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Showing papers by "University of Iowa published in 2006"


Journal ArticleDOI
TL;DR: Among healthy postmenopausal women, calcium with vitamin D supplementation resulted in a small but significant improvement in hip bone density, did not significantly reduce hip fracture, and increased the risk of kidney stones.
Abstract: Background The efficacy of calcium with vitamin D supplementation for preventing hip and other fractures in healthy postmenopausal women remains equivocal. Methods We recruited 36,282 postmenopausal women, 50 to 79 years of age, who were already enrolled in a Women's Health Initiative (WHI) clinical trial. We randomly assigned participants to receive 1000 mg of elemental calcium as calcium carbonate with 400 IU of vitamin D3 daily or placebo. Fractures were ascertained for an average follow-up period of 7.0 years. Bone density was measured at three WHI centers. Results Hip bone density was 1.06 percent higher in the calcium plus vitamin D group than in the placebo group (P<0.01). Intention-to-treat analysis indicated that participants receiving calcium plus vitamin D supplementation had a hazard ratio of 0.88 for hip fracture (95 percent confidence interval, 0.72 to 1.08), 0.90 for clinical spine fracture (0.74 to 1.10), and 0.96 for total fractures (0.91 to 1.02). The risk of renal calculi increased with...

1,765 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
TL;DR: This work summarizes commonly employed models and presents their mathematical development as nucleation, geometrical contraction, diffusion, and reaction order.
Abstract: Many solid-state kinetic models have been developed in the past century. Some models were based on mechanistic grounds while others lacked theoretical justification and some were theoretically incorrect. Models currently used in solid-state kinetic studies are classified according to their mechanistic basis as nucleation, geometrical contraction, diffusion, and reaction order. This work summarizes commonly employed models and presents their mathematical development.

1,437 citations


Journal ArticleDOI
TL;DR: The genomic analysis of miRNAs in the human chromosome 19 miRNA cluster (C19MC) revealed that they are interspersed among Alu repeats, and these findings extend the current view of miRNA origins and the transcriptional machinery driving their expression.
Abstract: Prior work demonstrates that mammalian microRNA (miRNA or miR) expression requires RNA polymerase II (Pol II). However, the transcriptional requirements of many miRNAs remain untested. Our genomic analysis of miRNAs in the human chromosome 19 miRNA cluster (C19MC) revealed that they are interspersed among Alu repeats. Because Alu transcription occurs through RNA Pol III recruitment, and we found that Alu elements upstream of C19MC miRNAs retain sequences important for Pol III activity, we tested the promoter requirements of C19MC miRNAs. Chromatin immunoprecipitation and cell-free transcription assays showed that Pol III, but not Pol II, is associated with miRNA genomic sequence and sufficient for transcription. Moreover, the mature miRNA sequences of approximately 50 additional human miRNAs lie within Alu and other known repetitive elements. These findings extend the current view of miRNA origins and the transcriptional machinery driving their expression.

