Fructose metabolism as a common evolutionary pathway of survival associated with climate change, food shortage and droughts.

Mass extinctions occur frequently in natural history. While studies of animals that became extinct can be informative, it is the survivors that provide clues for mechanisms of adaptation when conditions are adverse. Here, we describe a survival pathway used by many species as a means for providing adequate fuel and water, while also providing protection from a decrease in oxygen availability. Fructose, whether supplied in the diet (primarily fruits and honey), or endogenously (via activation of the polyol pathway), preferentially shifts the organism towards the storing of fuel (fat, glycogen) that can be used to provide energy and water at a later date. Fructose causes sodium retention and raises blood pressure and likely helped survival in the setting of dehydration or salt deprivation. By shifting energy production from the mitochondria to glycolysis, fructose reduced oxygen demands to aid survival in situations where oxygen availability is low. The actions of fructose are driven in part by vasopressin and the generation of uric acid. Twice in history, mutations occurred during periods of mass extinction that enhanced the activity of fructose to generate fat, with the first being a mutation in vitamin C metabolism during the Cretaceous-Paleogene extinction (65 million years ago) and the second being a mutation in uricase that occurred during the Middle Miocene disruption (12-14 million years ago). Today, the excessive intake of fructose due to the availability of refined sugar and high-fructose corn syrup is driving 'burden of life style' diseases, including obesity, diabetes and high blood pressure.

Geochemical and sulfate isotopic evolution of flowback and produced waters reveals water-rock interactions following hydraulic fracturing of a tight hydrocarbon reservoir.

Although multistage hydraulic fracturing is routinely performed for the extraction of hydrocarbon resources from low permeability reservoirs, the downhole geochemical processes linked to the interaction of fracturing fluids with formation brine and reservoir mineralogy remain poorly understood. We present a geochemical dataset of flowback and produced water samples from a hydraulically fractured reservoir in the Montney Formation, Canada, analyzed for major and trace elements and stable isotopes. The dataset consists in 25 samples of flowback and produced waters from a single well, as well as produced water samples from 16 other different producing wells collected in the same field. Additionally, persulfate breaker samples as well as anhydrite and pyrite from cores were also analyzed. The objectives of this study were to understand the geochemical interactions between formation and fracturing fluids and their consequences in the context of tight gas exploitation. The analysis of this dataset allowed for a comprehensive understanding of the coupled downhole geochemical processes, linked in particular to the action of the oxidative breaker. Flowback fluid chemistries were determined to be the result of mixing of formation brine with the hydraulic fracturing fluids as well as coupled geochemical reactions with the reservoir rock such as dissolution of anhydrite and dolomite; pyrite and organic matter oxidation; and calcite, barite, celestite, iron oxides and possibly calcium sulfate scaling. In particular, excess sulfate in the collected samples was found to be mainly derived from anhydrite dissolution, and not from persulfate breaker or pyrite oxidation. The release of heavy metals from the oxidation activity of the breaker was detectable but concentrations of heavy metals in produced fluids remained below the World Health Organization guidelines for drinking water and are therefore of no concern. This is due in part to the co-precipitation of heavy metals with iron oxides and possibly sulfate minerals.

Evolution, language and analogy in functional genomics.

Almost a century ago, Wittgenstein pointed out that theory in science is intricately connected to language. This connection is not a frequent topic in the genomics literature. But a case can be made that functional genomics is today hindered by the paradoxes that Wittgenstein identified. If this is true, until these paradoxes are recognized and addressed, functional genomics will continue to be limited in its ability to extrapolate information from genomic sequences.

Function-structure analysis of proteins using covarion-based evolutionary approaches: Elongation factors.

The divergent evolution of protein sequences from genomic databases can be analyzed by the use of different mathematical models. The most common treat all sites in a protein sequence as equally variable. More sophisticated models acknowledge the fact that purifying selection generally tolerates variable amounts of amino acid replacement at different positions in a protein sequence. In their "stationary" versions, such models assume that the replacement rate at individual positions remains constant throughout evolutionary history. "Nonstationary" covarion versions, however, allow the replacement rate at a position to vary in different branches of the evolutionary tree. Recently, statistical methods have been developed that highlight this type of variation in replacement rates. Here, we show how positions that have variable rates of divergence in different regions of a tree ("covarion behavior"), coupled with analyses of experimental three-dimensional structures, can provide experimentally testable hypotheses that relate individual amino acid residues to specific functional differences in those branches. We illustrate this in the elongation factor family of proteins as a paradigm for applications of this type of analysis in functional genomics generally.

SIRE-1, a copia/Ty1-like retroelement from soybean, encodes a retroviral envelope-like protein.

The soybean genome hosts a family of several hundred, relatively homogeneous copies of a large, copia/Ty1-like retroelement designated SIRE-1. A copy of this element has been recovered from a Glycine max genomic library. DNA sequence analysis of two SIRE-1 subclones revealed that SIRE-1 contains a long, uninterrupted, ORF between the 3' end of the pol ORF and the 3' long terminal repeat (LTR), a region that harbors the env gene in retroviral genomes. Conceptual translation of this second ORF produces a 70-kDa protein. Computer analyses of the amino acid sequence predicted patterns of transmembrane domains, alpha-helices, and coiled coils strikingly similar to those found in mammalian retroviral envelope proteins. In addition, a 65-residue, proline-rich domain is characterized by a strong amino acid compositional bias virtually identical to that of the 60-amino acid, proline-rich neutralization domain of the feline leukemia virus surface protein. The assignment of SIRE-1 to the copia/Ty1 family was confirmed by comparison of the conceptual translation of its reverse transcriptase-like domain with those of other retroelements. This finding suggests the presence of a proretrovirus in a plant genome and is the strongest evidence to date for the existence of a retrovirus-like genome closely related to copia/Ty1 retrotransposons.

