scispace - formally typeset
Search or ask a question

Showing papers by "University of Louisville published in 2008"


Journal ArticleDOI
TL;DR: It is suggested that microRNA profiling of circulating tumor exosomes could potentially be used as surrogate diagnostic markers for biopsy profiling, extending its utility to screening asymptomatic populations.

2,296 citations


Journal ArticleDOI
TL;DR: The significant difference in total exosome and miRNA levels between lung cancer patients and controls, and the similarity between the circulating exosomal miRNAs and the tumor-derived miRNA patterns, suggest that circulating exOSomal miRNA might be useful as a screening test for lung adenocarcinoma.

1,199 citations


Journal ArticleDOI
TL;DR: This guideline provides evidence-based recommendations on managing benign paroxysmal positional vertigo (BPPV), which is the most common vestibular disorder in adults, with a lifetime prevalence of 2.4 percent.
Abstract: Objective This update of a 2008 guideline from the American Academy of Otolaryngology-Head and Neck Surgery Foundation provides evidence-based recommendations to benign paroxysmal positional vertigo (BPPV), defined as a disorder of the inner ear characterized by repeated episodes of positional vertigo. Changes from the prior guideline include a consumer advocate added to the update group; new evidence from 2 clinical practice guidelines, 20 systematic reviews, and 27 randomized controlled trials; enhanced emphasis on patient education and shared decision making; a new algorithm to clarify action statement relationships; and new and expanded recommendations for the diagnosis and management of BPPV. Purpose The primary purposes of this guideline are to improve the quality of care and outcomes for BPPV by improving the accurate and efficient diagnosis of BPPV, reducing the inappropriate use of vestibular suppressant medications, decreasing the inappropriate use of ancillary testing such as radiographic imaging, and increasing the use of appropriate therapeutic repositioning maneuvers. The guideline is intended for all clinicians who are likely to diagnose and manage patients with BPPV, and it applies to any setting in which BPPV would be identified, monitored, or managed. The target patient for the guideline is aged ≥18 years with a suspected or potential diagnosis of BPPV. The primary outcome considered in this guideline is the resolution of the symptoms associated with BPPV. Secondary outcomes considered include an increased rate of accurate diagnoses of BPPV, a more efficient return to regular activities and work, decreased use of inappropriate medications and unnecessary diagnostic tests, reduction in recurrence of BPPV, and reduction in adverse events associated with undiagnosed or untreated BPPV. Other outcomes considered include minimizing costs in the diagnosis and treatment of BPPV, minimizing potentially unnecessary return physician visits, and maximizing the health-related quality of life of individuals afflicted with BPPV. Action Statements The update group made strong recommendations that clinicians should (1) diagnose posterior semicircular canal BPPV when vertigo associated with torsional, upbeating nystagmus is provoked by the Dix-Hallpike maneuver, performed by bringing the patient from an upright to supine position with the head turned 45° to one side and neck extended 20° with the affected ear down, and (2) treat, or refer to a clinician who can treat, patients with posterior canal BPPV with a canalith repositioning procedure. The update group made a strong recommendation against postprocedural postural restrictions after canalith repositioning procedure for posterior canal BPPV. The update group made recommendations that the clinician should (1) perform, or refer to a clinician who can perform, a supine roll test to assess for lateral semicircular canal BPPV if the patient has a history compatible with BPPV and the Dix-Hallpike test exhibits horizontal or no nystagmus; (2) differentiate, or refer to a clinician who can differentiate, BPPV from other causes of imbalance, dizziness, and vertigo; (3) assess patients with BPPV for factors that modify management, including impaired mobility or balance, central nervous system disorders, a lack of home support, and/or increased risk for falling; (4) reassess patients within 1 month after an initial period of observation or treatment to document resolution or persistence of symptoms; (5) evaluate, or refer to a clinician who can evaluate, patients with persistent symptoms for unresolved BPPV and/or underlying peripheral vestibular or central nervous system disorders; and (6) educate patients regarding the impact of BPPV on their safety, the potential for disease recurrence, and the importance of follow-up. The update group made recommendations against (1) radiographic imaging for a patient who meets diagnostic criteria for BPPV in the absence of additional signs and/or symptoms inconsistent with BPPV that warrant imaging, (2) vestibular testing for a patient who meets diagnostic criteria for BPPV in the absence of additional vestibular signs and/or symptoms inconsistent with BPPV that warrant testing, and (3) routinely treating BPPV with vestibular suppressant medications such as antihistamines and/or benzodiazepines. The guideline update group provided the options that clinicians may offer (1) observation with follow-up as initial management for patients with BPPV and (2) vestibular rehabilitation, either self-administered or with a clinician, in the treatment of BPPV.