1,433 citations


Journal ArticleDOI
27 Dec 2006-JAMA
TL;DR: The results suggest that for many women, discontinuation of alendronate for up to 5 years does not appear to significantly increase fracture risk, however, women at very high risk of clinical vertebral fractures may benefit by continuing beyond 5 years.
Abstract: ContextThe optimal duration of treatment of women with postmenopausal osteoporosis is uncertain.ObjectiveTo compare the effects of discontinuing alendronate treatment after 5 years vs continuing for 10 years.Design and SettingRandomized, double-blind trial conducted at 10 US clinical centers that participated in the Fracture Intervention Trial (FIT).ParticipantsOne thousand ninety-nine postmenopausal women who had been randomized to alendronate in FIT, with a mean of 5 years of prior alendronate treatment.InterventionRandomization to alendronate, 5 mg/d (n = 329) or 10 mg/d (n = 333), or placebo (n = 437) for 5 years (1998-2003).Main Outcome MeasuresThe primary outcome measure was total hip bone mineral density (BMD); secondary measures were BMD at other sites and biochemical markers of bone remodeling. An exploratory outcome measure was fracture incidence.ResultsCompared with continuing alendronate, switching to placebo for 5 years resulted in declines in BMD at the total hip (−2.4%; 95% confidence interval [CI], −2.9% to −1.8%; P<.001) and spine (−3.7%; 95% CI, −4.5% to −3.0%; P<.001), but mean levels remained at or above pretreatment levels 10 years earlier. Similarly, those discontinuing alendronate had increased serum markers of bone turnover compared with continuing alendronate: 55.6% (P<.001) for C-telopeptide of type 1 collagen, 59.5% (P < .001) for serum N = propeptide of type 1 collagen, and 28.1% (P<.001) for bone-specific alkaline phosphatase, but after 5 years without therapy, bone marker levels remained somewhat below pretreatment levels 10 years earlier. After 5 years, the cumulative risk of nonvertebral fractures (RR, 1.00; 95% CI, 0.76-1.32) was not significantly different between those continuing (19%) and discontinuing (18.9%) alendronate. Among those who continued, there was a significantly lower risk of clinically recognized vertebral fractures (5.3% for placebo and 2.4% for alendronate; RR, 0.45; 95% CI, 0.24-0.85) but no significant reduction in morphometric vertebral fractures (11.3% for placebo and 9.8% for alendronate; RR, 0.86; 95% CI, 0.60-1.22). A small sample of 18 transilial bone biopsies did not show any qualitative abnormalities, with bone turnover (double labeling) seen in all specimens.ConclusionsWomen who discontinued alendronate after 5 years showed a moderate decline in BMD and a gradual rise in biochemical markers but no higher fracture risk other than for clinical vertebral fractures compared with those who continued alendronate. These results suggest that for many women, discontinuation of alendronate for up to 5 years does not appear to significantly increase fracture risk. However, women at very high risk of clinical vertebral fractures may benefit by continuing beyond 5 years.Trial Registrationclinicaltrials.gov Identifier: NCT 00398931

1,295 citations


Journal ArticleDOI
TL;DR: In this paper, the authors used Deci, Spiegel, Ryan, Koestner, & Kauffman's (1982) teacher-student laboratory paradigm to randomly assign 72 pairs of same-sex preservice teachers into the role of either teacher or student.
Abstract: Teachers with an autonomy-supportive style rely on different instructional behaviors to motivate their students than do teachers with a controlling style. In the present investigation, the authors tested which of these instructional behaviors actually correlated positively or negatively with students' autonomy. The authors used Deci, Spiegel, Ryan, Koestner, & Kauffman's (1982) teacher-student laboratory paradigm to randomly assign 72 pairs of same-sex preservice teachers into the role of either teacher or student. From videotapes of the 10-min instructional episode, raters scored 11 hypothesized autonomy-supportive behaviors and 10 hypothesized controlling behaviors. Correlational analyses confirmed that students perceived the functional significance of 8 instructional behaviors as autonomy supports and 6 instructional behaviors as autonomy thwarts. The discussion focuses on the interpretation and classroom implications of these data.

1,221 citations


Journal ArticleDOI
TL;DR: It is shown that microglia from mice lacking Gi-coupled P2Y12 receptors exhibit normal baseline motility but are unable to polarize, migrate or extend processes toward nucleotides in vitro or in vivo, implying that P2 Y12 is a primary site at which nucleotide act to induce microglial chemotaxis at early stages of the response to local CNS injury.
Abstract: Microglia are primary immune sentinels of the CNS. Following injury, these cells migrate or extend processes toward sites of tissue damage. CNS injury is accompanied by release of nucleotides, serving as signals for microglial activation or chemotaxis. Microglia express several purinoceptors, including a G(i)-coupled subtype that has been implicated in ATP- and ADP-mediated migration in vitro. Here we show that microglia from mice lacking G(i)-coupled P2Y(12) receptors exhibit normal baseline motility but are unable to polarize, migrate or extend processes toward nucleotides in vitro or in vivo. Microglia in P2ry(12)(-/-) mice show significantly diminished directional branch extension toward sites of cortical damage in the living mouse. Moreover, P2Y(12) expression is robust in the 'resting' state, but dramatically reduced after microglial activation. These results imply that P2Y(12) is a primary site at which nucleotides act to induce microglial chemotaxis at early stages of the response to local CNS injury.

