Showing papers by "University at Buffalo published in 2005"

TM-align: a protein structure alignment algorithm based on the TM-score.

Abstract: We have developed TM-align, a new algorithm to identify the best structural alignment between protein pairs that combines the TM-score rotation matrix and Dynamic Programming (DP). The algorithm is approximately 4 times faster than CE and 20 times faster than DALI and SAL. On average, the resulting structure alignments have higher accuracy and coverage than those provided by these most often-used methods. TM-align is applied to an all-against-all structure comparison of 10 515 representative protein chains from the Protein Data Bank (PDB) with a sequence identity cutoff <95%: 1996 distinct folds are found when a TM-score threshold of 0.5 is used. We also use TM-align to match the models predicted by TASSER for solved non-homologous proteins in PDB. For both folded and misfolded models, TM-align can almost always find close structural analogs, with an average root mean square deviation, RMSD, of 3 A and 87% alignment coverage. Nevertheless, there exists a significant correlation between the correctness of the predicted structure and the structural similarity of the model to the other proteins in the PDB. This correlation could be used to assist in model selection in blind protein structure predictions. The TM-align program is freely downloadable at http://bioinformatics.buffalo.edu/TM-align.

Growth, Beta and Agency Costs as Determinants of Dividend Payout Ratios

Abstract: A model of optimal dividend payout is presented in which increased dividends lower agency costs but raise the transactions cost of external financing. The optimal dividend payout ratio minimizes the sum of these two costs. A cross-sectional test of the model relates dividend payout to the fraction of equity held by insiders, the past and expected future revenue growth of the firm, the firm's beta coefficient, and the number of common stockholders. The coefficients of all variables are significant in the predicted directions. The results indicate that investment policy influences dividend policy.

Metabolic Syndrome A Comprehensive Perspective Based on Interactions Between Obesity, Diabetes, and Inflammation

Abstract: Received June 28, 2004; revision received August 26, 2004; accepted October 15, 2004 The original description of the metabolic syndrome by Reaven1 consisted of obesity, insulin resistance, hypertension, impaired glucose tolerance or diabetes, hyperinsulinemia and dyslipidemia characterized by elevated triglyceride, and low HDL concentrations All of the features described above are risk factors for atherosclerosis, and thus, metabolic syndrome constituted a significant risk for coronary heart disease2–5 (Table) The features of obesity/overweight and insulin resistance also provided a significant risk for developing type 2 diabetes5,6 The risks for coronary heart disease and diabetes with metabolic syndrome are greater than those for simple obesity alone, and therefore, an understanding of the pathogenesis and through it, a rational approach to its therapy are of prime importance View this table: Classic Biological Effects of Insulin and Classic Metabolic Syndrome Based on Resistance to the Metabolic Effects of Insulin As our understanding of the action of insulin evolves to comprehensively include the recent discoveries,7 we can better see that insulin resistance is the basis of most if not all of the features of this syndrome The original conceptualization of this syndrome was on the basis of resistance to the metabolic actions of insulin Thus, hyperinsulinemia, glucose intolerance, type 2 diabetes, hypertriglyceridemia, and low HDL concentrations could be accounted for by resistance to the actions of insulin on carbohydrate and lipid metabolism Although the features described above would to some extent explain the atherogenesis, Reaven has maintained that hyperinsulinemia itself contributes to atherogenicity, and thus, insulin is atherogenic, leading to the coronary heart disease and cerebrovascular disease associated with this syndrome Obesity probably leads to hypertension through (1) increased vascular tone created by a reduced bioavailability of NO because of increased oxidative stress,8 (2) increased asymmetric dimethylarginine (ADMA) concentrations,9 (3) increased sympathetic …

Identification of microRNAs of the herpesvirus family

Abstract: Epstein-Barr virus (EBV or HHV4), a member of the human herpesvirus (HHV) family, has recently been shown to encode microRNAs (miRNAs). In contrast to most eukaryotic miRNAs, these viral miRNAs do not have close homologs in other viral genomes or in the genome of the human host. To identify other miRNA genes in pathogenic viruses, we combined a new miRNA gene prediction method with small-RNA cloning from several virus-infected cell types. We cloned ten miRNAs in the Kaposi sarcoma-associated virus (KSHV or HHV8), nine miRNAs in the mouse gammaherpesvirus 68 (MHV68) and nine miRNAs in the human cytomegalovirus (HCMV or HHV5). These miRNA genes are expressed individually or in clusters from either polymerase (pol) II or pol III promoters, and share no substantial sequence homology with one another or with the known human miRNAs. Generally, we predicted miRNAs in several large DNA viruses, and we could neither predict nor experimentally identify miRNAs in the genomes of small RNA viruses or retroviruses.

