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Showing papers by "University of Alabama published in 2008"


Journal ArticleDOI
TL;DR: These revised definitions of invasive fungal disease are intended to advance clinical and epidemiological research and may serve as a useful model for defining other infections in high-risk patients.
Abstract: BACKGROUND: Invasive fungal diseases are important causes of morbidity and mortality. Clarity and uniformity in defining these infections are important factors in improving the quality of clinical studies. A standard set of definitions strengthens the consistency and reproducibility of such studies. METHODS: After the introduction of the original European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group definitions, advances in diagnostic technology and the recognition of areas in need of improvement led to a revision of this document. The revision process started with a meeting of participants in 2003, to decide on the process and to draft the proposal. This was followed by several rounds of consultation until a final draft was approved in 2005. This was made available for 6 months to allow public comment, and then the manuscript was prepared and approved. RESULTS: The revised definitions retain the original classifications of "proven," "probable," and "possible" invasive fungal disease, but the definition of "probable" has been expanded, whereas the scope of the category "possible" has been diminished. The category of proven invasive fungal disease can apply to any patient, regardless of whether the patient is immunocompromised, whereas the probable and possible categories are proposed for immunocompromised patients only. CONCLUSIONS: These revised definitions of invasive fungal disease are intended to advance clinical and epidemiological research and may serve as a useful model for defining other infections in high-risk patients.

4,389 citations


Journal ArticleDOI
24 Sep 2008-JAMA
TL;DR: In this study involving 10 geographic regions in North America, there were significant and important regional differences in out-of-hospital cardiac arrest incidence and outcome.
Abstract: Context The health and policy implications of regional variation in incidence and outcome of out-of-hospital cardiac arrest remain to be determined. Objective To evaluate whether cardiac arrest incidence and outcome differ across geographic regions. Design, Setting, and Patients Prospective observational study (the Resuscitation Outcomes Consortium) of all out-of-hospital cardiac arrests in 10 North American sites (8 US and 2 Canadian) from May 1, 2006, to April 30, 2007, followed up to hospital discharge, and including data available as of June 28, 2008. Cases (aged 0-108 years) were assessed by organized emergency medical services (EMS) personnel, did not have traumatic injury, and received attempts at external defibrillation or chest compressions or resuscitation was not attempted. Census data were used to determine rates adjusted for age and sex. Main Outcome Measures Incidence rate, mortality rate, case-fatality rate, and survival to discharge for patients assessed or treated by EMS personnel or with an initial rhythm of ventricular fibrillation. Results Among the 10 sites, the total catchment population was 21.4 million, and there were 20 520 cardiac arrests. A total of 11 898 (58.0%) had resuscitation attempted; 2729 (22.9% of treated) had initial rhythm of ventricular fibrillation or ventricular tachycardia or rhythms that were shockable by an automated external defibrillator; and 954(4.6% of total) were discharged alive. The median incidence of EMS-treated cardiac arrest across sites was 52.1 (interquartile range [IQR], 48.0-70.1) per 100 000 population; survival ranged from 3.0% to 16.3%, with a median of 8.4% (IQR, 5.4%-10.4%). Median ventricular fibrillation incidence was 12.6 (IQR, 10.6-5.2) per 100 000 population; survival ranged from 7.7% to 39.9%, with a median of 22.0% (IQR, 15.0%-24.4%), with significant differences across sites for incidence and survival (P Conclusion In this study involving 10 geographic regions in North America, there were significant and important regional differences in out-of-hospital cardiac arrest incidence and outcome.

1,799 citations


Journal ArticleDOI
TL;DR: The guideline includes data on the epidemiology, clinical features, diagnosis, and treatment of many viral, bacterial, fungal, protozoal, and helminthic etiologies of encephalitis and provides information on when specific etiologic agents should be considered in individual patients with encephalopathy.
Abstract: Guidelines for the diagnosis and treatment of patients with encephalitis were prepared by an Expert Panel of the Infectious Diseases Society of America. The guidelines are intended for use by health care providers who care for patients with encephalitis. The guideline includes data on the epidemiology, clinical features, diagnosis, and treatment of many viral, bacterial, fungal, protozoal, and helminthic etiologies of encephalitis and provides information on when specific etiologic agents should be considered in individual patients with encephalitis.

