bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validity of pressure ulcer diagnosis using digital photography
Authors: Baumgarten Mona , Margolis David J. , Selekof Joan L. , Moye Nancy , Jones Patricia S. , Shardell Michelle 
Published: March 2009

ABSTRACTThe purpose of this study was to evaluate the validity of digital photographs for the assessment of the presence of pressure ulcers stage 2 or higher. Participants were 48 patients (28 white and 20 black) with pressure ulcers identified in the course of a wound specialist's routine clinical practice at the University of Maryland Medical Center. One pressure ulcer and one unaffected skin area were photographed on each participating patient. The gold standard diagnosis (stage 2 pressure ulcer vs. stage 1 or no pressure ulcer) was recorded by the wound specialist based on bedside examination. The photographs were reviewed blindly by another wound expert. The sensitivity of the blinded assessment was 97% (95% confidence interval [CI] 91–100%). The specificity was 97% (95% CI 92–100%). The sensitivity and specificity were both 100% in the white patients. In black patients, the sensitivity and specificity were 92% (95% CI 75–100%) and 93% (95% CI 82–100%), respectively. These results suggest that the use of photographic images to assess the presence or absence of a pressure ulcer stage 2 or higher has a high degree of validity. Since blinded outcome assessment is one of the cornerstones of good clinical trial design, photography offers the potential to strengthen future studies.
Interactions between extracellular matrix and growth factors in wound healing
Authors: Schultz Gregory S. , Wysocki Annette 
Published: March 2009

ABSTRACTDynamic interactions between growth factors and extracellular matrix (ECM) are integral to wound healing. These interactions take several forms that may be categorized as direct or indirect. The ECM can directly bind to and release certain growth factors (e.g., heparan sulfate binding to fibroblast growth factor‐2), which may serve to sequester and protect growth factors from degradation, and/or enhance their activity. Indirect interactions include binding of cells to ECM via integrins, which enables cells to respond to growth factors (e.g., integrin binding is necessary for vascular endothelial growth factor‐induced angiogenesis) and can induce growth factor expression (adherence of monocytes to ECM stimulates synthesis of platelet‐derived growth factor). Additionally, matrikines, or subcomponents of ECM molecules, can bind to cell surface receptors in the cytokine, chemokine, or growth factor families and stimulate cellular activities (e.g., tenascin‐C and laminin bind to epidermal growth factor receptors, which enhances fibroblast migration). Growth factors such as transforming growth factor‐β also regulate the ECM by increasing the production of ECM components or enhancing synthesis of matrix degrading enzymes. Thus, the interactions between growth factors and ECM are bidirectional. This review explores these interactions, discusses how they are altered in difficult to heal or chronic wounds, and briefly considers treatment implications.
Venous ulcers: A reappraisal analyzing the effects of neuropathy, muscle involvement, and range of motion upon gait and calf muscle function
Authors: Shiman Michael I. , Pieper Barbara , Templin Thomas N. , Birk Thomas J. , Patel Asha R. , Kirsner Robert S. 
Published: March 2009

ABSTRACTChronic venous insufficiency is a complex disease that can result in severe sequelae including venous ulceration. Though the exact progression from chronic venous insufficiency to venous ulcer remains unclear, the high cost and burden of this disease on patients and society is quite clear. Sustained ambulatory venous pressures or venous hypertension plays an integral role in the development of venous ulceration and involves the failure of the calf muscle pump system. Standard of care involves compression therapy to assist the calf muscle pump. However, several cofactors may contribute to or exacerbate this disease and understanding their impact may provide insight into new treatment modalities. Nerve involvement, which may result in neuropathic pain and muscle dysfunction, alterations in mobility and a decrease in range of motion may lead to gait alterations all affecting calf muscle pump function. In this paper, we analyze these cofactors and discuss possible treatment options to target them. Physicians treating this disease should be aware of the numerous factors involved in its development. Exploring new treatment options may 1 day lessen the burden and suffering caused by venous insufficiency.
Connexin mimetic peptides improve cell migration rates of human epidermal keratinocytes and dermal fibroblasts in vitro
Authors: Wright Catherine S. , Van Steensel Maurice A. M. , Hodgins Malcolm B. , Martin Patricia E. M. 
Published: March 2009