Relations in biomedical ontologies

Abstract: To enhance the treatment of relations in biomedical ontologies we advance a methodology for providing consistent and unambiguous formal definitions of the relational expressions used in such ontologies in a way designed to assist developers and users in avoiding errors in coding and annotation. The resulting Relation Ontology can promote interoperability of ontologies and support new types of automated reasoning about the spatial and temporal dimensions of biological and medical phenomena.

A practical clinical approach to diagnosis of fetal alcohol spectrum disorders: clarification of the 1996 institute of medicine criteria.

Abstract: Background. The adverse effects of alcohol on the developing human represent a spectrum of structural anomalies and behavioral and neurocognitive disabilities, most accurately termed fetal alcohol spectrum disorders (FASD). The first descriptions in the modern medical literature of a distinctly recognizable pattern of malformations associated with maternal alcohol abuse were reported in 1968 and 1973. Since that time, substantial progress has been made in developing specific criteria for defining and diagnosing this condition. Two sets of diagnostic criteria are now used most widely for evaluation of children with potential diagnoses in the FASD continuum, ie, the 1996 Institute of Medicine (IOM) criteria and the Washington criteria. Although both approaches have improved the clinical delineation of FASD, both suffer from significant drawbacks in their practical application in pediatric practice. Objective. The purpose of this report is to present specific clarifications of the 1996 IOM criteria for the diagnosis of FASD, to facilitate their practical application in clinical pediatric practice. Methods. A large cohort of children who were prenatally exposed to alcohol were identified, through active case-ascertainment methods, in 6 Native American communities in the United States and 1 community in the Western Cape Province of South Africa. The children and their families underwent standardized multidisciplinary evaluations, including a dysmorphology examination, developmental and neuropsychologic testing, and a structured maternal interview, which gathered data about prenatal drinking practices and other demographic and family information. Data for these subjects were analyzed, and revisions and clarifications of the existing IOM FASD diagnostic categories were formulated on the basis of the results. Results. The revised IOM method defined accurately and completely the spectrum of disabilities among the children in our study. On the basis of this experience, we propose specific diagnostic criteria for fetal alcohol syndrome and partial fetal alcohol syndrome. We also define alcohol-related birth defects and alcohol-related neurodevelopmental disorder from a practical standpoint. Conclusions. The 1996 IOM criteria remain the most appropriate diagnostic approach for children prenatally exposed to alcohol. The proposed revisions presented here make these criteria applicable in clinical pediatric practice. Pediatrics 2005;115:39–47; fetal alcohol syndrome, fetal alcohol spectrum disorders, diagnostic criteria, mental retardation, developmental disabilities.

Evidence-based assessment of attention deficit hyperactivity disorder in children and adolescents.

Abstract: This article examines evidence-based assessment practices for attention deficit hyperactivity disorder (ADHD). The nature, symptoms, associated features, and comorbidity of ADHD are briefly described, followed by a selective review of the literature on the reliability and validity of ADHD assessment methods. It is concluded that symptom rating scales based on the Diagnostic and Statistical Manual of Mental Disorders (4th ed. [DSM-IV]; American Psychiatric Association, 1994), empirically and rationally derived ADHD rating scales, structured interviews, global impairment measures, and behavioral observations are evidence-based ADHD assessment methods. The most efficient assessment method is obtaining information through parent and teacher rating scales; both parent and teacher ratings are needed for clinical purposes. Brief, non-DSM based rating scales are highly correlated with DSM scales but are much more efficient and just as effective at diagnosing ADHD. No incremental validity or utility is conferred by structured interviews when parent and teacher ratings are utilized. Observational procedures are empirically valid but not practical for clinical use. However, individualized assessments of specific target behaviors approximate observations and have both validity and treatment utility. Measures of impairment that report functioning in key domains (peer, family, school) as well as globally have more treatment utility than nonspecific global measures of impairment. DSM diagnosis per se has not been demonstrated to have treatment utility, so the diagnostic phase of assessment should be completed with minimal time and expense so that resources can be focused on other aspects of assessment, particularly treatment planning. We argue that the main focus of assessment should be on target behavior selection, contextual factors, functional analyses, treatment planning, and outcome monitoring.

