Showing papers by "University of Colorado Denver published in 2004"
Columbia University1, University of Michigan2, University of California, Davis3, Baylor College of Medicine4, University of Massachusetts Medical School5, Mayo Clinic6, University of Washington7, University of Arkansas for Medical Sciences8, University of California, San Francisco9, Cleveland Clinic10, University of Colorado Denver11
TL;DR: The improvement in median survival of nearly two months with docetaxel and estramustine, as compared with mitoxantrone and prednisone, provides support for this approach in men with metastatic, androgen-independent prostate cancer.
Abstract: background Mitoxantrone-based chemotherapy palliates pain without extending survival in men with progressive androgen-independent prostate cancer. We compared docetaxel plus estramustine with mitoxantrone plus prednisone in men with metastatic, hormoneindependent prostate cancer. methods We randomly assigned 770 men to one of two treatments, each given in 21-day cycles: 280 mg of estramustine three times daily on days 1 through 5, 60 mg of docetaxel per square meter of body-surface area on day 2, and 60 mg of dexamethasone in three divided doses before docetaxel, or 12 mg of mitoxantrone per square meter on day 1 plus 5 mg of prednisone twice daily. The primary end point was overall survival; secondary end points were progression-free survival, objective response rates, and post-treatment declines of at least 50 percent in serum prostate-specific antigen (PSA) levels. results Of 674 eligible patients, 338 were assigned to receive docetaxel and estramustine and 336 to receive mitoxantrone and prednisone. In an intention-to-treat analysis, the median overall survival was longer in the group given docetaxel and estramustine than in the group given mitoxantrone and prednisone (17.5 months vs. 15.6 months, P=0.02 by the log-rank test), and the corresponding hazard ratio for death was 0.80 (95 percent confidence interval, 0.67 to 0.97). The median time to progression was 6.3 months in the group given docetaxel and estramustine and 3.2 months in the group given mitoxantrone and prednisone (P<0.001 by the log-rank test). PSA declines of at least 50 percent occurred in 50 percent and 27 percent of patients, respectively (P<0.001), and objective tumor responses were observed in 17 percent and 11 percent of patients with bidimensionally measurable disease, respectively (P=0.30). Grade 3 or 4 neutropenic fevers (P=0.01), nausea and vomiting (P<0.001), and cardiovascular events (P=0.001) were more common among patients receiving docetaxel and estramustine than among those receiving mitoxantrone and prednisone. Pain relief was similar in both groups. conclusions The improvement in median survival of nearly two months with docetaxel and estramustine, as compared with mitoxantrone and prednisone, provides support for this approach in men with metastatic, androgen-independent prostate cancer.
3,554 citations
TL;DR: Biopsy-detected prostate cancer, including high-grade cancers, is not rare among men with PSA levels of 4.0 ng per milliliter or less--levels generally thought to be in the normal range.
Abstract: Background The optimal upper limit of the normal range for prostate-specific antigen (PSA) is unknown. We investigated the prevalence of prostate cancer among men in the Prostate Cancer Prevention Trial who had a PSA level of 4.0 ng per milliliter or less. Methods Of 18,882 men enrolled in the prevention trial, 9459 were randomly assigned to receive placebo and had an annual measurement of PSA and a digital rectal examination. Among these 9459 men, 2950 men never had a PSA level of more than 4.0 ng per milliliter or an abnormal digital rectal examination, had a final PSA determination, and underwent a prostate biopsy after being in the study for seven years. Results Among the 2950 men (age range, 62 to 91 years), prostate cancer was diagnosed in 449 (15.2 percent); 67 of these 449 cancers (14.9 percent) had a Gleason score of 7 or higher. The prevalence of prostate cancer was 6.6 percent among men with a PSA level of up to 0.5 ng per milliliter, 10.1 percent among those with values of 0.6 to 1.0 ng per mi...
2,425 citations
Lund University1, University of Colorado Denver2, University of California, San Diego3, University of Grenoble4, Mayo Clinic5, University of Hawaii6, University of Washington7, University of Portland8, University of Melbourne9, University of Medicine and Dentistry of New Jersey10, University of Lyon11, University of Edinburgh12, University College London13, University of Michigan14
TL;DR: The CEAP classification for chronic venous disorders was developed in 1994 by an international ad hoc committee of the American Venous Forum, endorsed by the Society for Vascular Surgery, and incorporated into "Reporting Standards in Venous Disease" in 1995.
1,695 citations
TL;DR: Pulmonary arterial hypertension has a multifactorial pathobiology and recent genetic and pathophysiologic studies have emphasized the relevance of several mediators in this condition, including prostacyclin, nitric oxide, ET-1, angiopoietin- 1, serotonin, cytokines, chemokines, and members of the transforming-growth-factor-beta superfamily.