1,192 citations


Journal ArticleDOI
TL;DR: Combined analysis of the C2 and BF haplotypes and CFH variants shows that variation in the two loci can predict the clinical outcome in 74% of the affected individuals and 56% ofThe controls, expanding and refine the understanding of the genetic risk for AMD.
Abstract: Age-related macular degeneration (AMD) is the most common form of irreversible blindness in developed countries. Variants in the factor H gene (CFH, also known as HF1), which encodes a major inhibitor of the alternative complement pathway, are associated with the risk for developing AMD. Here we test the hypothesis that variation in genes encoding other regulatory proteins of the same pathway is associated with AMD. We screened factor B (BF) and complement component 2 (C2) genes, located in the major histocompatibility complex class III region, for genetic variation in two independent cohorts comprising approximately 900 individuals with AMD and approximately 400 matched controls. Haplotype analyses identify a statistically significant common risk haplotype (H1) and two protective haplotypes. The L9H variant of BF and the E318D variant of C2 (H10), as well as a variant in intron 10 of C2 and the R32Q variant of BF (H7), confer a significantly reduced risk of AMD (odds ratio = 0.45 and 0.36, respectively). Combined analysis of the C2 and BF haplotypes and CFH variants shows that variation in the two loci can predict the clinical outcome in 74% of the affected individuals and 56% of the controls. These data expand and refine our understanding of the genetic risk for AMD.

1,106 citations


Journal ArticleDOI
TL;DR: Phylogenetic analyses of the components of the human elongation control machinery indicate that the number of mechanisms utilized to regulate P-TEFb function increased as organisms developed more complex developmental patterns.

1,071 citations


Journal ArticleDOI
TL;DR: Chronic behavioral stress results in higher levels of tissue catecholamines, greater tumor burden and more invasive growth of ovarian carcinoma cells in an orthotopic mouse model, and β-adrenergic activation of the cAMP–PKA signaling pathway is identified as a major mechanism by which behavioral stress can enhance tumor angiogenesis in vivo and thereby promote malignant cell growth.
Abstract: Chronic stress promotes tumor growth and angiogenesis in a mouse model of ovarian carcinoma

1,046 citations


Journal ArticleDOI
08 Feb 2006-JAMA
TL;DR: A dietary intervention that reduced total fat intake and increased intakes of vegetables, fruits, and grains did not significantly reduce the risk of CHD, stroke, or CVD in postmenopausal women and achieved only modest effects on CVD risk factors, suggesting that more focused diet and lifestyle interventions may be needed to improve risk factors and reduce CVDrisk.
Abstract: ContextMultiple epidemiologic studies and some trials have linked diet with cardiovascular disease (CVD) prevention, but long-term intervention data are needed.ObjectiveTo test the hypothesis that a dietary intervention, intended to be low in fat and high in vegetables, fruits, and grains to reduce cancer, would reduce CVD risk.Design, Setting, and ParticipantsRandomized controlled trial of 48 835 postmenopausal women aged 50 to 79 years, of diverse backgrounds and ethnicities, who participated in the Women's Health Initiative Dietary Modification Trial. Women were randomly assigned to an intervention (19 541 [40%]) or comparison group (29 294 [60%]) in a free-living setting. Study enrollment occurred between 1993 and 1998 in 40 US clinical centers; mean follow-up in this analysis was 8.1 years.InterventionIntensive behavior modification in group and individual sessions designed to reduce total fat intake to 20% of calories and increase intakes of vegetables/fruits to 5 servings/d and grains to at least 6 servings/d. The comparison group received diet-related education materials.Main Outcome MeasuresFatal and nonfatal coronary heart disease (CHD), fatal and nonfatal stroke, and CVD (composite of CHD and stroke).ResultsBy year 6, mean fat intake decreased by 8.2% of energy intake in the intervention vs the comparison group, with small decreases in saturated (2.9%), monounsaturated (3.3%), and polyunsaturated (1.5%) fat; increases occurred in intakes of vegetables/fruits (1.1 servings/d) and grains (0.5 serving/d). Low-density lipoprotein cholesterol levels, diastolic blood pressure, and factor VIIc levels were significantly reduced by 3.55 mg/dL, 0.31 mm Hg, and 4.29%, respectively; levels of high-density lipoprotein cholesterol, triglycerides, glucose, and insulin did not significantly differ in the intervention vs comparison groups. The numbers who developed CHD, stroke, and CVD (annualized incidence rates) were 1000 (0.63%), 434 (0.28%), and 1357 (0.86%) in the intervention and 1549 (0.65%), 642 (0.27%), and 2088 (0.88%) in the comparison group. The diet had no significant effects on incidence of CHD (hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.90-1.06), stroke (HR, 1.02; 95% CI, 0.90-1.15), or CVD (HR, 0.98; 95% CI, 0.92-1.05). Excluding participants with baseline CVD (3.4%), the HRs (95% CIs) for CHD and stroke were 0.94 (0.86-1.02) and 1.02 (0.90-1.17), respectively. Trends toward greater reductions in CHD risk were observed in those with lower intakes of saturated fat or trans fat or higher intakes of vegetables/fruits.ConclusionsOver a mean of 8.1 years, a dietary intervention that reduced total fat intake and increased intakes of vegetables, fruits, and grains did not significantly reduce the risk of CHD, stroke, or CVD in postmenopausal women and achieved only modest effects on CVD risk factors, suggesting that more focused diet and lifestyle interventions may be needed to improve risk factors and reduce CVD risk.Clinical Trials RegistrationClinicalTrials.gov Identifier: NCT00000611