979 citations


Journal ArticleDOI
TL;DR: An overview of the fundamental principles of operation of this technology and the influence of geometric and software parameters on image quality and patient radiation dose are provided.

919 citations


Journal ArticleDOI
TL;DR: A review of prospectively collected patient-reported outcomes data shows the minimum detectable change (MDC) appears as a statistically and clinically appropriate MCID value.

911 citations


Journal ArticleDOI
17 Jan 2008-Nature
TL;DR: It is found that partial loss of function of the ribosomal subunit protein RPS14 phenocopies the disease in normal haematopoietic progenitor cells, and also that forced expression of RPS 14 rescues the disease phenotype in patient-derived bone marrow cells.
Abstract: Somatic chromosomal deletions in cancer are thought to indicate the location of tumour suppressor genes, by which a complete loss of gene function occurs through biallelic deletion, point mutation or epigenetic silencing, thus fulfilling Knudson's two-hit hypothesis. In many recurrent deletions, however, such biallelic inactivation has not been found. One prominent example is the 5q- syndrome, a subtype of myelodysplastic syndrome characterized by a defect in erythroid differentiation. Here we describe an RNA-mediated interference (RNAi)-based approach to discovery of the 5q- disease gene. We found that partial loss of function of the ribosomal subunit protein RPS14 phenocopies the disease in normal haematopoietic progenitor cells, and also that forced expression of RPS14 rescues the disease phenotype in patient-derived bone marrow cells. In addition, we identified a block in the processing of pre-ribosomal RNA in RPS14-deficient cells that is functionally equivalent to the defect in Diamond-Blackfan anaemia, linking the molecular pathophysiology of the 5q- syndrome to a congenital syndrome causing bone marrow failure. These results indicate that the 5q- syndrome is caused by a defect in ribosomal protein function and suggest that RNAi screening is an effective strategy for identifying causal haploinsufficiency disease genes.

865 citations


Journal ArticleDOI
01 Feb 2008-Science
TL;DR: The results show that the mammalian oocyte serves as the headquarters of programming of follicleactivation and that the oocyte PTEN-PI3K pathway governs follicle activation through control of initiation of oocyte growth.
Abstract: In the mammalian ovary, progressive activation of primordial follicles from the dormant pool serves as the source of fertilizable ova. Menopause, or the end of female reproductive life, occurs when the primordial follicle pool is exhausted. However, the molecular mechanisms underlying follicle activation are poorly understood. We provide genetic evidence that in mice lacking PTEN (phosphatase and tensin homolog deleted on chromosome 10) in oocytes, a major negative regulator of phosphatidylinositol 3-kinase (PI3K), the entire primordial follicle pool becomes activated. Subsequently, all primordial follicles become depleted in early adulthood, causing premature ovarian failure (POF). Our results show that the mammalian oocyte serves as the headquarters of programming of follicle activation and that the oocyte PTEN-PI3K pathway governs follicle activation through control of initiation of oocyte growth.

736 citations


Journal ArticleDOI
17 Jul 2008-Oncogene
TL;DR: The demonstration that miR-21 promotes cell transformation supports the concept that mir-21 functions as an oncogene by a mechanism that involves translational repression of the tumor suppressor Pdcd4.
Abstract: MicroRNAs (miRNAs) are small noncoding RNA molecules that negatively control expression of target genes in animals and plants. The microRNA-21 gene (mir-21) has been identified as the only miRNA commonly overexpressed in solid tumors of the lung, breast, stomach, prostate, colon, brain, head and neck, esophagus and pancreas. We initiated a screen to identify miR-21 target genes using a reporter assay and identified a potential miR-21 target in the 3'-UTR of the programmed cell death 4 (PDCD4) gene. We cloned the full-length 3'-UTR of human PDCD4 downstream of a reporter and found that mir-21 downregulated, whereas a modified antisense RNA to miR-21 upregulated reporter activity. Moreover, deletion of the putative miR-21-binding site (miRNA regulatory element, MRE) from the 3'-UTR of PDCD4, or mutations in the MRE abolished the ability of miR-21 to inhibit reporter activity, indicating that this MRE is a critical regulatory region. Western blotting showed that Pdcd4 protein levels were reduced by miR-21 in human and mouse cells, whereas quantitative real-time PCR revealed little difference at the mRNA level, suggesting translational regulation. Finally, overexpression of mir-21 in MCF-7 human breast cancer cells and mouse epidermal JB6 cells promoted soft agar colony formation by downregulating Pdcd4 protein levels. The demonstration that miR-21 promotes cell transformation supports the concept that mir-21 functions as an oncogene by a mechanism that involves translational repression of the tumor suppressor Pdcd4.