858 citations


Journal ArticleDOI
TL;DR: The LysM RLK1-mediated chitin signaling pathway is unique, but it may share a conserved downstream pathway with the FLS2/flagellin- and EFR/EF-Tu–mediated signaling pathways.
Abstract: Chitin, a polymer of N -acetyl-d-glucosamine, is found in fungal cell walls but not in plants. Plant cells can perceive chitin fragments (chitooligosaccharides) leading to gene induction and defense responses. We identified a LysM receptor-like protein (LysM RLK1) required for chitin signaling in Arabidopsis thaliana . The mutation in this gene blocked the induction of almost all chitooligosaccharide-responsive genes and led to more susceptibility to fungal pathogens but had no effect on infection by a bacterial pathogen. Additionally, exogenously applied chitooligosaccharides enhanced resistance against both fungal and bacterial pathogens in the wild-type plants but not in the mutant. Together, our data indicate that LysM RLK1 is essential for chitin signaling in plants (likely as part of the receptor complex) and is involved in chitin-mediated plant innate immunity. The LysM RLK1-mediated chitin signaling pathway is unique, but it may share a conserved downstream pathway with the FLS2/flagellin- and EFR/EF-Tu–mediated signaling pathways. Additionally, our work suggests a possible evolutionary relationship between the chitin and Nod factor perception mechanisms due to the similarities between their potential receptors and between the signal molecules perceived by them.

741 citations


Journal ArticleDOI
14 May 2008-JAMA
TL;DR: Clopidogrel reduces the frequency of early thrombosis of new arteriovenous fistulas but does not increase the proportion of fistulas that become suitable for dialysis.
Abstract: Context The arteriovenous fistula is the preferred type of vascular access for hemodialysis because of lower thrombosis and infection rates and lower health care expenditures compared with synthetic grafts or central venous catheters. Early failure of fistulas due to thrombosis or inadequate maturation is a barrier to increasing the prevalence of fistulas among patients treated with hemodialysis. Small, inconclusive trials have suggested that antiplatelet agents may reduce thrombosis of new fistulas. Objective To determine whether clopidogrel reduces early failure of hemodialysis fistulas. Design, Setting, and Participants Randomized, double-blind, placebo-controlled trial conducted at 9 US centers composed of academic and community nephrology practices in 2003-2007. Eight hundred seventy-seven participants with end-stage renal disease or advanced chronic kidney disease were followed up until 150 to 180 days after fistula creation or 30 days after initiation of dialysis, whichever occurred later. Intervention Participants were randomly assigned to receive clopidogrel (300-mg loading dose followed by daily dose of 75 mg; n = 441) or placebo (n = 436) for 6 weeks starting within 1 day after fistula creation. Main Outcome Measures The primary outcome was fistula thrombosis, determined by physical examination at 6 weeks. The secondary outcome was failure of the fistula to become suitable for dialysis. Suitability was defined as use of the fistula at a dialysis machine blood pump rate of 300 mL/min or more during 8 of 12 dialysis sessions. Results Enrollment was stopped after 877 participants were randomized based on a stopping rule for intervention efficacy. Fistula thrombosis occurred in 53 (12.2%) participants assigned to clopidogrel compared with 84 (19.5%) participants assigned to placebo (relative risk, 0.63; 95% confidence interval, 0.46-0.97; P = .018). Failure to attain suitability for dialysis did not differ between the clopidogrel and placebo groups (61.8% vs 59.5%, respectively; relative risk, 1.05; 95% confidence interval, 0.94-1.17; P = .40). Conclusion Clopidogrel reduces the frequency of early thrombosis of new arteriovenous fistulas but does not increase the proportion of fistulas that become suitable for dialysis. Trial Registration clinicaltrials.gov Identifier: NCT00067119

680 citations


Journal ArticleDOI
TL;DR: A model in which the regulatory focus of employees at work mediates the influence of leadership on employee behavior indicates that each leadership style incrementally predicts disparate outcomes after controlling for the other style and dispositional tendencies.
Abstract: In this research, the authors test a model in which the regulatory focus of employees at work mediates the influence of leadership on employee behavior. In a nationally representative sample of 250 workers who responded over 2 time periods, prevention focus mediated the relationship of initiating structure to in-role performance and deviant behavior, whereas promotion focus mediated the relationship of servant leadership to helping and creative behavior. The results indicate that even though initiating structure and servant leadership share some variance in explaining other variables, each leadership style incrementally predicts disparate outcomes after controlling for the other style and dispositional tendencies. A new regulatory focus scale, the Work Regulatory Focus (WRF) Scale, also was developed and initially validated for this study. Implications for the results and the WRF Scale are discussed.