Journal ArticleDOI
TL;DR: Daily supplementation of calcium with vitamin D for seven years had no effect on the incidence of colorectal cancer among postmenopausal women, and the long latency associated with the development of colorescopy cancer, along with the seven-year duration of the trial, may have contributed to this null finding.
Abstract: Background Higher intake of calcium and vitamin D has been associated with a reduced risk of colorectal cancer in epidemiologic studies and polyp recurrence in polyp-prevention trials. However, randomized-trial evidence that calcium with vitamin D supplementation is beneficial in the primary prevention of colorectal cancer is lacking. Methods We conducted a randomized, double-blind, placebo-controlled trial involving 36,282 postmenopausal women from 40 Women’s Health Initiative centers: 18,176 women received 500 mg of elemental calcium as calcium carbonate with 200 IU of vitamin D3 twice daily (1000 mg of elemental calcium and 400 IU of vitamin D3) and 18,106 received a matching placebo for an average of 7.0 years. The incidence of pathologically confirmed colorectal cancer was the designated secondary outcome. Baseline levels of serum 25-hydroxyvitamin D were assessed in a nested case–control study. Results The incidence of invasive colorectal cancer did not differ significantly between women assigned to calcium plus vitamin D supplementation and those assigned to placebo (168 and 154 cases; hazard ratio, 1.08; 95 percent confidence interval, 0.86 to 1.34; P = 0.51), and the tumor characteristics were similar in the two groups. The frequency of colorectal-cancer screening and abdominal symptoms was similar in the two groups. There were no significant treatment interactions with baseline characteristics. Conclusions Daily supplementation of calcium with vitamin D for seven years had no effect on the incidence of colorectal cancer among postmenopausal women. The long latency associated with the development of colorectal cancer, along with the seven-year duration of the trial, may have contributed to this null finding. Ongoing follow-up will assess the longer-term effect of this intervention. (ClinicalTrials.gov number, NCT00000611.)

Journal ArticleDOI
TL;DR: Extensive experimental evidence shows that DPLL(T) systems can significantly outperform the other state-of-the-art tools, frequently even in orders of magnitude, and have better scaling properties.
Abstract: We first introduce Abstract DPLL, a rule-based formulation of the Davis--Putnam--Logemann--Loveland (DPLL) procedure for propositional satisfiability. This abstract framework allows one to cleanly express practical DPLL algorithms and to formally reason about them in a simple way. Its properties, such as soundness, completeness or termination, immediately carry over to the modern DPLL implementations with features such as backjumping or clause learning.We then extend the framework to Satisfiability Modulo background Theories (SMT) and use it to model several variants of the so-called lazy approach for SMT. In particular, we use it to introduce a few variants of a new, efficient and modular approach for SMT based on a general DPLL(X) engine, whose parameter X can be instantiated with a specialized solver SolverT for a given theory T, thus producing a DPLL(T) system. We describe the high-level design of DPLL(X) and its cooperation with SolverT, discuss the role of theory propagation, and describe different DPLL(T) strategies for some theories arising in industrial applications.Our extensive experimental evidence, summarized in this article, shows that DPLL(T) systems can significantly outperform the other state-of-the-art tools, frequently even in orders of magnitude, and have better scaling properties.

