scispace - formally typeset
Search or ask a question

Showing papers by "University of Alabama published in 2006"


Journal ArticleDOI
TL;DR: Treatment of locoregionally advanced head and neck cancer with concomitant high-dose radiotherapy plus cetuximab improves locoreGional control and reduces mortality without increasing the common toxic effects associated with radiotherapy to the head andneck.
Abstract: BACKGROUND We conducted a multinational, randomized study to compare radiotherapy alone with radiotherapy plus cetuximab, a monoclonal antibody against the epidermal growth factor receptor, in the treatment of locoregionally advanced squamous-cell carcinoma of the head and neck. METHODS Patients with locoregionally advanced head and neck cancer were randomly assigned to treatment with high-dose radiotherapy alone (213 patients) or high-dose radiotherapy plus weekly cetuximab (211 patients) at an initial dose of 400 mg per square meter of body-surface area, followed by 250 mg per square meter weekly for the duration of radiotherapy. The primary end point was the duration of control of locoregional disease; secondary end points were overall survival, progression-free survival, the response rate, and safety. RESULTS The median duration of locoregional control was 24.4 months among patients treated with cetuximab plus radiotherapy and 14.9 months among those given radiotherapy alone (hazard ratio for locoregional progression or death, 0.68; P = 0.005). With a median follow-up of 54.0 months, the median duration of overall survival was 49.0 months among patients treated with combined therapy and 29.3 months among those treated with radiotherapy alone (hazard ratio for death, 0.74; P = 0.03). Radiotherapy plus cetuximab significantly prolonged progression-free survival (hazard ratio for disease progression or death, 0.70; P = 0.006). With the exception of acneiform rash and infusion reactions, the incidence of grade 3 or greater toxic effects, including mucositis, did not differ significantly between the two groups. CONCLUSIONS Treatment of locoregionally advanced head and neck cancer with concomitant highdose radiotherapy plus cetuximab improves locoregional control and reduces mortality without increasing the common toxic effects associated with radiotherapy to the head and neck. (ClinicalTrials.gov number, NCT00004227.)

4,705 citations


Journal ArticleDOI
19 Oct 2006-Nature
TL;DR: It is indicated that there may have been at least four independent losses of the flagellum in the kingdom Fungi, and the enigmatic microsporidia seem to be derived from an endoparasitic chytrid ancestor similar to Rozella allomycis, on the earliest diverging branch of the fungal phylogenetic tree.
Abstract: The ancestors of fungi are believed to be simple aquatic forms with flagellated spores, similar to members of the extant phylum Chytridiomycota (chytrids). Current classifications assume that chytrids form an early-diverging clade within the kingdom Fungi and imply a single loss of the spore flagellum, leading to the diversification of terrestrial fungi. Here we develop phylogenetic hypotheses for Fungi using data from six gene regions and nearly 200 species. Our results indicate that there may have been at least four independent losses of the flagellum in the kingdom Fungi. These losses of swimming spores coincided with the evolution of new mechanisms of spore dispersal, such as aerial dispersal in mycelial groups and polar tube eversion in the microsporidia (unicellular forms that lack mitochondria). The enigmatic microsporidia seem to be derived from an endoparasitic chytrid ancestor similar to Rozella allomycis, on the earliest diverging branch of the fungal phylogenetic tree.

