Showing papers by "University of Alabama at Birmingham published in 2006"
University of Alabama at Birmingham1, University of Wisconsin-Madison2, Autonomous University of Barcelona3, Eli Lilly and Company4, University of Texas MD Anderson Cancer Center5, University of Virginia6, University of the Witwatersrand7, University of Colorado Boulder8, Gdańsk Medical University9, University of Alabama10, Merck KGaA11, ImClone Systems12
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
TL;DR: This article identified transforming growth factor-beta (TGF-beta) as a cytokine critical for commitment to Thelper-17 (T(H)17) development, which is required for host protection against a bacterial pathogen, Citrobacter rodentium.
Abstract: A new lineage of effector CD4+ T cells characterized by production of interleukin (IL)-17, the T-helper-17 (T(H)17) lineage, was recently described based on developmental and functional features distinct from those of classical T(H)1 and T(H)2 lineages. Like T(H)1 and T(H)2, T(H)17 cells almost certainly evolved to provide adaptive immunity tailored to specific classes of pathogens, such as extracellular bacteria. Aberrant T(H)17 responses have been implicated in a growing list of autoimmune disorders. T(H)17 development has been linked to IL-23, an IL-12 cytokine family member that shares with IL-12 a common subunit, IL-12p40 (ref. 8). The IL-23 and IL-12 receptors also share a subunit, IL-12Rbeta1, that pairs with unique, inducible components, IL-23R and IL-12Rbeta2, to confer receptor responsiveness. Here we identify transforming growth factor-beta (TGF-beta) as a cytokine critical for commitment to T(H)17 development. TGF-beta acts to upregulate IL-23R expression, thereby conferring responsiveness to IL-23. Although dispensable for the development of IL-17-producing T cells in vitro and in vivo, IL-23 is required for host protection against a bacterial pathogen, Citrobacter rodentium. The action of TGF-beta on naive T cells is antagonized by interferon-gamma and IL-4, thus providing a mechanism for divergence of the T(H)1, T(H)2 and T(H)17 lineages.
2,945 citations
TL;DR: The article provides a methodological overview of priority, implementation, and mixing in the sequential explanatory design and offers some practical guidance in addressing those issues.
Abstract: This article discusses some procedural issues related to the mixed-methods sequential explanatory design, which implies collecting and analyzing quantitative and then qualitative data in two consecutive phases within one study. Such issues include deciding on the priority or weight given to the quantitative and qualitative data collection and analysis in the study, the sequence of the data collection and analysis, and the stage/stages in the research process at which the quantitative and qualitative data are connected and the results are integrated. The article provides a methodological overview of priority, implementation, and mixing in the sequential explanatory design and offers some practical guidance in addressing those issues. It also outlines the steps for graphically representing the procedures in a mixed-methods study. A mixed-methods sequential explanatory study of doctoral students’ persistence in a distance-learning program in educational leadership is used to illustrate the methodological dis...
2,123 citations
Ohio State University1, Fred Hutchinson Cancer Research Center2, University of Cincinnati3, University of Iowa4, University of California, Davis5, University of Alabama at Birmingham6, University of Arizona7, University of Washington8, Rush University Medical Center9, Wake Forest University10, University of Nevada, Reno11, University of Texas at San Antonio12, Kaiser Permanente13, University of Pittsburgh14, University of California, Los Angeles15, Stony Brook University16, Baylor College of Medicine17, University of North Carolina at Chapel Hill18, Wayne State University19, Howard University20, George Washington University21, University of California, Irvine22, University of Tennessee Health Science Center23, Medical College of Wisconsin24, University of California, San Diego25, Rutgers University26, University of Florida27, National Institutes of Health28, Harvard University29, University of Minnesota30, University of Massachusetts Boston31, University of Miami32, Emory University33, University of Wisconsin-Madison34, Stanford University35, Northwestern University36, University at Buffalo37, Brown University38, Yeshiva University39
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
TL;DR: Th17 lineage development is reviewed, emphasizing similarities and differences with established effector and regulatory T cell developmental programs that have important implications for immune regulation, immune pathogenesis, and host defense.
1,452 citations
TL;DR: Cognitive training resulted in improved cognitive abilities specific to the abilities trained that continued 5 years after the initiation of the intervention, and booster training for the speed of processing group showed a significant effect on the performance-based functional measure of everyday speed ofprocessing.