Journal ArticleDOI
TL;DR: In this article, the authors investigate whether firms with strong corporate governance benefit from higher credit ratings relative to firms with weaker governance and find that credit ratings are negatively associated with the number of blockholders and CEO power, and positively related to takeover defenses, accrual quality, earnings timeliness, board independence, board stock ownership, and board expertise.

Journal ArticleDOI
TL;DR: This review integrates clinical, cellular and molecular studies to provide a mechanistic understanding of the interface between biological and behavioural influences in cancer, and identifies novel behavioural or pharmacological interventions that might help improve cancer outcomes.
Abstract: Stress does not cause cancer per se, but depression and a lack of social support might influence cancer progression and clinical outcome. Can identification of the molecular and biological mechanisms involved be used to improve patient treatment? Epidemiological studies indicate that stress, chronic depression and lack of social support might serve as risk factors for cancer development and progression. Recent cellular and molecular studies have identified biological processes that could potentially mediate such effects. This review integrates clinical, cellular and molecular studies to provide a mechanistic understanding of the interface between biological and behavioural influences in cancer, and identifies novel behavioural or pharmacological interventions that might help improve cancer outcomes.

Journal ArticleDOI
TL;DR: A population-based estimate was formulated, based on one large institution's experience in terms of its fraction of patients with OA presenting to lower-extremity adult reconstructive clinics with Oa of posttraumatic origin, that approximately 12% of the overall prevalence of symptomatic OA is attributable to posttraumatic OA of the hip, knee, or ankle.
Abstract: Although posttraumatic osteoarthritis (OA) is a common and important entity in orthopedic practice, no data presently exist regarding its prevalence or its relative burden of disease. A population-based estimate was formulated, based on one large institution's experience in terms of its fraction of patients with OA presenting to lower-extremity adult reconstructive clinics with OA of posttraumatic origin. The relative proportion of these patients undergoing total joint replacement provided a basis for extrapolating institutional experience with posttraumatic OA to a populationwide estimate because the numbers of lower-extremity total joint arthroplasty procedures performed were reliably tabulated both within the institution and populationwide. By this methodology, approximately 12% of the overall prevalence of symptomatic OA is attributable to posttraumatic OA of the hip, knee, or ankle. This corresponds to approximately 5.6 million individuals in the United States being affected by posttraumatic OA sufficiently severe to have caused them to present for care by an orthopedic lower-extremity adult reconstructive surgeon. Further, based on the relative prevalence of OA versus rheumatoid arthritis, and their relative impacts as assessed by the SF-36 (Short-Form 36) lower-extremity physical composite scores, about 85.5% of the societal costs of arthritis are attributable to OA. The corresponding aggregate financial burden specifically of posttraumatic OA is Dollars 3.06 billion annually, or approximately 0.15% of the total U.S. health care direct cost outlay.

Journal ArticleDOI
TL;DR: In this paper, a quantitative review of 93 studies examining relationships between team design features and team performance is presented. But the effect varies depending on task type and team member heterogeneity and performance.

Journal ArticleDOI
08 Feb 2006-JAMA
TL;DR: Among postmenopausal women, a low-fat dietary pattern did not result in a statistically significant reduction in invasive breast cancer risk over an 8.1-year average follow-up period, and the nonsignificant trends observed indicate that longer, planned, nonintervention follow- up may yield a more definitive comparison.
Abstract: ContextThe hypothesis that a low-fat dietary pattern can reduce breast cancer risk has existed for decades but has never been tested in a controlled intervention trial.ObjectiveTo assess the effects of undertaking a low-fat dietary pattern on breast cancer incidence.Design and SettingA randomized, controlled, primary prevention trial conducted at 40 US clinical centers from 1993 to 2005.ParticipantsA total of 48 835 postmenopausal women, aged 50 to 79 years, without prior breast cancer, including 18.6% of minority race/ethnicity, were enrolled.InterventionsWomen were randomly assigned to the dietary modification intervention group (40% [n = 19 541]) or the comparison group (60% [n = 29 294]). The intervention was designed to promote dietary change with the goals of reducing intake of total fat to 20% of energy and increasing consumption of vegetables and fruit to at least 5 servings daily and grains to at least 6 servings daily. Comparison group participants were not asked to make dietary changes.Main Outcome MeasureInvasive breast cancer incidence.ResultsDietary fat intake was significantly lower in the dietary modification intervention group compared with the comparison group. The difference between groups in change from baseline for percentage of energy from fat varied from 10.7% at year 1 to 8.1% at year 6. Vegetable and fruit consumption was higher in the intervention group by at least 1 serving per day and a smaller, more transient difference was found for grain consumption. The number of women who developed invasive breast cancer (annualized incidence rate) over the 8.1-year average follow-up period was 655 (0.42%) in the intervention group and 1072 (0.45%) in the comparison group (hazard ratio, 0.91; 95% confidence interval, 0.83-1.01 for the comparison between the 2 groups). Secondary analyses suggest a lower hazard ratio among adherent women, provide greater evidence of risk reduction among women having a high-fat diet at baseline, and suggest a dietary effect that varies by hormone receptor characteristics of the tumor.ConclusionsAmong postmenopausal women, a low-fat dietary pattern did not result in a statistically significant reduction in invasive breast cancer risk over an 8.1-year average follow-up period. However, the nonsignificant trends observed suggesting reduced risk associated with a low-fat dietary pattern indicate that longer, planned, nonintervention follow-up may yield a more definitive comparison.Clinical Trials RegistrationClinicalTrials.gov Identifier: NCT00000611