1,501 citations
TL;DR: In this paper, the authors randomly assigned patients at increased risk for perioperative cardiac complications and clinically significant coronary artery disease to undergo either revascularization or no revascularisation before elective major vascular surgery.
Abstract: Background The benefit of coronary-artery revascularization before elective major vascular surgery is unclear. Methods We randomly assigned patients at increased risk for perioperative cardiac complications and clinically significant coronary artery disease to undergo either revascularization or no revascularization before elective major vascular surgery. The primary end point was long-term mortality. Results Of 5859 patients scheduled for vascular operations at 18 Veterans Affairs medical centers, 510 (9 percent) were eligible for the study and were randomly assigned to either coronary-artery revascularization before surgery or no revascularization before surgery. The indications for a vascular operation were an expanding abdominal aortic aneurysm (33 percent) or arterial occlusive disease of the legs (67 percent). Among the patients assigned to preoperative coronary-artery revascularization, percutaneous coronary intervention was performed in 59 percent, and bypass surgery was performed in 41 percent. T...
1,167 citations
TL;DR: In this paper, the prevalence of diabetic retinopathy among adults 40 years and older in the United States was estimated by pooled analysis of data from 8 population-based eye surveys.
Abstract: Objective: To determine the prevalence of diabetic retinopathy among adults 40 years and older in the United States.Methods: Pooled analysis of data from 8 population-based eye surveys was used to estimate the prevalence, among persons with diabetes mellitus (DM), of retinopathy and of vision-threatening retinopathy-defined as proliferative or severe nonproliferative retinopathy and/or macular edema. Within strata of age, race/ethnicity, and gender, US prevalence rates were estimated by multiplying these values by the prevalence of DM reported in the 1999 National Health Interview Survey and the 2000 US Census population.Results: Among an estimated 10.2 million US adults 40 years and older known to have DM, the estimated crude prevalence rates for retinopathy and vision-threatening retinopathy were 40.3% and 8.2%, respectively. The estimated US general population prevalence rates for retinopathy and vision-threatening retinopathy were 3.4% (4.1 million persons) and 0.75% (899000 persons). Future projections suggest that diabetic retinopathy will increase as a public health problem, both with aging of the US population and increasing age-specific prevalence of DM over time.Conclusion: Approximately 4.1 million US adults 40 years and older have diabetic retinopathy; 1 of every 12 persons with DM in this age group has advanced, vision-threatening retinopathy.
1,092 citations
TL;DR: The open technique is superior to the laparoscopic technique for mesh repair of primary hernias and rates of recurrence after repair of recurrent hernia were similar in the two groups.
Abstract: BACKGROUND Repair of inguinal hernias in men is a common surgical procedure, but the most effective surgical technique is unknown. METHODS We randomly assigned men with inguinal hernias at 14 Veterans Affairs (VA) medical centers to either open mesh or laparoscopic mesh repair. The primary outcome was recurrence of hernias at two years. Secondary outcomes included complications and patient-centered outcomes. RESULTS Of the 2164 patients who were randomly assigned to one of the two procedures, 1983 underwent an operation; two-year follow-up was completed in 1696 (85.5 percent). Recurrences were more common in the laparoscopic group (87 of 862 patients [10.1 percent]) than in the open group (41 of 834 patients [4.9 percent]; odds ratio, 2.2; 95 percent confidence interval, 1.5 to 3.2). The rate of complications was higher in the laparoscopic-surgery group than in the open-surgery group (39.0 percent vs. 33.4 percent; adjusted odds ratio, 1.3; 95 percent confidence interval, 1.1 to 1.6). The laparoscopic-surgery group had less pain initially than the open-surgery group on the day of surgery (difference in mean score on a visual-analogue scale, 10.2 mm; 95 percent confidence interval, 4.8 to 15.6) and at two weeks (6.1 mm; 95 percent confidence interval, 1.7 to 10.5) and returned to normal activities one day earlier (adjusted hazard ratio for a shorter time to return to normal activities, 1.2; 95 percent confidence interval, 1.1 to 1.3). In prespecified analyses, there was a significant interaction between the surgical approach (open or laparoscopic) and the type of hernia (primary or recurrent) (P=0.012). Recurrence was significantly more common after laparoscopic repair than after open repair of primary hernias (10.1 percent vs. 4.0 percent), but rates of recurrence after repair of recurrent hernias were similar in the two groups (10.0 percent and 14.1 percent, respectively). CONCLUSIONS The open technique is superior to the laparoscopic technique for mesh repair of primary hernias.
869 citations
TL;DR: The study concluded that the discipline needs to oversee the training of family physicians who are committed to excellence, steeped in the core values of the discipline, competent to provide family medicine’s basket of services within the New Model, and capable of adapting to varying patient needs and changing care technologies.
