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David G. Greenhalgh

Other affiliations: University of Vermont, Mallinckrodt, Max Planck Society  ...read more
Bio: David G. Greenhalgh is an academic researcher from Shriners Hospitals for Children. The author has contributed to research in topics: Population & Burn injury. The author has an hindex of 62, co-authored 447 publications receiving 16963 citations. Previous affiliations of David G. Greenhalgh include University of Vermont & Mallinckrodt.


Papers
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TL;DR: The state of knowledge regarding wound healing is described, both what is known and what is not known, and to recap the priorities set by the breakout sessions of the Burn State of the Science: Research meeting.
Abstract: Overall, burns are smaller than 20 years ago, but even small burns can leave patients with debilitating scars. The management of the burn wound and resultant scarring requires the integration of multiple disciplines. Despite our best efforts, the evaluation and treatment of burn wounds and burn scars has not been completely elucidated. The purpose of this work is to describe the state of knowledge regarding wound healing, both what is known and what is not known, and to recap the priorities set by the breakout sessions of the Burn State of the Science: Research meeting. Wound challenges in 2007 include wound coverage for patients with extensive full-thickness burns, management of donor sites and partial-thickness burns, and reduction of longterm morbidity from burn scars.

1,601 citations

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TL;DR: In normal mice, elevated VEGF mRNA levels during the period when granulation tissue formation occurs are found, suggesting that a defect in V EGF regulation might be associated with wound healing disorders.

772 citations

Journal Article
TL;DR: The effectiveness of rPDGF-BB and rbFGF suggest that recombinant growth factors may be useful in the treatment of patients with deficient wound repair, and all parameters of healing but not to a greater extent than either growth factor alone.
Abstract: To examine the effects of recombinant growth factors in vivo, impaired wound healing was studied in genetically diabetic C57BL/KsJ-db/db mice Large full-thickness skin wounds made on the backs of these mice exhibited significant delays in the entry of inflammatory cells into the wound, the formation of granulation tissue, and in wound closure when compared to their nondiabetic littermates Recombinant human platelet-derived growth factor (rPDGF-BB, 1 or 10 micrograms), recombinant human basic fibroblast growth factor (rbFGF, 1 micrograms), or combinations of both were applied topically to the wounds for 5 to 14 days after wounding Diabetic mouse wounds treated with rPDGF-BB or rbFGF had many more fibroblasts and capillaries in the wound bed at 10 and 21 days than did wounds treated with the vehicle alone The animals treated with growth factors also had significantly greater wound closure at 21 days than those treated with the vehicle Combinations of rPDGF-BB and rbFGF improved all parameters of healing but not to a greater extent than either growth factor alone The effectiveness of rPDGF-BB and rbFGF suggest that recombinant growth factors may be useful in the treatment of patients with deficient wound repair

717 citations

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TL;DR: It is proved that this classical susceptible-infected-susceptible epidemic model is formulated as a stochastic differential equation (SDE) for the number of infectious individuals and that this SDE has a unique global positive solution.
Abstract: In this paper we extend the classical susceptible-infected-susceptible epidemic model from a deterministic framework to a stochastic one and formulate it as a stochastic differential equation (SDE) for the number of infectious individuals $I(t)$. We then prove that this SDE has a unique global positive solution $I(t)$ and establish conditions for extinction and persistence of $I(t)$. We discuss perturbation by stochastic noise. In the case of persistence we show the existence of a stationary distribution and derive expressions for its mean and variance. The results are illustrated by computer simulations, including two examples based on real-life diseases.

577 citations

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TL;DR: The goal of the consensus conference was to develop and publish standardized definitions for sepsis and infection-related diagnoses in the burn population, which will improve the capability of performing more meaningful multicenter trials among burn centers.
Abstract: Because of their extensive wounds, burn patients are chronically exposed to inflammatory mediators. Thus, burn patients, by definition, already have "systemic inflammatory response syndrome." Current definitions for sepsis and infection have many criteria (fever, tachycardia, tachypnea, leukocytosis) that are routinely found in patients with extensive burns, making these current definitions less applicable to the burn population. Experts in burn care and research, all members of the American Burn Association, were asked to review the literature and prepare a potential definition on one topic related to sepsis or infection in burn patients. On January 20, 2007, the participants met in Tucson, Arizona to develop consensus for these definitions. After review of the definitions, a summary of the proceedings was prepared. The goal of the consensus conference was to develop and publish standardized definitions for sepsis and infection-related diagnoses in the burn population. Standardized definitions will improve the capability of performing more meaningful multicenter trials among burn centers.