Abstract: ContextCognitive training has been shown to improve cognitive abilities in older adults but the effects of cognitive training on everyday function have not been demonstrated.ObjectiveTo determine the effects of cognitive training on daily function and durability of training on cognitive abilities.Design, Setting, and ParticipantsFive-year follow-up of a randomized controlled single-blind trial with 4 treatment groups. A volunteer sample of 2832 persons (mean age, 73.6 years; 26% black), living independently in 6 US cities, was recruited from senior housing, community centers, and hospitals and clinics. The study was conducted between April 1998 and December 2004. Five-year follow-up was completed in 67% of the sample.InterventionsTen-session training for memory (verbal episodic memory), reasoning (inductive reasoning), or speed of processing (visual search and identification); 4-session booster training at 11 and 35 months after training in a random sample of those who completed training.Main Outcome MeasuresSelf-reported and performance-based measures of daily function and cognitive abilities.ResultsThe reasoning group reported significantly less difficulty in the instrumental activities of daily living (IADL) than the control group (effect size, 0.29; 99% confidence interval [CI], 0.03-0.55). Neither speed of processing training (effect size, 0.26; 99% CI, −0.002 to 0.51) nor memory training (effect size, 0.20; 99% CI, −0.06 to 0.46) had a significant effect on IADL. The booster training for the speed of processing group, but not for the other 2 groups, showed a significant effect on the performance-based functional measure of everyday speed of processing (effect size, 0.30; 99% CI, 0.08-0.52). No booster effects were seen for any of the groups for everyday problem-solving or self-reported difficulty in IADL. Each intervention maintained effects on its specific targeted cognitive ability through 5 years (memory: effect size, 0.23 [99% CI, 0.11-0.35]; reasoning: effect size, 0.26 [99% CI, 0.17-0.35]; speed of processing: effect size, 0.76 [99% CI, 0.62-0.90]). Booster training produced additional improvement with the reasoning intervention for reasoning performance (effect size, 0.28; 99% CI, 0.12-0.43) and the speed of processing intervention for speed of processing performance (effect size, 0.85; 99% CI, 0.61-1.09).ConclusionsReasoning training resulted in less functional decline in self-reported IADL. Compared with the control group, cognitive training resulted in improved cognitive abilities specific to the abilities trained that continued 5 years after the initiation of the intervention.Trial Registrationclinicaltrials.gov Identifier: NCT00298558
1,356 citations
TL;DR: In just a few years, microarrays have gone from obscurity to being almost ubiquitous in biological research, and points of consensus are emerging about the general approaches that warrant use and elaboration.
Abstract: In just a few years, microarrays have gone from obscurity to being almost ubiquitous in biological research. At the same time, the statistical methodology for microarray analysis has progressed from simple visual assessments of results to a weekly deluge of papers that describe purportedly novel algorithms for analysing changes in gene expression. Although the many procedures that are available might be bewildering to biologists who wish to apply them, statistical geneticists are recognizing commonalities among the different methods. Many are special cases of more general models, and points of consensus are emerging about the general approaches that warrant use and elaboration.
1,349 citations
TL;DR: The virologic target for patients with treatment failure is now a plasma HIV-1 RNA level below 50 copies/mL, making delivery of state-of-the-art care challenging.
Abstract: Context Guidelines for antiretroviral therapy are important for clinicians worldwide given the complexity of the field and the varied clinical situations in which these agents are used. The International AIDS Society–USA panel has updated its recommendations as warranted by new developments in the field. Objective To provide physicians and other human immunodeficiency virus (HIV) clinicians with current recommendations for the use of antiretroviral therapy in HIVinfected adults in circumstances for which there is relatively unrestricted access to drugs and monitoring tools. The recommendations are centered on 4 key issues: when to start antiretroviral therapy; what to start; when to change; and what to change. Antiretroviral therapy in special circumstances is also described. Data Sources and Study Selection A 16-member noncompensated panel was appointed, based on expertise in HIV research and patient care internationally. Data published or presented at selected scientific conferences from mid 2004 through May 2006 were identified and reviewed by all members of the panel. Data Extraction and Synthesis Data that might change previous guidelines were identified and reviewed. New guidelines were drafted by a writing committee and reviewed by the entire panel. Conclusions Antiretroviral therapy in adults continues to evolve rapidly, making delivery of state-of-the-art care challenging. Initiation of therapy continues to be recommended in all symptomatic persons and in asymptomatic persons after the CD4 cell count falls below 350/µL and before it declines to 200/µL. A nonnucleoside reverse transcriptase inhibitor or a protease inhibitor boosted with low-dose ritonavir each combined with 2 nucleoside (or nucleotide) reverse transcriptase inhibitors is recommended with choice being based on the individual patient profile. Therapy should be changed when toxicity or intolerance mandate it or when treatment failure is documented. The virologic target for patients with treatment failure is now a plasma HIV-1 RNA level below 50 copies/mL. Adherence to antiretroviral therapy in the short-term and the long-term is crucial for treatment success and must be continually reinforced.