1,682 citations


Journal ArticleDOI
01 Nov 2006-JAMA
TL;DR: The Extremity Constraint Induced Therapy Evaluation (EXCITE) trial as mentioned in this paper showed that a 2-week program of constraint-induced movement therapy (CIMT) for patients more than 1 year after stroke who maintain some hand and wrist movement can improve upper extremity function that persists for at least 1 year.
Abstract: ContextSingle-site studies suggest that a 2-week program of constraint-induced movement therapy (CIMT) for patients more than 1 year after stroke who maintain some hand and wrist movement can improve upper extremity function that persists for at least 1 year.ObjectiveTo compare the effects of a 2-week multisite program of CIMT vs usual and customary care on improvement in upper extremity function among patients who had a first stroke within the previous 3 to 9 months.Design and SettingThe Extremity Constraint Induced Therapy Evaluation (EXCITE) trial, a prospective, single-blind, randomized, multisite clinical trial conducted at 7 US academic institutions between January 2001 and January 2003.ParticipantsTwo hundred twenty-two individuals with predominantly ischemic stroke.InterventionsParticipants were assigned to receive either CIMT (n = 106; wearing a restraining mitt on the less-affected hand while engaging in repetitive task practice and behavioral shaping with the hemiplegic hand) or usual and customary care (n = 116; ranging from no treatment after concluding formal rehabilitation to pharmacologic or physiotherapeutic interventions); patients were stratified by sex, prestroke dominant side, side of stroke, and level of paretic arm function.Main Outcome MeasuresThe Wolf Motor Function Test (WMFT), a measure of laboratory time and strength-based ability and quality of movement (functional ability), and the Motor Activity Log (MAL), a measure of how well and how often 30 common daily activities are performed.ResultsFrom baseline to 12 months, the CIMT group showed greater improvements than the control group in both the WMFT Performance Time (decrease in mean time from 19.3 seconds to 9.3 seconds [52% reduction] vs from 24.0 seconds to 17.7 seconds [26% reduction]; between-group difference, 34% [95% confidence interval {CI}, 12%-51%]; P<.001) and in the MAL Amount of Use (on a 0-5 scale, increase from 1.21 to 2.13 vs from 1.15 to 1.65; between-group difference, 0.43 [95% CI, 0.05-0.80]; P<.001) and MAL Quality of Movement (on a 0-5 scale, increase from 1.26 to 2.23 vs 1.18 to 1.66; between-group difference, 0.48 [95% CI, 0.13-0.84]; P<.001). The CIMT group achieved a decrease of 19.5 in self-perceived hand function difficulty (Stroke Impact Scale hand domain) vs a decrease of 10.1 for the control group (between-group difference, 9.42 [95% CI, 0.27-18.57]; P=.05).ConclusionAmong patients who had a stroke within the previous 3 to 9 months, CIMT produced statistically significant and clinically relevant improvements in arm motor function that persisted for at least 1 year.Trial Registrationclinicaltrials.gov Identifier: NCT00057018

1,662 citations


Journal ArticleDOI
TL;DR: One year of oral cyclophosphamide in patients with symptomatic scleroderma-related interstitial lung disease had a significant but modest beneficial effect on lung function, dyspnea, thickening of the skin, and the health-related quality of life.
Abstract: BACKGROUND We conducted a double-blind, randomized, placebo-controlled trial to determine the effects of oral cyclophosphamide on lung function and health-related symptoms in patients with evidence of active alveolitis and scleroderma-related interstitial lung disease. METHODS At 13 clinical centers throughout the United States, we enrolled 158 patients with scleroderma, restrictive lung physiology, dyspnea, and evidence of inflammatory interstitial lung disease on examination of bronchoalveolar-lavage fluid, thoracic highresolution computed tomography, or both. Patients received oral cyclophosphamide (≤2 mg per kilogram of body weight per day) or matching placebo for one year and were followed for an additional year. Pulmonary function was assessed every three months during the first year, and the primary end point was the forced vital capacity (FVC, expressed as a percentage of the predicted value) at 12 months, after adjustment for the baseline FVC. RESULTS Of 158 patients, 145 completed at least six months of treatment and were included in the analysis. The mean absolute difference in adjusted 12-month FVC percent predicted between the cyclophosphamide and placebo groups was 2.53 percent (95 percent confidence interval, 0.28 to 4.79 percent), favoring cyclophosphamide (P<0.03). There were also treatment-related differences in physiological and symptom outcomes, and the difference in FVC was maintained at 24 months. There was a greater frequency of adverse events in the cyclophosphamide group, but the difference between the two groups in the number of serious adverse events was not significant. CONCLUSIONS One year of oral cyclophosphamide in patients with symptomatic sclerodermarelated interstitial lung disease had a significant but modest beneficial effect on lung function, dyspnea, thickening of the skin, and the health-related quality of life. The effects on lung function were maintained through the 24 months of the study.

1,330 citations


Journal ArticleDOI
21 Jul 2006-Science
TL;DR: Elevated expression of Rab1, the mammalian YPT1 homolog, protected against αSyn-induced dopaminergic neuron loss in animal models of PD, suggesting synucleinopathies may result from disruptions in basic cellular functions that interface with the unique biology of particular neurons to make them especially vulnerable.
Abstract: Alpha-synuclein (αSyn) misfolding is associated with several devastating neurodegenerative disorders, including Parkinson9s disease (PD). In yeast cells and in neurons αSyn accumulation is cytotoxic, but little is known about its normal function or pathobiology. The earliest defect following αSyn expression in yeast was a block in endoplasmic reticulum (ER)–to–Golgi vesicular trafficking. In a genomewide screen, the largest class of toxicity modifiers were proteins functioning at this same step, including the Rab guanosine triphosphatase Ypt1p, which associated with cytoplasmic αSyn inclusions. Elevated expression of Rab1, the mammalian YPT1 homolog, protected against αSyn-induced dopaminergic neuron loss in animal models of PD. Thus, synucleinopathies may result from disruptions in basic cellular functions that interface with the unique biology of particular neurons to make them especially vulnerable.