Randomized trials stopped early for benefit: a systematic review

Abstract: ContextRandomized clinical trials (RCTs) that stop earlier than planned because of apparent benefit often receive great attention and affect clinical practice. Their prevalence, the magnitude and plausibility of their treatment effects, and the extent to which they report information about how investigators decided to stop early are, however, unknown.ObjectiveTo evaluate the epidemiology and reporting quality of RCTs involving interventions stopped early for benefit.Data SourcesSystematic review up to November 2004 of MEDLINE, EMBASE, Current Contents, and full-text journal content databases to identify RCTs stopped early for benefit.Study SelectionRandomized clinical trials of any intervention reported as having stopped early because of results favoring the intervention. There were no exclusion criteria.Data ExtractionTwelve reviewers working independently and in duplicate abstracted data on content area and type of intervention tested, reporting of funding, type of end point driving study termination, treatment effect, length of follow-up, estimated sample size and total sample studied, role of a data and safety monitoring board in stopping the study, number of interim analyses planned and conducted, and existence and type of monitoring methods, statistical boundaries, and adjustment procedures for interim analyses and early stopping.Data SynthesisOf 143 RCTs stopped early for benefit, the majority (92) were published in 5 high-impact medical journals. Typically, these were industry-funded drug trials in cardiology, cancer, and human immunodeficiency virus/AIDS. The proportion of all RCTs published in high-impact journals that were stopped early for benefit increased from 0.5% in 1990-1994 to 1.2% in 2000-2004 (P<.001 for trend). On average, RCTs recruited 63% (SD, 25%) of the planned sample and stopped after a median of 13 (interquartile range [IQR], 3-25) months of follow-up, 1 interim analysis, and when a median of 66 (IQR, 23-195) patients had experienced the end point driving study termination (event). The median risk ratio among truncated RCTs was 0.53 (IQR, 0.28-0.66). One hundred thirty-five (94%) of the 143 RCTs did not report at least 1 of the following: the planned sample size (n = 28), the interim analysis after which the trial was stopped (n = 45), whether a stopping rule informed the decision (n = 48), or an adjusted analysis accounting for interim monitoring and truncation (n = 129). Trials with fewer events yielded greater treatment effects (odds ratio, 28; 95% confidence interval, 11-73).ConclusionsRCTs stopped early for benefit are becoming more common, often fail to adequately report relevant information about the decision to stop early, and show implausibly large treatment effects, particularly when the number of events is small. These findings suggest clinicians should view the results of such trials with skepticism.

Genomic alterations in cultured human embryonic stem cells

Abstract: Cultured human embryonic stem cell (hESC) lines are an invaluable resource because they provide a uniform and stable genetic system for functional analyses and therapeutic applications. Nevertheless, these dividing cells, like other cells, probably undergo spontaneous mutation at a rate of 10(-9) per nucleotide. Because each mutant has only a few progeny, the overall biological properties of the cell culture are not altered unless a mutation provides a survival or growth advantage. Clonal evolution that leads to emergence of a dominant mutant genotype may potentially affect cellular phenotype as well. We assessed the genomic fidelity of paired early- and late-passage hESC lines in the course of tissue culture. Relative to early-passage lines, eight of nine late-passage hESC lines had one or more genomic alterations commonly observed in human cancers, including aberrations in copy number (45%), mitochondrial DNA sequence (22%) and gene promoter methylation (90%), although the latter was essentially restricted to 2 of 14 promoters examined. The observation that hESC lines maintained in vitro develop genetic and epigenetic alterations implies that periodic monitoring of these lines will be required before they are used in in vivo applications and that some late-passage hESC lines may be unusable for therapeutic purposes.