ABSTRACTNonhealing cutaneous wounds, a major cause of morbidity and mortality, are difficult to treat. Recent studies suggest that significant increases in skin wound‐healing rates occur by altering gap junction intercellular communication (GJIC). As migration of keratinocytes and fibroblasts is an important feature of wound healing, this study investigated whether migration rates in cultured normal human epidermal keratinocytes and dermal fibroblasts could be altered by modulating GJIC via connexin mimetic peptides. First, HeLa cells stably transfected with connexin43 (Cx43), Cx40, or Cx26 were used as a model to determine connexin specificity and the doses of connexin mimetic peptides required to attenuate GJIC. Gap26 and Gap26M inhibited GJIC dose dependently and were nonconnexin specific, whereas Gap27 was Cx43‐selective. Skin keratinocytes and fibroblasts expressed a variety of connexins, with Cx43 predominating. Cx43 protein expression was reduced at leading edges 3 hours after scraping confluent monolayers, resolving at 24 hours. Gap26M and Gap27 significantly increased migration rates across scrapes in keratinocytes and fibroblasts by blocking gap junction functionality. GJIC inhibition can thus directly influence keratinocyte and fibroblast migration. Furthermore, our results support the therapeutic potential of connexin mimetic peptides to aid wound closure, and provide a simple approach to screening new agents.
Microbial diversity in chronic open wounds
Authors: Frank Daniel N. , Wysocki Annette , Specht‐Glick Dee Dee , Rooney Alejandro , Feldman Robert A. , St. Amand Allison L. , Pace Norman R. , Trent Jonathan D. 
Published: March 2009

ABSTRACTChronic wounds expose the dermal matrix and underlying tissue to a diversity of microbes from the body and surrounding environment. We determined the microbial diversity of 19 chronic wounds using both molecular methods (sequence analysis of rRNA genes) and routine clinical culturing methods using swab samples. We identified 93 phylotypes in 2,653 rRNA clone sequences and found that compared with other environments, the microbial diversity of chronic wounds is relatively well characterized, i.e., 95% of sequences have ≥97% identity with known human commensals. In total, 75% of sequences belonged to four well‐known wound‐associated phylotypes: Staphylococcus (25%), Corynebacterium (20%), Clostridiales (18%), and Pseudomonas (12%). Approximately 0.5% of sequences (seven phylotypes) belonged to potentially new species. Individual wound samples contained four to 22 phylotypes, but in all wounds only a few (one to three) phylotypes were dominant. In more than half the wound specimens, polymerase chain reaction and culturing methods gave different diversity and dominance information about the microbes present. This exploratory study suggests that combining molecular and culturing methods provides a more complete characterization of the microbial diversity of chronic wounds, and can thereby expand our understanding of how microbiology impacts chronic wound pathology and healing.
Sensation Seeking, Overconfidence, and Trading Activity
Authors: GRINBLATT MARK , KELOHARJU MATTI 
Published: March 2009

ABSTRACTThis study analyzes the role that two psychological attributes—sensation seeking and overconfidence—play in the tendency of investors to trade stocks. Equity trading data from Finland are combined with data from investor tax filings, driving records, and mandatory psychological profiles. We use these data, obtained from a large population, to construct measures of overconfidence and sensation seeking tendencies. Controlling for a host of variables, including wealth, income, age, number of stocks owned, marital status, and occupation, we find that overconfident investors and those investors most prone to sensation seeking trade more frequently.
Equilibrium Portfolio Strategies in the Presence of Sentiment Risk and Excess Volatility
Authors: DUMAS BERNARD , KURSHEV ALEXANDER , UPPAL RAMAN 
Published: March 2009

ABSTRACTOur objective is to identify the trading strategy that would allow an investor to take advantage of “excessive” stock price volatility and “sentiment” fluctuations. We construct a general equilibrium “difference‐of‐opinion” model of sentiment in which there are two classes of agents, one of which is overconfident about a public signal, while still optimizing intertemporally. Overconfident investors overreact to the signal and introduce an additional risk factor causing stock prices to be excessively volatile. Consequently, rational investors choose a conservative portfolio; moreover, this portfolio depends not just on the current price divergence but also on their prediction about future sentiment and the speed of price convergence.
Risk in Dynamic Arbitrage: The Price Effects of Convergence Trading
Authors: KONDOR PÉTER 
Published: March 2009