1,314 citations


Journal ArticleDOI
TL;DR: The GAIT trial as discussed by the authors evaluated the efficacy and safety of glucosamine and chondroitin sulfate as a treatment for knee pain from osteoarthritis in 1583 patients.
Abstract: Background Glucosamine and chondroitin sulfate are used to treat osteoarthritis. The multicenter, double-blind, placebo- and celecoxib-controlled Glucosamine/chondroitin Arthritis Intervention Trial (GAIT) evaluated their efficacy and safety as a treatment for knee pain from osteoarthritis. Methods We randomly assigned 1583 patients with symptomatic knee osteoarthritis to receive 1500 mg of glucosamine daily, 1200 mg of chondroitin sulfate daily, both glucosamine and chondroitin sulfate, 200 mg of celecoxib daily, or placebo for 24 weeks. Up to 4000 mg of acetaminophen daily was allowed as rescue analgesia. Assignment was stratified according to the severity of knee pain (mild [N=1229] vs. moderate to severe [N=354]). The primary outcome measure was a 20 percent decrease in knee pain from baseline to week 24. Results The mean age of the patients was 59 years, and 64 percent were women. Overall, glucosamine and chondroitin sulfate were not significantly better than placebo in reducing knee pain by 20 perce...

1,199 citations


Journal ArticleDOI
01 Nov 2006-Sleep
TL;DR: A systematic review of psychological and behavioral interventions for persistent insomnia was conducted by the American Academy of Sleep Medicine (AASM) in 1999 as mentioned in this paper, which provided an update of the evidence published since the original paper.
Abstract: Background Recognition that psychological and behavioral factors play an important role in insomnia has led to increased interest in therapies targeting these factors. A review paper published in 1999 summarized the evidence regarding the efficacy of psychological and behavioral treatments for persistent insomnia. The present review provides an update of the evidence published since the original paper. As with the original paper, this review was conducted by a task force commissioned by the American Academy of Sleep Medicine in order to update its practice parameters on psychological and behavioral therapies for insomnia. Methods A systematic review was conducted on 37 treatment studies (N = 2246 subjects/patients) published between 1998 and 2004 inclusively and identified through Psyclnfo and Medline searches. Each study was systematically reviewed with a standard coding sheet and the following information was extracted: Study design, sample (number of participants, age, gender), diagnosis, type of treatments and controls, primary and secondary outcome measures, and main findings. Criteria for inclusion of a study were as follows: (a) the main sleep diagnosis was insomnia (primary or comorbid), (b) at least 1 treatment condition was psychological or behavioral in content, (c) the study design was a randomized controlled trial, a nonrandomized group design, a clinical case series or a single subject experimental design with a minimum of 10 subjects, and (d) the study included at least 1 of the following as dependent variables: sleep onset latency, number and/or duration of awakenings, total sleep time, sleep efficiency, or sleep quality. Results Psychological and behavioral therapies produced reliable changes in several sleep parameters of individuals with either primary insomnia or insomnia associated with medical and psychiatric disorders. Nine studies documented the benefits of insomnia treatment in older adults or for facilitating discontinuation of medication among chronic hypnotic users. Sleep improvements achieved with treatment were well sustained over time; however, with the exception of reduced psychological symptoms/ distress, there was limited evidence that improved sleep led to clinically meaningful changes in other indices of morbidity (e.g., daytime fatigue). Five treatments met criteria for empirically-supported psychological treatments for insomnia: Stimulus control therapy, relaxation, paradoxical intention, sleep restriction, and cognitive-behavior therapy. Discussion These updated findings provide additional evidence in support of the original review's conclusions as to the efficacy and generalizability of psychological and behavioral therapies for persistent insomnia. Nonetheless, further research is needed to develop therapies that would optimize outcomes and reduce morbidity, as would studies of treatment mechanisms, mediators, and moderators of outcomes. Effectiveness studies are also needed to validate those therapies when implemented in clinical settings (primary care), by non-sleep specialists. There is also a need to disseminate more effectively the available evidence in support of psychological and behavioral interventions to health-care practitioners working on the front line.

1,135 citations


Journal ArticleDOI
TL;DR: In this paper, a multi-dimensional measure of work-family enrichment is developed and validated using five samples, consisting of three dimensions from the family to work direction (development, affect, and efficiency).