665 citations



Journal ArticleDOI
TL;DR: Results indicated that higher PCL Total, Factor 1 (F1), and Factor 2 (F2) scores were moderately associated with increased antisocial conduct, and multiple regression analyses indicated that the information used to assess psychopathy did not have a unique influence on effect sizes after accounting for the influence of other moderator variables.
Abstract: The present meta-analysis integrated effect sizes from 95 non-overlapping studies (N=15,826) to summarize the relation between Hare Psychopathy Checklists and antisocial conduct. Whereas prior meta-analyses focused on specific subdomains of the literature, we used broad inclusion criteria, incorporating a diversity of samples, settings, methodologies, and outcomes in our analysis. Our broad perspective allowed us to identify general trends consistent across the entire literature and improved the power of our analyses. Results indicated that higher PCL Total, Factor 1 (F(1)), and Factor 2 (F(2)) scores were moderately associated with increased antisocial conduct. Study effect sizes were significantly moderated by the country in which the study was conducted, racial composition, gender composition, institutional setting, the type of information used to score psychopathy, and the independence of psychopathy and transgression assessments. However, multiple regression analyses indicated that the information used to assess psychopathy did not have a unique influence on effect sizes after accounting for the influence of other moderator variables. Furthermore, racial composition of the sample was related to the country in which the study was conducted, making it unclear whether one or both of these moderators influenced effect sizes. We provide potential explanations for the significant findings and discuss implications of the results for future research.

628 citations


Journal ArticleDOI
TL;DR: It is shown that HIV-1 env genes, other viral genes, and even full-length viral genomes responsible for productive clinical infection can be identified by SGA analysis of plasma virus sampled at intervals typical in large-scale vaccine trials and that pathways of viral diversification and immune escape can be determined accurately.
Abstract: Accurate identification of the transmitted virus and sequences evolving from it could be instrumental in elucidating the transmission of human immunodeficiency virus type 1 (HIV-1) and in developing vaccines, drugs, or microbicides to prevent infection. Here we describe an experimental approach to analyze HIV-1 env genes as intact genetic units amplified from plasma virion RNA by single-genome amplification (SGA), followed by direct sequencing of uncloned DNA amplicons. We show that this strategy precludes in vitro artifacts caused by Taq-induced nucleotide substitutions and template switching, provides an accurate representation of the env quasispecies in vivo, and has an overall error rate (including nucleotide misincorporation, insertion, and deletion) of less than 8 x 10(-5). Applying this method to the analysis of virus in plasma from 12 Zambian subjects from whom samples were obtained within 3 months of seroconversion, we show that transmitted or early founder viruses can be identified and that molecular pathways and rates of early env diversification can be defined. Specifically, we show that 8 of the 12 subjects were each infected by a single virus, while 4 others acquired more than one virus; that the rate of virus evolution in one subject during an 80-day period spanning seroconversion was 1.7 x 10(-5) substitutions per site per day; and that evidence of strong immunologic selection can be seen in Env and overlapping Rev sequences based on nonrandom accumulation of nonsynonymous mutations. We also compared the results of the SGA approach with those of more-conventional bulk PCR amplification methods performed on the same patient samples and found that the latter is associated with excessive rates of Taq-induced recombination, nucleotide misincorporation, template resampling, and cloning bias. These findings indicate that HIV-1 env genes, other viral genes, and even full-length viral genomes responsible for productive clinical infection can be identified by SGA analysis of plasma virus sampled at intervals typical in large-scale vaccine trials and that pathways of viral diversification and immune escape can be determined accurately.