1,050 citations
Memorial Hospital of South Bend1, Howard University2, Northwestern University3, George Washington University4, Harvard University5, Stanford University6, Yeshiva University7, University of Pittsburgh8, Fred Hutchinson Cancer Research Center9, University of California, San Diego10, Rutgers University11, University of Alabama at Birmingham12, University of Florida13, University of Minnesota14, Ohio State University15, University of Massachusetts Medical School16, University of Miami17, Emory University18, University of California, Davis19, National Institutes of Health20, University of Wisconsin-Madison21, University of Iowa22, Kaiser Permanente23, University at Buffalo24, Wake Forest University25, Brown University26, Pfizer27, University of Arizona28, Rush University Medical Center29, University of Nevada, Reno30, University of Texas at San Antonio31, University of California, Los Angeles32, University of Cincinnati33, Stony Brook University34, Baylor College of Medicine35, University of North Carolina at Chapel Hill36, Wayne State University37, University of California, Irvine38, University of Tennessee Health Science Center39, Medical College of Wisconsin40
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
1,000 citations
University at Buffalo1, Medical College of Wisconsin2, Fred Hutchinson Cancer Research Center3, Pfizer4, Memorial Hospital of Rhode Island5, University of Nevada, Reno6, University of Miami7, University of Minnesota8, University of Massachusetts Medical School9, Emory University10, National Institutes of Health11, University of California, Davis12, Yeshiva University13, University of Wisconsin-Madison14, Stanford University15, Northwestern University16, University of Iowa17, Kaiser Permanente18, University of Arizona19, University of Washington20, Rush University Medical Center21, Wake Forest University22, University of Texas at San Antonio23, University of California, Los Angeles24, University of California, San Diego25, University of Cincinnati26, Baylor College of Medicine27, University of North Carolina at Chapel Hill28, Wayne State University29, Howard University30, George Washington University31, University of California, Irvine32, Ohio State University33, University of Tennessee Health Science Center34, University of Pittsburgh35, Stony Brook University36, Rutgers University37, University of Alabama at Birmingham38, University of Florida39, Harvard University40
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.)
970 citations
TL;DR: Isoconversional analysis of polymer kinetics has been studied extensively over the past decade as discussed by the authors and has been applied to a wide range of applications, including thermal degradation, crosslinking, glass transition, and glass and melt crystallization.
Abstract: Summary: Isoconversional kinetic analysis involves evaluating a dependence of the effective activation energy on conversion or temperature and using this dependence for making kinetic predictions and for exploring the mechanisms of thermally stimulated processes. The paper discusses major results obtained by the authors in the area of the isoconversional analysis of polymer kinetics over the past decade. It provides a brief introduction to isoconversional methods and surveys the impact made by isoconversional analysis in several application areas that include kinetic predictions, thermal degradation, crosslinking (curing), glass transition, and glass and melt crystallization. It is concluded that isoconversional analysis has been used broadly and fruitfully because it presents a fortunate compromise between the single-step Arrhenius kinetic treatments and the prevalent occurrence of processes whose kinetics are multi-step and/or non-Arrhenius.
An isoconversional method applies the Arrhenius equation to a narrow temperature region, ΔT related to a given extent of conversion.
Montreal General Hospital1, McGill University2, University of Pittsburgh3, SUNY Downstate Medical Center4, Toronto Western Hospital5, Johns Hopkins University School of Medicine6, University of Calgary7, University of Birmingham8, Hanyang University9, University College London10, NHS Lanarkshire11, Yeshiva University12, University of North Carolina at Chapel Hill13, Lund University14, University of Alabama at Birmingham15, Université de Montréal16, Dalhousie University17, University of British Columbia18, University of Western Ontario19, Royal University Hospital20, University of Manitoba21, Northwestern University22
TL;DR: The Lupus Survival Study Group data are reviewed and particularly the data from the State University of New York Health Science Center at Brooklyn, NY is reviewed.