The Antitumor Activities of Flavonoids

Abstract: The flavonoids are polyphenolic compounds found as integral components of the human diet. They are universally present as constituents of flowering plants, particularly of food plants. The flavonoids are phenyl substituted chromones (benzopyran derivatives) consisting of a 15-carbon basic skeleton (C6-C3-C6), composed of a chroman (C6-C3) nucleus (the benzo ring A and the heterocyclic ring C), also shared by the tocopherols, with a phenyl (the aromatic ring B) substitution usually at the 2-position. Different substitutions can typically occur in the rings, A and B. Several plants and spices containing flavonoid derivatives have found application as disease preventive and therapeutic agents in traditional medicine in Asia for thousands of years. The selection of a particular food plant, plant tissue or herb for its potential health benefits appears to mirror its flavonoid composition. The much lower risk of colon, prostate and breast cancers in Asians, who consume more vegetables, fruits and tea than populations in the Western hemisphere do, raises the question of whether flavonoid components mediate the protective effects of diets rich in these foodstuffs by acting as natural chemopreventive and anticancer agents. An impressive body of information exists on the antitumor action of plantflavonoids. In vitro work has concentrated on the direct and indirect actions of flavonoids on tumor cells, and has found a variety of anticancer effects such as cell growth and kinase activity inhibition, apoptosis induction, suppression of the secretion of matrix metalloproteinases and of tumor invasive behavior. Furthermore, some studies have reported the impairment of in vivo angiogenesis by dietary flavonoids. Experimental animal studies indicate that certain dietary flavonoids possess antitumor activity. The hydroxylation pattern of the B ring of the flavones and flavonols, such as luteolin and quercetin, seems to critically influence their activities, especially the inhibition of protein kinase activity and antiproliferation. The different mechanisms underlying the potential anticancer action of plant flavonoids await further elucidation. Certain dietary flavonols and flavones targeting cell surface signal transduction enzymes, such as protein tyrosine and focal adhesion kinases, and the processes of angiogenesis appear to be promising candidates as anticancer agents. Further in vivo studies of these bioactive constituents is deemed necessary in order to develop flavonoid-based anticancer strategies. In view of the increasing interest in the association between dietary flavonoids and cancer initiation and progression, this important field is likely to witness expanded effort and to attract and stimulate further vigorous investigations.

A Proposed Model Linking Inflammation to Obesity, Diabetes, and Periodontal Infections

Abstract: Background: Obesity is an important risk factor for diabetes, cardiovascular disease, and periodontal disease. Adipocytes appear to secrete proinflammatory cytokines which may be the molecules linking the pathogenesis of these diseases. We evaluated the relationship between obesity, periodontal disease, and diabetes mellitus insulin resistance as well as the plasma levels of tumor necrosis factor alpha (TNFα) and its soluble receptors (sTNFα) to assess the relationship of inflammation to obesity, diabetes, and periodontal infections.Methods: The relationship between periodontal disease, obesity, and insulin resistance was examined in the Third National Health and Nutrition Examination Survey (NHANES III). In a population of 12,367 non-diabetic subjects, the variable body mass index (BMI) was used as an assessment of obesity and periodontal disease was assessed by mean clinical attachment loss. The plasma levels of TNFα and sTNFα were assessed in subsets of 1,221 adults from Erie County, New York, who repr...

Exploring the syntax-semantics interface

Abstract: Language is a system of communication in which grammatical structures function to express meaning in context. While all languages can achieve the same basic communicative ends, they each use different means to achieve them, particularly in the divergent ways that syntax, semantics and pragmatics interact across languages. This book looks in detail at how structure, meaning, and communicative function interact in human languages. Working within the framework of Role and Reference Grammar (RRG), Van Valin proposes a set of rules, called the 'linking algorithm', which relates syntactic and semantic representations to each other, with discourse-pragmatics playing a role in the linking. Using this model, he discusses the full range of grammatical phenomena, including the structures of simple and complex sentences, verb and argument structure, voice, reflexivization and extraction restrictions. Clearly written and comprehensive, this book will be welcomed by all those working on the interface between syntax, semantics and pragmatics.

Global standard for the composition of infant formula: recommendations of an ESPGHAN coordinated international expert group.

Abstract: The Codex Alimentarius Commission of the Food and Agriculture Organization of the United Nations (FAO) and the World Health Organization (WHO) develops food standards, guidelines and related texts for protecting consumer health and ensuring fair trade practices globally. The major part of the world's population lives in more than 160 countries that are members of the Codex Alimentarius. The Codex Standard on Infant Formula was adopted in 1981 based on scientific knowledge available in the 1970s and is currently being revised. As part of this process, the Codex Committee on Nutrition and Foods for Special Dietary Uses asked the ESPGHAN Committee on Nutrition to initiate a consultation process with the international scientific community to provide a proposal on nutrient levels in infant formulae, based on scientific analysis and taking into account existing scientific reports on the subject. ESPGHAN accepted the request and, in collaboration with its sister societies in the Federation of International Societies on Pediatric Gastroenterology, Hepatology and Nutrition, invited highly qualified experts in the area of infant nutrition to form an International Expert Group (IEG) to review the issues raised. The group arrived at recommendations on the compositional requirements for a global infant formula standard which are reported here.