524 citations


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TL;DR: The goal of this review is to provide a general overview of current knowledge on the process of apoptosis including morphology, biochemistry, the role of apoptoses in health and disease, detection methods, as well as a discussion of potential alternative forms of apoptotic proteins.
Abstract: The process of programmed cell death, or apoptosis, is generally characterized by distinct morphological characteristics and energy-dependent biochemical mechanisms. Apoptosis is considered a vital component of various processes including normal cell turnover, proper development and functioning of the immune system, hormone-dependent atrophy, embryonic development and chemical-induced cell death. Inappropriate apoptosis (either too little or too much) is a factor in many human conditions including neurodegenerative diseases, ischemic damage, autoimmune disorders and many types of cancer. The ability to modulate the life or death of a cell is recognized for its immense therapeutic potential. Therefore, research continues to focus on the elucidation and analysis of the cell cycle machinery and signaling pathways that control cell cycle arrest and apoptosis. To that end, the field of apoptosis research has been moving forward at an alarmingly rapid rate. Although many of the key apoptotic proteins have been identified, the molecular mechanisms of action or inaction of these proteins remain to be elucidated. The goal of this review is to provide a general overview of current knowledge on the process of apoptosis including morphology, biochemistry, the role of apoptosis in health and disease, detection methods, as well as a discussion of potential alternative forms of apoptosis.

10,744 citations

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TL;DR: A precise definition of the basic reproduction number, R0, is presented for a general compartmental disease transmission model based on a system of ordinary differential equations and it is shown that, if R0<1, then the disease free equilibrium is locally asymptotically stable; whereas if R 0>1,Then it is unstable.
Abstract: A precise definition of the basic reproduction number, Ro, is presented for a general compartmental disease transmission model based on a system of ordinary dierential equations. It is shown that, if Ro 1, then it is unstable. Thus,Ro is a threshold parameter for the model. An analysis of the local centre manifold yields a simple criterion for the existence and stability of super- and sub-threshold endemic equilibria for Ro near one. This criterion, together with the definition of Ro, is illustrated by treatment, multigroup, staged progression, multistrain and vectorhost models and can be applied to more complex models. The results are significant for disease control.

7,106 citations

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TL;DR: Threshold theorems involving the basic reproduction number, the contact number, and the replacement number $R$ are reviewed for classic SIR epidemic and endemic models and results with new expressions for $R_{0}$ are obtained for MSEIR and SEIR endemic models with either continuous age or age groups.
Abstract: Many models for the spread of infectious diseases in populations have been analyzed mathematically and applied to specific diseases. Threshold theorems involving the basic reproduction number $R_{0}$, the contact number $\sigma$, and the replacement number $R$ are reviewed for the classic SIR epidemic and endemic models. Similar results with new expressions for $R_{0}$ are obtained for MSEIR and SEIR endemic models with either continuous age or age groups. Values of $R_{0}$ and $\sigma$ are estimated for various diseases including measles in Niger and pertussis in the United States. Previous models with age structure, heterogeneity, and spatial structure are surveyed.

5,915 citations

01 Mar 2007
TL;DR: An initiative to develop uniform standards for defining and classifying AKI and to establish a forum for multidisciplinary interaction to improve care for patients with or at risk for AKI is described.
Abstract: Acute kidney injury (AKI) is a complex disorder for which currently there is no accepted definition. Having a uniform standard for diagnosing and classifying AKI would enhance our ability to manage these patients. Future clinical and translational research in AKI will require collaborative networks of investigators drawn from various disciplines, dissemination of information via multidisciplinary joint conferences and publications, and improved translation of knowledge from pre-clinical research. We describe an initiative to develop uniform standards for defining and classifying AKI and to establish a forum for multidisciplinary interaction to improve care for patients with or at risk for AKI. Members representing key societies in critical care and nephrology along with additional experts in adult and pediatric AKI participated in a two day conference in Amsterdam, The Netherlands, in September 2005 and were assigned to one of three workgroups. Each group's discussions formed the basis for draft recommendations that were later refined and improved during discussion with the larger group. Dissenting opinions were also noted. The final draft recommendations were circulated to all participants and subsequently agreed upon as the consensus recommendations for this report. Participating societies endorsed the recommendations and agreed to help disseminate the results. The term AKI is proposed to represent the entire spectrum of acute renal failure. Diagnostic criteria for AKI are proposed based on acute alterations in serum creatinine or urine output. A staging system for AKI which reflects quantitative changes in serum creatinine and urine output has been developed. We describe the formation of a multidisciplinary collaborative network focused on AKI. We have proposed uniform standards for diagnosing and classifying AKI which will need to be validated in future studies. The Acute Kidney Injury Network offers a mechanism for proceeding with efforts to improve patient outcomes.

5,467 citations

01 Feb 2009
TL;DR: This Secret History documentary follows experts as they pick through the evidence and reveal why the plague killed on such a scale, and what might be coming next.
Abstract: Secret History: Return of the Black Death Channel 4, 7-8pm In 1348 the Black Death swept through London, killing people within days of the appearance of their first symptoms. Exactly how many died, and why, has long been a mystery. This Secret History documentary follows experts as they pick through the evidence and reveal why the plague killed on such a scale. And they ask, what might be coming next?

5,234 citations