Administrative simplification: healthcare reform and TQM.

Administrative simplification is a key element of the Clinton healthcare reform proposal. Healthcare leaders, however, "cannot lay the entire burden of administrative simplification on outsiders," says Ellen J. Gaucher, Senior Associate Director of The University of Michigan Hospitals. There are numerous opportunities to use the principles of total quality management to improve operational and financial performance in healthcare organizations.

A vision for world-class quality in health care.

When we talk about world-class health care, we are finding that we are in a position where the purchasers of our services find there is little or no value for the health-care dollars they are spending. Even the father of American Quality, W. Edwards Deming, has listed the high cost of health care as one of the seven deadly diseases, so we know that we are in trouble. According to a 1989 study, the public tells us that 32% of the time the value of health care they receive is good to excellent, and 65% of the time it is fair to poor. When we look at what our physicians say, 76% of them believe that we get good value for health-care dollars as opposed to 23% who think it is fair to poor. As I have been thinking about what world-class quality would mean, one of the things that comes to mind is the fact that health care is now consuming 15% of the gross national product. We are approaching an expenditure level of one trillion dollars. If our results were good, we could feel comfortable resting on our laurels, because for those we serve in the American health-care system, we serve them very well. But our results are not good. We are 23rd in the world in infant mortality, and we are 16th in the world for life expectancy. The real tragedy in the American health-care system is that 37 million Americans are uninsured. Obviously this cannot continue.(ABSTRACT TRUNCATED AT 250 WORDS)

Applying critical pathways to neurosurgery patients at the University of Michigan Medical Center.

UNLABELLED: Project Overview: In April 1990, The University of Michigan Hospitals began a major, multidisciplinary project to standardize care processes in order to increase efficiency and reduce costs while maintaining the quality of clinical care. A team of nurses began the project by developing critical pathways for two neurosurgery procedures--lumbar laminectomy and transphenoidal pituitary tumor resection. The pathways were reviewed by physicians and other staff from other disciplines and were implemented in January of 1991. KEY FINDINGS: Data from the first 14 months show a decrease in patients' average lengths of stay in both the intensive care unit (ICU) and routine care unit. Costs and variance data are being analyzed and further improvements to the pathways are being made. Eleven critical paths are now being used for neurosurgery patients. In retrospect, participants learned that physicians should be involved at the earliest stages of critical pathway development and in the process of implementation.

Lessons learned in developing a total quality management process.

While the barriers to TQM implementation are many and the lessons learned can be very painful, we are convinced the results are well worth the effort. TQM implementation is a long term strategic approach and while results can be fairly quick, organizational cultural change and strategic redirection take time. Progress can be very slow. By reducing waste, rework, and variation we can both improve quality and reduce cost. The ultimate goal of TQM is to have organizational members using the quality tools in their daily work life. As an increasing number of health care organizations move through the four phases of implementation, sharing lessons learned can help us understand how to evaluate our quality processes and sustain the improvement process.

The leader's role in implementing total quality management.

Quality experts state that ineffective leadership can hinder and even destroy efforts to implement total quality management (TQM). However, they rarely discuss the specific actions leaders should take in implementing TQM and when leaders should take them. This article discusses a four-phase TQM implementation model that includes specifications for leadership actions at each step.

The practical zealot. Interview by Joe Flower.

In 1987, Ellen Gaucher took an unusual trip. As senior associate director of the University of Michigan's sprawling 11,000-employee Medical Center, she was invited to a conference about a movement that was rapidly growing in the word of business--total quality. The occasion was the organizational conference of the National Demonstration Project on Quality Improvement in Health Care, led by the Harvard Community Health Plan in Boston. Gaucher was skeptical at first. Total quality seemed a great way to make better cars, light bulbs, and aluminum siding, but would it work in a service industry? More to the point, would it work in an industry as complex, as critical, as pressured, as high-tech, as human, and as intellectual as healthcare? But by the second day, she says, "I was sold that this was what we had needed for a long time." She hurried back to Michigan like a missionary trekking into cannibal country. Today, not only is the University Medical Center deep in a total quality conversion experience, so is the University itself, through its president, James J. Duderstadt. He was exposed to the idea through Gaucher: In his ex-officio position as chairman of the Medical Center's board, he had experienced her vivid and enthusiastic educational efforts. Gaucher has related her intense experiences with TQ at conferences, in articles, in the 1990 book, Transforming Healthcare Organizations (winner of the Hamilton Award given by the American College of Healthcare Executives for the best book of the year) as well as the forthcoming Total Quality in Healthcare (both co-authored with Richard Coffey). (ABSTRACT TRUNCATED AT 250 WORDS)

Intrapreneurship: tapping employee creativity.

Seeking ways to produce new products, processes, and programs that would result in cost savings or increased revenue for nursing services and the institution, as well as attracting and retaining bright, creative nursing employees, the authors developed a pilot program to allow intrapreneurs to "run with" their ideas. The authors discuss the mechanics of their program development, implementation, and evaluation as well as examples of innovative projects under development by nursing employees.