689 citations


Journal ArticleDOI
TL;DR: The utility of an “activity score” (AS) system to simplify genotype interpretation and improve phenotype prediction was evaluated and was most accurate if ethnicity was considered; among subjects with genotypes containing a CYP2D6*2 allele, CYP1D6 activity was significantly slower in African Americans compared to Caucasians.
Abstract: Inferring CYP2D6 phenotype from genotype is increasingly challenging, considering the growing number of alleles and their range of activity. This complexity poses a challenge in translational research where genotyping is being considered as a tool to personalize drug therapy. To simplify genotype interpretation and improve phenotype prediction, we evaluated the utility of an "activity score" (AS) system. Over 25 CYP2D6 allelic variants were genotyped in 672 subjects of primarily Caucasian and African-American heritage. The ability of genotype and AS to accurately predict phenotype using the CYP2D6 probe substrate dextromethorphan was evaluated using linear regression and clustering methods. Phenotype prediction, given as a probability for each AS group, was most accurate if ethnicity was considered; among subjects with genotypes containing a CYP2D6*2 allele, CYP2D6 activity was significantly slower in African Americans compared to Caucasians. The AS tool warrants further prospective evaluation for CYP2D6 substrates and in additional ethnic populations.

680 citations


Journal ArticleDOI
TL;DR: Three studies provide the first extensive effort to understand the correlates of the search for meaning in a multistudy research program, and highlight the importance of basic personality dispositions in understanding theSearch for meaning and its correlates.
Abstract: Although several theories assert that understanding the search for meaning in life is important, empirical research on this construct is sparse. Three studies provide the first extensive effort to understand the correlates of the search for meaning in a multistudy research program. Assessed were relations between search for meaning and well-being, cognitive style, and the Big Five, Big Three, Approach/Avoidance, and Interest models of personality, with a particular emphasis on understanding the correlates of search for meaning that are independent of presence of meaning. Conceptual models of the relation between search and presence were tested. Findings suggest that people lacking meaning search for it; the search for meaning did not appear to lead to its presence. Study 3 found that basic motive dispositions moderated relations between search for meaning and its presence. Results highlight the importance of basic personality dispositions in understanding the search for meaning and its correlates.

672 citations


Journal ArticleDOI
TL;DR: An overview of recent literature on the structure and stability of unimolecular G-rich quadruplex structures that are relevant to drug design and for in vivo function and the unifying theme in this review is energetics.
Abstract: In this review, we give an overview of recent literature on the structure and stability of unimolecular G-rich quadruplex structures that are relevant to drug design and for in vivo function The unifying theme in this review is energetics The thermodynamic stability of quadruplexes has not been studied in the same detail as DNA and RNA duplexes, and there are important differences in the balance of forces between these classes of folded oligonucleotides We provide an overview of the principles of stability and where available the experimental data that report on these principles Significant gaps in the literature have been identified, that should be filled by a systematic study of well-defined quadruplexes not only to provide the basic understanding of stability both for design purposes, but also as it relates to in vivo occurrence of quadruplexes Techniques that are commonly applied to the determination of the structure, stability and folding are discussed in terms of information content and limitations Quadruplex structures fold and unfold comparatively slowly, and DNA unwinding events associated with transcription and replication may be operating far from equilibrium The kinetics of formation and resolution of quadruplexes, and methodologies are discussed in the context of stability and their possible biological occurrence

Journal ArticleDOI
TL;DR: A role of AMP-activated protein kinase (AMPK) as a potent counterregulator of inflammatory signaling pathways in macrophages is demonstrated and it is found that AMPK negatively regulated LPS-induced IκB-α degradation and positively regulated Akt activation, accompanied by inhibition of glycogen synthase kinase β and activation of CREB.
Abstract: Herein, we demonstrate a role of AMP-activated protein kinase (AMPK) as a potent counterregulator of inflammatory signaling pathways in macrophages. Stimulation of macrophages with anti-inflammatory cytokines (i.e., IL-10 and TGFβ) resulted in the rapid phosphorylation/activation of AMPK, whereas stimulation of macrophages with a proinflammatory stimulus (LPS) resulted in AMPK dephosphorylation/inactivation. Inhibition of AMPKα expression by RNA interference dramatically increased the mRNA levels of LPS-induced TNF-α, IL-6, and cyclooxygenase-2. Likewise, expression of a dominant negative AMPKα1 in macrophages enhanced TNF-α and IL-6 protein synthesis in response to LPS stimulation, while diminishing the production of IL-10. In contrast, transfection of macrophages with a constitutively active form of AMPKα1 resulted in decreased LPS-induced TNF-α and IL-6 production, and heightened production of IL-10. In addition, we found that AMPK negatively regulated LPS-induced IκB-α degradation and positively regulated Akt activation, accompanied by inhibition of glycogen synthase kinase β and activation of CREB. Thus, AMPK directs signaling pathways in macrophages in a manner that suppresses proinflammatory responses and promotes macrophage polarization to an anti-inflammatory functional phenotype.