ABSTRACTI develop an equilibrium model of convergence trading and its impact on asset prices. Arbitrageurs optimally decide how to allocate their limited capital over time. Their activity reduces price discrepancies, but their activity also generates losses with positive probability, even if the trading opportunity is fundamentally riskless. Moreover, prices of identical assets can diverge even if the constraints faced by arbitrageurs are not binding. Occasionally, total losses are large, making arbitrageurs' returns negatively skewed, consistent with the empirical evidence. The model also predicts comovement of arbitrageurs' expected returns and market liquidity.
Catastrophic Risk and Credit Markets
Authors: GARMAISE MARK J. , MOSKOWITZ TOBIAS J. 
Published: March 2009

ABSTRACTWe provide a model of the effects of catastrophic risk on real estate financing and prices and demonstrate that insurance market imperfections can restrict the supply of credit for catastrophe‐susceptible properties. Using unique micro‐level data, we find that earthquake risk decreased commercial real estate bank loan provision by 22% in California properties in the 1990s, with more severe effects in African–American neighborhoods. We show that the 1994 Northridge earthquake had only a short‐term disruptive effect. Our basic findings are confirmed for hurricane risk, and our model and empirical work have implications for terrorism and political perils.
What Drives the Disposition Effect? An Analysis of a Long‐Standing Preference‐Based Explanation
Authors: BARBERIS NICHOLAS , XIONG WEI 
Published: March 2009

ABSTRACTWe investigate whether prospect theory preferences can predict a disposition effect. We consider two implementations of prospect theory: in one case, preferences are defined over annual gains and losses; in the other, they are defined over realized gains and losses. Surprisingly, the annual gain/loss model often fails to predict a disposition effect. The realized gain/loss model, however, predicts a disposition effect more reliably. Utility from realized gains and losses may therefore be a useful way of thinking about certain aspects of individual investor trading.
Work Ethic, Employment Contracts, and Firm Value
Authors: IAN CARLIN BRUCE , GERVAIS SIMON 
Published: March 2009

ABSTRACTWe analyze how the work ethic of managers impacts a firm's employment contracts, riskiness, growth potential, and organizational structure. Flat contracts are optimal for diligent managers because they reduce risk‐sharing costs, but they attract egoistic agents who shirk and unskilled agents who add no value. Stable, bureaucratic firms with low growth potential are more likely to gain value from managerial diligence. Firms that hire from a virtuous pool of agents are more conservative in their investments and have a horizontal corporate structure. Our theory also yields several testable implications that distinguish it from standard agency models.
Creditor Rights, Enforcement, and Bank Loans
Authors: BAE KEE‐HONG , GOYAL VIDHAN K. 
Published: March 2009

ABSTRACTWe examine whether differences in legal protection affect the size, maturity, and interest rate spread on loans to borrowers in 48 countries. Results show that banks respond to poor enforceability of contracts by reducing loan amounts, shortening loan maturities, and increasing loan spreads. These effects are both statistically significant and economically large. While stronger creditor rights reduce spreads, they do not seem to matter for loan size and maturity. Overall, we show that variation in enforceability of contracts matters a great deal more to how loans are structured and how they are priced.
Financial Constraints, Debt Capacity, and the Cross‐section of Stock Returns
Authors: HAHN JAEHOON , LEE HANGYONG 
Published: March 2009

ABSTRACTBuilding on a model of corporate investment under collateral constraints, we develop and test a hypothesis on the differential effect of debt capacity on stock returns across financially constrained and unconstrained firms. Consistent with the hypothesis, we find that debt capacity is a significant determinant of stock returns only in the cross‐section of financially constrained firms, after controlling for beta, size, book‐to‐market, leverage, and momentum. The findings suggest that cross‐sectional differences in corporate investment behavior arising from financial constraints, predicted by theories of imperfect capital markets and supported by empirical evidence, are reflected in the stock returns of manufacturing firms.
Mutations in Conserved Amino Acids in the KCNQ1 Channel and Risk of Cardiac Events in Type‐1 Long‐QT Syndrome
Authors: JONS CHRISTIAN , MOSS ARTHUR J. , LOPES COELI M. , MCNITT SCOTT , ZAREBA WOJCIECH , GOLDENBERG ILAN , QI MING , WILDE ARTHUR A. M. , SHIMIZU WATARU , KANTERS JORGEN K. , TOWBIN JEFFREY A. , ACKERMAN MICHAEL J. , ROBINSON JENNIFER L. 
Published: March 2009