Trading Volume, Information Asymmetry, and Timing Information

Abstract: This paper investigates trading volume before scheduled and unscheduled corporate announcements to explore how traders respond to private information. I show that cumulative trading volume decreases inversely to information asymmetry prior to scheduled announcements, while the opposite relation holds for volume after the announcement. In contrast, trading volume before unscheduled announcements increases dramatically and shows little relation to proxies for information asymmetry. I investigate the behavior of market makers and find that they act appropriately by increasing price sensitivity before all announcements, implying that they extract timing information from their order books. TRADING VOLUME PLAYS a critical role in financial markets. It facilitates the price discovery process, enables investors to share financial risks, and ensures that corporations can raise funds needed for investment. Trading volume is generally characterized as either informed or uninformed (liquidity trading). Although both types of trading volume are studied in the finance literature,' their relative importance remains poorly understood. In this paper, I study trading volume prior to important corporate announcements, when information asymmetry2 is likely to be the greatest. The analysis provides insights into how informed and liquidity traders, along with market makers, respond to asymmetric information in the market. Finance theory provides ambiguous predictions about trading volume prior to corporate announcements. When liquidity trading is exogenous and inelastic to price, as in Kyle (1985), trading volume increases in information asymmetry. This is because informed traders attempt to exploit their private information. However, if liquidity traders have timing discretion, as in Admati

Instability of the DSM-IV Subtypes of ADHD From Preschool Through Elementary School

Abstract: Context The DSM-IV definition of attention-deficit/hyperactivity disorder (ADHD) distinguished 3 subtypes that had not been extensively studied. Objective To determine whether the ADHD subtypes are stable enough over time to be valid. Design Longitudinal study with a greater-than 89% retention rate in 7 assessments over 8 years. Setting Outpatient clinics. Participants Volunteer sample of 118 4- to 6-year-olds who met DSM-IV criteria for ADHD, including impairment in 2 settings in at least 1 assessment. Main Outcome Measure Meeting DSM-IV criteria for the subtypes of ADHD during years 2 through 8. Results The number of children who met criteria for ADHD declined over time, but most persisted. Children who met criteria for the combined subtype (CT, n = 83) met criteria for ADHD in more subsequent assessments than children in the predominantly hyperactive-impulsive subtype (HT, n = 23). Thirty-one (37%) of 83 CT children and 6 (50%) of 12 children in the predominantly inattentive subtype (IT) met criteria for a different subtype at least twice in the next 6 assessments. Children of the HT subtype were even more likely to shift to a different subtype over time, with HT children who persisted in ADHD mostly shifting to CT in later assessments. The subtypes exhibited consistently different mean levels of hyperactive-impulsive symptoms during years 2 through 8 that corresponded with their initial subtype classifications, but initial subtype differences in inattention symptoms diminished in later years. Conclusions In younger children, the CT and IT may be stable enough to segregate groups for research, but they seem too unstable for use in the clinical assessment of individual children. Children rarely remain in the HT classification over time; rather, they sometimes desist from ADHD but mostly shift to CT in later years. Using continuous ratings of hyperactivity-impulsivity symptoms as a diagnostic qualifier should be considered as an alternative to classifying nominal subtypes of ADHD in DSM-V .

Testosterone and Dihydrotestosterone Tissue Levels in Recurrent Prostate Cancer

Abstract: Purpose: Prostate cancer eventually recurs during androgen deprivation therapy despite castrate levels of serum androgens. Expression of androgen receptor and androgen receptor–regulated proteins suggests androgen receptor activation in recurrent prostate cancer. Many groups have pursued mechanisms of ligand-independent androgen receptor activation but we found high levels of testicular androgens in recurrent prostate cancer tissue using RIA. Experimental Designs: Prostate specimens from 36 men were procured preserving blood flow to prevent ischemia and cyropreserved immediately. Recurrent prostate cancer specimens from 18 men whose cancer recurred locally during androgen deprivation therapy and androgen-stimulated benign prostate specimens from 18 men receiving no hormonal treatments were studied. Tissue levels of testosterone and dihydrotestosterone were measured in each specimen using liquid chromatography/electrospray tandem mass spectrometry. Testosterone and dihydrotestosterone levels were compared with clinical variables and treatment received. Results: Testosterone levels were similar in recurrent prostate cancer (3.75 pmol/g tissue) and androgen-stimulated benign prostate (2.75 pmol/g tissue, Wilcoxon two-sided, P = 0.30). Dihydrotestosterone levels decreased 91% in recurrent prostate cancer (1.25 pmol/g tissue) compared with androgen-stimulated benign prostate (13.7 pmol/g tissue; Wilcoxon two-sided, P P > 0.2). Conclusions: Recurrent prostate cancer may develop the capacity to biosynthesize testicular androgens from adrenal androgens or cholesterol. This surprising finding suggests intracrine production of dihydrotestosterone and should be exploited for novel treatment of recurrent prostate cancer.