Abstract: Objective. To examine mortality rates in the largest systemic lupus erythematosus (SLE) cohort ever assembled. Methods. Our sample was a multisite international SLE cohort (23 centers, 9,547 patients). Deaths were ascertained by vital statistics registry linkage. Standardized mortality ratio (SMR; ratio of deaths observed to deaths expected) estimates were calculated for-all deaths and by cause. The effects of sex, age, SLE duration, race, and calendar-year periods were determined. Results. The overall SMR was 2.4 (95% confidence interval 2.3-2.5). Particularly high mortality was seen for circulatory disease, infections, renal disease, non-Hodgkin's lymphoma, and lung cancer. The highest SMR estimates were seen in patient groups characterized by female sex, younger age, SLE duration < 1 year, or black/African American race. There was a dramatic decrease in total SMR estimates across calendar-year periods, which was demonstrable for specific causes including death due to infections and death due to renal disorders. However, the SMR due to circulatory diseases tended to increase slightly from the 1970s to the year 2001. Conclusion. Our data from a very large multicenter international cohort emphasize what has been demonstrated previously in smaller samples. These results highlight the increased mortality rate in SLE patients compared with the general population, and they suggest particular risk associated with female sex, younger age, shorter SLE duration, and black/African American race. The risk for certain types of deaths, primarily related to lupus activity (such as renal disease), has decreased over time, while the risk for deaths due to circulatory disease does not appear to have diminished. (Less)
TL;DR: When patients present to specialized clinics after travel to the developing world, travel destinations are associated with the probability of the diagnosis of certain diseases, and diagnostic approaches and empiric therapies can be guided by these destination-specific differences.
Abstract: BACKGROUND Approximately 8 percent of travelers to the developing world require medical care during or after travel. Current understanding of morbidity profiles among ill returned travelers is based on limited data from the 1980s. METHODS Thirty GeoSentinel sites, which are specialized travel or tropical-medicine clinics on six continents, contributed clinician-based sentinel surveillance data for 17,353 ill returned travelers. We compared the frequency of occurrence of each diagnosis among travelers returning from six developing regions of the world. RESULTS Significant regional differences in proportionate morbidity were detected in 16 of 21 broad syndromic categories. Among travelers presenting to GeoSentinel sites, systemic febrile illness without localizing findings occurred disproportionately among those returning from sub-Saharan Africa or Southeast Asia, acute diarrhea among those returning from south central Asia, and dermatologic problems among those returning from the Caribbean or Central or South America. With respect to specific diagnoses, malaria was one of the three most frequent causes of systemic febrile illness among travelers from every region, although travelers from every region except sub-Saharan Africa and Central America had confirmed or probable dengue more frequently than malaria. Among travelers returning from sub-Saharan Africa, rickettsial infection, primarily tick-borne spotted fever, occurred more frequently than typhoid or dengue. Travelers from all regions except Southeast Asia presented with parasite-induced diarrhea more often than with bacterial diarrhea. CONCLUSIONS When patients present to specialized clinics after travel to the developing world, travel destinations are associated with the probability of the diagnosis of certain diseases. Diagnostic approaches and empiric therapies can be guided by these destination-specific differences.
TL;DR: It is estimated that each year in the United States approximately 340,000 non-Hispanic white persons, 130,000non-Hispanic black persons, and 50,000 Mexican American women of childbearing age experience a primary CMV infection.
Abstract: BACKGROUND Cytomegalovirus (CMV) is a leading cause of congenital illness and disability, including hearing loss and mental retardation. However, there are no nationwide estimates of CMV seroprevalence among pregnant women or the overall population of the United States. METHODS To determine CMV prevalence in a representative sample of the US population, we tested serum samples for CMV-specific immunoglobulin G from participants aged > or =6 years (n=21,639) in the third National Health and Nutrition Examination Survey (1988-1994). RESULTS The prevalence of CMV infection was 58.9% in individuals > or =6 years old. CMV seroprevalence increased gradually with age, from 36.3% in 6-11-year-olds to 90.8% in those aged > or =80 years. CMV seroprevalence differed by race and/or ethnicity as follows: 51.2% in non-Hispanic white persons, 75.8% in non-Hispanic black persons, and 81.7% in Mexican Americans. Racial and/or ethnic differences in CMV seroprevalence persisted when controlling for household income level, education, marital status, area of residence, census region, family size, country of birth, and type of medical insurance. Among women, racial and/or ethnic differences were especially significant; between ages 10-14 years and 20-24 years, seroprevalence increased 38% for non-Hispanic black persons, 7% for non-Hispanic white persons, and <1% for Mexican Americans. CONCLUSIONS On the basis of these results, we estimate that each year in the United States approximately 340,000 non-Hispanic white persons, 130,000 non-Hispanic black persons, and 50,000 Mexican American women of childbearing age experience a primary CMV infection. Given the number of women at risk and the significance of congenital disease, development of programs for the prevention of CMV infection, such as vaccination or education, is of considerable public health importance.