Journal ArticleDOI
TL;DR: In this paper, the authors reviewed the available literature on positive airway pressure (PAP) titration for sleep related breathing disorders (SRBDs), including obstructive sleep apnea (OSA).
Abstract: Positive airway pressure (PAP) devices are used to treat patients with sleep related breathing disorders (SRBDs), including obstructive sleep apnea (OSA). After a patient is diagnosed with OSA, the current standard of practice involves performing attended polysomnography (PSG), during which positive airway pressure is adjusted throughout the recording period to determine the optimal pressure for maintaining upper airway patency. Continuous positive airway pressure (CPAP) and bilevel positive airway pressure (BPAP) represent the two forms of PAP that are manually titrated during PSG to determine the single fixed pressure of CPAP or the fixed inspiratory and expiratory positive airway pressures (IPAP and EPAP, respectively) of BPAP for subsequent nightly usage. A PAP Titration Task Force of the American Academy of Sleep Medicine reviewed the available literature. Based on this review, the Task Force developed these recommendations for conducting CPAP and BPAP titrations. Major recommendations are as follows: (1) All potential PAP titration candidates should receive adequate PAP education, hands-on demonstration, careful mask fitting, and acclimatization prior to titration. (2) CPAP (IPAP and/or EPAP for patients on BPAP) should be increased until the following obstructive respiratory events are eliminated (no specific order) or the recommended maximum CPAP (IPAP for patients on BPAP) is reached: apneas, hypopneas, respiratory effort-related arousals (RERAs), and snoring. (3) The recommended minimum starting CPAP should be 4 cm H2O for pediatric and adult patients, and the recommended minimum starting IPAP and EPAP should be 8 cm H2O and 4 cm H2O, respectively, for pediatric and adult patients on BPAP. (4) The recommended maximum CPAP should be 15 cm H2O (or recommended maximum IPAP of 20 cm H2O if on BPAP) for patients or = 12 years. (5) The recommended minimum IPAP-EPAP differential is 4 cm H2O and the recommended maximum IPAP-EPAP differential is 10 cm H2O (6) CPAP (IPAP and/or EPAP for patients on BPAP depending on the type of event) should be increased by at least 1 cm H2O with an interval no shorter than 5 min, with the goal of eliminating obstructive respiratory events. (7) CPAP (IPAP and EPAP for patients on BPAP) should be increased from any CPAP (or IPAP) level if at least 1 obstructive apnea is observed for patients or = 12 years. (8) CPAP (IPAP for patients on BPAP) should be increased from any CPAP (or IPAP) level if at least 1 hypopnea is observed for patients or = 12 years. (9) CPAP (IPAP for patients on BPAP) should be increased from any CPAP (or IPAP) level if at least 3 RERAs are observed for patients or = 12 years. (10) CPAP (IPAP for patients on BPAP) may be increased from any CPAP (or IPAP) level if at least 1 min of loud or unambiguous snoring is observed for patients or = 12 years. (11) The titration algorithm for split-night CPAP or BPAP titration studies should be identical to that of full-night CPAP or BPAP titration studies, respectively. (12) If the patient is uncomfortable or intolerant of high pressures on CPAP, the patient may be tried on BPAP. If there are continued obstructive respiratory events at 15 cm H2O of CPAP during the titration study, the patient may be switched to BPAP. (13) The pressure of CPAP or BPAP selected for patient use following the titration study should reflect control of the patient's obstructive respiration by a low (preferably 3 hr).

