process of the diseased heart.Ph.D., Biomedical Engineering -- Drexel University, 201