Abstract: BACKGROUND Recognizing fundamental fl aws in the fragmented US health care systems and the potential of an
679 citations
Book•
16 Aug 2004TL;DR: SPSS for Intermediate Statistics as mentioned in this paper is a tool to help students learn to analyze and interpret research data using SPSS by demonstrating how to compute a variety of statistics covered in intermediate statistics courses.
Abstract: This book helps students learn to analyze and interpret research data using SPSS by demonstrating how to compute a variety of statistics covered in intermediate statistics courses. This edition features SPSS 15.0, but it can also be used with SPSS 16 & 17 or earlier versions.
Each chapter introduces several related statistics in a user-friendly manner and provides instructions on how to run them and interpret the outputs. The book reviews research designs and how to assess the assumptions, accuracy, and reliability of data. The authors demonstrate how to: choose an appropriate statistic based on the research design and level of measurement; use SPSS to help answer research questions; and interpret and write about SPSS outputs. The examples use real data contained on the book's CD.
The 3rd edition features:
Instructor's Resource materials (available on request) with answers to interpretation questions, extra SPSS problems and course support for instructors
Four extra SPSS problems in each chapter for additional practice
A new chapter on multilevel linear modeling with SPSS
Post-hoc tests in addition to contrasts in the Factorial ANOVA and ANCOVA chapter
Coverage of odd ratios and effect sizes for logistic and discriminant analyses
How to compute and interpret post-hoc power demonstrated for each statistic
An expanded Appendix, Getting Started and Other Useful SPSS Commands, including how to work with the output; import and export files; select cases; and split and merge files.
SPSS for Intermediate Statistics, 3rd Edition provides:
The key SPSS windows needed to perform the analyses
Display of the outputs readers can expect to produce with call-out boxes to highlight what to focus on
Interpretation sections and questions to help students better understand the output and write about the results
Charts and tables to help select an appropriate statistic and interpret statistical significance and effect sizes
Lab assignments organized around the way students proceed in every step of a research project
Appendices on getting started with SPSS, a brief review of basic statistics, and answers to the odd-numbered interpretation questions
Twenty data sets on the book's CD along with a quick reference guide and how to make tables and figures.
This inexpensive paperback is intended as a supplemental text for advanced undergraduate or graduate courses on intermediate/advanced statistics and/or research methods taught in departments of psychology, education, human development, and other applied and health sciences, and/or for researchers in these areas looking to have a handy reference for SPSS.
Instructor's Resource materials are free upon adoption. View www.researchmethodsarena.com.
629 citations
TL;DR: It is demonstrated that older male carriers of premutation alleles of the FMR1 gene are at high risk of developing fragile X-associated tremor/ataxia syndrome (FXTAS), and older men with ataxia and intention tremor should be screened for the F MR1 mutation.
Abstract: ContextPremutation expansions (55-200 CGG repeats) of the fragile X mental
retardation 1 (FMR1) gene are frequent in the general
population, with estimated prevalences of 1 per 259 females and 1 per 813
males. Several articles have recently described the presence of late-onset
neurological symptoms in male carriers of premutation (FMR1) alleles. The main clinical features described in this newly identified
syndrome are cerebellar ataxia and intention tremor. Additional documented
symptoms include short-term memory loss, executive functional deficits, cognitive
decline, parkinsonism, peripheral neuropathy, lower-limb proximal muscle weakness,
and autonomic dysfunction.ObjectiveTo study the penetrance of the fragile X–associated tremor/ataxia
syndrome (FXTAS) among premutation carriers.Design, Setting, and ParticipantsFamily-based study of 192 individuals (premutation carriers and controls)
whose families belong to the Northern or Southern California Fragile X Associations.
Data were collected (March 2002-April 2003) through a survey and a standardized
neurological examination, which was videotaped and subsequently scored in
a blinded fashion.Main Outcome MeasuresPenetrance of intention tremor and ataxia among adult carriers (aged
≥50 years) of premutation expansions of the FMR1 gene.ResultsData from the survey of 192 individuals demonstrated an age-related
penetrance of the combination of reported intention tremor and gait ataxia
in male carriers (17%, 38%, 47%, and 75% [lower-bound estimates] for participants
aged 50-59, 60-69, 70-79, and ≥80 years, respectively). The male carrier
group had an age-adjusted 13-fold increased risk (95% confidence interval,
3.9-25.4; P = .003) of combined intention tremor
and gait ataxia when compared with male controls. The clinical examination
data from 93 individuals demonstrated that male carriers experienced more
difficulties on each of 3 standardized neurological rating scales compared
with controls (P<.05). Female carrier scores were
also higher than those of female controls (P<.05)
on 2 of the 3 neurological rating scales, but no participant was identified
with probable or definite FXTAS.ConclusionsThe study demonstrates that older male carriers of premutation alleles
of the FMR1 gene are at high risk of developing FXTAS.