Journal ArticleDOI
TL;DR: The possible functions of cathepsin D and its various forms in cells and organisms during physiological and pathological conditions are reviewed.
Abstract: For years, it has been held that cathepsin D (CD) is involved in rather non-specific protein degradation in a strongly acidic milieu of lysosomes. Studies with CD knock-out mice revealed that CD is not necessary for embryonal development, but it is indispensable for postnatal tissue homeostasis. Mutation that abolishes CD enzymatic activity causes neuronal ceroid lipofuscinosis (NCL) characterized by severe neurodegeneration, developmental regression, visual loss and epilepsy in both animals and humans. In the last decade, however, an increasing number of studies demonstrated that enzymatic function of CD is not restricted solely to acidic milieu of lysosomes with important consequences in regulation of apoptosis. In addition to CD enzymatic activity, it has been shown that apoptosis is also regulated by catalytically inactive mutants of CD which suggests that CD interacts with other important molecules and influences cell signaling. Moreover, procathepsin D (pCD), secreted from cancer cells, acts as a mitogen on both cancer and stromal cells and stimulates their pro-invasive and pro-metastatic properties. Numerous studies found that pCD/CD level represents an independent prognostic factor in a variety of cancers and is therefore considered to be a potential target of anti-cancer therapy. Studies dealing with functions of cathepsin D are complicated by the fact that there are several simultaneous forms of CD in a cell—pCD, intermediate enzymatically active CD and mature heavy and light chain CD. It became evident that these forms may differently regulate the above-mentioned processes. In this article, we review the possible functions of CD and its various forms in cells and organisms during physiological and pathological conditions.

Journal ArticleDOI
TL;DR: The results show that classifier performance deteriorates with even modest class imbalance in the training data and it is shown that BP is generally preferable over PSO for imbalanced training data especially with small data sample and large number of features.

Journal ArticleDOI
TL;DR: The vaccine adjuvant monophosphoryl lipid A is a detoxified form of the endotoxin lipopolysaccharide, and is among the first of a new generation of Toll-like receptor agonists likely to be used as vaccine adjuvants on a mass scale in human populations.
Abstract: The development of non-infectious subunit vaccines greatly increases the safety of prophylactic immunization, but also reinforces the need for a new generation of immunostimulatory adjuvants. Because adverse effects are a paramount concern in prophylactic immunization, few new adjuvants have received approval for use anywhere in the developed world. The vaccine adjuvant monophosphoryl lipid A is a detoxified form of the endotoxin lipopolysaccharide, and is among the first of a new generation of Toll-like receptor agonists likely to be used as vaccine adjuvants on a mass scale in human populations. Much remains to be learned about this compound’s mechanism of action, but recent developments have made clear that it is unlikely to be simply a weak version of lipopolysaccharide. Instead, monophosphoryl lipid A’s structure seems to have fortuitously retained several functions needed for stimulation of adaptive immune responses, while shedding those associated with pro-inflammatory side effects.

Journal ArticleDOI
TL;DR: The hypothesis that high fructose consumption may not only lead to liver damage through overfeeding but also may be directly pro-inflammatory by increasing intestinal translocation of endotoxin is supported.

Proceedings Article
01 Jan 2008
TL;DR: In this paper, two methods of neural network training are explored: classical backpropagation (BP) and particle swarm optimization (PSO) with clinically relevant training criteria for computer-aided medical diagnosis.
Abstract: This study investigates the effect of class imbalance in training data when developing neural network classifiers for computer-aided medical diagnosis. The investigation is performed in the presence of other characteristics that are typical among medical data, namely small training sample size, large number of features, and correlations between features. Two methods of neural network training are explored: classical backpropagation (BP) and particle swarm optimization (PSO) with clinically relevant training criteria. An experimental study is performed using simulated data and the conclusions are further validated on real clinical data for breast cancer diagnosis. The results show that classifier performance deteriorates with even modest class imbalance in the training data. Further, it is shown that BP is generally preferable over PSO for imbalanced training data especially with small data sample and large number of features. Finally, it is shown that there is no clear preference between oversampling and no compensation approach and some guidance is provided regarding a proper selection.

Journal ArticleDOI
TL;DR: This paper found that eudaimonic behaviors were more strongly related to well-being than behaviors directed toward obtaining pleasure or material goods, and that doing good may be an important avenue by which people create meaningful and satisfying lives.

Journal ArticleDOI
TL;DR: SMART-COP is a simple, practical clinical tool for accurately predicting the need for IRVS that is likely to assist clinicians in determining CAP severity.
Abstract: BACKGROUND: Existing severity assessment tools, such as the pneumonia severity index (PSI) and CURB-65 (tool based on confusion, urea level, respiratory rate, blood pressure, and age >or=65 years), predict 30-day mortality in community-acquired pneumonia (CAP) and have limited ability to predict which patients will require intensive respiratory or vasopressor support (IRVS). METHODS: The Australian CAP Study (ACAPS) was a prospective study of 882 episodes in which each patient had a detailed assessment of severity features, etiology, and treatment outcomes. Multivariate logistic regression was performed to identify features at initial assessment that were associated with receipt of IRVS. These results were converted into a simple points-based severity tool that was validated in 5 external databases, totaling 7464 patients. RESULTS: In ACAPS, 10.3% of patients received IRVS, and the 30-day mortality rate was 5.7%. The features statistically significantly associated with receipt of IRVS were low systolic blood pressure (2 points), multilobar chest radiography involvement (1 point), low albumin level (1 point), high respiratory rate (1 point), tachycardia (1 point), confusion (1 point), poor oxygenation (2 points), and low arterial pH (2 points): SMART-COP. A SMART-COP score of >or=3 points identified 92% of patients who received IRVS, including 84% of patients who did not need immediate admission to the intensive care unit. Accuracy was also high in the 5 validation databases. Sensitivities of PSI and CURB-65 for identifying the need for IRVS were 74% and 39%, respectively. CONCLUSIONS: SMART-COP is a simple, practical clinical tool for accurately predicting the need for IRVS that is likely to assist clinicians in determining CAP severity.