Background: Type‐1 long‐QT syndrome (LQT1) is caused by mutations in the KCNQ1 gene. The purpose of this study was to investigate whether KCNQ1 mutations in highly conserved amino acid residues within the voltage‐gated potassium channel family are associated with an increased risk of cardiac events. Methods and Results: The study population involved 492 LQT1 patients with 54 missense mutations in the transmembrane region of the KCNQ1 channel. The amino acid sequences of the transmembrane region of 38 human voltage‐gated potassium channels were aligned. An adjusted Shannon entropy score for each amino acid residue was calculated ranging from 0 (no conservation) to 1.0 (full conservation). Cox analysis was used to identify independent factors associated with the first cardiac event (syncope, aborted cardiac arrest, or death). Patients were subcategorized into tertiles by their adjusted Shannon entropy scores. The lowest tertile (score 0–0.469; n = 146) was used as a reference group; patients with intermediate tertile scores (0.470–0.665; n = 150) had no increased risk of cardiac events (HR = 1.19, P = 0.42) or aborted cardiac arrest/sudden cardiac death (HR = 1.58, P = 0.26), and those with the highest tertile scores (>0.665; n = 196) showed significantly increased risk of cardiac events (HR = 3.32, P <0.001) and aborted cardiac arrest/sudden cardiac death (HR = 2.62, P = 0.04). The increased risk in patients with the highest conservation scores was independent of QTc, gender, age, and beta‐blocker therapy. Conclusions: Mutations in highly conserved amino acid residues in the KCNQ1 gene are associated with a significant risk of cardiac events independent of QTc, gender, and beta‐blocker therapy.
Cellular/intramuscular myxoma and grade I myxofibrosarcoma are characterized by distinct genetic alterations and specific composition of their extracellular matrix
Authors: Willems Stefan M. , Mohseny Alex B. , Balog Crina , Sewrajsing Raj , Briaire‐de Bruijn Inge H. , Knijnenburg Jeroen , Cleton‐Jansen Anne‐Marie , Sciot Raf , Fletcher Christopher D. M. , Deelder André M. , Szuhai Karoly , Hensbergen Paul J. , Hogendoorn Pancras C. W. 
Published: March 2009

AbstractCellular myxoma and grade I myxofibrosarcoma are mesenchymal tumours that are characterized by their abundant myxoid extracellular matrix (ECM). Despite their histological overlap, they differ clinically. Diagnosis is therefore difficult though important. We investigated their (cyto) genetics and ECM. GNAS1‐activating mutations have been described in intramuscular myxoma, and lead to downstream activation of cFos. KRAS and TP53 mutations are commonly involved in sarcomagenesis whereby KRAS subsequently activates c‐Fos. A well‐documented series of intramuscular myxoma (three typical cases and seven cases of the more challenging cellular variant) and grade I myxofibrosarcoma (n= 10) cases were karyotyped, analyzed for GNAS1, KRAS and TP53 mutations and downstream activation of c‐Fos mRNA and protein expression. ECM was studied by liquid chromatography mass spectrometry and expression of proteins identified was validated by immunohistochemistry and qPCR. Grade I myxofibrosarcoma showed variable, non‐specific cyto‐genetic aberrations in 83,5% of cases (n= 6) whereas karyotypes of intramuscular myxoma were all normal (n= 7). GNAS1‐activating mutations were exclusively found in 50% of intramuscular myxoma. Both tumour types showed over‐expression of c‐Fos mRNA and protein. No mutations in KRAS codon 12/13 or in TP53 were detected. Liquid chromatography mass spectrometry revealed structural proteins (collagen types I, VI, XII, XIV and decorin) in grade I myxofibrosarcoma lacking in intramuscular myxoma. This was confirmed by immunohistochemistry and qPCR. Intramuscular/cellular myxoma and grade I myxofibrosarcoma show different molecular genetic aberrations and different composition of their ECM that probably contribute to their diverse clinical behaviour. GNAS1 mutation analysis can be helpful to distinguish intramuscular myxoma from grade I myxofibrosarcoma in selected cases.
Desmoplastic cellular neurothekeoma: Clinicopathological analysis of twelve cases
Authors: Zedek Daniel C. , White Wain L. , McCalmont Timothy H. 
Published: March 2009