Since male premutation carriers are relatively common in the general population,
older men with ataxia and intention tremor should be screened for the FMR1 mutation, especially if these signs are accompanied
by parkinsonism, autonomic dysfunction, or cognitive decline, regardless of
family history.
589 citations
Cedars-Sinai Medical Center1, NewYork–Presbyterian Hospital2, University of California, Los Angeles3, University of North Carolina at Chapel Hill4, University of Alabama at Birmingham5, University of California, San Francisco6, University of Hamburg7, Université catholique de Louvain8, Mayo Clinic9, Rush University Medical Center10, University of Duisburg-Essen11, University of Padua12, University of Barcelona13, Oregon Health & Science University14, Erasmus University Rotterdam15, Tufts University16, University of Córdoba (Spain)17, University of Toledo18, University of Colorado Denver19
TL;DR: This is the first prospective, randomized, controlled trial of an extracorporeal liver support system, demonstrating safety and improved survival in patients with fulminant/subfulminant hepatic failure.
Abstract: Objective: The HepatAssist liver support system is an extracorpo-real porcine hepatocyte-based bioartificial liver (BAL). The safety and efficacy of the BAL were evaluated in a prospective. random-ized, controlled, multicenter trial in patients with severe acute liver failure. Summary Background Data: In experimental animals with acute liver failure, we demonstrated beneficial effects of the BAL. Similarly, Phase I trials of the BAL in acute liver failure patients yielded promising results. Methods: A total of 171 patients (86 control and 85 BAL) were enrolled. Patients with fulminant/subfulminant hepatic failure and primary nonfunction following liver transplantation were included. Data were analyzed with and without accounting for the following confounding factors: liver transplantation, time to transplant, disease etiology, disease severity, and treatment site. Results: For the entire patient population, survival at 30 days was 71% for BAL versus 62% for control (P = 0.26). After exclusion of primary nonfunction patients, survival was 73% for BAL Versus 59% for control (it = 147; P= 0.12). When Survival was analyzed accounting for confounding factors. in the entire patient Population, there was no difference between the 2 groups (risk ratio = 0.67; P = 0.13). However, survival in fulminant/subfulminant hepatic failure patients was significantly higher in the BAL compared with the control group (risk ratio 0.56: P = 0.048). Conclusions: This is the first prospective, randomized, controlled trial of an extracorporeal liver support system, demonstrating safety and improved survival in patients with fulminant/subfulminant hepatic failure.
Abstract: The authors provide a cautionary note on reporting accurate eta-squared values from multifactor analysis of variance (ANOVA) designs. They reinforce the distinction between classical and partial eta-squared as measures of strength of association. They provide examples from articles published in premier psychology journals in which the authors erroneously reported partial eta-squared values as representing classical etasquared values. Finally, they discuss broader impacts of inaccurately reported etasquared values for theory development, meta-analytic reviews, and intervention programs.
Long Island Jewish Medical Center1, University of Colorado Denver2, Thomas Jefferson University3, University of Texas MD Anderson Cancer Center4, University of California, San Francisco5, University of Wisconsin-Madison6, Henry Ford Health System7, University of California, Los Angeles8, University of Texas Southwestern Medical Center9, Riverview Hospital10
TL;DR: These guidelines are an educational tool designed to assist practitioners in providing appropriate radiologic care for patients and are not intended, nor should they be used, to establish a legal standard of care.
Abstract: These guidelines are an educational tool designed to assist practitioners in providing appropriate radiologic care for patients. They are not inflexible rules or requirements of practice and are not intended, nor should they be used, to establish a legal standard of care. For these reasons and those set forth below, the developers of this guideline cautions against the use of these guidelines in litigation in which the clinical decisions of a practitioner are called into question. The ultimate judgment regarding the propriety of any specific procedure or course of action must be made by the physician or medical physicist in light of all the circumstances presented. Thus, an approach that differs from the
TL;DR: The data suggest that the large S glycoprotein of SARS-CoV may use both ACE2 and CD209L in virus infection and pathogenesis, and several other enveloped viruses including Ebola and Sindbis also useCD209L as a portal of entry.