Journal ArticleDOI
TL;DR: In this paper, the authors explored whether the relationships among public service motivation, job satisfaction, and the turnover intentions of public employees were mediated by P-O fit, and they found that PSM had no significant relationship to the job satisfaction and turnover intentions when the person-organization (P-O) fit was considered.
Abstract: Many in public administration hypothesize that public service motivation (PSM) has a direct positive impact on the attitudes and behaviors of public employees. However, there are inconsistencies in the PSM literature that challenge this hypothesis. This study sought to find out whether person-organization (P-O) fit can provide a reason for these inconsistencies. Specifically, this study explored whether the relationships among PSM, job satisfaction, and the turnover intentions of public employees were mediated by P-O fit. Using a sample of 205 employees drawn from three public organizations in the states of Oregon, Indiana, and Kentucky, this study found that PSM had no significant relationship to the job satisfaction and turnover intentions of public employees when P-O fit was considered. The implications of this study and areas of future research are discussed.

Journal Article
TL;DR: The evidence for the effectiveness of long-term opioids in reducing pain and improving functional status for 6 months or longer is variable and the recommendation is 2A - weak recommendation, high-quality evidence: with benefits closely balanced with risks and burdens.
Abstract: BACKGROUND Opioid abuse has continued to increase at an alarming rate since our last opioid guidelines were published in 2005. Available evidence suggests a continued wide variance in the use of opioids, as documented by different medical specialties, medical boards, advocacy groups, and the Drug Enforcement Administration. OBJECTIVES The objectives of opioid guidelines by the American Society of Interventional Pain Physicians (ASIPP) are to provide guidance for the use of opioids for the treatment of chronic non-cancer pain, to bring consistency in opioid philosophy among the many diverse groups involved, to improve the treatment of chronic non-cancer pain, and to reduce the incidence of abuse and drug diversion. DESIGN A broadly based policy committee of recognized experts in the field evaluated the available literature regarding opioid use in managing chronic non-cancer pain. This resulted in the formulation of the review and update of the guidelines published in 2006, a series of potential evidence linkages representing conclusions, followed by statements regarding the relationships between clinical interventions and outcomes. METHODS The elements of the guideline preparation process included literature searches, literature synthesis, consensus evaluation, open forum presentations, formal endorsement by the Board of Directors of the American Society of Interventional Pain Physicians, and peer review. Based on the criteria of the U.S. Preventive Services Task Force, the quality of evidence was designated as Level I, II, and III, with 3 subcategories in Level II, with Level I described as strong and Level III as indeterminate. The recommendations were provided from 1A to 2C, varying from strong recommendation with high quality evidence to weak recommendation with low-quality or very low-quality evidence. RESULTS After an extensive review and analysis of the literature, which included systematic reviews and all of the available literature, the evidence for the effectiveness of long-term opioids in reducing pain and improving functional status for 6 months or longer is variable. The evidence for transdermal fentanyl and sustained-release morphine is Level II-2, whereas for oxycodone the level of evidence is II-3, and the evidence for hydrocodone and methadone is Level III. There is also significant evidence of misuse and abuse of opioids. The recommendation is 2A - weak recommendation, high-quality evidence: with benefits closely balanced with risks and burdens; with evidence derived from RCTs without important limitations or overwhelming evidence from observational studies, with the implication that with a weak recommendation, best action may differ depending on circumstances or patients' or societal values. CONCLUSION Opioids are commonly prescribed for chronic non-cancer pain and may be effective for short-term pain relief. However, long-term effectiveness of 6 months or longer is variable with evidence ranging from moderate for transdermal fentanyl and sustained-release morphine with a Level II-2, to limited for oxycodone with a Level II-3, and indeterminate for hydrocodone and methadone with a Level III. These guidelines included the evaluation of the evidence for the use of opioids in the management of chronic non-cancer pain and the recommendations for that management. These guidelines are based on the best available evidence and do not constitute inflexible treatment recommendations. Because of the changing body of evidence, this document is not intended to be a \"standard of care.\