TL;DR: By sequence analysis of endemic SIVcpz strains, this work could trace the origins of pandemic and nonpandemic HIV-1 to distinct, geographically isolated chimpanzee communities and establish P. t.
Abstract: Human immunodeficiency virus type 1 (HIV-1), the cause of human acquired immunodeficiency syndrome (AIDS), is a zoonotic infection of staggering proportions and social impact. Yet uncertainty persists regarding its natural reservoir. The virus most closely related to HIV-1 is a simian immunodeficiency virus (SIV) thus far identified only in captive members of the chimpanzee subspecies Pan troglodytes troglodytes. Here we report the detection of SIVcpz antibodies and nucleic acids in fecal samples from wild-living P. t. troglodytes apes in southern Cameroon, where prevalence rates in some communities reached 29 to 35%. By sequence analysis of endemic SIVcpz strains, we could trace the origins of pandemic (group M) and nonpandemic (group N) HIV-1 to distinct, geographically isolated chimpanzee communities. These findings establish P. t. troglodytes as a natural reservoir of HIV-1.
TL;DR: Treatment of prehypertension with candesartan appeared to be well tolerated and reduced the risk of incident hypertension during the study period, and treatment of pre Hypertension appears to be feasible.
Abstract: Background Prehypertension is considered a precursor of stage 1 hypertension and a predictor of excessive cardiovascular risk. We investigated whether pharmacologic treatment of prehypertension prevents or postpones stage 1 hypertension. Methods Participants with repeated measurements of systolic pressure of 130 to 139 mm Hg and diastolic pressure of 89 mm Hg or lower, or systolic pressure of 139 mm Hg or lower and diastolic pressure of 85 to 89 mm Hg, were randomly assigned to receive two years of candesartan (Atacand, AstraZeneca) or placebo, followed by two years of placebo for all. When a participant reached the study end point of stage 1 hypertension, treatment with antihypertensive agents was initiated. Both the candesartan group and the placebo group were instructed to make changes in lifestyle to reduce blood pressure throughout the trial. Results A total of 409 participants were randomly assigned to candesartan, and 400 to placebo. Data on 772 participants (391 in the candesartan group and 381 in the placebo group; mean age, 48.5 years; 59.6 percent men) were available for analysis. During the first two years, hypertension developed in 154 participants in the placebo group and 53 of those in the candesartan group (relative risk reduction, 66.3 percent; P<0.001). After four years, hypertension had developed in 240 participants in the placebo group and 208 of those in the candesartan group (relative risk reduction, 15.6 percent; P<0.007). Serious adverse events occurred in 3.5 percent of the participants assigned to candesartan and 5.9 percent of those receiving placebo. Conclusions Over a period of four years, stage 1 hypertension developed in nearly two thirds of patients with untreated prehypertension (the placebo group). Treatment of prehypertension with candesartan appeared to be well tolerated and reduced the risk of incident hypertension during the study period. Thus, treatment of prehypertension appears to be feasible. (ClinicalTrials.gov number, NCT00227318.)
TL;DR: This review highlights gender-specific issues in ischemic heart disease presentation, evaluation, and outcomes with a special focus on the results derived from the National Institutes of Health-National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation study.
Fred Hutchinson Cancer Research Center1, Kaiser Permanente2, University of California, Los Angeles3, University of Pittsburgh4, University of Massachusetts Medical School5, University of Minnesota6, University of Florida7, Harvard University8, University of Miami9, Ohio State University10, Emory University11, University of California, Davis12, National Institutes of Health13, University of Wisconsin-Madison14, University of Alabama at Birmingham15, Stanford University16, University of Arizona17, Northwestern University18, Wake Forest University19, University at Buffalo20, University of Iowa21, Yeshiva University22, Howard University23, Pfizer24, Brown University25, University of Washington26, Rush University Medical Center27, University of Nevada, Reno28, University of Texas at San Antonio29, University of Cincinnati30, Baylor College of Medicine31, University of North Carolina at Chapel Hill32, Wayne State University33, George Washington University34, University of California, Irvine35, University of Tennessee Health Science Center36, Medical College of Wisconsin37, Stony Brook University38, University of California, San Diego39, Rutgers University40
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
TL;DR: The convergent evolution of these remarkably different adaptive immune systems involved innovative genetic modification of innate-immune-system components.
