Predicting Unethical Physician Behavior At Scale: A Distributed Computing Framework

As the amount of publicly shared data increases, developing a robust pipeline to stream, store and process data is critical, as the casual user often lacks the technology, hardware and/or skills needed to work with such voluminous data. In this research, the authors employ Amazon EC2 and EMR, MongoDB, and Spark MLlib to explore 28.5 gigabytes of CMS Open Payments data in an attempt to identify physicians who may have a high propensity to act unethically, owing to significant transfers of wealth from medical companies. A Random Forest Classifier is employed to predict the top decile of physicians who have the highest risk of unethical behavior in the following year, resulting in an F-Score of 91%. The data is also analyzed by an anomaly detection algorithm that correctly identified a highprofile case of a physician leaving his prestigious position, as he failed to disclose anomalously-large transfers of wealth from medical companies

The transition state and cognate concepts

This review aims firstly to clarify the meanings of key terms and concepts associated with the idea of the transition state, as developed by theoreticians and applied by experimentalist, and secondly to provide an update to the meaning and significance of the transition state in an era when computational simulation, in which complexity is being increasingly incorporated, is commonly employed as a means by which to bridge the realms of theory and experiment. The relationship between the transition state and the potential-energy surface for an elementary reaction is explored, with discussion of the following terms: saddle point, minimum-energy reaction path, reaction coordinate, activated complex, transition structure, intrinsic reaction coordinate, transition vector, transition-state structure, and transition state. Structural information determined by the application of computational methods to simple systems or inferred from empirical studies is critically discussed in the light of various complications. Consequently, the relationship between the transition state and the free-energy surface for an elementary reaction within a condensed system is explored, with discussion of collective variables, minimum free-energy paths, variational transition-state theory, transmission coefficients, more about reaction coordinates, and equicommittors. It is noted that any visual picture of a transition state is necessarily an average view, and an updated definition of the transition state is proposed.</p

Vascular endothelial growth factors and vascular permeability

Vascular endothelial growth factors (VEGFs) are key regulators of permeability. The principal evidence behind how they increase vascular permeability in vivo and in vitro and the consequences of that increase are addressed here. Detailed analysis of the published literature has shown that in vivo and in vitro VEGF-mediated permeability differs in its time course, but has common involvement of many specific signalling pathways, in particular VEGF receptor-2 activation, calcium influx through transient receptor potential channels, activation of phospholipase C gamma and downstream activation of nitric oxide synthase. Pathways downstream of endothelial nitric oxide synthase appear to involve the guanylyl cyclase-mediated activation of the Rho–Rac pathway and subsequent involvement of junctional signalling proteins such as vascular endothelial cadherin and the tight junctional proteins zona occludens and occludin linked to the actin cytoskeleton. The signalling appears to be co-ordinated through spatial organization of the cascade into a signalplex, and arguments for why this may be important are considered. Many proteins have been identified to be involved in the regulation of vascular permeability by VEGF, but still the mechanisms through which these are thought to interact to control permeability are dependent on the experimental system, and a synthesis of existing data reveals that in intact vessels the co-ordination of the pathways is still not understood

The Youngest Victims: Children and Youth Affected by War

In 1989, the United Nation Convention on the Rights of the Child declared, “[state parties] shall take all feasible measures to ensure protection and care of children who are affected by an armed conflict.” In addition to attempting to secure the welfare of children in armed conflict, the Convention went on to ban the recruitment and deployment of children during armed conflict. Despite the vast majority of sovereign nations signing and ratifying this agreement, this treaty, unfortunately, has not prevented children and youth from witnessing, becoming victims of, or participating in political, ethnic, religious, and cultural violence across the past three decades. This chapter offers an “ecological perspective” on the psychosocial consequences of exposure to the trauma of war-related violence and social disruption

Development and validation of a NANOGold™ immunoassay for the detection of vascular endothelial growth factor (VEGF) in human serum using inductively coupled plasma mass spectrometry

This work aimed to develop and validate a NANOGold based assay, quantified using inductively coupled plasma mass spectrometry (ICP-MS), for the detection of human vascular endothelial growth factor (hVEGF) in serum. The initial assay range based on calibration standards was 62.5-2000 pg/mL with a detection limit of approximately 30 pg/mL. After validation using spiked validation controls, a quantification range between 175 and 1928 pg/mL was obtained. The inter-assay precision was between 2.3 and 18.9% with accuracy between -8.8 and -3.1%. Additional performance parameters, including dilutional linearity, matrix specificity and time-factored drift, were within +/-20%, as defined by the validation acceptance criteria for the validation of macromolecule immunoassays used within our clinical environment. Serum samples from healthy donors were analysed to determine the endogenous levels of VEGF present; these ranged from 164 to 580 pg/mL with a mean of 273 pg/mL. The intra- and inter-assay precision obtained from the healthy donor samples were 1.3-10.7% and 4.2-17.5%, respectively. This demonstration of a validated immunoassay opens further possibilities, utilising the simultaneous detection capabilities of ICP-MS for the detection of multiple analytes in a single validated immunoassay, for routine use within a clinical environment