Abstract: Angiotensin-converting enzyme 2 (ACE2) is a receptor for SARS-CoV, the novel coronavirus that causes severe acute respiratory syndrome [Li, W. Moore, M. J., Vasilieva, N., Sui, J., Wong, S. K., Berne, M. A., Somasundaran, M., Sullivan, J. L., Luzuriaga, K., Greenough, T. C., et al. (2003) Nature 426, 450–454]. We have identified a different human cellular glycoprotein that can serve as an alternative receptor for SARS-CoV. A human lung cDNA library in vesicular stomatitis virus G pseudotyped retrovirus was transduced into Chinese hamster ovary cells, and the cells were sorted for binding of soluble SARS-CoV spike (S) glycoproteins, S590 and S1180. Clones of transduced cells that bound SARS-CoV S glycoprotein were inoculated with SARS-CoV, and increases in subgenomic viral RNA from 1–16 h or more were detected by multiplex RT-PCR in four cloned cell lines. Sequencing of the human lung cDNA inserts showed that each of the cloned cell lines contained cDNA that encoded human CD209L, a C-type lectin (also called L-SIGN). When the cDNA encoding CD209L from clone 2.27 was cloned and transfected into Chinese hamster ovary cells, the cells expressed human CD209L glycoprotein and became susceptible to infection with SARS-CoV. Immunohistochemistry showed that CD209L is expressed in human lung in type II alveolar cells and endothelial cells, both potential targets for SARS-CoV. Several other enveloped viruses including Ebola and Sindbis also use CD209L as a portal of entry, and HIV and hepatitis C virus can bind to CD209L on cell membranes but do not use it to mediate virus entry. Our data suggest that the large S glycoprotein of SARS-CoV may use both ACE2 and CD209L in virus infection and pathogenesis.
Columbia University1, Harvard University2, University of Alabama at Birmingham3, Federal University of Rio de Janeiro4, Brown University5, University of Barcelona6, International AIDS Society7, Stanford University8, University of British Columbia9, University of California, San Diego10, University of Colorado Denver11, Istituto Superiore di Sanità12, United States Department of Veterans Affairs13
TL;DR: In this article, a 16-member noncompensated panel of physicians with expertise in HIV-related basic science and clinical research, and HIV patient care was designed to have broad US and international representation for areas with adequate access to antiretroviral management.
Abstract: ContextSubstantial changes in the field of human immunodeficiency virus (HIV)
treatment have occurred in the last 2 years, prompting revision of the guidelines
for antiretroviral management of adults with established HIV infection.ObjectiveTo update recommendations for physicians who provide HIV care regarding
when to start antiretroviral therapy, what drugs to start with, when to change
drug regimens, and what drug regimens to switch to after therapy fails.Data SourcesEvidence was identified and reviewed by a 16-member noncompensated panel
of physicians with expertise in HIV-related basic science and clinical research,
antiretroviral therapy, and HIV patient care. The panel was designed to have
broad US and international representation for areas with adequate access to
antiretroviral management.Study SelectionEvidence considered included published basic science, clinical research,
and epidemiological data (identified by experts in the field or extracted
through MEDLINE searches using terms relevant to antiretroviral therapy) and
abstracts from HIV-oriented scientific conferences between July 2002 and May
2004.Data ExtractionData were reviewed to identify any information that might change previous
guidelines. Based on panel discussion, guidelines were drafted by a writing
committee and discussed by the panel until consensus was reached.Data SynthesisFour antiretroviral drugs recently have been made available and have
broadened the options for initial and subsequent regimens. New data allow
more definitive recommendations for specific drugs or regimens to include
or avoid, particularly with regard to initial therapy. Recommendations are
rated according to 7 evidence categories, ranging from I (data from prospective
randomized clinical trials) to VII (expert opinion of the panel).ConclusionFurther insights into the roles of drug toxic effects, drug resistance,
and pharmacological interactions have resulted in additional guidance for
strategic approaches to antiretroviral management.
TL;DR: In this paper, the IL-18 was measured in human urine to determine whether it might serve as a marker of acute tubular necrosis (ATN) in mice, including healthy controls, patients with different forms of acute renal failure, and patients with other renal diseases.
Virginia Commonwealth University1, Saint Louis University2, University of Southern California3, University of Washington4, University of Colorado Denver5, University of Michigan6, University of California, Irvine7, University of Connecticut8, University of Texas Southwestern Medical Center9, Harvard University10, National Institutes of Health11, United States Department of Veterans Affairs12
TL;DR: The most effective therapy currently available for treatment of chronic hepatitis C virus (HCV) is the combination of peginterferon and ribavirin, which was evaluated in patients who were nonresponders to previous interferon-based therapy as discussed by the authors.
TL;DR: This program of prenatal and infancy home-visiting by nurses continued to improve the lives of women and children at child age 6 years, 4 years after the program ended, with an urban, primarily black sample.