Journal ArticleDOI
TL;DR: This data indicates that the survival among patients with laryngeal cancer during the past 2 decades in the United States has decreased, but there has been an increase in the nonsurgical treatment of larynGEal cancer.
Abstract: Background: Survival has decreased among patients with laryngeal cancer during the past 2 decades in the United States. During this same period, there has been an increase in the nonsurgical treatment of laryngeal cancer. Objective: The objectives of this study were to identify trends in the demographics, management, and outcome of laryngeal cancer in the United States and to analyze factors contributing to the decreased survival. Study Design: The authors conducted a retrospective, longitudinal study of laryngeal cancer cases. Methods: Review of the National Cancer Data Base (NCDB) revealed 158,426 cases of laryngeal squamous cell carcinoma (excluding verrucous carcinoma) diagnosed between the years 1985 and 2001. Analysis of these case records addressed demographics, management, and survival for cases grouped according to stage, site, and specific TNM classifications. Results: This review of data from the NCDB analysis confirms the previously identified trend toward decreasing survival among patients with laryngeal cancer from the mid-1980s to mid-1990s. Patterns of initial management across this same period indicated an increase in the use of chemoradiation with a decrease in the use of surgery despite an increase in the use of endoscopic resection. The most notable decline in the 5-year relative survival between the 1985 to 1990 period and the 1994 to 1996 period occurred among advanced-stage glottic cancer, early-stage supraglottic cancers, and supraglottic cancers classified as T3N0M0. Initial treatment of T3N0M0 laryngeal cancer (all sites) in the 1994 to 1996 period resulted in poor 5-year relative survival for those receiving either chemoradiation (59.2%) or irradiation alone (42.7%) when compared with that of patients after surgery with irradiation (65.2%) and surgery alone (63.3%). In contrast, identical 5-year relative survival (65.6%) rates were observed during this same period for the subset of T3N0M0 glottic cancers initially treated with either chemoradiation or surgery with irradiation. Conclusions: The decreased survival recorded for patients with laryngeal cancer in the mid-1990s may be related to changes in patterns of management. Future studies are warranted to further evaluate these associations.

Journal ArticleDOI
TL;DR: Positron-emission tomography has become an important tool for evaluating tumors, detecting occult cancer, and staging and restaging tumors.
Abstract: Positron-emission tomography has become an important tool for evaluating tumors, detecting occult cancer, and staging and restaging tumors. This review includes a slideshow with scans from 10 patients with common cancers.

Journal ArticleDOI
TL;DR: The authors used firms' disclosures of internal control problems prior to audits mandated by Section 404 of the Sarbanes-Oxley Act (SOX) to investigate the economic factors that expose firms to internal control failure risks and managements' incentives to discover and report internal control deficiencies (ICDs).
Abstract: This paper uses firms' disclosures of internal control problems prior to audits mandated by Section 404 of the Sarbanes-Oxley Act (SOX) to investigate the economic factors that expose firms to internal control failure risks and managements' incentives to discover and report internal control deficiencies (ICDs). We find that firms making pre-SOX 404 ICD disclosures typically have more complex operations, recent changes in organization structure, more accounting risk exposure, fewer resources to invest in internal control and higher incidence of auditor resignation relative to firms that do not report internal control problems. Regarding incentives to discover and report internal control problems, we find that ICD firms have more prior SEC enforcement actions and restatements of financial statements, are more likely to use a dominant audit firm, and are more likely to have concentrated institutional ownership. Our findings are important in developing expectations about determinants of internal control problems across all SEC registrants including non-accelerated filers that are not yet required to comply with SOX 404, as well as providing baseline evidence for evaluating the discovery and reporting of ICDs under mandated internal control audits.