TL;DR: In this paper, the authors report on the feasibility and early outcomes of the program, which scaled-up human immunodeficiency virus/acquired immunoviciency syndrome (HIV/AIDS) care and treatment services at primary care clinics in Lusaka using predominately nonphysician clinicians.
Abstract: ContextThe Zambian Ministry of Health has scaled-up human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) care and treatment services at primary care clinics in Lusaka, using predominately nonphysician clinicians.ObjectiveTo report on the feasibility and early outcomes of the program.Design, Setting, and PatientsOpen cohort evaluation of antiretroviral-naive adults treated at 18 primary care facilities between April 26, 2004, and November 5, 2005. Data were entered in real time into an electronic patient tracking system.InterventionThose meeting criteria for antiretroviral therapy (ART) received drugs according to Zambian national guidelines.Main Outcome MeasuresSurvival, regimen failure rates, and CD4 cell response.ResultsWe enrolled 21 755 adults into HIV care, and 16 198 (75%) started ART. Among those starting ART, 9864 (61%) were women. Of 15 866 patients with documented World Health Organization (WHO) staging, 11 573 (73%) were stage III or IV, and the mean (SD) entry CD4 cell count among the 15 336 patients with a baseline result was 143/μL (123/μL). Of 1142 patients receiving ART who died, 1120 had a reliable date of death. Of these patients, 792 (71%) died within 90 days of starting therapy (early mortality rate: 26 per 100 patient-years), and 328 (29%) died after 90 days (post-90-day mortality rate: 5.0 per 100 patient-years). In multivariable analysis, mortality was strongly associated with CD4 cell count between 50/μL and 199/μL (adjusted hazard ratio [AHR], 1.4; 95% confidence interval [CI], 1.0-2.0), CD4 cell count less than 50/μL (AHR, 2.2; 95% CI, 1.5-3.1), WHO stage III disease (AHR, 1.8; 95% CI, 1.3-2.4), WHO stage IV disease (AHR, 2.9; 95% CI, 2.0-4.3), low body mass index (<16; AHR,2.4; 95% CI, 1.8-3.2), severe anemia (<8.0 g/dL; AHR, 3.1; 95% CI, 2.3-4.0), and poor adherence to therapy (AHR, 2.9; 95% CI, 2.2-3.9). Of 11 714 patients at risk, 861 failed therapy by clinical criteria (rate, 13 per 100 patient-years). The mean (SD) CD4 cell count increase was 175/μL (174/μL) in 1361 of 1519 patients (90%) receiving treatment long enough to have a 12-month repeat.ConclusionMassive scale-up of HIV and AIDS treatment services with good clinical outcomes is feasible in primary care settings in sub-Saharan Africa. Most mortality occurs early, suggesting that earlier diagnosis and treatment may improve outcomes.
TL;DR: Gender-specific issues in ischemic heart disease presentation, evaluation, and outcomes are highlighted with a special focus on the results published from the National Institutes of Health-National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE) study.
TL;DR: The metabolic syndrome and its individual components are common in PCOS, particularly among women with the highest insulin levels and BMI, and Hyperinsulinemia is a likely common pathogenetic factor for both PCOS and the metabolic syndrome.
Abstract: Context: Polycystic ovary syndrome (PCOS) and the metabolic syndrome have many features in common and may share the same pathogenesis. Objective: This study was performed to determine the prevalence and predictors of the metabolic syndrome in PCOS. Design: The clinical, hormonal, and oral glucose tolerance test results were analyzed in 394 PCOS women who were screened for participation in a multicenter trial to evaluate the effects of troglitazone on ovulation and hirsutism. Setting: A multicenter clinical trial is presented. Patients or Other Participants: The subjects were women with PCOS who had or lacked the metabolic syndrome. Main Outcome Measures: Waist circumference, fasting glucose, high-density lipoprotein cholesterol and triglyceride concentrations, and blood pressure were the main outcome measures. Results: Twenty-six (6.6%) subjects had diabetes; among the 368 nondiabetics, the prevalence for individual components comprising the metabolic syndrome were: waist circumference greater than 88 cm ...