Abstract: OBJECTIVE: To test, with an urban, primarily black sample, the effects of prenatal and infancy home visits by nurses on mothers' fertility and economic self-sufficiency and the academic and behavioral adjustment of their children as the children finished kindergarten, near their sixth birthday. METHODS: We conducted a randomized, controlled trial of a program of prenatal and infancy home-visiting in a public system of obstetric and pediatric care in Memphis, Tennessee. A total of 743 primarily black women at or =2 sociodemographic risk characteristics (unmarried, Language: en
TL;DR: Urinary tract infections are among the most common bacterial infections and account for a significant part of the workload in clinical microbiology laboratories, with the increase in resistance to some antimicrobial agents particularly the resistance to trimethoprim-sulfamethoxazole seen in E. coli.
Abstract: Urinary tract infections (UTIs) are among the most common bacterial infections and account for a significant part of the workload in clinical microbiology laboratories. Enteric bacteria (in particular, Escherichia coli) remain the most frequent cause of UTIs, although the distribution of pathogens that cause UTIs is changing. More important is the increase in resistance to some antimicrobial agents, particularly the resistance to trimethoprim-sulfamethoxazole seen in E. coli. Physicians distinguish UTIs from other diseases that have similar clinical presentations with use of a small number of tests, none of which, if used individually, have adequate sensitivity and specificity. Among the diagnostic tests, urinalysis is useful mainly for excluding bacteriuria. Urine culture may not be necessary as part of the evaluation of outpatients with uncomplicated UTIs, but it is necessary for outpatients who have recurrent UTIs, experience treatment failures, or have complicated UTIs, as well as for inpatients who develop UTIs.
TL;DR: It is proposed that insulin and ghrelin cells share a common progenitor and that Nkx2.2 and Pax4 are required to specify or maintain differentiation of the beta cell fate.
Abstract: The pancreatic islet is necessary for maintaining glucose homeostasis. Within the pancreatic islet, the homeodomain protein Nkx2.2 is essential for the differentiation of all insulin-producing β cells and a subset of glucagon-producing α cells (1). Mice lacking Nkx2.2 have relatively normal sized islets, but a large number of cells within the mutant islet fail to produce any of the four major islet hormones. In this study we demonstrate that Nkx2.2 mutant endocrine cells have been replaced by cells that produce ghrelin, an appetite-promoting peptide predominantly found in the stomach. Intriguingly, normal mouse pancreas also contains a small population of ghrelin-producing cells, defining a new islet “e” cell population. The expansion of ghrelin-producing cells at the expense of β cells may be a general phenomenon, because we demonstrate that Pax4 mutant mice display a similar phenotype. We propose that insulin and ghrelin cells share a common progenitor and that Nkx2.2 and Pax4 are required to specify or maintain differentiation of the β cell fate. This finding also suggests that there is a genetic component underlying the balance between insulin and ghrelin in regulating glucose metabolism.
TL;DR: The genome-wide view of mitotic and meiotic cohesin binding provides an important framework for the exploration of cohesins and cohesion in other genomes.
Abstract: In eukaryotic cells, cohesin holds sister chromatids together until they separate into daughter cells during mitosis. We have used chromatin immunoprecipitation coupled with microarray analysis (ChIP chip) to produce a genome-wide description of cohesin binding to meiotic and mitotic chromosomes of Saccharomyces cerevisiae. A computer program, PeakFinder, enables flexible, automated identification and annotation of cohesin binding peaks in ChIP chip data. Cohesin sites are highly conserved in meiosis and mitosis, suggesting that chromosomes share a common underlying structure during different developmental programs. These sites occur with a semiperiodic spacing of 11 kb that correlates with AT content. The number of sites correlates with chromosome size; however, binding to neighboring sites does not appear to be cooperative. We observed a very strong correlation between cohesin sites and regions between convergent transcription units. The apparent incompatibility between transcription and cohesin binding exists in both meiosis and mitosis. Further experiments reveal that transcript elongation into a cohesin-binding site removes cohesin. A negative correlation between cohesin sites and meiotic recombination sites suggests meiotic exchange is sensitive to the chromosome structure provided by cohesin. The genome-wide view of mitotic and meiotic cohesin binding provides an important framework for the exploration of cohesins and cohesion in other genomes.
TL;DR: These modifications of the standard transsphenoidal approach are useful for lesions within the boundaries noted above, they offer excellent alternatives to transcranial approaches for these lesions, and they avoid prolonged exposure time and brain retraction.