1,030 citations


Journal ArticleDOI
01 Sep 2006-Sleep
TL;DR: In this paper, the authors present expert consensus recommendations for a standard set of research assessments in insomnia, reporting standards for these assessments, and recommendations for future research, which are not intended to be static but must be periodically revised to accommodate further developments and evidence in the field.
Abstract: Study objectives To present expert consensus recommendations for a standard set of research assessments in insomnia, reporting standards for these assessments, and recommendations for future research. Participants N/A. Interventions N/A. Methods and results An expert panel of 25 researchers reviewed the available literature on insomnia research assessments. Preliminary recommendations were reviewed and discussed at a meeting on March 10-11, 2005. These recommendations were further refined during writing of the current paper. The resulting key recommendations for standard research assessment of insomnia disorders include definitions/diagnosis of insomnia and comorbid conditions; measures of sleep and insomnia, including qualitative insomnia measures, diary, polysomnography, and actigraphy; and measures of the waking correlates and consequences of insomnia disorders, such as fatigue, sleepiness, mood, performance, and quality of life. Conclusions Adoption of a standard research assessment of insomnia disorders will facilitate comparisons among different studies and advance the state of knowledge. These recommendations are not intended to be static but must be periodically revised to accommodate further developments and evidence in the field.

973 citations


Journal ArticleDOI
TL;DR: In this paper, the authors investigated the complex interrelationships between satisfaction with the retailer, hedonic and utilitarian shopping value, and important retail outcomes, and found that both hedonics and utilitarian values are found to influence key retail outcomes.

857 citations


Journal ArticleDOI
TL;DR: C and 35/37Cl NMR relaxation measurements on several model systems demonstrate that the solvation of cellulose by the ionic liquid 1-n-butyl-3-methylimidazolium chloride involves hydrogen-bonding between the carbohydrate hydroxyl protons and the IL chloride ions in a 1 ratio 1 stoichiometry.

Journal ArticleDOI
TL;DR: In this paper, the simultaneous effects of normal transpiration through and tangential movement of a semi-infinite plate on self-similar boundary layer flow beneath a uniform free stream is considered.

Journal ArticleDOI
TL;DR: Scores for low-contrast letter acuity and contrast sensitivity correlate well with RNFL thickness as a structural biomarker, supporting validity for these visual function tests as secondary clinical outcome measures for MS trials.

Journal ArticleDOI
TL;DR: In this article, the authors combine findings from 155 samples of more than 31,000 salespeople to test alternative models of antecedents and consequences of adaptive selling behavior (ASB) and customer orientation (CO).
Abstract: The authors combine findings from 155 samples of more than 31,000 salespeople to test alternative models of antecedents and consequences of adaptive selling behavior (ASB) and customer orientation (CO). A random-effects meta-analysis yields average values for 28 different correlations ranging from −.16 to .35, 19 of which are significant. Controlling for salesperson gender and selling experience, structural equation modeling indicates that ASB increases self-rated, manager-rated, and objective measures of performance, whereas CO increases only self-rated performance. Both ASB and CO increase job satisfaction. Tests of reciprocal relationships indicate that ASB increases CO and job satisfaction increases performance rather than vice versa. Selling experience increases performance but not job satisfaction, and saleswomen rate their performance and satisfaction slightly higher than salesmen do. The magnitudes of the relationships indicate that ASB and selling experience have greater effects than CO ...

Journal ArticleDOI
TL;DR: The Resources for Enhancing Alzheimer's Caregiver Health (REACH) study as discussed by the authors found that the intervention had no detectable effect on the number of care recipients who were institutionalized.
Abstract: Caring for a family member with dementia is extremely stressful, contributes to psychiatric and physical illness, and increases the risk for death (1, 2). The accumulating evidence on the personal, social, and health effects of dementia caregiving has generated a broad range of intervention studies, including randomized trials aimed at decreasing the burden and stress of caregiving. Several studies have demonstrated statistically significant effects in reducing caregiver burden, lowering caregiver depression, and delaying institutionalization of care recipients (1, 3, 4) through either targeted interventions that treat a specific caregiver problem, such as depression, or broad-based multicomponent interventions that include counseling, case management, and telephone support. Persistent limitations of caregiver intervention research are the paucity of well-controlled randomized trials, the limited range of outcomes examined, small sample sizes and insufficient power, geographic limitations, inadequate racial or ethnic variation, and a scarcity of comprehensive multicomponent interventions (4). Indeed, none of the 41 randomized clinical trials published in the last 5 years met Consolidated Standards of Reporting Trials (CONSORT) recommendations for reporting randomized trials (5), and many have serious methodologic problems that call into question the reported findings (4). To address these limitations, the National Institute on Aging and the National Institute of Nursing Research funded a multisite research program designed to develop and test an effective caregiver intervention: the Resources for Enhancing Alzheimer's Caregiver Health (REACH) study. We performed the study in 2 phases. In the first phase (REACH I), we tested several different interventions at 6 U.S. sites to identify the most promising approaches to decreasing caregiver burden and depression (6). Results from the study showed that active treatments were superior to control conditions in reducing caregiver burden and that active engagement in skills training statistically significantly reduced caregiver depression (7, 8). The existing literature and findings from REACH I helped guide the design of the REACH II intervention (7, 8). We based the REACH II study on the premise that caregivers can have problems in several areas at varying levels of intensity, and thus, interventions must be responsive to variations in needs among caregivers. The findings from REACH I also suggest that interventions that use active techniques, such as role-playing and interactive practice, are more effective at improving outcomes, such as depression symptoms, compared with more passive methods, such as providing information (7). We based the REACH II intervention on these assumptions and designed the intervention to maximize outcomes by systematically targeting several problem areas, tailored the intervention to respond to the needs of each individual, and actively engaged the caregiver in the intervention process. We hypothesized that participants assigned to the intervention would do better than those in the control group on several indicators of caregiver quality of life, including depression, burden, self-care, and social support and care recipient problem behaviors, and that these differences would be largest among Hispanic or Latino persons because they have lower access to support services (8). In additional analyses, we assessed the effects of treatment on rates of caregiver clinical depression and care recipient institutional placement, as well as the benefits derived from study participation. Context Providing care for patients with dementia can pose enormous burdens that may be eased with assistance and support. Needs may differ by race or ethnicity. Contributions The investigators randomly assigned Hispanic, black, and white dementia caregivers to receive written educational materials or an intensive intervention to improve caregiver quality of life. The specific interventions were determined by caregivers, were delivered via trained personnel and telephone support groups, and targeted several dimensions of need. The study found that quality of life improved for Hispanic and white caregivers and for black spousal caregivers in the intervention group but not in the control group. The intervention had no detectable effect on the number of care recipients who were institutionalized. Cautions The study used only a single 6-month follow-up assessment, combined heterogeneous cultures and ethnicities into 3 groups, and excluded some ethnicities. Implications An intensive intervention targeting several dimensions of caregiver need improved caregiver quality of life without an apparent effect on care recipient institutionalization. The effect did not differ by caregiver race or ethnicity. —The Editors