University of Washington1, University of Tennessee Health Science Center2, University of Arizona3, Rutgers University4, University of Iowa5, Rush University Medical Center6, Fred Hutchinson Cancer Research Center7, Pfizer8, Brown University9, University of Nevada, Reno10, University of Texas at San Antonio11, Kaiser Permanente12, University of California, Los Angeles13, University of Cincinnati14, Baylor College of Medicine15, University of North Carolina at Chapel Hill16, Wayne State University17, Howard University18, George Washington University19, University of California, Irvine20, Ohio State University21, Medical College of Wisconsin22, University of Pittsburgh23, Stony Brook University24, University of California, San Diego25, University of Alabama at Birmingham26, Harvard University27, University of Minnesota28, Yeshiva University29, University of Massachusetts Medical School30, University of Miami31, University of Florida32, Emory University33, University of California, Davis34, National Institutes of Health35, University of Wisconsin-Madison36, Stanford University37, Northwestern University38, Wake Forest University39, University at Buffalo40
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
Washington University in St. Louis1, Cornell University2, California Institute of Technology3, Max Planck Society4, Search for extraterrestrial intelligence5, University of Nevada, Reno6, United States Geological Survey7, Arizona State University8, Lockheed Martin Corporation9, American Museum of Natural History10, Ames Research Center11, University of Chicago12, Space Science Institute13, Honeybee Robotics14, Smithsonian Institution15, Massachusetts Institute of Technology16, State University of New York System17, University of Mainz18, Harvard University19, Glenn Research Center20, Texas A&M University21, Ohio State University22, University of Copenhagen23, University of Tennessee24, Goddard Space Flight Center25, University of Arizona26, University of Alabama at Birmingham27
TL;DR: In this paper, the authors show that the surface enrichment is the result of a minor amount of transport and deposition by aqueous processes on the surface of olivine-bearing basalts.
Abstract: Spirit landed on the floor of Gusev Crater and conducted initial operations on soil covered, rock-strewn cratered plains underlain by olivine-bearing basalts. Plains surface rocks are covered by wind-blown dust and show evidence for surface enrichment of soluble species as vein and void-filling materials and coatings. The surface enrichment is the result of a minor amount of transport and deposition by aqueous processes. Layered granular deposits were discovered in the Columbia Hills, with outcrops that tend to dip conformably with the topography. The granular rocks are interpreted to be volcanic ash and/or impact ejecta deposits that have been modified by aqueous fluids during and/or after emplacement. Soils consist of basaltic deposits that are weakly cohesive, relatively poorly sorted, and covered by a veneer of wind blown dust. The soils have been homogenized by wind transport over at least the several kilometer length scale traversed by the rover. Mobilization of soluble species has occurred within at least two soil deposits examined. The presence of mono-layers of coarse sand on wind-blown bedforms, together with even spacing of granule-sized surface clasts, suggest that some of the soil surfaces encountered by Spirit have not been modified by wind for some time. On the other hand, dust deposits on the surface and rover deck have changed during the course of the mission. Detection of dust devils, monitoring of the dust opacity and lower boundary layer, and coordinated experiments with orbiters provided new insights into atmosphere-surface dynamics.
Journal Article•
Vanderbilt University Medical Center1, Duke University2, St. Joseph Hospital3, Henry Ford Health System4, University of Tennessee5, University of Alabama at Birmingham6, Harvard University7, Vanderbilt University8, Yale University9, University of Erlangen-Nuremberg10, Mercy Medical Center (Baltimore, Maryland)11
TL;DR: This list of hospitals and institutes that specialise in nuclear medicine, including Vanderbilt University Medical Center, Durham, North Carolina, and the Institute of Medical Physics, Erlangen-Nurnberg, Germany, are represented.
Abstract: The purpose of these guidelines is to assist physicians in recommending, performing, interpreting, and reporting the results of 18F-FDG PET/CT for oncologic imaging of adult and pediatric patients.
PET is a tomographic scintigraphic technique in which a computer-generated image of local radioactive
TL;DR: Kidney enlargement resulting from the expansion of cysts in patients with ADPKD is continuous and quantifiable and is associated with the decline of renal function.
Abstract: Background Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive enlargement of cyst-filled kidneys. Methods In a three-year study, we measured the rates of change in total kidney volume, total cyst volume, and iothalamate clearance in patients with ADPKD. Of a total of 241 patients, in 232 patients without azotemia who were 15 to 46 years old at baseline we used magnetic-resonance imaging to correlate the total kidney volume and total cyst volume with iothalamate clearance. Statistical methods included analysis of variance, Pearson correlation, and multivariate regression analysis. Results Total kidney volume and total cyst volume increased exponentially, a result consistent with an expansion process dependent on growth. The mean (±SD) total kidney volume was 1060±642 ml at baseline and increased by a mean of 204±246 ml (5.27±3.92 percent per year, P<0.001) over a three-year period among 214 patients. Total cyst volume increased by 218±263 ml (P<0.001) during the same perio...