Abstract: OBJECTIVE: The traditional boundaries of the transsphenoidal approach may be expanded to include the region from the cribriform plate of the anterior cranial base to the inferior clivus in the anteroposterior plane, and laterally to expose the cavernous cranial nerves and the optic canal. We review our combined experience with these variations on the transsphenoidal approach to various lesions of the sellar and parasellar region. METHODS: From 1982 to 2003, we used the extended and parasellar transsphenoidal approaches in 105 patients presenting with a variety of lesions of the parasellar region. This study specifically reviews the breadth of pathological lesions operated and the complications associated with the approaches. RESULTS: Variations of the standard transsphenoidal approach have been used in the following series: 30 cases of pituitary adenomas extending laterally to involve the cavernous sinus, 27 craniopharyngiomas, 11 tuberculum/diaphragma sellae meningiomas, 10 sphenoid sinus mucoceles, 18 clivus chordomas, 4 cases of carcinoma of the sphenoid sinus, 2 cases of breast carcinoma metastatic to the sella, and 3 cases of monostotic fibrous dysplasia involving the clivus. There was no mortality in the series. Permanent neurological complications included one case of monocular blindness, one case of permanent diabetes insipidus, and two permanent cavernous cranial neuropathies. There were four cases of internal carotid artery hemorrhage, one of which required ligation of the cervical internal carotid artery and resulted in hemiparesis. The incidence of postoperative cerebrospinal fluid fistulae was 6% (6 of 105 cases). CONCLUSION: These modifications of the standard transsphenoidal approach are useful for lesions within the boundaries noted above, they offer excellent alternatives to transcranial approaches for these lesions, and they avoid prolonged exposure time and brain retraction. Technical details are discussed and illustrative cases presented.
TL;DR: The tests performed using CAIM and six other state-of-the-art discretization algorithms show that discrete attributes generated by the CAIM algorithm almost always have the lowest number of intervals and the highest class-attribute interdependency.
Abstract: The task of extracting knowledge from databases is quite often performed by machine learning algorithms. The majority of these algorithms can be applied only to data described by discrete numerical or nominal attributes (features). In the case of continuous attributes, there is a need for a discretization algorithm that transforms continuous attributes into discrete ones. We describe such an algorithm, called CAIM (class-attribute interdependence maximization), which is designed to work with supervised data. The goal of the CAIM algorithm is to maximize the class-attribute interdependence and to generate a (possibly) minimal number of discrete intervals. The algorithm does not require the user to predefine the number of intervals, as opposed to some other discretization algorithms. The tests performed using CAIM and six other state-of-the-art discretization algorithms show that discrete attributes generated by the CAIM algorithm almost always have the lowest number of intervals and the highest class-attribute interdependency. Two machine learning algorithms, the CLIP4 rule algorithm and the decision tree algorithm, are used to generate classification rules from data discretized by CAIM. For both the CLIP4 and decision tree algorithms, the accuracy of the generated rules is higher and the number of the rules is lower for data discretized using the CAIM algorithm when compared to data discretized using six other discretization algorithms. The highest classification accuracy was achieved for data sets discretized with the CAIM algorithm, as compared with the other six algorithms.
Max Planck Society1, Washington University in St. Louis2, Harvard University3, University of Michigan4, Yale University5, Rice University6, University of Hamburg7, University of Leeds8, Abastumani Astrophysical Observatory9, Boston University10, Massachusetts Institute of Technology11, University of Colorado Denver12
TL;DR: In this paper, the authors used a simple synchrotron self- Compton model to model the spectral energy distribution (SED) of a set of TeV blazars with good broadband data, to look for a connection of the jet properties to the properties of the central accreting black hole.
Abstract: Following the detection of strong TeV gamma ray flares from the BL Lac object 1 ES 1959+650 with the Whipple 10 m Cerenkov telescope on 2002 May 16 and 17, we performed intensive target of opportunity radio, optical, X-ray, and TeV ?ray observations from 2002 May 18 to August 14. Observations with the X-ray telescope RossiX-Ray Timing Explorer and the Whipple and HEGRA gamma-ray telescopes revealed several strong flares, enabling us to sensitively test the X-ray--gamma-ray flux correlation properties. Although the X-ray and gamma-ray fluxes seemed to be correlated in general, we found an orphan gamma-ray flare that was not accompanied by an X-ray flare. While we detected optical flux variability with the Boltwood and Abastumani observatories, the data did not give evidence for a correlation of the optical flux variability with the observed X-ray and 7-ray flares. Within statistical errors of about 0.03 Jy at 14.5 GHz and 0.05 Jy at 4.8 GHz, the radio fluxes measured with the University of Michigan Radio Astronomy Observatory stayed constant throughout the campaign; the mean values agreed well with the values measured on 2002 May 7 and June 7 at 4.9 and 15 GHz with the Very Large Array and at 4.8 GHz with archival flux measurements. After describing in detail the radio, optical, X-ray and gamma-ray light curves, and spectral energy distributions (SEDs), we present initial modeling of the SED with a simple synchrotron self- Compton model. With the addition of another TeV blazar with good broadband data, we consider the set of all TeV blazars, to begin to look for a connection of the jet properties to the properties of the central accreting black hole thought to drive the jet. Remarkably, the temporal and special X-ray and gamma-ray emission characteristics of TeV blazars are very similar, even though the mass estimates of their central black holes differ by up to 1 order of magnitude.