Journal ArticleDOI
16 Feb 2006-Nature
TL;DR: A Josephson supercurrent is reported through the strong ferromagnet CrO2, from which it is inferred that it is a spin triplet supercurrent, and the underlying physical explanation is a conversion from spin singlet pairs to spin triplets at the interface.
Abstract: In general, conventional superconductivity should not occur in a ferromagnet, though it has been seen in iron under pressure. Moreover, theory predicts that the current is always carried by pairs of electrons in a spin singlet state, so conventional superconductivity decays very rapidly when in contact with a ferromagnet, which normally prohibits the existence of singlet pairs. It has been predicted that this rapid spatial decay would not occur if spin triplet superconductivity could be induced in the ferromagnet. Here we report a Josephson supercurrent through the strong ferromagnet CrO2, from which we infer that it is a spin triplet supercurrent. Our experimental set-up is different from those envisaged in the earlier predictions, but we conclude that the underlying physical explanation for our result is a conversion from spin singlet pairs to spin triplets at the interface. The supercurrent can be switched with the direction of the magnetization, analogous to spin valve transistors, and therefore could enable magnetization-controlled Josephson junctions.

Journal ArticleDOI
TL;DR: It is proposed that tumor exosomes contribute to the growth of tumors by blocking IL-2-mediated activation of NK cells and their cytotoxic response to tumor cells.
Abstract: Many tumor cells shed specialized membrane vesicles known as exosomes. In this study, we show that pretreatment of mice with exosomes produced by TS/A or 4T.1 murine mammary tumor cells resulted in accelerated growth of implanted tumor cells in both syngeneic BALB/c mice and nude mice. As implanted TS/A tumor cells grew more rapidly in mice that had been depleted of NK cells, we analyzed the effects of the tumor-derived exosomes on NK cells. The tumor-derived exosomes inhibit NK cell cytotoxic activity ex vivo and in vitro as demonstrated by chromium release assays. The treatment of mice with TS/A tumor exosomes also led to a reduction in the percentages of NK cells, as determined by FACS analysis, in the lungs and spleens. Key features of NK cell activity were inhibited, including release of perforin but not granzyme B, as well as the expression of cyclin D3 and activation of the Jak3-mediated pathways. Human tumor cell lines also were found to produce exosomes that were capable of inhibiting IL-2-stimulated NK cell proliferation. Exosomes produced by dendritic cells or B cells did not. The presentation of tumor Ags by exosomes is under consideration as a cancer vaccine strategy; however, we found that pretreatment of mice with tumor exosomes blunted the protective effect of syngeneic dendritic cells pulsed ex vivo with tumor exosomes. We propose that tumor exosomes contribute to the growth of tumors by blocking IL-2-mediated activation of NK cells and their cytotoxic response to tumor cells.