621 citations


Journal ArticleDOI
TL;DR: In this article, the authors selectively review studies of impression management published since 1988 and identify strengths, limitations, and future research directions in three key areas: research investigating the use of IM at the individual level of analysis, research that applies IM theory, concepts, and thinking to better understand organizational phenomena, and research investigating organizational-level IM (e.g., how firms create legitimacy).

550 citations


Journal ArticleDOI
TL;DR: In this paper, the authors identify the universities and research scholars who have had the greatest impact on the field of management during the past quarter century and the factors that influence their impact.

Journal ArticleDOI
TL;DR: In this article, the critical role of entrepreneurial orientation (EO) in firm performance has been widely studied in the U.S. context, however, the examination of this key construct in emerging regions such as Chi...
Abstract: The critical role of entrepreneurial orientation (EO) in firm performance has been widely studied in the U.S. context. However, the examination of this key construct in emerging regions such as Chi...

Journal ArticleDOI
TL;DR: The National Registry of Myocardial Infarction (NHRI) has been used to study the characteristics and hospital mortality of patients with either ST elevation (STEMI) or non-ST elevation (NSTEMI). as mentioned in this paper found that the proportion of NSTEMI increased from 14.2% to 59.1% from 1990 to 2006.

Journal ArticleDOI
TL;DR: It is demonstrated that high mobility group box 1 acquires proinflammatory activity through binding to proinflammatory mediators, such as IL-1β.
Abstract: High mobility group box 1 protein (HMGB1), originally characterized as a nuclear DNA-binding protein, has also been described to have an extracellular role when it is involved in cellular activation and proinflammatory responses In this study, FLAG-tagged HMGB1 was inducibly expressed in the presence of culture media with or without added IL-1beta, IFN-gamma, or TNF-alpha HMGB1 purified from cells grown in culture media alone only minimally increased cytokine production by MH-S macrophages and had no effect on murine neutrophils In contrast, HMGB1 isolated from cells cultured in the presence of IL-1beta, IFN-gamma, and TNF-alpha had enhanced proinflammatory activity, resulting in increased production of MIP-2 and TNF-alpha by exposed cells IL-1beta was bound to HMGB1 isolated from cells cultured with this cytokine, and purified HMGB1 incubated with recombinant IL-1beta acquired proinflammatory activity Addition of anti-IL-1beta Abs or the IL-1 receptor antagonist to cell cultures blocked the proinflammatory activity of HMGB1 purified from IL-1beta-exposed cells, indicating that such activity was dependent on interaction with the IL-1 receptor These results demonstrate that HMGB1 acquires proinflammatory activity through binding to proinflammatory mediators, such as IL-1beta

Journal ArticleDOI
TL;DR: An expert international panel consisting of the Mycoses Study Group and the European Organization for Research and Treatment of Cancer was convened to propose guidelines for assessing treatment responses in clinical trials of IFDs and for defining study outcomes.
Abstract: Invasive fungal diseases (IFDs) have become major causes of morbidity and mortality among highly immunocompromised patients. Authoritative consensus criteria to diagnose IFD have been useful in establishing eligibility criteria for antifungal trials. There is an important need for generation of consensus definitions of outcomes of IFD that will form a standard for evaluating treatment success and failure in clinical trials. Therefore, an expert international panel consisting of the Mycoses Study Group and the European Organization for Research and Treatment of Cancer was convened to propose guidelines for assessing treatment responses in clinical trials of IFDs and for defining study outcomes. Major fungal diseases that are discussed include invasive disease due to Candida species, Aspergillus species and other molds, Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitis. We also discuss potential pitfalls in assessing outcome, such as conflicting clinical, radiological, and/or mycological data and gaps in knowledge.