Journal Article
TL;DR: This paper presents a meta-modelling study of the response of positron emission tomography (PET) to radiolysis (radiolysis) and its applications to nuclear medicine and Radiology.
Abstract: Many therapeutic clinical trials have proposed using a measure of metabolic change to assess therapeutic response rather than relying on conventional anatomic measurements of changes in tumor size on CT or MRI. PET assessment of changes in 18F-FDG uptake by tumors is gaining acceptance as such a

Journal ArticleDOI
TL;DR: These guidelines represent the current recommendations on the diagnosis and management of prolactinomas based upon comprehensive analysis and synthesis of all available data.
Abstract: In June 2005, an ad hoc Expert Committee formed by the Pituitary Society convened during the 9th International Pituitary Congress in San Diego, California. Members of this committee consisted of invited international experts in the field, and included endocrinologists and neurosurgeons with recognized expertise in the management of prolactinomas. Discussions were held that included all interested participants to the Congress and resulted in formulation of these guidelines, which represent the current recommendations on the diagnosis and management of prolactinomas based upon comprehensive analysis and synthesis of all available data.

Journal ArticleDOI
08 Feb 2006-JAMA
TL;DR: A low-fat dietary pattern intervention did not reduce the risk of colorectal cancer in postmenopausal women during 8.1 years of follow-up, and secondary analyses suggested potential interactions with baseline aspirin use and combined estrogen-progestin use status.
Abstract: ContextObservational studies and polyp recurrence trials are not conclusive regarding the effects of a low-fat dietary pattern on risk of colorectal cancer, necessitating a primary prevention trial.ObjectiveTo evaluate the effects of a low-fat eating pattern on risk of colorectal cancer in postmenopausal women.Design, Setting, and ParticipantsThe Women’s Health Initiative Dietary Modification Trial, a randomized controlled trial conducted in 48 835 postmenopausal women aged 50 to 79 years recruited between 1993 and 1998 from 40 clinical centers throughout the United States.InterventionsParticipants were randomly assigned to the dietary modification intervention (n = 19 541; 40%) or the comparison group (n = 29 294; 60%).The intensive behavioral modification program aimed to motivate and support reductions in dietary fat, to increase consumption of vegetables and fruits, and to increase grain servings by using group sessions, self-monitoring techniques, and other tailored and targeted strategies. Women in the comparison group continued their usual eating pattern.Main Outcome MeasureInvasive colorectal cancer incidence.ResultsA total of 480 incident cases of invasive colorectal cancer occurred during a mean follow-up of 8.1 (SD, 1.7) years. Intervention group participants significantly reduced their percentage of energy from fat by 10.7% more than did the comparison group at 1 year, and this difference between groups was mostly maintained (8.1% at year 6). Statistically significant increases in vegetable, fruit, and grain servings were also made. Despite these dietary changes, there was no evidence that the intervention reduced the risk of invasive colorectal cancer during the follow-up period. There were 201 women with invasive colorectal cancer (0.13% per year) in the intervention group and 279 (0.12% per year) in the comparison group (hazard ratio, 1.08; 95% confidence interval, 0.90-1.29). Secondary analyses suggested potential interactions with baseline aspirin use and combined estrogen-progestin use status (P = .01 for each). Colorectal examination rates, although not protocol defined, were comparable between the intervention and comparison groups. Similar results were seen in analyses adjusting for adherence to the intervention.ConclusionIn this study, a low-fat dietary pattern intervention did not reduce the risk of colorectal cancer in postmenopausal women during 8.1 years of follow-up.Clinical Trials RegistrationClinicalTrials.gov Identifier: NCT00000611