Journal ArticleDOI
01 Feb 2006-Sleep
TL;DR: Actigraphy proved to be a satisfactory objective measure of sleep on 4 of 5 sleep parameters, but these results are specific to this particular instrument using this particular algorithm and should not be construed as a blanket endorsement of actigraphy for measuring insomnia.
Abstract: Study Objective: Actigraphy, a method of inferring sleep from the presence or absence of wrist movement, has been well validated against polysomnography in trials with people without insomnia. However, the small amount of literature on validation with insomniacs has revealed an actigraphy bias toward overscoring sleep. The current validation trial with insomniacs used the largest number of subjects to date in such research and attracted participants with diverse demographic characteristics. Design: People with insomnia slept 1 night in the laboratory while simultaneously being monitored by polysomnography, actigraphy (high-sensitivity algorithm of the Mini Mitter AW64 Actiwatch™), and morning sleep diary. Setting: Sleep disorders center. Participants: Participants were 57 volunteers from the community, 26 men and 31 women, ranging in age from 21 to 87 years. All participants satisfied conservative criteria for insomnia. The sample included subjects with primary insomnia, subjects with comorbid insomnia, and hypnotic users with current insomnia complaints. Interventions: N/A. Measurements and Results: Actigraphy was successfully validated on 4 measures of sleep pattern—number of awakenings, wake time after sleep onset, total sleep time, and sleep efficiency percentage—based on nonsignificant mean differences and significant correlation between actigraphy and polysomnography. Sleep-onset latency with actigraphy was not significantly different from polysomnography but was weakly correlated with polysomnography. Hypnotic use contributed to actigraphic overscoring of sleep. Conclusions: Actigraphy proved to be a satisfactory objective measure of sleep on 4 of 5 sleep parameters, but these results are specific to this particular instrument using this particular algorithm and should not be construed as a blanket endorsement of actigraphy for measuring insomnia.


Journal ArticleDOI
01 Nov 2006-Brain
TL;DR: In this paper, the role of TLR4 in the amyloidogenesis in vivo, determined the amounts of cerebral Abeta in Alzheimer's disease mouse models with different genotypes of TLRs using three distinct methods.
Abstract: Deposits of amyloid beta-protein (Abeta) in neuritic plaques and cerebral vessels are a pathological hallmark of Alzheimer's disease. Fibrillar Abeta deposits are closely associated with inflammatory responses such as activated microglia in brain with this disease. Increasing lines of evidence support the hypothesis that activated microglia, innate immune cells in the CNS, play a pivotal role in the progression of the disease: either clearing Abeta deposits by phagocytic activity or releasing cytotoxic substances and pro-inflammatory cytokines. Toll-like receptors (TLRs) are a family of pattern-recognition receptors in the innate immune system. Exogenous and endogenous TLR ligands activate microglia. To investigate the role of TLR4 in the amyloidogenesis in vivo, we determined the amounts of cerebral Abeta in Alzheimer's disease mouse models with different genotypes of TLR4 using three distinct methods. We show that mouse models (Mo/Hu APPswe PS1dE9 mice) homozygous for a destructive mutation of TLR4 (Tlr(Lps-d)/Tlr(Lps-d)) had increases in diffuse and fibrillar Abeta deposits by immunocytochemistry, fibrillar Abeta deposits by thioflavine-S staining and buffer-soluble and insoluble Abeta by ELISA in the cerebrum, as compared with TLR4 wild-type mouse models. Although the differences in these parameters were less significant, mouse models heterozygous for the mutation (Tlr(Lps-d)/) showed co-dominant phenotypes. Consistent with these observations in vivo, cultured microglia derived from Tlr(Lps-d)/Tlr(Lps-d) mice failed to show an increase in Abeta uptake after stimulation with a TLR4 ligand but not with a TLR9 ligand in vitro. Furthermore, activation of microglia (BV-2 cell) with a TLR2, TLR4 or TLR9 ligand, markedly boosted ingestion of Abeta in vitro. These results suggest that TLR signalling pathway(s) may be involved in clearance of Abeta-deposits in the brain and that TLRs can be a therapeutic target for Alzheimer's disease.