TL;DR: Repeat doses of aerosolized adeno-associated serotype 2 vector containing cystic fibrosis transmembrane conductance regulator (CFTR) complementary DNA (cDNA) tgAAVCF were safe and well tolerated, and resulted in encouraging trends in improvement in pulmonary function in patients with CF and mild lung disease.
University of New Mexico1, University of Pennsylvania2, Tufts University3, Johns Hopkins University4, University of Colorado Denver5, University of Minnesota6, Boston Children's Hospital7, Medical College of Wisconsin8, Virginia Commonwealth University9, University at Buffalo10, Pennsylvania State University11
TL;DR: Low-dose hydrocortisone therapy for prophylaxis of early adrenal insufficiency did not improve survival without BPD in the overall study population; however, treatment of chorioamnionitis-exposed infants significantly decreased mortality and improved survivalWithout BPD.
Abstract: Background. Infants developing bronchopulmonary dysplasia (BPD) show decreased cortisol response to adrenocorticotropic hormone. A pilot study of low-dose hydrocortisone therapy for prophylaxis of early adrenal insufficiency showed improved survival without BPD at 36 weeks’ postmenstrual age, particularly in infants exposed to histologic chorioamnionitis. Methods. Mechanically ventilated infants with birth weights of 500 to 999 g were enrolled into this multicenter, randomized, masked trial between 12 and 48 hours of life. Patients received placebo or hydrocortisone, 1 mg/kg per day for 12 days, then 0.5 mg/kg per day for 3 days. BPD at 36 weeks’ postmenstrual age was defined clinically (receiving supplemental oxygen) and physiologically (supplemental oxygen required for O2 saturation ≥90%). Results. Patient enrollment was stopped at 360 patients because of an increase in spontaneous gastrointestinal perforation in the hydrocortisone-treated group. Survival without BPD was similar, defined clinically or physiologically, as were mortality, head circumference, and weight at 36 weeks. For patients exposed to histologic chorioamnionitis (n = 149), hydrocortisone treatment significantly decreased mortality and increased survival without BPD, defined clinically or physiologically. After treatment, cortisol values and response to adrenocorticotropic hormone were similar between groups. Hydrocortisone-treated infants receiving indomethacin had more gastrointestinal perforations than placebo-treated infants receiving indomethacin, suggesting an interactive effect. Conclusions. Prophylaxis of early adrenal insufficiency did not improve survival without BPD in the overall study population; however, treatment of chorioamnionitis-exposed infants significantly decreased mortality and improved survival without BPD. Low-dose hydrocortisone therapy did not suppress adrenal function or compromise short-term growth. The combination of indomethacin and hydrocortisone should be avoided.
TL;DR: It is concluded that patients with HPS (based on a combination of low PaO2 and nonpulmonary factors) and patients with PortoPH were frequently denied OLT because of pre‐OLT test results and comorbidities.
TL;DR: The authors concluded that programs aimed at preventing human immunodeficiency virus transmission should emphasize the influence of substance use during sex on increased risk behavior.
Abstract: Prior reports associating substance use with sexual risk behavior have generally used summary measures and have not adjusted for participants' background levels of substance use. In this 1999-2001 US study (the EXPLORE study), the authors determined whether substance use during sex was independently associated with sexual risk during recent sexual episodes, as reported by 4,295 human immunodeficiency virus-negative men who have sex with men. The main outcome measure was serodiscordant unprotected anal sex (SDUA). The influence of participant-level characteristics was examined by using repeated-measures logistic models. In assessing the influence of episode-level predictors on SDUA, the influence of participant-level characteristics, including 6-month substance use, was removed by using conditional logistic regression, in effect making each participant his own control. The authors also adjusted for partner characteristics. Eleven percent of participants reported heavy alcohol use, 37% used poppers, 19% sniffed cocaine, and 13% used amphetamines. In the participant-level analysis, use of poppers, amphetamines, and sniffed cocaine as well as heavy alcohol use in the prior 6 months were independently associated with SDUA. In the conditional analysis, consumption of > or = 6 alcoholic drinks or use of poppers, amphetamines, or sniffed cocaine just before or during sex was independently associated with SDUA. The authors concluded that programs aimed at preventing human immunodeficiency virus transmission should emphasize the influence of substance use during sex on increased risk behavior.
TL;DR: The performance characteristics of a combined solid-phase extraction isolation and high-performance liquid chromatography-electrospray ionization mass spectrometry analytical procedure for routine determination of the presence and concentration of human-health pharmaceuticals are described.