Journal ArticleDOI
TL;DR: An N-ethyl-N-nitrosourea–induced mutant mouse, alien (aln), is described, which has abnormal primary cilia and shows overactivation of the SHH pathway, suggesting that anterograde IFT is required for GLI activation and that retrograde IFT modulates this event.
Abstract: Characterization of previously described intraflagellar transport (IFT) mouse mutants has led to the proposition that normal primary cilia are required for mammalian cells to respond to the sonic hedgehog (SHH) signal. Here we describe an N-ethyl-N-nitrosourea–induced mutant mouse, alien (aln), which has abnormal primary cilia and shows overactivation of the SHH pathway. The aln locus encodes a novel protein, THM1 (tetratricopeptide repeat–containing hedgehog modulator-1), which localizes to cilia. aln-mutant cilia have bulb-like structures at their tips in which IFT proteins (such as IFT88) are sequestered, characteristic of Chlamydomonas reinhardtii and Caenorhabditis elegans retrograde IFT mutants. RNA-interference knockdown of Ttc21b (which we call Thm1 and which encodes THM1) in mouse inner medullary collecting duct cells expressing an IFT88–enhanced yellow fluorescent protein fusion recapitulated the aln-mutant cilial phenotype, and live imaging of these cells revealed impaired retrograde IFT. In contrast to previously described IFT mutants, Smoothened and full-length glioblastoma (GLI) proteins localize to aln-mutant cilia. We hypothesize that the aln retrograde IFT defect causes sequestration of IFT proteins in aln-mutant cilia and leads to the overactivated SHH signaling phenotype. Specifically, the aln mutation uncouples the roles of anterograde and retrograde transport in SHH signaling, suggesting that anterograde IFT is required for GLI activation and that retrograde IFT modulates this event.

Book ChapterDOI
TL;DR: The capacity of this virus to persist in the midst of intense inflammation suggests that its persistence could serve as a trigger for the induction of host-vs-graft responses or alternatively host responses to HCMV could contribute to the inflammatory milieu characteristic of chronic allograft rejection.
Abstract: Infections with human cytomegalovirus (HCMV) are a major cause of morbidity and mortality in humans with acquired or developmental deficits in innate and adaptive immunity. In the normal immunocompetent host, symptoms rarely accompany acute infections, although prolonged virus shedding is frequent. Virus persistence is established in all infected individuals and appears to be maintained by both a chronic productive infections as well as latency with restricted viral gene expression. The contributions of the each of these mechanisms to the persistence of this virus in the individual is unknown but frequent virus shedding into the saliva and genitourinary tract likely accounts for the near universal incidence of infection in most populations in the world. The pathogenesis of disease associated with acute HCMV infection is most readily attributable to lytic virus replication and end organ damage either secondary to virus replication and cell death or from host immunological responses that target virus-infected cells. Antiviral agents limit the severity of disease associated with acute HCMV infections, suggesting a requirement for virus replication in clinical syndromes associated with acute infection. End organ disease secondary to unchecked virus replication can be observed in infants infected in utero, allograft recipients receiving potent immunosuppressive agents, and patients with HIV infections that exhibit a loss of adaptive immune function. In contrast, diseases associated with chronic or persistent infections appear in normal individuals and in the allografts of the transplant recipient. The manifestations of these infections appear related to chronic inflammation, but it is unclear if poorly controlled virus replication is necessary for the different phenotypic expressions of disease that are reported in these patients. Although the relationship between HCMV infection and chronic allograft rejection is well known, the mechanisms that account for the role of this virus in graft loss are not well understood. However, the capacity of this virus to persist in the midst of intense inflammation suggests that its persistence could serve as a trigger for the induction of host-vs-graft responses or alternatively host responses to HCMV could contribute to the inflammatory milieu characteristic of chronic allograft rejection.