TL;DR: The factors that specify differentiation of IL-17-producing effector T-cells from naïve T-cell precursors are being rapidly discovered and are providing insights into mechanisms by which signals from cells of the innate immune system guide alternative pathways of Th1, Th2 or Th17 development.
Veterans Health Administration1, University of Kentucky2, Nagoya City University3, Vanderbilt University4, University of Florida5, University of California, Davis6, Michigan State University7, Johns Hopkins University8, University of Alabama at Birmingham9, James Cook University10, University of Wisconsin-Madison11, University of Aberdeen12, University of Pennsylvania13, University of Tokyo14, Genentech15, National Research Council16
TL;DR: This paper showed that the cornea expresses soluble VEGF receptor-1 (sVEGFR-1; also known as sflt-1) and that suppression of this endogenous VEGGF-A trap by neutralizing antibodies, RNA interference or Cre-lox-mediated gene disruption abolishes corneal avascularity in mice.
Abstract: Corneal avascularity-the absence of blood vessels in the cornea-is required for optical clarity and optimal vision, and has led to the cornea being widely used for validating pro- and anti-angiogenic therapeutic strategies for many disorders. But the molecular underpinnings of the avascular phenotype have until now remained obscure and are all the more remarkable given the presence in the cornea of vascular endothelial growth factor (VEGF)-A, a potent stimulator of angiogenesis, and the proximity of the cornea to vascularized tissues. Here we show that the cornea expresses soluble VEGF receptor-1 (sVEGFR-1; also known as sflt-1) and that suppression of this endogenous VEGF-A trap by neutralizing antibodies, RNA interference or Cre-lox-mediated gene disruption abolishes corneal avascularity in mice. The spontaneously vascularized corneas of corn1 and Pax6+/- mice and Pax6+/- patients with aniridia are deficient in sflt-1, and recombinant sflt-1 administration restores corneal avascularity in corn1 and Pax6+/- mice. Manatees, the only known creatures uniformly to have vascularized corneas, do not express sflt-1, whereas the avascular corneas of dugongs, also members of the order Sirenia, elephants, the closest extant terrestrial phylogenetic relatives of manatees, and other marine mammals (dolphins and whales) contain sflt-1, indicating that it has a crucial, evolutionarily conserved role. The recognition that sflt-1 is essential for preserving the avascular ambit of the cornea can rationally guide its use as a platform for angiogenic modulators, supports its use in treating neovascular diseases, and might provide insight into the immunological privilege of the cornea.
TL;DR: Investigation of plausible contributors to the obesity epidemic beyond the two most commonly suggested factors, reduced physical activity and food marketing practices found supportive evidence that in many cases is as compelling as the evidence for more commonly discussed putative explanations.
Abstract: Putative contributors to the secular increase in obesity: exploring the roads less traveled
TL;DR: This study can be used to evaluate individual state surveillance data, and to help plan for public health care and educational needs, and provides valuable data on racial/ethnic patterns of selected major birth defects.
Abstract: BACKGROUND: In the United States, birth defects affect approximately 3% of all births, are a leading cause of infant mortality, and contribute substantially to childhood morbidity. METHODS: Population-based data from the National Birth Defects Prevention Network were combined to estimate the prevalence of 21 selected defects for 1999–2001, stratified by surveillance system type. National prevalence was estimated for each defect by pooling data from 11 states with active case-finding, and adjusting for the racial/ethnic distribution of US live births. We also assessed racial/ethnic variation of the selected birth defects. RESULTS: National birth defect prevalence estimates ranged from 0.82 per 10,000 live births for truncus arteriosus to 13.65 per 10,000 live births for Down syndrome. Compared with infants of non-Hispanic (NH) white mothers, infants of NH black mothers had a significantly higher birth prevalence of tetralogy of Fallot, lower limb reduction defects, and trisomy 18, and a significantly lower birth prevalence of cleft palate, cleft lip with or without cleft palate, esophageal atresia/tracheoesophageal fistula, gastroschisis, and Down syndrome. Infants of Hispanic mothers, compared with infants of NH white mothers, had a significantly higher birth prevalence of anencephalus, spina bifida, encephalocele, gastroschisis, and Down syndrome, and a significantly lower birth prevalence of tetralogy of Fallot, hypoplastic left heart syndrome, cleft palate without cleft lip, and esophageal atresia/tracheoesophageal fistula. CONCLUSIONS: This study can be used to evaluate individual state surveillance data, and to help plan for public health care and educational needs. It also provides valuable data on racial/ethnic patterns of selected major birth defects. Birth Defects Research (Part A), 2006. © 2006 Wiley-Liss, Inc.