Applying management science methods to health care diagnostics

The purpose is to encourage the growth of data analytics, total quality management and computer methods including artificial intelligence in the growth of procedures to diagnose and treat those inflicted with disease or indications of the spread of infectious diseases. With the rapid advances in machine intelligence, we have seen the development of the application of machine learning in business forecasting, analyzing treatment data and the results of analytic and diagnostic tests. This is important especially because of the world wide pandemic and the severe Covid-19 pandemic in the United States

Approximating Mexican highways with slime mould

Plasmodium of Physarum polycephalum is a single cell visible by unaided eye. During its foraging behavior the cell spans spatially distributed sources of nutrients with a protoplasmic network. Geometrical structure of the protoplasmic networks allows the plasmodium to optimize transport of nutrients between remote parts of its body. Assuming major Mexican cities are sources of nutrients how much structure of Physarum protoplasmic network correspond to structure of Mexican Federal highway network? To find an answer undertook a series of laboratory experiments with living Physarum polycephalum. We represent geographical locations of major cities by oat flakes, place a piece of plasmodium in Mexico city area, record the plasmodium's foraging behavior and extract topology of nutrient transport networks. Results of our experiments show that the protoplasmic network formed by Physarum is isomorphic, subject to limitations imposed, to a network of principle highways. Ideas and results of the paper may contribute towards future developments in bio-inspired road planning

Diabetes status and post-load plasma glucose concentration in relation to site-specific cancer mortality: findings from the original Whitehall study

ObjectiveWhile several studies have reported on the relation of diabetes status with pancreatic cancer risk, the predictive value of this disorder for other malignancies is unclear. Methods: The Whitehall study, a 25year follow-up for mortality experience of 18,006 men with data on post-challenge blood glucose and self-reported diabetes, allowed us to address these issues. Results: There were 2158 cancer deaths at follow-up. Of the 15 cancer outcomes, diabetes status was positively associated with mortality from carcinoma of the pancreas and liver, while the relationship with lung cancer was inverse, after controlling for a range of potential covariates and mediators which included obesity and socioeconomic position. After excluding deaths occurring in the first 10years of follow-up to examine the effect of reverse causality, the magnitude of the relationships for carcinoma of the pancreas and lung was little altered, while for liver cancer it was markedly attenuated. Conclusions: In the present study, diabetes status was related to pancreatic, liver, and lung cancer risk. Cohorts with serially collected data on blood glucose and covariates are required to further examine this area

Mesofluidic Devices for DNA-Programmed Combinatorial Chemistry

Hybrid combinatorial chemistry strategies that use DNA as an information-carrying medium are proving to be powerful tools for molecular discovery. In order to extend these efforts, we present a highly parallel format for DNA-programmed chemical library synthesis. The new format uses a standard microwell plate footprint and is compatible with commercially available automation technology. It can accommodate a wide variety of combinatorial synthetic schemes with up to 384 different building blocks per chemical step. We demonstrate that fluidic routing of DNA populations in the highly parallel format occurs with excellent specificity, and that chemistry on DNA arrayed into 384 well plates proceeds robustly, two requirements for the high-fidelity translation and efficient in vitro evolution of small molecules

Highly Parallel Translation of DNA Sequences into Small Molecules

A large body of in vitro evolution work establishes the utility of biopolymer libraries comprising 1010 to 1015 distinct molecules for the discovery of nanomolar-affinity ligands to proteins.[1], [2], [3], [4], [5] Small-molecule libraries of comparable complexity will likely provide nanomolar-affinity small-molecule ligands.[6], [7] Unlike biopolymers, small molecules can offer the advantages of cell permeability, low immunogenicity, metabolic stability, rapid diffusion and inexpensive mass production. It is thought that such desirable in vivo behavior is correlated with the physical properties of small molecules, specifically a limited number of hydrogen bond donors and acceptors, a defined range of hydrophobicity, and most importantly, molecular weights less than 500 Daltons.[8] Creating a collection of 1010 to 1015 small molecules that meet these criteria requires the use of hundreds to thousands of diversity elements per step in a combinatorial synthesis of three to five steps. With this goal in mind, we have reported a set of mesofluidic devices that enable DNA-programmed combinatorial chemistry in a highly parallel 384-well plate format. Here, we demonstrate that these devices can translate DNA genes encoding 384 diversity elements per coding position into corresponding small-molecule gene products. This robust and efficient procedure yields small molecule-DNA conjugates suitable for in vitro evolution experiments