Removal of Antibiotics in Wastewater: Effect of Hydraulic and Solid Retention Times on the Fate of Tetracycline in the Activated Sludge Process

Abstract: A study was conducted to examine the influence of hydraulic retention time (HRT) and solid retention time (SRT) on the removal of tetracycline in the activated sludge processes. Two lab-scale sequencing batch reactors (SBRs) were operated to simulate the activated sludge process. One SBR was spiked with 250 μg/L tetracycline, while the other SBR was evaluated at tetracycline concentrations found in the influent of the wastewater treatment plant (WWTP) where the activated sludge was obtained. The concentrations of tetracyclines in the influent of the WWTP ranged from 0.1 to 0.6 μg/L. Three different operating conditions were applied during the study (phase 1HRT: 24 h and SRT: 10 days; phase 2HRT: 7.4 h and SRT: 10 days; and phase 3HRT: 7.4 h and SRT: 3 days). The removal efficiency of tetracycline in phase 3 (78.4 ± 7.1%) was significantly lower than that observed in phase 1 (86.4 ± 8.7%) and phase 2 (85.1 ± 5.4%) at the 95% confidence level. The reduction of SRT in phase 3 while maintaining a consta...

Dietary fiber intake and risk of colorectal cancer: a pooled analysis of prospective cohort studies.

Abstract: Context: Inconsistent findings from observational studies have continued the controversy over the effects of dietary fiber on colorectal cancer. Objective: To evaluate the association between dietary fiber intake and risk of colorectal cancer. Design, Setting, and Participants: From 13 prospective cohort studies included in the Pooling Project of Prospective Studies of Diet and Cancer, 725 628 men and women were followed up for 6 to 20 years across studies. Study- and sex-specific relative risks (RRs) were estimated with the Cox proportional hazards model and were subsequently pooled using a random-effects model. Main Outcome Measure: Incident colorectal cancer. Results: During 6 to 20 years of follow-up across studies, 8081 colorectal cancer cases were identified. For comparison of the highest vs lowest study- and sex-specific quintile of dietary fiber intake, a significant inverse association was found in the age-adjusted model (pooled RR=0.84; 95% confidence interval [CI], 0.77-0.92). However, the association was attenuated and no longer statistically significant after adjusting for other risk factors (pooled multivariate RR=0.94; 95% CI, 0.86-1.03). In categorical analyses compared with dietary fiber intake of 10 to <15 g/d, the pooled multivariate RR was 1.18 (95% CI, 1.05-1.31) for less than 10 g/d (11% of the overall study population); and RR, 1.00 (95% CI, 0.85-1.17) for 30 or more g/d. Fiber intake from cereals, fruits, and vegetables was not associated with risk of colorectal cancer. The pooled multivariate RRs comparing the highest vs lowest study- and sex-specific quintile of dietary fiber intake were 1.00 (95% CI, 0.90-1.11) for colon cancer and 0.85 (95% CI, 0.72-1.01) for rectal cancer (P for common effects by tumor site=.07). Conclusions: In this large pooled analysis, dietary fiber intake was inversely associated with risk of colorectal cancer in age-adjusted analyses. However, after accounting for other dietary risk factors, high dietary fiber intake was not associated with a reduced risk of colorectal cancer. ©2005 American Medical Association. All rights reserved.

Leadership and levels of analysis: A state-of-the-science review

Abstract: The purpose of this article is to present a comprehensive, qualitative, narrative review of the leadership literature with an explicit focus on levels-of-analysis issues. Focusing on conceptual and empirical publications (books, book chapters, and journal articles) over the last 10 years in 17 areas of leadership research, we reviewed and coded 348 journal articles and book chapters for the degree of appropriate inclusion and use of levels of analysis in theory formulation, construct/variable measurement, data analytic techniques, and inference drawing. In general, while the literature on leadership is vast and growing, relatively few studies in any of the areas of leadership research have addressed levels-of-analysis issues appropriately in theory, measurement, data analysis, and inference drawing. Nevertheless, the findings reported are encouraging, as levels issues are still relatively new to the leadership field and some progress clearly has been made in the last decade. The implications of the current state-of-the-science for future research and the advancement of study in leadership are discussed.