Journal ArticleDOI
06 Sep 2006-JAMA
TL;DR: High-quality instruments were identified for evaluating the EBP competence of individual trainees, determining the effectiveness of EBP curricula, and assessing EBP behaviors with objective outcome measures.
Abstract: ContextEvidence-based practice (EBP) is the integration of the best research evidence with patients' values and clinical circumstances in clinical decision making. Teaching of EBP should be evaluated and guided by evidence of its own effectiveness.ObjectiveTo appraise, summarize, and describe currently available EBP teaching evaluation instruments.Data Sources and Study SelectionWe searched the MEDLINE, EMBASE, CINAHL, HAPI, and ERIC databases; reference lists of retrieved articles; EBP Internet sites; and 8 education journals from 1980 through April 2006. For inclusion, studies had to report an instrument evaluating EBP, contain sufficient description to permit analysis, and present quantitative results of administering the instrument.Data ExtractionTwo raters independently abstracted information on the development, format, learner levels, evaluation domains, feasibility, reliability, and validity of the EBP evaluation instruments from each article. We defined 3 levels of instruments based on the type, extent, methods, and results of psychometric testing and suitability for different evaluation purposes.Data SynthesisOf 347 articles identified, 115 were included, representing 104 unique instruments. The instruments were most commonly administered to medical students and postgraduate trainees and evaluated EBP skills. Among EBP skills, acquiring evidence and appraising evidence were most commonly evaluated, but newer instruments evaluated asking answerable questions and applying evidence to individual patients. Most behavior instruments measured the performance of EBP steps in practice but newer instruments documented the performance of evidence-based clinical maneuvers or patient-level outcomes. At least 1 type of validity evidence was demonstrated for 53% of instruments, but 3 or more types of validity evidence were established for only 10%. High-quality instruments were identified for evaluating the EBP competence of individual trainees, determining the effectiveness of EBP curricula, and assessing EBP behaviors with objective outcome measures.ConclusionsInstruments with reasonable validity are available for evaluating some domains of EBP and may be targeted to different evaluation needs. Further development and testing is required to evaluate EBP attitudes, behaviors, and more recently articulated EBP skills.

Journal ArticleDOI
TL;DR: The phylogeny suggests that Chytridiomycota is not monophyletic and there are four major lineages of chytrids: Rozella spp.
Abstract: Chytridiomycota (chytrids) is the only phylum of true Fungi that reproduces with motile spores (zoospores). Chytrids currently are classified into five orders based on habitat, zoospore characters and life cycles. In this paper we estimate the phylogeny of the chytrids with DNA sequences from the ribosomal RNA operon (18S+5.8S+28S subunits). To our surprise the morphologically reduced para- sites Olpidium and Rozella comprise two entirely new, and separate, lineages on the fungal tree. Olpidium brassicae groups among the Zygomycota, and Rozella spp. are the earliest branch to diverge in the fungal kingdom. The phylogeny also suggests that Chytri- diomycota is not monophyletic and there are four major lineages of chytrids: Rozella spp., Olpidium brassicae, the Blastocladiales and a ''core chytrid clade'' containing the remaining orders and families and the majority of flagellated fungi. Within the core chytrid group 11 subclades can be identified, each of which correlates well with zoospore ultrastructure or morphology. We provide a synopsis of each clade and its morphological circumscription. The Blastocla- diales appears to be the sister taxon of most nonflagellated fungi. Based on molecular phyloge- netic and ultrastructural characters this order is elevated to a phylum, the Blastocladiomycota.

Journal ArticleDOI
TL;DR: In this article, the authors viewed turnover as a key predictor in determining unit-level unit-levy performance and used it as a predictor of the unit level performance of employees.
Abstract: Most turnover research positions employee turnover as the dependent variable and focuses on identifying its antecedents. In this study, we viewed turnover as a key predictor in determining unit-lev...

Journal ArticleDOI
TL;DR: Being optically transparent with the above optimal properties, Cr-doped In2O3 emerges as a viable candidate for the development of spin electronics.
Abstract: The search for an ideal magnetic semiconductor with tunable ferromagnetic behaviour over a wide range of doping or by electrical gating is being actively pursued as a major step towards realizing spin electronics. A magnetic semiconductor having a high Curie temperature, capable of independently controlled carrier density and magnetic doping, is crucial for developing spin-based multifunctional devices. Cr-doped In2O3 is such a unique system, where the electrical and magnetic behaviour—from ferromagnetic metal-like to ferromagnetic semiconducting to paramagnetic insulator—can be controllably tuned by the defect concentration. An explicit dependence of magnetic interaction leading to ferromagnetism on the carrier density is shown. A carrier-density-dependent high Curie temperature of 850–930 K has been measured, in addition to the observation of clear magnetic domain structures in these films. Being optically transparent with the above optimal properties, Cr-doped In2O3 emerges as a viable candidate for the development of spin electronics.