Journal ArticleDOI
TL;DR: The authors used path analysis to test a model that posits that relevant personality traits will have both direct relationships with counterproductive work behaviors (CPBs) and indirect relationships to CPBs through the mediating effects of job satisfaction.
Abstract: This study used path analysis to test a model that posits that relevant personality traits will have both direct relationships with counterproductive work behaviors (CPBs) and indirect relationships to CPBs through the mediating effects of job satisfaction. Based on a sample (n = 141) of customer service employees, results generally supported the hypothesized model for both boss- and self-rated CPBs. Agreeableness had a direct relationship with interpersonal counterproductive work behaviors (CPB-I); Conscientiousness had a direct relationship with organizational counterproductive work behaviors (CPB-O); and, job satisfaction had a direct relationship to both CPB-I and CPB-O. In addition, job satisfaction partially mediated the relationship between Agreeableness and both CPB-O and CPB-I. Overall, results show that personality traits differentially predict CPBs and that employees’ attitudes about their jobs explain, in part, these personality‐behavior associations.

Journal ArticleDOI
TL;DR: In this article, the authors argue that students' classroom engagement depends, in part, on the supportive quality of the classroom climate in which they learn and that teachers most engage students when they offer high levels of autonomy support and structure.
Abstract: Students are sometimes proactive and engaged in classroom learning activities, but they are also sometimes only reactive and passive. Recognizing this, in this article I argue that students’ classroom engagement depends, in part, on the supportive quality of the classroom climate in which they learn. According to the dialectical framework within self‐determination theory, students possess inner motivational resources that classroom conditions can support or frustrate. When teachers find ways to nurture these inner resources, they adopt an autonomy‐supportive motivating style. After articulating what autonomy‐supportive teachers say and do during instruction, I discuss 3 points: teachers can learn how to be more autonomy supportive toward students; teachers most engage students when they offer high levels of both autonomy support and structure; and an autonomy‐supportive motivating style is an important element to a high‐quality teacher‐student relationship.

Journal ArticleDOI
TL;DR: Functional fecal incontinence is a common, but underrecognized symptom, which is equally prevalent in men and women, and can often cause considerable distress, and the clinical features are useful for guiding diagnostic testing and therapy.

Journal ArticleDOI
TL;DR: Recently, compelling evidence has emerged that the innate immune system and, more specifically, uncontrolled regulation of the complement alternative pathway plays a central role in the pathobiology of AMD.
Abstract: Today, the average life expectancy in developed nations is over 80 years and climbing. And yet, the quality of life during those additional years is often significantly diminished by the effects of age‐related, degenerative diseases, including age‐related macular degeneration (AMD), the leading cause of blindness in the elderly worldwide. AMD is characterized by a progressive loss of central vision attributable to degenerative and neovascular changes in the macula, a highly specialized region of the ocular retina responsible for fine visual acuity. Estimates gathered from the most recent World Health Organization (WHO) global eye disease survey conservatively indicate that 14 million persons are blind or severely visually impaired because of AMD. The disease has a tremendous impact on the physical and mental health of the geriatric population and their families and is becoming a major public health burden.Currently, there is neither a cure nor a means to prevent AMD. Palliative treatment options for the l...

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TL;DR: Using 1 year of aerosol optical thickness (AOT) retrievals from the MODerate resolution Imaging Spectro-radiometer (MODIS) on board NASA's Terra and Aqua satellite along with ground measurements of PM2.5 mass concentration, the authors assess particulate matter air quality over different locations across the global urban areas spread over 26 locations in Sydney, Delhi, Hong Kong, New York City and Switzerland.

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TL;DR: This study replicated findings on the association of the ADS with SAA and determined whether the ADS is clinically useful for preventing anticholinergic adverse effects, and examined modifications that did not appear useful in optimizing the ADS.
Abstract: Anticholinergic Drug Scale (ADS) scores were previously associated with serum anticholinergic activity (SAA) in a pilot study. To replicate these results, the association between ADS scores and SAA was determined using simple linear regression in subjects from a study of delirium in 201 long-term care facility residents who were not included in the pilot study. Simple and multiple linear regression models were then used to determine whether the ADS could be modified to more effectively predict SAA in all 297 subjects. In the replication analysis, ADS scores were significantly associated with SAA (R2 = .0947, P < .0001). In the modification analysis, each model significantly predicted SAA, including ADS scores (R2 = .0741, P < .0001). The modifications examined did not appear useful in optimizing the ADS. This study replicated findings on the association of the ADS with SAA. Future work will determine whether the ADS is clinically useful for preventing anticholinergic adverse effects.