Folate-receptor-mediated delivery of InP quantum dots for bioimaging using confocal and two-photon microscopy.

Abstract: A novel method for the synthesis of highly monodispersed hydrophillic InP−ZnS nanocrystals and their use as luminescence probes for live cell imaging is reported. Hydrophobic InP−ZnS nanocrystals are prepared by a new method that yields high-quality, luminescent core−shell nanocrystals within 6−8 h of total reaction time. Then by carefully manipulating the surface of these passivated nanocrystals, aqueous dispersions of folate-conjugated nanocrystals (folate-QDs) with high photostability are prepared. By use of confocal microscopy, we demonstrate the receptor-mediated delivery of folic acid conjugated quantum dots into folate-receptor-positive cell lines such as KB cells. These folate-QDs tend to accumulate in multivescicular bodies of KB cells after 6 h of incubation. Receptor-mediated delivery was confirmed by comparison with the uptake of these particles in folate-receptor-negative cell lines such as A549. Efficient two-photon excitation of these particles and two-photon imaging using these particles a...

Comparative Value Relevance Among German, U.S., and International Accounting Standards: A German Stock Market Perspective:

Abstract: In recent years, German companies have reported consolidated financial statements under German GAAP, U.S. GAAP, or International Accounting Standards (IAS). Market observers, researchers, and regulators have argued that financial statements prepared under the shareholder (or investor) model, such as U.S. GAAP or IAS, provide better information than financial statements prepared under the stakeholder model (German GAAP). They further have argued that U.S. GAAP is more rigorously defined and, therefore, provides information superior to that under IAS. We investigate comparative value relevance, measured as the slope coefficient of the returns/earnings regression. Within our sample of German companies traded on German stock exchanges, the value relevance of U.S. GAAP- and IAS-based earnings is higher than that of German GAAP-based earnings. Our result holds only for profit observations, suggesting that reporting regime does not have an influence on the quality of earnings in the case of loss firms. However, ...

Do spatial effecfs really matter in regression analysis

Abstract: A substantial hotly of applied statistical and econometric analysis in regional science and geography deals with data collected for aggregate spatial units of observation. These data are typically affected by a variety of measurement problems, resulting in spatial dependence and spatial heterogeneity. However, most of the empirical work fails to take this into account. In this paper, we address the issue of the extent to which spatial effects matter in applied regression analysis. An overview of the formal methodological problems is given, and related to the literature in spatial statistics and spatial econometrics.

Need for expertise based randomised controlled trials.

Abstract: Surgical procedures are less likely to be rigorously evidence based than drug treatments because of difficulties with randomisation. Expertise based trials could be the way forward Although conventional randomised controlled trials are widely recognised as the most reliable method to evaluate pharmacological interventions,1 2 scepticism about their role in nonpharmacological interventions (such as surgery) remains.3–6 Conventional randomised controlled trials typically randomise participants to one of two intervenions (A or B) and individual clinicians give intervention A to some participants and B to others. An alternative trial design, the expertise based randomised controlled trial, randomises participants to clinicians with expertise in intervention A or clinicians with expertise in intervention B, and the clinicians perform only the procedure they are expert in. We present evidence to support our argument that increased use of the expertise based design will enhance the validity, applicability, feasibility, and ethical integrity of randomised controlled trials in surgery, as well as in other areas. We focus on established surgical interventions rather than new surgical procedures in which clinicians have not established expertise. Investigators have used the expertise based design when conventional randomised controlled trials were impossible because different specialty groups provided the interventions under evaluation—for example, percutaneous transluminal coronary angioplasty versus coronary artery bypass graft surgery.7–9 In 1980, Van der Linden suggested randomising participants to clinicians committed to performing different interventions in an area in which a conventional randomised controlled trial was possible.10 Since that time, however, the expertise based design has been little used, even in areas where it has high potential (such as, surgery, physiotherapy, and chiropractic). ### Differential expertise between procedures Because it takes training and experience to develop expertise in surgical interventions, individual surgeons tend to solely or primarily use a single surgical approach to treat a specific problem.10 11 …

Endocrine control of body composition in infancy, childhood, and puberty.