Blood pressure and site-specific cancer mortality: evidence from the original Whitehall study

Studies relating blood pressure to cancer risk have some shortcomings and have revealed inconsistent findings. In 17498 middle-aged London-based government employees we related systolic and diastolic blood pressure recorded at baseline examination (1967-1970) to the risk of cancer mortality risk at 13 anatomical sites 25 years later. Following adjustment for potential confounding and mediating factors, inverse associations between blood pressure and mortality due to leukaemia and cancer of the pancreas (diastolic only) were seen. Blood pressure was also positively related to cancer of the liver and rectum (diastolic only). The statistically significant blood pressure-cancer associations seen in this large-scale prospective investigation offering high power were scarce and of sufficiently small magnitude as to be attributable to chance or confounding

Real-Time Imaging and Quantification of Amyloid-β Peptide Aggregates by Novel Quantum-Dot Nanoprobes

Background: Protein aggregation plays a major role in the pathogenesis of neurodegenerative disorders, such as Alzheimer’s disease. However, direct real-time imaging of protein aggregation, including oligomerization and fibrillization, has never been achieved. Here we demonstrate the preparation of fluorescent semiconductor nanocrystal (quantum dot; QD)-labeled amyloid-b peptide (QDAb) and its advanced applications. Methodology/Principal Findings: The QDAb construct retained Ab oligomer-forming ability, and the sizes of these oligomers could be estimated from the relative fluorescence intensities of the imaged spots. Both QDAb coaggregation with intact Ab42 and insertion into fibrils were detected by fluorescence microscopy. The coaggregation process was observed by real-time 3D imaging using slit-scanning confocal microscopy, which showed a typical sigmoid curve with 1.5 h in the lag-time and 12 h until saturation. Inhibition of coaggregation using an anti-Ab antibody can be observed as 3D images on a microscopic scale. Microglia ingested monomeric QDAb more significantly than oligomeric QDAb, and the ingested QDAb was mainly accumulated in the lysosome. Conclusions/Significance: These data demonstrate that QDAb is a novel nanoprobe for studying Ab oligomerization an

Propagation of RML Prions in Mice Expressing PrP Devoid of GPI Anchor Leads to Formation of a Novel, Stable Prion Strain

PrPC, a host protein which in prion-infected animals is converted to PrPSc, is linked to the cell membrane by a GPI anchor. Mice expressing PrPC without GPI anchor (tgGPI- mice), are susceptible to prion infection but accumulate anchorless PrPSc extra-, rather than intracellularly. We investigated whether tgGPI− mice could faithfully propagate prion strains despite the deviant structure and location of anchorless PrPSc. We found that RML and ME7, but not 22L prions propagated in tgGPI− brain developed novel cell tropisms, as determined by the Cell Panel Assay (CPA). Surprisingly, the levels of proteinase K-resistant PrPSc (PrPres) in RML- or ME7-infected tgGPI− brain were 25–50 times higher than in wild-type brain. When returned to wild-type brain, ME7 prions recovered their original properties, however RML prions had given rise to a novel prion strain, designated SFL, which remained unchanged even after three passages in wild-type mice. Because both RML PrPSc and SFL PrPSc are stably propagated in wild-type mice we propose that the two conformations are separated by a high activation energy barrier which is abrogated in tgGPI− mice