Journal ArticleDOI
TL;DR: Subanalyses of pooled data from week 48 indicate that maraviroc provides a valuable treatment option for a wide spectrum of patients with R5 HIV-1 infection who have been treated previously.
Abstract: BACKGROUND: We conducted subanalyses of the combined results of the Maraviroc versus Optimized Therapy in Viremic Antiretroviral Treatment-Experienced Patients (MOTIVATE) 1 and MOTIVATE 2 studies to better characterize the efficacy and safety of maraviroc in key subgroups of patients. METHODS: We analyzed pooled data from week 48 from the two studies according to sex, race or ethnic group, clade, CC chemokine receptor 5 (CCR5) delta32 genotype, viral load at the time of screening, the use or nonuse of enfuvirtide in optimized background therapy (OBT), the baseline CD4 cell count, the number of active antiretroviral drugs coadministered, the first use of selected background agents, and tropism at baseline. Changes in viral tropism and the CD4 count at treatment failure were evaluated. Data on aminotransferase levels in patients coinfected with hepatitis B virus (HBV) or hepatitis C virus (HCV) were also analyzed. RESULTS: A treatment benefit of maraviroc plus OBT over placebo plus OBT was shown in all subgroups, including patients with a low CD4 cell count at baseline, those with a high viral load at screening, and those who had not received active agents in OBT. Analyses of the virologic response according to the first use of selected background drugs showed the additional benefit of adding a potent new drug to maraviroc at the initiation of maraviroc therapy. More patients in whom maraviroc failed had a virus binding to the CXC chemokine receptor 4 (CXCR4) at failure, but there was no evidence of a decrease in the CD4 cell count at failure in such patients as compared with those in whom placebo failed. Subanalyses involving patients coinfected with HBV or HCV revealed no evidence of excess hepatotoxic effects as compared with baseline. CONCLUSIONS: Subanalyses of pooled data from week 48 indicate that maraviroc provides a valuable treatment option for a wide spectrum of patients with R5 HIV-1 infection who have been treated previously. (ClinicalTrials.gov numbers, NCT00098306 and NCT00098722.)

Journal ArticleDOI
TL;DR: The results of two studies indicate that people who are high in openness to new experience and high in neuroticism are likely to be bloggers, indicating that personality factors impact the likelihood of being a blogger and have implications for understanding who blogs.

Journal ArticleDOI
15 Nov 2008-Cancer
TL;DR: The risk, severity, and patient-reported outcomes of radiation-induced mucositis among head and neck cancer patients were prospectively estimated in this article, and the detrimental effects on QOL and functional status are significant, and opioid analgesia provides inadequate relief.
Abstract: BACKGROUND. The risk, severity, and patient-reported outcomes of radiation-induced mucositis among head and neck cancer patients were prospectively estimated. METHODS. A validated, patient-reported questionnaire (OMDQ), the FACT quality of life (QOL), and the Functional Assessment of Chronic Illness Therapy (FACIT) fatigue scales were used to measure mucositis (reported as mouth and throat soreness), daily functioning, and use of analgesics. Patients were studied before radiotherapy (RT), daily during RT, and for 4 weeks after RT. RESULTS. Contrary to previous reports, the risk of mucositis was virtually identical in the 126 patients with oral cavity or oropharynx tumors (99% overall; 85% grade 3-4) compared with 65 patients with tumors of the larynx or hypopharynx (98% overall; 77% grade 3-4). The mean QOL score decreased significantly during RT, from 85.1 at baseline to 69.0 at Week 6, corresponding with the peak of mucositis severity. The mean functional status score decreased by 33% from 18.3 at baseline to 12.3 at Week 6. The impact of mucositis on QOL was proportional to its severity, although even a score of 1 or 2 (mild or moderate) was associated with a significant reduction in QOL (from 93.6 at baseline to 74.7 at Week 6). Despite increases in analgesic use from 34% at baseline to 80% at Week 6, mean mucositis scores exceeded 2.5 at Week 6. CONCLUSIONS. Mucositis occurs among virtually all patients who are undergoing radiation treatment of head and neck cancers. The detrimental effects on QOL and functional status are significant, and opioid analgesia provides inadequate relief. Preventive rather than symptom palliation measures are needed. Cancer 2008;113:2704–13. � 2008 American Cancer Society.