Abstract: Body composition exhibits marked variations across the early human lifetime. The precise physiological mechanisms that drive such developmental adaptations are difficult to establish. This clinical challenge reflects an array of potentially confounding factors, such as marked intersubject differences in tissue compartments; the incremental nature of longitudinal intrasubject variations in body composition; technical limitations in quantitating the unobserved mass of mineral, fat, water, and muscle ad seriatim; and the multifold contributions of genetic, dietary, environmental, hormonal, nutritional, and behavioral signals to physical and sexual maturation. From an endocrine perspective (reviewed here), gonadal sex steroids and GH/IGF-I constitute prime determinants of evolving body composition. The present critical review examines hormonal regulation of body composition in infancy, childhood, and puberty.

A two-fluid model for avalanche and debris flows

Abstract: Geophysical mass flows—debris flows, avalanches, landslides—can contain O (10 6 –10 10 )m 3 or more of material, often a mixture of soil and rocks with a significant quantity of interstitial fluid. These flows can be tens of meters in depth and hundreds of meters in length. The range of scales and the rheology of this mixture presents significant modelling and computational challenges. This paper describes a depth-averaged ‘thin layer’ model of geophysical mass flows containing a mixture of solid material and fluid. The model is derived from a ‘two-phase’ or ‘two-fluid’ system of equations commonly used in engineering research. Phenomenological modelling and depth averaging combine to yield a tractable set of equations, a hyperbolic system that describes the motion of the two constituent phases. If the fluid inertia is small, a reduced model system that is easier to solve may be derived.

Aqueous ferrofluid of magnetite nanoparticles: Fluorescence labeling and magnetophoretic control.

Abstract: A method is presented for the preparation of a biocompatible ferrofluid containing dye-functionalized magnetite nanoparticles that can serve as fluorescent markers. This method entails the surface functionalization of magnetite nanoparticles using citric acid to produce a stable aqueous dispersion and the subsequent binding of fluorescent dyes to the surface of the particles. Several ferrofluid samples were prepared and characterized using Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA), BET surface area analysis, transmission electron microscopy (TEM), and SQUID magnetometry. In addition, confocal fluorescence microscopy was used to study the response of the fluorescent nanoparticles to an applied magnetic field and their uptake by cells in vitro. Results are presented on the distribution of particle sizes, the fluorescent and magnetic properties of the nanoparticles, and the nature of their surface bonds. Biocompatible ferrofluids ...

Preferred analysis methods for Affymetrix GeneChips revealed by a wholly defined control dataset

Abstract: Background As more methods are developed to analyze RNA-profiling data, assessing their performance using control datasets becomes increasingly important.

Effect of exogenous surfactant (calfactant) in pediatric acute lung injury : a randomized controlled trial

Abstract: ContextDespite evidence that patients with acute lung injury (ALI) have pulmonary surfactant dysfunction, trials of several surfactant preparations to treat adults with ALI have not been successful. Preliminary studies in children with ALI have shown that instillation of a natural lung surfactant (calfactant) containing high levels of surfactant-specific protein B may be beneficial.ObjectiveTo determine if endotracheal instillation of calfactant in infants, children, and adolescents with ALI would shorten the course of respiratory failure.Design, Setting, and PatientsA multicenter, randomized, blinded trial of calfactant compared with placebo in 153 infants, children, and adolescents with respiratory failure from ALI conducted from July 2000 to July 2003. Twenty-one tertiary care pediatric intensive care units participated. Entry criteria included age 1 week to 21 years, enrollment within 48 hours of endotracheal intubation, radiological evidence of bilateral lung disease, and an oxygenation index higher than 7. Premature infants and children with preexisting lung, cardiac, or central nervous system disease were excluded.InterventionTreatment with intratracheal instillation of 2 doses of 80 mL/m2 calfactant or an equal volume of air placebo administered 12 hours apart.Main Outcome MeasuresVentilator-free days and mortality; secondary outcome measures were hospital course, adverse events, and failure of conventional mechanical ventilation.ResultsThe calfactant group experienced an acute mean (SD) decrease in oxygenation index from 20 (12.9) to 13.9 (9.6) after 12 hours compared with the placebo group’s decrease from 20.5 (14.7) to 15.1 (9.0) (P = .01). Mortality was significantly greater in the placebo group compared with the calfactant group (27/75 vs 15/77; odds ratio, 2.32; 95% confidence interval, 1.15-4.85), although ventilator-free days were not different. More patients in the placebo group did not respond to conventional mechanical ventilation. There were no differences in long-term complications.ConclusionsCalfactant acutely improved oxygenation and significantly decreased mortality in infants, children, and adolescents with ALI although no significant decrease in the course of respiratory failure measured by duration of ventilator therapy, intensive care unit, or hospital stay was observed.