Journal ArticleDOI
TL;DR: This paper surveys many existing schemes in the literature of background removal, surveying the common pre-processing algorithms used in different situations, presenting different background models, and the most commonly used ways to update such models and how they can be initialized.
Abstract: Identifying moving objects is a critical task for many computer vision applications; it provides a classification of the pixels into either foreground or background. A common approach used to achieve such classification is background removal. Even though there exist numerous of background removal algorithms in the literature, most of them follow a simple flow diagram, passing through four major steps, which are pre-processing, background modelling, foreground de- tection and data validation. In this paper, we survey many existing schemes in the literature of background removal, sur- veying the common pre-processing algorithms used in different situations, presenting different background models, and the most commonly used ways to update such models and how they can be initialized. We also survey how to measure the performance of any moving object detection algorithm, whether the ground truth data is available or not, presenting per- formance metrics commonly used in both cases.

Journal ArticleDOI
TL;DR: In this article, the authors showed that SnO2 nanowire-based dye-sensitized solar cells exhibit an open circuit voltage of 560mV, which is 200mV higher than that using nanoparticles.
Abstract: In this report, we show for the first time that SnO2 nanowire based dye sensitized solar cells exhibit an open circuit voltage of 560 mV, which is 200 mV higher than that using SnO2 nanoparticle based cells. This is attributed to the more negative flat band potential of nanowires compared to the nanoparticles as determined by open circuit photo voltage measurements made at high light intensities. The nanowires were employed in hybrid structures consisting of highly interconnected SnO2 nanowire matrix coated with TiO2 nanoparticles, which showed an open circuit voltage of 720 mV and an efficiency of 4.1% compared to 2.1% obtained with pure SnO2 nanowire matrix. The electron transport time constants for SnO2 nanowire matrix were an order of magnitude lower and the recombination time constants are about 100 times higher than that of TiO2 nanoparticles. The higher efficiency observed for DSSCs based on hybrid structure is attributed to the band edge positions of SnO2 relative to that of TiO2 and faster electron transport in SnO2 nanowires.

Journal ArticleDOI
TL;DR: The results suggest that team history may be necessary but not sufficient for teams to overcome the problems with the use of lean digital networks as a communication environment, but may present a window of opportunity for social capital to develop, which in turn allows teams to perform just as well as in either communication environment.
Abstract: To understand the impact of social capital on knowledge integration and performance within digitally enabled teams, we studied 46 teams who had a history and a future working together. All three dimensions of their social capital (structural, relational, and cognitive) were measured prior to the team performing two tasks in a controlled setting, one face-to-face and the other through a lean digital network. Structural and cognitive capital were more important to knowledge integration when teams communicated through lean digital networks than when they communicated face-to-face; relational capital directly impacted knowledge integration equally, regardless of the communication media used by the team. Knowledge integration, in turn, impacted team decision quality, suggesting that social capital influences team performance in part by increasing a team’s ability to integrate knowledge. These results suggest that team history may be necessary but not sufficient for teams to overcome the problems with the use of lean digital networks as a communication environment. However, team history may present a window of opportunity for social capital to develop, which in turn allows teams to perform just as well as in either communication environment.

Journal ArticleDOI
TL;DR: The aldo-keto reductase (AKR) superfamily comprises enzymes that catalyze redox transformations involved in biosynthesis, intermediary metabolism, and detoxification that play an important role in the phase II detoxification of a large number of pharmaceuticals, drugs, and xenobiotics.
Abstract: The aldo-keto reductase (AKR) superfamily comprises enzymes that catalyze redox transformations involved in biosynthesis, intermediary metabolism, and detoxification. Substrates of AKRs include glucose, steroids, glycosylation end-products, lipid peroxidation products, and environmental pollutants. These proteins adopt a (β /α )8 barrel structural motif interrupted by a number of extraneous loops and helixes that vary between proteins and bring structural identity to individual families. The human AKR family differs from the rodent families. Due to their broad substrate specificity, AKRs play an important role in the phase II detoxification of a large number of pharmaceuticals, drugs, and xenobiotics.

Journal ArticleDOI
01 Dec 2008-Alcohol
TL;DR: It is concluded that patients with alcohol-induced liver injury have altered bowel flora compared to healthy controls and short-term oral supplementation with B. bifidum and L. plantarum 8PA3 was associated with restoration of the bowel flora and greater improvement in alcohol- induced liver injury than standard therapy alone.