Journal ArticleDOI
TL;DR: A broad overview of the physics of OCT, the unique properties of this method with respect to imaging retinal architecture, and the applications that are being developed for OCT to understand mechanisms of tissue injury within the brain are provided.
Abstract: Multiple sclerosis is characterized by both demyelination and neurodegeneration. The lack of myelin in the retina makes this an ideal structure in which to visualize the latter process. In this Review, Frohman et al. describe the novel use of retinal imaging technology, and in particular optical coherence tomography (OCT), to model the disease process in multiple sclerosis. They suggest that OCT could ultimately be used to identify strategies aimed at neuroprotection in the CNS. The pathophysiology of multiple sclerosis (MS) is characterized by demyelination, which culminates in a reduction in axonal transmission. Axonal and neuronal degeneration seem to be concomitant features of MS and are probably the pathological processes responsible for permanent disability in this disease. The retina is unique within the CNS in that it contains axons and glia but no myelin, and it is, therefore, an ideal structure within which to visualize the processes of neurodegeneration, neuroprotection, and potentially even neurorestoration. In particular, the retina enables us to investigate a specific compartment of the CNS that is targeted by the disease process. Optical coherence tomography (OCT) can provide high-resolution reconstructions of retinal anatomy in a rapid and reproducible fashion and, we believe, is ideal for precisely modeling the disease process in MS. In this Review, we provide a broad overview of the physics of OCT, the unique properties of this method with respect to imaging retinal architecture, and the applications that are being developed for OCT to understand mechanisms of tissue injury within the brain.

Journal ArticleDOI
TL;DR: In this paper, CoFe 2 O 4 nanoparticles were synthesized, dispersed in water, and investigated as heating agents for magnetic thermo-drug delivery and hyperthermia.

Journal ArticleDOI
TL;DR: Five previously unreported gene products are revealed that significantly protect against age- and dose-dependent α-syn-induced degeneration in the dopamine neurons of transgenic worms, and one gene reported to cause neurodegeneration in knockout mice.
Abstract: Genomic multiplication of the locus-encoding human α-synuclein (α-syn), a polypeptide with a propensity toward intracellular misfolding, results in Parkinson's disease (PD) Here we report the results from systematic screening of nearly 900 candidate genetic targets, prioritized by bioinformatic associations to existing PD genes and pathways, via RNAi knockdown Depletion of 20 gene products reproducibly enhanced misfolding of α-syn over the course of aging in the nematode Caenorhabditis elegans Subsequent functional analysis of seven positive targets revealed five previously unreported gene products that significantly protect against age- and dose-dependent α-syn-induced degeneration in the dopamine neurons of transgenic worms These include two trafficking proteins, a conserved cellular scaffold-type protein that modulates G protein signaling, a protein of unknown function, and one gene reported to cause neurodegeneration in knockout mice These data represent putative genetic susceptibility loci and potential therapeutic targets for PD, a movement disorder affecting ≈2% of the population over 65 years of age

Journal ArticleDOI
TL;DR: In this article, the authors review the relevant literature, address conceptual and methodological issues associated with extant cross-cultural consumer services research and suggest theories and approaches in regards to future research in the area.

Journal ArticleDOI
TL;DR: The current review examines the existing literature around three major themes: the definition ofxiety in dementia, the properties of available instruments for assessment, and the clinical characteristics of anxiety in this population.

Journal ArticleDOI
TL;DR: In this article, the authors employ U.S. data over a 30-year sample period to test the relationship between macroeconomic conditions and capital structure adjustment speed using both two-stage and integrated partial adjustment dynamic capital structure models.
Abstract: Studies show that capital structure choice varies over time and across firms and that macroeconomic conditions are important factors in analyzing firms' financing choices. However, studies have largely ignored the impact of macroeconomic conditions on the adjustment speed of capital structure toward targets. Hackbarth et al. (2006) develop a contingent model for analyzing the impact of macroeconomic conditions on dynamic capital structure choice. Allowing for dynamic capital structure adjustments, their model predicts that firms should adjust their capital structure faster in booms than in recessions. We employ U.S. data over a 30 year sample period to test the relationship between macroeconomic conditions and capital structure adjustment speed using both two-stage and integrated partial adjustment dynamic capital structure models. We find evidence supporting the prediction from Hackbarth et al's theoretical framework that firms adjust to target leverage faster in good states than in bad states, where states are defined by term spread, default spread, GDP growth rate, and market dividend yield. Our results also support the pecking order theory in that under-levered firms adjust faster than firms that are over-levered. We find evidence favoring the market timing theory implication that under-levered firms have less incentive to adjust toward target leverage when stock market performance is good, as measured by dividend yield on the market and price-output ratio. Robustness tests demonstrate that our speed of capital structure adjustment cannot be simply explained by firm size, the degree of deviation from target, or by the definition of debt ratio. Our results are also robust to potential boundary issues.