Background: Cellular neurothekeoma is a benign lesion most commonly found on the face and upper extremities in the first two decades of life.Methods: Retrospective clinicopathologic review of 12 examples of cellular neurothekeoma typified by prominent stromal sclerosis, a distinctive variant that we refer to as desmoplastic cellular neurothekeoma.Results: The mean age was 30 years (range, 3–55 years, 3 males, 9 females). The site was the head and neck in 3 cases, upper extremity in 4, lower extremity in 2, and trunk/abdomen in 3. All cases showed fascicles of slightly spindled and polygonal cells arrayed haphazardly in a prominent sclerotic background in the dermis and superficial subcutis. The cells displayed pale cytoplasm with indistinct membranes and vesicular nuclei with a single nucleolus. Lesional cells expressed NKI/C3, laminin, CD68, and CD10 and lacked expression of S‐100 protein, EMA, and CD34. Clinical follow up was available on 10 cases with a mean duration of 24 months (range, 11–42 months) with no local recurrences or metastases.Conclusions: The immunohistochemical staining pattern, clinical findings, and benign nature are similar to “conventional” cellular neurothekeomas. The differential diagnosis includes desmoplastic melanocytic lesions, desmoplastic spindle cell carcinoma, dermatofibroma, “immature” scar, plexiform fibrohistiocytic tumor, perineurioma, and piloleiomyoma.
Germline variation of the melanocortin‐1 receptor does not explain shared risk for melanoma and thyroid cancer
Authors: Bauer Jürgen , Weng Julie , Kebebew Electron , Soares Paula , Trovisco Vitor , Bastian Boris C. 
Published: March 2009

Background:  Recently, germline variants of the melanocortin‐1 receptor (MC1R) have been shown to be associated with an increased risk for BRAF mutant but not BRAF wild‐type cutaneous melanoma. Similar to melanoma, BRAF mutations are also commonly found in papillary thyroid carcinomas. Furthermore, patients with melanoma have an increased risk for thyroid carcinoma and vice versa.Methods:  To determine whether MC1R variation also represents a risk factor for BRAF mutant thyroid carcinomas, we sequenced BRAF and MC1R in two separate case–control cohorts.Results:  We demonstrate that MC1R is expressed in normal and neoplastic thyroid epithelial cells, albeit at lower levels than in melanocytes. In the first cohort of 66 follicular and 62 papillary thyroid carcinomas (PTC), and 128 matched controls from the San Francisco Bay Area we found no association between the number of MC1R variant alleles and thyroid cancer. Patients with BRAF‐mutated tumors had a higher frequency of MC1R variant alleles than their matched controls (P = 0.039). However, contrary to the findings in melanoma, the odds ratio for having a BRAF mutant cancer decreased from 3.9 for carriers of one MC1R allele to 1.5 for carriers of two or more alleles. As the frequency of MC1R alleles varies highly among different ethnic populations, we analysed a second, ethnically more homogeneous cohort from Spain and Portugal, and found no association with PTC nor with BRAF‐mutated PTC.Conclusion:  Our data indicate that the strong association between BRAF mutations and MC1R variants previously found in melanoma does not extend to thyroid cancer.
LRP5 sequence and polymorphisms in the baboon
Authors: Doubleday Alison F. , Kaestle Frederika A. , Cox Laura A. , Birnbaum Shifra , Mahaney Michael C. , Havill Lorena M. 
Published: March 2009

AbstractBackground  LRP5 is known to have an important relationship with bone density and a variety of other biological processes. Mapping to human chromosome 11q13.2, LRP5 shows considerable evolutionary conservation. Orthologs of this gene exist in many species, although comparison of human LRP5 with other non‐human primates has not been performed until now.Methods  We reported the complementary DNA (cDNA) sequence and deduced amino acid sequence for baboon LRP5, and compared the baboon and human sequences. cDNA sequences for 21 baboons were examined to identify single‐nucleotide polymorphisms (SNPs).Results  Sequences of coding regions in human and baboon LRP5 showed 97– 99% homology. Twenty‐five SNPs were identified in the coding region of baboon LRP5.Conclusion  The observed degree of coding sequence homology in LRP5 led us to expect that the baboon may serve as a useful model for future research into the role(s) of this gene in primate metabolic diseases.