Journal ArticleDOI
TL;DR: In this paper, the authors compared laparoscopic left-sided pancreatectomy (LLP) with traditional open-left-sided pancreatic surgery (OLP) in a multicenter experience.
Abstract: OBJECTIVES To compare perioperative outcomes of laparoscopic left-sided pancreatectomy (LLP) with traditional open left-sided pancreatectomy (OLP) in a multicenter experience. SUMMARY AND BACKGROUND DATA LLP is being performed more commonly with limited data comparing results with outcomes from OLP. METHODS Data from 8 centers were combined for all cases performed between 2002-2006. OLP and LLP cohorts were matched by age, American Society of Anesthesiologists, resected pancreas length, tumor size, and diagnosis. Multivariate analysis was performed using binary logistic regression. RESULTS Six hundred sixty-seven LPs were performed, with 159 (24%) attempted laparoscopically. Indications were solid lesion in 307 (46%), cystic in 295 (44%), and pancreatitis in 65 (10%) cases. Positive margins occurred in 51 (8%) cases, 335 (50%) had complications, and significant leaks occurred in 108 (16%). Conversion to OLP occurred in 20 (13%) of the LLPs. In the matched comparison, 200 OLPs were compared with 142 LLPs. There were no differences in positive margin rates (8% vs. 7%, P = 0.8), operative times (216 vs. 230 minutes, P = 0.3), or leak rates (18% vs. 11%, P = 0.1). LLP patients had lower average blood loss (357 vs. 588 mL, P < 0.01), fewer complications (40% vs. 57%, P < 0.01), and shorter hospital stays (5.9 vs. 9.0 days, P < 0.01). By MVA, LLP was an independent factor for shorter hospital stay (P < 0.01, odds ratio 0.33, 95% confidence interval 0.19-0.56). CONCLUSIONS In selected patients, LLP is associated with less morbidity and shorter LOS than OLP. Pancreatic fistula rates are similar for OLP and LLP. LLP is appropriate for selected patients with left-sided pancreatic pathology.

Journal ArticleDOI
TL;DR: 3PO markedly attenuates the proliferation of several human malignant hematopoietic and adenocarcinoma cell lines and is selectively cytostatic to ras-transformed human bronchial epithelial cells relative to normal human bronachial epithel cells.
Abstract: 6-phosphofructo-1-kinase, a rate-limiting enzyme of glycolysis, is activated in neoplastic cells by fructose-2,6-bisphosphate (Fru-2,6-BP), a product of four 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isozymes (PFKFB1-4). The inducible PFKFB3 isozyme is constitutively expressed by neoplastic cells and required for the high glycolytic rate and anchorage-independent growth of ras-transformed cells. We report herein the computational identification of a small-molecule inhibitor of PFKFB3, 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO), which suppresses glycolytic flux and is cytostatic to neoplastic cells. 3PO inhibits recombinant PFKFB3 activity, suppresses glucose uptake, and decreases the intracellular concentration of Fru-2,6-BP, lactate, ATP, NAD+, and NADH. 3PO markedly attenuates the proliferation of several human malignant hematopoietic and adenocarcinoma cell lines (IC50, 1.4-24 micromol/L) and is selectively cytostatic to ras-transformed human bronchial epithelial cells relative to normal human bronchial epithelial cells. The PFKFB3 enzyme is an essential molecular target of 3PO because transformed cells are rendered resistant to 3PO by ectopic expression of PFKFB3 and sensitive to 3PO by heterozygotic genomic deletion of PFKFB3. Importantly, i.p. administration of 3PO (0.07 mg/g) to tumor-bearing mice markedly reduces the intracellular concentration of Fru-2,6-BP, glucose uptake, and growth of established tumors in vivo. Taken together, these data support the clinical development of 3PO and other PFKFB3 inhibitors as chemotherapeutic agents.

Journal ArticleDOI
TL;DR: The current understanding regarding the role of NF-κB in skeletal muscle with particular reference to different models of muscle wasting and the development of novel therapy is outlined.
Abstract: Skeletal muscle atrophy/wasting is a serious complication of a wide range of diseases and conditions such as aging, disuse, AIDS, chronic obstructive pulmonary disease, space travel, muscular dystrophy, chronic heart failure, sepsis, and cancer. Emerging evidence suggests that nuclear factor-kappa B (NF-κB) is one of the most important signaling pathways linked to the loss of skeletal muscle mass in various physiological and pathophysiological conditions. Activation of NF-κB in skeletal muscle leads to degradation of specific muscle proteins, induces inflammation and fibrosis, and blocks the regeneration of myofibers after injury/atrophy. Recent studies employing genetic mouse models have provided strong evidence that NF-κB can serve as an important molecular target for the prevention of skeletal muscle loss. In this article, we have outlined the current understanding regarding the role of NF-κB in skeletal muscle with particular reference to different models of muscle wasting and the development of novel therapy.