Journal ArticleDOI
TL;DR: Findings support the need for built environments and transportation policies that facilitate safe, active transport to recreation sites for youth physical activity.
Abstract: GROW, H. M., B. E. SAELENS, J. KERR, N. H. DURANT, G. J. NORMAN, and J. F. SALLIS. Where Are Youth Active? Roles of Proximity, Active Transport, and Built Environment. Med. Sci. Sports Exerc., Vol. 40, No. 12, pp. 2071–2079, 2008. Purpose: This study examined factors related to two sources of physical activity for youth: active use of recreation sites and active transport to recreation sites. Methods: Parents of children (n = 87) and matched pairs of parents and adolescents (n = 124 pairs) in three US cities reported on youths’ active use of, proximity to, and walking/biking to 12 recreation sites and on neighborhood walkability and safety. Multivariate regression models evaluated factors associated with youths’ frequent site use and active transport to sites. Results: Proximity to the site was associated with frequent use of large parks and public open space. Walking/biking to the site was associated with frequent use of most sites (indoor recreation sites, small and large parks, basketball courts, walking/running tracks, school recreation sites, playgrounds, and public open space). After controlling for proximity and demographic factors, active transport to sites remained significantly associated (P G 0.05) with frequent use of four sites for children (indoor recreation, walking/running tracks, school recreation facilities, and public open space) and all but three sites for adolescents (indoor recreation, playfields/courts, and beach/ lake/rivers). Adolescents’ active transport to more sites was most positively related to higher perceived traffic safety and to better pedestrian infrastructure and was negatively related to crime threat. Adolescents with driver’s licenses walked/biked to recreation sites less often. Conclusions: Active transport was strongly associated with the use of multiple recreation sites by children and adolescents, even when accounting for proximity and demographic factors. Adolescents living in neighborhoods with better traffic safety walked/ biked to more recreation sites for physical activity. Findings support the need for built environments and transportation policies that

Journal ArticleDOI
TL;DR: In this paper, the authors used field characteristics, U-Pb detrital zircon dating, and geochemistry to define the first-order stratigraphic architecture of the Indian passive margin sequence in the eastern Himalaya.

Journal ArticleDOI
01 Nov 2008-Diabetes
TL;DR: These findings point to a molecular mechanism in humans by which higher triglycerides and CRP can be coupled with lower plasma glucose concentrations and position GCKR in central pathways regulating both hepatic triglyceride and glucose metabolism.
Abstract: OBJECTIVE Using the genome-wide-association approach, we recently identified the glucokinase regulatory protein gene ( GCKR , rs780094) region as a novel quantitative trait locus for plasma triglyceride concentration in Europeans. Here, we sought to study the association of GCKR variants with metabolic phenotypes including measures of glucose homeostasis, to evaluate the GCKR locus in samples of non-European ancestry, and to fine-map across the associated genomic interval. RESEARCH DESIGN AND METHODS We performed association studies in 12 independent cohorts comprising a total of >45,000 individuals representing several ancestral groups (whites from Northern and Southern Europe, whites from the United States, African Americans from the United States, Hispanics of Caribbean origin, and Chinese, Malays and Asian Indians from Singapore). We conducted genetic fine-mapping across the ∼417 kilobase region of linkage disequilibrium spanning GCKR and 16 other genes on chromosome 2p23 by imputing untyped HapMap SNPs and genotyping 104 SNPs across the associated genomic interval.. RESULTS We provide comprehensive evidence that GCKR rs780094 is associated with opposite effects on fasting plasma triglyceride (p meta =3x10 -56 ) and glucose (p meta =1x10 -13 ) concentrations. In addition, we confirmed recent reports that the same SNP is associated with C-reative protein level (p=5x10 -5 ). Both fine mapping approaches revealed a common missense GCKR variant (rs1260326, Pro446Leu, 34% frequency, r 2 =0.93 with rs780094) as the strongest association signal in the region. CONCLUSIONS- These findings point to a molecular mechanism in humans by which higher triglycerides and C-reactive protein can be coupled with lower plasma glucose concentrations and position GCKR in central pathways regulating both hepatic triglyceride and glucose metabolism.