Journal ArticleDOI
TL;DR: The most severe floods in the Poyang Lake since 1950, and ranked in descending order of severity, occurred in 1998, 1995, 1954, 1983, 1992, 1973, and 1977.
Abstract: Poyang Lake in Jiangxi Province is the largest freshwater lake in China and is historically a region of significant floods. Annual events of peak lake stage and of severe floods have increased dramatically during the past few decades. This trend is related primarily to levee construction at the periphery of the lake and along the middle of the Changjiang (Yangtze River), which protects a large rural population. These levees reduce the area formerly available for floodwater storage resulting in higher lake stages during the summer flood season and catastrophic levee failures. The most severe floods in the Poyang Lake since 1950, and ranked in descending order of severity, occurred in 1998, 1995, 1954, 1983, 1992, 1973, and 1977. All of these floods occurred during or immediately following El Ni˜ no events, which are directly linked to rainfall in central China. The 2-year recurrence interval for maximum annual lake stage during El Ni˜ no years is 1.2 m higher than during non-El Ni˜ no years. The 10-year recurrence interval is 1.4 m higher during El Ni˜ no years than during non-El Ni˜ no years. Copyright  2006 Royal Meteorological Society.

Journal ArticleDOI
TL;DR: Self-reported racial discrimination was more common in men than in women and in those with higher educational attainment, independent of gender, and discrimination was statistically significantly associated with worse physical and mental health in both men and women, before and after adjustment for age, education, income, and skin color.

Journal ArticleDOI
TL;DR: Evidence to date suggests that amphibian declines will have large-scale and lasting ecosystem-level effects, including changes in algal composition, which will likely be greatest in neotropical highland streams.
Abstract: Amphibians can be important consumers in both aquatic and terrestrial habitats and may represent an important energetic link between the two, particularly in the tropics, where amphibian species richness and abundance are high. In the past 20 years, amphibian populations have declined dramatically around the world; numbers have decreased catastrophically in protected upland sites throughout the neotropics, usually resulting in the disappearance of over 75% of amphibians at a given site, particularly those species that breed in streams. Most studies of amphibian declines have focused on identifying causes and documenting changes in adult abundance, rather than on their ecological consequences. Here, we review evidence for the potential ecological effects of catastrophic amphibian declines, focusing on neotropical highland streams, where impacts will likely be greatest. Evidence to date suggests that amphibian declines will have large-scale and lasting ecosystem-level effects, including changes in algal com...

Journal ArticleDOI
TL;DR: The results indicate that the wetland sediments contained organisms such as Geobacter sp.
Abstract: The potential for microbially-mediated anaerobic redox cycling of iron (Fe) was examined in a first-generation enrichment culture of freshwater wetland sediment microorganisms. MPN enumerations revealed the presence of significant populations of Fe(III)-reducing (ca. 108 cells mL-1) and Fe(II)-oxidizing, nitrate-reducing organisms (ca. 105 cells mL-1) in the sediment used to inoculate the enrichment cultures. Nitrate reduction commenced immediately following inoculation of acetate-containing (ca. 1 mM) medium with a small quantity (1% vol/vol) of wetland sediment, and resulted in the transient accumulation of NO2- and production of a mixture of end-products including NH4+. Fe(III) oxide (high surface area goethite) reduction took place - after NO3- was depleted and continued until all the acetate was utilized. Addition of NO3 after Fe(III) reduction ceased resulted in the immediate oxidation of Fe(II) coupled to reduction of + NO3-to NH4 . No significant NO2- accumulation was observed during nitrate-dependent Fe(II) oxidation. No Fe(II) oxidation occurred in pasteurized controls. Microbial community structure in the enrichment was monitored by DGGE analysis of PCR amplified 16s rDNA and RT-PCR amplified 16S rRNA, as well as by construction of 16S rDNA clone libraries for four different time points during the experiment. Strong similarities in dominant members of the microbial communitymore » were observed in the Fe(III) reduction and nitrate-dependent Fe(II) oxidation phases of the experiment, specifically the common presence of organisms closely related (= 95% sequence similarity) to the genera Geobacter and Dechloromonas. These results indicate that the wetland sediments contained organisms such as Geobacter sp. which are capable of both + dissimilatory Fe(III) reduction and oxidation of Fe(II) with reduction of NO3-reduction to NH4 . Our findings suggest that microbially-catalyzed nitrate-dependent Fe(II) oxidation has the potential to contribute to a dynamic anaerobic Fe redox cycle in freshwater sediments.« less

Journal ArticleDOI
TL;DR: The Pareto distribution is a simple model for nonnegative data with a power law probability tail as mentioned in this paper, and there is a natural upper bound that truncates the probability tail.
Abstract: The Pareto distribution is a simple model for nonnegative data with a power law probability tail. In many practical applications, there is a natural upper bound that truncates the probability tail. This article derives estimators for the truncated Pareto distribution, investigates their properties, and illustrates a way to check for fit. These methods are illustrated with applications from finance, hydrology, and atmospheric science.

Journal ArticleDOI
TL;DR: The non-flammability of ionic liquids (ILs) is often highlighted as a safety advantage of ILs over volatile organic compounds (VOCs), but the fact that many ILs are not flammable themselves does not mean that they are safe to use near fire and/or heat sources.